UWorld
# alkaptonuria
" Congenital AR deficiency of *homogentisic acid oxidase*, impaired breakdown of TYROSINE and PHENYLALANINE. .... Impaired *formation of fumarate* following symptoms: - ↑ homogentistic acid → excreted in urine (if the URINE is left standing it will turn very dark/black!!!! ) - homogentisate also polymerizes and deposits in joints → debilitating joint arthritis, ankylosis, and arthralgias (toxic to cartilage) - the joints are NOT hot/tender, but can be swolen - dark "blue-black" joints/cartilage/skin (usually the ear, nose, cheeks) from the homogentisate deposition (called ochronosis) - brown hyper-pigmented sclera
# Lead poisoning and sideroblastic anemia
" Lead denatures enzymes, including *aminolevulinic acid dehydratase (ALAD)* !!!!!!!! and Ferrochelatase. There is a buildup of aminolevulinic acid (ALA)....which is involved in hemoglobin synthesis (thus, microcytic anemia results). High levels of *pyridoxal phosphate* (which is a cofactor in ALA synthesis) are seen!!!! Associated with abdominal colic with diarrhea, encephalopathy, peripheral neuropathy
# β-thalassemia major overview
" Most severe form- has a gene signature of (β0/β0), meaning that both β-thalassemia alleles are non-functioning. As a result, there is zero β-globin production. β-thalassemia major (β0/β0) presents with severe anemia approximately 6 months after birth because the HbF (A2Y2) does not require β-globin!!! Once they swtich to HbA after 6 months (A2B2), they get side effects!!! Blood smear shows microcytic, hypochromic RBCs with target cells and nucleated RBCs. Note, extramedullary hematopoiesis results in nucleated RBCs. Hb electrophoresis shows: (!!!!!) little or no HbA (no B-chains)!!!! with increased HbA2 increased HbF.
# labs for sideroblastic anemia
" Think that it is an 'iron overloaded state"" because iron keeps building up in mitochondria of erythroid precursor cell, iron causes free radical formation, cell dies, and iron leaks out. Bone marrow macrophages eat iron to store it (↑ Ferritin), but there's also high in blood - ↓ TIBC - ↑ serum iron - ↑ % saturation
# Sideroblastic anemia
" due to a defect in protoporphyrin synthesis, which leads to microcytic anemia. (heme= Fe+protoporphyrin)!!!! Protoporphyrin is synthesized via complex series of rxns *in erythroblasts. *
# Vitamin K function and activates what??
" gamma-carboxylates glutamate residues and thereby activates: - 4 pro-coagulants: clotting factors 2, 7, 9, 10 - 2 anti-coagulants: protein C, protein S
# Thalassemias
" microcytic anemias that are due to defects in synthesis (!!!!) of α- or β-globin chains of hemoglobin. Decreased globin leads to decreased hemoglobin Note: it is *decreased synthesis of the chains* which is a thalassemia... alterations of the globin chain (ie, sickle cell) are not considered a thalassemia!!! Clinically significant thalassemias are inherited in an autosomal recessive fashion.... divided into α-Thalassemia or β-Thalassemia
# β-Thalassemia- which chromosome??
" results from mutations (NOT DELETIONS) in β-globin genes. Common genetic mechanisms include point mutations or small deletions within promoter regions or splice sites. There are 2 copies of the β-globin gene, one on each copy of chromosome 11. Mutations can result in absent (β0- aka 'beta null') production of β-globin chains. Mutations can also result in decreased (B+- aka 'beta plus') production of β-globin chains So, patient can theoretically have many variations of (β, β+, β0)
# β-thalassemia minor
" β-thalassemia minor (β/β+) is the mildest form and is usually asymptomatic. Blood smear shows microcytic, hypochromic anemia with *increased RBC count and target cells * !!!!! Hb electrophoresis (best diagnostic test for thalassemias!!!!) shows: - slightly decreased HbA (below 97% which is normal levels!!!) - increased HbA2 3.5%-5% (normal is 2.5%) - increased HbF to 2% (normal is 1%)
# Vitamin B3
"(niacin): precursor for NADH and NADPH. (B3= NADH = 3ATP's) • niacin may be administered in the form of nicotinic acid to raise HDL and lower LDL.
# B1 is a coenzyme for what enzymes? (!!!)
", thiamine pyrophosphate (TPP), is an important coenzyme for several reactions, notably: • dehydrogenase enzymes (e.g. pyruvate dehydrogenase complex, α-ketoglutarate dehydrogenase complex, and branched-chain ketoacid dehydrogenase). • transketolase, an enzyme of the non-oxidative portion of the pentose phosphate pathway.
# Lab measures of iron status
"1) Serum iron- 2) TIBC- Total Iron Binding Capacity... measures amount of Transferrin molecules in blood 3) % saturation- How many of of the transferrin molecules are bound by iron 4) Serum ferritin- how much iron is present in bone marrow macrophages and liver
# Collagen synthesis step 1 (in the RER fibroblast)
"1) Synthesis of pre-procollagen (α-chains) occurs in rER, with a key repeating sequence of glycine-X-Y. (!!!!!) X is usually proline, Y is usually hydroxyproline or hydroxylysine. (note: glycine is always in every 3rd AA in collagen!!!! ) 2) Some proline & lysine residues are hydroxylated in the rER lumen; this process requires vitamin C as a cofactor: 3) Some hydroxylated amino acids are further glycosylated with galactose or glucose → collagen is a glycoprotein 4) The post-translationally modulated chains then combine into a TRIPLE HELIX (now called procollagen) and are sent to the Golgi and then secreted extracellularly
# causes of microcytic anemia
"1) iron deficiency anemia 2) Anemia of chronic disease 3) sideroblastic anemia- problem with protoporphyrin. 4) thalassemia- problem with the globin chains!! 5) lead poisoning
# causes of niacin deficiency
"1. Hartnup disease 2. In carcinoid syndrome, excess tryptophan metabolism converts tryptophan to serotonin. 3. Prolonged isoniazid use decreases niacin levels by depletion of pyridoxal phosphate, B6, which is necessary for endogenous synthesis of niacin!!
# Stages of iron deficiency (!!!)
"1. Storage of iron is depleted (↓ ferritin, ↑ TIBC reflecting *increased serum transferitin*)... note, when ferritin ↓TIBC ↑, always) Also note: ↑ TIBC is due to a decrease in the total number of binding sites occupied by iron. Remember that TIBC and Transferrin always change in the SAME direction!!! 2. Serum iron is depleted (↓ serum iron, ↓ % saturation) 3. Normocytic anemia INITIALLY (as iron isn't as available, bone marrow makes fewer, but normal size RBC's) (!!!) 4. Microcytic, hypochromic anemia (Bone marrow makes fewer AND smaller RBC's): ↓ MCV (microcytic) 5. ↑ FEP- Free Erythrocyte Protoporphyrin (because Heme: Fe + Protoporphyrin...... Fe is down, but Proto is fine, so more free)
# α-thalassemia 3 or 4 allele deletions
"3. If 3 alleles are deleted, the patient will develop a severe microcytic, hypochromic anemia. The β-globin chains form β2β2- tetramers (HbH) which precipitate and damage RBCs. Note, HbH is detectable by electrophoresis. 4. If 4 alleles are deleted, hydrops fetalis (!!!) will develop which is lethal in-utero!! (poor oxygen delivery, congestive heart failure, death) If 4 alleles are deleted, γ-globin chains form tetramers (Hb Barts) which precipitate and damage RBCs. Note, Hb Barts is detectable by electrophoresis. !!!!!!!!!!!
# trisomy 18 (Edward syndrome)
"95% of conceptuses with trisomy 18 die before birth. Of the live-born babies, 90-95% will die within the first year. • High mortality due to cardiac, renal, and CNS defects (severe mental retardation, central apnea); patients are prone to sepsis Physical findings: clenched hands with overlapping fingers, micrognathia, low-set ears, and prominent occiput. (!!!) rocker bottom feet.
# Type IV dyslipoproteinemia aka hypertriglyceridemia
"AD inherited.... • Due to hepatic overproduction of VLDL, the characteristic lab findings are increased serum VLDL and triglycerides. • Patients present with pancreatitis. facial flushing (induced by prostaglandins, NOT histamine)....
# histone acetylation vs methylation
"Acetylation (negative charge) of positively charged histones weakens the DNA-histone bonds and makes DNA ACCESSABLE to transcription factors and DNA polymerases acetylation makes active, methylation makes mute
cystic fibrosis
"An autosomal recessive defect in CFTR, a transmembrane ATP chloride channel on chromosome 7 (usually a deletion of Phe 508) !!!! The mutation causes a *misfolded protein *and the protein is retained in the RER instead of transported to the cell membrane!!! In respiratory and epithelium *exocrine glands*, normal CFTR allows active luman *sodium chloride secretion*... while *mutated* CFTR causes DECREASED CHLORIDE SECRETION so there is HIGH levels of chloride intracellularly, and thus, INCREASED SOCIUM and H2O REABSORPTION . results in thickened DEHYDRATED MUCUS secretions, severely affecting function of the pancreatic, pulmonary, and reproductive systems, causing mucus plugs. In *sweat glands*, normal CFTR reabsorbs chloride, and enhances socium reabsorption. While *mutated* CFTR diminishes sodium chloride reabsorption and thus, increases sweat tonicity. So, we sweat out a ton of NaCl.
# Wilson Disease aka hepatolenticular degeneration
"Auto-recessive defect in ATP7B (!!) gene, involved in ATP mediated hepato *copper transport*. There is *decreased ceruloplasmin, and decreased secretion of copper* !!!! Copper cannot be put into either bile or ceruloplasmin (liver synthesized protein which carries 90% of copper), builds up in hepatocytes, leaks in serum, deposits in tissue (principally affects the liver, the CNS and the eyes) and leads to hydroxyl free radical damage.
# pernicious anemia neurological signs and spinal tracts (!!!)
"B12 deficiency → defect in propionate (odd-chained fatty acid) metabolism → defect in synthesis of CNS myelin →* subacute combined degeneration* !!! (which "combined" means it degenerates both the *ascending dorsal column*, and *descending corticospinal*(!!) ) due to demyelination of: 1) Dorsal aka posterior columns → *impaired position/vibration* sense (positive Romberg test) 2) Lateral corticospinal tracts → signs of upper motor lesion (hyperreflexia, ↑ muscle tone, positive Babinski with toes upgoing/extending and fanning out upon stimulation of plantar aspect of foot) 3) Spinocerebellar tracts → ataxic gait 4) *axonal degeneration of the peripheral nerves*- causes numbness/parsthesis.
# Rb mutations and what tumors result??
"BOTH copies must be knocked out. Sporatic mutations likely to lead to unilateral retinoblastoma (tumor in back of eye) Germline (familial) mutations likely to lead to bilateral retinoblastoma and osteosarcoma.
# BCl-2
"Bcl-2 is a proto-oncogene named for its role in the pathogenesis of B-Cell Lymphoma.* Bcl-2 (encoded by the BCL2 gene) blocks apoptotic* mechanisms in 2 ways: 1) Bcl-2 normally resides in the cytoplasm and on the mitochondrial membrane, controlling permeability. This prevents the leakage of apoptotic effectors, thus preventing cell death. 2) Binds Apaf-1 in cytosol, and inhibits its activation by cyt c.
# Cytotoxic CD8+ T-cell pathways
"CD8+ t-cells recognize antigens on MHC-1, kill cell that expresses antigen by apoptosis. CD8+ t-cell secretes: -perforin which creates pores in membrane of target cells - granzymes, which then enter the pore and activates caspases
# myotonic dystrophy type 1 overview/mechanism (!!!)
"CTG trinucleotide repeat expansion of the gene for myotonic dystrophy protein kinase (DMPK gene) on chromosome 19. Leads to abnormal expression of myotonin protein kinase • Autosomal dominant inheritance. *type 1 fibers are more often affected!!* Signs of myotonic dystrophy include: muscle weakness and wasting, myotonia (prolonged muscle contractions), Since type 1 fibers are more affected, may show inability to loosen grip after handshake, or inability to release doorknob !!!! Also cataracts, frontal balding, testicular atrophy, and cardiac conduction abnormalities
# severe combined immunodeficiency SCID overview
"Caused by defects in early stem cell differentiation → marked deficiency of BOTH B and T cells ∴ BOTH humoral and cell-mediated immune responses are affected. High incidence of malignant lymphomas!!!
# pseudo gout (!!!)
"Clinically resembles gout, but it is NOT gout. Due to deposition of *calcium pyrophosphate* (not monosodium ureate).... Synovial fluid examination shows *rhomboid (!!!!) /square/rod shaped crystals* that have *weak positive bifringence* under polarized light !!! It USUALLY involves the knee!! Crystals are *blue* when parallel (opposite of gout).
# treat Wilson's disease (!!!)
"D- Penicillamine (copper chelater) is main !!!! - Zinc (inhibits Cu absorption)
# Gout
"Deposition of *mono-sodium urate* crystals in the tissues, especially the joints!!! Mono-sodium urate is derived from *uric acid*, so it is due to *hyperuricemia* in the blood In *gout*, we have increased uric acid (hyperuricemia) in blood either via: 1) too much uric acid into the blood (10%) 2) too little uric acid is filtered by the blood (90% )
# type 2a dislipoproteinemia/familial hypercholesterol findings
"Due to defective LDL receptor, LDL cannot be cleared from the blood. More IDL is converted into LDL. findings include: - increased serum LDL AND increased serum cholesterol leading to *increased risk of atherosclerosis and coronary artery disease.*
# microcytic anemia
"Erythroblast keeps dividing, and with each division, cells become smaller, so *microcytosis* is due to an ""extra"" division. - Always due to decreased production of Hb. If there isn't enough Hb, RBC's divide an extra time to try and maintain concentration of Hb.
# Hemochromatosis
"Excess iron leading to deposition in tissues (called hemosiderosis) and organ damage (hemochromatosis, DAMAGE due to iron deposition) Damage caused by free radicals. Iron forms free radicals.... Also direct DNA damage. Can be primary, or secondary.
# Extramedullary hematopoiesis
"Extramedullary hematopoiesis in the liver and spleen results in hepatosplenomegaly. Hypersplenism, from extramedullary hematopoiesis and increased extravascular hemolysis, can result in splenic infarction and abdominal pain. Note, the increased hemolysis can also lead to bilirubin gallstones leading to RUQ pain. Extramedullary hematopoiesis in the skull results in crewcut appearance on x-ray (!!!). Extramedullary hematopoiesis in the facial bones results in characteristic chipmunk facies (!!!!). Extramedullary hematopoiesis results in increased erythroid precursors leading to an increased risk of aplastic crisis from parvovirus B19 infection (!!!!) - this virus affects erythroid precursors and shuts them down. Normally, it only lasts a week or two, and has little effect because people normally have more than enough RBC reserve. However, these people don't have enough reserve for even a day or so.
# SGLT2 inhibitors for diabetes
"FLOZIN" !! Canagliflozin, dapagliflozin SGLT2 is a *transport protein that is responsible for resorbing 90% of filtered glucose in the proximal tubule*. They are *oral anti-diabetic agents* that work by *decreasing proximal tubular resorption of glucose*, thereby promoting *significant urinary glucose loss*. It is *very important to monitor renal function* !!! Side effects are *urinary tract and genital mycotic infections* due to glucosuria. Increased osmotic diuresis can *also cause symptomatic hypotension*.
# Normal hemoglobin types
"Fetal- (alpha 2, gamma 2) Hemoglobin A- (alpha 2, beta 2) Hemoglobin A2 (alpha 2, delta 2).... So, think that alpha is most important chain."
# Marfan syndrome
"Fibrillin polymers form a sheath of microfibrils that surrounds elastin !!! Defects in the fibrillin gene FBN1 cause Marfan syndrome, which is autosomal dominant because the defective fibrillin prevents proper multimerization of fibrillin.
# parovirus B19 presentation
"Fifth disease (*erythema infectiosum; slapped cheeks disease*): !!! low-grade (!!) fever for 7-10 days → classic erythematous macular rash starts on the the face (""slapped cheeks"") and appears after resolution of the fever → 2-3 days after the slapped cheeks first appear, the rash may spread to the trunk / extremities where it takes on a lacy, reticular pattern. Adults: joint pain/polyarthralgia (immune complexes) and/or edema, rash is less common in adults.
# Vitamin B9 deficiency
"Folate Folate is converted to tetrahydrafolate (THF), which is a carbon carrier critical for synthesis of nitrogenous bases (particularly thiamine, adenine, and guanine) in nucleic acids, especially in states of rapid cell division (pregnancy, erythropoiesis). • Deficiency leads to neural tube defects & megaloblastic anemia..... NO neurological symptoms
fragile X overview
"Fragile X syndrome is caused by expanded *trinucleotide CGG repeats* in the promoter segment of the *FMR1 gene on the long arm X-chromosome*. The expanded promoter segment *enhances methylation* leading to silencing of the FMR1 gene. The area of repeats does not stain and "appears broken"!!!!! • Silencing of the FMR1 gene leads to decreased synthesis of FMRP protein!!!!
fragile x findings
"Fragile X syndrome is more common in males (because they have 1 X chromosome!!!) and presents with MILD mental retardation, as well as ""X""tra large, - macro orchidism (enlarged testes) - large jaw/forearm - long face and large everted ears The most common complication associated with Fragile X syndrome is mitral valve prolapse.
# sickle cell trait vs disease labs
"Hb electrophoresis confirms both PRESENCE and AMOUNT of HbS. Disease: 90% HbS, 8% HbF, 2% HbA2, NO HbA!!! Trait: 55% HbA, 43% HbS, 2% HbA2
# secondary gout
"Hyperuricemia due to a known cause, ... but gout is not the main clinical manifestation of the perturbation/disease): often due to conditions such as: - Leukemia and myeloproliferative disorders- there is a lot of cell turnover, which means a lot of turnover of nucleus, so we breakdown a lot of purines and pyramidines, and the breakdown of *purines* is uric acid -- renal insufficiency (kidney has to excrete uric acid) - Lesch Nyhan syndrome
# macrocytic anemia!!!
"MCV > 100. Most commonly due to B12/folate deficiency (megaloblastic anemia), which are DNA precursors! ↓ DNA synthesis → RBCs grow larger than normal before dividing - cell has ~1 less division (contrast to microcytic which has ~1 more division)
# peroxisome
"Membrane-enclosed organelle involved in *catabolism of very-long-chain fatty acids, ODD numbered branched-chain fatty acids, *and amino acids."
# Microtubules and movement of substances
"Microtubules can also serve as a substrate along which dynein and kinesin can move. This process requires hydrolysis of ATP. • Dynein moves retrograde (+ to -): the ""minus"" end of the microtubule • Kinesin moves anterograde (- to +): the ""plus"" end of the microtubule, where new subunits are added ... ie, in neurotransmitter containing secretory vesicles
# Polymerase chain reaction overview
"Molecular biology laboratory procedure used to isolate and amplify a desired fragment of DNA. Once the gene is isolated/amplified, often other techniques can be used, such as genetic sequencing. It is useful as a diagnostic tool (e.g., neonatal HIV, herpes encephalitis), especially since it is fast to complete. We must know the sequence of the *region flanking the target DNA in order to make primers!!!!!* .... We do not need to know the target DNA sequence (that is what we are looking for).
# causes of sideroblastic anemia
"Most common (!!!) congenital defect is due to defect in enzyme aminolevulinic acid synthetase (ALAS) which is enzyme in rate limiting step (requires B6)!!!! Acquired: -Lead poisoning - Vitamin B6 deficiency
# primary gout
"Most common form of Gout, the etiology of hyperuricemia is unknown (but is either overproduction, decreased excretion, combo of both, but unknown exact cause)
# Primary vs secondary hemochromatosis
"Normally, the enterocyte takes up iron, and releases it into blood when needed.
# how does sideroblastic anemia get its name
"Note: while protoporphyrin is being generated, iron is transferred to erythroid precursors, enters mitochondria to combine with protoporphyrin and form heme. If protoporphyrin is deficient, iron keeps going in and is trapped in the mitochondria and it piles up... this creates a ring of *iron-laden mitochondria around the nucleus of erythroid precursors, called a RING SIDEROBLAST.* !!!!!
# parovirus B19
"Now called erythrovirus!! Only (!!!) single stranded DNA virus). Smallest DNA Virus!!!!!!!!! Respiratory transmission - vertical (mother to fetus), - transfusions/transplants; infects/lyses erythroblasts. (!!!) Can cause severe aplastic anemia in kids w/ chronic anemia (e.g. sickle cell) b/c it preferentially infects erythroblasts. It *replicates in the bone marrow*!!!!!!!!!
oculomotor nerve lesion and vision (CN III)
"Out and down" eye .....due to the unopposed actions of the superior oblique and lateral rectus muscles.) Mydriasis (fixed-dilated pupil)- Enlarged pupil, nonreactive pupil (blurry vision) ptosis (CN III also innervates the levator palpebrae superioris, which serves to elevate the upper eyelid. A lesion would thus result in ptosis (droopy upper eyelid) Vertical AND horizontal diplopia Blurry vision- *lack of accommodation*. # what is the feared cause of CN III palsy ? • Uncal (transtentorial) herniation • Aneurysms of the posterior communicating artery!!!
# acute gout
"Painful arthritis due to deposition of uric acid as *mono-sodium urate* ... the crystals trigger an acute inflammation where *the crystals activate neutrophils*, and *neutrophils cause intense inflammation* !!! leading to painful arthritis of the great toe/first MTP... this is called *podagra* - Excruciating, sudden, unexpected, burning pain, as well as swelling, redness, warmth, and stiffness in the affected joint.
# trisomy 13 Patau
"Patau (puberty). Severe mental retardation. *Holoprosencephaly*(failure of brain to develop into hemispheres) microcephaly • Polydactyly , CLEFT LIP/PALATE, small eyes • Heart defects: PDA, VSD, ASD, dextrocardia Abdominal wall defects (umbilical hernia, pyloric stenosis) rocker bottom feet. .... It is the most severe
# Vitamin B2
"Riboflavin. key component of FAD (used in *succinate dehydrogenase* of the TCA cycle, aka complex II of the electron transport chain) and FMN (used in NADH dehydrogenase, aka complex I of the electron transport chain), which are used as cofactors for redox reactions. Think B2=FAD (2 ATP)"
# Anemia
"Technically defined as reduction in circulating RBC mass. Hb, Hct, and RBC count used as surrogate markers for RBC mass. Hb < 13.5g/dl in males: Hb < 12.5g/dl in females
# dystrophin
"The primary location of the dystrophin protein is in skeletal and cardiac muscle where *dystrophin links the actin cytoskeleton to the extracellular matrix . * - Mutations are *often spontaneous* because dystrophin is the largest gene in the human genome, so because of its huge size, there is an increased risk for spontaneous deletions/mutations.
# what cell finding of Hb is found in G6P-deficiency
"These stressors cause Hb to precipitate as Heinz bodies, which are removed by splenic macrophages, which results in *bite cells*. (cells which look like a macrophage took a 'bite' out of them" ( "bite into Heinz ketchup") !! *Heinz bodies stain with *crystal violet* !!!!* Leads to predominantly intravascular hemolysis. (also some extravascular)
# treat Hereditary spherocytosis
"Treat with splenectomy (because problem is in the spleen which eats them!!) Splenectomy will cure the hemolytic anemia, not the underlying RBC defect so spherocytes still persist.
# Name the trinucleotide repease diseases (!!!)
"Tri hunting my fried eggs" ... huntington disease, myotonic dystrophy, Friedrich ataxia, Fragile X..... = C_G Hunting (A)- CAG repeats MyoTonic (T) CTG repeats FraGile-X(G) CGG repeats Friedrich = GAA repeats!!!
# sideroblastic anemia is caused by what B vitamin deficiency?
"Very first step is succinyl CoA into Aminolevulinic acid (ALA) via the enzyme aminolevulinic acid synthetase (ALAS), *using Vitamin B6 as cofactor !! (rate limiting step)* 2. ALA converted to porphobilinogen using enzyme aminolevulinic acid dehydratase (ALAD). 3. additional reactions convert porphobilinogen into protoporphyrin 4. Protoporphyrin attaches with iron by enzyme Ferrochelatase to make heme (final rxn occurs in mitochondria).
# anemia presentation
"Weakness, fatigue, dynpnea: - pale conjunctiva and skin - headache/lightheaded - * angina, especially w/ preexisting CVD**
# Duschenes (Duchenne) X-linked muscular dystrophy
"X-linked recessive frameshift mutation. Degerative disorder that begins to present around age 3-5.......characterized by weakness in pelvic muscles initially (ie, difficulty walking), that progresses superiorly., muscle wasting, with *replacement of skeletal muscle with adipose tissue. (pseudohypertrohy of calves especially). * - due to *deletions* of *dystrophin* ""Duschene's deleted dystrophin"
# direct factor Xa inhibitors
"Xaban" !! (rivaroxaban, apixaban) It basically makes the person like Glanzmann thrombasthena!! They increase the PT and aPTT.... But do NOT affect the thrombin time!!!! (TT) (note, heparin prolongs aPTT and TT, but NOT PT) Factor Xa is located at the junction of BOTH intrinsic and extrinsic pathways!!!
Sarcomere image
"ZI Ales Hrebesky Memorial" Z, A, H, M - I-band - I-band is the zone of thin filaments that is not superimposed by thick filaments..... ∴ the I band is the most common site for muscle strains.!!! A-band - contains the entire length of a single thick filament. • H-band is the zone of the thick filaments that is NOT superimposed by the thin filaments. • Inside the H-zone is a thin M-line (from the German "Mittelscheibe", the disc in the middle of the sarcomere) formed of cross-connecting elements of the cytoskeleton. - Shortening of the H band and I band ("HI") - The A band maintains its same length during contraction
# Thiazolidinediones
"ZONE" Commonly used medications include rosiglitazone, and pioglitazone. Mechanism: Improves insulin target sensitivity. It *binds to PPAR-γ (peroxisome proliferator activating receptor-gamma)* in the nucleus..... causing increased insulin receptor number and sensitivity, as well as decreased hepatic gluconeogenesis.(!!!) Increases GLUT4 transporters, and *induces differentiation of preadipocytes to adipocytes* (so they are sensitive to insulin).!! They also *increase levels of adiponectin* (!!!!!!!) , a cytokine secreted by fat cells.... which improves insulin sensitivity. Note: this medication often takes a while to work because it works by influencing gene transcription which takes time (!!!!!!!!)
#methotrexate main side effect and reversal
"a folate analogue, competitively inhibits dihydrofolate reductase, an enzyme required for activation of methylene tetrahydrofolate.... thus it decreases dTMP, decreases DNA and protein synthesis.... and is used as an anticancer drug. the intermediate *dihydrofolic acid polyglutamate* accumulates within the treated cells!! It can cause bone marrow suppression, but it is reversed by administering *leucovorin* which is a *tetrahydrofolate derivative* in order to provide *folinic acid* to "rescue" !!! Methotrexate can also cause (!!!) Stomatitis (painful mouth ulcers) -hepatotoxicity (hepatitis, fibrosis, cirrhosis) Also *PULMONARY FIBROSIS*!!!!
# Vitamin B6
"active form is pyridoxal phosphate (PLP). This is a cofactor in: • transamination reactions (AST/ALT) • deamination reactions • decarboxylation (example: glycine + succinyl-CoA → aminolevulinic acid)
# Base excision repair (!!!)
"corrects single depurinated, or otherwise damaged bases, with the use of special N-glycosylase enzymes 1) The glycosylases create an AP (apurinic and apyrimidinic) site by removing the nitrogenous base without interrupting the phosphodiester backbone. 2) This site is recognized by *AP ENDONUCLEASES* which then excises the abasic sugar 3) A lyase completeds the removal of the AP site by removing the sugar phosphate 4_ DNA Pol I (prokaryotic) or DNA Pol β (human) then replaces the damaged base 5) DNA ligase seals the New DNA strand
# Amanita phalloides (mushroom)
"death cap" mushroom that is responsible for most mushroom deaths. They destroy the liver cells by binding to *DNA-dependent RNA polymerase II" which HALTS mRNA synthesis !!!! Symptoms start 6-24 hours after infestion and include abdominal pain, comiting, severe diarrhea.
# Bisphosphonates
"dronates"... they are *structural analogues of pyrophosphate*, bind hydroxyapatite on bone, prevent demineralization by inhibiting osteoclast differentiation and induce their apoptosis Side Effects: Heartburn, pill esophagitis, osteonecrosis of the jaw.
# alcoholic hypoglycemia
"ethanol is metabolized to acetaldehyde, which is then into acetate.... During BOTH steps, NADH is generated. Since NADH is backed up, more pyruvate is conerted to lactate.... And oxaloacetate is diverted to malate which inhibits gluconeogenesis (!!!) ... Oxaloacetate + NADH → Malate + NAD+ .... Pyruvate and oxaloacetate depletion leads to inhibition of gluconeogenesis and stimulation of fatty acid synthesis, which results in fasting hypoglycemia. • Dihydroxyacetone phosphate is reduced to glycerol 3-phosphate, which further stimulates fatty acid synthesis. Dihydroxyacetone phosphate + NADH → Glycerol 3-phosphate + NAD+
# treat B thallassemia major
"generally require chronic(!!!) blood transfusions. Chronic blood transfusions increase the risk of secondary(!!) hemochromatosis because iron builds up in various tissues (pancreas, heart, skin).
# what causes oxidative stress in G6PD
"infection: Drugs ( primaquine, sulfas, nitros) - fava beans (particularly in Meditteranian)
# intravascular hemolysis
"intravascular hemolysis destruction of RBC within blood vessels, causes Hb to be released into blood, and the body binds a very minimal amount of it with haptoglobin (!!) , which takes the Hb to spleen to be reprocessed. Because increased Hb-haptoglobin complex is formed, the patient's free haptoglobin levels decrease. (!!!!) - Mostly, Hb levels build up in blood (creating hemoglobinemia), and since Hb IS water soluble, there is a hemoglobinuria. also, *hemosiderinuria * is found!!!!!!. As Hb goes through renal tubules, some Hb is taken up by renal tubular cells where it is destroyed and broken down, the iron piles up, and it accumulates as hemosiderin! - eventually, the cells slough off, and days later (!!!), patients have hemosiderinuria !!!
# imprinting
"is gene silencing via methylation which occurs in the germ line PRIOR to fertilization. "remember, methyl makes mute" At a single locus,only 1 allele is active,the other is inactive(imprinted/inactivated by methylation)...deletion of active allele = disease Imprinting is a normal epigenetic modification (less than 1% of genes) of the genome that results in monoallelic gene expression. In other words, in cases of imprinting, only one chromosome's alleles (the NON-imprinted allele) in a pair are expressed. • Maternally imprinted means that maternal genes are not expressed. Paternally imprinted means that paternal genes are not expressed.
# vitamin b12 deficiency consequences
"macrocytic megaloblastic anemia with hypersegmented PMNs, and neuropathy:
# B-thalassemia major pathophysiology
"no β chains, so α-globin chains form α2α2 tetramers which precipitate and damage RBCs. These damaged RBCs then undergo extravascular hemolysis in spleen. They also cause ineffective erythropoiesis, which usually occurs in central axial skeleton, but because there is such severe anemia, we have massive EPO release, and hematopoeisis is expanded (extramedullary) into marrow of skull, facial bones, liver, spleen.
# aplastic anemia
"normocytic anemia, Aplastic anemia is a disease in which the bone marrow, and the blood stem cells that reside there, are damaged. This causes a deficiency of *all three blood cell types (pancytopenia)*: red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia). There is a compensatory increase in EPO !!! There is *NO SPLENOMEGALY* !! Myelofibrosis has MASSIVE splenomegaly!
# BCL-2 overexpression (!!)
"overexpressed in *Follicular lymphoma*. (B-cell lymphoma, second most common non-Hodgkin lymphoma)
# Vitamin B5
"pantothenic acid:... aka ""pent-o-thenic"" acid.... needed to form coenzyme-A (CoA). CoA is very important in early TCA cycle, it *binds to oxaloacetate* and enhances the conversion to citrate.
#Wilson disease manifestations
"presents usually in childhood, leads to: - Cirrhosis (cirrhosis doesn't normally happen in those young!!!!!) - - Risk of HCC, hepatosplenomegaly, renal disease - Dementia (Cu deposition in cerebral cortex) - Psudoparkinsons (Cu deposits in putamen) - Hemiballismus (Cu deposits in *subthalamic nucleus*) !!!! - difficulty speaking - Chorea (abnormal, involuntary movt) - Kayser-Fleisher rings in *Cornea*!!, encircling the edge of the iris
# pathophys of anemia of chronic disease, what cytokine involved???
"related to the persistent release of inflammatory mediators. HEPCIDIN, a *liver peptide hormone* that strongly regulates iron, is high in inflammation because Inflammatory state → IL-6 production which - ↑ hepcidin.
# α-Thalassemia overview
"results from deletions of entire α-globin genes. There are 4 copies of the α-globin gene, two on each copy of chromosome 16.
# DNA promoters are often rich in what?
"site where RNA polymerase II and transcription factors (TFs) bind to DNA upstream (!!!). often contains A-T rich sequences of TATA or CAAT boxes)
#narcolepsy criteria
"sleep attacks" where patients suddenly fall asleep Recurrent lapses into sleep or naps a MINIMUM of 3x per week, for 3 months. There is often daytime sleepiness. • True REM sleep during these attacks • Commonly associated with cataplexy, where the patient suddenly loses all muscle tone upon intense emotions (ie laughing) → and then becomes clumsy or collapses to the ground Commonly experience intrusions of REM sleep including hypnagogic (upon falling asleep), hypnopompic (upon awakening) hallucinations (ie, hearing voices).... Also sleep paralysis (inability to move upon awakening). They CAN feel refreshed after naps.
# corpus callosum damage
"split brain" syndrome. Appear normal but have lack of interhemispheric transfer of information. Ie, cannot retrieve with one hand an object palpated by the other.
# anti-cholinesterases
"stigmines" (neostigmine, pyridostigmine, physostigmine). They can REVERSE cholinesterase overdose like in *atropine poisoning* or Note, Physostigmine inhibits Ach esterase BOTH peripherally and centrally because it is able to penetrate the blood prain barrier. !!!! Neostigmine does NOT readily cross the blood brain barrier, so it only acts peripherally!!!!!!
# scurvy signs
"swollen, spongy and purplish gums that are bleed often o bleeding into the skin (bruising) o loose teeth o bulging of the eyes (proptosis) o scaly, dry and brownish skin o very dry, brittle hair that curls (""corkscrew"" hair) o slow wound healing o bleeding into the joints (hemarthrosis) and muscles, which causes swelling over the bones of the arms and legs
# tetraclycines
"tetra= tRNA" Prevents amino-acyl tRNA from binding to the A-site of the 30S ribosome
# 5-HT3 antagonists
"tron" ie ondansetron, graniestron, dolasetron. They block vagus nerve mediated nausea AND block serotonin in the *chemoreceptor trigger zone*, thus they *prevent vomiting, especially in chemo patients!!!!!*
# What toxin inhibits RNA polymerases?
"α-amanitin found in Amanita phalloides (death cap mushrooms), inhibits RNA polymerase II. Causes severe hepatotoxicity if ingested.
# treat acute gout
"• For acute attacks, the goal of treatment is simply to reduce pain and inflammation: - NSAIDs (naproxen or indomethacin are most important!! ) - Colchicine - Glucocorticoids: If there is either no response or poor tolerance of NSAIDs and colchicine, give oral prednisone
# pyruvate kinase deficiency anemia
"• Pyruvate Kinase deficiency mutations of PKLR gene: autosomal recessive, leads to a NORMOCYTIC anemia Lack of Heinz bodies within RBCs on peripheral blood smear—vs. G6PD deficiency, a disease in which Heinz bodies are characteristic findings
# pyruvate kinase deficiency hemolysis
"• Pyruvate kinase is an ATP-producing enzyme in the glycolytic pathway. Since RBCs can only produce ATP via glycolysis, this deficiency severely effects the ability of RBCs to produce energy. Decreased ATP production in the RBC → altered membrane integrity → hemolysis This causes *splenic work hypertrophy* to remove defective erythrocytes. !!!!!!!
# Labs for Wilson Disease -
"↑ free copper, but decreased total copper. - Increase urinary free copper - decrease serum ceruloplasmin!!!!! - Increase copper on liver biopsy The total copper in the body is composed of bound and unbound fractions. ceruloplasmin accounts for most of The bound fraction. Because of *The decreased ceruloplasmin*, total copper levels decrease but free copper levels are increased."
Osteomalacia/ rickets labs
# defective mineralization with low vitamin D in adults. Weak bones, increased fracture (ep weight bearing areas, hip, vertebrae). Decreaed 25 (OH) vitamin D (aka calcidiol) Decreased serum Ca (vit D deficiency), serum phosphate (vit D deficiency and PTH increase)) Compensatory Increased PTH (b/c low calcium) and alkaline phosphatase. (!!!) Alkaline phosphatase is always elevated whenever there is activation of osteoblasts. Alkaline phosphatase creates alkaline environment for osteoblasts.... here they are active, but ineffective b/c of poor mineralization.
Cell CD identifiers
# B-cells have CD 19 and CD20 !!!!!!!!!!!!! T cells have CD-2 and CD3... Macrophages have CD14 !!!
Dopamine medications
# Dopamine agonists such as cabergoline (first line), bromocriptine, and Pergolide are used to treat prolactinomas!! Often, this medical management is sufficient treatment. If necessary, transsphenoidal resection is performed. Recall that some psychiatric meds act by decreasing dopamine levels. As such, they can cause ↑ prolactin release which ↓ gonadotropin release. This is in part why many psych meds have the side effects of reduced libido, amenorrhea and galactorrhea. Important ones to remember: Haloperidol (antipsychotic) Diazepam (aka Valium) (anxiolytic) Imipramine (TCA)
GTO vs muscle spindle
# Golgi tendon organ sensory recrptors arranged IN SERIES at the junction of muscle and tendon. They are INSENSITIVE to changes in muscle LENGTH, but they are involved in TENSION where they contact inhibitory interneurons in the spine to shut off alpha motor neurons. #Muscle spindles Arranged IN PARALLEL, and are sensitive to muscle LENGTH.
# • Hypovolemia and hypokalemia, both side effects of loop diuretics, can exacerbate a metabolic alkalosis.
# Hypovolemia (contraction alkalosis) can exacerbate a metabolic alkalosis by 2 mechanisms: • *Angiotensin II stimulates the Na+-H+ exchanger in the proximal tubule, thereby increasing HCO3- reabsorption.* • Aldosterone *stimulates H+ secretion* by the apical H+ ATPase of alpha intercalated cells in the collecting tubule. . # Hypokalemia can exacerbate a metabolic alkalosis by 2 mechanisms: • *Low serum K+ stimulates H+-K+ exchangers located on the surface of all cells. H+ ions move from the ECF to ICF to maintain electrical neutrality. *Sequestering of H+ ions within cells exacerbates a metabolic alkalosis. • Low serum K+ stimulates H+-K+ exchangers on the apical surface of alpha intercalated cells. Increased H+ secretion induces the production of new HCO3-, which is secreted to the blood via the basolateral HCO3--Cl- exchanger.
# Benzodiazepine toxicity and withdrawl
# Intoxication: minor respiratory depression, somnolence (sleepiness), slurred speech, ataxia, some amnesia, confusion. Falls are common in elderly, ESPECIALLY long acting ones. Withdrawal: sleep disturbance, depression, rebound anxiety Long acting benzos, high risk of severe drowsiness and falls Short acting benzos, high risk of physical dependence.
# Loop diuretic usage
# Loop diuretics are used for *high-volume diuresis*, such as in *pulmonary edema* or decreasing fluid overload in *heart failure*. Because of its short duration of activity, it is *not very useful for the treatment of hypertension*. Because of its calcium-wasting effect, it can be used to treat hypercalcemia.
cyanide poisoning signs
# Often from a fire, (or nitroprusside!!!!!) presents as: -rapidly developing flushing, dyspnea, dizziness, nausea, vomiting, tachycardia, and smell of 'bitter almonds" on breath (not seen in carbon monoxide).,
primary hemochromatosis
# Primary hemochromatosis- Hereditary condition where enterocyte loses ability to take up iron, whatever is taken up spills in blood, deposits in tissue as hemosiderosis, damages as hemochromatosis. Due to *Muation in HFE gene*. HFE protein NORMALLY controls expression of *proteins involved in iron absorption.*!!!!!!!!! Mutations in HFE cause *enterocytes and hepatocytes to FALSELY detect low iron levels*, so they respond by: 1) Enterocytes increase iron absorption by the lumen 2)Hepatocytes *decrease hepcinin synthesis*, which in turn leads to iron overload in circulation.
#methylxanthines (theophylline, aminophylline)
# Theophylline (!!!) *aminophylline* in intravenous form): Theophylline has 2 major mechanisms by which it causes bronchodilation: • Inhibition of phosphodiesterase (PDE), which increases levels of cAMP • Blockade of adenosine receptors (adenosine is a potent bronchoconstrictor, thus it causes bronchodilation). Theophylline Theophylline has a low therapeutic index, and can be quite toxic. Life threatening toxicities of theophylline include: • Seizures (!!!!!!!!!!) • Hypotension • Cardiac arrhythmias (!!!!!) Some of the other side effects that are not life threatening include: • Metabolic abnormalities (hypokalemia, metabolic acidosis, hyperglycemia) • Abdominal pain • Vomiting • Coarse muscle tremor
Vemurafenib
# a BRAF kinase inhibitor, may benefit patients with metastatic or unresectable melanoma exhibiting a BRAF V600E mutation.
# TNF-α inhibitors — Etanercept, Infliximab, Adalimumab.
# etanercept "cept" meant a "receptor molecule" etanercept is a TNF-a inhibitor added with Methotrexate in mod/severe RA in those that failed it respond to methotrexate alone. It is a FUSION PROTEIN that links a soluble TNF-a receptor toto the Fc component of human IgG1.... And it *thus reduces the activity of TNF-a by acting as a DECOY*!!!!! # infliximab A monoclonal antibody to TNF-a. Used in Crohn's, UC, RA, ankylosing spondylitis, psoriasis. It can cause infection, reactivation of TB!!!!
Hip flexors, extensors, abductors
# hip flexors Iliopsoas Rectus femoris TFL # hip extensors Gluteus maximus Hamstrings (Semitendinosus,Semimembranosus, Biceps femoris) # hip abductors Gluteus medius and minimus
visceral vs parietal pleura
# visceral pleura Covers ALL surfaces of the lungs # parietal pleura Covers remainder of the pleura which is NOT in contact with the lungs: divided into costal pleura mediastinal pleura diaphragmatic pleura cervical pleura Note: the mediastina/diaphragmatic pleurs allows sharp/localized pain by the *phrenic nerve* to the back of the neck/shoulder..... this is *worsened by inspiration*. The *cervical pleura* is sensory innervated by *intercostal nerves*.
repression vs supression
#Repression immature defense mechanism, *involuntary* withholding an idea or feeling from conscious awareness. Ie, not remembering a traumatic experience. Ie, child who was abused does not remember the event until seeing it happen to another child. #suppression- mature defense mechanism, involves intentionally postponing the exploration of anxiety-provoking thoughts by substituting other thoughts, thus delaying the coping. Ie, a women who focuses on her children's needs instead of thinking about her father's cancer diagnosis. Student who "doesn't worry" for 6 weeks after USMLE
class III
#class III anti-arrhythmics- Amiodarone, sotalol, dofetilide, ibutilide. !!!! block K+ channels..... and thus prolong repolarization. • Class III AAs increase the action potential (AP) duration and increase effective refractory period (ERP). • Class III AAs do not interfere with the function of the Na+ channel and thus do not affect conduction velocity. • By blocking K+ channels and slowing repolarization, Class III AAs result in slowed atrial-ventricular myocyte depolarization and the potential to *prolong the QT interval. !!!!!!!!!!! * (NO effect on QRS!*
treat malignant hyperthermia
#dantroline muscle relaxant, uncouples skeletal muscle excitation-contraction coupling by *binding to ryanodine receptor*, and *prevents the accumulation of intracellular calcium*. The ONLY specific/effective treatment for malignant hyperthermia.
anion gap vs non-anion gap metabolic acidosis
#metabolic acidosis and anion gap # causes of increased Anion gap acidosis MUDPILES Methanol, Metformin • Uremia - advanced, chronic renal failure • Diabetic ketoacidosis (β-hydroxybutyrate, acetoacetate) • Phenformin, Paraldehyde • Iron, Isoniazid • Lactic acidosis - from shock, hypoxia, exercise, poor tissue perfusion, enzyme deficicncies etc. • Ethanol, Ethylene glycol • Rhabdomyolysis • Salicylates - with concomitant respiratory alkalosis #Examples of normal anion gap acidosis include (FUSED CARS): • Fistula (small bowel, pancreatic) - loss of HCO3- • Ureterogastric conduits (i.e. urine-diverting colostomy) - loss of HCO3- • Saline administration - gain of Cl- • Endocrine (i.e. hyperparathyroidism - a cause of type 2 renal tubular acidosis, Addison's disease - aldosterone deficiency) • Diarrhea - loss of HCO3- • Carbonic anhydrase inhibitors (i.e. acetazolamide - most common cause of type 2 renal tubular acidosis in adults) - loss of HCO3- • Acid infusion (i.e. NH4Cl, hyperalimentation with total parenteral nutrition if arginine HCl or lysine HCl are used as amino acids) - gain of Cl- • Renal tubular acidosis • Spironolactone administration
#Turner syndrome
(45, XO females) is the most common cause of primary amenorrhea. • Hormonal testing would reveal increased FSH and LH due to decreased estrogen
#Klinefelter's syndrome overview and hormonal manifestations (!!)
(47, XXY males) is a sex chromosome disorder caused by meiotic non-disjunction. Buccal smear preps usually shows a Barr body (an inactivated X chromosome). Dysgenesis in the seminiferous tubules leads to Leydig cell damage Leydig cell damage leads to *decreased inhibin, which then allows increased FSH, LH, and aromatase* (!!!!) • Aromatase decreases testosterone by converting it to estradiol • Low sperm count • Decreased testosterone and increased estrogen ultimately cause feminization
# net filtration pressure
(Capillary hydrostatic pressure - Bowman hydrostatic pressure) *minus* (Capillary oncotic pressure -bowman oncotic pressure) > 0 = capillaries to interstitium <0 = interstitium to capillaries
#Glycogen storage deficiency 3
(Cori's): defective *α-1,6-glucosidase (glycogen debrancher enzyme)* → Presents with both liver and muscle involvement, there is -hypoglycemia - hepatomegaly - ketoacidosis - muscle weakness/hypotonia (not seen in Von Gierke) milder than Type I (von Gierke's), normal blood lactate levels Assumulation of glycogen, but the *molecules have shorter outer branches* → single glucose residue • Glycogenolysis is defective but gluconeogenesis is still functional.
filtration pressure
(Glomerular capillary hydrostatic pressure - bowman capsule hydrostatic) - (Glomerular capillary oncotic pressure - Bowman capsule oncotic pressure) If positive, there is net fluid from capillary into interstitium. If negative, there is net fluid from the interstitium into the capillary.
#glycogen storage deficiency 7
(Tarui's): defective muscle phosphofructokinase. Tarui's presents with: • exercise-induced muscle cramps and weakness • growth retardation
# Miliary tuberculosis
(aka "disseminated tuberculosis") is a form of tuberculosis that is characterized by a wide dissemination into the human body and by the tiny size of the lesions. Prognosis is poor with 100% fatality if not treated. Miliary tuberculosis is more common in HIV+ patients, but others with miliary tuberculosis have no recognizable high-risk factors.
# Carbonic anhydrase inhibitors
(e.g., acetazolamide) are diuretics that *act in the PCT* by inhibiting the reabsorption of filtered HCO3-. • In addition to its use as a weak diuretic, acetazolamide can also be used to: o alkalinize the urine (!!) o treat glaucoma (↓ secretion of aqueous humor → ↓ intraocular pressure) o treat metabolic alkalosis o treat altitude sickness
#Androgen Insensitivity
(formerly testicular feminization) is due to impaired androgen receptors. This impairment leads to underdevelopment of male genitalia in the male fetus, and under virilaization (biological development of sex differences, changes that make a male body different from a female body) of the male adolescent during puberty. • Androgen insensitive patients have a 46 XY karyotype.
# Anticholinergics in asthma (!!)
(ipratropium, tiotropoum) Blocks VAGAL mediated acetylcholine-induced bronchoconstriction !! Best used for maintenance and is more effective for COPD patients
# Non-selective MAOi's Side effects
(reason they are not used as first line agents): orthostatic hypotension, weight gain, sexual dysfunction, sleep dysfunction. - hypertensive crisis with β agonists and tyramine (cheeses, chicken liver, beer, and red wines) ingestion !!!!! • Hypertensive crisis: large amounts of stored catecholamines are released resulting in headaches, tachycardia, nausea, hypertension, cardiac arrhythmias, and stroke ... consider this if hypertensive crisis at social event like a wine and cheese
# Lack of Protein C or S
(these proteins NORMALLY inactivate factors V and VIII in clotting cascade (!!), which amplify clotting cascade.... so lack of proteins C and S mean *more amplification by factors V and VIII and thus a hypercoaguable state*.... note, risk for Warfarin skin necrosis (feared complication)
# Type 1 glycogen storage
(von Gierke's): deficient *glucose-6-phosphatase (liver, kidney)* → defective glycogenolysis and gluconeogenesis → *severe hypoglycemia* (seizures, hypoxic brain damage), increased lactate *• Hepatorenomegaly* - glycogen accumulates in liver and kidney because excess G-6-P stimulates glycogen synthesis and inhibits glycogenolysis .... Causes large abdomen • * Hyperlipidemia *→ skin xanthomas and ↑ VLDL • *Hyperuricemia -* ↓ free phosphate due to G6-Pase defect → ↑ AMP → AMP degraded to uric acid → ↑ uric acid → predisposes to gout • * Fasting lactic acidosis -* ↑ lactate → ↓ uric acid excretion by kidneys • *Ingestion of galactose or fructose → no increase in blood glucose* • *Administration of glucagon, epinephrine, or other gluconeogenic stimulus → no increase in blood glucose *
#GGT levels (!!)
(γ-glutamyl transpeptidase) is elevated in EtOH abuse • High concentrations in renal, prostatic, pancreatic, and hepatobiliary tissue → nonspecific • GGT is important for differentiating bone or the biliary system as the source of elevated ALP. (!!!!!!) Biliary disease results in elevated ALP and GGT while bone disease only results in elevated ALP.
# types of aortic dissection
) *Proximal* aortic dissections (*type A* dissections involve the *Ascending* aorta) are more common than 2) *distal* aortic dissections (type B dissections involve the descending aorta only). Also, proximal dissections are more dangerous.
#Kallman syndrome pathophys
* Failure of the olfactory bulb to develop* results in Kallmann Syndrome, which presents with both *bilateral anosmia as well as hypogonadism*, the latter being a consequence of the fact that Gonadotropin Releasing Hormone (GnRH) secreting neurons initially arise in the olfactory bulb before migrating to the medial preoptic nucleus of the hypothalamus. • Without GnRH neurons, the hypothalamus secretes decreased GnRH leading to decreased LH, FSH, and testosterone/estrogen (which accounts for hypogonadism). !!!!!!! Secondary sex characteristic are absent!!
#17 hydroxylase deficiency presentation
* Males will be born with ambiguous external genitalia and undescended testes .* Since female genitalia is the default pathway, *females will appear sexually normal at birth.* However, since androgens are essential to puberty, and they cannot synthesize androgens, both males and females will present with a *lack of secondary sexual development at puberty* Both males and females will have *Hypertension (from salt and water retention) and hypokalemia* are present in both sexes, from excess mineralcorticoids.
Hypogammaglobulinemia in nephrotic syndrome
* due to *loss of immunoglobulins in urine* → humoral immunodeficiency with *↑ susceptibility to infection*, especially staphylococcal and pneumococcal infections
# glucose 6 phosphate deficiency
*"X-linked recessive* disorder resulting in reduced half life(!!!) of G6PD !! Has BITE CELLS RBC's are normally exposed to oxidative stress, particularly H2O2, but they use glutathione to protect against oxidative stress by neutralizing H2O2, with gluatione becoming oxidized in the process. intravascular hemolysis → hemoglobinuria (dark urine), hemoglobinemia and jaundice (!!!!!) also BACK PAIN because hemoglobin is nephrotoxic, and these symptoms usually occur a few hours after oxidative stress.
#influenza vaccination
*A killed virus and attenuated intranasal vaccine* is available that is reformulated each year because of drifts. "the influenza vaccine is thought to prevent serious cases of the flu by *increasing host circulating IgA (mucosal) and IgG (circulation) antibodies against Hemagglutinin (HA)* of the selected viral strains. Upon exposure to the live influenza virus, these antibodies *interfere with the binding of HA to the sialic acid - containing oligosaccharides* of the host cell plasma membrane glycoprotein receptors." *Influenza vaccines are designed to impair viral entry into host cells via targeting of HA.*
# Acute non-erosive gastritis
*Acute nonerosive gastritis*: H pylori. Usually asymptomatic. Typically starts in antrum causing intense inflammation → over time may involve entire gastric mucosa → chronic gastritis Chronic H. pylori infection is assoc w/ ↑ risk of MALT lymphoma
# complications of dilated cardiomyopathy
*Biventricular* dilated cardiomyopathy leads to an inability to move fluids throughout the body accordingly and to maintain proper pressures, manifesting as *pleural effusions and edema*. Other Complications include *mitral* and *tricuspid* valve regurgitation... also arrhythmia. Also Dilatation of cardiac tissue disrupts the electrical conduction system, leading to left and/or right *bundle branch blockages*, and often presents as atrial and ventricular *arrhythmias*.
# Huntington's Disease
*Degeneration* of GABAergic neurons in the *caudate nucleus* (part of the *striatum*, along with *putamen*) of the *basal ganglia*. "Caudate loses Ach & Gaba" (CAG repeats) This "removes the inhibitory hold of the cortex" which leads to random firing called *chorea*. Note: the *caudate nucleus* is just below the *lateral ventricles*.... So losing of it causes the ventricles to dilate, called *hydrocephalus ex vacuo*.
# Prosthetic endocarditis bug
*Early* prosthetic valve endocarditis occurs *within 2 months* of the valve replacement and is most often caused by *Staphylococcus aureus* *Late* prosthetic valve endocarditis occurs *after 2 months* of the valve replacement and is usually caused by *Staphylococcus epidermis*,
# Acute erosive gastritis
*Erosive gastritis* : mucosal barrier disruption via ↓ prostaglandin synthesis. Note, the lesions are *multiple and shallow* and only involve the mucosa.
What dopamine agonist can be used in malignant HTN?
*Fenoldopam* is a DA1 (dopamine) receptor agonist that causes *arteriolar dilation and natriuesis*!!!!! and ALSO increases renal perfusion in addition to lowering BP. (!!!!!!!!!!!!!)
# folate absorption
*Folate is obtained via green vegetables, and fruits, absorbed in the jejunum (!!!!). The enzyme intestinal conjugase (which is inhibited by phenytoin) is required for absorption.
# Temporal aka Giant Cell Arteritis overview
*GRANULOMATOUS large vessel vasculitis* involving *superficial temporal* and *ophthalmic* arteries. (branches of carotid) Most common form of vasculitis in older adults, classically *over 50* and *females* Biopsy shows* inflammed tunica media* with Giant cells (granulomatous inflammation) with tunica intimal fibrosis. Note, lesions are segmental, so when you biopsy, you have to take a long piece because only a segment of it (not entire) has the vasculitis.... also just because it is negative does NOT rule out disease (you may have taken sample without the vasculitis segment)
# FAP is associated with what else?
*Gardner syndrome*- FAP + osteomas (benign tumor of bone) of the mandible and skull, as well as epidermal cysts and thyroid tumors. *Turcot syndrome*: FAP + CNS tumors (particularly medulloblastoma and glial tumors)
# 2nd most common colorectal cancer pathway
*HNPCC* (Lynch syndrome): MMR/microsatellite instability pathway Micosattellites are non-coding sequences of DNA, they are copied every time with DNA replication.... but if there is a *defect* with *mismatch repair (MMR)* genes *MLH1 and MSH2*, this leads to *microsatellite instability*, result in the accumulation of mutations in microsatellites, predisposing to carcinogenesis. Microsattellite= repeating sequence of bases (ie, CACACACA) This is a sign that other genes are unstable, and leads to risk of *Colorectal, ovarian and endometrial carcinoma. * These cancers usually arise *de novo* (not from a precursor adenoma) at relatively early age, and *usually* right sides (!!)
# Wiskott-Aldrich Syndrome
*Humoral immunodeficiency* (B and T cell) caused by an X-linked recessive defect in the WASP (Wiskott-Aldrich syndrome protein) gene. Big thing is decreased IgM!!! Classic triad—"TIE": 1. Profound Thrombocytopenia (<70,000 platelets/mm2)—may result in purpura and bleeding 2. Recurrent pyogenic Infections—eg, otitis media, pneumonia... because patients *cannot mount a humoral 3. Chronic Eczema (!!)
# igA Nephropathy aka (Berger's disease):
*IgA immune complex* is deposited in the *glomerular mesangium* - Most common cause of NEPHRITIC SYNDROME worldwide Characterized by painless *recurrent episodes* of hematuria, with *RBC casts* (if the glomerulus bleeds, they get casted* .... occurs in children that *occurs 1-3 days* after an infection of *mucosal tissue* (eg, genitourinary tract, gastrointestinal tract).
# Mallory Weiss syndrome
*LONGITUDINAL esophageal MUCOSAL tear* at *GE junction* caused by *severe vomiting* . Seen in Chronic alcoholics, bulimics (they vomit a lot)!!! (note: vomiting leads to metabolic alkalosis)! As vomit goes up, there is *high intra-abdominal pressure* which creates a tear of the mucosa. The tear leads to bleeding and *PAINFUL hematemesis* w/ associated pain. (esophageal varicies are painless)
# signs typical of mitochondrial diseases:
*Lactic acidosis* is due to decreased oxidative phosphorylation *even though plasma and tissue oxygen levels are normal. * • *Hypotonia and muscle disease* are due to decreased muscle ATP levels. o This often presents with *ragged red fibers* in muscle histological specimens. This is due to increased numbers of mitochondria, as well as other cellular changes, in muscle cells in an attempt to produce more ATP. o Ophthalmoplegia due to extraocular muscle damage. • CNS disorders such as seizures, cerebral palsy, movement disorders and neurological deterioration. • Dysphagia, sensorneural hearing loss, heart defects.
# what changes to heart 5-10 days
*Macrophages* then come in and phagocytose the dead cells Then 10-14 days, *granulation tissue and neovascularization* (!!!) Then eventually (2+ weeks), collagen deposition, fibrosis, scarring
#Meconium ileus:
*Meconium ileus is a complication in newborn cystic fibrosis where the meconium is thickened due to the lack of NaCl.* The thickened meconium obstructs mid-ileum, causing *proximal small bowel dilatation, bowel wall thickening, and congestions. * Meconium is *green fecal* matter. Presents with signs of small bowel obstruction: - bilious vomiting - abdominal distension - air fluid
# pseudomonas aeruginosa
*Nonlactose fermenting, oxidase-positive, motile, gram negative rod. Most common cause of malignant oritis externa in elderly diabetics!!! * Major Pseudomonas aeruginosa synthesizes *exotoxin A, which inhibits host protein production by ADP-ribosylation of EF2*.!!!!!! In addition, P. aeruginosa contains endotoxin from LPS. P. aeruginosa is an opportunistic pathogen that can cause infections that can be remembered with the mnemonic *PSEUDO MESH:* • Pneumonia (especially in Cystic Fibrosis and intubated patients)!!!!!!!!!! • Sepsis • External otitis • UTI • Diabetic/IV drug Osteomyelitis • Malignant otitis externa in diabetes • Ecthyma gangrenosum (rapidly progressive, necrotic cutaneous lesion) in immunocompromised patients • Skin infections in burn patients and those with extensive wounds • Hot tub folliculitis
# Polyarteritis Nodosa lesions
*Ongoing*/recurrent insults → lesions are of different ages. -early lesions are *transmural* lesions (whole wall inflammed) with *fibrinoid necrosis*. Lesion heals, and leads to fibrosis ("like" a *NODE* of fibrous tissue) Gives "string of pearls" appearance on imaging. Early lesion weakens wall and causes *aneurysms* ("string of pearls!!) Dx depends on imaging: arteriograms showing microaneurysms in small/medium arteries of abdominal organs
Rheumatic fever and heart
*Pancarditis* (inflammation of the entire heart) of rheumatic fever refers to endocarditis, myocarditis (leading to early death from heart failure), and pericarditis with pericardial effusions. Endocarditis: high pressure valves are most affected, forming tiny vegetations. Frequency of valves affected is *mitral > aortic >> tricuspid* Myocarditis: Note: Myocarditis is most common cause of acute RF death, !!! and myocarditis is characterized by *Aschoff bodies* with *Anitschkow cells*! There is also *pericarditis* which leads to a friction rub.
# Infantile Aortic Coarctation
*Pre*ductal coarctation: - so the narrowing of the aorta is *distal* to the *aortic arch*, but *proximal* to the *ligamentum arteriosum* (remnant of the ductus arteriosus). It is often associated with a PDA. Blood goes RA -> RV, to pulmonary trunk. Some of the blood goes through the ductus arteriosus. these infants typically develop *differential cyanosis*, with well perfused upper extremities and *cyanotic lower extremities*.!!! (diminished femoral pulses, leg cramps). Very associated with *Turner syndrome* !!!
# -Polyarteritis Nodosa
*Segmental TRANSMURAL necrotizing vasculitis* of *small and medium-sized muscular arteries* (does not involve arterioles, capillaries, or venules)... involves *most organs* (but *lung is spared*) !!! Destruction of arterial *media* and *internal elastic* lamina. *Ongoing*/recurrent insults → lesions are of different ages. Results in aneurysmal nodules, which may rupture Frequency of arterial involvement: - Kidney > Heart > Liver > GI
# Most common bug in infective endocarditis
*Streptococci viridans* are the most common cause of infective endocarditis. They are a large group of commensal (low-pathogenic) bacteria. !!!!! Can only infect previously damaged valves, and results in *small* vegetations which do not destroy valves. Streptococcus viridans is a large group of commensal (non-pathogenic) gram-positive bacteria: S. mutans causes dental caries; S. sanguinis is the most common cause of subacute endocarditis; S. mitis can also cause bacterial endocarditis. !!!!!!!!!!!!! Viridans make DEXTRANS (extracellular polysaccharides) from glucose BUT, in IV/drug users, *staph aures* is the most common. it *most often affects the tricuspid* valve (bacteria gets in through skin, hits blood, RA-> tricuspid). !!!!!!!!!! Unlike *Streptococci viridans* in *infective*... here, *staph aureus* can infect *NORMAL VALVES*... and can progress to *acute endocarditis* , which results in LARGE vegetations that *destroy* the valves
# Endocarditis in colorectal carcinoma (!!!)
*Streptococcus bovis* has been implicated in the development of colorectal cancer and subsequent endocarditis. ALWAYS do a colonoscopy if suspect Strep Bovie endocarditis!!!
# Initial phase of MI
*Subendocardial necrosis* is first (most distal from coronary artery) involving *less than 50%* of myocardial thickness. EKG shows *ST-depression* initally.... THEN it progresses to envolve transmural infarct, which gives ST-elevation. Q-waves indicative of an *old infarct*
# hyperparathyroidism bone changes
*Subperiosteal resorption and thinning of cortical bones, with cystic degeneration.* !!!!! It usually happens in the appendicular skeleton (pectoral girdle, pelvic girdle, limbs) Also happens in the medial side of 2nd and 3rd phalanges of the hand. -a granular "salt and pepper" appearance of the skull (!!!)
# Meckel's diverticulum
*True diverticulum* (so it contains ALL 3 layers, mucosa, submucosa, muscular layer) in the small bowel and is *connected to the ileum!!!* .....due to a persistent vitelline aka omphalomesenteric duct. Can be either: 1) completely persistent vitelline duct (passing meconium via umbilicus, called a *vitelline fistula*) 2) *partial closing* (which is Meckel's) . In Meckel's, the *patent portion is attached to the ileum*!!! Most common congenital GI anomaly (2% of population) - often found during first 2 years of life May contain *ectopic gastric or pancreatic tissue* (!!!!) (gastric is most common, also pancreatic, colonic, jejunal, even endometrial.... *intermittent rectal bleeding* (can be major) from the ectopic gastric tissue, periublinicul pain, ulcers Also assoc w/ intussusception/volvulus Technetium-99m scan diagnoses it!!!!!!!! A technetium-99m (99mTc) pertechnetate scan, also called Meckel scan, is the investigation of choice to diagnose Meckel's diverticula in children. This scan detects gastric mucosa; since approximately 50% of symptomatic Meckel's diverticula have ectopic gastric or pancreatic cells contained within them,[10] this is displayed as a spot on the scan distant from the stomach itself.
# Gross heart infarct
*appears pale red*, and starts to turn *yellow* (yellow because of the WBC's!!!!)
Crigler-Najjar syndrome!!!
*autosomal resessive*....near ABSENCE of UGT, cannot conjugate bilirubin, so massive increase of UCB Leads to kernicterus (bilirubin deposit in the brain).... usually fatal in a few years. !!
# what areas of the brain are deficient in Ach in alzheimers?
*basal nueleus of Meynert( which participates in memory and cognition) - hippocamps
calcium stones
*calcium sparing diuretics (thiazides)* since they decrease the excretion of calcium and therefore decrease the calcium concentration in the urine. potassium *citrate*, as *citrate binds to free calcium and prevents calcium stone precipitation*. !!!!!!!
# complications of sickling and hemolysis
*extravascular hemolysis* leads to anemia, jaundice, high UCB, high LDH, and *low haptoglobin* !!!! - Risk of Viral infection (esp. parvovirus B19) → aplastic crises with major ↓ in hemoglobin concentration
# Zenker's diverticulum
*false diverticulum* (mucosa, submiucosa only) in the esophagus.... It occurs SECONDARY to *cricopharyngeal dysfunction*!!! The subsequent esophageal dysmotility causing ↑ esophageal pressure and causes the diverticula through a defect in muscular wall. S/Sx: halitosis (food sticks in the diverticulum), dysphagia/obstruction (Sx of root cause) Cricopharyngeal disfunction is caused by *diminished relaxation of the pharyngeal muscles* during swallowing. It causes *high dysphasia* in the throat, with coughing/choking. FOOD ASPIRATION can occur and lead to PNEUMONIA.
# biliary sludge
*gallbladder hypomotility* due to *slow/incomplete gallbladder emptying in response to CCK*. It is made up of cholesterol crystals, calcium bilirubinate, mucus.... And is a *precursor to stones*. Causes include: - pregnancy Rapid weight loss Prolonged use of total parenternal nutrition Spinal cord injuries
# Fungal meningitis findings.
*lymphocytes* because they *fight the fungi*. Glucose is VERY LOW because the fungi consumes the glucose!!
# Hyperplastic arterio*lo*sclerosis
*malignant HTN!!! leads to hyperplasia of smooth muscle which gives *"onion skinning"* of the walls of small arteries and arterioles, associated with fibrinoid deposition and vessel wall necrosis
Medulloblastoma:
*malignant tumor* which is derived from *neuro-ectodermal tissue*... specifically the *granular cells of cerebellum*!!!! It is ALWAYS in the cerebellum, usually the Vermis!! 2nd most common brain tumor, and *most common MALIGNANT BRAIN tumor in children !!!!!!! * Histology reveals sheets of PRIMITIVE CELLS with MANY MITOTIC FIGURES....... "small, round-blue cells* with *scant cytoplasm* , and *Homer-Wright rosettes* may be present!! (Homer-Wright rosettes are when the small round-blue cells wrap around the pink area of *neuritic processes*... form a "rosette" around the neuritic process) Has a poor prognosis because the tumor grows rapidly, it can then enter 4th ventricular space and *cause hydrocephalus*.... and via the CSF it can drop down to the spinal cord, known as a *drop metastasis* !!!
# Ependymoma
*malignant* tumor of the *ependymal cells* which *line the ventricular space* usually seen in children, which means it is *beneath the tentorium*, and the location is in the *4th ventricle*. As it grows out into the ventricular space, it *blocks the flow of CSF* and can thus present with *hydrocephalus* !!!! *Perivascular pseudo-rosettes* are found on histology where a ventral blood vessel is surrounded by the tumor cells, with 'pink material' in.
carcinoid tumor
*malignant*, low grade, Neuroendocrine tumor, most commonly in the *small bowel* where it grows as a submucosal polyp-like nodule, encroaching into lumen of small bowel. Tests positive for *chromogranin* !! (b/c it is a neuroendocrine tumor) Produce 5HT (serotonin) into *portal vein*, but *asymptomatic* unless 5HT gets beyond liver's *first-pass metabolism* where it is broken down by MAO... BUT we do have increased urinary secretion of *5 HIAA* (5 hydroxyindoleacetic acid) a degradation product of *serotonin*. !!!!! This happens UNLESS the primary location is an extra-intestinal site, such as the lung.
# Aortic stenosis murmur
*mid systolic* ejection "click" followed by a *crescendo-decrescendo murmur*... it *radiating to the carotids*. Heard loudest at *second intercostal space at the right sternal border*
# Nephrotic syndrome—Membranous nephropathy (membranous glomerulopathy)
*most common nephrotic syndrome* in *Caucasion adults* (!!!!) Pathophysiology: - *Immune complexes deposit* on the *glomerular epithelial basement membrane* , so they are *subepithelial*.... which causes *thick glomorular basement membrane* on H & E. !!!!!!!!!
Aortic stenosis overview
*narrowing* of aortic valve orifice. 1) increased risk with congenital *bicuspid* aortic value (because most people normally have 3 cusps for aortic valve). 2) fibrosis and calcification from "wear and tear". Triad of SAD symptoms: - Syncope (↓ blood flow to brain) - Angina (↓ blood flow through coronary arteries in diastole), -Dyspnea (especially exertional!!) There is a decrease in left ventricular preload!!!!!!! (decreased CO, also pulmonary congestion)
Kawasaki Disease
*necrotizing medium-sized vessel* vasculitis involving *coronary arteries* (!!!) Kawasaki disease most often occurs in *children under the age of 5* (especially *Asian* children), and is more common in *boys* than in girls. Kawasaki disease is the leading cause of acquired heart disease in children in developed countries!!! Common physical findings in Kawasaki disease include very vague symptoms: - fever - conjunctival injection - erythema and edema of hands and feet !!! - desquamated rash !!! - cervical lymphadenopathy (!!) - oral erythema - cracked lips !!! - strawberry-appearing tongue (glossitis). !!!! Because it involves *coronary arteries*, cardiovascular symptoms of Kawasaki disease include - Thrombosis with myocardial infarction (yes, in a 4 year old) !!! - an abnormal ECG - ventricular aneurysm with rupture (due to weakening of wall) !!!!
# gout crystals
*needle shaped crystals* which have *negative birefringence under polarized light* !!!! (this means that when crystals lay flat, they are yellow! Think "lay low = yellow".... Crystals are also yellow under parallel light (yeLLow under paraLLel....blue perpendicular).
# Mitral stenosis murmur
*opening snap followed by an early mid-DIASTOLIC, low pitched rumbling.* Best heart at mitral area. *The best indicator of the SEVERITY is the length of time between S2 and the opening snap!!!!* As MS worsens, LA pressures increase due to impaired blood movement. The *MORE severe MS is, the SHORTER the gap between S2 and the opening snap. *
# urge incontinence
*overactivity of the detrusor muscle* resulting in the frequent production of small volumes of urine. Urge incontinence is treated with *MUSCARINIC anticholinergics*, which act to *reduce parasympathetic stimulation of detrusor muscle contraction. * MS patients are at risk for URGE incontinence because the *CNS cannot inhibit the detrusor (thus there is detrusor overactivity* and uninhibited bladder contraction).
# Multiple myeloma
*plasma cell neoplasm* which is characterized by diffuse involvement of the skeleton. It is the most common PRIMARY malignancy of bone (most common malignancy to involve bone is actually metastatic carcinoma). Serum IL-6 often elevated which drives production of plasma cells, and also drives production of OAF (IL-1)!!!!!!!!!!!!! Because MM originates in the bone marrow, it is essentially a leukemia. However, unlike other leukemias, myeloma cells are B cells that have undergone somatic hypermutation to become plasma cells.
mesothelioma histology
*pleural thickening* is the most important by far. *electrom microscopy* shows cells with numerous, long, slender microvilli and abundant tonofilaments.!!!!!!!!
# nsaid's and renal failure
*preglomerular resistance INCREASES with NSAID's* because prostaglandins are vasodilators. In patients with states of volume depletion (heart failure, cirrhosis), there is an INCREASED secretion of vasoconstrictors, angiotensin II, norepinephrine. Thus, in these cases, prostaglandins are essential to maintain renal blood flow and counteract vasoconstrictive effects *at the afferent arteriole.* therefore, in volume depleted patients, NSAID's cause renal flow and thus, GFR to DECREASE, causing ischemia and acute renal failure.
# Mitral Valve prolapse
*prolapse* of the mitral valve into the *left atrium* during *systole*, and results from excess mitral valve leaflet tissue or myxomatous degeneration of the valve or the chordae tendineae. Etiology not fully known, but it is associated with genetic disorders: Marfan's syndrome, Ehlers-Danlos syndrome, and autosomal dominant polycystic kidney disease. !!!
seconadary TB
*secondary*(!!!) TB arises with *reactivation* of TB, commonly due to *AIDS* or *aging*.... , an *apical cavitary lesion* occurs at *apex* of lung (oxygen tension highest) (!!!!) Can lead to *miliary TB* or *tuberculous bronchopneumonia*
# Viral meningitis findings *!!!)
*very high lymphocytes* because they *fight the virus*. Normal CSF glucose because the virus does NOT consume glucose like bacteria/fungi does moderately raised protein levels
If a screening test is positive in 250 of 1000 affected patients..... and positive in 100 of 1000 healthy controls. .....How many false positives would be expected in a population of 100,000, with disease prevalence of 10%??
+ - + 250 100 - 750 900 Sensitivity= 250/1000= 0.25 Specificity= 900/1000= 0.9 Disease prevalence= 10% , this means that 10,000 people have the disease 90,000 do NOT have disease Sensitivity = 25%, so 25% will be diagnosed correctly..... so TP = 250 Specifity= 90%... so there are 90,000 x 0.9 TN's = 81,000 + - + 250 - 81,000 Next, fill in the rest. + - + 2,500 9,000 - 7,500 81,000
# lead poisoning other findings/presentation
- "bluish pigmentation" aka Lead lines (Burton lines) on the metaphyses of long bones on Xray. .... - rRNA degradation is inhibited so RBC's retain aggregates of rRNA (basophilic stippling).... - Wrist/foot drop (peripheral neuropathy) - encephalopathy - abdominal colic. (concentration, headaches, constipation)
# Excess corticosteroids and Cushing syndrome
- #1 cause, leads to bilateral adrenal atrophy of the *Zona Fasiculata and Reticularis* due to negative feedback by steroids shutting down ACTH
Potter deformity
- *Facial deformities*: Potter facies—flattened "parrot beak" nose, low-set ears, micrognathia (recessed chin) - Limb deformities: rocker-bottom feet, club feet (talipes equinovarus)
# von Hippel Lindau syndrome:
- *autosomal dominant* disease associated with deletions in VHL gene on chromosome 3p... the VHL gene is a tumor suppressor, so this results in over activation of HIF (transcription factor) patients often develop - RCC, especially multifocal and/or bilateral RCCs !!! (may lead to increased EPO production) - cavernous hemangiomas in skin, mucosa, organs Also increased risk for *hemangioblastoma* of the *cerebellum*!! - Also *retinal angioma*, and *bilateral pheochromocytoma*
# Sarcoiditis eye
- Anterior uveitis
Ulcerative colitis
- Autoimmune etiology - Mucosal/submucosal inflammation - *Rectum/colon* (starts in rectum and moved up to *cecum* at furthest) - "lead pipe" appearance - SMOKING decreases risk - Crypt abscesses (!!!!) (neutrophils in cypts!!) !!!!!!!!! - ulcers, bleeding/bloody diarrhea, NO granulomas (Th2 mediated!!!!) - psudopolyps - risk for colorectal cancer !!!! (risk is based on *duration of disease* and *extent of involvement*) - Toxic Megacolon risk (could rupture)!!!!! Diagnose this with Xray !!!! - LEFT lower quadrant pain
# complications of gallstones
- Biliary Colic- -Acute cholecystitis- - Chronic cholecystitis - Ascending cholangitis - Gallstone ileus - Gallbladder cancer
# Familial PAH:
- Caused by an *inactivating mutation* in the *BMPR2 gene* (!!!) which normally functions to inhibit vascular smooth muscle proliferation (thus, we get smooth muscle proliferation)!!! The gene mutation predisposes to disease. A second insult (infection, drugs, ion channel defect) then *activates the disease process* which - increases endothelin (vasoconstrictor) !!!!! - decreases Nitroic oxide (vasodilator) - decreasing prostacyclin end result is : vasoconstriction smooth muscle proliferation thrombosis of pulmonary arteries/arterioles endothelial ccell growth
# Primary sclerosing cholangitis complications
- Cirrhosis (late complication) - increase risk for cholangiocarcinoma (cancer of bile ducts), and/or pancreatic and colorectal carcinomas. Diagnose with Endoscopic retrograde cholangiopancreatography (ERCP)
# Nitroprussive side effects and contraindications
- Cyanide toxicity can occur with prolonged use because the CN − groups can detach as well. (!!!) As with any drug mentioned that *decreases afterload*, reflex *tachycardia* can occur as the baroreceptors sense decreased blood pressure and enact compensatory changes.
# Histrionic cluster B:
- Excessively extroverted and emotional, dramatic - Sexually provocative and attention seeking behavior - Overly concerned with appearance - Inability to maintain intimate relationships
#GIP Stimuli for secretion
- Fatty acids in the lumen of the small intestine - Amino acids in the lumen of the small intestine - Oral glucose in the lumen of the small intestine Clinical Correlate Oral glucose is more effective than intravenous glucose in causing insulin release → improved glucose utilization.
# Minor Jones criteria:
- Fever - Arthralgia (however, arthralgia cannot be used as a minor criteria if polyarthritis is counted as a major criteria) - ↑ serum levels of acute phase reactants (eg, CRP, ESR)
# Narcissistic cluster B:
- Grandiosity - Envy - Sense of entitlement - Lack of empathy, but requests excessive admiration - May react to criticism with rage - May demand "top" physician, best health care
# Secretin Stimuli for secretion:
- H+ in duodenal lumen - Fatty acids in duodenal lumen
#somatostatin Stimuli for secretion:
- H+ in the GI lumen. #somatostatin effects inhibits GH (growth hormone) and TSH (thyroid stimulating hormone) secretion. Inhibits BOTH insulin and glucagon inhibits gastrin, gastric acid AND cck (slows gastric emptyting) inhibits pancreatic juice secretions
neurofibromatosis 1 aka Von Recklinghausen's disease
- Have 6+ cafe-au-lait spots (!!) (brown birth marks) - cutaneous neurofibromas - note, neurofibromas's are made of SCHWANN cells. - axillary freckling (Crowe;s sign) - Lisch nodules in the iris!! (pigmented iris hamartomas).... Along with CNS tumors such as optic gliomas and astrocytomas.
HbA1c diabetes
- HbA1c ≥ 6.5% is now part of the diagnostic criteria.
# atherosclerosis complications
- Hypertension (renal artery atherosclerosis may activate the renin-angiotensin-aldosterone system) - Aneurysms (weakening of vessel wall) - Ischemia from narrowing of medium size vessel (symptoms appear after *70% stenosis!!!!*) — e.g., peripheral vascular disease (popliteal) - ischemic heart disease (coronary artery) - ischemic bowel disease (i.e., mesenteric artery ischemia) (!!!!!) Thrombosis — - MI (coronary artery) - stroke (Middle cerebral artery) - small bowel infarction
# Diagnose celiac
- IgA or IgG antibodies to deamidated gliadin. - Antiendomysial IgA antibodies - Celiac patients are more likely to be IgA deficient, so important to test for IgG
ACE inhibitor side effects !!!
- Impaired bradykinin metabolism by ACE → ↑ bradykinin levels → dry cough AND angioedema (!!!) The angioedema often involves the tongue/lips/eyelids!!!! Can cause problems breathing!! - ↓ Angiotensin II → ↓ aldosterone release → hyperkalemia !!! - ↓ Angiotensin II → less constriction of efferent arterioles → ↓ GFR → up to 30% ↑ in serum Creatinine is expected in most patients within 2-5 days of initiating ACE inhibitor therapy. - Taste disturbance (metallic taste) - Rash - Headache, fatigue, nausea - Hypotension
# Antisocial cluster B:
- Inability to conform to social norms - Criminality - Disregard for and violation of rights of others - Considered conduct disorder if the patient is < 18 years old
# Spongiform encephalopathy etiologies
- Inherited a bad gene which results in *increased conversion* of alpha to beta form... - transmitted: if somehow you are "infected" (!!!) with a beta prion protein, it will go back and convert all the others
sarcoidosis in lung
- Interstitial inflammation → fibrosis → restrictive lung disease → patients often present with progressive dyspnea and chronic nonproductive cough, with dry patchy rales (crackles) on exam - Chest x-ray: diffuse interstitial infiltrates, often with bilateral hilar adenopathy (hilar lymph nodes may get so big that they're sometimes called "potato nodes") (!!!!!!)
# Dependent Cluster C personality disorder:
- Lack of self-confidence - Lets others assume responsibility
# Schizoid cluster A:
- Lifelong pattern of voluntary social withdrawal, very distant. (Schiz out!!!!) - Limited emotional expression, content with social isolation, no close relationships, no intimacy!!! - Unlike avoidant personality disorder, schizoid IS happy/content with social isolation, they do NOT desire to be social. -There is NO psychosis
Follicular carcinoma thyroid
- More common in females, and patients age 40-60. RAS mutations often seen! FNA unfortunately cannot distinguish between follicular adenoma and carcinoma. Need to see capsule (carcinoma goes beyond the capsule!!!!!), so need to see gross specimin, or examine capsule under microscope to ensure no extension beyond capsule. - Propensity for hematogenous (blood) spread, (!!!) thus can present with distant metastasis (liver, bone, lungs). - Generally good prognosis.
Minimal change disease
- Most common cause *nephrotic syndrome in children*. (think that nephrotic happens in "minimal people"), often with a recent history of a respiratory infection or routine immunization. - usually idiopathic, but may be associated with Hodgkin lymphoma (!!!!) Normally, glomerular filtration layer contains 1) *endothelial cells* which sit on top of a 2) *basement mebrane* , upon which sits the 3) *foot processes of podocytes* which are *epothelial cells* In minimal-change disease, you have flattening aka *effacement of the Podocyte foot processes* (!!!!!!!!!!!!!) via production of *T-cells and cytokines. podocytes and podocyte foot processes *lose their negative charge*, so we get *"highly selective" proteinuria with hypoalbuminemia*!!!! —ie, most of the protein lost in urine is *albumin*, which has a *low molecular weight* and *abundant negative charge*, so it is *easily filtered* by a damaged charge barrier that has lost a significant amount of its native negative charge) We do NOT lose immunoglobulin
#What types of Glaucoma are there
- Open(wide) angle glaucoma - closed angle glaucoma - congenital glaucoma
# Obsessive compulsive cluster C personality disorder:
- Orderly, stubborn, perfectionist - Misnomer because there are no obsessions nor compulsions - Preoccupation with control - Ego-syntonic, unlike OCD patients that are ego-dystonic
# Papillary carcinoma thyroid
- Papillary Carcinoma: > 80% of thyroid cancer cases - Common in women, particularly in their 20s or 30s, especially those who have been exposed to ionizing radiation in childhood (ie, radiation for severe acne). !!!!!!!!!!!!
# Kidneys in Henoch- Schonlein Purpura
- Renal (!!): IgA immune complex is deposited in the kidney mesangium (called *IgA nephropathy*):
# right sided varicoceles
- Retroperitoneal fibrosis or IVC thrombosis can cause right-sided varicocele - Right sided varicoceles warrant work up for a right sided retroperitoneal mass
# pancost tumor aka superior sulcus tumor causes
- Severe pain in shoulder region, radiating to axilla/scapula (due to involvement of lower brachial plesus). - Arm paresthesia, weakness, muscle atrophy. - Horner syndrome (involvement of cervical sympathetic ganglia) - extension of tubor into intervertebral foramina causing spinal cord compression/paraplegia. - SVC syndrome - hoarseness
# Avoidant cluster C:
- Shy, sensitive to rejection, socially withdrawn - Feelings of inadequacy, inferiority complex - Desires relationship with others (vs. schizoid which does NOT) , but they fear rejection. They often participate only in situations they will be liked.
# clinical findings of TTP & HUS
- Skin and mucosal bleeding (in both cases, platelet microthrombi form using them up) - microangiopathic hemolytic anemia (shearing of RBCs → schistocytes, anemia) - fever - renal insufficiency (more commonly HUS- kids!! ) - CNS abnormalities (more commonly TTP- adults!!)!!!!
# Paranoid cluser A :
- Suspicious, mistrustful, litigious - Attributes responsibility for problems to others - Projection is the main defense mechanism
# Borderline cluster B personality disorder:
- Unstable mood, behavior and interpersonal relationships - Suicide attempts, self mutilation - Boredom, emptiness, and loneliness - Impulsiveness, very violent - Splitting is the major defense mechanism used - Best treatment is dialectical behavior therapy (DBT) 3x more often in women than men
# HCV and carrier
- Up to 85% of adults can be chronic carrier - Virus mutates a lot. RNA virus, so RNA polymerase has no proofreading, leads to variable genome.
# Normal pressure Hydrocephalus
- Usually occurs in OLDER adults. Can cause dementia in adults, it is *usually idiopathic* NPH is characterized by normal intracranial pressures......Due to *a gradual increase in CSF* which then *dilates the ventricles*.... thus stretching of the *corona radiata* !!!! which are the *nerve fibers running along the edge of the ventricles*.... Stretching of these results in a *triad* of: "wet, wacky, wobbly" - urinary incontinence "wet"., this occurs because of the *stretching of the corona radiata* leads to DISRUPTION of the signal from cortex to the micturition center. - gait instability "wobbly" - dementia "whacky"!!!!!! Because this is due to increased CSF, it: -improves with a LP CT shows symmetrical enlargement of the ventricles!!!
# Congenital heart left-to-right shunts
- Ventricular septal defect (VSD) - Atrial septal defect (ASD) - Patent ductus arteriosus (PDA)
#kinds of small vessel vasculitis
- Wegener Granulomatosis - Microscopic Polyangitis - Churg-Strauss Syndrome - Henoch-Schonlein Purpura
# Treat BPH
- a1 antagonist *terazosin* (or *doxazosin*) to relax smooth muscle of prostate, but this ALSO benefits hypertensive patients by systemic vaso relaxation -If patient is normotensive, give a *selective* a-1A antagonist (*tamsulosin*) to avoid the *a-1B effects on smooth muscle 5-AR inhibitor, takes months for results. Avoid caffeine
# Juxtaglomerula apparatus
- consists of JG cells (which are moderate smooth muscle in the AFFERENT arteriole, and release renin in response to decreased BP/GFR at afferent arteriole). i. decreased blood pressure in the afferent arteriole (!!!) ii. decreased Na+ delivery (to the macula densa!!!) in the distal convoluted tubule iii. increased sympathetic stimulation (Beta-1 receptors) Renin convertes angiotensinogen to angiotensin I Angiotensin I to angiotensin II by ACE
# Diffuse systemic sclerosis:
- diffuse sclerosis of skin at onset Almost any organ can be involved, but *Esophagus is often involved*. Resulting in disordered motility (dysphagia for solids and liquids). If there is fibrosis of esophagus, there is no peristalsis of esophagus. - early visceral (organ) involvement → rapid, malignant course with death secondary to *respiratory failure (most common cause of death)*, kidney failure (*scleroderma renal crisis*), heart failure. Most common initial finding in systemic sclerosis is Raynaud's phenomenon secondary to digital vasculitis.
vitamin D
- increases intestinal absorption of calcium and phosphorous - increases renal absorption of calcium Endogenous vitamin D is produced by *photoconversion of 7-dehydrocholesterol to cholecalciferol AKA vitamin D3* in sun-exposed skin (most important source) in the stratum basale !!! Next, vitamin D is hydroxylated in the liver to produce calcidiol (25-hydroxycholecalciferol) by the P450 system • Calcidiol is then hydroxylated to the active form, calcitriol (1,25-dihydroxycholecalciferol) in the kidneys by the enzyme 1-α-hydroxylase
# Polycythemia vera S/Sx
- itching and peptic ulcer after bathing !!!!! (also have extra mast cells which are loaded with histamine, bathing sets off mast cells !!!! ) blood gets loaded with RBCs, becomes hyperviscious. - Splenomegaly !!!! - Burning pain in the hands due to micro thrombi occlusion of vessels. Also seen in essential thrombocythemia. - Blurry vision, headache, stroke, TIA - increased risk of venous thrombosis (this is the MOST common cause of Budd Chiari syndrome!!!) - flushed face (plethoric) due to congestion - Gout: Due to increased cell turnover with release of nucleic acids.
# gonad (testicle, ovary) venous drainage
- left ovary/testes into left gonadal (spermatic/ovarian) vein, then left renal vein, then IVC - right ovary/testes into the right gonadal vein, then IVC
# Limited systemic sclerosis: (CREST)!!!
- limited sclerosis of skin at onset (fingers, forearm, face) - late or no visceral involvement → relatively benign course A subset of patients with limited systemic sclerosis develop CREST syndrome: Calcinosis: dystrophic calcification of subcutaneous tissue (nodules) OR antiCentromere antibody in 90% of patients Raynaud's phenomenon secondary to digital vasculitis. Raynaud's is caused by cutaneous vasospasm ( Esophageal dysmotility: ↓ peristalsis AND ↓ lower esophageal sphincter tone (!!!) due to *fibrous replacement of esophageal muscle* → acid reflux and dysphagia for solids and liquids!!!! → ↑ risk of Barrett esophagus and subsequent esophageal adenocarcinoma!!!!!! Sclerodactyly: hard/swollen/tight-appearing skin usually on the dorsa of fingers/toes Telangiectasia: punctate small blood vessel dilations
# Coagulative necrosis
- most common form of necrosis !!!! often caused by interruption of blood supply → *tissue ischemia* → intracellular accumulation of lactic acid → denaturation of structural proteins FIRST, and THEN denaturation of intracellular enzymes Necrotic tissue that remains firm, cellular proteins coagulate so that *cell shape and structure are preserved*. "Tissue dies, but *general structure of tissue remains, cells and their architcture are present*, but *NUCLEI DISAPPEAR"*!!!!!!!! Seen with ischemia in ANY organ except brain. Occurs most commonly in organs supplied by end arteries with limited collateral circulation such as heart, kidney, and spleen Area of *infarcted tissue* often kinda *WEDGE SHAPED and PALE*. Usually when a vessel goes into tissue it branches in two... if you stop blood, everything around it dies (wedge shaped). Wedge POINTS to area of occlusion. Can get "Red infarction" if blood re-enters tissue, and tissue is loosely organizes (ie, pulmonary or testicular infarcts).
# Primary sclerosing cholangitis test findings
- periductal fibrosis with 'onion skin' appearance - "string of pearls" with fibrosis pearls, and 'dilation' string in ducts seen on endoscopic retrograde cholangiopancreatography (ERCP), the gold standard for PSC. In PSC, bile ducts become infiltrated with lymphocytes, which results in chronic inflammation and eventually leads to ductal destruction. This continued destruction leads to fibrosis and results in constriction of bile ducts. Laboratory values of PSC will suggest a cholestatic pattern: conjugated bilirubin >50%, bilirubinuria, absent urobilinogen,* increased alkaline phosphatase and gamma-glutamyl transferase (GGT).* !!!!
# Thyroid hormone synthesis
- phenylalanine is converted into tyrosine (!!!) - *thyroglobin* pushed into follicular lumen - Cell takes iodide (I-) , brings in cell (via Na/I transporter), when *stimulated by TSH*!!!.... it then pushes Iodide (I-) into follicular lumen where it is oxidized to I2 (iodine) via *thyroid peroxidase * (!!!!!!) - *tyrosine* on Thyroglobin added to I2 (iodine) (step called organification) results in Thyroglobin with monoiodotyrosine (MIT) and diiodotyrosine (DIT) Produces t3 when mono+di... and t4 when di+di thyroglobulin is stored in the follicular lumen. Upon stimulation by TSH, follicular cells endocytoses thyroglobulin and lysosomal enzymes digest thyroglobulin, releasing T3 and T4 into the circulation.
# *Liver angiosarcomas* are associated with exposure to either
- polyvinyl chloride (PVC) (a plastic widely used in many industries!!) - arsenic (found in cigarette smoke!!!) - thorium dioxide, which is the primary ingredient in the X-ray contrast medium Thorotrast. It expresses CD31 !!! (endothelial cell marker)
DNA pol I:
- proofreading: 3'-5' exonuclease activity - DNA repair: 5'-3' polymerase activity - RNA primase removal: 5'-3' exonuclease activity (only one that has 5-e exonuclease!!!!!!!!!) !! It *removes the RNA primer* used by DNA Polymerase III< as part of *DNA repair*.
# *unstable atherosclerotic plaque*
- thin fibrous cap - rich lipid core - active inflammation (!!!) - High levels of activated macrophages/which secrete high levels of metaoproteinases which *degrade collagen* !!!!!! thus LOW levels of collagen !
Treat cyanide poisoning
- use *sodium thiosulfate/ * to chelate this CN- by *giving sulfur groups!!!* and *yield thiocyanate* which is renally excreted
# Summary of Labs in Anemia of Chronic Disease:
- ↑ Ferritin (iron stores normal/elevated) - ↑ FEP - ↓ MCV - ↓ Serum Iron, - ↓ % Saturation of Transferrin - ↓ TIBC
DNA pol II:
-"when DNA Pol III reaches the ""prior"" RNA primer on the lagging strand, this enzyme degrades the primer and fills in appropriate DNA nucleotides - DNA ligase then closes any remaining breaks in the new strand DNA repair: 5'-3' polymerase activity
# labs in folate and b12 deficiency
--↑ serum homocysteine (B12 deficiency and Folate deficiency) !!!!! - ↑ serum methylmalonic acid aka MMA in B12 only, methylmalonic acid is normal in folate deficiency!!) !!!!!!!!!!!!! In B12, "Neurological symptoms are due to failure of Methylmalonyl CoA → Succinyl CoA.
hydrocephalus
-ANY increase in CSF, leading to compression of surrounding CNS tissue. • The expansion of the CSF compartment often leads to the radiographic finding of enlarged ventricles. There are 2 main classifications of hydrocephalus: communicating and non-communicating
# SLE labs
-Anti-neutrophil antibody (ANA) is sensitive (not specific) for screening.... Anti- dsDNA antibody and anti-Sm (Smith) are very specific!! Note: Anti-dsDNA antibody is associated with disease activity, and renal nephritis (!!!) so if titers are high, it predicts poor prognosis. - anticardiolipin antibody, which gives a false positive test for syphilius (on VDRL and RPR tests). Cardiolipin is found in mammal inner mitochondrial membrane. These tests look for anti-cardiolipin antibodies. - Another antibody is *lupus-anticoagulant*... this gives falsely-elevated PTT because it interferes with lipids used in PTT test. Note, these patients with lupus anticoagulant can also develop *antiphospholipid antibody syndrome*!!!!
# Primary Biliary cirrhosis
-Autoimmune *granulomatous destruction of inrahepatic bile ducts*!!!!.....CD8 LYMPHOCYTE mediated. - Also destruction of the portal tracts. - causes an *insidious form of hepatic cirrhosis*. - Unknown etiology but there is an *anti-mitochondrial antibody present in serum*!!!
Huntington's disease presentation
-Chorea - progression to dementia/depression!!! - mood disturbances (!!) like aggressiveness, flat effect, changed personality (!!) - suicide common cause of death - - Athetoid movements (hallmark of basal ganglia insult) = slow writhing hand movements
# Chronic pancreatitis clinical features (!!!)
-Epigastric abdominal pain radiates to back (can be 'attacks', or constant). - Pancreatic insufficiency (enzyme deficiency leading to *malabsorption* with steatorrhea , fat soluble vitamin deficiencies) Amylase and lipase are NOT helpful because pancreatic enzyme secretion decreases with damaged pancreas. - dystrophic calcification of pancreas, increased risk for pancreatic carcinoma - extensive damage can cause secondary diabetes mellitus - stools that float (fatty)
chronic pancreatitis histology
-Extensive fibrosis/destruction, *loss of acinar cells*. • Pancreatic ducts are frequently dilated and contain protein plugs. • A chronic inflammatory infiltrate consisting of mononuclear macrophages and lymphocytes is usually seen around the ducts and lobules. • The islets of Langerhans become embedded in fibrotic tissue and may fuse. Over time, the islets are destroyed as well → endocrine symptoms. • Imaging often reveals calcium deposition (dystrophic calcification) in the pancreatic parenchyma.
# Clinical features of endocarditis (!!!)
-Fever is most common, also chills, fatigue, and rigors relating to the bacteremia. -Heart murmur may be present, also *septic emboli* (!!!) may occur where pieces of the valve break off and contain bacteria. These septic emboli can cause: (!!!) - Janeway Lesions - Osler nodes Also, septic emboli can cause *splinter hemorrhage* in nails... and overall the patient can develop *anemia of chronic disease*
# Primary sclerosing cholangitis overview and presentation
-Inflammation/fibrosis/destruction of BOTH intrahepatic/extrahepatic bile ducts - Eitology is unknown, but it is likely autoimmune, since it is associated with ulcerative colitis, p-ANCA often positive (also seen in UC!!!! ). Patient presents same as primary and secondary biliary cirrhosis (obstructive jaundice, pruitis, hepatosplenomegaly)
# Vitamin D deficiency
-Lack of sun exposure - poor diet - malabsorption - liver 25-hydroxylation impairment (converts vitamin D into 25-hydroxyvitamin D (calcidiol), which is the major circulatory form of the vitamin. - impaired Kidney 1α-hydroxylation (converts calcidiol into calcitriol, which is main active form)
# What leads to DIC?
-Obstetric causes (amniotic fluid contains tissue thromboplasin which activates coagulation) - Sepsis (especially with E.Coli or N.Meningitidis),!!!!!!!! endotoxins from the bacterial cell wall, also macrophage cytokines (TNF, IL-1) induce endothelial cells to make tissue factor (think severe urinary infection!!!!!!) - adenocarcinoma- Mucin activates coagulation - Acute promyelocytic leukemia - rattlesnake bite (venom) -Acute pancreatitis -Trauma -Transfusion reaction
# T-ALL
-Presents commonly as *anterior mediastinal mass (thymus)* which is MORE likely than B-ALL to - compress the great vessels causing SVC syndrome!!!!!!! - compress the esophagus causing dysphagia,!!!!!!!!!!!!!!! , also commonly in teenagers -Surface marker: CD1, CD2, CD3, CD4, CD7 (CD10 is a B-cell specific marker, so it is not present!!!). Note: it is also considered to be a LYMPHOMA because it is a thymic MASS, not a leukemia.... leukemia means floating around in blood).
# labs in DIC (!!!)
-Thrombocytopenia -↑ PT and ↑ PTT (!!) -Microangiopathic hemolytic anemia (→ schistocytes aka "helmet cells") -↑ Bleeding time -Because it is a consumptive coagulopathy, ↓↓ coagulation factors (Factor V, Factor VIII) (!!!!) ↓ fibrinogen (!!!) !!!!! ↑ Fibrin split products (D-dimers) as the excessive clotting activates fibrinolysis (plasmin) ... this is the BEST screening test for DIC !!!! !!!!!!!!!!
# Crohns
-Unclear (infection?) etiology -Transmural inflammation, which gives *higher risk of fistulas* !!! (perianal, utinary bladder, vagina) !!!! - SKIP lesions in ANY portion of GI tract, mouth to anus - *Noncaseating GRAULOMAS* and *lymphoid aggregates* (Th1 mediated) !!! !!! - SMOKING increases risk - Strictures (dense fibrosis lead to obstruction and reduction of lumen... also *creeping fat*), Bowell Wall thickens "STRING sign" - Anal fistulas (Because the disease is transmural, the weakened walls rupture)!!!! - Kidney stones -calcium oxalate nephrolithiasis....*increased oxalate* in blood, binds to calcium in kidney (!!!) . - Macrocytic Anemia/ malabsorption - slight risk for CR cancer - May or may not have bloody diarrhea - *COBBLESTONE* musoca- - *RIGHT* lower quadrant pain
# Causes of cirrhosis
-alcohol abuse -viral hepatitis - non-alcoholic steatohepatitis (NASH). - biliary disease and iron overload - Hemochromatosis - Wilson Disease (young people!!!)
# Primary billary cirrhosis labs
-antimitochondrial antibodies (!!) - increase serum ANA- antinuclear antibody, IgM - Increased alkaline phosphatase
# Chronic cholecystitis
-chronic inflammation of gallbladder due to chemical inflammation from longstanding cholelithiasis (gallstones) -Results in Rokitansky-Aschoff sinus formation- gallbladder mucosa 'dives down' in between gallbladder smooth muscle - Vague RUQ pain ESPECIALLY after eating - porcelain gallbladder is late complication (wall of gallbladder is calcified) - treat by cholecystectomy (remove gallbladder) especially if porcelain gallbladder to avoid cancer risk
# Caseating granulomas
-exhibits central necrosis - characteristic of TB and fungal infection - for TB, do AFB stain!! - for fungal infection, do GMS stain (aka silver stain)
#von Willebrand disease findings (!!!!!)
-increased bleeding time and PTT (vWF helps stabilize factor 8, so we lose this) !!! but NORMAL PT and INR NORMAL platelet count!!! Abnormal ristocetin test (decreased agglutination is diagnostic!!!) (!!!!!!!) vWD generally presents with mucosal type bleeding (similar to other platelet defects) as well as menorrhagia. It does NOT present with hematoma and hemarthrosis that is typical of the hemophilias.
# Microscopic polyangiitis
-p-anca positive !!! small vessel necrotizing vasculitis that *affects capillaries, arterioles, and venules* .... It involves multiple organs, especially lung and kidney. all lesions are at the same stage of inflammation: it is similar to Wegener's, but unlike in Wegener's: - granulomatous inflammation is absent -there is NO Nasopharyngeal involvement here The most common clinical manifestations are: 1. Constitutional symptoms (weight loss, fevers, malaise, joint and muscle aches) 2. Kidney inflammation (necrotizing glomerulonephritis) 3. Skin lesions (most commonly palpable purpura of the lower extremities) 4. Peripheral nerve damage (mononeuritis multiplex: damage to two or more separate peripheral nerves) 5. Lung involvement (pulmonary capillaritis leading to alveolar hemorrhage)
#Primary Biliary cirrhosis presentation
-pruritus aka itching (before jaundice) - obstructive jaundice (b/c knocking out of bile ducts), so pale stools, dark urine. - painful hepatosplenomegaly - Xanthelasma (yelloish fat depot under skin/eyelids, late finding)!!! - late cirrhosis -• The portal hypertension in primary biliary cirrhosis may develop BEFORE the cirrhosis, which is unique among liver diseases!!! -Fat soluble vitamin deficiency!!!!!!!!!!!
# Collagen synthesis in the Golgi
. The C- and N-terminal regions are cleaved by proteases, and procollagen is transformed into tropocollagen (insoluble) !!!!! Collagen synthesis step 3 (crosslinking): Cross-linking occurs at lysine and hydroxylysine residues of two neighboring (parallel) tropocollagen molecules → collagen fibrils that reorganize throughout life...... this requires copper!!!
# ACE inhibitors and GFR (!!)
... Angiotensin 2 binds to smooth muscle in the renal efferent arteriole, thus contracting them and increasing GFR... it acts via Gq proteins and phospholipase C. ace inhibitors prevent AT2 formation... thus, less smooth muscle activation, *more dilation of EFFERENT arteriole*, and decreased GFR (creatinine will go UP!!!!) It does this because *dilation of efferent arteriole REDUCES filtration fraction*.
Sporothrix schenckii
... a dimorphic fungi that often enters the body via thorn pricks !!!!!! The fungi then spreads along the lymphatics and forms subcutaneous nodules/ulcers.
# resistance in series
1 divided by Total resistance TOTAL RESISTANCE: If R1=R4 alll are equal to 2, then RT= (1/2 + 1/2 + 1/2 + 1/2) = 2 Total resistance thus equals 1/RT... here, since RT = 2.... it is 1/2 Answer = 0.5
# Prokaryotic RNA polymerases
1 kind, made of 5 subunits and can synthesize all the 3 kinds of RNA
# Diastolic murmurs
1) Aortic/Pulmonic Regurgitation 2) Mitral/Tricuspid Stenosis
# Systolic murmurs
1) Aortic/Pulmonic Stenosis 2) Mitral/Tricuspid Regurgitation 3) Mitral Valve Prolapse 4) Ventricular Septal Defect
# 4 main types of kidney stones
1) Calcium oxalate (low pH) and/or calcium phosphatate (high pH) 2) ammonium magnesium phosphate 3) uric acid 4) cystine.
Physician fee methods
1) Capitation 2) Discounted fee for service 3) fee for service 4) salary
#twins
1) Dizygotic (fraternal) twins (80%) develop from TWO ZYGOTES (2 eggs fertilized by *2 different sperm* at the moment of conception... thus, the sex MAY differ!!!) Dizygotic twins will always have two chorions (and therefore two placentas), and two amniotic sacs. 2) Monozygotic (identical) twins (20%) develop from ONE ZYGOTE (1 egg plus 1 sprm).....The number of placentas depends on the number of chorions. They are the same sex, genetically identical!!!
# Oxytocin functions:
1) During labor: stimulates cervical, vaginal distention and uterus contraction 2) After labor: in the presence of oxytocin, nipple stimulation will "let down" breast milk
# Estrogen and Cholelithiasis
1) Estrogen *increases HMG CoA reductase( and cholesterol synthesis)*, so bile is supersaturated w/cholesterol !! 2) increase lipoprotein receptors on hepatocytes which increases cholesterol uptake Progesterone makes gallbladder hypomobile. !!!!
causes of Cushings
1) Excess corticosteroids 2) Primary adrenal adenoma/hyperplasia/carcinoma (one adrenal is big, opposite adrenal is small), producing ACTH 3) ACTH secreting pituitary adenoma (both adrenals are big)- Cushing DISEASE!!! 4) Paraneoplastic ACTH secretion (usually small cell lung carcinoma, both adrenals are big)
# carbon monoxide CO poisoning
1) Hb can't bind to O2: CO has much greater affinity for hemoglobin than does oxygen → it decreases oxygen binding capacity 2) Hb can't unload O2 to tissues. CO causes a left shift of the oxyhemoglobin curve → less O2 is unloaded to the tissues. Anytime this curve shifts to the left, there is a problem with utilization of oxygen (ie causing tissue hypoxia). 3) CO binds cytochrome oxidase → disrupts oxidative phosphorylation. The O2 that is delivered can't even be used Early sign is cherry red skin and mucus membranes, headache (!!!), leads to confusion, coma, death.
# Hep B serology markers (5)
1) Hep B Surface Antigen (HBsAg) - indicates recent/active infection 2) Anti-HBs ...... the antibody to HBsAG, it indicates immunity to HBsAg (vaccination OR cleared HBsAg) 3) Hep B e-antigen (HBeAG) and HBV-DNA- indicates active viral transmission and thus, high risk of transmission !! If levels are persistent, it is likely chronic infection!!!! 5) Anti HBV core antibody IgM (anti-HBc IgM)- acute/recent infection 6) Anti HBV core antibody IgG (anti-HBc IgG)- prior exposure/chronic infection
# labs in dermatomyositis
1) Increased creatine kinase (indicates muscle damage)!!!!!!! 2) Positive anti-Jo-1 antibody is the HALLMARK of the disease!!!! 3) Positive ANA (if malar rash and positive ANA, do NOT assume lupus until we have either a positive dsDNA OR anti-Jo-1 antibody) 4) positive anti-SRP, positive anti- Mi-2 .
# Neutrophil arrival and function steps
1) Margination 2) Rolling 3) Activation 4) Tight binding 5) diapedesis (Transmigration) THEN 6)chemotaxis) 7) Phagocytosis 8) Destruction of phagocytosed material
# 2 mechanisms of diabetes complications (!!!)
1) Non-enzymatic glycosylation (NEG) of vascular basement membrane ("sticking" sugar on vascular basement membrane). 2) osmotic damage
# Destruction of phagocytosed material occurs in 2 ways:
1) O2 dependent killing (most effective) 2) O2 independent killing
What 2 ways can intracerebral neoplasms raise ICP?
1) Obstruction of normal CSF flow - 2) disruption of blood brain barrier causing increased permeability and blood vessel leak into the interstitium. (called Vasogenic edema!!)
causes of radial nerve injury
1) Prolonged compression of the axilla (e.g., inappropriate/prolonged use of crutches; *"Saturday night palsy" — pass out drunk with arms hanging over a chair, a balcony, etc.*) due to its course inferior to the tendon of latissimus dorsi 2) Midshaft humeral fracture due to its course in the radial groove on the surface of the midshaft humerus with profunda brachii (deep brachial artery) 3) *Radial head subluxation* - aka "nursemaids elbow" damages the *annular ligament* !!!!!! ... common injury in kids. (especially under 5)
# S/Sx observed in patients with CGD (chronic granulomatous disease):
1) Recurrent infections (e.g., osteomyelitis; deep soft tissue abscesses; severe pneumonia) w/ catalase-positive organisms → - lymphadenopathy - hypergammaglobulinemia - ↑ white blood cell count
# Primary hyperparathyroidism
1) Single benign *PT adenoma*: 80% of cases 2) Sporadic Hyperplasia of parathyroid glands: 20% of cases 3) MEN (multiple endocrine neoplasia) I and IIA Symptoms bases on increased PTH/hypercalcemia: - Nephrolithiasia (kidney stone, usually Calcium oxalate) - Nephrocalcinosis (calcium deposited in tubules on kidney, can lead to polyurea) - Constipation, depression
# gastric acid secretion phases
1) cephalic 2) gastric - 3) intestinal Cephalic phase- mediated primary by cholinergic/vagal mechanisms. Triggered by thought/sight/smell/taste of food, and * vagus nerve stimulation from chewing and swallowing* !!! Gastric phase- mediuated by presence of gastrin (which stimulated acid secretion) and is triggered by food/distension of stomach, and presence of protein/acids !!! Intestinal phase- occurs in the presence of chyme in the duodenum, causing initial stimulation and subsequent inhibition of gastric acid secretion.
# what are the 3 possibilities of primary TB infection?
1) latent TB infection 2) Resolution (bacterial clearance and SCAR formation) 3) progressive primary TB (failed immune response results in progressive lung consolidation, necrosis, which then progresses to *military TB*)
# skin changes in dermatomyositis:
1) rash on the *upper eyelids* (called a *helioptrope rash* !!!) "Raccoon eyes" 2) Malar rash (do NOT assume lupus automatically with 'malar rash'!!!!!) 3) Gottron's sign- Red papules on the elbows, knuckles and knees. (!!!) 4) Shawl sign: erythema of the chest and shoulders 5) V-sign: erythema in a V-shaped distribution over the anterior neck and chest
#Gq receptors
1. Activates phospholipase C, which cleaves membrane phospholipid PIP2 into: IP3 and DAG. 2. IP3 diffuses through the cytoplasm to bind to receptors in the ER and release calcium. 3. DAG stays bound to cell membrane 4. Calcium and DAG combine to *activate protein kinase C*.
#TCA side effects: (!!!)
1. Antihistaminic (sedation and weight gain) 2. Antiadrenergic *alpha 1* (orthostatic HYPOtension, tachycardia, and arrhythmias) 3. Anticholinergic *muscarinic* (dry mouth, dilated pupils, tachycardia, hyperthermia, confusion, constipation/intestinal ileus, and urinary retention !!!) 4. can cause Anti-cholinergic sides .... "red as a beet (flushing), dry as a bone (anhidrosis), hot as a hair, blind as a bat (blurred vision), mad as a hatter (hallucinations/delirium), full as a flask (urinary retention)"
# PCR steps
1. Denaturation—DNA is denatured by heating to generate 2 separate strands 2. Annealing—during cooling, excess premade *DNA primers complementary to the 5'and 3' of the desired DNA anneal to a specific sequence* 3. Elongation—heat-stable DNA polymerase replicates the DNA sequence following each primer. These steps are repeated multiple times for DNA sequence amplification." PCR gel "Agarose gel electrophoresis—used for size separation of PCR products (smaller molecules travel further); compared against DNA ladder."
# HIV genes and products
1. Env (codes for gp160, which is cleaved into gp120 and gp41) !!!! 2. gag (codes for p24, capsid protein, and is also located in the core. Antibodies to p24 can act as an early serologic marker of infection) 3. pol- reverse transcriptase, integrase HIV envelople protin* gp120 binds to CD4 protein as the PRIMARY RECEPTOR* and uses *chemokine receptor CCR5 as coreceptor ((on macrophages in early infection) AND and CXCR4 (on T-cells in late infection). !!* CCR5 mutations can confer protection against HIV. Homozygous mutations have been shown to give immunity against HIV, and heterozygous mutations have been shown to have a higher resistance to HIV infection. *gp41 mediates viral-cell fusion* and syncytia formation. • Rev is a regulatory protein that regulates viral RNA transport of unspliced viral transcripts out of the nucleus. Rev and Tat are essential for HIV replication. • Tat is a regulatory protein that transcriptionally activates other viral genes. Tat and Rev are essential for HIV replication. • Nef is a cytoplasmic accessory protein that enhances viral replication through down-regulation of CD4 and MHC-I expression. Pol gene mutations responsible for resistance to HIV reverse transcriptase inhibitors!!!
# important Note: Myeloid stem cell can mature into
1. Erythtoblast (RBCs) 2. Myeloblast (neutrophils, basophils, eosinophils) 3. Monoblast (monocytes) 4. Megakaryoblast (megakaryocytes)
# Diagnose syphilis (!!)
1. First, screen with the *VDRL (venereal disease research lab)* or RPR (rapid plasma reagin) tests, which are relatively sensitive tests for syphilis 2. If the VDRL or RPR tests are positive → then confirm with the *FTA-ABS* (fluorescent treponemal antispirochetal antibodies ) test, which is a specific test for syphilis!!!!!! If VDRL (-) and FTA (+): the patient has been successfully treated If VDRL (+) and FTA (-): it is a false positive
# paranasal sinus'
1. Frontal 2. Ethmoidal 3. Sphenoidal 4. Maxillary
# charcteristics of anaplastic tumors
1. Giant, multinucleated tumor cells (!!!) 2. Significant variation in the shape/size of cells (cellular pleomorphism) 3. High *nucleus to cytoplasm * ratio because of *very large nuclei* 4. Numerous mitotic figures
# Primary brain tumors in adults (by most frequent)
1. Glioblastoma multiforme 2. Meningioma 3. Acoustic neuroma
# α-thalassemia 1 or 2 allele deletions
1. If 1 allele is deleted, patient is asymptomatic. 2. If 2 alleles are deleted, this is known as α-thalassemia trait. The patient will develop a mild hypochromic anemia with increased RBC count. This is not a clinically significant anemia. Cis-deletions (same chromosome) of 2 alleles are prevalent in Asian populations. This is WORSE than trans-deletion because it increases the risk of hydrops fetalis and severe α-thalassemia in offspring. Trans-deletions of 2 alleles are prevalent in African populations."
anaesthetics general side effects on the body
1. Increase cerebral blood flow and ICP (decrease vascular resistance) 2. ALL are respiratory depressant 3. Decrease GFR and RPF 4. Decrease hepatic flow 5. Decrease cardiac output
# IgA deficiency presentation !!!
1. Infections, especially those involving mucosal surfaces — e.g., URIs (upper respiratory tract infections) 2. Anaphylactic reactions to transfused blood containing IgA (!!!!)...... (because their immune system perceives IgA in the transfused blood as "foreign" → produce anti-IgA antibodies (IgG) which attack the transfused IgA) ∴ patients with IgA deficiency should receive blood transfusions with blood that lacks IgA (e.g., blood from patients who are also IgA deficient) 3. Diarrhea 4. Milk allergies
Clinical features of cirrhosis
1. Portal hypertension because of mostly *fibrosis obstructing blood flow through portal vein* , which causes: - Ascites (fluid in peritoneal cavity from *increased hydrostatic pressue*) - splenomegaly and hypersplenism (consumption of platelets and RBCs from enlarged spleen) - distended abdomen ( - Portosystemic shunts (esophageal varicies, hemorrhoids, caput medusae) - liver failure - hepatorenal syndrome (rapidly developing kidney vasoconstriction/failure due to liver. Often requires liver transplant) 2. Decreased detoxification (mental changes, asterixis, b/c NH4)... but is REVERSABLE. -Also, excess estrogen and its sides. (palmar erythema, spider nevi, gynecomastia, testicular atrophy) 3. Decreased protein synthesis (hypoambuminemia leading to edema, coagulopathy due to decrease clotting factors, epoxide reductase) Also Anorexia, Weight loss, Weakness, Hepatocellular carcinoma
# avascular necrosis of femoral head is associated with:
1. Sickle cell disease- due to thrombotic occlusion of arteries 2. Injury to vessel wall (vasculitis) in SLE 3. High dose steroids/alcohol
# risk factors for pancreatic cancer (!!!!)
1. Smoking is THE most important environmental risk, It doubles the risk. 2. Diabetes increases risk 3. Chronic pancreatitis 4. Genetic predisposition (
# what are the 3 ways Down Syndrome can occur?
1. Trisomy 21, from meiotic nondisjunction of chromosome 21. The nondisjunction is almost always maternal origin. 2. Unbalanced Robertsonial translocations. (46 chromosomes, but an extra arm of chromosome 21 is attached to another chromosome, ie, chromosome 14!!!!!!!) 3. Mosaicism.
# catecholamine synthesis and reuptake
1. Tyrosine → DOPA (via tyrosine hydroxylase) *rate limiting step 2. DOPA → Dopamine (via DOPA decarboxylase) 3. Vesicular uptake 4. Dopamine → Norepinephrine (dopamine b-hydroxylase) • Metabolism in the synaptic cleft by COMT (1/3rd) OR • Reuptake into the proximal axon (2/3rd) Once back in the cytoplasm, it is either repackaged into vesicles or metabolized by cytoplasmic MAO.
# stages of duchenne DMD
1. difficulty walking (clumsy, slow, waddling) 2. Gower sign (progressive weakness in *proximal muscles*, need to use hands to stand 3. Calf pseudohypertrophy 4. Asymmetric weakness of paraspinal muscles leading to *kyphoscoliosis*.
# Adenoma-carcinoma sequence
1. if patient develops mutation in *APC gene* (adenomatous polyposis coli) this creates risk for *development of a small polyp*. 2. Next, a *KRAS mutation* allows *increase in size* of polyp because of uncontrolled cell proliferation. 3. if we get *p53 mutation* AND *DCC mutation* (along with *high COX expression*) we get progression to adenocarcioma from the polyp. Note: ASPIRIN protects against this by inhibitng COX (!!!!) COX-2 is BAD and promotes the adenoma-carcinoma sequence.
# Risk factors for CIN and invasive cervical cancer
1. infection with HPV (16, 18 mostly) 2. Immunosupression (HIV) 3. Multiple sexual partners 4. Cigarette smoking!!!
# Edema is caused by...
1.inc. capillary hydrostatic pressure(inc.capilary pressure and heart failure) 2.low plasma proteins...(dec. plasma colloid osmotic pressure.nephrotic symdrome ,liver failure) 3. inc. capillary pemiability (toxin,infection,burns) 4.inc. interestitial fluid colloid osmotic pressure(lymphatic blockage)
#11 hydroxylase deficiency
11 hydroxylase is needed CORTISOL, but it converts WEAK mineralcorticoids into strong mineralcorticoids.... so, 11-hydroxylase deficiency still leaves us some weak mineralcorticoids ( 11-deoxycorticosterone) (!!!), so we may not get salt wasting (doesn't get hyponatermia, hyperkalemia, and hypovolemia.) Therefore, 11-hydroxylase deficiency presents clinically with hypertension (low renin) !!!! and *ambiguous female genitalia (from excess androgens) !!!! *
# thyroid radioactive isotopes
131I, a radioisotope of iodide, can be used to ablate follicular cells. 131I selectively targets follicular cells, through incorporatation into storage follicules. These condensations emit low energy beta radiation, which only delivers very local radiation, sparing nearby important neurovascular structures. Furthermore, its short half life (1 week) prevents patients from long term necessary radiation precautions (handling grand-children, going on planes etc). In *very low doses*, 131I is rarely used for nuclear medicine imaging to assess the regional functionality of the thyroid gland. However, 123I is the usual isotope used in imaging to determine the activity of the thyroid gland, since it is harmless to thyroid cells.
class 1 antiarrythmics
1b- Lidocaine is very specific for ischemic myocardium!!! Class 1c PROLONGS the QRS duration to a greater extent at HIGHER heart rates. (QRS is normal at rest, prolonged at high HR)
paclitaxel coating in stents
2 complications of stents: - acute silent thrombosis - Restenosis due to intimal hyperplasia paclitaxel is a antineoplasmic agent that binds b-tubulin and PREVENTS microtubule breakdown... thus, the cell cycle is arrested in the M-phase, and intimal hyperplasia cannot occur.
#causes of acute pancreatitis
2 most common causes are alcohol and gallstones, by far other causes of acute pancreatitis: -Trauma (especially children in car accidents b/c of seatbelt overlies abdomen instead of pelvis - Hypercalcemia (calcium activates enzymes) - hyperlipidemia (give fibrates!!) - Drugs (steroids, sulfa drugs), scorpion venum, Mumps (tends to infect pancreas) - rupture of posterior duodenal rupture
# Extrinsic receptor-ligand pathway (apoptosis).. What CD? (!!!!)
2 pathways of extrinsic: 1) FAS ligand binds FAS death receptor (CD95) on target cell. Ie, NEGATIVE selection for T-cells in thymus.... OR 2) immune cell (cytotoxic T cell) mediates FAS mediated extrinsic apoptosis
# Melanoma growth phases
2 phases: 1) Starts with *Radial growth phase* which grows *horizontally* along the epidermis and superficial dermis... during this there is a *low risk* of metastasis, because the *key risk* for metastasis and worse the prognis is *depth of growth* !!!! 2) a *vertical growth phase* where it grows deep into the dermis. This *increases the risk* for metastasis and worsens prognosis.
HLA class 2
2 polypeptide chains, alpha and beta. *These are expressed ONLY on APC's.* (macrophages, dendritic cells, B-cells) HLAs corresponding to MHC class II *(DP, DQ, and DR) * present antigens from *outside of the cell* to CD4+ T-lymphocytes. These particular antigens stimulate the multiplication of *CD4 T-helper cells*, which in turn stimulate antibody-producing B-cells to produce antibodies to that specific antigen. In contrast to MHC-I proteins, MHC-II proteins present antigens from *extracellular organisms that have been phagocytosed and digested by the APCs.*... so they act against *bacteria*. HLAs corresponding to MHC class III encode components of the complement system.
# Other causes of secondary hyperparathyroidism
2) Malabsorption syndromes (chronic pancreatitis, small bowel disease, celiac !!): fat soluble vitamin D cannot be reabsorbed, which leads to hypocalcemia. Tx : Calcitriol (vitamin D) and phosphate binders such as aluminum hydroxide or calcium carbonate 3) Rickets - Vitamin D or calcium deficiency which results in increased PTH secretion 1) Pseudo-hypoparathyroidism is an autosomal dominant disorder marked by end organ resistance to PTH which causes the parathyroid glands to release excess PTH → resulting in mental retardation, and short fourth and fifth metacarpals (called the "knuckle-knuckle-dimple-dimple" sign).
#21 hydroxylase deficiency
21 hydroxylase converts both: 1) progesterone into 11-deoxycorticosterone (in zona glomeruloa) 2) 17-OH-progesterone into 11-deoxycortisol (in zona fasciculate) 21 hydroxylase is needed for BOTH weak/strong (in that order) mineral corticoids and glucocorticoids, so if 21 hydroxylase is cut out, then it is shunted to *sex steroids* ↓ In end products aldosterone and cortisol ↑ In precursor 17-hydroxyprogesterone ↑ In end products 17-ketosteroids testosterone and DHT ↑ renin
# adenosine deaminase deficiency
2nd most common cause of SCID !!! (after X-linked recessive). Autosomal recessive. Adenosine deaminase normally converts deoxyadenosine, which is toxic to lymphocytes, to deoxyinosine, which is not harmful. The mechanism by which ADA deficiency leads to SCID is unclear. However, proposed mechanisms include: • Enzyme deficiency leads to an *accumulation of adenosine*, which is converted into deoxyadenosine (dADA) and its derivatives. These are toxic to rapidly dividing immature lymphocytes, particularly T cells (leading to a greater reduction in T lymphocytes than B lymphocytes).
# TCA Toxicity and most common side of death !!
3 C's - Convulsions, Coma, Cardiotoxicity (*due to inhibition of fast Na+ channels → slowed cardiac conduction → prolonged QRS)* (!!!!!) - ventricular arrhythmias - Respiratory depression - hypotension - Hyperpyrexia
# MEN 1 (Wermer syndrome)
3 P's 1) Pancreatic endocrine tumor (e.g., Zollinger-Ellison(gastrinoma), insulinoma, glucagonoma, VIPoma) 2) Parathyroid hyperplasia and hyperparathyroidism (thus, high calcium) 3) Pituitary adenoma (e.g., prolactinoma, maybe GH) prolactinonma would cause decreased libito, infertility
# Antiphospholipid antibodies in SLE
3 tested: 1) anti-cardiolipin 2) Lupus anticoagulant 3) Anti- B2- glycoprotein I
# frontal lobe syndrome
3 types
uric acid stones
3rd most common type of kidney stone. *Hot arid climates*, an *acidic pH* and a *low urine volume* are risk factors. These are the most common stones in *patients with gout, or hyperuricemia* from a *leukemia or myeloproliferative disorder.* These stones are *radiolucent on X-ray*!! . (ALL others are radiopaque- visible), but CAN be seen on CT and ultrasound.!!!!!
# Diagnostic mneumonic for SLE
4 out of "SOAP BRAIN MD" - serositis (ie, of pleura of lung, or serosa of heart) -Oral ulcers -Arthritis in 2+ joints (NON-errosive, little deformity) - Photosensitivity (rash via sun) - blood disorders - renal disorders - ANA positive - Neurologic disorders (seizures, psychosis) - Malar butterfly rash, sparing nasal folds - Discoid rash- circular, erythematous with scaling and it scars) - Raynaud phenomenon (arterial vasospasm of artery and turns it white.... over time with ischemia it turns blue... then when vasospasm releases it turns red)
# Obstructive lung diseases
4 total lung diseases, normal inspiration flow pattern, there is an *obstruction* to getting air *out*.... results in *hyperinflated* lungs !!!! 1) Chronic bronchitis 2) asthma 3) emphysema 4) bronchiectasis
crohns regions
50% ileum and colon 30% terminal ileum alone 20% colon alone B/c terminal ileum so involved, can get less bloody diarrhea, and more malabsorption.
5α-reductase (5-AR aka 5-alpha reductase) deficiency!!!
5α-reductase deficiency is a AR inherited disorder resulting in an inability to convert testosterone to dihydrotestosterone (DHT). *Limited to genetic males (46 XY). * Testosterone is responsible for development of male genitalia during embryogenesis, spermatogenesis,. DHT mediates development of external genitalia (penis/scrotum), growth of prostate, facial hair and hairline recession. At birth, *external genitalia are predominantly female OR very underdeveloped for males*..... and patients are often raised as females. Then, virilization (enlargement of the phallus, increases in body hair and muscularity, voice deepening, no breast development) occurs during puberty due to increasing levels of testosterone. Patient has male internal organs, and person fails to menstruate.
# Low risk HPV
6, 11. Classically produces *condyloma*, a *warty neoplasm of squamous epithelium*, which can be apparent anywhere in lower reproductive tract (vulva, vagina, cervix).
fluid compartments
60-40-20 rule 60% of body is water. 2/3 of that (40% total body) is intracellular 1/3 of that (20% total body) is extracellular ECF is further divided into: ¾ of the 20% is interstitial ¼ of the 20% is plasma
# normal distribution
68% in 1 SD 95% in 2 SD 99.7% in 3 SD Ie, if mean is 220, and SD of 10 68% are between 210-230 95% are between 200-240.... Thus 2.5% are below 200, 2.5% are above 240.
# Mallory Weiss patients are at risk for what??
75% of patients also have hiatal hernia Also has risk of progressing to *Boerhaave syndrome*. Boerhaave syndrome refers specifically to *TRANSMURAL rupture of esophagus NOT caused by endoscopy*.... it is caused by severe retching/vomiting. This causes air in mediastinum which tracks up to region of neck, forms *subcutaneous emphysema* which is air bubbles beneath the skin, and when you push on it, it crackles like rice crispies.
# Type IV Hypersensitivity
: Cell-mediated or delayed type response, sometimes referred to as delayed type hypersensitivity (DTH). Initiated by antigen-activated T cells (including both CD4 and CD8 cells) !!! Involved in the pathogenesis of many infectious and autoimmune disease processes. 3 main types: granulomatous, tuberculin type, candida extract skin test, and contact response !!!
neonatal RDS presentation
:Usually within 30 minutes of delivery, *increased difficulty in respiration* is observed and within a few hours significant and *progressive cyanosis* is evident. CXR shows bilateral ground glass appearance. Sub-costal and intercostal retractions due to *increased inspiratory efforts* . . ABGs will show hypoxemia, hypercapnea and acidosis. # NRDS seen in which conditions NRDS is most commonly seen in infants who are: - Preterm - C-section delivery (vaginal birth is a MAJOR STRESS which results in increase cortisol) - Infants of diabetic mothers (baby produces too much insulin which *inhibits* surfactant).
# Charcot-Bouchard aneurysms (!!)
= microaneurysms that occur in the *small perforating arteries of the brain*—for example: - Lenticulostriate vessels (most common site) - Thalamoperforator vessels - Paramedian branches of the basilar artery - Superior cerebellar arteries - Anterior inferior cerebellar arteries Lilely to damage the: (!!!!!!!!) - Basal ganglia - cerebellum - thalamus -pons Most common cause of Deep intracranial hemorrhage !!!!!!!!
Antibody structure
A "Y" shaped molecule made of 2 heavy chains and 2 light chains, which are termed based on their molecular weights. The tips of the "Y" are the variable regions that recognize antigens, the tips involve both heavy and light chains IgM and IgG can bind complement.
# imporforate anus aka anal atresia
A "dimple" instead of anal opening. Often a *failure to pass meconium* in 24 hours. Often associated with *genitourinary* malformations: - Fistulas (urorectal, urovesical, urovaginal) fistulas !! - renal agenesis - hypospadias - epispadias - bladder extrophy
primary TB complexes
A *Ghon focus* is a granuloma located near the pleura in either the *upper part of the lower lobe* or the *lower part of the upper lobe*; the center of the Ghon focus often undergoes *caseous necrosis, fibrosis and calcification*!!!! A *Ghon complex* is a Ghon focus + regional (usually perihilar) lymphadenopathy. A Ranke complex is a Ghon complex that has undergone progressive fibrosis and subsequent calcification, which makes it radiologically detectable.
# Seborrheic Keratosis
A *benign proliferation of squamous cells*, commonly arises in the elderly. Shows a *raised, discolored plaque*, which* has a classic "stuck on" appearance, like you can almost peal it away (because only the top layers of the epidermis are involved)*!!! Hallmark on histology is that it contains *circular spaces* with *abundant pink keratin* , called *pseudocysts*.
# cyclosporine
A *calcineurin inhibitor* ....calcineuron dephosphorylates nuclear factor of activated T cells (NFAT), which enters the nucleus and binds to an IL-2 promoter. Calcineurin inhibition leads to a *decrease in the synthesis of IL-2 by CD4+ Th cells, thereby decreasing T-lymphocyte proliferation. * • Used in *organ transplants* and can also be used to treat rheumatoid arthritis and recalcitrant psoriasis.
# Melanoma (!!!)
A *malignant neoplasm of melanocytes*, and is the *most fatal skin cancer* Remember it is S-100 positive and has metastatic potential. Cells are melanocytes with a pale halo of cytoplasm normally in the *basal* layer of epidermis. Risk factors are still sunlight, albinism, xeroderma pigmentosum. An additional risk factor is *dysplastic nevus syndrome*.
Subacute cerebellar degeneration
A *paraneoplastic* syndrome associated with cancers: - small cell lung cancer - breast, ovarian, uterine cancer Present with worsening dizziness, limb/truncal ataxia, dysarthria, visual disturbances. It is an *autoimmune* condition where tumor cells cross react with *purkinje neuron antigens* which lead to rapid onset degeneration of the cerebellum.
# *Streptococcus pneumoniae*-
A Lancet shaped, *gram positive encapsulated bacteria !!!! It is the: -MOST common bacteriemia in sickle cell!! (H.Influenza is the next most common!!!!) -most common cause of *community acquired* pneumonia!!!!!! usually in middle aged to elderly adults. It is seen in HIV patients, but with >400 CD4+ - Most common cause of adult meningitis!!!! ! Undergoes Transformation- direct uptake of naked DNA OLDER ADULTS are at risk of pneumococcal pneumonia. !!!! They should be vaccinated with *vaccine against outer polysaccharide capsule. The polysaccharide causule inhibits phagocytosis and causes disease!!! *
# selegiline
A MAO-B inhibitor, it decreases CENTRAL dopamine degradation.
modafinil
A NON amphetamine stimulant. It may enhance dopamine.... It is FIRST LINE
# flutamide
A NSAID used to treat prostate cancer. It is an *oral competitive androgen-receptor antagonist* competes with test and DHT for the AR!!! This increases BLOOD test levels to increase, thus suppressing GnRH
# Varenicline
A PARTIAL nicotinic receptor agonist, that competes with nicotine for the receptor!! It can help with smoking withdrawl by reducing cravings AND it removes the nicotine binding induced rewards!!!! Because it is partial, is results in LESS dopamine release and LESS stimulation of the reward pathways than nicotine
# thiopental
A SHORT acting barbiturate, used for induction of anesthesia. After equibrium with the brain it will then RAPIDLY distribute to skeletal muscle and adipose tissue.
#shigella and gastroenteritis
A VERY LOW number of bacteria are required to cause it. (10-500)!!!! Patients present early with non-bloody, watery, voluminous diarrhea caused by enterotoxin in the small intestine. Dysentery occurs within hours to days and then involves frequent, small, bloody, mucoid stools with abdominal cramps and tenesmus. shigella binds to the M-cells (microfold) in the mucosa, and then spreads, and it causes inflammation, ulceration, and leakage of blood/mucus into the lumen!!!
#desensitization
A behavioral technique based on classical conditioning, in which an individual is exposed to the frightening stimulus in INCREASING doses in conjunction with *relaxation procedures*.... Patient becomes gradually less scared
Schwannoma: (!!!)
A benign tumor of *schwann cells* in the PNS . Can involve the *cranial nerves* or the *spinal nerves* . Very common to involve CN8 at the *cerebello-pontine angle* in the cranium!! (present with hearing loss/tinnitus) Histology: *OVAL Nuclei arranged in "palisades"* Tumor is *S100 positive* !!!!
glomangioma
A benign, *glomous body* tumor that is a red-blue lesion under the nailbed. The tumor originates from *modified smooth muscle cells* that control the *thermoregulatory functions of dermal glomus bodies*. *glomus bodies* are numerous small, neurovascular organs found in: - dermis of nail bed - pads of fingers/toes - ears Each glomus body is composed of an afferent arteriole connected to a richly innervated, muscular arteriovenous anastomoses.... Which is then connected to an efferent vein. The role of a glomus body is to: - shunt blood away from skin surface in cold tems to prevent heat loss - direct blood flow to skin in hot environments to dissipate heat
# porcelain gallbladder
A bluish, brittle, calcium laden gallbladder in patients with chronic cholecystitis. Cholecystectomy is recommended because of very high risk (1/3) of gallbladder carcinoma!!!!
# Clostridium tetani
A bug with EXOTOXIN (tetanospasmin). It is often found in soil or rusty nails. The diagnosis is clinical!!! (there are no good serum/imaging tests) *Travels from wound then retrograde to motor neuron axons and then to spinal cord!! * Tetanospasmin cleaves SNARE proteins *required for neurotransmitter release of inhibitory neurostransmitters GABA and glycine from Renshaw cells in the spine*, thus, there is *uncontrolled firing of motor neurons. * The excessive muscle contraction (tetanus) causes rigid paralysis and often presents clinically as: • *Trismus ("lockjaw")* due to jaw muscle contraction. • Risus sardonicus ("ironic smile of tetanus") due to facial muscle contraction. • *Opisthotonos (pronounced arching of back)* due to contraction of back extensor muscles.
Schizophrenia
A chronic mental disorder with periods of psychosis, disturbed behavior/thoughts, and decline in function lasting at LEAST 6 months. - It is characterized by both "positive" and "negative" psychotic symptoms. - Diagnosis requires at LEAST two positive OR negative symptoms. 1 of those MUST be delusions, hallucinations or disorganized speech.
# Bacteroides fragilis
A common organism in *intra-abdominal infections* like a perforated appendix, or intra-abdominal ascess
caudal regression syndrome
A condition where infants are born with *agenesis of the sacrum and occasionally lumbar spine* !! They experience flaccid lower legs.
# cystic hygroma
A cystic lymphatic malformation (lymphangioma), usually occurs on the left side of the neck on posterior triangle!! They are soft, compressible, and CAN transilluminate. They are very associated with chromosomal aneuploidy!! (ie, Turner, trisomies 13, 18, 21)
# Spongiform Encephalopathy
A degenerative disease due to accumulation of *prion protein*- infectious proteins with NO DNA or RNA!!! - Prion protein in the brain is *NORMALLY* in the *alpha-helical* configuration, called PrPc. If PRP is converted into PrPsc, which is in a *beta pleated sheath* configuration (!!!!!, this results in production of a pathological protein that damages the brain and results in *spongiform encephalopathy* in 2 ways: 1) it feeds back on PrP and results in increased PrP(sc) in the *beta pleated* confirmation.... 2) PrP(sc) cannot be degraded, so it accumulates in the neurons and glial cells, damaging them, resulting in *intracellular vacuoles* which are like *spongy white holes in the gray matter*. !!!!!!
# Gallstone ileus
A large gallstone passes through a fistula from the gallbladder into the small bowel where it obstructs the *ileocecal valve*. Gas is seen within the gallbladder and patients present with s/sx of small bowel obstruction. !!!!!
# Truncus Arteriosus
A large ventricular septal defect in which one single large vessel arising from *both ventricles*, as the *truncus arteriosus fails to fully divide* into pulmonary and aortic trunks. You get mix of deoxygenated blood from RV which mixes in a pool of oxygenated blood from LV in a pool before pulmonary and aortic circulation separate.... so presents with *early cyanosis*. As a result of this cyanotic birth defect, un-oxygenated blood intended to go to the lungs and oxygenated blood entering the systemic system, mix and create oxygenation problems.
# salmonella typhi aka typhoid fever
A life threatening illness, usually occurs in developing countries by fecal-oral route. Presents with: week 1: initial diarrhea/constipation, - escalating fever Week 2:- abdominal pain, - formation of a rash aka rose spots on chest/abdomen week 3: hepatosplenomegaly, intestinal bleeding
Primary syphilis
A localized (!!!) ONLY disease presenting with PAINLESS *chancre* (ulcerated lesions).
fourth heart sound
A low frequency, late diastolic atrial gollop sound that occurs *BEFORE S1* AFTER the onset of P wave (coincides with ventricular filling). (de-Lub-dub!!!) Sign of *diastolic dysfunction*. It occurs when there is a *rise in end-diastolic ventricular pressure* caused by *atrial contraction against a STIFFENED LEFT VENTRICLE*. (so it occurs IMMEDIATELY after atrial contraction) Best heard with bell over cardiac apex with patient in left lateral position. Occurs in conditions such as: Ventricular hypertrophy, acute MI, long standing HTN, aortic stenosis,
atropine
A muscarinic antagonist, so it is an anticholinergic. • Causes mydriasis (dilates pupil) and cycloplegia • PREVENTS bradycardia, asystole, heart block: at high or toxic doses, HR ↑ These effects are due to the inhibition of parasympathetic tone on the heart → increase HR • Inhibits salivary/sweat/mucus gland airway secretions • Decreases stomach acid secretions • Decreases gut motility • Can be used to treat symptoms of organophosphate poisoning
Scopolamine
A muscarinic antagonist. • Treats motion sickness. Might be able to inhibit other cholinergic effects like diarrhea, cramping, sweating, nauaea. • Causes mydriasis and cycloplegia. Can also cross blood brain barrier and result in CNS manifestations of anticholinergic toxidrome. Also causes dry mouth, palpitations, urinary retention.
dystonia
A neurological movement disorder characterized by *sustained, involuntary muscle contractions* . These movements may affect: - a *single muscle* - group of muscles - entire body
# Measles (rubeola)
A paramyxovirus, caused by *rubeola virus* 10-14d incubation period followed by prodrome: fever and *4 C's of measles*: Conjunctivitis (photophobia) Cough Coryza Koplik's spots- small white spots on the buccal mucosa!!!) Infects respiratory epithelial cells, replicates and lyses them → spreads to mucosa (*koplik spots)* → 1-2 days later → dermis (maculopapular rash *starting at head and workings its way down*)
# hibernating myocardium
A phenomenon that occurs due to *repetive ischemia/hypoperfusion* of the myosides, which results in a chronic but REVERSIBLE loss of contractile function. When revascularization occurs via CABG or balloon angioplasty, contractile function can occur over hours, days, weeks and months,.
amiodarone
A potassium channel blocker. • include *pulmonary fibrosis, hepatotoxicity, hypothyroidism/hyperthyroidism,* corneal deposits, *blue or gray photo dermatitis*, neurologic effects, constipation, and cardiovascular effects. • Patients must have pulmonary (PFTs), liver (LFTs) and thyroid function tests (TFTs) (!!!!!!) periodically when using amiodarone.
# Isoniazid (INH)
A prodrug, activated by *bacterial catalase-peroxidase.*... it then inhibits *mycolic acid synthesis* the mycobacterial cell wall, causing TB to stop dividing!!!! Remember, *mycobacteria are ACID FAST staining because of high lipid content.... And mycolic acid is the major lipid* In monotherapy, resistance rapidly develops because of *decreasing the activity of bacterial catalase-peroxidase*.
Ubiquitin
A protein found in ALL eukaryotic cells that undergoes ATP dependent attachment to other proteins, labeling them for degradation by the proteasome. Impairment of ubiquitin-proteasome system can contribute to *neurodegenerative diseases* (Parkinsons, Alzheimers) hbecause it doesn't degrade abnormally folded proteins.
# giardia lambilia
A protozoan in both cyst and trophozoite forms. The cyst form is infections, and is located in - sweage - freshwater streams/lakes contaminated by animal feces *Patients often have a hx of camping or travel!!!! * After being ingested, the cyst matures into a binucleate flagellated trophozoite, that has *"kite-like" appearance!!! * The trophozoite then *attaches to the small bowel mucosa, but does NOT damage or invade it!!! *But it *DOES cause malabsorption, leading to greasy, frothy, foul spelling diarrhea and excessive flatulence. * Stool microscopy shows ova and parasites!!! IgA is the major defense against Giardia !!!! Treat Giardia with metronidazole!!!!!!!
# granuloma and foreign body
A retained foreign body (ie, sutures) causes a granulomatous response.
# Henoch- Schonlein Purpura (!!!) (HSP)
A small vessel vasculitis that commonly affects the skin, GI tract, kidneys and joints. (!!!) Also characterized by IgA-anti-IgA immune complex deposition in blood vessels. Generally follows a *viral upper respiratory infection*.....often viral or Group A Streptococcus.... (because when you get this, you develop IgA to protect mucosal sites.... *patients with this disorder have IgA immune complexes deposited!!!!! * It is the *most common vasculitis in kids* (!!!!!)
fetal screening
A triple test of: - AFP- maternal AFP increases with weeks gestation as it is produced by fetal liver, GI tract. - hCG - estradiol is performed between 16-18 weeks. Abnormal triple test is an indication for fetal ultrasonography (USG). !!! If USG shows development is normal for gestational age, do amniocentesis. Most often, high levels of hCG on amniocentesis are due to *dating error* where women UNDERESTIMATE how long they've been pregnant.
Hyperacute Rejection: aka *hemolytic transfusion reaction*
A type 2 Hypersensitivity that occurs in *minutes to hours*. Presents with: - fever/chills - chest/back pain - hemoglobinuria (redish brown colored urine) Presence of *preformed antibodies* (IgM, IgG) against the donor's HLA or ABO antigens at time of transplantation leads to *complement mediated lysis*→ rejection of the transplant *within minutes to hours*. • The transplant must be immediately removed to prevent a severe systemic inflammatory response. Hyperacute rejection can be avoided by transplanting only tissue which is *HLA or ABO-compatible with the patient* !!! The tissue becomes *mottled and cyanosis*. !!!!! Perfusion through the organ decreases immediately due to the antibodies *forming fibrinoid necrosis and thrombotic occlusion.*
# Which hepatitis virus' have a vaccine
A, B (and thus D)
identify brain structures
A. Caudate (c-shaped) B. Internal capsule C. Insular cortex D. Putamen E. Globus pallidus F. Amygdala
cardiac pressure loop
A. Isovolumetric contraction: begins with the CLOSURE of the Mitral Value (S1 sound!!) The LV contracts and intraventricular pressure rises but NO blood leaves the ventricle because the AORTIC VALVE is still closed !! B. Ventricular ejection: Aortic valve opens, blood squeezed into circulation C. Isovolumetric relaxation: CLOSURE of aortic value (S2 sound). Pressure in the ventricle decreases but NO blood enters the ventricle because both the AORTIC and MITRAL valves are closed !! D. Ventricular filling. Beings by OPENING of the mitral valve. Mitral stenosis is best heard here!!!! C-A= Diastole A-C= systole
aortic deceleration injury
A/B. Ascending aorta C. *aortis isthmus*.... This ares is most at risk to rupture in TRAUMA (ie, SUDDEN deceleration in a motor vehicle) !!!!!!
#treat aspirin toxicity
ABC's Activated charcoal to absort Sodium bicarbonate is given in a significant aspirin overdose (salicylate level greater than 35 mg/dl 6 hours after ingestion) regardless of the serum pH as it enhances elimination of aspirin in the urine.
# diagnose myasthenia gravis
ACH receptor antibodies • The Edrophonium (Tensilon) test • Electromyography - including both the Jolly test and single fibre EMG
#tuberous sclerosis
AD inherited disorder affecting *tuberin and hamartin proteins*, which regulate cell growth and differentiation. Strong association with tumors such as: cortical tumors, subependymal hamartomas in the brain renal angiomyolipomas cardiac rhabdomyomas astrocytomas pulmonary lymphangioleiomyomatosis. Findings include hypopigmented "ash-leaf" spots. Patients present with intellectual disability and epilepsy.
# Neurofibromatosis
AD inherited disorder, caused by mutations in NF1 gene (chromosome 17q) or NF2 gene on chromosome 22q
Huntington's disease inheritance
AD inherited.... Due to expanded *CAG repeat* in the *huntingtin gene* located on chromosome 4 (Mnemonic: "hunt 4") .....CAG= polyglutamin Anticipation is due to *further expansion of the trinucleotide repeat during SPERMATOGENESIS* !! It is highly due to *histone DEacetylation* !!!! (this silences genes necessary for neuron survival). (remember, "acetylation makes active")
#adh aka vasopressin aka antidiuretic
ADH functions: 1) Moderate vasoconstriction and prostaglandin release (V1 receptors) 2) Antidiuretic effect, increases passive water reabsorption in *MEDULLARY SEGMENT of renal collecting ducts (V2 receptors)* (!!!) thus decreasing serum osmolarity, and increasing urine osmolarity 3) increases reabsorption *of urea*.
# Adult Aortic Coarctation
AKA Post*ductal coarctation: narrowing of the aorta is *distal* to *ligamentum arteriosum* (remnant of the ductus arteriosus).... it is NOT associated with a PDA 30-40% of cases are also associated with bicuspid aortic valve!! Blood goes RA all the way to LV no problem... but once it exits LV, it is more difficult for blood to go through aortic arch, and more of it goes through initial branches of aorta. This creates *hyper-tension in UPPER extremities, hypo-tension and weak pulses in lower extremities.* !!!!!!!!!! *claudication* of lower extermities is seen. !!!!!!!!
FAP and APC
APC acts as a "scaffold" protein for β-catenin, *preventing β-catenin* from entering the nucleus and initiating transcription. APC gene mutation leads to *RISK* for *development of polyp* because of accumulation of β-catenin in the nucleus → un-controlled transcriptional activation. It is a *tumor supressor gene* so you have to knock out *both copies* to develop the risk, somatically. But, it is possible to *INHERIT ONE bad copy*, this is *Familial adenomatous polyposis* syndrome FAP is an inherited condition characterized by hundreds to thousands of colonic adenomatous polyps that typically begin to emerge in the second and third decades of life.
#Leukocyte adhesion deficiency
AR inherited defect of *integrins* !!!!!!!!!!!! (C18 subunit) essential β2-integrin on lymphocytes, macrophages, and neutrophils !!!! Clinical features: -delayed separation of umbilical cord within first few weeks of life!! (normally it dies, falls off via necrosis via inflammation/neutrophils). !!! - Increased circulating neutrophils (leukocytosis, 6-10x normal) - poor wound healing - - Recurrent bacterial infections that LACK PUS (!!!)
# Dubin- Johnson syndrome !!!
AR inherited deficiency of bilirubin canalicular transport protein ((cMOAT) which is responsible for hepatic excretion of bilirubin.) Normally, UCB is conjugated into CB in hepatocyte, then CB is dumped in bile canaliculi via canalicular transport proteins. If deficient canalicular transport protein, *CONNJUGATED BILIRUBIN builds up in liver and spills out into blood*. Not clinically significant, BUT liver is pitch dark/black, and there is *a dense pigment with EPINEPHRINE within the lysosomes* !!! !!
#IL-12 receptor deficiency
AR inherited deficiency... Discovered in otherwise healthy patients with disseminated *mycobacterial, fungal and salmonella infections* because IL-12 activates NK cells and induces Th1 formation, we have decreased levels of TH1 and NK cells!!! ..... also, since IFN-y is often released from Th1 cells, levels of IFN-y decrease (!!!) So, we *supplement with IFN-y* !!!! IFN-γ is still secreted in an IL-12 independent manner so granulomas form, but the infection is inadequately controlled by the cell-mediated immunity Presents often after BCG vaccine. !!!
#Chediak-Higashi Syndrome (!!!)
AR inherited protein trafficking defect LYST (lysosomal trafficking) protein - characterized by *impaired phagolysosome formation* (cell cannot move phagosome across tracks using microtubules to lysosome). - *Albinism* (melanocytes CAN produce melanin, but cannot distribute it to keratinocytes!!! ) - Increased risk of pyogenic infections- → recurrent pyogenic staph and strep Infections -Neutropenia/leukopenia (neutrophils cannot divide properly) - Giant (abnormally large) granules in leukocytes - Defective primary hemostasis (granules are not properly distributed) - Peripheral neuropathy
# Friedreich Atexia inheritance
AR inherited, unstable trinucleotide repeat *GAA* in the *frataxin gene*!!!! (which is *essential for mitochondrial iron regulation*) , causes decrease gene product of frataxin (less translation).... so if we cannot regulate this, we increase the *risk of free radicals via the fentin reaction* - presents in *early childhood*
# hemoglobin C, what mutation??
AR mutation in same codon is mutated as in HbS (β-chain, codon 6), except lysine (not valine!) is substituted for the glutamic acid. Mnemeonic: think ""hemoglobin C has LyCine"" This occurs less frequently than sickle cell disease. HbC homozygotes have milder disease than HbS homozygotes, there is some mild normocytic anemia due to extravascular hemolysis.
# Acute respiratory distress syndrome (ARDS)
ARDS is an acute lung injury due to an inciting event (trauma, sepsis, acute pancreatitis, amniotic fluid embolism, shock) causing complement activation and subsqeuent *diffuse damage* to *alveolar-capillary interface.* There is *progressive hypoxemia REFRACTORY to oxygen therapy* !!! This causes an an increase in alveolar capillary permeability with *leakage of plasma proteins*, RBCS (red blood cells), WBCS (white blood cells), PMNS (polymorphonuclear leukocytes) into alveoli and interstitium. So there is: - non-cardiogenic pulmondary edema in the alveolar spaces!! - *NORMAL pulmonary-capillary wedge pressure (PCWP)*!!!! (determining Left Atria pressure is NORMAL). !!!! - Pao2/FIO2 < 200 This damage causes *formation of an intra-alveolar hyaline membrane* (hallmark of it!!!). Consequences: 1) Increased hyaline membrane formation *impairs gas exchange* (because it is thickened).... and leads to hypoxemia/cyanosis refractory to increased oxygenation 2) Neutrophils cause destruction of *Type I and II pneumocytes* (!!!) → loss of surfactant → *atelectasis*. This causes the formation of an intrapulmonary shunt (A V/Q mismatch with no V)
# Atrial septal defect
ASD is an opening in the *atrial septum* that allows movement of blood between atria, initially *left-to-right*. - Most common type is ostium secundum, but ostium primum type is associated with Down Syndrome. Atrial septal defect is characterized by a loud S1 with a *wide, fixed split S2.*!!!!!!!!!! What happens is that as blood crosses over from LA to RA, there is *extra blood volume on right side, * results in *delayed closure of pulmonary valve* .. this causes *splitting* of S2 (as S2 is when aortic and pulmonary valves close). Can also lead to a *paradoxical embolus*, where an embolus that originates on the right side and would normally lodge in pulmonary vasculature, goes through the septal defect and lodges in brain or systemic. Note: The splitting does NOT CHANGE with respiration.
Cardiac impulses conduction pathway
AV note to common bundle, then bundle branches..... then Purkinje, then the ventricle myocardium Purkinje system is fastest, AV node is the SLOWEST. Atrial system is higher then ventricle system. Purkinje>atria>ventricle>AV node
# ruptured ectopic pregnancy
Abdominal pain vaginal bleeding hemodynamic instability (ie, Orthostatic hypotension!!!)
# Hydatidiform mole
Abnormal conception characterized by *swollen and edematous villi* with *excess proliferation of trophoblasts* which surround them. The uterus expands as if normal pregnancy is present.... but uterus is *larger than normal* and *HCG is higher than expected*. Clasically, for a complete mole, the woman will begin to pass *grape like masses* (which are the large, edematous villi) during the *second trimester*. But in the western world, usually diagnosed by routine ultrasound in *early first trimester*, so there are *no fetal heart sounds*... that present as a *snow-storm appearance* (lucent and echogenis) on ultrasound*.
#Endometriosis
Abnormal placement of endometrial glands AND stroma located outside the uterine endometrial lining. → cyclic bleeding cyclic symptoms according to hormonal status — e.g., symptoms may worsen leading up to menstruation Endometriosis presentation: Presents with: - dysmenorrhea (menstural pain, because the tissue is in an abnormal location and still cycles) and pelvic pain. - infertility. - - Dyspareunia (painful sexual intercourse)!!!! - Dyschezia (painful defecation) !!!!! - but there is a *normal sized uterus*
Renal agenesis
Absence of kidney formation, can be either unilateral or bilateral. unilateral agenesis leads to *hypertrophy of other* kidney... but as it hypertrophies, it increases risk for hyperfiltration later in life. *bilateral* agenesis failure of fetal renal excretion → *oligohydramnios (↓ amniotic fluid)* !!!→ multiple anomalies (*Potter phenotype*) and early death:
# atrial fibrillation ECG
Absent P waves Irregularly irregular R-R Narrow QRS The AV NODE REFRACTORY PERIOD is what regulated the number of atrial impulses which reach the ventricle.
# Hirschsprung's disease presentation, diagnosis and treatment
Absent peristalsis in the affected segment of colon causes constipation (or failure to pass meconium), distal obstruction, and megacolon from *dilation*. Most infants with Hirschsprung disease fail to pass meconium within the first 24 to 48 hours of life. !!!!!! There are other signs of *BOWEL obstruction*, such as abdominal distention and bilious vomiting!!! The bowel is full of stool, but there is an *empty rectal vault* on DRE Diagnosis: *rectal suction (!!!) biopsy* to confirm absence of ganglion cells. Standard biopsy only gets a piece of mucosa, NOT submucosa, as needed!!!!
# Absolute polycythemia vs relative polycythemia
Absolute = A true ↑ total RBC mass. Relative- *Decreased plasma volume* Due to volume depletion: - Sweating - Diarrhea - Burns
carboxyl tails to plasma membrane
Accomplished by palmitoylation, which increases protein hydrophobicity by anchorin receptor carboxyl tails to plasma membrane.
# AML (Acute myelogenous (myeloblastic) leukemia)
Accumulation of *myeloblasts, which are characterized by staining for myeloperoxidase (MPO!!)*-. The Myeloblast accumulation suppresses the growth/multiplication of other hematopoietic precursors from the bone marrow, so it presents with: - anemia, fatigue, palor - thrombocytopenia (petechiae, hemorrhages) - neutropenia (fever, opportunistic infections) MPO detected via: - chemical study to determine if enzyme is there: - presence of crystal aggregates called Auer rods (!!!)
Acetaminophen (Paracetamol) overview
Acetaminophen is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer) medication that *lacks the peripheral anti-inflammatory properties* present in traditional NSAIDs. • Unlike aspirin (non-selective COX inhibitor), acetaminophen is highly selective for the COX-2 enzyme, and thus does not inhibit the production of the pro-clotting chemicals (e.g. thromboxanes). • Acetaminophen reversibly inhibits cyclooxygenase in the CNS but is inactivated peripherally.
# Types of diutetics
Acting from most proximal to most distal!! 1. Carbonic anhydrase inhibitors 2. osmotic agents (aka Mannitol) !!! 3. Loop Diuretics 4. Thiazide diuretics: 5. K-sparing diuretics
Aspergillus A's
Acute Angle Allergic Aspergillosis/Asthma Aspergilloma Angioinvasive Aflatoxin Amphotericin B
# ITP presentation
Acute form usually in children following a VIRAL infection or immunization, and is self-limited (usually clears in a few weeks) Chronic form usually in adults, especially women of child bearing age. Can be primary, or secondary to something else (ie, SLE). Patients present with petechiae/purpura, menorrhagia (heavy menstrual bleeding) , nosebleeds Labs: *Thrombocytopenia* (!!!!) with HIGH levels of megakaryocytes, but in the ABSENCE of splenomegaly. But normal PT/PTT (coagulation cascade is normal)
# pituitary apoplexy
Acute hemorrhage into the pituitary gland. Presents similar to SAH (severe headache... BUT here there is bitemporal hemianopsia!!!) There is hypopituitaryism, it is critical to treat with corticosteroids to prevent hypotension
# Acute ACALCULOUS cholecystitis
Acute inflammation of the gallbladder, in the ABSENCE of gallstones. Most commonly happens in hospitalized patients with causes of *gallbladder stasis*, and then there is *bacterial overgrowth*. - sepsis - immunosuppression - TPN - major trauma There is often JAUNDICE and PALPABLE gallbladder, which is NOT seen in CALCULOUS cholecysticis.
# Gallbladder carcinona
Adenocarcinoma arising from glandular epithelium that lines the gallbladder wall - gallstones are major risk factor, especially with *porcelain gallbladder* Classically presents as cholecystitis in ELDERLY women. Normally cholecystitis affects middle age, so if there is an elderly woman with cholecystitis, be wary of Gallbladder carcinoma. Vast majority of stones are asymptomatic. Symptoms occur when stones obstruct common bile duct or pancreatic duct
# adenovirus
Adenovirus infection can lead to: • Pharyngitis • Respiratory tract infection (rhinitis, sore throat, and atypical pneumonia) • Conjunctivitis • *Hemorrhagic cystitis (UTI with dysuria and hematuria!!!)* • Gastroenteritis • Pharyngoconjunctival fever is an adenoviral syndrome associated with *outbreaks in summer camps in association with swimming pools or lakes!!!!* Patients present with o Benign follicular conjunctivitis o Febrile pharyngitis o Cervical adenitis
# treat IBS
Adequate fiber important, eliminate irritant foods (coffee, spices, fatty foods) - antispasmodic-anticholinergic (ie, dicyclomine) - Loperamide for diarrhea (serotonin 3 antagonist) - Lubiprostone for constitipation (Cl- channel activator)
# ulcerative colitis colorectal carcinoma characteristics
Affects younger patients. More likely to arise from flat, non-polypoid dysplastic lesions (this makes their diagnosis more difficult) Be *multifocal* in nature Develop EARLY P53 mutations and Develop LATE APC mutations (this is the opposite of sporadic CRC!!) Higher histological grade
# What changes happen to the heart 1-3 days after MI ??
After acute inflammation, there is healing, neutrophils come in and there is coagulation necrosis.
# Hyperthyroid diagnosis
After confirming thyrotoxicosis with TSH and free thyroid hormone level assays, 123I uptake may help determine the etiology of the thyrotoxicosis: Graves disease: Diffusely ↑ 123I uptake in the whole thyroid gland. # Toxic multinodular goiter: Uneven moderately high 123I uptake with occasional autonomous "hot" nodules demonstrating ↑ 123I uptake. # Thyroiditis: ↓ 123I uptake Exogenous thyroid hormone intake: ↓ 123I uptake
transmigration
After crawling, they migrate out of the vasculature by squeezing in between the cells via *integrin attachment to PECAM-1* !!! ( Platelet ejdothelial cell adhesion molecule 1.
# intestinal atherosclerosis (!! )
Aka chronic mesenteric ischemia. Patients typically have a history of smoking and atherosclerotic vascular disease, such as coronary artery disease or peripheral vascular disease. It is caused by *atherosclerotic narrowing* of the : - celiac trunk - SMA - IMA Characterized by: 1) epigastric/periumbilical pain *30-60 mins after food*. This is because the arteries CANNOT dilate in response to blood flow demand for digestion 2) Weight loss is common (because eating hurts). • Symptoms may progress and cause thrombus formation, which ultimately leads to acute-on-chronic mesenteric ischemia.
cryptorchidism
Aka undescended testes. If the testes do not descend, the *seminiferous tubules which contain sertoli cells become atrophic*..... this results in low sperm count. Also, inhibin is NOT released and thus FSH is elevated!! Leydig cell function is usually unaffected. (secondary sex characteristics are normal)
Alcohol acute pancreatitis
Alcohol creates contraction at sphincter of Oddi @ Ampula, which enters duodenum. Decreases drainage of pancreas enzymes and increases risk of premature activation
# alcoholics and lung infections/abscess
Alcoholics are much more likely to develop infections/abscesses involving combinations of ANAEROBIC bacteria, and also aerobic bacteria. They are at major risk of *aspiration pneumonia* because alcohol impairs the gag/cough reflex!!!! They also have terrible oral hygiene, increasing the risk. *Clindamycin* is the antibiotic of choice for lung abscesses!!!!! Also at risk are: - seizure disorder - stroke -dementia
transcription factors
All nucleated cells in the body possess the entire genome. Transcription factors specific for each individual tissue allow only those genes relevant to a cell's specific type and function to be expressed. Transcription factors dictate differentiation.
staph vs strep
All staph are gram positive cocci that form clusters. Staph are catalase positive!!! Strep are catalase negative !!! Coagulase positive staph= staph aures Coagulase negative staph= the other kinds of staph
# Atopic asthma pathogensis (!!)
Allergens induce TH2 phenotype in CD4+ T cells in *genetically susceptible* individuals TH2 cells secrete: (memorize!!!!) - IL-4 - IL-5 - IL-10 IL-4 allows plasma cell to class switch to IgE IL-5 calls in *eosinophils* IL-10- inhibits production of Th1, stimulates Th2 to enhance overall reaction.
aspirgillus and lungs
Allergic bronchopulmonary aspergillosis is an IgE-mediate type I and III hypersensitivity reaction, most often seen in individuals suffering from asthma or cystic fibrosis. Increased levels of IgE leads to eosinophilia, causing intense inflammation of airways and mucus plugs in terminal bronchioles. Repeated attacks may lead to bronchiectasis and interstitial lung disease. Migratory pattern of pulmonary infiltrates may be seen on imaging. Aspergilloma is a fungus ball that develops in a preexisting cavity in the lung usually from an old tuberculosis site. This can invade blood vessels and cause massive hemoptysis. Invasive aspergillosis involves invasion of lung tissue and the bloodstream in an immunocompromised host (especially in individuals with Chronic Granulomatous Disease), which can occlude blood vessels and lead to pulmonary infarction.
# allopurinol
Allopurinol is a structural isomer of hypoxanthine , and also a* xanthine-oxidase inhibitor*, drug used primarily to treat hyperuricemia (excess uric acid in blood plasma) *due to over-production of uric acid* (24-hour urine uric acid level >600mg) . Allopurinol therefore decreases both uric acid formation and purine synthesis and is used in chronic gout
# allupurinol uses
Allopurinol is also commonly used as prophylaxis with chemotherapeutic treatments for lymphoma and leukemia, which can rapidly result in very high uric acid concentrations due to widespread cell death (tumor lysis syndrome) Allopurinol prolongs the half-life of azathioprine and 6-mercaptopurine.!!! It enhances the bone marrow toxicity of cyclophosphamide Other established indications for allopurinol therapy include ischemic reperfusion injury, kidney stones with a uric acid component (uric acid nephrolithiasis) and protozoal infections (Leishmaniasis)
#Malingering
Also a *conscious* simulation of physical illness, however the goal is for *external 2° gain*.... Ie for *financial or other obvious gain (avoiding work, obtaining drugs)* • Complaints stop after gain is achieved (as opposed to factitious disorder)
# Contact dermatitis
Also a Pruitic, erythematous, oozing rash with vesicles and edema.... Which is due to *contact exposure to allergen*!!! (NOT associated with asthma and allergic rhinitis*) There are often *linear patterns* rash. !!!! • Arises as a result of two essential stages: 1) an induction phase, which primes and sensitizes the immune system for an allergic response. It takes 10-14 days. 2) an elicitation phase, in which this response is triggered 2-3 days after reexposure. • Therefore, ACD is termed a *type IV delayed hypersensitivity* reaction involving a cell-mediated allergic response *Spongiosus dermatitis* is the end result!!!! (spongiosus=accumulation of fluid)
# diagnose Reye syndrome
Also elevated liver serum transaminases (ALT and AST) over 3x normal, fatty changes in liver Autopsy: biopsy of liver, kidney, brain demonstrates *microvesicular steatosis*
# Renal cell carcinoma presentation
Although most patients with RCCs remain asymptomatic, some patients may present with constitutional S/Sx (e.g., fever, weakness, weight loss) and at least some of the "classic triad": 1. Flank pain — i.e., CVA (costovertebral angle) tenderness 2. Palpable flank mass 3. Hematuria (most common)
chest/lung compliance
Alveolar pressure is ALWAYS positive, resulting in *collapsing force on the lungs*. The chest wall transmits an EXPANDING force to the lungs, so it is MOSTLY on the negative pressure (except the end of expiration). The center of these is the FRC, where airway pressure= 0, but INTRAPLEURAL pressure is negative (around -5). Ie, think about when we get a stab wound into the pleura. The negative intrapleueal pressure causes a pneumothorax as the *lung collapses inward*.
where does a coin end up swallowing??
Always in the right lung. If upright/semi-upright it is the basilar segment of the lower lobe. If supine, it end up in the: - posterior segment of upper lobe OR - superior segment of lower lobe
#amphetamine
Amphetamines increase presynaptic release of NE and, to a lesser extent, acts as a reuptake inhibitor., which increases the cytoplasmic concentration of catecholamines (NE, dopamine)
# cerebral amyloid angiopathy
Amyloid deposition around the cerebral vessels in the brain, which weakens them, and is the *most common cause of recurrent hemorrhagic stroke*. These strokes are smaller and less severe than hypertensive hemorrhagic strokes. They involve the cerebral arteries, while hypertensive strokes tend to involve the basal ganglia.
# probenecid
An *uricosuric drug*, primarily used in treating chronic gout and hyperuricemia, *that increases uric acid removal in the urine*. The kidney's organic anion transporter (OAT) reclaims uric acid from the urine and returns it to the plasma.... Probenecid interferes with the OAT transporter!! If probenecid (an organic acid) is administered to a patient, the OAT binds to probenecid instead of to uric acid, preventing the reabsorption of uric acid in the PCT. As a result, *more uric acid leaves the body in the urine* , lowering the uric acid concentration in the plasma It also Inhibits *renal SECRETION of penicillin!!* Patients who use probenecid need to drink 2 L of fluid daily at the inception of therapy in order to reduce their urinary concentration and thereby reduce the risk of renal stones. Avoid these in patients who excete large amounts of uric acid!!!!!!!!!
tubular fluids and excretion/reabsorption
An UPWARD slope means that increased os a substance as fluid moves along the tubule, so it is either SECRETED or NOT reabsorbed. The concentrations of PAH, creatinine, inulin and urea incease as fluid runs along the proximal tubule. A DOWNWARD slope means that there is REABSORPTION of the substances
Primidone
An anti-epileptic that is metabolized to* phenobarbital* and phenyl-ethy-lmalonamide (PEMA). It is first line (or propranolol) for *BENIGN essential tremor*!!!!!
# metyrapone test:
An indicator of HPA axis integrity. Metyrapone *inhibits cortisol synthesis by blocking 11-β-hydroxylase* (responsible for the conversion of 11-deoxycortisol into cortisol). Therefore, in normal patients (intact HPA axis), metyrapone administration results in: - ↓ cortisol - ↑ ACTH - ↑ 11-deoxycortisol levels... which is further metabolized into 17-hydroxycorticosteroids, thus - ↑ urinary 17-hydroxycoritcosteroids. In a patient with *adrenocortical insufficiency* the response to metyrapone administration is: ABNORMAL - ↓ cortisol as usual - ↑ ACTH as usual BUT there is* no ↑ in 11-deoxycortisol OR 17-hydroxycorticosteroid. (!!)*
# Complications of RA
Anemia of chronic disease, due to chronic inflammatory state resulting in the production of *acute phase reactants* such as *hepsidin* ,which blocks the ability to use iron stored in the macrophages !!!! RA-associated anemia of chronic disease can result in the following lab value changes: • decreased serum Fe • increased serum ferritin • decreased serum transferrin (TIBC) - Secondary amyloidosis- chronic inflammation results in production of *acute phase reactants* such as *SAA* which is produced by the liver, which gets converted to AA, which is deposited in tissues. *vasculitis*of multiple organs *Baker's cyst* which is swelling of the bursae behind the knee
# Angina pectoris
Angina pectoris is pain caused by a *decrease in myocardial perfusion* that normally presents as tightness, squeezing, or heaviness in the chest area. It is due to coronary artery narrowing or spasm. The pain episodes caused by angina pectoris normally lasts *5-10 minutes* unless it has progressed to an ongoing infarction. Angina pectoris is the *most common syndrome of ischemic heart disease* and can present as either: - stable - unstable - prinzmetal angina.
# Angiosarcoma associations
Angiosarcoma is associated with *radiation therapy* and is especially common in those receiving radiation to treat *breast cancer* and *Hodgkin's lymphoma.*!!!!!!!!!!! It is especially associated with chronic lymphedema!
# angiotensin II
Angiotensin II acts: - on AT1 receptors on vascular smooth muscle directly to cause vasoconstriction and increase BP - In the *proximal convoluted tubule PCT* , angiotensin II stimulates Na+/H+ exchange, causing increased Na+ (and thus water reabsorption)... while it promotes secretion of H+ into the tubular lumen. The secretion of H+ into the tubular lumen THEN combines with bicarb, forming carbonic acid, which dissociates into H20+ CO2.... BOTH H2O and CO2 then diffuse into the proximal concoluted tubule cell, reform carbonic anhydrase, and dissociate into H+ and HCO3-..... THEN reabsorption of bicarbonate HCO3- into the blood. (contraction alkalosis) (basically, H+ keeps on "cycling" (not really secreted) but HCO3- is reabsorbed). - on the adrenal gland, causing the zona glomerulosa to stimulate aldosterone (and also vasoconstricts ↑ TPR) - Aldosterone promotes activity of the Na+/K+ ATPase pump (in the distal convoluted tubule and the collecting duct, Shifts Na+ into the blood (H20 follows)..... ↑ plasma volume ↑ CO = ↑ MAP (↑ TPR due to ATII also contributes to this) - causes ADH release - Acts on hypothalamus to stimulate thirst
if risk of carrying a mutated allele for cystic fibrosis is 1/30 in caucasians and 1/100 in Asians, what are the chances that a kid of the two will suffer with the disease??
Answer, since each person has two alleles, probability that both events occur is: (1/2 X 1/30) X (1/2 X 1/100) = 1/60 x 1/200 =1/12000
# Antacids
Antacids neutralize gastric acid and raise gastric pH. Common antacids include: • Aluminum hydroxide • Magnesium hydroxide • Calcium carbonate All antacids can alter the pharmacokinetics of other drugs by changing gastric and urinary pH, delaying gastric emptying, and/or chelation. All antacids can also *cause hypokalemia by inducing metabolic alkalosis*, which causes K+ entry into cells and excessive renal K+ loss
hypothalamus
Anterior pituitary controlling hormones (TRH, GnRH, GHRH, CRH) controls hunger, temperature, autonomic, sexual uges. OVLT (senses changes in osmolarity) - Supraoptic nucleus (ADH is made here) - Paraventricular nucleus (makes oxytocin)
treat anthrax
Anthrax, especially in later stages, is fatal without early, aggressive treatment. Treatment is *doxycyline or ciprofloxacin. *
# What anti CD is used in acute transplants prevention?
Anti CD-3 receptor antibodies (muromonab CD3). They block this because CD-3 is required for proper function of T-cell receptors.
# what drugs cause Torsades de pointes
Anti arhythmics, phenothiazides, and TCA's. Sotalol
subacute cerebellar degeneration antibodies
Anti-yo, Anti-P/Q, and anti-Hu.
#Eaton-Lambert syndrome (!!!)
Antibodies against *presynaptic PQ-type voltage-gated calcium channels* at the NMJ, so we cannot release Ach. Classically seen as a *paraneoplastic syndrome*, most commonly co-occurring with small cell lung carcinoma (60% of patients) (!!!) but is also associated with other malignancies (eg, lymphoma). Resolved with removal of the tumor. Involves the *proximal muscles*, but weakness is actually IMPROVED with use..... and here, the *eyes spared*. Usually begins with proximal symmetric involvement of limbs, especially the proximal legs → difficulty climbing stairs or rising from a seated position, gait abnormalities *autonomic symptoms* often occur!!! Anti-cholinesterase will NOT improve symptoms (because ACH isn't released) It actually IMPROVES with use/stimulation (unlike myasthenia gravis!!)!!!!!!!
# Sclerosis autoantibodies
Antibodies against DNA topoisomerase I (anti-Scl-70) and RNA polymerase III (anti-RNA Pol-III) are more common in diffuse systemic sclerosis !!!!! Anti-centromere are more common in CREST syndrome (which occurs in a subset of patients with limited/localized systemic sclerosis) !!!!!!! ANA is positive in 70-90% of patients with diffuse or limited systemic sclerosis
Supracondylar fracture of the distal humerus → proximal median nerve injury
Ape hand (loss of thumb opposition)
# acid fast stain
Apply an aniline dye (carbolfuchsin) and then decolonize with an acid (ie, HCl, alcohol)... it identifies Mycolic acid!!
superior orbital fissue
Area where all of the following enter the orbit CN III CN IV V1 CN VI
# arginase deficiency
Arginase is the enzyme which converts arginine into urea and ornithine. presents as spasticity
brown pigment stones
Arise from biliary tract infection! This results in the release of B-glucuronidase by injured hepatocytes and bacteria!! Causes the buildup of UCB in the bile.
black pigment stones
Arise from hemolysis
# arsenic poisoning (!!!)
Arsenic poisoning interferes with lipoic acid cofactor containing enzymes, including the pyruvate dehydrogenase complex (PDC), α-ketoglutarate dehydrogenase, and branched-chain α-keto acid dehydrogenase. Signs of arsenic poisoning are similar to PDC deficiency (lactic acidosis and neurological disturbances). Additional signs of arsenic poisoning are *garlic-scented breath, "rice-water" stools that are often bloody, and vomiting. *!!!!!
# CO2 vs O2 and cerebral blood flow
As PaCO2 increases, so does cerebral flow (and vice versa). This is because *pCO2 is THE most potent cerebrodilator*. Only VERY LOW PaO2 increases cerebral flow.
# complication of duodenal ulcer
As with any ulcer, perforation and bleeding are serious complications. Posterior duodenal ulcers have the risk of - *rupturing the gastroduodenal artery* (hemorrhage) .!!!! - acute pancreatitis Note, these are both complications of *posterior duodenal ulcers*.... however note that *anterior* duodenal ulcers ARE more common in practice. NOTE: Duodenal ulcers are RARELY malignant.
pneumoconioses location mnemomic:
Asbestos is from the roof (seen in roofers, insulation) but affects the floor (lower lobes) Siliva/coal are from the ground, but affect the roof (upper lobes) !!!!
Asbestosis
Asbestosis is a *pneumoconiosis* associated with the inhalation of asbestos particles. Classically seen in construction, roofers, plumers, shipyard workers. Asbestos causes: - fibrosis of lung - fibrosis of the pleura - cancer of the lung - cancer of the pleura (mesothelioma)
Aspergillus fumigatus vs Mucormycosis
Aspergillus- acutely angled (V-shaped, less than 45 degrees) SEPTATE hyphae. Mucormycosis (rizopus) is BROAD angled NON-SEPTATE hyphae
# what is the treatment for TIA's?
Aspirin, prevents ischemic strokes
# increased bleeding time
Assessment of PLATELET function. Increased in: Thrombocytopenia Von willebrand disease Defects of platet aggregation Aspirin DIC
# myasthenia gravis is associated with?
Associated with *thymus abnormalities* like *thymic follicular B-cell hyperplasia* (due to antibody producing B-cells in the thymus) or *thymoma* !!! (if you have either of these and we *remove the thymus*, then *symptoms improve*!!!) !! So it *often presents with a anterior mediastinal mass* !!!!!!
# EBV and lymphoma
Associated with both 1) Hodgkin's lymphoma: 2) Burkitt's lymphoma ((also known as small noncleaved non-Hodgkin's lymphoma):
# Squamous cell carcinoma of lung paraneoplasm (!!!)
Associated with paraneoplastic syndrome producing *hyperparathyroidism* via ectopic *PTHrP* ( (parathyroid hormone related peptide) production..... leads to *hypercalcemia* of malignancy. PTHrP is structurally very similar to PTH.
alveolar hyperventilation
Assuming normal rate of metabolic CO2 production, *HYPOcapnia implies alveolar hyperventilation*. Hypocapnia= low PaCO2 Can result from a *ventilation-perfusion mismatch* that causes decreased O2 and CO2 exchange (ie, pneumonia or PE). The resultant hypoxemia stimulates peripheral chemoreceptors which increases respiratory drive, and leads to excessive breathing (and thus, CO2 excretion, causing hypocapnia). But, the *hypoxemia persists* since blood flowing through the highly oxygenated lungs *cannot absorb the extra O2*. This needs to be treated by Oxygen, and treating the underlying condition. Without it, respiratory muscle fatigue will occur.
# Schizoaffective disorder
At LEAST 2 weeks of STABLE mood but with psychotic symptoms, plus a mood disorder like major depressive, manic, or both (mixed) Psychosis occurs in the ABSENSE of major mood episodes (mania, depression!!!!!).... But the mood episodes must be there most of the time.
# ataxia-telangiectasia presentation
Ataxia refers to poor coordination (*there is cerebellar atrophy*!!! ). Ususally there is *truncal ataxia* as a toddler which presents to *perhiperal ataxia* with chorea, athetosis, dystonia, myocolnus..... and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease.... Development of ocular telangiectasias, usually by age 5 "patients have a median lifespan of 20 years due to *severe, recurrent sinopulmonary infections*!!!! ..... - It weakens the immune system because of *defective antibodyclass switching* causing a predisposition to infection because of *IgA deficiency* (and other Ig deficiency as well) !!! Also a risk of *CANCER* !! (ineffective DNA repair)
Atypical antipsychotics
Atypical Antipsychotics: block 5-HT2, dopamine, α1, and H1 receptors and are associated with less extrapyramidal side effects than traditional antipsychotics , such as olanzapine, risperidone, and quetiapine, are less likely to cause extra-pyramidal symptoms but are more likely to cause metabolic effects and other miscellaneous side effects. (sedation, weight gain, constipation, headaches)
#Gilbert syndrome
Auto-recessive mildly low UGT (uridine glucuronyl transferase) activity.... Due to a mutation in the *TATA BOX* promoter upstream,. Increased UCB (indirect, unconjugated) because liver hepatocytes cannot take up the UCB. Liver function test, complete blood count, blood smear and reticulocyte count are ALL normal. *Patients develop mild jaundice during times of stress (infection, fasting, etc) etc.!!! *
# Heparin induced thrombocytopenia
Autoantibody IgG formed against the Heparin/PF4 complex. (Type II Hypersensitivity) These immune complexes induce activation of platelets → patients become hyper-coagulant and are at risk for thrombosis and thromboembolic events (!!!) Patients generally present 5-14 days following heparin treatment with signs/symptoms of thrombocytopenia and arterial or venous thrombosis. Note: the presence of heparin is required to trigger platelet activation. Thus, all heparin administration should be immediately stopped in patients suspected of having HIT!! # treat heparin induced thrombocytopenia Treat with *direct thrombin inhibitors* which bind to the thrombin active sites. lepirudin argatroban hirudin
# Dermatitis herpetiformis
Autoimmune deposition of *IgA* at the tips of the *dermal papillae* , which contain blood vessels to feel the epidermis. Deposition here results in a tiny blister, which *resembles* blisters that look like herpes. Presents as *pruritic vesicles and bullae* that are *grouped together*, distributed over *extensor surfaces*, including the elbows, knees, buttocks, and shoulders There is a *strong association with celiac disease* !!!! The IgA antibodies that are deposited are actually *antibodies against gliadin* which *cross react* with *reticulin fibers attaching basement membrane to dermis*. SO, if we treat celiac, the dermatitis herpetaformis also improves !!!!! (gluten free diet)
# Multiple Sclerosis
Autoimmune destruction of *CNS myelin AND oligodendrocytes !!!!! There is loss of myelin sheaths, and depletion of the oligodendrocytes. marked by unpredictable relapses with long asymptomatic remissions. Most common chronic CNS disease of young adults, more commonly in women. Peripheral nerves NOT affected, only CNS (Remember: the optic nerve is an extension of the CNS, not a true peripheral nerve) • Environmental triggers → activate helper T cells whose receptors recognize CNS myelin basic protein and other antigens → multiple foci of demyelination plaques in the cortex, spinal cord, optic nerve, and paraventricular areas Genetic susceptibility is *HLA-DR2*.... more commonly seen in *regions AWAY from the equator* !!!!
pemphigus vulgaris
Autoimmune destruction of the *desmosomes* in the *stratum spinosum*, due to an *IgG antibody against desmoglein* (desmoglein is the "glue" that attaches adjacent epidermal cells via attachment points called desmosomes) !! This creates a big vesicle in between the basal cells (which are intact to the basement membrane by *hemidesmosomes*) , and the rest of the epidermis. Called *tombstone appearance* because the basal cells still attached to the basement membrane. *acantholysis* (separation of keratinocytes) occurs in the *stratum spinosum* This *easily ruptures* because of thin epidermis. positive Nikolsky sign (gentle rubbing of unaffected skin → separation of epidermis) a *biopsy with immunofluorescence* shows *IgG surrounding the keratinocytes* , which is called a *fish net* appearance. !!! Very important to note it can involve the *oral musoca* as well!!! (ie, lip surface) !!!!
Bullous Pemphigoid
Autoimmune destruction of the *hemidesmosomes*, due to an *IgG antibody against the in the type XVII collagen components of hemidesmosomes in the basement membrane* at the *dermal-epidermal junction*, giving a *LINEAR pattern immunofluorescence* The *entire epidermis* is lifted off the dermis, so we get a *subepidermal* blister of the skin, with the *oral musoca spared* !!!! The tense bullae *do not rupture very easily* because the wall is thicker because it contains the *entire epidermis*
Adrenal glands
B Zona glomerulosa -->Aldosterone other options C -zona fasciculata, D -zona reticularis, E -adrenal medulla
# treat Graves disease
B-blockers - Thioamide (blocks peroxidase, ability to produce thyroid hormone) - radioiodine (taken up by thyroid, and 'ablate' or destroys... use I131 (versus the 123 used in imaging studies) - corticosteroids (used to control Graves ophthalmopathy!!!)
# BCL2 and follicular lymphoma
BCL2 stabilizes mitochodrial membrane by prohibiting cytochrome C from leaking from mitrochondria into cytoplasm. This BLOCKS apoptosis, which is what you usually want. Note: you actually WANT apoptosis in follicle more than almost any other place, because in follicle we get somatic hypermutation of B cells where they are challenged with 'selection', and vast majority fail (undergo apoptosis), some pass. This translocation allows cells that should have died, to survive.
# Meningioma
BENIGN tumor of *arachnoid cells*.... more commonly in females, likely due to the fact that estrogen somehow may promote it, as the tumor DOES have a receptor for estrogen. The tumor forms a *round mass* that is *attached to the dura* which is visable on imaging.... This mass can press on the *cortex* and cause *seizures* as well as contralateral spastic paresis of the leg* !! (it compresses, but does NOT invade).
# ways to inactivate Hep A
BOIL for a minute water chlorination bleach UV irradiation
Carbamazepine sides
BONE MARROW suppression (leading to anemia, agranulocytosis, thrombocytopenia) - it is HEPATOTOXIC - can cause SIADH
# anthrax transmission
Bacillus anthracis is transmitted via skin contact, inhalation, or ingestion of spores and often occurs in individuals exposed to *infected herbivores, their skins, and carcasses. Common in wool!!! * • Bacillus anthracis spores are present in dry soil and in the gastrointestinal tract of animals. • Exposure to infected cows, goats, and *other herbivores*, and their *carcasses, skins, furs,* and other products can cause naturally-occurring anthrax infection. • *When exposed to harsh conditions, Bacillus anthracis forms spores. * Spores can survive in dry soil and goat skin for many years. Grazing herbivores ingest spores on grass and acquire alimentary canal anthrax. Spores are excreted in feces. Humans can acquire spores via close contact with infected animal products. Once exposed to suitable conditions in humans or animals, the spores revert to metabolically active bacteria.
Cystic fibrosis defects
Bacteria stick to viscid mucous and aren't cleared → inflammation, infection • Respiratory tract → recurrent Pseudomonas and Staph pneumonias, chronic bronchitis, bronchiectasis, nasal polyps (especially newborns!!) • Pancreas → pancreatic insufficiency (steatorrhea, malabsorption), fat soluble vitamin deficiency..... Intestinal tract → meconium ileus, obstructive cirrhosis (from ↑ bile viscosity) • Mutations in CFTR can cause congenital bilateral absence of the vas deferens → male infertility !!!!!!!!!
# Hep B histology (!)
Ballooning degeneration, hepatocyte necrosis, and portal inflammation, like all hepatitis... but the cytoplasm is fulled with *spheres and tubules of HBsASG), and the cytoplasm then becomes finely granular "ground glass)
# Becker muscular dystrophy
Basically the same disease as DMD, but here, the dystrophin gene is *point mutated* instead of deleted! So some of the protein is still produced, and the disease is milder clinically.
# Name the X-linked recessive disorders
Be Wise, Fools' GOLD Heeds Silly Hope • Bruton's Agammaglobulinemia • Wiskott-Aldrich • Fabry's disease • G6PD deficiency • Ocular albinism . • Lesch-Nyhan • Duchenne's (and Becker's) muscular dystrophy • Hunter's Syndrome • SCID (severe combined immunodeficiency) • Hemophilia A and B
# Sarcoidosis and salivary gland
Be careful to differentiate it with *Sjogren syndrome* !! (can't chew cracker, dirt in eyes, dental risk) ... if biopsy shows *non caseating granulomas* it is sarcoidosis, not Sjogren syndrome.
# Calcium channel blocker uses (!)
Because *nifedipine* has vascular preference and *dilates the veins more than arteries*...... it is used to treat *Raynaud disease* to prevent the vasoconstriction of the distal digits. It is used in hypertension because it is a vasodilator. (!!!) *Verapamil* works on the ventricle and is therefore used to treat *arrhythmias, and angina*!!!!! It *SLOWS AV NODE CONDUCTION*!!!! But can lead to Bradycardia, and heart blocks. Nifedipine is useful for *bradycardia* !!! it would be *VERY BAD* to use *nifedipine* for *angina* because it acts on the blood vessels, causing *vasodilation*and *reflex tachycardia*, making angina worse! ( do NOT use Calcium channel blockers for *malignant hypertension* for this very reason!)
# B-blocker sides
Because beta blockade causes *decreased AV conduction*, it can *precipitate heart block* (prolongs the PR interval!!!!!!!!!) - bradycardia - CNS effects (seizures, sedation, sleep alterations) nonselective beta blockers can cause *bronchospasm*, DYSPNEA and WHEEZE due to prevention of β2 mediated bronchodilation (do NOT give to asthmatics/COPD)!!! !!! β 1-blockade may also *mask* the adrenergic symptoms of hypoglycemia. *β2 blockade is less clinically useful because *preventing bronchial dilation is not helpful*, although preventing cerebral vasodilation makes β2 blockade attractive for migraine headache prophylaxis.* NOTE: do NOT give either non-selective beta-blockers OR selective beta-2 blockers in asthmatics, or COPD!!!!.
Hydralazine side effects
Because it is a *direct arteriolar dilator*, it will lower blood pressure, triggering the baroreceptors to increase sympathetic flow. This leads to: - decrease vagal tone of the heart, leading to *reflex tachycardia* - increased RAAS leading to sodium retention and *edema*. - fluid retention can occur (combine with a diuretic) !!! *Cerebral vasodilation* is implicated in migraines, so *headache* is also a potential side effect. *Angina* or *coronary artery disease* is a contraindication because the reflex tachycardia can *increase myocardial oxygen consumption* and lead to worsening disease. Thus, we often *combine it with beta blockers* to prevent tachycardia. Also it is associated with Lupus-like syndrome with malar rash, kidney dysfunction, arthlagia, etc... (high yield!!!)
# why do RBC's have low chloride in arterial blood,, but HIGH chloride in venous blood) ?
Because of *chloride shift*. Hb carries CO2 as either: Hb-NH-CO2 HCO3- Bicarb diffuses out, chloride in.
# CK-MB
Begins to rise 4-6 hours after onset. - peaks at 24 hours - and returns to normal within 2-3 days Re-elevation of CK-MB can diagnose a *re-infarction between *3 and 10 days post myocardial infarction, however *troponin cannot diagnose re-infarction* between days 3 and 10 because troponin is still elevated from the first infarction!
# metanephros development
Begins with development of the *ureteric bud*, which sprouts off from the caudal end of the mesonephric duct. The ureteric bud then gives rise to the metanephric mesoderm. - Ureteric bud gives rise to collecting system of the kidney, including: Collecting tubules and collecting ducts Major.minor calyces Renal pelvis Ureter - Metanephric blastema (aka metanephric mesoderm) gives rise to Glomeruli, Bowman's space, proximal tubules, Loop of Henle, Distal convoluted tubule.
#treat somatic symptom / pain disorder
Behavioral therapy is the first line, may also include physio or psychotherapy TCA's and venlafaxine can be appropriate Schedule *regular visits* with the SAME (GP?) provider (!!) to MONITOR them !!!!
# Benign vs Malignant hypertension
Benign hypertension: Mild or moderate elevation in blood pressure. *Clinically silent*, with the *vessels and organs damaged over time* Malignant hypertension: accelerated clinical course involving *systolic BP > 180 mmHg and/or diastolic BP > 120 mmHg*
# Neoplastic, aka adenomatous polyps
Benign neoplastic prolifferation of glands, but is *premalignant*, and can progress to *adenocarcinoma* via the *adenoma-carcinoma sequence* 3 types: ranked in order of increasing malignant potential: tubular adenoma → tubulovillous adenoma → villous adenoma (villious is the villain!!)
# beriberi
Beriberi has a dry (muscle wasting, sensory neuropathy, motor impairment, peripheral neuropathy) - wet (congestive *high pressure* heart failure marked by peripheral edema, cardiomegaly, dilated cardiomyopathy) component !! )
# Eosinophils/ eosinophilia
Bilobed nucleus. Intracellular granules stain well with acid (e.g. eosin) dyes, hence "eosinophilic" Granules contain cytotoxins: major basic protein, eosinophil peroxidase, histaminase and arylsulfatase. Defends against *parasites: *e.g., helminths → eosinophilia is a marker for some parasitic infections When a parasite enters the blood, it is first bound by free IgE. The resultant antigen-antibody complex binds an IgE Fc receptor located on the eosinophil cell curface. The eosinophil then releases *major basic protein* and other enzymes from its granules. This is an example of ADCC !!!!!!! ( Major basic protein is a toxic component of the lysosomal granules and is an important mediator in the death of parasites and protozoa.) Also upregulated in allergic reactions (esp. drug reactions) and collagen vascular diseases (e.g. rheumatoid arthritis, Churg-Strauss vasculitis)
Basophils
Bilobed nucleus. Intracellular granules stain well with basic dyes, hence "basophilic" Granules contain: Heparin Histamine → key role in mediating allergic reactions Leukotrienes and cytokines are synthesized on demand
# heparin aka unfractionated heparin
Binds tightly to the antithrombin III site and causes a conformational change in antithrombin III (a natural anticoagulant), thus, this catalyzes the reaction between antithrombin III and the serine protease clotting factors → *inactivates both thrombin AND Xa* !!!! Given for immediate anticoagulation (DVT/PE, MI, stroke): immediate onset if IV, ~30 minutes if SC *commonly used as prophylasis against immobilization for DVT* !!!! (ie, *knee/hip surgery* Heparin does not cross the placenta (heparin is water soluble, warwarin is lipid soluble) , and thus is safer than warfarin in pregnancy.
# von willebrand factor
Binds to both GP Ib-IX on platelets, which thus mediates their binding to *damaged subendothelial collagen*. ALSO functions as a *carrier protein for factor VIII* . In the absence of vWF, factor VIII is rapidly degraded!!! (ie, 2 hour half like, instead of 12 hour half life)
#Bipolar Disorder
Bipolar Disorder I: Diagnosis requires at least one episode of mania. Many patients with Bipolar I have also experienced a major depressive episode, but this is not required for diagnosis Bipolar Disorder II: Diagnosis requires episodes of both hypomania and major depression
# Sucralfate/bismuth
Bismuth and sucralfate are SULFATE-ALLUMINUM and both *coat the ulcer base, neutralizing acid and allowing the HCO3- gradient to be re-established in mucous layer. * • Sucralfate is safe in pregnancy because it is not absorbed systemically. There is also no major change in gastric pH, leading to decreased risk of aspiration pneumonia from the gastrointestinal tract. Used mostly in ULCERS
# Blastomyces
Blastomycosis is a fungal infection of humans and other animals caused by the organism Blastomyces dermatitidis, a *dimorphic fungi. * It involves the *LUNGS in innumocompetent people.,* Acute asymptomatic infection Acute or chronic pneumonia that can lead to granulomas in the lung • *Extrapulmonary disease most commonly involving the skin and bones in the IMMUNOCOMPROMISED* The manifestations of blastomycosis in can be remembered with the mnemonic *BLAS*to • Bone (lytic lesions) • Lung • And Skin
Blastomycosis areas
Blastomycosis is transmitted via *inhalation of spores (conidia) typically from moist soil which is EAST OF THE MISSISISPPI RIVER. * Blastomycosis is endemic in the *southeastern and south-central states that border the Mississippi and Ohio River basins, Great Lakes, and a small portion of New York and Canada* along the St. Lawrence River.
# Subdural hematoma
Bleed in the arachnoid (*subdural* ) usually due to *rupture of cortical bridging vein*, which are often easily ruptured. Seen in elderly, shaken babies, whiplash. ... even blunt trauma The CT shows a CRESCENT shape lesion. It DOES cross suture lines, but CANNOT cross falx, tentorium. Presents with *gradual, progressive neurologic signs*.... again, *herniation* is the lethal complication, due to mass effect or increased intracranial pressure
# Intracerebral hemorrhage
Bleeding into the *brain parenchyma* Often usually due to *chronic Hypertension* which causes *small vessel vasculopathy* → predisposes to the formation of *Charcot-Bouchard aneurysms* in the DEEP BRAIN structures, which may rupture due to the increased wall stress caused by hypertension
calcium channel blockers
Block voltage dependent *L type* calcium channels in both *cardiac*, and *smooth muscle cells*, causing inotropy and vasodilation. ↓ TPR (total peripheral resistance) ∴ ↓ afterload Recall that the *L-type calcium channels* mediate *phase 2* of the myocyte action potential, which *normally* allows *calcium influx* and *calcium-induced calcium* release to initiate myocyte contraction ● Cardiac L-type channels: Verapamil > diltiazem > nifedipine (Verapamil likes the Ventricles!!! ) *Verapamil* and Diltiazam (are NON dihydropyridine* calcium channel blockers, so they cause bradycardia!!!! Nifedipene causes reflex tachycardia!!! ● Vascular L-type channels: nifedipine > diltiazem > verapamil (the exact opposite as the above)
Ethosuxamide
Blocks T-type calcium channels which trigger/sustain rhythmical burst in thalamic neurons! it is used for ABSENCE seizures!!!!!!!
# Myelofibrosis blood labs (!!!)
Blood smear for a patient with myelofibrosis may show poikilocytosis (red-blood cells (RBCs) with different shapes), anisocytosis (RBCs of different sizes), nucleated RBCs, polychromasia, and *teardrop shaped RBCs* called *dacrocytes*!!!!!!!! CBC for a patient with myelofibrosis will show anemia, leukopenia or leukocytosis, and thrombocytopenia or thrombocytosis. Flow cytometry will show an increase in +CD34 cells. Bone marrow aspirate from a patient with myelofibrosis may show a dry tap. It may also show neutrophilic and megakaryocytic hyperplasia.
# Hep C transmission
Blood, IVDU (especially w/HIV) (not really sexual)
# MS clinical features
Blurred vision in ONE eye (Optic neuritis, usually first sign, blurry vision or sudden painful loss of vision). Painful ocular movements (!!!!) Vertigo and *scanning speech* if the *brainstem* is involved!! (resembles 'drunk speech'). *Internuclear ophthalmoplegia* if it involves the *medial longitudinal fasiculus* *Hemiparesis* or *unilateral loss of sensation* if it involves the *cerebral white matter* Lower extremity loss of sensation OR weakness (if it involves spinal cord) Bowel/bladder/sexual dysfunction if it involves the *autonomic nervous system*.
# treat SCID
Bone marrow transplant is the mainstay of SCID treatment (without bone marrow transplant, SCID infants will die within the first year of life). ADA deficiency can be treated with enzyme replacement therapy. • X-linked Severe Combined Immunodeficiency (SCID) was the first human disease to be successfully treated with gene therapy, involving the insertion of a normal γ-chain gene in transplanted bone marrow stem cells. *Adenosine deaminase (ADA) deficiency SCID has also been treated with gene therapy, where a vector "infects" and introduced a normal ADA gene into T cell precursors. *
# Hodgkins vs non-Hodgkins lymphoma
Both Hodgkin's lymphoma and non-Hodgkin's lymphoma are lymphomas, a type of cancer that begins in a subset of white blood cells called *lymphocytes*. The main difference between Hodgkin's and non-Hodgkin's lymphoma is in the specific lymphocyte each involves. Hodgkin's have Reed-Sternberg cell.... if is not present, the lymphoma is classified as non-Hodgkin's.
#meissner corpuscles vs pacinian corpuscles
Both are large, myelinated fibers which adapt quickly *Meissner's corpuscles* are located immediately below the dermis in the dermal papillae in *glabrous(hairless) skin* (fingertips, soles of feet, palms, lips, genitaliia)!! Involved in fine/light touch and position sense *Pacinian corpuscles* are located in the deep skin, ligaments and joints.... involves in vibration, course touch, and pressure.!! "pacinian packs a punch".
elastase inhibitors
Both neutrophils and macrophages produce elastase. Neutrophil elastase is inhibited by alpha1 antitrypsin. Macrophage elastase inhibited by tissue inhibitors of metalloproteinases (TIMPs). Note: both neutrophil and macrophage elastase can degrade each others (but not their own) inhibitors.
# Botulinum toxin vs Tetanus toxin
Botulinum toxin (botox) and tetanus toxin (tetanospasmin)—both cleave the releasing protein synaptobrevin, thereby inhibiting neurotransmitter release. However, although they share a similar mechanism, these toxins affect the release of different neurotransmitters: Tetanus toxin cleaves synaptobrevin → *inhibits release of GABA and glycine → rigid paralysis.* Botulinum toxin cleaves synaptobrevin → *inhibits release of ACh → flaccid paralysis. *
# myocardial shunting
Brief ischemic episodes (<30 mins) followed by reprofusion. It can progress to hibernating myocardium*.
# Classic X-Linked Agammaglobinemia (Bruton's) presentation
Bruton agammaglobulinemia is usually diagnosed in male infants when levels of maternal IgG decline (around 4-6 months of age) — affected children often present with a long history of recurrent bacterial !!!! infections. Also enterovirus (affects mucosal surface of GI tract), and *Giardia infections!!!!! * AVOID live vaccines (ie polio)
# Buerger disease
Buerger disease (thromboangiitis obliterans) is a *necrotizing medium-sized vessel SEGMENTAL vasculitis* with *digital vessel thrombosis* and *damage to neurovascular compartment.* (the vasculitis extends into veins and nerves!!!!) Buerger disease most commonly occurs in *male smokers between the ages of 25 and 50 (usually under the age of 40)*. VERY VERY VERY associated with smoking!!! Either CAUSED by smoking, or due to a HYPERSENSITIVITY TO SMOKING. Physical symptoms involve the *lower extremities in 100% of the cases*, and are characterized by resting pain on the forefoot, with possible *ischemic ulcers* or *gangrene of the foot and toes*. Physical symptoms involve the *upper extremities in 40-50%* of the cases that are characterized by *upper limb ischemia with ulceration and gangrene* and *Raynaud phenomenon* (vasospasm cuts blood supply to fingers, then become white, then blue with cyannosis, then red as blood returns) . Amputation resulting from ischemia and gangrene is a common complication.
# what medications can increase the risk of seizures?
Bupropion (antidepressant) Clozapine isoniazid if given without pyridoxine Ciprofloxacin (antibiotic) Imipenem (antibiotic)
# What CD's are used to identify B and T cells?
CD20 B cells CD3 is T-cells
Centriacinar emphysema
CENTRIACINAR emphysema is caused by smoking, and affects upper lobes. Centriacinar (Centrilobular) emphysema there is *enlarged respiratory bronchiole* but *spared alveoli* !!!! . Commonly caused by *smoking* and primarily affects the *upper lobes* of the lung (because once smoke is in the lung, it goes *up*... thick of blowing out a match, and smoke rises).!!!!!!!
# What is the most common form of spongiform encephalopathy?? !!!
CJD (Creutzfeldt Jakob disease) Usually sporadic, but in rare cases may be due to exposure to *prion infected human tissue* (ie, corneal transplant, etc) Presents as a long incubation period, followed by *very very rapidly progressing dementia* (weeks!!!!!).... Associated with *ataxia* (because cerebellum is involved) and *startle myoclonus* (involuntary muscle contractions with minimal stimuli).
# CML diagnosis (!)
CML must be distinguished from leukemoid reaction (ie infection, which also produces high WBC's !!! ) 3 key ways to distinguish: 1) CML granulocytes have very low leukocyte alkaline phosphatase (LAP) activity (!!!) (compare to leukemoid reaction which have high levels) 2) CML is associated with increased basophils 3) look for t(9;22) translocation.
CMV retinitis
CMV is the most common cause of retinitis in HIV patients!!!!! CD4+ cells usually <50!!!! Treat with CMV with *ganciclovir* !!!!!!!!! (Acyclovir is herpes!!!!)
# feared complication of measles
CNS (possible encephalitis) → *many years later* potential for *SSPE (Subacute Sclerosing Panencephalitis*).... a progressive encephalitis that is a rare and late manifestation of measles. It involves both gray and white matter causing slow CNS degeneration.
Mean arterial pressure
CO X TPR MAP= 2/3 diastolic pressure + 1/3 systolic pressure
non communicating hydrocephalus
CSF flow from the ventricules to the subarachnoid space IS impaired. Ventricles ABOVE the obstruction are enlarged, while those below it are normal. Due to congenital conditions - Arnold Chiari dandy walker OR due to mass effect
# Chronic bronchitis Xray
CXR: prominent vessels, large heart and moderate hyperinflation (compare to emphysema which has marked hyperinflation). Clinical findings include wheezing, crackles, and cyanosis
# EBV non-Hodgkins
Called Burkitt's lymphoma!! African form commonly presents as a mass on the maxilla or mandible; American form more commonly presents as an *abdominal mass with ascites!!* Lymphoid tissues have a "starry sky" appearance: - dark sky = many many many sheets of high-grade lymphocytes - stars = macrophages eating apoptotic high grade tumor Ki-67 fraction is near 100 !!!!! "8urkitt's" (8 looks like a B): Most common translocation = t(8;14): c-myc proto-oncogene ends up next to highly expressed Ig heavy-chain gene, and there is * c-myc overexpression*!!! Because Burkitt lymphoma exhibits a very high mitotic rate and rapid turnover of cells with high levels of apoptosis (!!!), it inherently can NOT express Bcl-2. Contrast this with follicular lymphoma where translocation causes overexpression of Bcl-2.
Langerhans cell tumor
Called Langerhans cell histiocytosis. Cells often have BIRBECK "tennis racket" granules seen on EM !!
#inferior gluteal nerve
Can be caused by a posterior hip dislocation • Can't jump, climb stairs, or rise from a seated position • Innervates gluteus maximus-principal extensor of the thigh
# Treat TB
Can be remembered with mnemonic: RIPE: Rifampin INH Pyrazinamide Ethambutol
# posterior hip dislocation
Can injure the superior gluteal nerve (L4-S1) or the inferior glureal nerve (L5-S2).
#caplan syndrome
Caplan syndrome is a disorder comprised of: • Rheumatoid arthritis (RA) • Intrapulmonary rheumatoid nodules • Pneumoconiosis
where are beta 1 receptors located ?
Cardiac and renal juxtaglomerular cells ONLY. It does NOT act on smooth muscle. Note, VASCULAR SMOOTH MUSCLE also contains *beta 2* receptors (think about it, clenbuterol for asthma is selective beta 2). increases atrial & ventricular cardiac muscle contractility Increases heart rate in SA node (chronotropic effect), and conduction at AV node increases cardiac O2 consumption!!!! Note, this is SPECIFIC for beta blockers! (nitrates ALSO increase HR) • increases renin (so b1 blockers decrease renin and the entire RAAS!!!!) • increases lipolysis via HSL (hormone sensitive lipase)
Cardiac tamponade:
Cardiac tamponade is compression of the heart by rapid accumulation of fluid in the pericardial sac. • The pericardial sac can withstand slowly developing effusion of up to 1500 mL before showing signs of cardiac tamponade; however, rapidly accumulating effusion of just 100 to 200 mL of fluid can be symptomatic.(!!!) The build-up of fluid prevents proper cardiac function, leading to insufficient cardiac filling. Cardiac tamponade affects cardiac hemodynamics by creating equilibrium of diastolic pressures in all 4 chambers. • Since the right side of the heart is under lower pressure, it is most susceptible to compression by pericardial effusion. !!!
# struck by lightening injury
Cardiac- arrest/arrhythmia Neurologic- peripheral nerve damage, seizure, confusion, respiratory arrest, autonomic dysfunction Dermatologic- *Lichtenberg figures* which are *erythematous cutaneous marks in a fern leaf pattern* Musculoskeletal- rhabdomyolisis, bone fractures Note, although the only skin lesion may not seem serious, it can be VERY serious
Distal median nerve injury
Carpal tunnel syndrome or dislocation of the lunate into the carpal tunnel causes : Cannot flex the first 3 fingers. • If a median nerve lesion is proximal to the bifurcation of the palmar branch (eg, supracondylar humeral fracture), then the sensation in the midpalm and thenar eminence will be compromised • However, if a median nerve lesion is distal to the bifurcation of the palmar branch (eg, carpal tunnel syndrome, dislocated lunate), then *the sensation in the midpalm and thenar eminence is usually intact *
# Catalase positize Chronic Granulomatous Disease organisms
Catalase-positive organisms are phagocytosed but CANNOT be killed because they *degrade their own H2O2 (!!)* (note, most bacteria, catalase negative ones, produce some H2O2 themselves).
Striatum is composed of:
Caudate + putamen
# ischemic colitis and watershed areas!!!
Cause of lower GI hemorrhage in the elderly. Patients present with crampy, abdominal pain, tenderness to palpitation, and bloody stool. Occurs via: 1) hypoperfusion secondary to fiminished cardiac output (ie, cardiac disease, prolonged shock) 2) occlusion of bowel vascular supply (atheroma, thrombosis, embolism). Iikely affects the watershed regions!!!
# Pineal germinomas:
Cause: 1. Precocious puberty due to EXCESS hCG 2. Adquductal compression leading to *obstructive hydrocephalus* 3. *Parinaud syndrome*, which is IMPAIRED UPWARD GAZE
# anthrax!!
Caused by *bacillus anthracis*. B. anthracis is the only bacteria with a protein capsule, specifically a *protein (poly-D-glutamate) capsule !!!!!!! . * Can cause cutaneous anthrax or pulmonary anthrax
# Diphtheria
Caused by *corynebacterium diphtheria*. C. diphtheriae *synthesizes an AB exotoxin (think A=active and B=binding)* from an encoded bacteriophage. The A exotoxin *inhibits protein synthesis by catalyzes intracellular ADP-ribosylation of EF-2, inhibiting EF-2 (Elongation Factor 2!!!!!!!!) and thereby preventing tRNA translocation from ribosomal A-sites to P-sites. * • This toxin results in cardiac (arrhythmia and myocarditis) and nervous (cranial and peripheral nerve palsy) effects. Patients with diphtheria typically present with • *Grayish-white pseudomembranes in oropharynx* that can lead to suffocation • *Cervical lymphadenopathy ("Bull's neck"* • *Myocarditis if left untreated* • *Culture of C. diphtheriae on cystine-tellurite agar will reveal black colonies.* !!!!!!!! • C. diphtheriae has a "Chinese letter" appearance under microscopy. Treatment includes- antitoxin for toxin neutralization *passive immunity*, this is the most important!!!! This produces IgG against the exotoxin B subunit, preventing disease!!!!!! penicillin or erythromycin for local colonization DTaP booster to prevent recolonization. (*active immunity*)
# bacterial vaginosis/ bacterial vaginalis
Caused by Gardnerella vaginalis !! Women with bacterial vaginosis are *mainly asymptomatic..... but symptomatic women typically present with off-white, thin, and homogenous vaginal discharge and/or fishy vaginal odor. * Diagnosis of bacterial vaginosis is made based on the presence of at least three of the following four criteria: • Homogenous, thin, grayish-white discharge that smoothly coats the vaginal walls • *Vaginal pH greater than 4.5 • Positive whiff-amine test, which is characterized by the presence of fishy odor when KOH is added to a sample of vaginal discharge • Clue cells on saline wet mount*
# mycobacterium avium complex (MAC)
Caused by NON-tuberculous mycobacteria, M avium and M intracellularae. They are still acid fast. Opportunistic infection in HIV, especially those with CD4 < 50 !! Presents with skin pallor, hepatosplenomegaly, elevated ALP and LDH... also general unwell (dever, weight loss, diarrhea) Treat with prophylactic *azithromycin* !!!!!!!
# squamous bronchial metaplasia
Caused by SMOKING,. Normally, the respiratory system is lined by pseudostratified columnar epithelium with goblet cells. Smoking causes chronic irritation and leads to *formation of squamous epithelium* !!! The squamous epithelium is *more resistant to irritation* (like in Barrett's !!!)... but it does NOT contain cilia or goblet cells, so there is no mucocilliatory clearance.
Berylliosis aka beryllium lung disease*
Caused by beryllium, a light alkali metal used in manufacturing for its nonsparking quality. It's used in *manufacturing* ceramic heat shields for nuclear weapons, *spacecraft*, and computer parts. It causes *granulomatous fibrosis* of the lungs, hilar lymph nodes, and systemic organs (sounds exactly like sarcoidosis!! Be careful!!! Look for aerospace workers, computer workers, etc. )!!!
# Communicating hydrocephalus
Caused by decreased resorption of CSF by the arachnoid granulations. Unlike non-communicating, there is no blockage of CSF flow. Usually results in *impaired CSF absorption by the arachnoid villi due to *inflammation and fibrosis via hemorrhage or infection* The main type of communicating hydrocephalus is normal pressure hydrocephalus (NPH), *Symmetrical enlargement of the brain ventricles*, due to obstruction of the arachnoid villi.
# syphilis overview, how is it viewed??
Caused by infection by the SPIROCHETE *treponema pallidum*. Can be primary, secondary, tertiary... and is treated with penicillin G. T. pallidum can be visualized with dark-field microscopy !!!!!!!!!!!!
# Vagus nerve stimulation on pulmonary system
Causes *M3 mediated bronchoconstriction* and *increased mucous gland stimulation*. This *increases airflow resistance andwork of breathing*!!!! ANTI-cholinergics (tiotropium, ipratropium) BLOCK this!!!!!
# rizopus
Causes *mucormycosis*, which presents as *paranasal infection in the immunocompromised or diabetics!!! * Also *facial pain, periorbital pain, and headaches*. The infection (by spore inhalation) ascends from the nasal passage to the sinus then sometimes the brain, leading to confusion, neurological defects and death. Black necrotic eschar in the nasal cavity is characteristic. Fungi show BROAD hyphae.
# trypanosoma cruzi
Causes achalasia in patients from Central or South America!! Dysphagia for liquids and difficulty belching, along with dilates esophagus and absent peristalsis in esophagus.
# Tetralogy of Fallot
Causes by *anterosuperior displacement of the infundibular septum*..... characterized by *four congenital* abnormalities that include: 1. right ventricular outflow stenosis of pulmonic tract 2. RV hypertrophy secondary to outflow obstruction 3. Ventricular septal defect (!!) 4. Overriding aorta that overrides the VSD (!!!) Blood goes RA-RV no problem, but then in RV it gets shunted *right to left* through aorta. A SEVERE systolic ejection murmur and systolic thrill is heard at left strernal border.
# Marijuana
Causes euphoria, anxiety, paranoid delusions, slowed time perception, .... Increased appetite, dry mouth, conjunctival injection (red eye)
#what cell changes are irreversible?
Cells can undergo changes that are irreversible. Cellular changes that are irreversible are anaplasia, neoplasia, and desmoplasia.
# SLE pathogenesis
Cells undergo apoptosis (ie, from DNA damage), and release nuclear debris. self reactive B-lymphocyte may be exposed, and it *produces anti-nuclear antigens. * Antigen-antibody complexes are deposited in multiple tissues, and this activates complement, which damages those tissues. (Type 3 HSR) S/Sx: joint/muscle/chest pain, headaches, fever, oral ulcers, rashes, damages serosa. Destruction of cells in the blood, so antibodies against: (this is Type 2 HSR!!!) It produces a *pancytopenia!!!!* - RBCs lead to anemia, - against platelets thryombocytopenia - against WBCs leads to leukopenia. Common death causes are renal failure and infection (antibodies destroy WBCs). 30% of patients get antiphospholipid syndrome (anti cardiolipin, lupus anticoagulant. Latter makes patient HYPER coaguable, produce thrombosis in both arteries (stroke) and veins (DVT, Budd Chiari in hepatic vein),
rapidly redistributed drug
Characteristic of rapidly redistributed drug..At first the drug is rapidly redistributed so the plasma level falls suddenly. This is followed by normal elimination which causes the characteristic change in the slope..
# Apoptosis morphology
Characterized by - cell shrinkage (becomes eosinophilic/pink) , - chromatin condensation (pyknosis), - membrane blebbing, -DNA fragmentation (karyorrhexis) - and formation of apoptotic bodies which are phagocytosed by MACROPHAGES.... 2 ways it occurs, either intrinsic or extrinsic pathways.
tertiary syphilis
Characterized by *gummas*, which are PAINLESS soft, non-cancerous growth resulting from the tertiary stage of syphilis. It is a *form of granuloma.* Gummas are most commonly found in the liver, but can also be found in brain, heart, skin, bone, testis, and other tissues, leading to a variety of potential problems including *neurological disorders* or *heart valve disease.* - Aortitis, aortic insufficiency, aortic aneurysm with *destruction of the vasa vasorum*. !!!!!!!! - Dorsal column demyelination: Neurosyphilis (tabes dorsalis) -Argyll-Robertson pupils (ARP= Accommodation Reflex Present .. And PRA = Pupillary Reflex Absent) - broad-based ataxia - stroke
# Bulimia Nervosa
Characterized by *loss of control binge eating* (ie, entire pizzas) FOLLOWED by feeling depressed about it, and then either: - Purging, which includes (vomiting or abuse of laxatives, diuretics, or enemas.) - Non-purging (excessive exercising, dieting, fasting) • Body weight is USUALLY normal or slightly overweight. (not always though) • Associated with esophageal tears (Mallory-Weiss syndrome) and rupture (Boerhaave syndrome), dental caries/erosions, swelling of parotid glands (facial swelling, electrolyte disturbances, menstrual irregularities, alkalosis, and dorsal hand calluses from inducing vomiting (Russell's sign), calluses on the knuckles.
Major Depressive Disorder:
Characterized by AT LEAST 5 of the following for 2 weeks with either depressed mood or anhedonia required for diagnosis with NO history of a manic or hypomanic episode: Remembered by the mnemonic SIG E CAPS Sleep disturbance Interest loss (anhedonia) Guilt or feelings of worthlessness Energy loss Concentration or Cognitive deficits Appetite loss Psychomotor retardation or agitation Suicidal ideations
# Chronic rejection: (!!!)
Characterized by episodic bouts of rejection *occurring months to years* after transplantation. It is *refractory* to immunosuppressants. • Involves both humoral and cellular mechanisms from the HOST....which *results in interstitial fibrosis, vascular occlusion, luminal narrowing, vascular wall thickening, loss of function*. There are SCANT inflammatory cells, but fibrosis!!
# VZV infection can cause
Chickenpox (varicella) Shingles (herpes-zoster) Encephalitis; pneumonia.
# Chlamydia trachomatis serotypes
Chlamydia trachomatis is divided into several serotypes. - A, B, C- chronic infection causes *trachoma* aka *follicular conjunctivitis* in Africa. (ABC= Africa, Blindness, Chronic Infection)...... transmitted by hand-eye contact, causing eye inflammation, corneal vascularization, scarring, and blindness. - D-K causes *urogenital infections* (PID, ectopics), and *neonatal conjunctivitis and pneumonia* (can be passed through birth canal) - L1-L3 causes *lymphogranuloma Venereum*
CELL at 50
Chloramphenicol Erythromycin (and other macrolides), Lincosamides (Clindamycin) Linezolid (50S subunit inhibitors)
#low potency typical anti-psychotics
Chlorpromazine, Thioridazine. ... more likely to cause NON-neurologic side effects (sedation, orthostatic hypotension)
# Barrett's esophagus
Chronic acid reflux causes damage of squamous epithelium of distal esophagus. There is healing and re-epithelialization in abnormally low pH environment, causes a *metaplasia* of cells of lower esophagus from normal *non-keratinizing squamous epithlium* to transform into a more acid-resistant *non-cilliated columnar epithelium w/ goblet cells* (similar to intestinal/stomach epithelium but without absorptive enterocytes) Histologic features of Barrett esophagus include: - presence of goblet cells in the esophagus. This defines the term intestinal metaplasia. Endoscopic findings of Barrett esophagus include: 1) Velvety, red mucosal patches occurring near the squamocolumnar junction. 2) This can cause migration of the Z-line more proximally. Barrett's is THE major risk factor for esophageal* adenocarcinoma* (most often occurs in the distal 1/3 of the esophagus) !! Adenoma is malignant prolifferation of glands... glands are NOT normally in esophagus, except from *Barrett's metaplasia*... which progresses to *adenocarcinoma* This is most common type of esophageal cancer in the West.
# fibromyalgia
Chronic disorder characterized by *widespread musculoskeletal pain* in association with: - stiffness - paresthesias - poor sleep and emotional disturbances Muscle pain and stiffness are MORE severe in the morning and WORSE with exercise. There is widespread tenderness in at least 11 points of muscles, joints and tendords, including - lateral epicondyle - medial fat pad of knee - spine of scapula
Chronic hemolysis and gallstones
Chronic hemolysis (sickle cell, thalassemia, hereditary spherocytosis) leads to increased levels of *unconjugated bilirubin* precipitates in bile as *calcium bilirubinate*. The stones are black, present in significant numbers, small and crumbly.
# Etiology Types of Primary Pulmonary Hypertension
Chronic hypoxia (COPD/ sleep apnea) (!!!!) Left Heart failure (!!) Idiopathic PAH Familial PAH
# HBV acute to chronic by age (!!!!)
Chronic infection develops in about 90 percent of children who are infected at birth through vertical transmission!!!! Results in "mildly elevated" liver enzymes!!! Chronic infection occurs in 20 to 50 percent of children who are infected between the ages of 1 and 5 years (immature immune systems), and in less than 5 percent of people infected with hepatitis B during adulthood
# Complications of hemochromatosis (!!!)
Cirrhosis of liver, 'bronze pancreas' Diabetes mellitus, 'bronze' skin. (triad) CHF/arrhythmias & testicular atrophy (iron deposits in heart and nuts), increased risk of hepatocellular carcinoma. Malabsorption (destroys pancreas), also destroys anterior pituitary (HPA/G f'ed) Degenerative joint disease, Patients with hemochromatosis have 200 fold increased risk of developing hepatocellular carcinoma (HCC)
# Wegener Granulomatosis S:Sx
Classically presents as sinusitis or *nasopharyngeal ulceration* in middle aged. (!!!!) AKA *saddle nose* !! Wegener granulomatosis symptoms include necrotizing granulomas in skin, upper and lower respiratory tract that can be seen as large nodular densities on x-ray.
# Follicular lymphoma
Classically presents in adults with ""waxing and waning"" lymphadenopathy (this means *size fluctuates*!!!) "Follicular"" — Fourteen: t(14;18) translocation → juxtaposition of bcl-2 (an oncogene that inhibits apoptosis) next to the IgH locus. This leads to overexpression of BCL2 → ↓ apoptosis, thus leading to a lymphoma. Lymph nodes are obliterated by characteristic neoplastic nodules: uniform, round, and isolated. These nodules are comprised of B-cells recapitulating the germinal centers of lymphoid follicles
# Ehlers Danlos syndrome classic type
Classified by skin hyperextensibility, abnormal wound healing, and excess joint hypermobility. Most patients with classic EDS have a mutation in one of the genes coding for *type V collagen*.
# clinical features of minimal change disease
Clinical features: - Young child (most commonly 2-6 years of age), sometimes with a recent history of respiratory infection or routine prophylactic immunization → presents with massive proteinuria and S/Sx of nephrotic syndrome, however renal function is usually good and there is usually *no hematuria or hypertension* !!!!
# Abetalipoproteinemia findings
Clinical findings present in the first few months of life and include: - failure to gain weight and grow - steatorrhea, large, bulky,foul smelling stools - abnormal star-shaped red blood cells (acanthocytes) due to deficiency of fat soluble vitamins (esp vitamin E) - ataxia, and night blindness.
# clinical uses of K+ sparing diuretics
Clinical uses: *Amiloride* is used in the treatment of heart failure when *hypokalemia is a concern*, such as concomitant loop diuretic use. *Spironolactone* is also used in severe heart failure as well as in *aldosterone-secreting tumors* before surgical correction.
ACE inhibitor uses
Clinical uses: ACE inhibitors are typically used in: - *hypertension* because they *decrease angiotensin II sympathetic activity, and aldosterone-induced fluid retention.* - * heart failure* because AT II causes maladaptive remodeling in the failed heart, thus ACE inhibition slows the progression of heart failure. (!!!!) Ace inhibitors COMBINED with ARB's are often used in diabetics to *slow progression of diabetic nephropathy!!!!!!* Pregnancy is a contraindication because the fetus requires a functioning RAA axis for renal development, and ACE inhibitor use is associated with *fetal renal agenesis*. !!!! *Renal insufficiency*, and ESPECIALLY renal artery stenosis is a contraindication because ACE inhibitors can *mildly decrease GFR*; those with renal failure cannot afford that drop and can *develop hyperkalemia from decreased renal potassium excretion*.
# Hydralazine uses
Clinical uses: Used for severe hypertension (usually in hospitals, not as home therapy) - often used in hypertension during pregnancy because it is *not teratogenic* (the beta blocker labetalol and the α 2 agonist methyldopa are other pregnancy-safe antihypertensives).
# cluster headache
Cluster headaches are *unilateral, DEBILITATING* headaches. characterized by periorbital / temporal pain as well as *ipsilateral autonomic symptoms in the face* (eg, lacrimation, tearing, rhinorrhea, sweating, miosis, ptosis) !!!!!! • Cluster headaches occur repeatedly within a "cluster" period of 3-6 weeks followed by month- or year-long periods without incidences. • Abortive therapy for cluster headaches is high flow O2 or sumatriptan.
gangrenous necrosis
Coagulative necrosis that resembles mummified tissue -Characteristic of ischemia of LOWER LIMB, also sometimes GI tract. Ie, diabetics get partial occlusion of popliteal artery via atherosclerosis. The ischemic/coagulative aspect is called "dry" gangrenous necrosis. If dead tissue becomes INFECTED, it then undergoes liquefactive necrosis (called 'wet gangrene').
# cholchicine
Colchicine binds to tubulin and stabilizes it to *inhibit microtubule polymerization*. In turn, this *impairs leukocyte chemotaxis and degranulation.*!!!! Colchicine *inhibits neutrophil motility, activity, and degranulation* leading to a net anti-inflammatory effect.!!! Once the treatment of choice for acute gout, colchicine is now a second-line approach because of its narrow therapeutic window and risk of toxicity. When used in classic hourly dosing regimens in acute gout, colchicine *causes adverse GI effects (especially when given orally), particularly diarrhea and vomiting, in 80% of patients* (!!!!!!!!!!!!!!!!!!!)
# The cold agglutinins test
Cold agglutinins are antibodies for RBC's that *cause agglutination/clumbing at LOW temperatures" Seen in: - MYCOPLASMA PNEUMONIAE, a form of atypical bacterial pneumonia, and is related to cold agglutinin disease!!! Mycoplasma pneumoniae shares antigens with human erythrocytes!!! - EBV - malignancy
# scleroderma and lungs
Collagen deposition in the pulmonary arterioles. Causes right heart failure.
# what develops in adults with aortic coarcation
Collateral circulations !! -..... The increased blood flow through the *intercostal arteries* may dilate these vessels, giving the classic appearance of *rib notching* on CXR (chest x-ray) !!! The *intercostal vessels* are often palpable !!! !! VERY at risk for hypertension associated complications: - LV failure - ruptured dissecting aortic aneurysm - berry aneurysms and ruptured intracranial aneurysms
# HCV treatment
Combination therapy with IFNα and ribavirin is the current treatment of choice for patients with evidence of chronic hepatitis due to hepatitis C.
Graft vs. Host Disease:
Common complication of *allogeneic bone marrow transplantation* in which functional immune *T cells* (BOTH CD4 and CD8) which are *in the donor marrow* recognize the *recipient MHC's* as foreign and mount an immunologic attack against the RECIPIENT!!! Usually presents as *diffuse maculopapular rash*. !!! A classic example of GvH occurs when tissue is transplanted from a parent donor to a child recipient. The parent's cells recognize the child's HLA as foreign (because of the contribution of the other parent) → mount an attack. The child does not recognize the parent's tissue as foreign and hence does not defend itself. !!!
hemorrhagic cystitis
Common effect of cyclophosphamide and ifosfamide use, because a metabolite of those called *acrolein* irritates the bladder mucosa and causes hematuria, dysuria, urinary frequency/urgency. Acrolein is the cyclophosphamide metabolite responsible for hemorrhagic cystitis Prevention can be accomplished via co-administration of MESNA (sodium-2-mercaptoethane sulfonate), which binds to and inactivates acrolein. !!!!!!!
# Multiple myeloma symptoms
Common features can be remembered with mnemonic: "MM patients can be crabby" → "CRABBI" HyperCalcemia (causing constipation)!! Renal insufficiency Anemia (fatigue)- NORMOCYTIC/NORMOCHROMIC !!!! Bence-Jones proteinuria Bone lesions (lytic) Infections Amiloidosis !!!!!!!!!! • Because immunoglobulin production is compromised, the most common cause of death is recurrent infection.
Paraseptal (Distal Acinar)
Commonly the culprit in healthy, young, tall males who present with spontaneous pneumothorax.
# Sulfonylureas (!!)
Commonly used medications include Glyburide (!!!), glipizide, and tolbutamide. Mechanism: ↑ Insulin secretion by *closure of ATP-gated K channel* in pancreatic β cell membrane!!! Remember that the GLUT2 transporters bring glucose into beta cells where it is metabolized to produce ATP via aerobic respiration. The rise in ATP closes ATP-gated K+ channels. When K+ channels are closed, the cell depolarizes causing voltage-gated Ca2+ channels to open. This release of Ca2+ triggers the release of insulin!!!
complete central vs partial central diabetes insipidus
Complete central diabetes insipidus increases urine osmolality over 50% in response to administration of desmopressim. Partial only increases it around 10%. This is because in partial central, there is some vasopressin already present.
# X-linked agammaglobulinemia (AKA Bruton's)
Complete lack of Ig's in the blood, due to disordered B-cell maturation where Naive B-Cells CANNOT mature to plasma cells. X-linked recessive ∴usually affects males only; heterozygous female carriers of the BTK mutation usually have NO symptoms. Caused by a mutation in the BTK (Bruton tyrosine kinase) gene. All lymphoid organs that normally contain mature B cells (lymph nodes, tonsils, adenoids, Peyer's patches, spleen) may be smaller. *Without B-cells, lymphoid follicles AND Germinal centers are histologically absent in these organs!!!! * ↑ susceptibility to bacterial (!!!!) infections (Cell-mediated immunity is unaffected → the immune response against viral infections remains robust)
lung compliance vs recoil
Compliance is the ability to stretch during inhalation! Recoil is the lung's ability to return to its pre=stretch size during expiration!! Compliance is decreased in pulmonary fibrosis, insufficient surfactant, or pulmonary edema !! *left heart failure* causes drop in left ventricular output and an increase in end-systolic pressure in the left heart chambers. This impairs return of blood from the pulmonary circulation to the left atrium... thus, backing up pressure in the pulmonary capillaries/veins. Increased hydrostatic pressure here causes *transudate* of fluid into the pulmonary system.... This *decreases lung compliance*. Lung compliance *INCREASES* in obstructive lung diseases emphysema/chronic bronchitis, this also *increases FRC*.
#Turner syndrome complictions
Complications associated with Turner syndrome include: • Preductal coarctation of the aorta !! • Bicuspid aortic valve !!!!!!! • Hypothyroidism • Renal problems due to a horseshoe kidney (!!!) • Ovarian dysgerminoma
# Complications of pulmonary artery hypertension (!!)
Complications include: - MASSIVE RV hypertrophy, RV dilation, and cor pulmonale (right heart failure).(!!!!!) - *atherosclerosis* of pulmonary trunk (high pressure on vessel increases risk of atherosclerosis) - there is DECREASED production of nitric oxide (vasodilator) but INCREASED production of endothelin (vasoconstrictor) - smooth muscle proliferation hypertrophy of pulmonary arteries (!!!!) - interlacing tufts of small vascular channels called *plexiform lesions* are seen with *severe, longstanding* disease. *think pulmonary hypertension with exertional dyspnea*
# Wegener granulomatosis in kidney (!!!)
Complications of Wegener granulomatosis are infarctions in the lungs and *rapidly progressive (crescentic) glomerulonephritis* (RPGN) in the kidney, which leads to *hematuria*.
# fatty streak appearance
Composed of *intracellular lipid foam cells*. Begin as multiple yellow spots 1mm in diameter. They can *be seen in aortas of children less than 1 year old*... and are actually *present in the aorta of ALL people over 10 years*.!!!! Not ALL fatty streaks progress to atherosclerotic plaques.
# concentric vs eccentric LV hypertrophy
Concentric- due to *pressure overload* from: - chronic HTN or aortic stenosis. (both *increase LV afterload) It *thickens the ventricular wall but the outer dimensions of the chamber are unchanged* !! Eccentric- due to *volume overload* from: - Aortic/mitral regurg - MI - Dilated cardiomegaly There is an *increased chamber size*.
# malignant hyperthermia
Condition that occurs due to hypersensitivity of skeletal muscles to: - inhalation anesthetics (especially halothane) - muscle relaxant succinylcholine Due to abnormal ryanodine receptors which releases a ton of calcium in the cytoplasm, which *stimulates ATP dependent reuptake by the SR*.... And excess ATP consumption generates heat.
bicornuate uterus
Condition where the uterus has two horns entering a common vagina • Etiology is incomplete/partial fusion of the paramesonephric ducts !!!!!!!!!!! • Clinically can present with urinary tract abnormalities and infertility • In pregnant women, bicornuate uterus is associated with ↑ risk of bleeding, spontaneous abortion, or premature delivery
Atopic dermatitis (aka, eczema)!!
Condition where you have a *pruritic, erythematous, oozing rash* with *vesicles and edema* that eventually *crust* into *thickened, scaly plaques*. This happens with *certain FOODS and environmental irritants!!!!* Often involves the *face* and *flexor* surfaces!! It is a *type 1 HSR* Associated with *asthma* and *allergic rhinitis*!!!
Contrast condyloma lata and condyloma accuminata
Condyloma lata is caused by secondary syphilis and is smooth, moist and flat. condyloma accuminata (venereal (genital) warts caused by HPV, are raised, cauliflower-like, bulky, dry lesions on / around genitalia.
# Condyloma
Condyloma- refers to an infection of the genitals. The two subtypes are: *Condyloma acuminata*, aka *genital warts* *Condylomata lata*, white lesions associated with secondary syphilis
# congenital rubella (rubella= German measles)
Congenital rubella occurs when a *pregnant woman is infected with rubella during the first trimester*, and the virus infects fetal cells transplacentally. The classic triad of -Sensorineural deafness (58% of patients) -Eye abnormalities—especially cataract and microphthalmia (43% of patients) , ie WHITE PUPILS!! - Congenital heart disease—especially patent ductus arteriosus (50% of patients) • Skin and musculoskeletal defects: o Purpuric "blueberry muffin" skin rash (dermal erythropoeisis) — may also be seen in congenital CMV o Radiolucent bone lesions — vs. the metaphyseal dystrophy and periostitis characteristic of congenital syphilis • Other defects: o Microcephaly!!!! — vs. the* macrocephaly characteristic of congenital toxoplasmosis*
aspergillus appearance
Conidiophores each have a terminal vesicle with outwardly radiating phialides and conidiospores attached, giving a "broom-like" appearance.
# Primary hyperaldosteronism
Conn syndrome*- which is a less commonly due to *adrenal adenoma* that is an *aldosterone secreting tumor*!!!!! high aldosterone, which *raises Na+, blood volume*, which goes to kidney and therefore* kidney DECREASES renin. *! As ECF increases, there is a rise on *atrial natriutetic peptide* ... this leads to only a mild increase in ECF volume. Thus, there is hypertension without significant edema OR hypernatremia, so *sodium level is relatively normal* !!!! *hypokalemia* from the excess aldosterone occurs (manifested by weakness/paresthesias !!!! ).... Increased H+ excretion leads to an *increase in bicarbonate* and thus, metabolic alkalosis.
tuberoinfundibular pathway (!)
Connects the *hypothalamus and the pituitary gland* Is responsible for *dopamine-dependent prolactin inhibition*. Antipsychotic action here cause an increase in prolactin, leading to galactorrhea, disruption of menstrual cycle, and sexual dysfunction.
# Influenza type b (Hib) vaccine:!!
Consists of: PRP capsular polysaccharide conjugated with either *tetanus or diphtheria* toxoid..... These additions cause *improved immunogenicity* by increasing T-cell mediated immune system response, leading to more effective memory B generation. Reduces incidence of:!!! - meningitis - pneumonia - sepsis - epiglottitis
# prokaryotic 30S ribosomal subunit
Contains a *16S rRNA sequence* that is COMPLEMENTARY to the *Shine-Dalgarno* sequence on mRNA
stroke volume depends on
Contractibility Preload (linear relationship)... Preload approximated by ventricular EDV Afterload (opposite) ... approximated by MAP and arteriole resistance
# Beta blockers are contraindicated with what group??
Contraindicated in cocaine users (risk of unopposed α-adrenergic receptor agonist activity).
# Prinzmetal angina tests
Coronary artery starts in the epicardium, and the spasm cuts off blood supply to the entire wall.... and the classic finding for *transmural ischemia* is *ST elevation* During an episode of prinzmetal angina pectoris, there is no elevations in troponin levels. # * Ergonovine* triggers vasospasm in susceptible patients including those with prinzmetal angina, used in diagnosis of it!!!!
# what is used to treat eye problems in Graves?
Corticosteroids, (prednisone) which reduce inflammatory infiltration
# ITP treatment
Corticosteroids. Children respond well, adults may respond initially but then relapse.
cortisol and catecholamine effects
Cortisol itself does NOT affect vascular reactivity, however, it DOES augment the vasoconstrictive effects of catecholamines. This is an example of a *permissive* effect, because cortisol itself does NOT have any effect on vascular reactivity.
# what is the most common fungi cause of meningitis, and in what patients? (!!)
Cryptococcus neoformans, and it occurs in *immunocompromised (ie, AIDS, organ transplant, cancer, steroids) patients. * It is a *Spherical fungus*, It is a budding yeast with a very prominent capsule (!!!!), clear halos. *Latex agglutination test* identifies polysaccharide capsule (more sensitive than India ink) Found in soil, pigeon droppings and transmitted by inhalation and *enters and infects the lungs!!!* Then spreads to brain. In cryptococcal meningitis, look for "soap bubble" lesions: fungus-filled cysts in gray matter of brain. occurs when CD4+ count is <50 !! *Treat with amphotericin B, flucytosine, followed by long term fluconazole.* !!!!!
# Burkitt lymphoma treatment
Cure occurs in 70-80% of children and adults when effective treatment is administered Burkitt lymphoma was one of the first malignancies shown to be treatable with chemotherapy. Due to its aggressive nature, treatment should begin within two days of diagnosis. The most commonly used agents are cyclophosphamide, vincristine, prednisone, and methotrexate/leucovorin.
# asthma "products"
Curschmann spirals- coiled mucinous spirals comprised of shed epithelium, often found in the sputum of asthmatics. Charcot-Leyden crystals- These are rhomboid crystals composed of *major basic protein* which is *produced by eosinophils* and represent an eosinophilic response usually associated with an allergic or parasitic process.
left ventricular pressure-volume curve
Curve 1 represents systolic disfunction, ie, dilated cardiomyopathy. Curve 2 represents reduced LV compliance indicating diastolic dysfunction, due to a stiffened left centricle. Ie, amyloidosis, sarcoidosis.
mitral regurge curves
Curve 1: inceased LA compliance as a result of CHRONIC mitral regurg. (higher volume at a lower pressure). Occurs due to valvular disfunction and ATRIAL DILATION, and increased compliance. They are more prone to A-FIB and mural thromboembolism. Cure 2: Near normal LA compliance in acute mitral regurg. Since there has not been enough time elapsed for LA adaption to the regurgant volume overload, *Pulmonary pressure rises significantly* !!!! So they develop *pulmonary hypertension and pulmonary edema!.
Cyanide
Cyanide poisoning: CN- preferentially binds to Fe3+ and *inactivates cytochrome c oxidase, the fourth and LAST complex in the electron transport chain* → stops cellular respiration... this is where 1/2O2 + 2H= H2O
# cell cycle g1
Cyclin D is expressed here and associates with CDK4 and 6 mnemonic: Donky Kong DK-64)....
# Syringomyelia condition
Cystic degeneration of the spinal cord. Arises with *trauma* or in *association with Arnold-Chiari* Usually occurs at *C8-T1*. Sensory loss of *pain and temperature* because it knocks out the *anterior white commissure* !!!! But there is *sparing of fine touch and position* in the *upper extremities* If it expands, it can knock out the *anterior horn*, resulting in a *lower motorneuron problem*... causing: - muscle atrophy/weakness - decreased tone - impaired reflexes - Kyphoscoliosis
# BCL-2 knocked out
Cyt c in the cytosol activates Apaf-1.... Apaf-1 NORMALLY induces activation of caspases (caspase 9 → caspase 3)... So, since BCL-2 is knocked out, then apaf-1 is NOT inhibited, .... So here there is excess apoptosis.
D1 vs D2 receptors
D1 is Gs- relaxes vascular smooth muscle D2 is Gi- modulates neurotransmitter release D1: CNS • regulate neuronal growth/development, mediate some behavioral responses, modulate D2-mediated events • renal vasodilation D2: CNS • dopamine control in brain (motor coordination, memory, psychosis)
# HPV
DNA virus that infects the *lower genital tract*. (vulva, vaginal canal, cervix). Characterized by *koilocytic change* histologically, with "crinkled" nuclei. Subdivided into *low risk* and *high risk* subtypes, based on *DNA sequencing*.... risk based on risk of developing subsequent carcinoma. Note: vast majority (~90%) of HPV infection is cleared by immune system... it is only when persistent infections occur where there is major risk.
# presentation of sickle in kids
Dactylitis = *Swollen hands/feet* due to vaso-occlusive infarcts of bones !!! This condition occurs early in life because *the affected bones still contain hematoietic marrow* !!!! There are small infarctions within the marrow, trabecular, and inner cortical layer of the bones of the hands, wrists, feet and ankles.
#Poliomyelitis
Damage to the *anterior motor horn* due to *polio virus infection* (paralytic poliomyelitis). Causes LOWER motor neuron disease. Polio has a *fecal oral transmission*. It then infects the *oropharynx and small intestine*... specifically, it replicates in the tonsils/Peyer's patches, causing *fever, sore throat, abdominal pain with nausea/vomiting*. It can THEN spread to the *CNS via blood* where it gets into the *anterior motor horn*. This knocks out the *lower motor neurons*, causing: - flaccid paralysis - muscle weakness/atrophy - decreased tone/reflexes - *negative* reflexes - fasiculations It can also cause aseptic meningitis!!!!!!!!!!!!!!!!!
# Erb's Palsy "waiter's tip"
Damages C5-C6 roots via trauma in adults or trauma during delivery in infants. With the deltoid and rotator cuff muscles are paralyzed due to injury of C5 and C6, the action of latissimus dorsi on the shoulder (extension, adduction, medial rotation) is unopposed → the arm hangs by the side (adduction) and is internally (medially) rotated Arm is adducted (by side), extended (straight down), medially rotated. Forearm pronated and hand flexed. Loss of abduction of shoulder (deltoid, supraspinatus) Loss of lateral rotation of the shoulder (infraspinatus) Loss of flexion/supination of forearm (biceps)
#daptomycin
Daptomycin is a cyclic lipopeptide that functions to cause rapid depolarization of the cell membrane. This acts to cause disruption of protein, DNA, RNA synthesis and eventual cell death.
# decongestants and tachyphylaxis
Decongestants are alpha agonists which cause vasoconstriction in the vessels of the nasal mucosa. BUT, tolerance rapidly builds up and their positive effects decline after days, which is called tachyphylaxis. This occurs due to decreased norepinephrine production because of the alpha-agonist leds to a compensatory vasodilation and congestion.
# normal morphological changes in the heart
Decrease in LV chamber apex-to-base dimension Development of a sigmoid-shaped ventricular septum - myocardial atrophy with increased collagen deposition - accumulation of *lipofuscin*.
# ARDS findings
Decreased FRC (functional reserve capacity) Profound V/Q mismatch causes ↑ A-a gradient and hypoxemia Pulmonary capillary wedge pressure is normal!! This is important for differentiating ARDS from cardiogenic causes of pulmonary edema. CHF/cardiogenic pulmonary edema always needs to be excluded as being present. The definitive way is to place a Swan-Ganz catheter and look for elevated Pulmonay Capillary Wedge Pressures (usually greater than 18 mmHg) for cardiogenic. ARDS is associated with pancreatitis!!!!!!!!!!!
inotrop resistance
Decreased TPR= exercise, fistula Increased TPR= sympathetic stimulation (ie, phenylephrine infusion)
# Clinical features of hypertrophic cardiomyopathy
Decreased cardiac output (heart wall is so full of muscle, you get *diastolic dysfunction* where you can't fill heart). Biopsy of hypertrophic cardiomyopathy Histopathologically, tissue samples are characterized by *"myocardial disarray"* which includes disoriented, tangled, and hypertrophied myocardial fibers.
what causes polyhydramnios ?
Decreased fetal swallowing- - duodenal/esophageal/intestinal atresia -anencephaly (gestational diabetes link!!) increased fetal urination- high cardiac output due to anemia, or twin to twin transfusion syndrome
oral contraceptives and female cancers
Decreases the risk of both ovarian and endometrial (think it gives them a break)
Alzheimers Disease
Degenerative disease of the neurons in the cortex, most common cause of *dementia*... severe decrease (90%+ of Ach!!! ). A decreased Ach level is due to *deficiency of choline acetyltransferase*. On the neurons, there is a receptor which is derived from *Amyloid precursor protein* . When this protein is broken down, it is normally broken down by an *alpha secretase* enzyme, which forms an *alpha product* which easily turns over. However, in *Alzheimers*, the *Amyloid precursor protein* is broken down by a *Beta secretase* which results in a *beta product* which CANNOT be turned over .... and it is deposited in the brain as *A-ß Amyloid*, causing *alzheimers*
Friedreich Atexia
Degenerative disorder of *cerebellum AND spinal cord tracts* presents as *ataxia* (*spinocerebellar tract damage*) with: - loss of vibratory sense/position proprioception (due to loss of *dorsal column*) !!! - muscle weakness in *lower extremities* and also arms -kyphoscoliosis!!!!!! - Loss of deep tendon reflexes - High plantar arches (pes cavus deformity of the foot)!!!!!!!!!!!! ! - These patients also often have *hypertrophic cardiomyopathy*/ murmurs/ atrial fib / tachcardia !!!!! (50%) This is the MOST likely cause of death!!! - 20% get diabetes
# Amyotrophic Lateral Sclerosis
Degenerative disorder of *upper and lower motor neurons* of the *corticospinal tract* Degeneration of the *anterior motor horn* leads to LMN signs: flaccid paralysis, muscle atrophy/weakness, *fasiculations*, Degeneration of the *lateral corticospinal tract* leads to *UMN signs* - spastic paralysis - hyperreflexia - increased muscle tone - upward going toes The *lack of sensory impairment* distinguishes ALS from syringomyelia, because in ALS, you have NO loss of pain/temp. !!!!
# Parkinson's disease
Degenerative loss of dopaminergic neurons in the *substantia nigra pars compacta* of the basal ganglia Normally, dopamine is released from the nigrostriatal neurons (i.e., neurons originating in the SNc → terminating in the striatum) to activate the EXCITATORY direct pathway (D1 receptors) and inhibit the INHIBITORY indirect pathway (D2 receptors).
sydenham's chorea
Delayed onset autoimmune reaction involving anti-streptococcal antibodies that *cross react with the basal ganglia* !!! There is restless/purposeless jerking, almost always months after a sore throat.
Pancreatic cancer / pancreatic carcinoma gene
Deletion in CPD4/SMAD4, which is located on chromosome 18q, is associated with pancreatic cancer. Mnemonic: DPC (CPD backwards) = "Deleted in Pancreatic Cancer".
# Hepatitis D
Delta hepatitis is caused by the hepatitis D virus (HDV). This small single-stranded circular RNA delta virus.
# Clinical features of Alzheimer's
Dementia is *memory loss, cognitive dysfunction, but NO loss is consciousness* - *Slow-onset* memory loss (takes years to develop, begins with recent memories, progesses to long term memories) - progressive disorientation, forget daily tasks - Lose motor and language skills - Behavior/personality changes (ie, apathy, anger) Patients eventually become mute and bedridden. Important to note that we *do not get focal neurologic deficits* early in the disease (pill rolling tremor, expressionless face, choria, etc etc)
#narcolepsy pathophys and diagnosis
Depletion of the *hypocretin-secreting neurons* in the lateral hypothalamus.... They have *low CSF levels of hypocretin-1*, or shortened REM sleep on polycomnography. !!! Treat with modafinil !!! SECOND line are amphetamines
# Dermatomyositis
Dermato- inflammation of the skin Myositis- inflammation of the muscle Dermatomyositis is an inflammatory disorder of both the skin and skeletal muscle. Presents as bilateral *proximal muscle weakness* (can't comb hair (shoulder), climb stairs (hip), anything involving the proximal limbs).... Distal involvement will present late. Etiology is unknown, but some cases are *associated with carcinoma*!!! (ie, gastric carcinoma). So if a patient presents with this, we MUST consider a carcinoma, especially in stomach. Treat with corticosteroids
# shared psychotic dirorder
Development of delusions in a person who is in close relationship with a delusional individual. The disturbance is NOT better explained by another psychotic disorder (ie, schizophrenia) or by the effects of another medical condition, medication, or drug etc. Ie, woman starts to believe her boyfriend's delusions.
# ischemic preconditioning
Development of resistance to infarction by cardiac myocytes exposure to repetitive, non-lethal ischemia !!!
CN III palsy and light reflex in diabetes
Diabetic mononeuropathy often involves cranial nerve III, BUT, it *spares* peripheral parasympathetic fibers, so it does NOT impair light reflex OR accommodation. Note: *medical causes* (diabetes)often SPARE the pupil... while surgical causes usually *involve the pupil early*.
Diagnose meningitis
Diagnosed by *lumbar puncture* performed between *L4-L5* (iliac crest) because *spinal cord ends at L2*... but the subarachnoid space and cauda equina continue until S2...... so needle at L4-L5 can still get fluid from *subarachnoid space* LP goes through: skin, ligaments, epidural space, dura, arachnoid..... but NOT pia !!!
#diagnose pheochromocytoma
Diagnosed by ↑ serum metanephrines and ↑ 24 hour urine metanephrine and VMA. (note: E broken down into 3-methoxy metanephrine (by COMT), NE broken down into Nor-metanephrine metanephrine and nor-metanehprine broken down into VMA by monoamine oxidase
# TB (mycobacterium) stain
Diagnosis is made with *Ziehl-Neelson (carbol fuchsin)*. The culture is stained with carbolfuchsin (red) and acid alcohol is applied to dissolve most bacterial cultures. M. tuberculosis doesn't dissolve in acid and remains red. This indicates active tuberculosis infection.
#Diagnose acute pancreatitis
Diagnosis: ↑ lipase (most specific), ↑ amylase, ↓ calcium • Calcium ↓ because precipitates as calcium-fatty acid soaps that are deposited into the pancreas • Ultrasound to look for gallstones.
# Diagnose aortic dissection
Diagnostic studies should follow rechecking bilateral BP and radial pulses for symmetry. Ruling out *acute coronary syndrome* is vital given the *similarities* in presentation with aortic dissection. CXR will be abnormal in 60-90% of cases with widening of mediastinum as the main feature (though not diagnostic) CT with contrast is quick and noninvasive way to detect Aortic dissections (80% sen. For proximal and >90% sen. for distal tears) TEE (transesophageal echocardiography) has >95% sensitivity for proximal tears and 80% for distal tears and can also be utilized to detect other cardiac abnormalities (pericardial disease, AI, etc) !!!!!
# long acting benzos
Diazepam Flurazepam Clorazepate
anaesthetic arteriovenous concentration gradient (!!)
Difference between concentration of a gas anesthetic in arterial and venous blood. It is a measure of SOLUBILITY. If tissue solubility of drug is high, a large amount is taken up from arterial blood (low venous concentration)... this means it has a slower onset of action because *a lot of it is absorbed by peripheral tissues*, and *slower equilibrium with the brain*. Anaesthetics with low peripheral tissue solubility have smaller arteriovenous gradients, and thus they act faster because there is *less peripheral tissue update*..... so here, *concentrations in the brain are reached faster*.
# IgA nephropathy must be differentiated from what ?
Differentiate IgA nephropathy from *PSGN (post-streptococcal glomerulonephritis)*. PSGN: - Occurs in kids 1-4 WEEKS post-infection (vs. 1-2 days post-infection in IgA nephropathy) !!!!!! - IgG immune complexes in PSGN (vs. IgA in IgA nephropathy) - ↓ serum C3 levels in PSGN (vs. IgA which cannot fix complement via the classic pathway ∴ normal C3 levels in IgA nephropathy)
# parietal lobe lesion
Difficulties with spatial and visual perception, writing, calculation, left-right differentiation, object identification.
# Pathologic features of Alzheimer's (!!!)
Diffuse cerebral atrophy of the brain. Atrophy is hallmarked by *narrowing of the gyri*, and *widening of the sulci* As a consequence of atrophy, the *ventricles dilate* and take up the space, and this is called *hydrocephalus ex vacuo*. Development of *neuritic plaques*, full of *A-beta Amyloid* which is *extracellular* which entraps *neurotic processes* Note: A-beta Amyloid can also deposit around the cerebral vessels of the brain, and this is called *cerebral Amyloid angiopathy* , which *weakens the wall of the vessels* and *increases risk of hemorrhage* !!! Formation of *neurofibrillary tangles*, which includes the *Tau protein*, which helps organize the *microtulules*... here, the Tau is *hyperphosphorylated* and thus can *no longer assist* in organizing microtubules, so they become tangled
#name the cardiac glycosides
Digoxin < Digitalis < Digitoxin Digoxin is eliminated by kidney Digitoxin is eliminated by liver Acts by increasing cardiac contractility. It does this by increasing availability of Ca2+ within the cardiac cells. - Digoxin binds to alpha subunit of NA/K ATPase in myocytes - Digitalis competed with K+ binding to the extracellular alpha subunit. Thus *disabling the Na/K exchange pumps* in the cell membranes, which* allow for the build-up of Na+ within the cells*, which *prevents the Ca2+ from being expelled* (resultant increased cardiac contractility). Also acts by INCREASING VAGAL TONE and vagus stimulation of AV node, which = slower HR. Allows for increased filling of ventricles on diastole.
Varicocele
Dilation of the *spermatic vein* due to impaired drainage. Presents as scrotal swelling with "bag of worm" appearance.... - Enlarges when standing and regresses when supine (venous pooling). Usually *left sided*, and this is because on the left side, there is an extra step where the *left spermatic vein drains into the renal vein* and THEN drains into the IVC. ... "left is longer".... Because *renal cell carcinoma tends to invade the renal vein*... on the left side, by blocking the left renal vein, it also blocks the left spermatic vein, causing a left sided varicocele. On the right side, the *right spermatic vein* drains directly into the IVC. Seen in a large percentage of infertile males because warm blood piles up, warms testes, causes infertility
Abciximab (!!)
Directly inhibits Gp IIb/IIIa.
# IBS irritable bowel syndrome
Disease of the entire gastrointestinal tract in which a person reacts to stress by developing symptoms (such as cramping and abdominal pain) associated with *alternating patterns of diarrhea and constipation.* Excessive amounts of *mucus may appear in feces*; other symptoms include flatulence, nausea, and loss of appetite. The condition is also known as irritable colon or spastic colitis. most common functional bowel disorder more common in females -abdominal pain *revealed by defecation* - feeling of incomplete defecation. (tenesmus) People with IBS more commonly than others have gastroesophageal reflux, symptoms relating to the genitourinary system, chronic fatigue syndrome, fibromyalgia, headache, backache and psychiatric symptoms such as depression and anxiety.
Meniere's disease
Disorder characterized by increased *volume of endolymph*, thought due to *defective resorption of endolymph*. The distention of endolymphatic system damages both the vestibular and cochlear components of the inner ear. Triad of EPISODIC: - Tinnitis - Vertigo - Hearing loss (sensorineural)
# Achondroplasia
Disorder of impaired cartilage proliferation in growth plate. due to an *AD inherited (!!) ACTIVATING (gain of function) point mutation* in Fibroblast-growth-factor-receptor-3 , FGFR3. (!!!!) Receptor is turned ON, which inhibits growth of cartilage at the *epiphyseal growth plate* which inhibits epiphyseal growth* !!
# What AA is important in tertiary/quarternary structure?
Disulfide bonds formed from the sulfhydryl group (-SH) of *two cysteine residues* !!!
#Common Variable Immunodeficiency (aka CVID)
Diverse group of disorders that share a failure of terminal B-cell maturation (primary antibody deficiency). Result: ↓ plasma cells with resultant *hypogammaglobulinemia* !!!!! , most often of IgA and IgG, can also be IgM. Normal number of circulating B cells (but low Ig's) Can develop during 20s-30s, presenting with recurrent bacterial infections (sinopulmonary and GI infections!!!!!!!) ↑ risk of autoimmune disease, bronchiectasis and lymphoma (!!)
# Lung cancer categories:
Divided clinically into: 1. small cell aka oat cell lung cancer (15%) 2. non-small cell lung cancer (85%), which includes : - adenocarcinoma (40%) - squamous cell carcinoma (30%) - large cell carcinoma (10%) - bronchoalveolar cell carcinoma aka bronchial carcinoid tumor *small cell carcinoma* is usually treated with *chemo* first, not surgery... while *non-small* usually treated with *surgery first*
#buspirone sides and benefits
Does not cause sedation (!!!), addiction/tolerance, and does not potentiate CNS depression of alcohol (useful in alcoholics) !!!!!! . This makes it useful in those who would likely abuse medications!!! Adverse effects are low but include headaches, dizziness, nervousness, and lightheadedness • No muscle relaxant properties which is particularly important in elderly patients
# pergolide
Dopamine agonist which directly stimulates D2 receptors. Provides only modest improvement, but its use may delay the introduction of levodopa for months/years.
Dopamine and cardiac output
Dopamine at low doses stimulates D1 receptors in the renal vasculature which increases GFR, renal flow. - at slightly higher doses, it stimulates B1 receptors increasing HR, CO, and systolic BP (diastolic BP unchanged) - at even higher doses, it stimulates alpha-1 receptors, causing a systemic and renal vasoconstriction which decreases both Renal blood flow and CO.
# how does dopamine inhibit prolactin ??
Dopamine inhibits prolactin by acting on D2 receptors of lactotrophs (prolactin producing cells of anterior pituitary). Note: if the pituitary is destroyed, then *prolactin is elevated* because *dopamine cannot inhibit prolactin*.
# treat lyme disease
Doxycycline or penicillin-type antibiotics (ceftriaxone)
# Hypertrophic cardiomyopathy and the Interventricular septum
Dramatic hypertrophy of the interventricular septum (IVS) may cause the *IVS to outgrow its vascular supply* leading to asymptomatic subendocardial *micro-infarcts* that generate *non-conducting, fibrotic scar* tissue and that may contribute to the characteristic histological findings and the generation of *arrhythmias*. In approximately 50% of patients with HCM, *prominent IVS hypertrophy* is accompanied by *systolic anterior motion aka SAM* of the MITRAL valve, which can cause dynamic *LVOT obstruction* and dynamic *mitral regurgitation*.!!!!! Increases with (!!!!): LVOT obstruction (and murmur intensity) varies based on LV end diastolic volume!! Increases with increasing preload: sudden standing valsva Decreases with squatting, hand grip, passive leg raise!!!!!!!!
# what can precipitate hepatic encephalopathy ?
Drugs (sedatives, narcotics) Hypovolemia (diarrhea, vomiting) Excessive nitrogen load (GI bleeding, constipation) Metabolic disturbances (hypokalemia, alkalosis, hypoglycemia) infections
red neurons
Due to *irreversible* acute neuronal injury. Due to transient ischemia, hypoxia, or episodic hypoglycemia. characterized by: - shrinkage of cell body - loss of Nissl substance - deeply eosinophilic cytoplasm - pyknosis of nucleus (shrunken and basophilic)
# familial dilated cardiomyopathy
Due to AD mutations in cardiac myocyte *cytoskeletal proteins* (dystrophin) or mitochondrial enzymes.
# TTP- Thrombotic thrombocytopenic purpura
Due to a deficiency in the vWF multimer cleaving protease ADAMTS-13, which NORMALLY degrades vWF multimers into smaller monomers...... Because of deficiency, we get *abnormal platelet adhesion* (!!!), resulting in formation of (color) WHITE microthrombi. !!!!
# dystrophin death
Due to cardiac (dilated cardiomyopathy) or respiratory muscle failure.
# ataxia-telangiectasia.
Due to defects in the ATM gene (chromosome 11), leads to *ineffective DNA double strand break repair and cell cycle arrest* ... Damage mostly to *X-ray/radiation* because X-rays have sufficient energy to cause double stranded breaks, NOT usually UV irradiation which causes thymine dimers.
# cardiovascular dysphagia (!!!)
Due to enlargement of the *left atrium* (mitral stenosis, left ventricular failure) which can compress esophagus. !!!!
# schistosomiasis
Due to freshwater snails. The snails excrete cercariae into fresh water. The cercariae then penetrate human skin and enter blood stream eventually reaching the liver to mature to adults. *They then migrate to: - intestine - urinary bladder* • Intestinal schistosomiasis is caused by infection due to Schistosoma mansoni and Schistosoma japonicum. The most common symptoms from intestinal schistosomiasis include • *Chronic or intermittent abdominal pain • Poor appetite • Diarrhea • Intestinal bleeding and iron deficiency* • Hepatosplenic schistosomiasis is caused by infection due to Schistosoma mansoni and Schistosoma japonicum. The most common symptoms of hepatosplenic schistosomiasis include • Hepatomegaly • Splenomegaly • Periportal fibrosis • Portal hypertension • Genitourinary schistosomiasis is caused by infection due to Schistosoma haematobium. In early infection, *terminal hematuria can be seen from eggs that are excreted in the urine.* In longstanding infection, dysuria and increased urinary frequency are common symptoms.
# Elastic fibers lost in emphysema
Due to imbalance of *proteases* compared to *anti-proteases* aka protease inhibitor..... main anti-protease is *alpha 1 anti-trypsin*. Proteases come from Neurtophils and alveolar macrophages!!!!! Bottom of lung has no defence mechanisms except *alveolar macrophage*. When macrophages and neutrophils eat them, there is some inflammation, and this inflammation produces *proteases* as a *by produce of inflammation*. Normally proteases to antiproteases are in balance, but in emphysema we have imbalance in the ratio. SMOKING increases proteases (big time)... while a-1-antitrypsin deficiency impairs antiproteases aka protease inhibitors.
# Staph aures food poisoning
Due to ingestion of preformed *enterotoxins* from staph aures, which makes it very rapid onset (2-6 hours). Foods classically associated with S. aureus enterotoxin-mediated food poisoning: - mayonnaise-containing foods (especially salads—potato salad, macaroni salad, tuna salad) !!!! - meat - poultry - milk/egg/dairy products - cream-filled pastries (eg, custards)
# biliary stones and total parenteral nutrition
Due to: 1) biliary stasis from absent enteral stimulation secondary to less CCK !!! 2) Ileal resection can result in supersaturation of hepatic bile with cholesterol
duodenum vs jejunum in fat metabolism
Duodenum is main site of DIGESTION Jejunum is main site of ABSORPTION Ileum is site of absorption of bile/B12
# tumor lysis syndrome and uric acid crystals
During chemotherapy a large number of tumor cells are destroyed and a number of intracellular ions (potassium phosphorous, uric acid) are released to kidneys. Uric acid is normally soluble at physiologic pH... but it *precipitates in an acidic environment*.. The *most acidic* pH part of the nephron is the *distal tubules and collecting ducts*. !!! To prevent tumor lysis syndrome, we ALKALYZE the urine, and excess hydration. So the combination of high pH plus high urine flow prevents crustal formation.
# when does most heart blood flow occur?
During diastole!! Flow is the LOWEST during systole (Q-T period)
# Stable angina tests
During stable angina pectoris episodes the *EKG may show an ST depression* that is *indicative of subendocardial ischemia* but *no ST elevation*.
# villous adenoma
Dysplasic epithelial cells form villi-like projections that extend from the poly surface down to the stroma. They are *larger* and more commonly sessile... they can have *velvety or cauliflower-like projections* !!!!! Villous adenomas have a HIGHER risk of progressing to adenocarcinoma than tubular adenomas, and cause more symptoms
# EBV infection of nasopharynx
EBV infection of nasopharyngeal epithelial cells may predispose to malignant transformation in certain patient populations → nasopharyngeal carcinoma (most common in China, Asia)
# below the pectinate line
Ectoderm. External hemorrhoids, anal fissures, squamous cell carcinoma. Inferior rectal artery (branch of internal pudendal artery) Venous drainage to inferior rectal vein, internal pudendal, internal iliac, IVC Lymphatic drainage- superficial inguinal
effect modification vs confounding in studied
Effect modification occurs when the effect of an exposure on an outcome is modified by another variable (ie, a study where smoking status modifies the effect of a ER agonist (exposure) on DVT incidence (outcome)) With *effect modification*, the different groups will have different measures of association Confounding would be the effect of age as a confounder that muddies shoe size and intelligence. It seems that those with larger shoe sizes are smarter, but they're really just older. If older and younger children were to be analyzed separately, there probably would be no correlation between shoe size and intelligence.
# efficacy and spare receptors
Efficacy = maximum effect!! In spare receptor theory, a maximal physiological effect of a drug is often met with increasing concentration of the drug, however maximal effect is reached before all receptors are bound (i.e. there are spare receptors left over). In spare receptor theory, a second messenger amplification system could lead to a maximal response despite only a few extracellular sites being activated. For example, G-coupled receptors. In the presence of spare receptors, noncompetitive antagonists act to "remove" the number of active receptors from the pool of receptors. • In low dose administration of a noncompetitive antagonist only the spare receptors are bound, allowing agonist to bind to available, or "non-spare," receptors. This causes a right shift in the dose-response curve. • In high dose administration of a noncompetitive antagonist, both spare and "non-spare" receptors are bound, preventing agonist to bind to any receptors. This results in a downward shift of the dose-response curve.
cardiac output
Either HR X stroke volume OR O2 consumption/ arteriovenous O2 difference
# type 1 hypersensitivity overview
Either anaphylactic (bee stings, some foods/drugs).....or atopic/allergic (hay fever, rhinitis, asthma, eczema, etc) Initial antigen exposure stimulates production of IgE antibodies‚ which attach to the surface of mast cells. • Re-exposure to same antigen → crosslinking of surface bound IgE molecules !!!! → degranulation of basophils and mast cells which *release histamine*. This initiates the immediate phase of the reaction. which causes itching; bronchospasm‚ wheezing‚ and shortness of breath; and vasodilation and edema formation with low blood pressure‚ weakness‚ and tissue swelling. • Immediate Phase: Release of histamine, tryptase (!!), kinogenase (!!!), prostaglandins, platelet aggregating factor, and ECF-A. Since no products need to be synthesized by the cell, this process is rapid. !!!!! While the initial phase is in progress, the cell also begins synthesizing leukotrienes and their derivatives as a part of the late phase of the reaction. The products of the late phase reaction are inflammatory and attract neutrophils and eosinophils. Eosinophils are recruited to the site of inflammation as a part of the late-phase reaction. Once present, they release several mediators, among them arylsulfatase and histaminase which can act to decrease the severity of inflammation. However, LTC4 and PAF are also released which overall activate mast cells to further release cytokines. Thus, eosinophils are now believed to amplify and sustain the inflammatory response, thus necessitating treatment with corticosteroids.
# cerebellar tumor in kids
Either pilocytic astrocytoma or medulloblastoma !!
# cardiac myocyte cycle
Electrical stimulus allows calcium from ECF to enter cell through voltage-dependent Ca2+ channels - calcium stimulates ryanodine receptors, causing MORE calcium release from the SR - Calcium from SR binds to Troponin C - Calmodulin binds and acticates Ca2+ ATP-ase which removes calcium from the cell by USING ATP. - Sarcolemmal Na+/Ca2+ ALSO removes calcium (3 sodium for 1 calcium) but does NOT use ATP.
# Small cell electron microscopy
Electron microscopy of small cell carcinomas frequently shows dense core neurosecretory granules. Small cell carcinomas commonly stain for neural markers like synaptophysin, CD57 and chromogranin (!!!!!!).
insulin resistance indication
Elevated BASELINE insulin during fasting is highly suggest insulin resistance. insulin resistance may occur due to: high FFA's and TAG's. Serine and threonine residue phosphorylation by serine kinases !! (note: TNF-a, catecholamines, glucocorticoids and glucagon increase insulin resistance this way!!!)
# hemolytic anemia labs (ie, hereditary spherocytosis)
Elevated LDH !!! Indirect bilirubinemia Lysing of blood cells in *hypotonic saline* (osmotic fragility test!!) Pidmented gallstones are a major complication because of increased indirect bilirubin precipitates as *calcium bilirubinate*, forming *billirubin pigmented gallstones*. ↑ risk for aplastic crisic with parvovirus B19 infection of erythroid precursors!!
Thyroid storm
Elevated catecholamines/hormone excess due to poor response to stress (ie, surgery, child birth)... usually occurs in those w/ Graves Disease So patient has signs of hyperthyroidism (goiter, hyperreflexia, etc) -presents as arrhythmia, hyperthermia, vomiting with hypovolemic shock (low BP), coma # treat thyroid storm (!!) PTU (propylthiouracil- inhibits peroxidase mediated oxidation, organification and coupling) propranolol (beta blocker) prednisone (corticosteroid) Propranolol also inhibits T4-> T3 peripherally by inhibiting iodothyronine deiodinase (!!!!!!)
# Emphysema
Emphysema is an *obstructive* lung condition highlighted by pathological enlargement of distal airways due to destruction of *alveolar walls and alveolar sacs* with *increased elastase* activity *Elastic recoil fibers* are *lost*, so *lung compliance increases* (!!!!)..... which result in *enlarged airspaces* and barrel chest. Pathoma: Normally think of lung as bunch of balloons, while in emphysema, think of air sacs as a *shopping bag*. Air shoots out of a balloon, not a shopping bag. Elastic tissue is destroyed → *collapse of small airways* when exhaling!!!! (due to loss of elastic tissue) → *air trapping* Prolonged expiration with *pursed lips* . Problem is we have collapse of small airway... having *pursed lips* creases some backpressure to help keep wall open and let air *in and out*... so they are called *pink puffers* (slightly hypoxic)!!!
# Subacute Sclerosing Panencephalitis (!!)
Encephalitis- swelling of brain Pan- means it involves BOTH grey and white matter .... characterized by *viral inclusions* within BOTH: - the neuron (gray matter) , - Oligodendrocytes (white matter) Progressive, debilitating encephalitis leading to death. Due to slow progressing, persistent infection of brain with *altered strain of measles virus*. !!! Measles as a *single stranded, RNA paramyxovirus* which produces *hemagglutinin!!!!* to mediate cell surface adhesion! The altered strain of measles associated with SSPE is resistant to immune detection since it does not produce Matrix (M) protein!!!! This keeps it intracellularly, away from the immune system. Infection occurs in infancy, neurologic signs arise years later
# Type 2 DM
End organ RESISTANCE to insulin, leading to metabolic disorder and hyperglycemia. Pathogenesis is related to obesity → insulin resistance (decreased glut 4 receptors). STRONG genetic predisposition (but no HLA association) The β-cells generally responds by increasing insulin secretion. This leads to a state of impaired glucose tolerance. When the β-cells get exhaused, AMYLOID is deposited in islet cells, diabetes occurs!!!!!
Cirrhosis
End stage liver damage, characterized by disruption of hepatic parenchyma by: - bands of fibrosis (mediated by TGF-B from STELLATE cells beneath endothelial cells which line sinusoids) - *regenerative nodules* of *proliferating hepatocytes* (with fibrosis bands separating nodules) - vascular architecture disrupted
# Endocarditis and kidneys
Endocarditis can sometimes progress to *diffuse proliferative glomerulonephritis* secondary to *immune complex* deposition
Endocarditis
Endocarditis is an infection of the endocardial surface of the heart, usually involving the *surface of cardiac valves*. Most cases are caused by a *bacterial infection*. Damaged endocardial surface (ie, mitral valve prolapse!!!) exposes subendothelial collagen, which develops *thrombotic vegetations* containing *platelets* and *fibrin*. These vegetations cause trapping of bacteria in them whenever there is Transient bacteremia (in blood). So, dental or surgical procedures, contaminated needle use, breaks in the epithelial barriers of the gut, oral cavity, or skin increase the risk of endocarditis in individuals with predisposing medical conditions.
#above the pectinate line.
Endoderm (hindgut). Comprises distal 1/3 transverse colon, descending colon, sigmoid colon, and rectum. Has internal hemorrhoids, adenocarcinoma. Superior rectal artery (branch of IMA) supplies it.!! Venous drainage: superior rectal vein, inferior mesenteric vein, portal system . Lymph- internal iliac.
# apoptosis!!!
Energy dependent, genetically programmed cell death, usually in single or small groups of cells. Always by *caspases!!!* Caspases are activated by: 1. *Initiation stimuli* through either : a) Intrinsic mitochondria mediated pathway ((Bcl-2, apaf-1, cytc etc....) This is induced by things like UV radiation, heat, hypoxia, toxins OR b) extrinsic, receptor-ligand induced pathway . (controlled by TNF or FAS-L!!!) 2. *Execution/Control stage*, either the (Bcl-2, apaf-1, cytc etc)... or 3. Both pathways converse *activating caspases*
# entacapone vs carbidopa
Entacapone inhibits COMT, carbidopa inhibits dopa decarboxylase. They BOTH inhibit the *peripheral breakdown* of L-Dopa, thus increasing quantities of L-Dopa that can cross blood brain barrier. They also reduce symptoms (vomiting, postural hypotension, hot flashes) Tolcapone also inhibits COMT but does so both centrally AND peripherally..... but it can cause hepatoxicity. COMT inhibitors are ONLY effective when combined with levodopa.
# risk factors for urothelial/transitional cell carcinoma
Environmental exposures account for the majority of cases!! Risks associated with bladder cancer include the following: *Smoking (Most Common)*... particularly *polycyclic aromatic hydrocarbons* in it!!! Occupational exposure (e.g. painters, rubber industry beauticians because of azo-dyes, aniline dyes industrial factory workers) Medications (e.g. *Cyclophosphamide* or *phenacetin*!!!!)
# Pancreatic carcinoma presentation
Epigastric abdominal pain, weight loss, pancreatitis (tumor blocks duct, increase risk of enzyme premature activation - Migratory thrombophlebitis (aka Trousseau syndrome....swelling/erythmea in extremities, in 10% of cases) (!!!!!!) - serum tumor marker is CA 19-9 (!!)
# Vitamin K is activated by what?
Epoxide reductase in the LIVER , so it is impaired in liver conditions ie cirrhosis!!!
# Gastric erosions vs gastric ulcers
Erosions are limited to the mucosa!! They do NOT penetrate THROUGH the muscularis (but may extend into it). Usually occur in the setting of *acute erosive gastropathy*. Gastric ulcers penetrate THROUGH the mucosal layer and into the submucosa!!!
# Esophageal *squamous cell* carcinoma (!!)
Esophageal cancer: most common form worldwide is squamous cell carcinoma (90%)- malignant prolifferation of squamous cells. Usually arises in middle or upper 1/3s. Prognosis is very very poor. These patients *present initially with dysphagia (commonly to solids only, but may progress to liquids) *& weight loss. Also *horse voice* if involves *recurrent laryngeal nerve*
#Huntington's and neurotransmitters
Especially depletes cholinergic and GABA-ergic neurons: - ↑ Dopamine - ↓ ↓ GABA - ↓ ↓ ACh
why do prolactin levels rise with pregnancy, but pregnant women do not lactate?
Estrogen and progesterone prevent prolactin from causing lactogenesis. Once they drop with birth, lactation begins
# Enveloped virus' and ether !!!
Ether F's up the lipid bilayer of a *viral envelope*!!!!!
#sarcoidosis etiology
Etiology not fully understood, likely due to an *overreaction by CD4+ T-cells* to an *unknown antigen*. CD4 T-helper release cytokines which cause development of *noncaseating granulomas*. In the lung, this causes a *restrictive* lung disease. Granulomas consist of macrophages, epithelioid cells, and multinucleated giant cells, surrounded by lymphocytes, monocytes, mast cells and fibroblasts. Histologically, *asteroid bodies* and Schaumann bodies are found within multinucleated giant cells. However, these may be seen in other granulomatous diseases as well.
#illness anxiety disorder (hypochondriasis)
Exaggerated concern with health and illness and associated with "doctor shopping" • Major fear of having a serious illness, even in the face of medical evidence to the contrary.
# Vitamin A excess
Excess (result of eating bear liver or isotretinoin therapy for skin conditions): increased intracranial pressure (papilledema, convulsions), liver toxicity (vitamin A is stored in the liver) splenomegaly, bone pain
# Syndrome of inappropriate ADH secretions (SIADH) (!!!!)
Excessive ADH secretion and thus excessive water retention - HYPOnatremia and LOW serum osmolality (hold too much water)... but HIGH urine osmolality. - very low serum sodium levels leads to mental status changes, cerebral edema, seizures - basically the body has very high levels of ADH so it in turn lowers aldosterone levels very low, so we piss out a ton of sodium to the point where urine osmolarity> serum osmolarity. • Patients with SIADH will generally present with *euvolemic hyponatremia !!!!* What happens is the increase in ECF volume then suppresses the RAAS system AND stimulates production of natriutetic peptides, causing an *increase excretion of sodium in the urine.* So, they present with NORMAL body fluid volume (euvolemia) with a LOW soium (hyponaternia)
#hypersomnolence disorder-
Excessive and impairing daytime sleepiness cannot be explained by another sleep disorder. They do NOT feel refreshed after naps.
# Cushings
Excessive cortisol, so muscle wasting (weakness, thin extremities) - Moon facies, buffalo hump, truncal obesity (excess glucose, so excess insulin, and fat stores in face, back, trunk) - abdominal striae (cortisol impairs collagen synthesis, so weak collagen leads to *easy blood vessel rupture)* - HTN (cortisol upregulated Alpha-1 receptors on arterioles to upregulate vascular tone - Osteoporosis, immune suppression
# Secondary hyperparathyroidism (!!!)
Excessive production of PTH due to disease process EXTRINSIC to parathyroid gland. Most common cause is chronic renal failure!!
# DKA (Diabetic ketoacidosis)
Excessive serum ketoacidosis (β-hydroxybutyrate >> acetoacetate), often with stress/infection (epi ↑ glucagon and thus ↑ lipolysis, glycogenolysis, glucogenesis). - Hyperglycemia (>300 mg/dl) - Metabolic acidosis (anion gap acidosis), low bicarb (<15 mQq/L) - Hyperkalemia (due to less insulin, and also due to acidosis buffering bringing H+ into cell and K+ out of cell.... however, a lot of K+ is lost in the urine (!!!) so *intracellular and total body K+ is low*) !!!! - Kussmaul respirations (rapid and deep breathing), -fruity" odor on breath (due to exhaled acetone) -abdominal pain,
# temporal lobe lesion
Experience language problems, difficulty with sensory innervation, impaired memory.
# passive aggressive behavior
Expressing aggression to another person by passively refusing to meet their needs. It allows a person to express their hostile feelings in a non-confrontational mannor. ie, ignoring , but NOT just this Individuals with passive-aggressive personality disorder appear to comply or act appropriately, but they actually behave negatively and passively resist.!!!!This personality disorder is a chronic condition, meaning that it lasts throughout life. They are stubborn and inefficient. Symptoms include: •Contradictory and inconsistent behavior—An individual with passive-aggressive personality disorder may appear enthusiastic to carry out others' requests, but he purposely performs in a manner that is not useful and sometimes even damaging. •Intentional avoidance of responsibility. Some behaviors that may be used to avoid responsibility include: •Procrastination—to delay or postpone needlessly and intentionally •Deliberate inefficiency—purposefully performing in an incompetent manner •Forgetfulness •Feelings of resentment toward others •Stubbornness •Argumentative, sulky, and hostile, especially toward authority figures •Easily offended •Resentful of useful suggestions from others •Blames others •Chronically impatient •Unexpressed anger or hostility
Exudate
Exudative: Protein and cell rich, (ie, neutrophil rich) !!! due to increased vessel permeability secondary to inflammation. Examples include: Pulmonary infarction, pulmonary infection (!!!) , or malignancy (malignant pleural effusions). Protein > 30 g/L Serum protein > 0.5 Specific gravity > 1.02 Serum LDH > 0.6 Pleural fluid LDH > 200 U/L
abducens nerve palsy ( CN VI)
Eye is deviated *medially* Palsy here causes HORIZONTAL diplopia
How does hypovolemia affect GFR, FF, RPF
FF= GFR/RPF Both GFR and RPF will decrease, BUT there is compensation leading to constriction of efferent arteriole so GFR does not decrease as much as RPF does. Thus, FF increases.
Fee for service vs discounted fee per service
FFS are paid for every service they provide, so they're more likely to order extra tests, encourage extra visits, more unnecessary procedures. Discounted FFS are more conservative when ordering tests and providing services, especially if expensive tests/services are greatly discounted.
# Hemophilia B
Factor 9 deficiency (aka Christmas disease) S/Sx are identical to Hemophilia A, including laboratory results demonstrating *isolated PTT prolongation*. Like hemophilia A, hemophilia B is also X-linked recessive. ↑ PTT is seen with factor deficiencies, DIC, vWD and anti-phospholipid syndrome (associated with SLE).
# PDA (patent ductus arteriosus):
Failure of *ductus arteriosus* to close, associated with *congenital rubella*. Ductus arteriosus shunts blood from *pulmonary artery* to the aorta at location *after* aortic branches* In utero, a patent ductus arteriosus (PDA) provides a right to left shunt as a normal part of the fetal cardiovascular circulation 3 days after birth, the ductus arteriosus will functionally close due to *↓ in PGE levels* (PGE promotes ductus arteriosus patency). This drop is triggered by the post-natal *increase in PaO2* (O2 inhibits PGE synthesis). PVR also falls in response to lung expansion and rise in PaO2. If the ductus arteriosus continues to remain open after birth, an *L-R shunt initially develops*, leading to excessive pulmonary blood flow. Complications resulting from a large shunt may include: pulmonary artery hypertension, ↑ pulmonary vascular resistance, RVH... eventually *shunt reverses* !!!! (deoxygenated blood is pumped, gives cyanosis preferably restricted to LOWER extremities)!!!!!!!!!
# Digeorge syndrome
Failure of development of the *3rd and 4th pouches* due to a microdeletion of genes at the long arm of chromosome 22 (22q11.2) !!! Also caused by mother alcohol drinking @ weeks 4-6 -hypoplasia and basically *absence of the thymus and parathyroid glands*, leads to - congenital *T cell deficiency*!!! - causing recurrent viral and fungal infections. The PARACORTEX is underdeveloped because this is where T-cells live!!! - tetany from hypocalcemia (hypo PTH) - heart defects (Tetralogy of Fallot, persistent truncus arteriosus, interrupted aortic arch) - Cleft palate (mandible) - ear deformity all leading to aka velocardiofacial syndrome (VCFS) Congenital heart disease is the most common cause of death. Severe immune deficiency is the second most common cause.
# orthostatic hypotension
Fall of >20mm systolic or >10mm diastolic. Standing pools 500-1000ml blood to legs in the *veins*. This causes 1) decreased Venous return 2) Decreased ventricular filling, drop in CO and BP 3) drop in BP evoked baroreceptor reflex 4) increased sympathetic tone raises peripheral vascular resistance through *alpha-1 stimulation of peripheral vasculature*, increasing venous return and CO
# Early onset Alzheimer's
Familial form, the key genetic form is a mutation in *presenilin 1* !! (chromosome 14).... (also *presenilin 2* from chromosome 1) Increased risk in patients with *Down's syndrome* !!! Because in Down Syndrome we have 3 copies of *Chromosome 21*.... and *Amyloid precursor protein (APP)* also comes from *chromosome 21* !!!!!!!!!
#felty syndrome
Felty syndrome is a disorder comprised of: • Rheumatoid arthritis (RA) • Splenomegaly • Leukopenia (autoimmune neutropenia)
#oligohydramnios causes in general
Fetal urination, lung fluid, and swallowing all play a vital role in the amniotic fluid volume levels. Fetal disorders affecting any one of these functions may affect the fluid volume. Examples include the following: • Premature rupture of membranes (PROM): Most Common • Uteroplacental insufficiency • Fetal tract abnormalities: renal agenesis (e.g. Potter Syndrome), AR polycystic kidneys , and posterior urethral valves (!!!)
# Second Generation Antihistamines:
Fexodenadine (!!!!!!) • Mechanism: Same as first generation antihistamines (histamine receptor inverse agonism), however because these agents are lipophobic and have decreased affinity for cholinergic receptors AND they do not have as many CNS side effects (ex: sedation) and as such are better for "daytime" formulations. • Adverse Effects: Most commonly mild anticholinergic effects such as dry eyes or dry mouth. Clinical Uses: • Acute allergy treatment • Allergy prophylaxis • Sleep Aid • Treamtment of motion sickness
# Fibromuscular dysplasia
Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory vascular disease that causes abnormal growth/thickening within the wall of an artery. FMD has been found in nearly every arterial bed in the body. However, the most common arteries affected are the renal and carotid arteries. There is a "string of beads" on the renal artery !!!! Will hear bruit!
# treat CML (!!!!)
First line is imatinib mesylate (Gleevec) which blocks this bcr-abl tyrosine kinase activity.
# bacterial Meninges fluid findings!!!!
Fluid is then analyzed after LP: *bacterial meningitis*- has *neutrophils* because they fight bacterial infection, and there is *low glucose* because the bacteria consumes the glucose! . Remember: serum glucose is *normally around 2/3 of serum* Shows *positive gram stain/culture*
# Central Pontine Myelinolysis (!!!)
Focal OSMOTIC DEMYELINATION at the white matter in the center of the PONS in the brainstep.... due to *rapid IV correction of hyponatremia*, particularly in *severe malnourishment* (ie, alcoholics, liver failure) !!!! Classically presents as *acute muscle weakness*, aka *locked in* syndrome.... patients voluntary movements are all impaired *except the eyes*, so they are "locked in" their own body!!
# What B vitamins do NOT wash out quickly?
Folate (B9) and Cobalamin (B12)
# Thyroid hormone functions
For thyroid hormone functions, remember the 4 B's. Brain maturation Bone growth (but too much = resorption) Beta-adrenergic effects (upregulates B1 on heart= increased CO, HR, SV, contractility) BMR ↑ (increased Na+/K+ activity= increased RR, O2 consumption, body temp)
# blood brain barrier
Formed by TIGHT JUNCTIONS in capillary beds of CNS. It does NOT allow passage of fluid and dissolved substances. Glucose and amino acids cross BBB slowly and require carrier mediated transport
# helmet cells
Formed in microangiopathic hemolytic anemia.... OR mechanical damage which *often occurs with a prosthetic valve* !! (ie, severe mitral insufficiency). Prosthetic vvalves produce excessive shear and turbulence, causing mechanical trauma to RBC's !!!!
pectinate line
Formed where endoderm (hindgut) meets the ectoderm. It divides the upper 2/3 and lower 1/3 of the anal canal.
# Vitelline duct cyst aka enterocyst
Forms if peripheral portions of the vitelline duct obliterate, but the *central portion remains* !!! This cyst is connected with the ileum and abdominal wall by fibrous bands.
# leucine zipper
Found in *zipper proteins*, it has a short *alpha helix with leucine residues at every 7th position*. Zipper proteins are *transcription factors* which *bind to DNA* and induce transcription .
club aka clara cells
Found in the ciliated epithelium, may secrete GAGs. Degrade toxins via cytochrome P450 pathway. Act as stem cells as well. Secrete club cell secretory protein - a surfactant-like molecule.
# drug bioavailability
Fraction of drug administered that reaches circulation unchanged. Oral bioavailability is *area under the oral curve* divided by *area under the IV curve*... so it is ALWAYS less than 1 !!!
# distal ulnar nerve injury
Fracture of the *hook of the hamate * often occurs as a result of *falling on an outstretched hand*. Often happens in *stick sports* ie tennis, lacrosse. ..... or *handlebar neuropathy*, Usually in cyclists due to gripping, it compresses the ulnar nerve at the wrist. Causes *claw hand*
# Proximal ulnar nerve lesions:
Fracture of the *medial epicondyle of the distal humerus* or *cubital tunnel syndrome. * Ulnar paradox (!!!) proximal lesion of the ulnar nerve (medial epicondyle of humerus fracture) *causing denervation to flexor carpi ulnaris and flexor digitorum profundus (FDP).* The paradox refers to the fact that *losing both the lumbricals and FDP from a proximal injury results in a less severe claw* (because the digits are paralyzed in extension) than what is observed in a distal injuring which spares the FDP resulting in flexion (clawing) of the digits.
fetal circulation
From the placenta, it uses the *left umbilical vein* and then goes through the *ductus venosus* to avoid hitting the liver, and then into the IVC, and then the heart. From the *IVC*, most of the blood is diverted from the right atria to the left atria through the *foramen ovale*, where it then circulates out of the aorta and into systemic circumation. Blood that escapes the *foramen ovale* and ends up in the right ventricle, is then diverted from the *pulmonary artery* to the *DESCENDING aorta* through the *ductus arteriosum*.
sweating
Function of the cholinergic postganglionic neurons of SNS *thoracic sympathetic trunk*. SNS postganglionic nerve innervate: - eccrine glands - apocrine glands. Eccrine glands is responsible for hyperhidrosis. The postganglionic sympathetic neurons that synapse on eccrine glands are cholingergic!! Eccrine (sweat) glands contain a secretory coil and a straight duct. • Eccrine glands are composed of three cell types: • Clear cells • Dark cells • Myoepithelial cells • Autonomic stimulation via acetylcholine (ACh) stimulates the eccrine glands to form an isotonic solution in the gland lumen. • Due to the active resorption of electrolytes by the sweat gland, sweat secreted by eccrine glands is a hypotonic solution. • Eccrine glands also excrete heavy metals, drugs, and organic molecul Apocrine sweat glands are glands that secrete a milky viscous fluid into the hair follicle, rather than directly to the surface of skin !!! Apocrine sweat glands are inactive until puberty !!!! • Apocrine sweat glands are found in or around the: o Axillae o Areola o Perianal region o External genitalia • Apocrine sweat is initially odorless, and starts to sting with breakdown by bacteria (!!!!)
#G-CSF (granulocyte colony-stimulating factor, filgrastim)
G-CSF (granulocyte colony-stimulating factor, filgrastim), is used to stimulate bone marrow to produce stem cells, neutrophils, and granulocytes such as in neutropenia.
# GABA-A vs GABA-B vs GABA-C
GABA-A and GABA-C are *ion channels* while *GABA-B is a G-protein*. GABA-A and GABA-B are in the brain, GABA-C is in the retina.
# filtration fraction and renal plasma flow equations (!!!)
GFR= RPF X FF RPF= Renal blood flow X ( 1-hematocrit) *decreasing renal blood flow* (ie, *renal stenosis!!!* would thus *increase filtration fraction*) RBF thus equals = RPF (measures by PAH!!!) / (1-hematocrit).
# what is the best estimate of GFR and RPF
GFR= creatinine (!!!) RPF= PAH clearance (depends on renal plasma flow). PAH is both freely filtered, and carrier transport secreted!!!!
# how does GI bleeding increase hepatic encephalopathy ?
GI bleeding causes increased nitrogen delivery to the gut in the form of hemoglobin... the nitrogen from hemoglobin is absorbed and then converted to ammonia.
# Cholelithiasis aka gallstones
Gallbladder stones- due to supersaturation precipitation of either cholesterol (75%) or bilirubin (25%) in bile. Also occurs when *decreased phospholipids (ie, lecithin) OR bile acids*... both these help solubilize cholesterol (!!!!)Excess cholesterol increases gallstones!! Cholestyramine use, gallbladder stasis (increase growth of bacteria which deconjugates bilirubin)
# anterior anterior two thirds of the tongue sensation
General/pain somatic afferent sensory information - *lingual nerve, a branch of the mandibular nerve (cranial nerve V3). * Taste- Chorda tympani, branch of the facial nerve (cranial nerve VII)
cough syncope
Generally occurs in overweight patients with COPD. Increased intrathoracic pressure during coughing decreases venous return to the heart, thus decreasing CO and cerebral perfusion. (basically the same as Valsalva)
opioid Intoxication
Generally presents with triad of: CNS depression, Respiratory depression, Miosis (pinpoint pupils).... Can progress to coma. Also can also include: Nausea, Vomiting, Constipation, bradycardia, Peripheral vasodilation Note: tolerance to *constipation and miosis* rarely occur (so they are always there) !!!!!!!!!!
# Asthma treatment (!!)
Generally, an inhaled *β 2-adrenergic agonist* such as *albuterol* is used alone to treat mild disease and acute asthma attacks. Other medications are used to control symptoms and prevent acute attacks. These include: - inhaled corticosteroids - long acting inhaled β 2-adrenergic agonists (e.g., salmeterol - leukotriene modifiers (e.g., montelukast) - Omalizumab (sub-q injection)!!!! and, less frequently, theophylline or cromolyn Oral corticosteroids are sometimes used for short periods to treat otherwise ncontrollable asthma exacerbations.
what is the most important factor for differences in bone mass in premenopausal women?
Genetics by far. Physical activity is more important in teenage and young adults.
# aminoglycosides
Gentimicin, Neomycin, Streptomycin. Bactericidal, *inhibit formation of initiation complexes* and inhibiting the 30S subunit, and cause misreading of mRNA.
alpha 2 receptors
Gi • decreases sympathetic outflow (suppress norepinephrine release) • decreases insulin release, induce glucagon release • decrease lipolysis • platelet aggregation • vasoconstriction • mediate synaptic transmission in nerve terminals
#What is Glaucoma?
Glaucoma is a group of diseases that cause loss of visual field because nerve fibres are damaged at the optic disc, which leads to pathological cupping of the optic disc. The term Glaucoma is usually used for damage caused by *raised intraocular pressure* due to the disruption in the balance of aqueous humor production by the ciliary processes and drainage by the trabecular meshwork, leading to optic nerve damage.
# Nephrotic syndrome (!!!)
Glomerular disorders with 1) Massive proteinuria (!!) (>3.5g/day),,, NephrOtic= prOtein!!!!! 2) *Hypoalbuminemia*— (!!!) 3) Generalized *pitting edema 4) Hyperlipidemia and hypercholesterolemia (due to upregulation of Lipoproteins after we piss out proteins!!!!!) 5) *Hypogammaglobulinemia* (risk of infections) 6) Hypercoagulable state
treat hypoglycemia
Glucagon injection in a non medical setting Dextrose (D50) in a medical setting
# stimulus control
Goal is to dissociate the bedroom from ALL activities that Aren't sleeping. Use bed ONLY for *sleep and sexual activity* (ie, don't watch TV in bed, eat in bed) Go to bed when sleepy Leave the bed and go to another room when unable to sleep right away!!
#alpha 1 receptors
Gq- • Vasoconstriction via increased vascular smooth muscle contraction • contraction of bladder, ureter, urethral sphincter • contraction of uterus (in pregnancy!!!) • contraction of seminal tract (ejaculation) • *contraction of pupillary dilator (mydriasis)* • constriction of sphincters in intestine
Staph aures microbio
Gram +, cocci in clusters, catalase +, coagulase +, β-hemolytic, forms yellow/golden colonies (aurei="golden"). Produces Protein A which binds to Fc portion of IgG activating complement!!!
# actinomycosis
Gram positive anaerobic bacteria. Found in dental caries and margina of gums in patients with poor dentition. Pulmonary actinomycosis develops by aspiration, and can be confused for lung abscess, malignancy or TB.
#Guillane Barre syndrome
Guillain-Barre Syndrome (GBS) is a *postinfectious* type IV hypersensitivity reaction that causes *SEGMENTAL demyelination* and *endoneural inflammatory inflammation* (!!!!) of the peripheral nervous system.
#Guillain Barre infections
Guillain-Barre Syndrome most commonly follows an *infection with Campylobacter jejuni* due to molecular mimicry between a LPS antigen and the GM1 ganglioside. Infectious diarrhea proceeds symptoms!!
#schwann cells are destroyed in what condition??
Guillain-Barre syndrome
# H1 vs H2 receptors
H1 is Gq.... Increases nasal/bronchial mucus, vascular permeability, mast cell degranulation bronchiole constriction/spasm H2 is Gs... increases gastric acid
# Polyarteritis Nodosa associated with what virus (!!! !)
HBV. !!Hepatitis B infection in 30% of these patients. Associated with serum HBsAg. (Hep B surface antigen)
RA Pathyphys
Hallmark is *synovitis* (inflammation of the synovium), which leads to formation of a *pannus*, which is *inflamed, granulation tissue* rich in inflammatory cells and fibroblasts! !!! This pannus leads to *destruction of the articular cartilage*, and *ankyloses* of the joint. Remember: Granulation tissue contains 3 things: -Blood vessels - fibroblasts - myofibroblasts... which have *contractile function*!!! When myofibroblasts contract here we get: - FUSION of the joint, called *ankylosis* - dragging of the joint in different directions (deviations of joints).
#high potency typical anti-psychotics
Haloperidol, Trifluoperazine, Fluphenazine.... Cause EPS symptoms !!!
adrenal crisis
Happens in pateints with *adrenal insufficiency*!! Presents as *shock* with a combination of hyponatremia, hyperkalemia, and hypoglycemia. Give IMMEDIATE corticosteroids
norepinephrine extravasation (!!)
Happens occasionally when norepinephrine is being infused... NE causes intense alpha-1 receptor vasoconstriction which can lead to the tissue to become cold, hard, pale.... Eventually necrosis. Treat with *phentolamine* (alpha-1 antaganist).
.# isosorbide MONOnitrate
Has the HIGHST (almost 100% bioavailability) when given orally.
# Hashimoto thyroiditis pathogenesis
Hashimoto thyroiditis is caused by autoimmune failure of self-tolerance to thyroid auto-antigens → thyroid cell death due to: 1) CD8+ T-cell mediated cell death 2) Cytokines activate TH1 → IFN-γ recruits and activates macrophages → follicle damage 3) Anti-thyryrotropin aka TSH receptor INHIBITORY antibodies: - Anti-Tg (thyroglobulin) antibodies - Anti-TPO (thyroid peroxidase) antibodies (aka antimicrosomal antibodies)— ... note do not mediate the diease, they are markers the thyroid has been damaged. (!!!!!!!) Associated with HLA-DR3 and HLA-DR5 (impt!) HLA-DR5 is also associated with pernicious anemia!!!
# nitrates sides
Headaches, facial flushing. (!!!!) Can sometimes cause hypotension and thus tachycardia, which actually increases O2 demand!! Treat this with a beta blocker!
#chronic rejection by organs (!!)
Heart- atherosclerosis Lungs- bronchiolitis obliterans!! (small airway bronchioles aka terminal bronchioles) liver- vanishing bile ducts kidney- vascular fibrosis and glomereulopathy !!!
# Hep B vs Hep C presentation
Hep B has 30-180 day incubation period, presentation is "serum sickness" ike wiyh Fever, malaise, skin rash, pruitis, LAD, joint pain Hep C is much more mild.!!!
# Hep B vs Hep C and hepatocellular carcinoma
Hep C is a RNA virus that LACKS reverse transcriptase (cannot be inserted into host genone). Because it is a RNA virus, the envelope proteins constantly mutate confurring immunity. Hep B is a DNA virus that integrates into host genome!! Because it is inserted into the host genome, risk of HCC remains elevated. It then replicates with reverse transcriptase!!! HBV in the genome can produce *HBx protein* which " - inactivates p53 activates multiple growth producing genes
# Hepatic encephalopathy
Hepatic encephalopathy (also known as portosystemic encephalopathy) is the occurrence of: - confusion/altered level of consciousness - asterixis - ataxia & hyperactive deep tendon reflexes - signs of chronic liver disease (jaundice, edema, ascites, palmar erythema, telangiectasias, caput medusa) and coma as a result of liver failure!! (hepatitis, HCC, etc) Encephalopathy occurs due to buildup of ammonia, which is normally converted to urea in the liver!! Ammonia can cross blood brain barrier, and causes: - increased inhibitory neurotransmission (GABA) - Impaired excitatory neurotransmitter release (glutamate) Hypeammonia toxicity *depletes glutaMATE and alpha-ketoglutarate in the brain!!!!*. There is *accumulation of glutaMINE*, which causes astrocyte swelling
# Hep E
Hepatitis E is the cause of another form of hepatitis that is spread by the fecal-oral route and therefore resembles hepatitis A. Classically, contaminated water and uncooked seafood. Hepatitis E virus is a UNENVELOPED RNA virus. Like hepatitis A, infection with this virus is frequently subclinical. When symptomatic, it causes only acute disease that may cause fulminate hepatitis to death, *ESPECIALLY in pregnant women.*
Epidural hematoma
Here, we get a fracture to the *temporal bone which ruptures the *middle meningeal artery*... which causes a *collection of blood between the dura and skull.* This creates a " biconvex lens shaped" lesion. We have a "lucid interval" before the patient is symptomatic. (ie, hit their head, get knocked out, and then feel okay).... as blood builds up, suddenly this hematoma expands and results in a lethal herniation. There is also CN3 palsy.
# Uncal herniation (aka Trans-tentorial) (!)
Herniation of the *medial aka uncus of the temporal lobe* herniates into the *tentorum cerebelli*... which is the area *between the cerebellum and brainstem* This compresses: 1) ipsilateral CN 3 (eyes down, out, dilated pupil, impairment of ocular movements on the *ipsilateral side* of the lesion) 2) ipsilateral Posterior Cerebral Artery- gives *contralateral homonymous hemianopsia* 3) Pull on *paramedian artery* giving *direct hemorrhages on brainstem* 4) contralateral Compression of crus cerebri (cerebral peduncle) .....BUT this causes *ipsilateral hemiparesis*
brain herniation
Herniation syndromes occur when the brain expands and displaces the contents of the intracranial cavity. Coma and death can result from compression of the brain stem by a herniation.
# HIV HAART and body fat
Highly active antiretroviral therapy (HAART) causes: 1) lipoathrophy- loss of subcutaneous fat from face, extremities, dur to *nucleoside reverse transcriptase inhibitors* 2) central fat deposition- seen with ANY form of HIV medication.
# Papillary carcinoma thyroid histo (!!!!)
Histologically, cells are described as having large "Orphan Annie eye nuclei" because of the characteristic shape they assume (white clearing in center of nucleus).. The nuclei contain *finely dispersed chromatin*, giving them a *ground glass' appearance. !!!! Look for characteristic *Orphan Annie eye nuclear inclusions* (nuclei with uniform staining, which appear empty), and *psammoma bodies (round concentric collection of calcium)* on light microscopy. -nuclear grooves. "papillary branching of epithelium". - Excellent prognosis.
Meningioma histology
Histology shows spindle cells with a "whirled pattern with psammoma bodies*!!!!
# small cell carcinoma
Histopathologically, small cell lung carcinoma has a distinct morphology consisting of *poorly differentiated*, *small, round, oval* or spindle shaped hyperchromatic, hypermitotic cells with a granular salt-and-pepper nuclear chromatin pattern. ALL small cell lung carcinomas are high grade, highly malignant and *widely metastatic. Small cell lung carcinomas are the *most aggressive* of all lung carcinomas Extensive necrosis is common in small cell lung carcinoma. Small cell lung cancer, like *squamous cell lung cancer*, more commonly *arises centrally* near the hilum or major bronchi !!! Mnemonic: when it starts with "S" it is associated with Smoking, "sen"tral, and maybe paraneoplastic syndrome.
#tricuspid regurge
Holosystolic, high-pitched "blowing murmur." Loudest at tricuspid area (lower left sternal border) and radiates to right sternal border, Enhanced by maneuvers that *increases total peripheral resistance and with with inspiration.*
What gives protein secondary structure (alpha helix, beta sheath) strength
Hydrogen bonds!!!
# treat sickle cell (!!)
Hydroxyurea to increase HbF. *Gardos channel blockers*. The *calcium-dependent (gardos) potassium channel* regulates the transport of potassium and water through the red blood cell membrane. When this is blocked, potassium and water efflux are REDUCED, which *decreases cellular dehydration (aka hydrates the cell)* and thus *decreases the polymerization of HbS!!!*
# niacin overdose (!!)
Hyperglycemia, hyperuricemia.
# Obstructive lung disease spirometry !!
Hyperinflated lungs!!! 1) ↑ RV (!!) 2) ↓ or normal FVC 3) ↓↓ FEV1 4) ↓ FEV1/FVC ratio (Normal 80%... so in obstructive it is <80%, ie < 70%) 5) ↑ TLC 6) ↑ Functional Residual Capacity
# clinical S:Sx of BPH
Hyperplasia around *periurethral area * compresses urethra - problems starting/stopping urination - impaired bladder emptying - dribbling - smooth muscle bladder hypertrophy (bladder must forcefully push against a narrowed urethral opening... this MAY cause a diverticuli/outpouching of bladder) Obstruction of bladder could result in a backup of fluid into the kidney causing *hydronephrosis*, causing *dilation of uterer*... and ultimately *dilation, damage, PRESSURE ATROPHY of kidney*!!
# BPH (benign prostate hyperplasia)
Hyperplasia of both the prostatic stroma AND glands. Despite pathologic hyperplasia, here there is NO increased risk of cancer. Driven by Testosterone --> DHT in the *stromal cells* which acts on ARs in both stromal and glands. This occurs in the *periurethral zone* of the prostate !!! → soft, rubbery nodule formation
# Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a condition characterized by hypertrophy of the myocardium, usually *left ventricle*, leading to hypercontractile, non-compliant myocardium. decreased left ventricular volume. (!!!!) Hypertrophic cardiomyopathy is functionally characterized by *diastolic dysfunction* and *INCREASED ejection fraction*. Classic history: "An otherwise healthy young athlete suddenly passes out and dies." Patients with this history usually succumb to sudden cardiac death, most commonly due to ventricular fibrillation
# acyl coa dehydrogenase deficiency
Hypoglycemia after prolonged fasting with VERY low levels of ketones. (impaired beta oxidation)
mullerian duct anomalies
Hypoplasia/agenesis of vagina/uterus Duplication of vagina, cervix, uterus Unicornuate, bicornuate and separate uterus
## Aortic Coarctation
Hypoplastic *narrowing* of the aorta during embryological development. Divided into: 1. Infantile form 2. Adult form
#CCK comes from what cells
I cells in the duodenum and jejunum
DNA pol III:
III (the main prokaryotic polymerase): adds DNA nucleotides to the hydroxyl group on the 3' end of the new strand (5'→3' synthesis), makes lagging/leading strands DNA Pol III also has a *3'→5 exonuclease activity* to correct mistakes during replication !!!!!!
# Multiple Myeloma bones
IL-6 drives Plasma cells, which produce osteoclast activating factor (IL-1!) !!! which activate RANK receptor on osteoclasts, and the osteoclasts are activated and they eat at bone which results in LYTIC, punched out lesions (particularly in vertebrae and skull). This results in bone pain, hypercalcemia, and increases risk of fracture.
# interferon gamma defects
INF-y is released by: Macrophages ingest mycobacteria and secrete IL-12. This stimulates T-Cells and NK cells to produce IFN-y. IFN-y binds to its receptor and leads to receptor dimerization and activation of JAK 1 and 2!!! This results in NUCULAR signaling via STAT, to promote killing of mycobacteria genes. IFN-y defects result in *disseminated mycobacterial disease* !!!! (can't wall it off in granuloma)
# cromolyn
INHIBITS mast cell degranulation. Used more for PREVENTION of acute attacks, rather than treating. Used in seasonal asthma, aspirin hypersensitivity, aspirin induced asthma.
#Kallmann Syndrome
Idiopathic Hypogonadotropic hypogonadism + anosmia (inability to smell) Functional absence of GnRH secretion from neurons or defect at the level of GnRH receptors results in hypogonadism. Often presents as delayed or disrupted puberty; small testes, failure to develop secondary sex characteristics, can't smell.
# TCA antidepressants
Ie, amitriptyline 1) blockage of NE and 5HT presynaptic reuptake- thus potentiating their effects. 2) blockage of Muscarinic cholinergic receptors 3) blockage of α1 adrenergic receptors 4) blockage of H1 histamine receptors
#classical conditioning
Ie, pavlov's dog.... Learning in which a natural response is elicited by a conditioned stimulus. Usually deals with INVOLUNTARY responses (ie, salivation)
migratory thrombophlebitis , aka Trousseau syndrome!!!
Ie, phlebitis in ams AND legs. Should ALWAYS make you think of "cancer". Hypercoagulability is a very common paraneoplastic syndrome seen most commonly in *adenocarcinomas* of the pancreas, colon or lung. Hypercoagulability occurs because adenocarcinomas produce a *thromboplastin-like substance* that is capable of causing chronic intravascular coagulations which are disseminated and migrate.
# chronic gout hallmark
If gout is poorly controlled, monosodium urate crystals may deposit in periarticular soft tissues..... leading to the hallmark formation of *tophi*, which are *white, chocolate uric acid crytals in soft tissues/joint* Renal failure due to deposition of uric acid in the tubules of the kidney damaging them
Nitrate tolerance
If nitrates are given "around the clock", tolerance develops. So, give it only morning and afternoon, then break in the evening.
# non-small cell carcinoma histopath summary
If we see *glands* or *mucus production* think *adenocarcinoma* If we see *keratin pearls or intracellular bridges* think *squamous cell carcinoma* If we don't see any of this, call it a *large cell carcinoma*
#reaction formation
Immature defense mechanism, replacing a warded off idea/feeling by an UNCONSCIOUSLY derived emphasis on its opposite. . Associated with obsessive compulsive disorder. The emphasis is on doing something which is *excessive and opposite* to ones own feelings. ie, person wants who wants to hurt animals becomes animal rights activist Porn star becomes anti-porn activist
# IgA nephropathy findings and assiciations
Immunofluorescence microscopy: - *Mesangial* (!!!) deposition of IgA*, often with C3 and properdin Electron microscopy: - Confirms the presence of mesangial deposits (!!!) When IgA nephropathy/Berger's has actions beyond the kidney, it is considered a VARIANT of HSP!! Associated with: - Henoch Schönlein purpura—purpuric skin rash (IgA-mediated small vessel vasculitis), hematuria (IgA-mediated kidney disease), abdominal pain (GI involvement), arthritis/arthralgia (joint involvement). - Celiac —IgA-mediated bowel disease (anti-gliadin IgA), Dermatitis herpetiformis—grouped vesicles on extensor surfaces
Nephrogenic diabetes insipidius
Impaired renal response to ADH due to inherited mutations in the V2 receptor, or secondary to - drugs (lithium)!! • demeclocycline, • hypercalcemia or • sickle cell disease. - amyloidosis In nephrogenic diabetes insipidus, hyperosmolality and hypernatremia occur despite a high plasma concentration of ADH. Similar to central diabetes Insipidus, but does NOT respond to desmopressin !!!! (b/c kidney cannot respond) to it.
# carnitine deficiency
Impairs fatty acid transport in the mitochondria and impaired beta-oxidation, thus restricting *ketone body production*
# Bohr effect
In *peripheral tissues*, high levels of CO2 and H+ facilitate UNLOADING of oxygen from hemoglobin to the tissues.
# Elastic arteries and Marfan syndrome (!!)
In Marfan syndrome, patients possess an autosomal dominant defect in fibrillin (!!!) synthesis, resulting in weak elastic tissue! This predisposes *dilation of the ascending aorta, causing aortic regurgitation * (valve annulus also dilates), and possible aortic dissection. !!!!! (most common cause of death!)
# Saline action on the heart
In a shock patient, the intravascular system is low, and the sympathetic system is MAXIMALLY STIMULATED. IV fluids increase intravascular volume and *ventricular preload*. The increased preload *increased end diastolic sarcomere length*.
#what other symptoms arise with reactive arthritis?
In addition to the classic symptomatic triad of urethritis, conjunctivitis, and arthritis, patients with reactive arthritis frequently develop: • Oral ulcers • Skin lesions • Very often causes *sacroilitis*.
# hepatitis liver enzymes
In alcoholic hepatitis, AST > ALT, because alcohol damages mitochondria, which is where AST is normally located. Vital hepatitis, ALT >> AST Note: the enzymes are mildly elevated.
lung resistance
In cases of increased elastic resistance, patients have STIFF LUNGS, such as pulmonary fibrosis, pulmonary edema, respiratory distress. Optimal breathing is many breaths that are very shallow. In cases of increased airflow resistance (asthma, COPD), patients breath better with slower, deeper breaths. bb
# Emphysema and gas values
In emphysema, PaCO2 and PaO2 are normal until *later in the disease course*. Contrast this with chronic bronchitis, in which PaCO2 and PaO2 are abnormal earlier on. PaCO2 is normal and incidence of cor pulmonale is low. Again, by contrast, patients with chronic bronchitis have elevated PaCO2 and higher incidence of developing cor pulmonale.
toxoplasmosis presentation
In immunocompetent individuals, the host response contains infections and patients present asymptomatically or with a mononucleosis-like illness such as sore throat, fever, and swollen lymph nodes. In immunocompromised individuals, *cysts rupture and release tachyzoites that leads to toxoplasmosis*. Patients present with: • Pneumonitis • Chorioretinitis ((cotton-like white/yellow scars on the retina)!!! • Encephalitis/seizures!!!! Congenital toxoplasmosis presents with the classic triad: !!!!!!! • Chorioretinitis (cotton-like white/yellow scars on the retina) • Hydrocephalus/seizures • Intracranial calcifications (multiple ring-enhancing lesions in the cortex and basal ganglia on head CT) Note that children can also often be born asymptomatic.
# Polymyalgia rheumatica
In large arteries., the tunica adventitia contains the *vasa vasorum*. Structures of the adventitia are *longitudinally oriented.* *an inflammatory rheumatic disorder of the synovium, bursa, and tenosynovium*.... Most common in women over 50. Primary symptoms of polymyalgia rheumatica include pain and stiffness of the neck, torso, shoulders, and hips. The pain and stiffness is often bilateral. • Systemic symptoms like fever, malaise, and weight loss may also be present in polymyalgia rheumatica. • In polymyalgia rheumatica, *muscle strength is normal (!!!!)* because pain is usually due to bursitis or tenosynovitis (and not myositis).
# where is CO2 used as a reactant??
In purine/pyramidine synthesis in cytosol!!!
# complications of hemolytic disease of newborn
In severe cases, causes anemia, jaundice (kernicterus), generalized edema The anemia also stimulates release of *immature, nucleated erythrocytes* and leads to *persistent extramedullary hematopoiesis in liver, spleen*. !!!
# Pudendal nerve block
In the *ischial spine*.... Blocking the pudendal nerve provides anesthesis to MAJORITY of perineum.
Parkingson's Disease neurons findings on histology
In the neurons of the SNpc, there are round, eosinophilic inclusions called *Lewy Bodies* ... they are composed of *alpha synuclein*!!
#vein embryology
In urtero, the body has 3 forms of veins: 1) Vitelline= which forms the venous veins 2) Umbilical- which degenerate 3) Cardinal veins, form the rest of systemic veins
aromatase deficiency
Inability to synthesize estrogens from androgens which occurs *early in embryonal life* . Since it is *autosomally recessive*, during pregnancy, there is *maternal virilization* due to the transfer of excess androgens into maternal circulation!!!! Increased serum testosterone and androstenedione. This causes: females: clitomegaly/ambiguous genitalia (but normal internal genitalia) at birth Primary amenorrhea, osteoporosis and tall stature (low estrogen delays fusion of epiphyses) !!! Males: nothing
# Thioamides (!!!)
Include PTU (propylthiouracil) and methimazole. These drugs interfere with the function of thyroid peroxidase, which catalyzes two reactions: 1. Oxidation of iodide ions (actively transported into follicular cells) into iodine (I2). 2. I2 molecules can then combine with tyrosine residues on thyroglobulin at the junction of the follicular cell membrane and follicular lumen, a process called organification. PTU also prevents cleavage of T4 to its active form T3 in the periphery. Despite this, however, methimazole is 10x more potent than PTU. • A rare (0.1-0.5%), but dangerous side effect of these two drugs is agranulocytosis, which is usually reversible upon drug withdrawal. !!!! Do a FBC if suspected!!!!! Most common side effect is rash.
# cholinergic agonists!!!
Increase GI motility (nausea, vomiting, abdominal craps and diarrhea). Decrease HR, cause bradycardia, hypotension. increase sweating, salivation, lacrimation.
# What is the major way the heart compensated with volume overload of aortic regurg???
Increase in the LV PRELOAD, aka the LV-EDV. Remember VOLUME overload leads to ECCENTRIC hypertrophy, and chamber dilation. Fibers are added in SERIES.
# tetracycline resistance
Increased EFFLUX of the drug within bacterial cell via an *active pump* OR formation of a protein that allows bacterial translation to keep occurring.
increased afterload
Increased afterload, b/c LV volume doesn't decrease as much, but pressure is higher.
#testosterone:LH levels and deficiency
Increased both testosterone and LH= defective androgen receptor Increased testostetrone but decreased LH= testosterone secreting tumor or exogenous steroids decreased testosterone but increased LH- primary hypogonadism decreased both: hypogonadotropic hypogonadism
increased contractility
Increased contractility because during systole, the LV volume gets smaller and LV pressure is higher.
#lithium and cardiac defects
Increased risk of Ebstein's cardiac anomaly: - opening of the tricuspid valve is displaced apicly towards the apex of the right ventricle of the heart, so there is DECREASED RV volume) - atrialization of the RV - malformation of the great vessels.
# MGUS monoclonal gammopathy of undetermined significance
Increased serum protein, so we do SPEP. SPEP gives a M-spike. But other features of multiple myeloma are all absent (no lytic lesions, hypercalcemia, AL amyloid, Bence-Jones) Occurs in 5-10% of elderly patients, 1% of that 5-10% will get multiple myeloma.
# Carotid Massage:
Increases baroreceptor activity which INCREASES Parasympathetic influence on the heart and ↓ sympathetic activity. This leads to *AV node refractory prolongation*, lowered HR (sinus bradycardia), ↓, BP Used to treat *paroxysmal supraventricular tachycardia*
# how does hepcidin act?
Inflammation and HIGH levels of iron stimulate release of hepcidin. High levels of hepcidin 'locks' iron into storage sites by *reducing the expression of FERROPORTIN* on enterocytes and macrophages in the bone marrow. Ferroportin is a *transmembrane protein that transfers intracellular iron into circulation* !!!! this limits iron transfer from macrophages in bone marrow, so we have impaired production of heme (despite the fact that iron stores are in fact adequate) ! Hepcidin also suppresses EPO production. High levels of hypoxia and increased EPO both lower hepcidin.
# Late phase of asthma
Inflammation from proteins such as *major basic protein* perpetuate broncho-constriction
# Polymyositis
Inflammatory disorder of skeletal muscle, that does NOT involve the skin. It presents clinically similar to dermatomyositis* (proximal muscle weakness), but there is no skin involvement. Shoulders often involved. !!!!!!* *endomysial inflammation* (!!!) is scattered throughout the muscle fascicle in between the fibers. Since it does NOT involve the nerves, the *reflexes are normal!!!*
#influenza structure
Influenza virus is *enveloped negative, single-stranded segmented orthomyxovirus (RNA). * • *Hemagglutinin (HA)* envelope protein binds sialic acid on cells, *facilitating ENDOCYTOSIS * • *Neuroaminidase (NA)* envelope protein *cleaves HA-sialic acid interaction during budding to permit viral spread. *
#ischemic colitis findings
Initially, mucosal hemorrhage, patchy necrosis. If it persists, the injury extends down into the muscularis with the bowel wall thickening and becoming edematous. Finally, transmural infarction is observed which may result in a bowel perforation
#superior gluteal nerve (!!!)
Innervates the gluteus medius and minimus. Can be caused by posterior hip dislocation, polio or L5 radiculopathy Manifests with loss of abduction of the hip *(+ Trendelenburg sign:* !!! ) an abnormal gait caused by weakness of the abductor muscles of the lower limb, gluteus medius and gluteus minimus) During the stance phase, the weakened abductor muscles allow the pelvis to tilt down on the opposite side. To compensate, the *trunk lurches to the weakened side* to attempt to maintain a level pelvis throughout the gait cycle. *The pelvis sags towards the opposite side* of the injured superior gluteal nerve
# Insulin actions
Insulin → ↓ blood amino acid concentration by: 1) ↑ AA uptake into cells and ↑ protein synthesis, ALSO it decreases protein degradation. Insulin → ↓ formation of FFAs (free fatty acids) from TGs and ketoacids in the blood by: Insulin → ↓ blood K levels by increasing Na-K+ ATPase activity. (but increases it into the cells Insulin → ↓ blood glucose concentrations by: 1) ↑ uptake of glucose by target cells 2) ↑ glycogen synthesis, and 3) ↓ gluconeogenesis.
# Classic triad of meckels:
Intermittent colicky abdominal pain (from INTUSSICEPTION!!!) Bilious vomiting currant jelly stools ALSO melena because of the Gastric bleeding!!!!!!!! ("black, tarry stools") Barium enema is both diagnostic and therapeutic.
# Chronic pyelonephritis:
Interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis. Due to vesicoureteral reflux (children) or obstruction (stones, tumors). Leads to *corticomedullary scarring* directly overlaying the deformity of renal pelvis and calyces: *blunting of calyces*. This blunting is not seen in acute pyelonephritis. The scarring at *upper and lower poles* is characterictic of *vesticoureteral reflux* Obstructive type: hydronephrosis → dilation of calyces and thinning of cortex In the later stages, *tubular atrophy* with *eosinophilic proteinaceous casts* which *appear like thyroid follicles*, phrase is called *thyroidization of the kidneys* Can lead to renal hypertension and end stage renal disease
# focal dystonias
Involve one muscle, or muscle group. 1) *cervical dystonia aka spasmodic torticollis* is the most common one. It is a painful condition in which your neck muscles contract involuntarily, causing your head to twist or turn to one side. Cervical dystonia can also cause your head to uncontrollably tilt forward or backward 2) Blepharospasm is 2nd most common one. It is *involuntary, forcible closure of eyelids*. Initial symptom is uncontrolled blinding, but it can cause complete closure of eyelids 3) 3rd common is *writers cramp* of hand.
# TGF- B
Involved in *tissue regeneration/repair*. "stimulates fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM due to inhibition of metallopproteinases." TGF-β- aids in angiogenesis by stabilizing newly formed vessels and is an important fibroblast growth factor and anti-inflammatory mediator.
glutathione s transferase
Involved in detoxification of chemical cartinogens, which converts toxic substances into inactive metabolites.
mesolimbic-mesocortical pathway (!)
Involved in regulating behavior. This area is *hyperactive in schizophrenia*, so *antipsychotics here repress the positive symptoms of schizophrenia*.
# SLE and heart
Involvement of heart on ALL 3 layers, endocarditis, myocarditis, pericarditis. Classic finding is *Libman-sacks endocarditis*. *pericarditis* is the most common cardiovascular manifestation !!!!!! Key feature of endocarditis is "wart like" vegetation on surface of heart values... usually they are on one surface of values, but Libman-Sacks are on BOTH sides of value.... They are deposition/inflammation of type 3 hypersensitivity
# Small-vessel Vasculitis
Involves arterioles, capillaries and venules. It may manifest as dermatological symptoms (rash, purpura) and/or have involvement of other organs as well. Lesions are all of the same age. Contrast with Polyarteritis nodosa, in which lesions are of different ages (suggesting recurrent insults).
#Ankylosing spondyloarthritis!!!
Involves the *sacroiliac joints* and the *spine* , Classically arises in young adults, mostly males. It is WORSE in the morning, gets bad over night. progresses in stages: - First, there is development of synovitis (inflammation of the synovia) and enthesitis (inflammation of the entheses - structures that attach ligaments and tendons to bone!!!!). • Next, bone destruction (mediated by osteoclasts, cathepsin K, and metalloproteinases) develops alongside bone production with formation of syndesmophytes (bony growths originating inside ligaments) at the sites of synovitis and enthesitis. • *Eventually, there is spinal fusion which is classically characterized on x-ray as a "bamboo spine". Note, the spinal fusion causes kyphosis.*
# what is the most common cause of uncal herniation ?
Ipsilateral brain lesion !!!!!!
# hemosiderin and iron.
Iron is carried by *transferitin*. Once deposited in cells, it binds to *apoferritin* to form *ferratin micelles*.... These micelles accumulate in tissues involved in RBC degradation (lymph nodes, bone marrow, spleen, liver* where they are *seen microscopically as hemosiderin!!* Hemosiderin is A golden yellow/brown pigment.!!!! This is seen in people that have hemolytic anemias or blood transfusions !!!
# iron in diet, where is it absorbed??
Iron is consumed in heme-form (meat) and non-heme-form (vegetables)... heme-form is more readily absorbed. Absorption occurs in duodenum and proximal jejunum(!!!), where enterocytes take it up, then transfer it into blood via ferroportin transporter. In blood, iron is bound to *transferrin which delivers it to liver and bone-marrow macrophages for storage* where it is stored as bound to ferritin.
#Isoniazid toxicity
Isoniazid toxicities include vitamin B6 depletion, which can cause *peripheral neuropathy, seizures, and hepatotoxicity(!!)* . neurotoxicity, depletes B6... so give *pyridoxine (B6) to prevent these. (!!!!!!!) * Additional toxicity is high anion gap metabolic acidosis A SLE like reaction !!!
# IgA protease (!!)
It *splits the IgA molecule at the hinge resion*..... what this does is it *allows the bacteria to adhere to the mucosa* (because the protease F's up IgA)
# what does constriction of the afferent arteriole cause on renal flow
It DECREASES both renal plasma flow (RPF) and GFR. Since Filtration fraction is GFR/RPF... then FF does not change. Constricting afferent decreases RPF and GFR Dilating afferent increases RPF and GFR
# MI and location
It USUALLY involves LV (RV and atria usually spared). Most common artery is *left anterior descending*, which gives infarction of both anterior wall of left ventricle, and anterior portion of IV septum. Transmural inflammatioin here would produce ST elevation in *leads V1 and V2* and also V3-V4. 2nd most- right coronary artery. (specifically, the *posterior descending artery branch*)..... which gives *posterior and INFERIOR* left ventricle wall infarct, and posterior IV septum. Transmural inflammation here produces ST evelation in leads *II, III, aVF* 3rd- left circumflex- gives occlusion of lateral wall of left ventrical. Transmural ischemia here causes *ST elevations in V5 and V6*.
# what does constriction of the efferent arteriole cause on renal flow
It also DECREASES RPF, however it increases GFR. Since FF is GFR/RPF... then it Increases FF.
Anterior nucleus hypothalamus
It cools the body via PSNS. • Clinical Correlate: Destruction of the anterior nucleus results in hyperthermia.
uretheral constriction and GFR
It decreases GFR, thus it also decreases FF
Hydralazine
It is a *direct arteriolar dilator*,....Hydralazine increases *cyclic guanosine monophosphate (cGMP)* levels, which *reduces* calcium release from the sarcoplasmic reticulum of smooth muscle, ultimately resulting in *smooth muscle relaxation*, and thus decreases BP. Since it dilates *arterioles* more than veins, there is good afterload reduction.
Carbamazepine
It is a *voltage gated sodium* channel antagonist. Used for Simple partial seizures, complex partial seizures, trigeminal neuralgia!!!!!!!!
Silicosis
It is currently the most common work related disease worldwide (!!!). Silicosis is seen in *sandblasters* and in *quarry mine* workers. Once silica gets in the macrophages, it *impairs macrophage phagolysosome formation*, and then the macrophage releases fibrogenic factors. This is the *ONLY* pneumoconiosis which *increases risk for TB* (MACROPHAGES (!!!) are laden with silica crystals, they are no longer able to successfully phagocytose the *mycobacteria tuberculosis* and present them to helper T cells. (!!!!) Because it increases risk for TB, it results in *birifrigent particles surrounded by fibrotic nodules* in *upper lobes* of lung. !!!!!
# Polycythemia (!!!) (aka erythrocytosis)....
It is defined as a Hematocrit > 52% in men, and >48% in women. a disease state in which the PROPORTION of blood volume that is occupied by red blood cells increases. Blood volume PORTIONS can be measured as hematocrit level. It can be due to an increase in the number of red blood cells[1] ("absolute polycythemia") or to a decrease in the volume of plasma ("relative polycythemia").[2]
pica
It is often seen with *iron deficiency anemia*..... and can also lead to anemia due to insufficient intake. Abnormal, consumption of nonfood and or non-stable food. Ie, chewing ICE is the most common. It is COMMON during pregnancy.
# Adenocarcinoma of lung (!!)
It is the MOST common subtype overall.... But lung adenocarcinoma is the "oddball" lung cancer: • It is more common in women than in men • It is still associated with smoking, but not as strongly as small cell and squamous lung cancers.!! • It arises more commonly in the periphery of the lung as opposed to central locations seen in squamous and small cell lung carcinomas. Aside from the classic p53, RB and p16 mutations seen in almost all types of lung carcinomas two genes of interest are commonly mutated in lung adenocarcinoma - KRAS (seen more in the smoker patient subpopulation) and EGFR (seen more in the women and nonsmoker patient subpopulation). (!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!)
# pulmonary capillary wedge pressure
It measures left atrial end diastolic pressure (LA-EDP) !! Normally, the LA-EDP is nearly equal to the LV-EDP (both less than 12!!!) *Mitral stenosis* elevates both LA-EDP, and thus, PCWP.... While LV-EDP is unaffected. This implies there is a resistance to flow between the left atrium, and left ventricle (ie, mitral stenosis).
# Obturator nerve:
It passes through the Obturator foramen!! • Can be caused by an *anterior hip dislocation* which presents with hip external rotation and extension • Presents with *inability to adduct the thigh*. and loss of sensation on medial thigh
Posterior hypothalamus
It warms the body via SNS. • Clinical Correlate: Destruction of the posterior nucleus results in hypothermia.
Major Jones criteria
Joints—migratory polyarthritis - O—carditis (think of the "O" as the rough shape of the whole heart, including *all three layers*-endocardium, myocardium, pericardium), which may include endocarditis, myocarditis, and/or pericarditis. - Nodules (subcutaneous) on extensor surfaces (eg, wrist, elbow, knee) - Erythema marginatum—macular rash starting on trunk/arms - Sydenham's chorea—rapid involuntay movement of face/arms (!!!!)
# K sparing diuretics
K sparing diuretics: 1. Aldosterone receptor antagonists — e.g., spironolactone, eplerenone 2. Na channel blockers — e.g., triamterene, amiloride
# western blot HIV
KNOWN HIV proteins separated via electrophoresis, then blotted onto a filter membrane, which is incubated with the suspected patient's serum. IF the patient is HIV+, their serum will contain anti-HIV antibodies, which will bind HIV protein on the membrane. THEN enzyme-linked anti-human IgG antibodies are added, which recognize and bind the patient's anti-HIV antibodies.
ketamine in opioid tolerance
Ketamine is a NMDA receptor antagonist. Glutamate is an excitatory neurotransmitter that *binds to NMDA receptors*. NMDA receptor activation can cause increased phosphorylation of opioid receptors, leading to *morphine tolerance*. By acting as a NMDA antagonist, ketamine *prevents glutamate* from achieving opioid tolerance.
# Squamous cell carcinoma histopath
Key features include (1)*squamous keratin pearls*, which stem from *abundant keratinization* by the malignant squamous cells and (2) *intercellular bridges*. Note Important concept: Regardless of where they are found in the body (skin, in the lung, on the vulva/cervix), *squamous keratin pearls* and *intracellular bridges* are suggestive of *squamous cell carcinoma*. They are not specific to carcinoma of a certain organ.
# noncaseating granulomas
LACK central necrosis arise due to: - reaction to foreign material (ie, breast implants leak, release foreign material, go into axillary lymph) - Sarcoidosis- production of non-caseating granulomas in multiple tissues, especially lung - Beryllium exposure - Crohn disease (histological mark of Crohn's!! Hystological mark of UC= crypt abscess) - Cat scratch disease (usually in NECK, stellate shape!!!)
#digoxin antidote
LAMPP • Lidocaine • Anti-dig Fab fragments • Magnesium for treatment of hypomagnesemia • Potassium for treatment of hypokalemia • Phenytoin for arrhythmias that do not respond to lidocaine
# Aortic regurgitation complications
LV dilation (to accommodate the volume of the backflow without increasing filling pressure or left atrial pressure) and *eccentric* hypertrophy.
#sarcoidosis labs (!!)
Lab work may show increased serum levels of ACE (!!!) (angiotensin converting enzyme) and gammaglobulins. Elevated calcium is seen as hypercalciuria (more common) or hypercalcemia (less common). Note, *ANY* disease with excess *non-caseating granulomas* can lead to excess a-1-hydroxylase (active vitamin D) (!!!!!!!!!!!!!!!!!) macrophages inside the granulomas convert vitamin D to its active form, resulting in elevated levels of 1,25-dihydroxyvitamin D Since there are non-caseating granulomas, there are *high levels of CD4!!!*. (CD4/CD8 > 2:1). !!
# Lactose intolerance
Lactose is also called *Galactosyl B-1, 4- glucose*. The enzyme LACTASE converts this INTO GALACTOSE. Occurs due to: - Primary lactose intolerance (enzyme defect throughout life) - SECONDARY to conditions like ciliac or gastroenteritis which DAMAGES the brush border.
# treat hepatic encephalopathy (!!)
Laculose, a nonabsorbable disaccharide that is degraded by colonic bacteria to form lactic acid and acetic acid. The GI tract becomes acidified and *NH3 is converted to NH4+* (!!!!). Peristalsis occurs.
# which way are DNA lagging and leading strands constructed and synthesized??
Lagging strand is constructed 3-5 Leading strand is constructed 5-3 Synthesis of both is ALWAYS 5-3.
#indirect inguinal hernia
Lateral to inferior epigastric artery. Goes through both Internal (deep) and External (superficial) induinal ring, and *into the scrotum*. Covered by all 3 layers of spermatic fascia. Occurs in infants (more so males) due to *failure of processus vaginalis* to close
Posterior inferior cerebellar artery stroke
Leads to WALLENBERG syndrome. contralateral loss of pain, temp ipsilateral deficits of CN V, VIII, IX, X, XI... and Horner's syndrome.
# Left heart failure symptoms
Left sided heart failure is generally said to be a *disease of symptoms* (rather than *signs like in RHF*) of *pulmonary congestion)!!!!*... the heart can't pump the blood forward, so it is *pumped backwards* and it *piles up in vessels of lung*. This increases the *hydrostatic pressure* and leads to pulmonary edema (!!!) Symptoms including: - dyspnea on exertion - orthopnea (!!!!) - paroxysmal nocturnal dyspnea. Fluid overload: the decreased cardiac output (less flow to kidney) causes an activation of *RAAS* system with retention of salt and water and *worsens* pulmonary congestion
left sided colorectal
Left sided tumors (descending colon) commonly present with a *napkin ring lesion* which *encircles the lumen* as lumen gets narrowed.... there is: - a change in bowel habits (thin stools, constipation, diarrhea, nausea/vomiting) - left lower quadrant pain or occult bleeding. FAP is more in *left side*
length vs time constant
Length constant (aka space constant) is a measure of how far along an axon an electrical impulse can propagate. Myelin increases membrane resistance, thus, it *increases length constant*. (demyelination would thus decrease the length constant). Time constant- time it takes for a change in membrane potential to achieve 63% of the new value. Demyelination would *increase the time constant*.
# Membranous nephropathy imaging
Light microscopy: - diffuse glomerular capillary wall thickening (later stages of the disease) Since there is *immune complex deposition* right under the podocyte (*subepithelial/subpodocyte* , these deposits *are detectible on immunofluoresence*, which shows *granular immunofluoresence* of *IgG and C3*.!!!! As these deposits sit underneath the podocyte, the podocyte responds by laying down additional basement membrane which generates a *dome* over the deposit, which gives a *spike* (in between deposits) and *dome* (the deposits) on EM. (spike and dome!!!!!) Silver stain → spike and dome pattern—the spikes are basement membrane material (colored black by the silver stain) and the domes are immune complex deposits (not colored by the silver stain).
# Minimal change disease imaging
Light microscopy: - *Normal-appearing glomeruli*!!!! , with * lipid-laden proximal tubular cells* Immunofluorescence: - No immune complex deposits, so it is *negative* (normal!!!! ) Electron microscopy: - *Diffuse effacement of podocyte (visceral epithelial cell) foot processes*!!!!!!!!! ONLY one abnormal!!!!
# Loop diutetic sides
Like thiazide diuretics, loop diuretics are *potassium-wasting diuretics* and therefore have the potential to cause *hypokalemia and a metabolic alkalosis*. Because the resorption of calcium and magnesium requires functional NaKCC cotransporter activity, *hypomagnesemia* and *hypocalcemia* can occur. *Endolymph* uses an NaKCC cotransporter as well; blockage can prevent normal electrolyte balance in the ear, *causing ototoxicity*.!!!! ↑ serum levels of: - Uric acid (hyperuricemia) → may precipitate gout
# Treat psoriasis
Likely autoimmune, so give *corticosteroids* . -* Calcipotriene* is a topical cream which binds to and *activates the Vitamin D receptor, a nuclear transcription factor, that inhibits keratinocyte proliferation and STIMULATE keratinocyte differentiation. * Since it is due to *excessive keratinocyte proliferation*, we could *damage the keratinocytes* by UV light (particularly UVA) !!!
#ectopic tissue as a result of thyroid impaired development!!
Lingual thyroid cyst- persistence of thyroid tissue at base of tongue, presents as base of tongue mass. Ectopic thyroid tissue can be found along the MIDLINE of the neck.
# Drug induced SLE (!!!)
Linked to drugs that are metabolized by *N-acetylation* in the liver!!!! most common are: hydralazine, procainamide, and isoniazid. The antibody here is an *antihistone antibody* (as opposed to Anti-dsDNA in regular SLE!!!). Very treatable, remove drug and it remits. Gives a positive ANA, and antihistone. Patients get rash, serositis, but *CNS and renal involvement are rare*
#listeria
Listeria monocytogenes is a non-spore forming beta-hemolytic, catalase-positive gram-positive bacillus. • L. monocytogenes causes *listeriosis (meningitis and sepsis). * • L. monocytogenes exhibits *tumbling motility extracellularly on light microscopy.(!!!!) * • L. monocytogenes is the *only gram-positive organism with endotoxin. (!!!)* • L. monocytogenes can* survive both intracellularly (in macrophages, neutrophils) and extracellularly. * • *L. monocytogenes can grow at cold temperatures, allowing survival in refrigerated food such as poorly pasteurized milk/cheeses, deli meats, and raw vegetables. !!!! * Transmission of L. monocytogenes occurs through • Ingestion of bacteria in food • Placental transmission • Vaginal transmission during birth • *People deficient in cell-mediated immunity such as pregnant women, neonates, the elderly, and AIDS patients have ineffective phagocytosis and are most susceptible!!!! . *
#what drugs and conditions increase lithium toxicity (!!)
Lithium toxicity is increased by: *thiazide diuretics (leads to increased proximal tubule absorption of sodium) NSAIDs, ACE inhibitors*, dehydration, salt deprivation, and impaired renal function Loop diuretics do NOT interfere with lithium.
# prevent Rubella !!!
Live- attenuated vaccine for non-pregnant females AND children!!
# diagnose Wilson's !!
Liver biopsy demonstrating quantitative copper >250 Low serum ceruloplasmin !!!! SLIT-LAMP shows *kayser-fleischer rings*
# portal hypertension anastomoses (!!!)
Liver cirrhosis and chronic portal HTN leads to dilated collateral vessels in the: Lower abdomen (paraumbilical veins) called *caput medusae* Lower rectum (superior rectal vein) called *hemorrhoids* Inferior end of esophagus (left gastric vein) called *esophageal varicies NOTE: Portal hypertension ALSO causes splenic vein hypertension and splenomegaly secondary to splenic vein blood accumulation.
# where do most anal fissures occur?
Longitudinal tear in the *mucosa*. 90% are posterior midline, distal to dentate !!! Pain is severe tearing pain w/ bowel movements. !!!!
# Osteoporosis
Loss of osteoid (organic bone matrix) from *trabecular aka spongy bone* !! ...... but mineralization is normal. So there is *trabecular thinning* with fewer interconnections. !!!! Depends on peak bone mass (around age 30, determined by diet, exercise, vit D receptor genetics) and loss thereafter. Primary osteoporosis 2 types: Type 1) Postmenopausal- affects cancellous bone mostly, due to estrogen deficiency increasting osteoclasts and decreasing osteoblasts. Vertebral body compression fracture is most common (leading to kyphosis aka Dowager's hump.... also Colles) Tye 2) Age related/senile. In patients over 75, affects both cancellous and cortical bone. Hip/pelvic/femoral neck fractures. Most likely to damage* medial femoral circumflex artery. !!! *
# Hypoparathyroidism
Low PTH b/c autoimmune damage, surgery (often ACCIDENTAL removal)... DiGeorge syndrome (failure to develop 3rd/4th pharyngeal pouch) LOW PTH and low serum free calcium - muscle spasms elicited w/ Trousseau sign or Chvostek sign
#aspirin use
Low dose (<300mg ) inhibits platelet aggregation Moderate dose (300-2400mg) intipyretic and analgesis high dose (>300mg) is anti-inflammatory
where are cochlea sounds heard?
Low frequency at the apex near helicotrema (wide and flexible) High frequency at the base (thin and rigid).
# what lab values predict cirrhosis prognosis?
Low serum albimun, elevated bilirubin, delayed PT
Lyme disease
Lyme disease showing *erythema migrans* !! Caused by Borrelia burgdorferi , via *tick bites* on camping trips. The primary reservoir hosts for B. burgdorferi are *rodents, in particular the white-footed mouse. The white-tailed deer act as intermediate hosts*, and are used as a food source for the larval and nymphal stages. • *Facial nerve palsy • Arthritis • Cardiac block • Erythema migrans* • Stage 1, or early-localized Lyme disease, is characterized *erythema migrans* and nonspecific findings that *resemble a viral syndrome.( Erythema migrans is rash that *BEGINS as a homogenous erythema (first pic) and may spread to develop a central clearing resembling a Bull's-eye rash. * • Stage 2, or early-disseminated Lyme disease, presents with *acute neural or cardiac involvement*s that occurs weeks to several months after the tick bite. This stage can present with: o *Lymphocytic meningitis* o Cranial nerve palsies, especially the* facial nerve (often bilateral) (asymmetric face!!!)* o Peripheral neuropathy o Atrioventricular heart block o Migratory arthralgias • Stage 3, or late Lyme disease, presents with *chronic arthritis of the large joints, usually the knee and encephalopathy. !!! *
# Hematopoetic stem cell divides into: (leukemia)
Lymphoblasts (>20% is acute lymphoblastic leukemia (ALL ) Myeloblasts (>20% is Acute Myeloid Leukemia (AML!!!) for ALL: Key marker is positive nuclear (!!) staining for TdT, a DNA polymerase (!!!!) which is found in Lymphoblasts, but NOT Myeloblasts, or mature lymphoblasts.
#LSD
Lysergic acid diethylamide. Causes: hallucinations (especially visual)!!!! delusions, flashbacks, psychosis, dilated pupils, marked anxiety/depression, weakness, nausea..... but very few behavioral changes. !!!!
# mycoplasma pneumoniae
M. pneumoniae is transmitted through *inhalation of respiratory droplets and commonly affects young people, especially those in close quarters (prisons, military bases).* • Inhaled organism *adheres to respiratory epithelium and inhibits ciliary motion and destroys the mucosa, causing inflammation without invasion into the mucosa. * Patients with M. pneumoniae infection typically present with atypical pneumonia (walking pneumonia) and can include symptoms such as • Fever • Headache • Myalgia • Tracheobronchitis • Non-productive cough *It requires cholesterol to grow, and it appears more severe on XRAY than the patient shows!!!!! * Note: When the body mounts an immune response against mycoplasma pneumoniae, it *ALSO destroys RBC's causing anemia!!!! * *Mycoplasma lack peptidoglycan!!!! *
#muscarinic receptors
M1- Stimulation = *memory formation/cognitive functioning* Inhibition = cofusion M2- stimulation = decreases HR and contractibility of the atria, and AV node conduction M3- increases exocrine gland secretion (lacrimal, salivary, gastric acid) - bronchoconstriction of lung - stimulates detrusor contraction of bladder (!!!!!) - increases gut peristalsis - contracts pupillary sphincter (miosis) !!! - ciliary muscle contraction (accommodation)!!!!!! M3 antagonists often used to combat overactive bladder@@@
# Macrolide toxicity
MACRO GI Motility Arrhythmia (prolonged QT) Cholestatic hepatitis Rash eOsinOphilia
#direct inguinal hernia
MEDIAL to inferior epidastric artery and bulges *directly through abdominal wall aka Heisselbach's triangle..... Goes through External (superficial) inguinal ring only. covered by external spermatic fascia. Usually in older men.
#pheochromocytoma is associated with what conditions?
MEN 2A AND MEN 2B Von-hippel-Lindau disease Neurofibromatosis type 1-
HLA class 1
MHC class I (HLA-A, HLA-B, and HLA-C*) (!!!) present VIRAL peptides from *INSIDE the cell* (including viral peptides if present). These peptides are produced from digested proteins that are broken down in the proteasomes. Foreign antigens attract killer T-cells (also called *CD8 positive- or cytotoxic T-cells*) that destroy cells. MHC-1 is on all nucleated cells (note: not on erythrocytes) It has a A heavy chain, and B2-microglobulin. !!!! So there are three main steps in preparing a class I display: generation of a peptide by the proteasome, transport of the peptide into the ER by the TAP transporter, and binding of the peptide to the groove of the MHC I molecule.
# ITP- idiopathetic/immune thrombocytopenia purpura (!!)
MOST common cause of thrombocytopenia in both children and adults Type 2 hypersensitivity- autoimmune production of IgG autoantibodies against (fibrinogen) receptor GpIIb/IIIa on the platelet surface. The autoantibodies are PRODUCED by plasma cells in the spleen, they then coat the platelets, and then the splenic macrophages then *destroy the coated platelets* !!!!
# Diagnose MS
MRI reveals periventricular plaques (areas of oligodendrocyte loss and reactive gliosis) with *preservation of axons* !!!! .... The lesions are *pink patches in the white matter*. CSF: electrophoresis shows ↑ proteins (IgG) often manifest as multiple oligoclonal bands, Lumbar puncture shows - *increased lymhocytes* - Increased immunoglobin with *oligoclonal IgG bands* - myelin basic protein present - normal glucose
# treat listeria
MUST include ampicillin!!!!!!
# Escherichia coli
MacConkey's agar is a differential media on which *E. Coli grows pink colonies* because it ferments lactose.!!!! that is virulent is transmitted by a fecal-oral route, and often is commonly associated with "traveler's diarrhea." • E. coli is part of the normal flora in human and animal intestines. It can cause illness in humans and animals. • *Consuming uncooked foods and unfiltered water* increases the risk of acquiring gastrointestinal E. Coli infection. E. coli can survive in water and on surfaces of foods • EHEC is contracted by consuming beef or foods contaminated with cow feces. LPS is released during its destruction, and it contains* Lipid A* which is responsible for the gram negative sepsis and endotoxic septic shock!!!!! Causes activation of macrophages, IL-1, TNF-a , and all the signs of septic shock (dever, hypotension, diarrhea, DIC)
hydrocephalus presentation in kids
Macrocephaly (head circumference 2DS's over the mean) Irritability Poor feeding Muscle hypertonicity, hyperreflexia (from upper motor neuron damage from stretching the brain !!!!) They also develop the setting sun sign, where upward gaze palsy manifests as a predominant downward gaze
# Hb and microcytic anemia
Made of heme (iron and protoporphyrin) + globin - If low iron, there is microcytic anemia (iron deficiency anemia) - if Iron is locked away in macrophages because of chronic inflammation, it is low (anemia of chronic disease) - Any circumstance which decreases production of protoporphyrin (sideroblastic anemia) - decreased production of globin chain (thalassemia)
# sleep hygiene
Maintain a regular sleep schedule Avoid naps Avoid caffeine after lunch Avoid alcohol or large meals near bed Make the bedroom quiet, dark and cool Exercise regularly but NOT near bedtime
#lateral hypothalamus
Makes you hungry. Destruction = starvation. The lateral nucleus consists of neuropeptide Y (NPY) and Agouti related protein (AgRP) containing neurons, which trigger hunger and food intake.
#malformation vs deformation
Malformation as a primary abnormality in the development process, an intrinsic process. Deformation is an abnormality that occurs due to *extrinsic mechanical forces*.
# succinylcholine sides
Malignant hyperthermia Severe hyperkalemia (causes both sodium influx and potassium efflux!!) Bradycardia
# Prostate Adenocarcinoma
Malignant proliferation of *prostatic glands* Most common cancer in men, 2nd most common cause of death Risk factors include age, race (African Americans > Caucasians > Asians)., and diet high in saturated fats Occurs usually in *posterior lobe peripheral zone* of the prostate, which is exactly where we feel DRE. Also, it is far away from periurethral zone, so usually does NOT produce urinary symptoms unless cancer grows. A *prostatic biopsy* is absolutely required to confirm presence of carcinoma... shows *small glands* which have *nuclei with dark nucleoli* !!! Presents as low back pain with increased: - Alkaline phosphatase (sign of osteoblastic activity, indicating bone is breaking down) - PSA - PAP (prostatic acid-phosphatase).
# Lymphoma
May arise in - lymph node (Non Hodgkin Lymphoma (60%)) or extra-nodal tissue. (Hodgkin Lymphoma (40%)
Minimal alveolar concentration
Measure of the POTENCY. It refers to the *concentration of anesthetic in the alveoli that renders 50% of the patients unresponsibe to painful stimuli*. MAC and potency are INVERSELY related!!! (higher MAC, lower potency)!!!! Is does not depend on the type of surgery, sex, weight, height, etc....
Buspirone
Mechanism of action: partial 5-HT1A (serotonin) receptor agonist (this receptor is thought to mediate anxiolytic and antidepressant effects) Alternative to benzodiazepines and venlafaxine for treating generalized anxiety disorder !! *Efficacy comparable to benzodiazepines but has a slower onset of action (takes 1-2 weeks for the effect) *
# Loop diuretics
Mechanism: *inhibition of Na-K-2Cl cotransport* in *thick ascending limb* of the loop of Henle ALSO promotes production of prostaglandins, promoting natriuresis by increasing GFR (!!!!!!) Efficacy of loop diuretics may be reduced with concurrent administration of an NSAID because of NSAID-induced prostaglandin inhibition!!!!
# Warfarin
Mechanism: IRREVERSIBLY Inhibits vitamin K-dependent γ-carboxylation of factors X, IX, VII, II ("1972"), protein C, and protein S "EX president, War, 10,9,7,2) → effects last 7-10 days after stopping therapy. Given for CHRONIC anticoagulation (atrial fibrillation, DVT/PE, cardiac valve replacements), Follow PT or INR (normalized version of PT)
# Ezetimibe:
Mechanism: selective inhibitor of dietary cholesterol absorption in small intestine brush border • LDL ↓↓ (incremental ↓↓↓↓ when used with statins) • Triglycerides ↓ (minimal effect when used alone, but incremental ↓↓ when used with statins) • Side effects: - when used alone: few adverse reactions - when used in combination with statins: myositis, increased LFTs (!!!)
what is the most common enzyme deficiency in beta oxidation ??
Medium chain acyl CoA dehydrogenase deficiency. (note, could also be short and long chain Acyl CoA dehydrogenase). Shows hypoglycemia after prolonged fasting with LOW ketones.
# What kinase mutation is seen often in melanoma?? !!
Melanoma is often driven by activating mutations in *BRAF kinase*. (!!!!!!!!!!!!) Valine is replaced with glutamine!
#treat alzheimers
Memantine (NMDA antagonist... it slows progression by preventing excitotoxicity mediated by Ca2+) Donepezil/galantimine/rivastigmine (Ach-Esterase inhibitors)
phenytonin
Metabolized by CYP450 !!! (it is an ACTIVATOR) Anti-convulsant used in grand mal (tonic clonic) seizures, SECOND LINE for status epilepticus (after benzos!!!!) . It BLOCKS voltage gated sodium channels in cortical neurons, and increases the refractory period. It *affects the CNS* and can cause ataxia and nystagmus. Main side effect is *gingival hyperplasia* after 3-4 months, due to increased expression of PDGF. Also: corse facial features.
microsomal monooxygenase
Metabolizes steroids, alcohol, toxins and other substances rendering them soluble and easier to excrete. Unfortunately, most chemical carcinogens enter the body in an INACTIVE state as pro-carcinogens, which are then converted into ACTIVE carcinogens by cytochrome p450 monoocygenase.
# Biguanides aka Metformin
Metformin is the important biguanide and the FIRST LINE agent for DM type II. Mechanism: Metformin activates AMPK (AMP-activated protein kinase) → ↑ expression of orphan nuclear receptor SHP (small heterodimer partner) → inhibits expression of liver PEPCK and glucose-6-phosphatase, thus *repressing hepatic gluconeogenesis.* !!!! It also* increases peripheral insulin sensitivity and utilization of glucose.*!!! Side effects: - GI distress (eg, diarrhea) - Weight loss - Lactic acidosis (rare, but 50% mortality when it occurs), especially in patients with underlying renal disease!!!!!
# Asthma test if spirometry is inconclusive (!!!)
Methacholine is a *cholinergic muscarinic agonist* that, when inhaled, causes the airways to spasm (contract involuntarily) and narrow if asthma is present. During this test, you inhale increasing amounts of methacholine aerosol mist before and after spirometry. The methacholine test is considered positive, meaning asthma is present, if the lung function drops by at least 20%. A bronchodilator is always given at the end of the test to reverse the effects of the methacholine.
#MRSA
Methicillin-resistant Staph Aures. It is resistant to ALL beta-lactam antibiotics because it has an *altered penicillin binding protein in its peptidoglycan cell wall which PREVENTS it from binding* ! !!!
# methotrexate
Methotrexate is a folate antimetabolite that inhibits DNA synthesis, repair, and cellular replication. It works via the following mechanisms: • Irreversibly binding and inhibiting dihydrofolate reductase, leading to reduced formation of reduced folates. Irreversibly binding and inhibiting thymidylate synthetase, leading to inhibition of purine and thymidylic acid synthesis
# types of headaches and overview
Migraine, tension, cluster Excruciatingly painful (disabling) headaches: • Migraine headaches • Cluster headaches Mildly / moderately painful (not disabling) headaches: • Tension headaches Unilateral headaches: • Migraine headaches • Cluster headache Bilateral headaches: • Tension headaches
# Mitral regurgitation overview
Mitral regurgitation, also known as mitral insufficiency, refers to the backflow of LV→LA during *systole*. Mitral valve prolapse is the *most common* cause of mitral regurgitation!!!! can also be caused by *papillary muscle damage* post myocardial infarction (MI)..Infectious causes of mitral regurgitation include *rheumatic heart disease* and infective endocarditis with valvular damage.
# Mitral Stenosis overview
Mitral stenosis is the narrowing of mitral valve due to *calcification or valvular damage* that results in *an increase in left-atrial pressure, and an increased left-atrial-left-ventricular pressure gradient.* Mitral stenosis results in increased left atrium pressures and pulmonary congestion. Almost all cases are *secondary to rheumatic heart disease*, which causes immune-mediated damage to the valve. This results in scarring and narrowing of the valve, causing *fusion of the commissures*, called a "fish mouth" valve.
# antiarrhythmics
Mnemonic: "Some Block Potassium Channels": - Sodium channel blockers (class I) - Beta blockers (class II) - Potassium channel blockers (class III) - Calcium channel blockers (class IV)
# Hemophilia A
Mnemonic: Think of it as hemophilia AAAight. (XR factor 8 deficiency) *↑ PTT, but all other labs (except decreased factor 8) are normal*!!! : normal bleeding time, normal PT, etc. presents as spontaneous/easy bleeding/bruising, and *hemarthroses (bleeding into the joint)... into weight bearing joints (knee, hip, ankle).* !!!!! It can actually lead to OA of the joint.
#identification
Modeling behavior after another person who is more powerful, though NOT always an admired person, it could be someone who is or is NOT admired. ie, could be a child identifying with their abuser.
Molluscum contagiosum.
Molluscum contagiosum. a poxvirus that causes localized skin infections. • Molluscum contagiosum is transmitted through direct skin contact or fomites. • Molluscum contagiosum most commonly presents *as single or multiple small, firm, flesh-colored papules with central umbilication. * • Histopathologic examination of a lesion of molluscum contagiosum reveals eosinophilic cytoplasmic inclusion bodies within keratinocytes known as Guarnieri bodies. • Molluscum contagiosum infection is usually self-limited in immunocompetent individuals. Immunosuppressed individuals have an increased risk for larger lesions and more widespread disease.
# Multiple myeloma and infections
Monoclonal antibody LACKS antigenic diversity, all antibodies are the same. So results in increased risk for infection, which is the MOST common cause of death.
# D-xylose
Monosaccharide, thus, like glucose and galactose, it does NOT require pancreatic enzymes for absorption. In fact, xylose can sometimes be used to differentiate if the cause of malabsorption is pancreatic or intestinal.
# Causes of Hypertrophic cardiomyopathy
Most HCM cases are caused by *genetic defects* with *autosomal dominant* inheritance and *variable penetrance*. In fact 60%-70% of the cases are of familial form. Mutations are in the structural elements of the myocardial *SARCOMERES*. *Myosin heavy chain* is most commonly mutated. Also possible are - cardiac Troponin T - α-tropomyosin - Myosin-binding protein C
# Sporadic Alzheimer's
Most cases are *sporadic*, seen in elderly with increase risk with aging. (Late onset Alzheimers) The risk is increased with the *Epsilon 4 allele* of *Apo-lipoprotein E* on (chromosome 19)!!!!!!!!! This *increases the conversion of APP to the beta form*, resulting in *increased A-beta amyloid* There is a *decreased risk* with the *Epsilon 2 allele* of *Apolipoprotein E* (also chromosome 19) !!!!!!!!!! (think of it as "4 is higher than 2")
Neutrophils overview
Most common WBC, highly motile 2-5 nucleus lobes; can become hypersegmented in vitamin B12 or folate deficiency Phagocytic, but also has granules Granules contain myeloperoxidase, lactoferrin, hydrolytic enzymes
# Dilated Cardiomyopathy
Most common cardiomyopathy, accounts for 90% of cases. a progressive dilation of *all 4 chambers* of the heart that leads to decreased contractility and heart failure resulting from *systolic dysfunction*. This condition is also known as congested cardiomyopathy. NORMAL thickness of ventricular walls. NORMAL cardiac arteries. Systolic dysfunction in dilated cardiomyopathy manifests as a *reduced ejection fraction* (<40%) and can be detected during physical exam as a *narrow pulse pressure* and *S3 heart sound* !!!! Dilated cardiomyopathy is characterized by *global enlargement* of the heart, which is visible with imaging.
humoral hypercalcemia
Most common cause of hypercalcemia in hospitals. Tumors produce a PTH like substance.
# Graves disease !!
Most common cause of hyperthyroid (85%).....Autoantibody (IgG) that stimulates TSH receptor ... (thyrotropin receptor STIMULATORY antibodies) - increase synthesis/release of thyroid hormone - classically occurs in child bearing age women - Is a type 2 hypersensitivity
# Causes of aortic regurgitation
Most common chronic cause is *dilation of the aortic root* due to connective tissue diseases, syphilitic aneurysm, or aging. (!!!!!!)
# ornithine transcarbamoylase deficiency (!!!)
Most common deficiency of urea cycle. often evident in the first few days of life (but may appear later) • ↑ orotic acid in blood and urine • ↓ BUN (no urea produced due to enzyme deficiency) • Hyperammonemia • Severe neurological abnormalities (lethargy, confusion) NO megaloblastic anemia!!!
#Neuroblastoma
Most common extracranial solid cancer in infancy. Occurs almost *exclusively in very young children * Neuroendocrine tumor derived from *neural crest of sympathetic nervous system. * Most often found in adrenal medulla but can also be found anywhere along sympathetic chain.
# CLL
Most common leukemia found in *adults* in the US. Chronic lymphocytic leukemia. Neoplastic proliferation of Naive B-cells which co-express CD-5 and CD-20 !!!!! (CD-5 is normally on a T-cell). Blood smear has increased lymphocytes with smudge cells on smear: (*smudge cells* occur as the leukemic cells are prone to mechanical disruption) hypogammaglobulinemia (cells do not produce immunoglobulin- so infection is most common cause of death)
# ALL- Acute lymphoblastic leukemia
Most common malignancy in children, Note: (also associated with Down Syndrome AFTER the age of 5:... "mnemonic: we ALL fall DOWN") - also the most responsive to therapy *There are 2 general types of ALL: B-ALL and T-ALL: (because the lymphoblast can either be a B-lymphoblast, or a T-lymphoblast)! * Classification is based on surface markers. But BOTH have TdT (!!)
cyclosporine side
Most common side effect of cyclosporine use is nephrotoxicity. • The most common cause of a rise in BUN and creatinine levels post-transplantation is from cyclosporine use. • Other adverse effects of cyclosporine include • Gingival hyperplasia • Hirsutism
# B-ALL
Most common type of ALL ( around 80%) -Presents as blood disorder, will generally metastasize to CNS. Presents as bleeding, fever, malaise, bone pain, hepatosplenomegaly. -Surface Markers: CD10 (aka CALLA), CD19, CD20 and CD22
# Renal cell carcinoma histology (!!)
Most common type of RCC = *clear cell adenocarcinoma*. Gross exam= yellow mas - nonpapillary growth pattern - polygonal-shaped cells with *clear or granular cytoplasm* ("clear" under the light microscope due to high intracellular glycogen and lipid content !!!!!! )
# Restrictive lung diseases due to
Most commonly due to *interstitial disease* of the lung... these are disorders where you get fibrosis of the *interstitium* Can also be due to *chest wall abnormalities* (ie obesity), Makes it difficult to get air in # Restrictive lung diseases include 1. Idiopathic pulmonary fibrosis 2. Pneumoconioses 3. Sarcoidosis 4. Hypersensitivity Pneumonitis 5. Respiratory distress
# Causes of dilated cardiomyopathy
Most commonly idiopathic, however, familial causes are known to be responsible for up to 50% of the cases. Other causes include: Alcohol abuse (!!) (Alcohol can lead to dilated cardiomyopathy through the toxic effects of acetaldehyde metabolites or from thiamine deficiency resulting from alcoholism.) Cocaine Doxorubicin !!!!!!!! (used for chemotherapy!!! ) - Coxsackie B virus (causes *myocarditis*)!!! - peripartum Cardiomyopathy - thiamine deficiency (wet beriberi)
# Fibrates:
Most effective triglyceride clearing agents, used in hypertriglyceride levels!!! (ie, high triglycerides causing pancreatitis!!!!) gemfibrozil, fenofibrate Mechanism: *activation of nuclear transcription factor PPARα*!!! → upregulation of lipoprotein lipase → increased clearance of triglyceride rich lipoproteins and increased HDL synthesis • LDL ↓ • HDL ↑ • Triglycerides ↓↓↓
# Gastric ulcers
Most gastric ulcers are located on the *lesser curvature* of the *distal stomach*. Usually due to H-pylori (about 50-60% of gastric ulcers), other causes could be NSAIDs and "bile reflux" Presents as epigastric pain which gets worse immediately before or during a meal (thus, they lose weight) Gastric ulcers carry the risk of rupturing the left gastric artery .(!!!!) Gastric ulcers are more likely to undergo malignant transformation to *gastric carcinoma* .. note that gastric carcinoma can also *create* ulcers. Benign ulcers are small, "punched out", and clear margins (no 'piling up' of edges).... malignant ulcers are larger, irregular, 'piling up' at edge'.
complete mole
Most molar pregnancies (90% in some studies) 90% of complete moles are the result of fertilization of an empty egg by 1 sperm (genetic material is "completely dad"). *The product is 46, XX due to duplication of haploid sperm* - 10% of complete moles the result of fertilization of an empty egg by 2 sperm. The products can be either 46, XX or 46, XY due to dispermy There is *no fetal tissue* because egg is empty (completely a mole). ALL of the villi are edematous aka hydropic (completely edematous). HCG is much higher because of the excess trophoblastation (suspect if > 100,000) Higher risk (2-3%) of choriocarcinoma!! NOTE: because of the risk, it is important to monitor hCG!!!!
rodent poisons
Most rodenticides contain brodifacoum, which DEPLETES vitamin K. Treat immediately with FFP and Vitamin K1.
# duodenal ulcers
Most ulcers (90%) involve the *proximal duodenum* (aka *duodenal bulb*) Almost always due to H-pylori which *colonizes in the antrum of the stomach* in the *pre-pyloric area*!!!!! *Chronic antral inflammation* leads to a *decrease in somatostatin producing DELTA CELLS*. Since somatostatin DECREASES gastrin, we thus have high levels of gastrin, which acts to INCREASE hydrogen secretion by patietal cells. This produces an extremely acidic gastric fluid that is NOT adequately neutralized by duodenal bicarbonate secretion. .... but rarely *may* be due to *ZE-syndrome* (Zollinger Ellison). Presents with epigastric pain which will generally *improve during a meal* (think "all acid is in stomach") and *cause pain hours after a meal*. Thus, patients GAIN WEIGHT. Note: unlike gastric ulcers, there is *destruction of somatostatin producing delta cells*... which leads to further increased acidity.
# MEN 2A vs MEN 2B
Multiple Endocrine neoplastia.... neoplasia in multiple endocrine organs. Note: multiple organs are affected because they *share neural crest cell* origin. !!!! MEN 2A ( syndrome) 1) Medullary PARAfollicular (c-cell) Thyroid carcinoma (secretes calcitonin), 2) Pheochromocytoma (adrenal gland) in 50% 3) *parathyroid adenoma(hyperplasia)* # MEN 2B aka MEN 3- 1) Medullary PARAfollicular (c-cell) Thyroid carcinoma (causing increased calcitonin) 2) Pheochromocytoma (adrenal gland) in 90% *3) mucocutaneous ganglioneuromas (particularly oral mucosa ) - marfanoid body habits (constellation of symptoms resembling those of Marfan syndrome, including long limbs, arachnodactyly, and hyperlaxity.) . *
anti-cholinesterase posioning !!!! (too much Ach)
Muscarinic effects are DUMMBELSS Diarrhea (excess stimulation of smooth muscle in GI urination (stimulation of detrusor) Miosis (constriction of pupillary sphincter) Bronchospasm (smooth muscle tone) Bradycarda Excitation (CNS/Skeletal) Lacrimation Sweating Salivation Increased Ach in the NMJ leads to *muscle fasiculations followed by PARALYSIS* !!! Often seen as a result of *organophosphate insectide poisoning*, so think of Farmers !! these agents (irreversibly inhibit both muscarinic and nicotinic cholinergic synapses*. Give them atropine, or pralidoxime !!! Atropine will only prevent the *muscarinic* side effects. It will have NO effect on nicotinic receptor effects (still paralyzed) !!!! Pralidoxime works against BOTH muscarinic and nicotinic antagonist.
muscarinic agonist actions
Muscarinic receptors are located on the ENDOTHELIAL surface, and binding of cholinomimetric agents promotes release of NO and *endothelium-derived relaxing factor*. NO then activates guanylate cyclase which increases cGMP, and cGMP then causes *calcium efflux* from the cells, which relaxes ENDOTHELIAL smooth muscle.
intermittent claudication
Muscle pain with exercise that resolvces very quickly with rest. It is almost always the result of atherosclerosis of larger arteries, causing ischemia during exercise. Once metabolic demand is decreased (stop exercising), the pain subsides.
# Post-Traumatic Stress Disorder
Must last LONGER than 4 weeks!!! emotional symptoms (fear, helplessness, horror), intrusive memories of the event (nightmares, flashbacks), guilt, and dissociative symptoms after a physiologic or psychological trauma, which is OUT of the range of normal experience (earthquake, fire, serious accident) Post traumatic stress disorder often follows *acute stress disorder* • Leads to avoidance of stimuli associated with the trauma and persistently increased arousal • Disturbance lasts *greater than one month* and causes distress or social/occupational impairment.
# Charcot-Marie-Tooth
Mutation in gene responsible for myelin synthesis. Abnormal myelin synthesis leads to decreased nerve conduction velocity.
a1-antitrypsin liver
Mutation results in a *misfolding of the protein*, and it *accumulates* within the ER of the *hepatocytes* it piles up and damages the cells, causing cirrhosis!! (purple/pink colored globules seen in hepatocytes... they are also *PAS* (periodic acid-Schiff) positive!!!!! ).
if in a disease of breast cancer mutations, of those with the mutations, 30 get the disease and 65 do not...... and in those WITHOUT the mutations, 20 get the disease and 75 do not..... what is the relative risk of the mutation???
Mutation: 30/ 30+65 = 30/95 = 0.32 No- mute: 20/ 20+75= 20/95 = 0.21 Relative risk = 0.32/ 0.21 = 1.5
# What changes happen to the heart 4 hours to 1 day of MI ??
Myocardial hypoxia → low ATP → impaired Na-K-ATPase → altered membrane potential (*high risk of arrhythmia*!!!), intracellular edema and cell death. - but within the day (usually *4-8 hours*), *wavy myofibers* (!!!!) are seen because *fibrinolysis* or *angioplasty of a MI* ..... 12-24 hours: The MI was due to thrombus, so this would destroy it. BUT when you return blood, you return *calcium*, which causes *contraction band necrosis*!!!! The necrotic tissue undergoes *karyolysis, pyknosis, and karyorrhexis*.) - Acute inflammation always follows necrosis, so there is edema which separates myocardial cells and neutrophil emigration starts around 24 hours
# Myoglobin in MI
Myoglobin: primary oxygen carrying molecule in cardiac and other types of muscle (∴ *lacks specificity* for the heart). Although *rarely used clinically*, measuring serum myoglobin levels in the setting of suspected MI has the following 2 advantages: 1. Serum myoglobin levels *rise very quickly after an MI — vs. troponin and CK-MB*, which begin to rise a couple hours after an MI (this is why the levels of the so-called cardiac enzymes (troponin, CK-MB) are "trended" over the course of several hours following admission)
# Non-enzymatic glycosylation
NEG in large/medium vessels, *leads to atherosclerosis* (and its complications like CAD, peripheral vascular occlusive disease, gangrene, cerebrovascular disease, MI) NEG in small vessels leads to *hyaline arteriolosclerosis* ('pink' material in wall of small blood vessels decreasing lumer.....classically occurs kidney) NEG of hemoglobin leads to HbA1c, which is a marker of glycemic control.
#neurofibromatosis 2
NF2 gene on chromosome 22q. This gene codes for a cytoskeletal protein *merlin*. Presents with diminished hearing, tinnitus, impaired balance. -juvenile cataracts *Bilateral acoustic neuromas*, meningiomas.
#Partial hydatiform mole
NORMAL OVUM fertilized by 2 sperm, so we have 69 chromosomes. (69 XXX, 69 XXY, 69 XYY) Fetal tissue IS present (partial mole = fetal parts) Villi are partially hydropic trophoblasts show partial (focal) proliferation around the hydropic villi minimal risk for choriocarcinoma # partal mole presentation just some vaginal bleeding and *crampy abdominal pain*
#aseptic meningitis
NORMAL glucose, marginally elevated protein and lymphocytic predominance. 90% due to *enterovirus*.!!!!!!! It shows All enteroviruses are picornaviruses and have an (+) sense ssRNA with fecal-oral transmission (includes poliovirus, coxsackieviruses, echoviruses, and hepatitis A virus).
# -Causes of erosive gastritis:
NSAIDs (most common) - EtOH, stress, chemotherapy (knock out rapidly turning over cells) - severe burns, called *Curling's ulcer*... and *shock*- both leads to *hypovolemia* and *less flow to stomach*.... Brain injury - *Cushing ulcer* !!! (increased ICP increases vagal stimulation which increased ACh, which *binds to parietal cell* to increase acid*
# Sodium channel blockers
Na channel blockers (block luminal Na channels in the *distal renal tubule* → ↓ reuptake of Na → ↓ efflux of K into the urine) — e.g., triamterene, amiloride Note: *normally*, to maintain ionic charge balance, *influx of Na* from the *distal tubule lumen* into the *principal cells* leads to *efflux of K* from the *principal cells*, where K+ then goes +into the urine in the distal tubule lumen*. Thus, blocking the luminal Na channels in the distal tubule prevents efflux of K into the urine, thereby retaining the K+ in the body.
# Necrosis
Necrosis is cell "murder", pathologic (NEVER physiologic) deaths of large groups of cells, followed by acute inflammation (!!!). Several types. -coagulative - liquefactive - gangrenous - Caseous - Fat -Fibrinoid
# Fat necrosis
Necrotic adipose tissue with 'chalky-white' appearance due to Ca2+ deposition. (!!) -Fatty acids combine with Ca2+ → chalky fat deposits that appear BLUE on staining..../. This is known as SAPONIFICATION.... Saponification is an example of dystrophic calcification. -These chalky Ca2+ deposits can sometimes be seen on X-ray in patients with chronic pancreatitis. !!! Often occurs in pancreas, fat necrosis of periplasmic fat
Neisseria meningitidis and Neisseria gonorrhoeae
Neisseria are diplococcic gram negative, with flattened sides sometimes referred to as kidney bean-shaped. • Neisseria produce IgA protease, which allows for *oropharynx colonization.* • Deficiency in the complement factors C5-C9, also known as the membrane attack complex (MAC), predisposes to Neisseria bacteremia. !!!!!!!!!! ! • Meningococcal meningitis (from N. meningitidis) often result in shock and disseminated intravascular coagulation that can lead to adrenal infarction, a syndrome known as Waterhouse-Friderichsen syndrome. !!!! • LOS (lipooligosaccharide !!!!!) is a component of the outer membrane of N. meningitidis. This acts as an endotoxin and is responsible for septic shock and hemorrhage, as seen in Waterhouse-Friderichsen syndrome. Plasma levels of LOS highly correlate with the severity of infection !!!!! (ie, high LOS causes a more severe shock, DIC, etc!!!!!!) N. Meningitis colonizes in the *nasopharynx*, then goes to the blood, then into the *choroid plexus*, then the meniges !!!!!!!!!!!! N. meningitidis causes meningitis and meningococcemia with petechial rash. N. gonorrheae ferments glucose; N. meningitidis ferments glucose and maltose. Note: Pilli are requires for infection!!!!!! The Pilli undergo antigenic variation!!!
# Myelofibrosis
Neoplastic prolifferation of mature myeloid cells, especially MEGAKARYOCYTES due to JAK2 kinase mutation (!!!!) Megakaryocytes produce excess platelet derived growth factor (PDGF), results in marrow fibrosis!!!! Once the bone marrow becomes fibrotic in myelofibrosis, hematopoiesis becomes extramedullary. This can be seen in any body tissue
# Polycythemia vera overview (!!!)
Neoplastic prolifferation of mature myeloid cells, especially RBC's, due to JAK2 *NON-Receptor Tyrosine kinase* mutation (!!!!) in myeloid stem cells. This makes *hematopoietic cells more sensitive to growth factors* !!!! JAK2 is a *non-receptor* tyrosine kinase associated with EPO receptor. (!!!!) Increased production of: - RBCs - Granulocytes - Mast cells - Platelets EPO levels are low!!!!! (basically it is massive increase in RBC's, so EPO is low as negative feedback)
# PSGN (poststreptococcal glomerulonephritis)
Nephritic syndrome which arises after *URI/pharynx ((eg, pharyngitis, sore throat, cough) ) OR skin infection* with a *nephritogenic strain* (strains that carry a *M-protein virulence factor*!!) of *group A β-hemolytic Streptococcus pyogenes* Skin infections include (eg, impetigo, erysipelas, scarlet fever). (!!!!!!!!!!!!!!) Note: It resolves SPONTANEOUSLY (treat with supportive therapy) 1-4 weeks to make antibodies and *form immune complexes*!! → *Subepithelial (subpodocyte)* immune complex deposition with prominent *"lumps, bumps and humps"* (!!!!) (type III hypersensitivity) in glomeruli with subsequent activation of alternative complement (!!!!!!) *These deposits are IgG, IgM, C3 !!!!!* * → 1) ↓ serum C3 level (because it is deposited!!!!);* normal C1 and C4 levels Sudden development of fever, nausea, malaise, and S/Sx of nephritic syndrome: - Hematuria (4+ blood on urine dipstick)—"smoky" or "tea-colored" or "cola-colored" (dark brown or reddish brown) urine; !!!!!!!!!!!!!!! RBC casts and dysmorphic RBCs on urinalysis - Mild to moderate proteinuria—usually <1g/day (always <3.5g/day) - Antisterptolysin O titer high (!!!) - Oliguria - Mild to moderate hypertension - Mild edema (eg, periorbital edema, pedal edema!!) NOTE: adults have around 25% chance of progressing to *rapidly progressive glomerulonephritis* and renal failure... children only around 1% chance.!!!!!!!!!!
# PSGN (poststreptococcal glomerulonephritis) bug
Nephritic syndrome which arises after *URI/pharynx or skin infection* with a *nephritogenic strain* (strains that carry a *M-protein virulence factor*!!) of *group A β-hemolytic Streptococcus pyogenes*!!!! ↑ risk of developing PSGN as a complication 1-4 weeks following common strep infections, including upper respiratory tract infections (eg, pharyngitis) or 1-6 weeks after skin infections (eg, impetigo, erysipelas, scarlet fever). (!!!!!!!!!!!!!!) Note: It resolves SPONTANEOUSLY (treat with supportive therapy)
# aminoglycoside toxicity
Nephrotoxic (expecially when used with cephalosporing), ototoxic (especially w loop diuretics)
# what molecules carry oxytocin and ADH ??
Neurophysins. They are carrier proteins produced within the neuronal cell bodies of the hypothalamic nuclei. Neurophysin II has a binding site for vasopressin and is involved in transport and packaging through the ER and Golgi into the neurosecretory granules. A point mutation here may lead to *autosomal dominant hereditary hypothalamic diabetes insipidus*.
injury and hepatic acute phase reactants and ESR
Neutrophils and macrophages release TNF-a, IL-1, IL-6 (!!!) They stimulate hepatic reactants: fibrinogen, ferritin, CRP, amyloid, complement. Fibrinogen coats erythrocytes to form *rouleau stacks* that sediment faster than individual erythrocytes... this is ESR !!! Negative consequences to the production (or downregulation) of acute phase reactants include: • Fever • Anemia of chronic disease • Behavioral changes (anorexia, somnolence, lethargy) • Muscle wasting • Cachexia Acute phase reactants that are downregulated during periods of inflammation include: • Albumin • Transferrin Downregulation of albumin production conserves amino acids for positively upregulated acute phase reactants. • Transferrin is a protein that is internalized by macrophages in order to sequester iron. This inhibits microbial iron scavenging.
Tight adhesion/crawling
Neutrophils are attached to the endothelium via binding of CD18 beta to Integrins (Mac-1, LFA-1)!!!! These bind to ICAM-1 !!!
Lymphogranuloma Venereum
Nexrotizing granulomatous inflammation of *inguinal lymphatics and lymph nodes* it is a STD caused by *chlamydia trachomatis*, especially *serotypes L1-L3*.
# niacin and cholesterol
Niacin decreases synthesis of hepatic tryglycerides and VLDL. !!!!!!!!! (!!!) It also decreases VLDL conversion to LDL, thus, decreasing LDL. Also increases HDL. (Niacin is the most effective antilipid for elevating serum HDL levels)
# Vitamin B3 deficiency (!!!!!!)
Niacin deficiency leads to glossitis and may lead to pellagra in severe deficiency (diarrhea, dermatitis, dementia). "The three D's of B3 deficiency".... Remember, tryptophan is precursor to niacin (!!!!)
#niemann pick disease
Niemann-Pick Disease is caused by deficiency in *sphingomyelinase*. This leads to an accumulation of sphingomyelin, with CNS involvement. presents with a LOSS OF MOTOR SKILLS, and progressive neurodegeneration, *massive hepatosplenomegaly*, *cherry-red spots on the macula (!!!!),* and foam cells due to accumulation of sphingomyelin and cholesterol. Die by age 3 usually.
# Nitroprusside
Nitroprusside has an iron core with cyanide (CN−) and nitric oxide (NO) groups attached. The NO can detach and cause increased cGMP levels similar to hydralazine and nitrates, in this case causing *both mixed arteriolar and venous dilation* and therefore *decreasing preload and afterload* !!!!! Clinical uses: Treatment of malignant hypertension (emergency!!!) because it acts quickly (the NO group is readily available) and is easily titrated.
# proliferative phase vs secretatory phase histology
Normal proliferative endometrium consists of nonbranching, nonbudding uniform glands evenly distributed throughout a uniform stroma. .... The glands are tubular, narrow, lined with pheu In the second half, the glands become more coiled, the cells acquire large cytoplasmic vacuoles and glycogen rich mucus is released. The stroma become edematous and the *now prominent spiral arteries* extend to the endometrial surface.
# why is essential fructosuria an incidental finding?
Normally in healthy individuals, only a very small amount of Fructose is phosphorylated into Fructose-6 phosphate. In Essential fructosuria, the main fate of fructose IS phosphorylation to fructose-6 phosphate by the enzyme *hexokinase*. Fructose-6-phosphate can then be further metabolized.
#beta blockers masking hypoglycemia
Normally signs of hypoglycemia include 1) neurogenic ones from excess catecholamines (initial)- sweating, diaphoresis, hunger, tingling, tremor, palpitations, chest pain, anxiety. .... These are BLOCKED by NON-selective beta blockers!!!! Blocked because beta blockers (especially non-selective ones with B2 antagonists) block the catecholamine response. neuroglycopenic ones from lack of glucose (happens later)- weakness, confusion, drowsiness, dizziness, syncope, blurred vision.
# Crohn's and kidney stones!!
Normally, bile acids are *reabsorbed* in the terminal ileum, then *recycled in the liver*, and then reused in the absorptive process. When the terminal ileum is damaged, bile acids are lost with feces (!!!!!!), which causes *impaired fat absorption*. The excess lipids in the bowel lumen then bind to calcium ions.... This makes calcium UNABLE to bind to oxalate in the intestine (!!!!).... So we have *increased absorption of oxalate*, and formation of oxalate stones !!!!
superior mesenteric artery syndrome
Normally, the SMA and aorta form a 45 degree angle. If the angle diminishes to less than 20 degrees, the *transverse portion of the duodenum* can get trapped between SMA and aorta, and cause small bowel obstruction. Narrowing of the angle occurs with: - low body weight - recent excessive weight loss - severe burns - general catabolism - bed rest - scoliosis surgery
Cleft lip
Normally, the two medial nasal processes fuse to form the intermaxillary segment. failure of fusion of the left or right maxillary process and the intermaxilliary segment (medial nasal process)
# Sickle cell anemia is what kind of anemia, what mutation
Normocytic anemia. Due to formation of HbS, due to a mutation at codon 6 where normal glutamic acid (hydrophillic) is *replaced with valine (hydrophobic)* .... *HydroPHOBIC interactions occur* and cause RBC's to sickle, stiffen and hemolyse.
# what is the best blot to detect gene expression?
Northern, b/c it detects mRNA.
# Right to left shunts
Note that the right-to-left shunt conditions all begin with the letter T, and thus can be remembered as the 5 T's. They ALL present with very early cyanosis, and require urgent surgical correction.
Hb electrophoresis
Note, Hemoglobin C has lyCine (a more positive AA), this *decreases negative charge* and it thus moves slower on gel electrophoresis. Speed through electrophoresis HbA > HbS > HbC
# Orthopnea
Note, more *specific* for left sided failure! dyspnea *laying flat* for few mins, because of increased venous return to the right side of the heart → worsening pulmonary congestion. But it is RELIEVED by sitting up!
Panacinar emphysema
Note: alpha-1 antitrypsin deficiency causes PANACINAR emphysema, which affects the lower lobes. - it is associated with a1-antitrypsin deficiency and *primarily affects the lower lobes of the lung* !!!! think "pan is a low object"
nicotinic vs muscarinic receptors
Note: nicotinic receptors are *ligand gated ionotropic*. There is immediate subsequent sodium/calcium influx, potassium efflux. *metabotropic* receptors use secondary messengers
# Steps in granuloma formation (!!!)
Note: they form from interaction between *macrophages, and CD4+ Th1 cells* Steps: 1) Macrophages present antigen via MHC-2 to CD4+ helper-T cells. 2) Macrophages secrete IL-12 (!!) inducing CD4+ helper cells to differentiate into Th1 subtype 3) activated TH1 cells secrete IFN-y (!!) which converts macrophages to epithelioid histiocytes and giant cells, forming the granuloma!!(!!) Occurs in both caseating, AND noncaseating granulomas
hydronephrosis
Obstruction of urine outflow which leads to dilation of renal pelvis/calyces/ureter. The dilation occurs PROXIMAL to the site of pathology, and it only impairs renal function if it affects all kidneys (bilateral, or if patient has one kidney). Bilateral hydronephrosis occurs when obstruction is *below the ureters* The excess pressure causes compression atrophy of the renal parenchyma (renal medulla and cortex). • Hydronephrosis caused by a bilateral PARTIAL obstruction presents with polyuria and nocturia secondary to impaired concentrating ability of the renal tubules. Patients are often hypertensive. • Hydronephrosis caused by a COMPLETE bilateral obstruction presents with oliguria or anuria and is a medical emergency.
imperforate hymen
Obstructive lesion of female genital tract. At birth, the mother's estrogen causes the child to have vaginal secretions which buildup mucocolpos (mucus in the vaginal canal). If undiagnosed, the mucus is reabsorbed by the child and will be asymptomatic *until menarche*. At that time, they present with *hematocolpos* (blood in the vaginal canal)!!! Causing: - pelvic pain, back pain - difficulty urinating/defacating *vaginal bulge or mass anterior to the rectum* !!!!
# secondary syphilis
Occurs 5-10 weeks later later, it is a disseminated disease with constitutional symptoms including fever, sore throat, malaise, lymphadenopathy. After secondary infection, the virus can become latent. Presents with symmetric, non-pruritic RASH on palms and soles of feet. This rash can be macular, papular or pustular in appearance. Can also have a *Condyloma lata*, which are smooth, flat, lesions that occur in moist, intertriginous regions (perianal area, vulva, scrotum). These lesions hold a high accumulation of spirochetes and are highly infectious
abscess formation
Occurs by release of lysosomal enzymes by neutrophils and macrophages, which difest offending pathogens, and tissue debris... but they also damage surrounding parenchyma.
# congenital bicuspid aortic stenosis
Occurs due to a congenital bicuspid aortic valve. This leads to *premature calcific aortic stenosis* in the 50's and 60's. (normally without the defect, it doesn't occur until 70's or 80's).
SVC syndrome
Occurs due to a tumor usually obstructing the SVC, commonly LUNG CANCER followed by lymphoma. S/Sx include: Causes "facial plethora", facial edema, neck (Jugular venous distension) and upper extremities (edema). Medical emergency, can raise ICP, cause headache, dizziness, risk of aneurysm/rupture in brain. *dilated collateral veins in the upper trunk* !!!
# brachiocephalic vein obstruction
Occurs from either external compression (lung tumor) or thrombotic occlusion with catheter in for a long time. The brachiocephalic vein drains the ipsilateral jugular AND subclavian. Bilateral brachiocephalics combine to form the SVC. If one brachiocephalic vein is obstructed, it is very similar to SVC syndrome, but only on one side of body. Brachiocephalic- one side of face, chest, neck, arms.
functional mitral regure
Occurs in conditions where hemodynamic factors (ie, pulmonary edema), end up causing LV dilation becsause of increased preload. Functional mitral regurge disappears when the fluid overload is corrected.
# Post-transcriptional RNA processing (!!!)
Occurs in eukaryotes in NUCLEUS. The initial transcript is heterogeneous nuclear RNA (hnRNA)... it is then modified by: 1) 5' capping- adds a 7-methylguanosine to the 5' end of the transcript, to protect the transcript from ribonucleases and is involved in initiating translation of mRNA 2) 3' poly-adenylation- poly-A tail facilitates the mRNA's exit from the nucleus and is also thought to protect the transcript from 3'→5' exonuclease activity 3) splicing of introns The capped, tailed, spliced transcript is now called mRNA, and it exits to cytosol"
# enterobius vermicularis
Occurs in school children and causes perianal pruritus. Diagnosed by scotch tape test. (tape is applied to the perianal region and examined for eggs after removal.) *Eggs are not found in the stool versus other nematodes.* treat with Albendazole.
# Osmotic damage diabetes
Occurs in the *nerves* (ie, peripheral neuropathy) Schwann cells take up glucose (without insulin), and aldose reductase converts it to sorbitol and fructose leading to osmotic damage.... since Schwann cells myelenate PNS, this caused a demyelenation is responsible for peripheral neuropathy (loss of sensation in distal extremities, also pressure ulcers). Pericytes of retinal blood vessels take up glucose without insulin, aldose reductase converts to sorbital, causing osmotic damage and death of pericytes, which weaken blood vessel walls causing a retinal aneurysm which can rupture. Glucose to lens, convert to sorbitol by aldose reductase, cause cataract.
# O2 independent killing
Occurs via enzymes present in leukocyte secondary granules (ie, lysozyme, and major basic protein).
supine hypotension syndrome
Occurs when a *pregnant woman lies down* and experiences *hypotension, pallor, sweating, nausea, dizziness*. Ie, BP 115/75 sitting..... 80/60 laying down It occurs due to *uterus obstructing the IVC*, which *reduces preload*.
# When is hCG shown on a pregnancy test ??
Once the blastocyst implants (approximately 6 days after ovulation) So SERUM appears between like 6-10 days (usually around 8)..... URINE appears 14 days after
Ethambutol
Only active against mycobacteria, a first line drug for active TB Mechanism: inhibits *carbohydrate polymerization* of arabinoglycan in cell walls by *inhibiting arabinosyl transferases, * therefore inhibits mycobacteria cell wall synthesis (analogous to β-lactams)
# duodenal layers
Only layer to contain *Brunners glands*. They secrete *alkaline mucus*.
# ileum histology
Only layer to contain *peyers patches*. (lymphoid aggregates).
# alveolar ventilation
Only refers to volume of air participating in gas exchange per minute. (Tidal volume - dead space) X breaths per minute
#open (wide) angle glaucoma causes and risk factors/treatment
Open angle glaucoma is most often idiopathic, but may also be due to mutations in the gene encoding the protein myocilin. Risk factors for open angle glaucoma include advanced age, African-American race, myopia, and diabetes mellitus. Treatments for open angle glaucoma include beta-blockers (Timolol) to BLOCK aqueous humor release in the CILLIARY EPITHELIUM*. ,carbonic anhydrase inhibitors, as Bicarbonate is required for aqueous humor production. (acetazolamide), and prostaglandin analogues (latanoprost) *increase the outflow* !!!!!
opioid vs non opioid analgesis
Opioid analgesics act primarily in the spinal cord and brain to inhibit the neurotransmission of pain. In contrast, nonopioid analgesics act primarily in peripheral tissues to inhibit the formation of algogenic or pain-producing substances such as prostaglandins. Because most of the nonopioid analgesics also exhibit significant antiinflammatory activity, they are called nonsteroidal antiinflammatory drugs (NSAIDs
#HIV vertical transmission
Oral thrush intestinal pneumonal severe lymphopenia ALL present within the first year of life!!!! Can be avoided with *maternal prophylaxis DURING PREGNANCY* with ZIDOVUDINE (ZDV, AZT), which is a *retroviral reverse transcriptase inhibitor* !!!!
# Segmented genome Virus'
Orthomyxovirus' and rotavirus' !!!!
# Other signs/symptoms of left CHF
Other symptoms include: fatigue, weakness, dulled mental status (↓ cerebral perfusion), and nocturnal cough *Hemoptysis* (coughing up blood) may occur in left heart failure due to rupture of engorged bronchial veins Brick red sputum: ↑ pressure in the alveolar capillaries → iron containing RBC's leak out → alveolar macrophages ingest the red blood cells, which *forms golden hemosiderin containing alveolar macrophages* (called "heart failure cells") !!! They WOULD stain with Prussian Blue because they contain iron!!!!!!
Female reproductive epithelium
Ovary- simple cuboidal Fallopian- simple columnar Vagina- stratified squamous Cervix- Has both stratified squamous (ecto) and simple columnar (endo) Uterus- simple (pseudostratified) columnar
# O2 dependent killing
Oxygen converted into Superoxide (O2-)... by *NADPH oxidase*, this is oxidative/respiratory burst!!! Superoxide can either: 1) cause *direct oxidative damage to bacterial membrane* 2) is coverted into *hydrogen peroxide* H2O2 via *superoxide dismutase*. Hydrogen peroxide into Hypoclhlorous acid HOCl (by myloperoxidase, into bleach)... causing *further* oxidative damage to the bacteria. THIS STEP is what makes pus/sputum green!!!
# Laplace's law
P= 2T/r So, assuming constant tension, a sphere with a smaller radius will collapse while a larger sphere will increase in size.
alveolar-arterial oxygen gradient
PAO2-PaO2 difference...... Difference between the partial pressure of oxygen in the alveoli, and the partial pressure of oxygen in the arterial blood. PAO2= 150- (PaCO2/0.8) ..... it is NORMALLY 10-15mmHg !! FiO2->PAO2 (alveoli)--PaO2 (dissolved in arterial blood)-> SaO2 (hemoglobin saturation FiO2= 0.21 (normally) PAO2= pressure in alveoli PaO2 = pressure in arterial blood
# Treat PDA
PDA is a continuous "machine like" murmur best heart at the upper left sternal border. give Indomethacin (mnemonic: "end"omethacin.... this decreases PGE, resulting in PDA closure). NOTE: NSAIDs can cause premature closure of PDA as a teratogen.
PE
PE is often silent!! (b/c lung has dual blood supply, pulmonary artery and bronchial artery... also because most emboli are small, and they usually self resolve) most common source is DVT of femoral, iliac, or popliteal veins. PE causes VQ mismatch by affecting PERFUSION!!!!
# PT measures which factors? (!!!)
PT measures factors VII, X, V, I (fibrinogen), II (prothrombin),
# Chronic renal failure and secondary hyperparathyroidism (aka renal osteodystrophy!!!! )
PTH is elevated due to nephron damage- the nephron damage causes decreased excretion of phosphate (!!!), Phosphate builds up in blood and binds free calcium. Thus, *lower serum free calcium* stimulates PT gland to secrete PTH. CRF (chronic renal failure) also results in decreased conversion/hydroxylation leading to the formation of active vitamin D, *thus there is also hypocalcemia*. all of this increases bone turnover, has hyperphosphatemia and inceased serum alkaline phosphatase. Diffuse done pain and muscle weakness common.
Post hepatic Jaundice - Stool - Urine - bilirubin
Pale stool Dark urine Conjugated bilirubin
Acute pancreatitis
Pancreatic injury or duct obstruction → enzymes leak into pancreas → autodigestion → more injury and enzyme leakage. This positive feedback cycle causes significant pancreatic edema and fat necrosis.
Other Acute pancreatitis complications
Pancreatic psuedocyst- fibrois tissue surrounds liquefactive necrosis..... Abdominal mass with PERSISTENT amylase elevation (normally amylase goes up, then down as acute pancreatitis resolves).... it can rupture, release enzymes in abdominal cavity causing hemorrhage - Pancreatic abscess (due to E.Coli... abdominal pain, high fever, persistent amylase)
# 4 types of thyroid carcinomas (!!)
Papillary, follicular, medullary, and anaplastic.
Kussmaul's sign
Paradoxical increase in JVP with inspiration. Found in chromic constrctive pericarditis, and other heart problems.
sympathetic stimulation and insulin release
Paradoxically, binding to alpha-2 receptors decreases insulin, and binding to beta-2 receptors increases it.... But normally, the alpha 2 effects of sympathetic binding is dominant!!! So, epinephrine would cause a decrease in insulin secretion. BUT, if you block a2 receptors, epinephrine will then stimulate insulin.
# parainfluenza / paramyoxy virus
Parainfluenza is the most common cause of croup (in children), aka laryngotracheobronchitis.!!!!!!!! Croup clinically presents with a harsh "seal" like bark and *inspiratory stridor*. Symptoms result due to inflammation of the larynx and subglottic airway. Classical radiographic finding is subglottic narrowing, called the "*steeple sign".* Adults tend to get a severe cold/upper respiratory tract infection instead of croup.
# renal carcinoma and hormone abnormality (!!!)
Paraneoplastic syndrome from ectopic hormone production occurs in 20% of RCC patients: - PTHrP → hypercalcemia - EPO → polycythemia (AAA) - ACTH → ↑ cortisol → Cushing syndrome - Renin → hypertension
# Small cell carcinoma paraneoplasic syndrome (!!!!)
Paraneoplastic syndromes associated with ACTH and ADH production are common with small cell carcinoma. (!!!!) Cushing's syndrome and a Cushingoid body habitus can develop with excessive ACTH secretion. (!!!) Electrolyte abnormalities such as hyponatremia can result due to SIADH. *Lambert-Eaton myasthenic syndrome*, which is a disorder of *muscle weakness* due to auto-antibodies directed against neuronal *pre-synaptic calcium channels*, can also be seen as a manifestation of small cell lung carcinoma. (!!!!)
#aversive conditioning
Part of classical conditioning.... Unwanted behaviors are punished by noxious and thus aversive stimuli ie, disulfiram paired with alcohol results in terrible headache/nausea/vomiting to help alcoholics stop drinking #stimulus generalization part of classical conditioning. Occurs when a new stimulus is similar to an old stimulus, and thus elicits the same response. Ie, a child fears nurses after getting a painful vaccine... and then the child also fears medical students.
# lung particle defenses by size
Particles less than 2 um reach the terminal bronchioles and alveoli, and are phagocytosized by macrophages Particles 2-10mm enter trachea/bronchi and cleared by mucocilliary escalator Particles 10-15 are trapped by upper respiratory tract.... And eliminated via coughing, sneezing When alveolar macrophages take up dust, they release cytokines, which induce injury/inflammation of alveolar cells. This releases growth factors (PDGF, IGF) which stimulate fibroblasts, collagen and fibrosis.... Which leads to *pneumoconiosis*.
# DIC (Disseminated Intravascular Coagulation) (!!!)
Pathologic (consumptive coagulopathy!!) activation of coagulation cascade, leads to: 1) Widespread microthrombi (fibrin clots) which blocks small vessels resulting in ischemia/infarcts 2) Consumption of platelets and factors which leads to bleeding, especially from IV sites and mucosal surfaces (!!!!!!) 3) In addition to consumption of coagulation proteins, plasminogen is activated → hemorrhage. Note: DIC is NOT a primary disorder, rather It is a complication of several different disease processes. You must always look for an underlying cause.
#Factitous disorders
Patient *consciously creates* physical and/or psychological symptoms in order to assume "sick role" and to get medical attention *(1° internal/psychological gain).* Factitious Disorder imposed on self (Munchausen syndrome) • Simulation of physical or psychiatric illness to receive attention from medical personnel • Manifested by a chronic history of multiple hospital admissions and willingness to receive invasive procedures Factitious Disorder imposed on another (Munchausen syndrome by proxy) • Simulation of illness *in another person, typically in a child by a parent,* or in the elderly by the caregiver. • Motivation is to *assume a sick role by proxy * • This is a *form of child/elder abuse must be reported * They DO voluntarily create the symptoms, basically to assume a "poor me sick role"
vaginal agenesis
Patient have no upper vagina (short vagina), variable uterine development (hypoplastic or absent, so patient cannot menstruate). Patients have NORMAL overies, so there is normal secondary sex characteristics.
# RPR TEST
Patient serum is mixed with cardiolipin, cholesterol, lecithin.
#dysthymic disorder (!!!)
Patients are chronically unhappy, but do not meet criteria for major depressive disorder. *At least 2 years* (!!!) necessary for diagnosis, and patient cannot be symptom free for longer than 2 months. 2 or more of: Poor appetite or overeating insomnia or hypersomnia low energy poor concentration low self esteem restlessness
# Somatic symptom and related disorder aka somatization disorder
Patients present with (claim) they have Multiple symptoms affecting *multiple parts of the body for months/years. !!!!!!!!!!!!!!* Associated with excessive, persistent thoughts/anxiety about symptoms and may co-occur with medical illness .... Per the DSM-V, the symptoms no longer need to originate from four different organ groups or body systems, as previous editions stated. However, the patients must be persistently symptomatic and the somatic symptoms are distressing to the point of being disruptive to the patient's daily routine. Used to be: -2 GI symptoms - 4 pain symptoms - one sexual symptom - 1 pseudoneurologic symptom. (!!!!!!!!!!!!!!!!!!!!!!!!!!) Patients undergo many tests, but they show up with no cause for them. More common in low socioeconomic groups and onset before 30 years of age with genetic influences
# SCID presentation and treatment
Patients present within the *first year of life* with: - recurrent opportunistic infections (bacterial, viral, fungal, protozoan). !!! - failure to thrive (!!) - chronic diarrhea (!!) - lesions of the throat and mouth, like *candidiasis*. !!!! - There is NO THYMUS shadow because of *severe T-cell deficiency*. DO NOT give live vaccines. Treat w/ Sterile isolation (bubble baby!!) also stem-cell transplant to generate B and T cells
# Asthma presentation
Patients relate a history of difficulty breathing, often with exposure to an allergen such as pollen, dust mite, cat dander, or mold, that *reverses* with *removal of the offending agent* or *bronchodilator therapy*. Also present with *episodic*: -dyspnea and wheezing - *productive* cough of mucus with *Curschmann spirals* and *Charcot-Leyden Crystals* - Asthma also results in the following abnormalities on physical exam 1. A decreased inspiration/expiration time ratio is caused by a prolonged expiration due to obstruction. 2. Pulsus paradoxus (exaggerated drop in blood pressure >10mmHg during inspiration)
# plummer vinson patients have increased risk of what cancer?
Patients with Plummer Vinson syndrome may have increased risk of developing esophageal squamous cell cancer.
# Myelofibrosis S/Sx
Patients with myelofibrosis most commonly present with severe fatigue, and may also complain of bone pain and/or severe constitutional symptoms (i.e. weight loss, fevers, night sweats). Patients may also be asymptomatic *Massive splenomegaly, due to extramedulklary hematopoiesis. (in 90% of patients).* !!!!!!! Myelofibrosis can progress to acute leukemia.
#neuroblastoma presentation
Patients with neuroblastoma can have variable clinical presentations due to location of tumor, metastasis sites, and tumor by-product production. Most commonly children will *present with abdominal fullness or distension.* Other symptoms include fatigue, bone pain (metastasis), changes in bowel or bladder habits, or weight loss/failure to thrive. Patients may also be asymptomatic. Physical exam of a patient with neuroblastoma most commonly *shows a large, tender, irregular, firm abdominal mass* which crosses midline (compared to Wilm's tumor). Hepatomegaly and blanching subcutaneous nodules may also be noted. Associated with spinal cord compression, weakness, bone lesions, swollen neck and abdomen *90% of cases have elevated catecholamines or its metabolites (dopamine, homovanillic acid (HVA), metanephrines and vanillylmandelic acid) !!!!! *
overflow incontinence
Patients with overflow incontinence present with perpetual urine dribbling and low urine flow. Overflow incontinence can be caused by: • Impaired detrusor muscle contractility (e.g., diabetic neuropathy) • Obstruction of the bladder outlet (e.g., BPH, tumor, cystocele) Overflow incompetence is associated with LONGSTANDING MS or *diabetic nephropathy* (due to inability to sense a full bladder, and also impaired detrusor activity causing incomplete emptying.
Schizotypal cluser A:
Peculiar appearance - Odd thought patterns (ie, magical beliefs such as superstitions/telepathic powers) - eccentric/odd behavior/speech - Interpersonal awkwardness, social isolation, social anxiety - NO psychosis..... best treatment is psychotherapy
# Collagen synthesis performed by what cells?
Performed by fibroblasts in RER
*Neuroleptic malignant syndrome* (NMS) (!!)
Perhaps the most feared complication of typical antipsychotics is an idiosyncratic reaction characterized by severe muscle rigidity, hyperreflexia, myoglobinuria and elevated plasma creatine kinase, fever/hyperthermia, autonomic instability, and altered mental status Rigidity/hyperthermia causes muscle damage/nectosis, which elevated blood creatine kinase, myoglobin broken down and pissed out, LDH elevated.... Can progress to rhabdomyolysis which leads to hyperkalemia, hyperphosphatemia, hyperuricemia, AND hypocalcemia. Stop all antipsychotics In addition, NMS can be treated with dantrolene (!!) or dopamine agonists such as bromocriptine to bring dopamine levels up.
diffuse esophageal spasm
Periodic, non-peristaltic (disorganized) contraction of the esophagus. Here, several segments contract at the same time (rather than sequentially), presenting the passage of food down. Barium esophagogram shows a *corkscrew esophagus*. Presents as Intermittent dysphasia, and occasional CHEST PAIN which is not associated with exertion and NOT relieved by rest, so it resembles unstable angina.
# large cell carcinoma of lung
Peripherally located, Large cell carcinoma has a poor prognosis, with overall 5 year survival rates less than 10%. In general, it responds poorly to chemotherapy and is removed surgically when possible.
Liver Zone I damage
Periportal zone. First affected by *viral hepatitis* and *ingested toxins*.
non-pacemaker action potential
Phase 0- influx of sodium as fast sodium channels open (class 1 antiarrythmics act here!!) Phase 1- brief repolarization, decrease in sodium conductance as sodium channels are inactivates, and increase in potassium Phase 2- calcium influx roughly balances potassium efflux Phase 3- mostly potassium efflux- (class 3 antiarrythmics act here mostly!!) Phase 4- balance
pacemaker action potential
Phase 0-upstroke of calcium Phase 3- repolarization (Ca inactivated, K efflux) Phase 4- slow depolarization (spontaneous depolarization due to increased inward Na conductance, known as the pacemaker ("funny") current. The funny current controls the rate of spontaneous activity of sinoatrial myocytes and hence the cardiac rate.
#Cardiac tamponade presentation:
Physical exam findings normally include increased heart rate, pulsus paradoxus, and Beck's Triad. • Pulsus paradoxus is a decrease in amplitude of systolic blood pressure by more than 10 mmHg during inspiration. (Note: A pulsus paradoxus smaller than 10 mm Hg is normal) • Beck's triad refers to the presence of absolute or relative: hypotension - elevated jugular venous pressure - muffled heart sounds. (!!!!!!!!!!!!!!!!!!) • Electrical alternans on EKG: beat to beat alternations of QRS height, which reflects the swinging motion of the heart in the pericardial fluid.
# heroin Overdose
Pinpoint pupils (Miosis) CNS/mental status depression Respitatory depression seizures.
# Multiple Myeloma Ig chain formation
Plasma cells overproduce Ig Light chain... normally plasma cell produces equal amount heavy and light.... this results in free light chain which circulates in the serum, and deposits in tissue, this is called PRIMARY (AL) amyloidosis. !!!!!!!! The free light chain is also excreted in the urine (a proteinuria), and this proteinuria is called *Bence-Jones proteins*!! !! The light chains can also deposit in the kidney tubules and lead to risk for renal failure ( This causes renal insufficiency → 2nd most common cause of death.)
#lung manifestations of RA
Pluritis with pleural effusions, Lung fibrosis, caplan syndrome
Pneumoconioses
Pneumoconiosis is caused by *environmental/occupational exposure* to very small (<2um) particles. The size and composition of the particulates predicate the disease. *Smaller particles* are *more pathogenic* because they settle in terminal airways. The *chemical composition* relates to the pathogenesis. Some minerals (silica) interact with free radicals and *cause cell membrane damage*. Others trigger resident or *interstitial macrophages* and precipitate an *inflammatory cascade* leading to *tissue injury and fibrosis*. Types: - coal workers - silicosis - berrylliosis - Asbestosis
order kinetics
Point 1- first order kinetics Point 2- begin to switch to zero order kinetics Point 3- zero order kinetics Zero order: • In zero-order kinetics, the elimination rate does not vary with drug intake or plasma concentration. • Drug plasma concentration decreases linearly with increased time. First order: constant fraction of drug eliminated per unit of time.
# osmotic laxatives
Polyethylene glycol, magnesium compounds. They are NON-absorbable substances which attract water into the intestinal lumen, distending the wall and promoting peristalsis.
# androgenic alopecia
Polygenic inheritance with variable penetrance.
# what is also associated with temporal arterieis
Polymyalgia rheumatic!!!! Characterized by neck, torso, shoulder and pelvic girdle pain, especially in the morning.
# Chronic Granulomatous Disease
Poor O2 dependent killing due to *deficiency in NADPH oxidase* causing neutrophils(!!!) to be unable to eradicate some bacteria/fungi. This defect in oxygen dependent bactericidal activity causes increased susceptibility for recurrent CATALASE POSITIVE bacterial infections.
# HCC markers and prognosis
Poor prognosis, often presented late, masked by cirrhosis Assoc with ↑ AFP (alpha fetoprotein), produced by injured/regenerating hepatocytes. (!!!)
# where does postive and negative selection for T-cells occur?
Positive in the *cortex* Negative in the *medulla* of the thymus
# GFAP
Positive stain in *glial* origin tumors Astrocytomas Enendymomas Oligodendrogliomas
# Positive vs negative operant conditioning reinforcement
Positive= desired reward comes from an action (mouse presses button and gets food) Negative reinforcement= the targeted behavior/response occurs as a result of removal of an adverse stimulus (ie, press a buttom to turn off an annoying noise.... Clean room to avoid nagging).
#Postpartum problems
Postpartum depression: symptoms begin within 4 wks post-delivery AND last for at least 2 weeks. Patients feel hopeless, helpless Postpartum psychosis: symptoms begin 2-3 wks post-delivery. Patients hallucinate, are delusional, may harm their children or themselves.
# what medication is given to protect thyroid in radioactive exposure?
Potassium iodide. This *competitively inhibits I131 from entering thyroid follicular cells*.
# Hyaline arteriolosclerosis in kidney
Preferential involvement of *efferent arteriole* increases pressure in glomerulus leading to glomerular hyperfiltration injury with microalbuminuria, leading to sclerosis of mesangium in the glomerulus, that eventually progresses to nephrotic syndrome, characterized by KIimmelstiel-Wilson nodules.
#congenital adrenal hyperplasia and 3 product groups
Pregnenalone can be converted into 3 groups: 1) Mineralcorticoids 2) glucocorticoids 3) sex steroids NOTE, think of them left to right the SAME as "salt, sugar, sex"!!!!!!!
# neonatal complications of gestational diabetes
Premature delivery Fetal macrosomia Transient Hypoglycemia (fetal hyperinsulinemia lasts a few days) Neural tube defects (caudal regression syndrome)!!! Transposition of great vessles
# housemaid's knee
Prepatellar bursa inflammation, located between the patella and skin.
# hyperaldosterone
Presents as HTN due to effects of HIGH aldosterone: -Principal cell both grabs Na+, and dumps K+ -a-intercalated cell increases SECRETION of H+ hypernatremia, hypokalemia, metabolic alkalosis. Also *MUSCLE WEAKNESS* !!!
# EBV Hodgkin's
Presents as mediastinal mass or nontender lymphadenopathy Constitutional "B" Sxs can mimic the presentation of mono (e.g., swollen lymph nodes, recurrent fevers)—a monospot should be ordered to rule out infectious mononucleosis prior to carrying out more extensive work-up for Hodgkin's Malignant cell = Reed-Sternberg cell: B-cell origin, CD15+, CD30+, binucleate with prominent nucleoli ("owl eyes")!!!! Mixed cellularity type (25%) has the most Reed-Sternberg cells - nasopharyngeal carcinoma (classically Chinese male, or African individual... presents as a neck mass b/c goes to neck lymph nodes)
# ethylene glycol use
Presents as: - sudden onset back pain - hematuria - oliguria - anion gap metabolic acidosis!!! Metabolized to: - glycolic acid which is toxic to the renal tubules. - oxalic acid, which precipitates as calcium oxalate crystals in the renal tubules. Calcium oxalate crystals are detected microscopical and folded like envelope in the urine. Kidneys experiencing BALLOONING and vacuolar degeneration, prideominantly in the proximal convoluted tubules.
treat acute neonatal narcotic withdrawl
Presents the same as opioid withdrawl, but in the infant of an opioid using mother. Treat with *tincture of opium*.
# hypothyroid myopathy
Presents with *proximal muscle weakness* and cramping. MYOEDEMA is a characteristic finding!
hemolytic disease of newborn
Prevention of erythroblastosis fetalis is required when the mother is Rh- and her fetus is Rh+ !!! • Rh- mothers (who are *type O bloodtype* become alloimmunized against the D-antigen during their first pregnancy with an Rh+ baby (Rh+ produces the D antigen). Hemolytic disease of the newborn is usually only a major problem in a subsequent pregnancy with a second Rh+ baby. • ( fetalis): *transplacental transfer of maternal anti-Rh IgG* (usually anti-RhD) binds to Rh+ fetal RBCs → fetal RBCs are destroyed (relative hypoxia, altered cellular metabolism) Erythroblastosis fetalis can be prevented by *administering RhoGAM, an anti-Rh IgG,* to an Rh-negative mother after 28 weeks of gestation and again within 72 hours of birth. !!!!!!!!!!!!!!!!!
#cocaine
Prevents the presynaptic REUPTAKE of norepinephrine/serotonin/dopamine, thereby indirectly causes an increased availability of these in synapse • Clinical application: local vasoconstriction and local anesthesia effects cocaine abuse: Thinned or perforated nasal septum, atropic nasal mucosa, chronic nasal discharge, headaches
# what is the most common CNS tumor in immunosuppressed patients? !!!
Primary CNS lymphoma. Associated with EBV !! It appears SIMILAR to toxoplasmosis in there are *multiple ring enhancing lesions*!!!! Most often from *diffuse large B-Cell*. They are high grade, microscopically dense, respond poorly to chemo.
#types of gain
Primary gain: what the symptom does for the patient's internal psychic economy Secondary gain: what the symptom gets the patient (money, avoidance of legal penalties) Tertiary gain: what the caretaker gains (like an MD on an interesting case)
# Hepatocellular Carcinoma (HCC) overview and presentation
Primary liver tumor that most commonly occurs in the setting of chronic liver disease (e.g. cirrhosis, chronic hepatitis) • Acquired: Hepatitis B/C, EtOH abuse, toxins (e.g. aflatoxin) • Genetic: Hemochromatosis, Wilson's disease, α-1-antitrypsin deficiency Note: the neoplastic changes for Viral HCC are *triggered when viral DNA is integrated into the genome of host hepatocytes*. Aflatoxins derived from Aspergillus- very high HCC in some countries who *store grains for extended periods*, Aspergillus grows on grains and releases Aflatoxins... Aflaxoxins when consumed increase HCC by mutation of p53. !!!!!!!!!!!! Often invades hepatic vein causing BUDD-CHIARI syndrome Clinical findings include: - Abdominal pain → most common presentation - Fever due to liver cell necrosis - Liver enlargement with ascities
#lung cancer spread
Primary lung cancer commonly spreads to: brain, adrenals, liver, and bone
Anterior shoulder dislocation
Primary presentation: Arm is externally rotated and abducted Anterior shoulder dislocation can result in axillary nerve injury. • Axillary nerve injury presents with anesthesia of upper lateral arm and paralysis/paresis of the deltoid and teres minor muscles. Flattening of the deltoid, protrusion of acromion.
Primary vs secondary vs adrenocortical insufficiency
Primary: aka Addison's Disease (!!!) : Absence of hormone production in all 3 cortical divisions due to autoimmune destruction of adrenal glands.. Note, those with OTHER autoimmune conditions (Diabetes, SLE, etc) are at risk of it. Result is: -hyponatremic (low sodium) volume contraction, hypotension - hyperkalemia - constipation, diarrhea, fatigue - skin hyperpigmentation (pro-opiomelanocortin (POMC) is the shared precursor molecule for both MSH and ACTH... so *elevated ACTH* occurs alongside elevated melanocyte-stimulating hormone (MSH)) - lack of aldosterone (low sodium, hypotension, high potassium) Because there is no aldosterone, we DO NOT piss out K+ and H+ !! So K+ and H+ accumulate!! Thus, *bicarb is low*. There is a *compensatory increase in chloride* since bicarb is low!! - no cortisol (high ACTH, hypotension, weight loss) Secondary: are the result of pituitary gland or hypothalamus dysfunction, resulting in decreased ACTH levels.
# hypocretin-1
Produced ONLY in neurons in the lateral hypothalamus. They promote wakefulness and *inhibit REM sleep*. They are ONLY detectable in the CSF
# Somatostatin produced by what cells
Produced by *δ cells* of pancreatic islets and intestinal mucosa, and neuroendocrine neurons in hypothalamus.
#secretin produced by
Produced by duodenal S cells. - ↑ Pancreatic secretions rich in HCO3- - ↑ HCO3- and H2O secretion by liver - ↑ Bile production - ↓ Gastric acid secretion
# B-ALL prognosis
Prognosis is based on cytogenetic abnormalities: More common one (especially in kids) is t(12;21... think '12 flipped') which has good prognosis t(9;22) has poor prognosis, more commonly seen in adults. Remember, the 9;22 translocation (Ph+, called Philidelphia!!) is commonly seen in CML, but it is also seen here
# where are the areas of the kidney prone to ischemia??
Prone to acute tubular necrosis (muddy brown casts) 1) Proximal tubule 2) thick ascending limb
diffusion across a semipermeable membrane
Proportional to: - concentration difference across the membrane - total surface area of the membrane - solubility of the substance Inversely proportional to: Membrane thickness molecular weight of the molecule
prostate cancer bone
Prostatic cancer spread spread to *lumbar spine* is common, and instead of punched out lytic lesions, we get *osteoblastic metastases* which leave *sclerotic lesions of bone*... by far the most common. -Other common sites of metastasis: Lung and Liver
#how to reverse heparin overdose (!!!!)
Protamine, it is positively charged and binds to negatively charged heparin !! (doesn't work against low molecular weight heparin)
# HIV protease inhibitors (!!!) NAVIR
Protease inhibitors prevent virally encoded proteases such as the HIV-1 protease (pol gene) from cleaving polyproteins into mature proteins. Protease inhibitors (-Navir) include (note, do NOT think just "vir"... always "NAVIR) o Indinavir (!!!)
femoral hernia
Protrudes through femoral canal: - below/lateral to pubic tubercle. - *BELOW inguinal ligament* - medial to the femoral vein More common in females, causes bowel incarceration and obstruction (nausea, vomiting, abdominal pain, distension). Impaired blood flow to the contents trapped in the hernia sac then occurs hours after incarceration, causing *strangulation*! This leads to ischemia/necrosis of the hernia sac
cervical sympathetic ganglion
Provides sympathetic innervation to tarsal muscle, lacrimal gland, salivary glands, radial muscles of eye
#treat borderline personality
Psychotherapy, maybe a mood stabilizer such as valproate or atypical antipsychotic
Pyrazinamide
Pyrazinamide is an anti-tuberculosis drug thought to *act in the acidic pH of phagolysosomes* where TB is found. The exact mechanism is controversial (some studies show that it inhibits activity of fatty acid synthase I).
# what is first line treatment for myasthenia gravis?
Pyridostigmine, neostigmine, phyridostigmine They are *anticholinesterases*.... They improve Myasthenia Gravis, BUT they lead to *GI effects* like cramping, diarrhea, nausea (due to increased ACh in other places!!) This can be treated with *scopolamine*..... which is a SELECTIVE muscarinine antagonist (works in the gut, does NOT decrease Ach at the motor end place thankfully)
# B6 deficiency and sideroblastic anemia
Pyridoxine (B6) deficiency causes sideroblastic anemia because it is a cofactor for the rate-limiting reaction of heme synthesis (ALAS enzyme) Most commonly secondary to INH (isoniazid) therapy for TB !!! "
# flow through a vessel equation
Q= (p1-p2) x r^4 / nL ie, if radius is decreased by 50%, then flow is decreased by a factor of 16 1/2) ^ 4 = 1/ 2x2x2x2 = 1/16
# quadrouple therapy
Quadruple therapy is used in regions with *clarithromycin-resistant H. pylori*. It includes a proton pump inhibitor (PPI), bismuth, and two antibiotics.
# Inappropriate polycythemia
RBC count increase WITHOUT hypoxic stimulus. No hypoxic stimuli → normal O2 saturation. Ectopic EPO production (e.g. from Renal Cell Carcinona, RCC !!!!!) → ↑ RBC production → ↑ RBC mass and RBC count
# Appropriate polycythemia
RBC count increase in response to chronic hypoxia. Hypoxic stimuli → ↓ O2 saturation due to: - High altitude - Primary lung disease - Cyanosis (due to heart disease or CO exposure) ↑ RBC count, RBC mass, and EPO. Plasma volume (PV)= normal.
# Eukaryotic RNA polymerases
RNA polymerase I makes rRNA (most numerous RNA) ""rampant"" RNA polymerase II makes nuclear RNA which is then processed into mRNA (largest RNA) ""massive"" !!!! RNA polymerase III makes tRNA (smallest RNA) ""tiny"" Note; There is NO proofreading functipon"
# Acute cholecystitis presentation
RUQ pain that RADIATES TO RIGHT SCAPULA, especially after a fatty meal!! Positive Murphy's sign fever, elevated WBC's, nausea, vomiting Increase serum alkaline phosphatase- because epithelium that lines gallbladder and biliary tract contains alkaline phosphatase, so as these cells die they release it.
# Rabies
Rabies virus glycoprotein *initially bind to nicotinic acetylcholine receptors (nAchRs) in the postsynaptic muscle* membrane of the neuromuscular junction. Eventually the* virions cross across the synaptic clef to bind to neural cell adhesion molecules (NCAMs) and enter motor neurons, *which shelter rabies virus from the host immune system. *Retrograde axonal transport eventually leads the rabies virus to the CNS*. • Replication and transcription of rabies virus occurs in *eosinophilic cytoplasmic inclusions called Negri bodies within neuron cell bodies in the spinal cord and CNS (especially Purkinje cells in the cerebellum and pyramidal cells of the hippocampus). * In the US: *rabid bats (most common).* [Note: another disease caused by bats (and birds) that can be problematic for cave explorers is the fungus Histoplasma capsulatum] • Developing Countries: Rabid dogs account for 90% of source [Note: the US is considered "canine-rabies free" due to widespread immunization of dogs] Common manifestations of rabies include a nonspecific, flu-like prodrome (malaise, anorexia, mild fever, headache, nausea, vomiting) followed by an acute neurologic syndrome that includes • Agitation • Persistent fever • Variable consciousness • Photophobia • *Painful spasms with swallowing and/or inspiration* • Pharyngeal muscle spasms cause dysphagia, which can lead to the avoidance of food and water known as hydrophobia. *Dysphagia along with hypersalivation due to autonomic dysfunction results in the "mouth foaming" seen in rabies encephalitis !!!!!* • Generalized flaccid paralysis and coma follow the acute neurologic phase, with *most patients dying within 2 weeks of becoming comatose. *
# Midshaft fracture of humerus
Radial nerve injury... often due to *fall with outstretched hand!!!* Also risks the *deep brachial artery* !!!!
# colonic polyps
Raised protrusions of colonic mucosa. 90% benign. Can be neoplastic (aka adenomatous.) or non-neoplastic
# Clinical findings of VSD
Range from asymptomatic to cyanosis and heart failure in severe or advanced disease. Frequent respiratory infections Failure to thrive Dyspnea SOB Heart failure = PND, orthopnea, lower extremity swelling, pulmonary edema Physical exam findings: * harsh holosystolic murmur* at the TRICUSPID AREA, *lower left sternal border* (the smaller the VSD, the louder the murmur) Loud pulmonic S2 Systolic thrill may be present Signs of heart failure including ascites, hepatomegaly, and edema
pure red cell aplasia
Rare form of anemia (pesents as palor, fatigue), due to marrow failure. Characterized by SEVERE hypoplasia of *erythrocyte* marrow element. WBC and platelet counts are normal!!! Associated with: - thyoma - lymphocytic leukemias - parovirus B19
# Henoch- Schonlein Purpura presentation (!!!)
Rash (!!!!) -symmetric *Palpable* purpuric rash (!!!) on buttocks, arms and legs (normally purpura is NOT palpable, but here it is because there is also inflammation along with vasculitis) . -Joints: transient nonmigratory arthralgia most commonly located in ankles and knees. (!!!) -Colicky Abdominal pain and PR bleeding (!!!), frequently associated with vomiting; these patients have ↑ risk of intussusception (!!!!)
# dress syndrome
Reaction to drugs, typically 2-8 weeks after starting anticonvulsants (phenytonin, carbamazepine!!!), allopurinol, or antibiotics. Patients develop: - fever - generalized lymphadenopathy - facial edema - diffuse skin rash!!! (eosinophilia!!)
#Reiter syndrome aka now called *Reactive arthritis*
Reactive arthritis is characterized by the symptomatic triad of • Urethritis - "Can't pee" • Conjunctivitis - "Can't see" • Inflammatory arthritis of large joints - "Can't climb a tree" Usually in young men weeks after a GI or *chlamydia* infection Joint aspirates are *ALWAYS NEGATIVE* !!!
cerebral arteries
Red arrow- *anterior cerebral artery*. .... Occlusion here causes *sensory/motor function impairment in CONTRALATERAL LEG/FOOT*. ... Severe bilateral occlusion can cause *behavioral symptoms and urinary incompetence Blue is - *internal carotic artery*. Green is *middle cerebral artery* Occlusion here causes *contralateral homonymous anopia*, and gaze *toward the side of the stroke*. Also causes *impaired motor control of hand, face/mouth, throat*. Can cause *Broca's aphasia* if it is in the DOMINANT HEMISPHERE (usually the left)... leading to expressive, non-fluent aphasia (meaning the patient understands written and spoken language but is unable to articulate or write). Patients ARE AWARE of the defect, and are frustrated. Broca=broken speech!!!! Cause *hemineglect* if in the non-dominant (usually the right)
#rifampin side effects(!!)
Red/orange body fuilds!!!!!!! rapid resistance if used alone because of *altered structure of the Rifampin binding site*, and unfortunately, the bacteria is then able to perform RNA synthesis*!!!
Vancomycin toxicity:
Redman syndrome... characterized by flushing, erythema, pruritus, and sometimes hypotension. The mechanism of red man syndrome is caused by a rapid infusion from the first dose of vancomycin causeing by* direct activation of mast cells,* ..... and it is NOT a IgE-mediated Type I hypersensitivity reaction
# genetic linkage disequilibrium "
Refers to the tendency of two different genes on the same chromosome to segregate together during recombination. The genes appear to be "linked." The closer two genes are, the more likely they are to remain linked..... Measured in a population and NOT a family. To estimate the probability of the 2 alleles appearing together, we multiply their occurance rates. If the observed frequency is much greater than the predicted occurane rate, the genes are in linkage disequilibrium.
Nigrostriatal pathway
Regulates *coordination of voluntary movements*. Here, *dopamine inhibits Ach*. High potency anti-psychotics can cause EPS here by *dopamine antagonism*.
# Aortic regurgitation overview
Regurgitation of ejected blood from the aorta back into the left ventricle during *early diastole*! (...leads to↓ peripheral arterial *diastolic BP*) Also, this ↑ LVEDV (left ventricular end-diastolic volume) → Frank-Starling mechanism causes *increase in stroke volume* during *systole*, causing *↑ systolic BP*) → wide *pulse pressure* (systolic-diastolic). !!! This above phenomenon leads to concept called *hyperdynamic circulation*, and shown with bounding femoral/carotid pulses, plusing nail bed, and head bobbing with *carotid pulses* !!!!!!!!!
# Cardiac enzyme troponin
Relative to other biomarkers (eg, CK-MB, LDH), cardiac forms of *troponin I* and *troponin T* (have *↑ sensitivity for myocardial damage*, and are ∴ currently the *preferred biomarkers* for detecting myocardial necrosis Begins to *rise 2-4 hours after onset* - peaks between ~24 hours - remains elevated for 7-10 days - returns to normal within 10-14 days
alkaline phosphatase kinds
Released by osteoblasts and liver mostly. Also placenta and intestine. Bone alkaline phosphatase is easy denatured by heat (bone=boil), while liver is NOT.
# BNP
Released by the ventricles due to prolonged hyemodynamic overload on the heart. Thus, the heart compensated by hypertrophy and increasing mRNA to increase BNP (B-type naturetic peptide) to attempt to improve naturesis and diuresis. They are used to diagnose congestive heart failure !!!
# treat hyperpyrexia
Remove clothes, take to cool environment, cold blankets, cold packs to groin and axilla. Also antipyretics like NSAIDs and acetaminophen.
Kidneys and blood flow
Renal vein has high PO2 !!!!! Although the kidneys receive nearly a quarter of the cardiac output it extracts relatively little oxygen. there is a marked discrepancy between cortical and medullary blood flow, and oxygen delivery and consumption. In the medulla, blood flow and oxygen supply are restricted by a tubulovascular anatomy specifically designed for urinary concentration.
# Rotavirus
Reoviruses are the only double-stranded RNA virus. !!!!! is the most common cause of viral gastroenteritis in infant/young children (both fatal and non-fatal).!!! *ROTA: "Right Out The Anus" * • Rotavirus has a fecal-oral transmission (common in preschools and day care centers). • Rotavirus contains a viral encoded non-structural protein (NSP4) which acts as an enterotoxin, causing non-bloody (non-inflammatory), watery diarrhea leading to dehydration, and death (without rehydration).
# Chronic rheumatic fever
Repeat exposure to *group A β-hemolytic streptococcal* causes relapse in acute phase.... and each relapse increases risk for *chronic rheumatic valvular disease* Chronic rheumatic valvular disease results in scarring of the valves (*mitral > aortic >> tricuspid*)... This scarring causes *stenosis*, most always in mitral valve, which leads to thickening of the chordae tendineae and cusps. If scarring of the aortic valve, leads to *fusion of the commissures*.!! ( Damaged valves can cause *endocarditis*.
# tRNA
Resembles a cloverleaf. It contains *unusual nucleosides* such as seudouridine and thymidine. tRNA has a *CCA sequence at its 3 end!!!* protein synthesis elongation begins when aminoacyl tRNA binds to the A-site: the ANTICODON is located on the opposite side
# " macrolide resistance"
Resistance includes *post-transcriptional methylation of the 23S bacterial rRNA, a component of the 50s subunit. *
high altitude blood values
Respiratory alkalosis !! PaO2 is low. This stimulates carotid and aortic chemoreceptors. PaCO2 is low (hyperventilation!!!) To compensate for respiratory alkalosis, the kidneys *excrete bicarbonate* in the urine (!!!!) , causing *bicarbonate* to be low *eventually* as a delayed response!!!
# Restrictive lung diseases
Restricted *filling* of the lung. ↓ pulmonary compliance (!!!!!) ↑ lung elasticity (!!!) . The INCREASED elastic recoil causes *AIRWAY WIDENING*, due to *RADICAL TRACTION* which is outward pulling by the surrounding fibrotic tissue. This leads to SUPERNORMAL expiratory flow rates. ↓ lung volumes Because *all lung volumes* are reduced (especially FVC), the *ratio of FEV1/FVC >80%.* ↓ FEV1, but ↓↓ FVC , so there is a HIGH FEV1/FVC !!! ↓ TLC is needed to determine restrictive lung disease (less than 80%) !!!
# Rheumatoid autoantibodies
Rheumatoid factor (autoantibodies (mostly IgM) directed against the *Fc portion of IgG)*: ..... RF occurs in about 5% of the human population. The incidence of RF increases with age and about 20% of people over 65 years of age have elevated RF Many other conditions are associated with a positive test for RF e.g. SLE, progressive systemic sclerosis, Sjogren's syndrome, TB, endocarditis, osteomyelitis *anti-CCP (anti-cyclic citrullinated peptide antibodies *= autoantibodies against citrulline-modified peptides): relatively specific(!!!) (95%) for rheumatoid arthritis
# Right heart failure
Right heart failure (RHF): "backward" failure, meaning *right ventricle cannot pump blood* from the *venous system into the lungs*, causing blood to accumulate behind it. *Most common cause of RHF is LHF.* Other causes: - cor pulmonale (right ventricular heart failure and hypertrophy as result of severe or chronic *pulmonary hypertension*. Lung disease causes hypoxia, which causes blood vessels in lung to constrict, and heart has to pump against constricted vessels ) - left-to-right shunt - tricuspid valve regurgitation
# RHF signs
Right sided heart failure is generally said to be a *disease of signs* (rather than symptoms like in LHF) of venous congestion including - painful hepatosplenomegaly (may lead to cirrhosis. : due to venous congestion of hepatic veins of the liver. If severe enough, can cause portal hypertension and ascites..... Ascites, though a main feature of liver disease, may also be a sign of right-sided heart failure. The presence of the hepato-jugular reflex, where pressing on the RUQ of the abdomen elicits a reflexive distention of the right jugular vein, can differentiate between hepatic failure and heart failure.) - peripheral edema (increase in venous hydrostatic pressure accumulating in dependent areas) - jugular venous distension ( increased venous pressure in the superior vena cava → increased pressure of jugular vein)
right sided colorectal
Right sided tumors (ascending colon) tend to grow as *raised lesion*, commonly present with fatigue and weakness due to *iron deficiency anemia* due to *bleeding* Right sided is more associated with *micosatellite instability* pathway.
# Risk factors for myelofibrosis
Risk factors for myelofibrosis include exposure to thorium dioxide (an ingredient in some contrast media), toluene, benzene, and ionizing radiation. Many cases have been seen in victims of the atomic bomb drop in Hiroshima.
# Complications of EBV mono
Risk for splenic rupture (avoid sports for 1 year!!!!) -Rash if exposed to penicillin - Dormancy of virus in B-cells (increases risk of recurrence, and risk of lymphoma!!)
Multiple myeloma blood smear
Rouleaux formation on blood smear due to increased serum protein, which decreases the charge between RBC's, so the RBC's pile up on each other like 'poker chips'. This is a sign of inflammation!!!
# portal triad
Runs through the *hepatoduodenal ligament* and is composed of: - hepatic artery - portal vein - common bile duct
staph epidermis
S. epidermidis, which is novobiocin sensitive. Contrast this with S. saprophyticus is novobiocin resistant. S. epidermidis is capable of generating a sticky, protective biofilm, facilitating colonization and infection of prosthetic devices including prosthetic heart valves and indwelling urinary catheters. Prosthetic valve endocarditis during the initial year after surgery is almost exclusively caused by S. epidermidis.
# S & SX of EBV mono
S/Sx of infectious mononucleosis include: Fatigue, fever, pharyngitis, anorexia Generalized tender lymphadenopathy Splenomegaly — danger of splenic rupture ∴ patients should avoid contact sports.
# Southern blot, Northern Blot, Western Blot
SNoW DRoP S-D (southern, DNA) N-R (northern, RNA) W-P (western, protein)
# Sarcoidosis in skin
Sarcoidosis skin findings include erythema nodosum, papules, plaques, or ulcers. Patients may also present with lupus pernio, a violaceous rash involving the nose and cheeks.
# Diagnose mono (!!!)
Screen via Monospot test, which detects *IgM heterophile antibodies* (have affinity to bind RBC's from another animal, This means that the patient's serum will agglutinate non-human (i.e. sheep) RBCs. Test usually turns positive within 1 week after infection. *If it is negative, it suggests CMV mononucleosis. * Confirm by testing for EBV viral capsid antigen.
# Vitamin C deficiency
Scurvy, due to *defective collagen hydroxylation* in the *RER lumen* !!!
# IgA
Second most common Ig in serum but MOST common in body (most in mucus membranes) In mucosal, salivery, tears and breast milk secretions, IgA exists dimer — 2 IgAs held together by a J-chain (similar to the J-chain in the pentameric form of IgM) → 4 antigen binding sites. • In serum, IgA exists as a monomer.
atrial natriuretic factor (ANF , ANP)
Secreted by cardiac myocytes in the atria in response to increased atrial pressure, basically a "check" on the RAAS system. It does this through *Increasing cGMP*!!!! Decreases aldosterone secretion. Dilates afferent arteriole (increases GFR), thus increasing both sodium and water excretion Relaxes vascular smooth muscle, producing vasodilation, so it decreases total peripheral resistance.
#Psoriatic arthritis
Seen in 10%-20% of cases of people with *psoriasis*... involves the axial AND peripheral joints... so DIP of the hands/feet are commonly involved, leading to formation of a *sausage finger/toe* (aka dactylitis) !!! • Telescoping of one phalanx into another at the DIP can also occur and leads to a characteristic "pencil-in-cup" deformity on x-ray.
Alveolar hypoventilation
Seen in conditions such as upper airway obstruction Reduced ventilator drive Respiratory fatigue Decreased chest wall compliance
# Secondary hyperaldosterone
Seen w/ RAAS activation (due to reasons such as atherosclerosis/coronary heart disease, cirrhosis etc..... ultimately *renal artery stenosis causes decreasing flow to kidney*, activating JGA, thus *high levels of renin renin*.... ultimately AT2 causes release of aldosterone) If the renal artery stenosis is unilateral, then *renin levels will be high* in both that renal vein and plasma.... However renin levels in other kidney will be slightly lower than normal. Renal artery stenosis is often heard by a "thrill" over the abdomen. !!! Could also be caused by a *renin secreting tumor* in the JGA cells !!!
#isolation of affect
Separating feelings from ideas/events. emotions concerning stressful events are neither experienced nor expressed—associated with obsessive-compulsive personality disorder. (For example, a patient with metastatic bone cancer shows no emotion when discussing his diagnosis with family members.) ie, describing a graphic murder in detail with no emotional response
Acute pancreatitis presentation
Severe Epigastric abdominal pain that *radiates to back*, usually with nausea, vomiting, fever. Pain is often worsened when the patient is supine, and *improves with sitting forward or assuming the fetal position* - periumbulical/flank hemorrhage - Shock (digest pancreas AND vessels in pancreas, hemorrhage causes shock)
# Biliary Colic-
Severe RUQ pain due to gallbladder contracting against cystic duct (!!!) Note: anything that causes *contraction of smooth muscles in the sphincter of oddi* can cause it, especially opioids and alcohol (!!!!)
Cretinism (aka congenital hypothyroidism)
Severe hpothyroidism in neonates and infants. Presents as : - Jaundice - Horse cry - hypotonia -mental retardation - short stature - enlarged tongue, umbilical protrusion and hernia, pot belly, puffy face/corse facial features Caused by: - maternal hypothyroidism during pregnancy - Thyroid agenesis (doesn't form thyroid) - dyshormonogenetic goiter (cannot produce thyroid hormone, most common deficient enzyme is thyroid peroxidase) - Iodine deficiency
# sciatica
Shooting pain down the *posterior thigh/leg*... usually due to compession at L5 or S1!!! Causes weakness of the hamstrings AND muscles below the knee! There is diminished ankle reflex but NOT knee reflex.
#Pompe ECG and blood
Short PR, giant QRS...... blood shows elevated CK, decreased leukocyte acid maltase.
#zolpidem
Short acting hypnotic structurally unrelated to benzos, so there is LESS tolerance and addiction!!!!! Still binds to GABAa to enhance action. Very rapid onset, used by short term treatment of anxiety, or before a flight. No muscle relaxation OR anticonvulsant properties
# Achondroplasia clinical features
Short extremities (dwarfism) with normal-sized head, torso and chest (they are large relative to the short limbs) due to *impaired endochondrial bone formation* (intramembranous formation is fine) Flat midface, prominent forehead.
# Chlamydia
Shows neutrophils but NO organisms (it does NOT gram stain!!) chlamydia is an *obligate intracellular organism* (cannot make own ATP!!), it enters mucosal surfaces as *elementary bodies* via endocytosis, they replicate into *reticulyte bodies* which are released as more *elementary bodies* which can infect again. Eventually heals with fibrosis, may result in *rectal strictures* especially if there is perineal involvement. C. trachomatis cell wall lacks muramic acid, a component bacterial cell walls, *and lacks peptidoglycan* !!!! For this reason, penicillins are not very effective in treating chlamydial infection. Treat with a macrolide!!!!!
#Statin sides
Side effects: - risk of rhabdomyolysis ESPECIALLY when combined with niacin or fibrates (!!!!), can lead to ATN (!!!) - ↑ LFTs (liver function tests) — i.e., ↑ serum levels of liver enzymes: ↑ AST, ↑ ALT - drug induced photosensitivity (!!!!)
# Calcium channel blocker sides
Side effects: Cardiac side effects include AV block from decreased L-type calcium channel activity preventing signal transmission, and cardiac depression. (especially Verapamil!!!!) Vascular side effects include peripheral edema, headache, flushing, and dizziness. (!!!!) - Both DHP (amlodipine) and non-DHP (verapamil) Ca channel blockers: constipation, gingival hyperplasia.
which drugs cause anti-muscarinic side effects (!!)
Sides are facial flushing and pupillary dilation !!!! Facial flushing because of inhibition of sweat glands causes fever and compensatory cutaneous vasodilation. hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter) Atropine TCA's (amitriptyline) H1 antagonists (diphenhydramine) neuroleptics anti-parkinsonians
# Psoriasis histology
Since it is due to *excessive keratinocyte proliferation*, one finding is we have *hyperplasia and increased thickness of epidermis*... which is called *acanthosis* ... however there is an increase in stratum spinosum and a decrease in stratum granulosum !!!!!!!! The increase in the stratum spinosum results in overall epidermal hyperplasia !!!! Silvery scale is due to *excessive keratin*... there is *para-keratosis* which is *hyperkeratosis with retention of nuclei* Collection of nuclei are in the stratum corneum, called *Monroe microabsysses* Elongation of the dermal papillae are seen, and *directly above* that is *thinning of the epidermis*, so if we pulled away the silvery scale, because the epidermis is so thin, we expose the blood vessels and get a *pinpoint bleed* !!!! (called *Auspitz's sign* !! )
# if average blood glucose of a normal distribution of 500 people is 90 with a SD of 5, how many people have a blood glucose greater than 95??
Since mean is 90, 68% of people have blood glucose between 85 and 95. That means 32% have a blood glucose outside this range, 16% above, and 16% below. Thus, the answer is 500x0.16, which means 80 people.
# absent menses in context of a normally developed 16 year old female
Since she has normal secondary sex characteristics, there are normal estrogens/gonadotropins. The cause is this likely eugonadotropic amenorrhea. Causes of eugonadotropic amenorrhea are likely to be mullerian abnormalities.
# aminoglycoside resistance
Since they inhibit the 30s ribosomal subunit, resistance is via mutation in the genes that code for ribosomes and produce altered structure ribosomes.
# why do calcium channel blockers not affect skeletal muscle??
Skeletal muscle does NOT require influx of extracellular calcium for excitation-contration coupling, but cardiac and smooth do. Skeletal mucle EC coupling starts when depolarization triggers opening of L-type calcium channels *within the T-tubules*. This opens RyR1 challens within SR to release intracellular calcium, to bind to *troponin C*. !!! In cariac muscle, depolarization causes L-type calcium *on plasma membrane* to open and influx extracellular calcium. This then binds and activates sarcoplasmic RyR2 channels.... And then acts similar to skeletal muscle (t tubules, etc) In smooth muscle, calcium enters cell from ECF trhough voltage gated L-type channels, and releases SR. Calcium then minds to calmodulin...
b2 receptors
Skeletal muscle, bronchi, uterus • vasodilation • bronchodilation • *relaxation of uterus* (!!!) • Increase lipolysis (but somehow increase insulin, wtf ?! )
# Marfan syndrome affects which systems?
Skeleton: tall, thin, long slender fingers, scoliosis Ocular: Ectopia lentis (lens dislocation... upward dislocation) Cardiovascular: Dilation of ascending aorta leading to aortic regurg, aortic dissection, mitral valve prolapse (MVP) Pulmonary: ↑ risk for spontaneous pneumothorax
# Meningitis
Skull attached to the *dura matter*.. Arachnoid matter is 2nd layer, the *pia matter* covers the brain. "PAD between brain and skull) The *dura matter* is the thick and "durable" layer. The *arachnoid matter* and *pia* matter are collectively called the *leptomeninges*. BOTH of these are thin. Meningitis is inflammation of the *leptomeninges*. Meningitis is usually due to *infection*
# what are the ways to treat insomnia ?
Sleep hygiene Stimulus control Relaxation Sleep restriction
Acetylation and SLE
Slow acetylators develop lupus more often .
Neutrophil activation
Slow rollins allows the leucocytes to *activate integrins* and induce a chemical change in their structure.
Argyll Robertson pupils
Small, irregular shape pupils that do NOT react to light, but do constrict with accommodation. highly specific for neurosyphillis!!!!
# Airway remodeling in asthma (!!!)
Smooth muscle hypertrophy is considered one of the common reactive changes associated with asthma. Submucosal gland hypertrophy → mucous plugging (!!!) Sub-basement membrane fibrosis as a result of collagen deposition ↑ vascularity Inflammatory infiltration most commonly with eosinophils
# caseous necrosis
Soft, friable necrotic tissue with *'cottage cheese' like appearance*. - occurs in *tuberculous granulomas and fungal granulomas.*!!!!!!!! - shares features of both coagulation and liquefaction necrosis. (think of "liquefactive necrosis with something mixed in"). Ie, infection created liquefactive necrosis, but 'soup' is 'thickened' by *fungal infection, or microbacteria (ie, TB)* Surrounded by *macrophages * other cells *forming a granuloma* !!!!!!
#Somatoform disorders
Somatoform disorders have physical symptoms that cause emotional distress without an organic cause ... .unlike facitious and malingering there is *NO attempt to deceive.* • Both illness production and motivation are unconscious drives. In other words, the patient does *NOT knowingly or purposefully produce their symptoms.* • More common in women.
# How long does it take a vasectomy to work?
Sometimes up to around 20 ejaculations and 3 months. *visible sperm* are still seen.
general anaesthetic liver complications (!!!)
Sometimes, inhaled halogenated anaesthetics (halothane, enflueane) can cause severe liver damage and *fulmanent hepatic failue* as it is metabolized there. Causes massive hepatic necrosis, liver tenderness, increased ALT, AST, bilirubin. !! There is a PROLONGED PT !!! NOTE: Most of the S:Sx of liver failure (decreased albumin, ascites, palmar erythema, gyno) are due to CHRONIC liver failure!! They are NOT seen in acute!
# adenomyosis
Special name for endometriosis (endometrial glands and stroma) in the myometrium !!! • Presents with menorrhagia, dysmenorrhea • Symmetrically enlarged, soft "boggy" uterus on bimanual exam that IS ENLARGED!!!!! (unlike endometriosis) • Diagnose with biopsy. Definitive treatment with hysterectomy
#sulfonylurea sides
Special notes: Glyburide dose must be decreased with renal failure. Glipizide must be reduced with hepatic failure. Also, care must be taken to prevent overadministration and subsequent *hypoglycemia*!!!!! Early generations can cuase disulfiram-like reactions (flushing, tachycardia, nausea, hyperventilation)!!! (especially with alcohol!!).
# heart failure diuretic treatment
Spironolactone is effective to add to standard therapy (ACEIs, digoxin, diuretic) because inhibiting aldosterone likely decreases the effects of aldosterone on ventricular remodeling and cardiac fibrosis!!!
# clostridium perfringens!!!
Spores abundant in soil. Causes gas gangrene (gas in the muscle)!!! I The main component *lecithinase splits phospholipid molecules. * It can be directly inoculated into tissue in the event of trauma to the skin or muscle. ... also causes LATE watery diarrhea!!!!
# Squamous cell carcinoma (lung)
Squamous, Smoker, Sentral. classically associated with a *central location* of origin, arising from the segmented bronchi. (Think about where smoke goes when inhaled). Squamous cell carcinoma of the lung is more common in males, arises centrally, and is strongly associated with smoking. *most common* tumor in male smokers (!!!!)
serotonin syndrome drugs
St John's Wort (Sinners and Saints!) SELlective Serotonin Reuptake Inhibitors Dextromethorphan TCAs MAO inhibitors MEperidine TRIPtans (anti-migrane medications) ONdansetron (anti-epetic) TRAMadol (analgesic) LINEzolid (antibiotic)
Stable angina
Stable angina is chest pain *precipitated by exertion* (e.g., walking uphill) where *oxygen demand exceeds oxygen supply* and is *relieved* by *rest* (decrease demand) or the administration of *nitrates* (vasodilates both arteries and more so, *veins) In the case of stable angina pectoris the decreased ability to perfuse is due to *fixed, high-grade stenosis of the coronary artery secondary to stable atherosclerotic plaque* Typically a *75% decrease (!!!)* in luminal area is necessary to cause stable angina pectoris. Note, *stable angina* leads to *reversible* injury to myocytes (*cellular swelling!!) ..... BUT Coronary artery disease (CAD) is often progressive, thus patients with stable angina pectoris often develop unstable angina and/or sustain myocardial infarction (MI).
# tumor stage vs tumor grade
Stage- how much the tumor spreads into adjacent tissues and distant organs.!!! Use TNM staging. size of primary lesion (T) spread to regional lymph nodes (N) (2nd most important prognostic factor) presence of metastases (M). (MOST important prognostic factor) Grade- degree of tumor differentiation, which indicated its malignant potential. Well differentiated (low grade) are likely to be benign, high grade (poorly differentiated, pleomorphic) are likely malignant. In CR cancer, STAGE is much more important than grade. If confined to Mucosa (stage A), prognosis is 90%+ If Muscularis (stage B), then it is around 75%. If Lymph (stage C) or mets (stage D), very poor prognosis.
# Catalae positive organisms
Staph. aureus (!) Burkholderia/pseudomonas cepacia Aspergillus (!) Nocardia (!)
# ACE inhibitor first dose hypotension
Starting a patient on a ACE inhibitor can sometimes cause severe hypotension and bradycardia. Predisposing factors include: hyponatremia, hypovolemia (!!) Low BP High renin or aldosterone. So, be VERY careful putting someone who is on a LOOP/Thiazide diuretic on an ACE inhibitor.!!!!!
Statins
Statins: In order of descending potency: rosuvastatin > atorvastatin > simvastatin > lovastatin ~ pravastatin > fluvastatin • Mechanism: inhibits HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway of cholesterol synthesis • Leads to ↑ production of LDL receptors. Increased LDL receptors on the hepatocyte increases LDL removal from blood --by receptor mediated endocytosis • LDL ↓↓ • HDL ↑ (minimal effect) • Triglycerides ↓
# malabsorption overview
Steatorrhea- (foul- smelling, bulky, floating, greasy stools with excess fat) 1. Pancreatic exocrine insufficiency 2. Intestinal mucosal defects- 3. Bacterial proliferation
# peripheral chemoreceptors
Stimulated more by HYPOXEMIA !! The aortic arch= both baroreceptors and chemoreceptors... innervated by CN X !!! carotid sinus = baro receptors carotid body = chemo receptors Carotid is innervated by CN IX !!!!!!!!!! Note: in patients with COPD, the response to CO2 is blunted!!!! Thus, O2 becomes a major factor in respiratory drive.
# Pre hepatic Jaundice , - Stool , - Urine, - bilirubin
Stool is Normal Urine is Normal but may appear brown after standing for period bilirubin unconjugated, so it does NOT appear in urine because it is NOT water soluble!!!
# Intra hepatic Jaundice , - Stool, - Urine, - bilirubin
Stool is normal Usually dark urine, but depends on how much bile flow obstruction Usually conjugated bilirubin
restless leg syndrome
Strange sensation in legs and uncontrollable urge to move them. Associated with inactivity and relieved by movement. restless leg syndrome occurs in: Middle/older age patients. Iron deficiency Chronic kidney disease Diabetes (esp neuropathy) # treat restless legs Avoid aggravating factors (ie alcohol, sleep deprivation) Supportive measures (exercise, leg massage, heating pads) Dopamine agonists (!!)
# Encapsulated bacteria with polysaccharide capsule!!! -
Streptococcus pneumoniae - haemophilus influenzae - Neisseria meningitides - Salmonella typhi. - E. Coli Their polysaccharide capsule can be used as vaccine antigens!!!!!!
stress incontinence
Stress incontinence is caused by a failure of the urethral sphincter to remain closed when there is a transient increase in intra-abdominal pressure. Patients with stress incontinence present with voiding in the presence of increased in intra-abdominal pressure (e.g., laughing, coughing, sneezing). Stress incontinence in women is most commonly due to insufficient strength of the pelvic floor muscles after childbirth or surgery. Stress incontinence in men is most commonly due to complications from prostate surgery. The first-line treatment for women with stress incontinence is bladder training and pelvic muscle exercise (Kegel exercises). • Kegel exercises strengthen the pubococcygeus muscle, which forms the floor of the pelvic cavity. Stress incontinence is treated medically with α-adrenergic agonists, which act to contract smooth muscle at the bladder neck, thereby increasing internal sphincter tone.
Granulocytes
Subclass of leukocytes; includes: basophils, neutrophils, and eosinophils
#complete mole presentation (!!!)
Suggested by new-onset hypertension and proteinuria BEFORE 20 weeks gestation (basically, preeclampsia before 20 weeks in likely a complete mole. Also vaginal bleeding enlarged uterus "size greater than date" hyperemesis hyper-thyroid risk of pre-eclampsia
# what nerve is at risk in thyroidectomy?
Superior laryngeal nerve- innervates cricothyroid !!
# surfactant composition
Surfactant production by *type II pneumocytes* is *greatly increased after the 35th gestational week* (but begins around 26 weeks).... thus the inverse correlation between NRDS and gestational age. Surfactant consists *primarily of lecithin, aka phosphatidylcholine.*... A *lecithin:sphingomyelin ratio of >2.0* in the amniotic fluid indicates fetal lung maturity. If the ratio is less than 2:1 in amnionic fluid, prophylactically treat mother with glucocorticoids. Can ALSO be assessed by foam stability index
IVC obstruction
Suspect in any patient with new, unexplained and severe lower extremity edema in the absence of an explanation for it (RHF, severe hepatic cirrhosis, nephrotic syndrome). Can occur with renal tumor !!
RA involves which joints:
Symmetric involvement of *PIP* joints of the fingers, wrists, elbows, knees. .... This usually is *worse in the morning* but improves throughout the day. • Note: the *DIP is spared* !!! (note: OA spares MCP) Ulnar deviation of the fingers • Boutonniere deformity: flexion of PIP joint, extension of DIP joint • Swan neck deformity: extension of PIP joint, flexion of DIP joint • "Z-thumb" deformity: thumb with fixed flexion and subluxation at the MCP joint, hyperextension of IP joint
Mnemonic for G-protein couples receptors
Sympathetic- a1, a2, b1, b2 ....."qiss" Parasympathetic- M1, M2, M3..... "qiq" Dopamine- D1, D2... "si" Histamine H1, H2...... "qs" Vasopressin V1, V2.... "qs"
# Temporal aka Giant Cell Arteritis S:sx
Symptoms of giant cell arteritis include: - temporal headache (unilateral headache) - jaw claudication which *occurs with eating*, giving *difficulty eating/chewing!!!!* - blindness in the *ipsilateral eye* due to ophthalmic artery vasculitis. (!!!) Giant cell arteritis is commonly associated with *polymyalgia rheumatica* (!!!!!) which is characterized by *flu like symptoms with muscle and joint pain*, and *normal serum creatine kinase* !!! A common laboratory finding in giant cell arteritis includes an *increased ESR* >100 and is used as a screening test. (!!!!) Treatment of giant cell arteritis is a *medical emergency* that consists of corticosteroids ASAP!! (high risk of blindness without treatment)
carcinoid syndrome
Symptoms that occur secondary to carcinoid neuroendocrine cells/tumors: - Flushing of skin - Secretory (watery, voluminous) diarrhea -Abdominal cramps with nausea and vomiting - Bronchoconstriction and/or bronchospasm → wheezing Hepatic vein brings serotonin into the *right heart* , which causes *carcinoid right heart disease*, due to fibrosis b/c of *collagen deposition* of valves, leading to: (!!!!!!!!) - tricuspid insufficiency/regurge or - pulmonic valve stenosis (TIPS)!!!!! Note, it does *NOT affect left side of heart b/c *lungs have some MAO* !!!!
# classic galactosemia presentation
Symptoms: vomiting, lethargy, poor growth, hepatic dysfunction (jaundice, coagulopathy, hepatomegaly), ascites, cataracts, mental retardation..... begins SOON after breastfeeding! These infants also have an ↑ risk for E. coli septicemia . • Treatment: galactose-free diet (avoid milk)!!!!!!!
#Necrotizing enterocolitis (NEC)
Syndrome of intestinal necrosis due to bacteria proliferating in an immature digestive/immune system, causing *ischemic necrosis of the terminal ileum/colon*. • *NEC is often seen in premature, formula-fed infants with immature immune/GI systems. * • Newborns with NEC can present with *abdominal distention/tenderness and rectal bleeding (hematochezia). * • Diagnosis is made via clinical symptoms along with *abdominal radiograph showing pneumatosis intestinalis (presence of gas in the bowel wall). * Risk factors: prematurity, birth weight < 1500g (gut immaturity!!) • Majority of infants who develop NEC are feeding well, healthy .... who then develop feeding intolerance !!! • Usually involves colon but can also involve entire GI tract As the disease progresses, the bowel becomes congested and gangrenous with the formation of *intramural gas collections*.
# acitrentin
Synthetic rerinoid used to treat psoriasis. ALL retinoids (vitamin A) are teratogenic!!!
#congenital syphilis
Syphilis is the 'S' in "ToRCHeS", Initially following birth, congenital syphilis may manifest as: 1) persistent rhinitis — clear rhinorrhea 2) lesions on palms and/or soles 3) hepatosplenomegaly, jaundice 4) hemolytic anemia, thrombocytopenia Features which manifest later (after the age of 2 years) in the course of congenital syphilis include: 1) Interstitial keratitis (a serious condition in which blood vessels grow into the cornea. Such growth can cause loss of the normal clearness of the cornea.) 2) Deafness, CN 8 damage 3) Frontal bossing 4) Hutchinson teeth, Mulberry molars 5) Perioral fissures, high-arched palate 6) Saddle nose 7) Saber shins
# Sarcoidosis
Systemic disease chatracterized by *noncaseating granulomas* in *multiple organs*, most notably the *lungs*,but also *bilateral hilar lymph nodes* (!!!!) but also effects skin and eyes (uveitis) commonly. !!!!!! Non-caseating granulomas LACK necrosis, but have epithelioid cells (activated macrophages) and multinucleated giant cells. !! Sarcoidosis is most common in young African American females. Patients commonly present with: - non-productive cough dyspnea chest pain fever skin involvement anorexia, arthralgias, blurry vision. Physical exam may show wheezing or crackles upon auscultation.
systemic mastocytosis
Systemic mastocytosis, often termed systemic mast cell disease (SMCD), is a myeloproliferative neoplasm characterized by infiltration of clonally derived mast cells in different tissues, including bone marrow (see the image below), skin, the gastrointestinal tract, the liver, and the spleen. The mast cells secrete excess histamine. Histamine in turn, causes gastric hypersecretion. Because gastric acid secretion increases, *this inactivates pancreatic and intestinal enzymes, causing diarrhea. * Often also presents with histamine mediated symptoms: syncope flushing hypotension, tcycardia Skin manifestations (pruitis, urticarial)
# Scleroderma
Systemic sclerosis (scleroderma) is a chronic disease with likely autoimmune etiology characterized by: 1. Widespread microvascular damage 2. Excessive interstitial and perivascular *collagen deposition* (fibrosis/sclerosis)!! Ischemia secondary to vasculitis of small arteries and cutaneous arterioles may cause cutaneous ulceration in the fingers/toes. Most common initial finding in systemic sclerosis is *Raynaud's phenomenon secondary to digital vasculitis.* Most common visceral complication of systemic sclerosis is esophageal dysmotility/reflux. There are two types of systemic sclerosis: - Diffuse - Limited/localized (CREST)
# Secondary amyloidosis
Systemis deposition of AA amyloid derived from SAA, an acute phase reactant, which is increased in chronic inflammatory states (autoimmune diseases, lupus, RA, Crohns, UC, chronic osteo myelitis) Also happens in malignancy, which leads to a chronic inflammatory state.... as well as Familial Mediterranean Fever.
# Calculate half life!!
T1/2= (Volume distribution X 0.7) / Clearance
Parkinsons disease features
TRAPES - *pill rolling tremor* at rest, which disappears with movement - rigidity (cogwheel) - Akinesia/bradykinesia - Postural instability - Expressionless - Shuffling gait
Aortic dissection.
Tear of *intima* leads to blood going through intima into *media*, forming a false/second lumen, and 'ripping across' the media of the aortic wall ... so it is an unstable media hematoma!!! REQUIRES 2 things: 1) a ton of stress, it usually occurs in proximal 10cm of aorta (pressure is very high) 2) MUST have pre-existing *weakness of the media* (most common cause of this is HTN) , or also inherited defects of connective tissue.
# Subacute DeQuervain granulomatous thyroiditis:!!!!!
Tender thyroid (!!!); in fact, subacute granulomatous thyroiditis is the most common cause of thyroid pain. However, unlike acute thyroiditis, there is NO lymphadenopathy. There is *reduced radioactive iodine uptake*. Preceded by flu-like illness with sore throat and fever, jaw pain, tender thyroid, and a markedly elevated ESR (erythrocyte sedimentation rate).!!!!!!!!!!! Causes can include mumps or coxsackievirus (viral). Histology: - lymphocytic infiltrate, - multinucleate giant cells surrounding fragments of colloid!!!!!!! (!!!) Early phase can manifest as hyperthyroidism, as damaged gland spills T4 (!!).... This *causes symptoms of thyrotoxicosis*. !!! After time, it MAY OR MAY NOT progresses to a state of hypothyroidism, but it *usually resolves after weeks* Treatment: aspirin, in severe disease can supplement with cortisol
# treat tinea
Terbinafine- acts by inhibiting the enzyme SQUALENE EPOXIDASE which in turn inhibits synthesis of fungal membrane ergosterol.
#tertiary syphilis and thoracic aortic aneurysm (!!!)
Tertiary syphilis causes *endarteritis* of the *vasa vasorum* of the ascending and transverse portions of the aortic arch, which generates luminal narrowing, decreased flow, and atrophy of the vessel wall, thus *weakening* it. (!!!!!!!!!!!) On gross examination the aorta has a *"tree bark" appearance*, due to scarring/fibrosis from the *endarteritis*.
anabolic steroids and acne
Test to DHT promotes both: 1) Follicular epidermal hyperproliferation 2) excessive sebum production
# what cells produce internal/external male genitals?
Testosterone promotes internal genitalia. (leydig cells). DHT produces external genitalia!!! (5AR deficiency thus has female genitalia at birth that masculinizes during puberty!!!) Sertoli cells produce Mullerian-inhibiting factor which prevents female internal genitalia.
what part of the brain is implicated in panic attacks ?
The *locus ceruleus* . It contains the enzyme dopamine B-hydroxylase which converts dopamine into NE.
# α-glucosidase inhibitors
The 2 commonly used medications include Acarbose and Miglitol. (!!!) Mechanism: Prevents DISACCHARIDES in the gut from their final degradation into monosaccharide by *brush border ENZYME inhibition prior to absorption.* !!! In other words, it simulates DISACCHARIDE deficiency (e.g. lactose intolerance), causing osmotic diarrhea and presenting more sugars to the colonic flora, which digests them, releasing gas and causing flatulence and is thus poorly tolerated by patients. Contraindicated in conditions of liver problems.
# Factor V "Leiden mutation (!!!)
The Leiden mutation is a mutation in the Factor V gene which causes* Arg → Gln (glutamine) substitution*, which *makes factor V resistant to cleavage by protein C (and maybe S*).... leads to *inability to shut off factor V, increased activity of it*, and hypercoaguable state. Heterozygotes have a 5x higher risk of venous thrombosis compared to 50x higher risk seen in homozygotes.!!!! increased likelihood of thrombosis, especially in unusual locations (mesenteric veins).... Also *repeated bouts of thrombosis. *
#cavernous hemangioma
The MOST common benign liver tumor. They consist of cavernous blood-filled bascular spaces lined by a single epithelial layer. • Associated with Von Hippel Lindau disease: hemangioblastomas, renal cell carcinoma, adenomas
# essential tremor
The MOST commonly diagnosed movement disorder. It is often AD inherited. It WORSENS when a posture is being maintained, ie, holding a cup of tea. Symptoms actually improve with alcohol.
#androgen insensitivity genitals
The SRY gene is present due to the presence of a Y chromosome, and it will produce Anti-Mullerian hormone (AMH) which leads to regression of Mullerian structures, so there is NO internal female genitals. Also, because testosterone and viable testosterone receptors are required to maintain the Wolffian structures, those structures will not develop in these individuals. This is because although testosterone is present, it cannot stimulate the androgen receptors. Likewise, there will not be the effect of DHT, which is required for external male genitalia development. Thus, the patient has female external genitalia with scant sexual hair and a rudimentary vagina; uterus and fallopian tubes are absent.
Schilling test overview
The Schilling test is done when a GI cause for *B12 deficiency* is suspected. Under normal circumstances, radioactive *B12 should be absorbed in the gut and excreted in the urine*. When there is a DEFECT IN ABSORPTION, LESS B12 is seen in the urine. 1. Schilling test part 1 "patient is given an oral dose of radiolabeled B12 followed by an intramuscular injection of nonradiolabeled B12 Normal test (>10%) means that there is normal absorption, and the problem is dietary deficiency of cobalamin (B12). !!! (means the body can handle it, they just aren't eating it). - positive if LOW URINE LEVELS < 5-10% of the radiolabeled B12 is detected in urine after 24 hours (indicates pernicious anemia OR malabsorption)!!!! 2. Schilling test part 2 (perform if part 1 is positive) "give ORAL INTRINSIC FACTOR + labeled B12, followed by IM injection of nonlabeled B12. - If urine B12 ↑ then it's pernicious anemia, caused by lack of IF. !! - . (if urine B12 still remains low), it's malabsorption (e.g. Crohn's disease, the fish tapeworm Diphyllobothrium latum)
# cyclin D-CDK4/6 complex ((!!!!)
The activated Cyclin D-CDK-64 complex *phosphorylates Rb tumor suppressor gene. * *hyper-Phosphorylated Rb IS INACTIVE*...... RB then *releases E2F transcription factor.* Summary: *Phosphoylation Inactivates Rb* (which activates cell cycle)!!! *Hypo-phosphorylated Rb is ACTIVE* which *holds E2F*, and thus HALTS cell cycle! E2F activates its target genes, including Cyclin D and other Cyclins (E and A), which are needed for progression of the cell cycle!!!!
sulfasalazine
The active component of sulfasalazine is 5-aminosalicylic acid (5-ASA). 5-ASA is thought to modulate local chemical mediators of the inflammatory response, especially leukotrienes!!!! It is thought to be a free radical scavenger or an inhibitor of tumor necrosis factor. • Sulfasalazine is used to treat some of the following conditions: o Juvenile rheumatoid arthritis o Rheumatoid arthritis o Ulcerative colitis o Crohn disease Toxicity: • Anorexia, nausea, vomiting • Sulfa toxicity (porphyria, Stevens Johnson syndrome, kidney failure, kernicterus) • Oligospermia (reversible)
Kluver-Bucy syndrome
The amygdala are part of the limbic system and bilateral lesions (*HSV-1 encephalitis, trauma) *can lead to Kluver-Bucy syndrome with the following symptoms: • Mnemonic: "*HIP HIP":* • Hyperphagia • *Increased oral exploratory behavior (putting everything in mouth)* • Placidity (no aggression) • Hypersexuality • Impaired memory (Anterograde Amnesia) • Psychic Blindness/Visual Agnosia (inability to recognize familiar objects/people)
#types of monozygotic twins
The chorion is set at day 3 !! 1) If cleavage occurs at day 1-3 as a Morula, BEFORE the chorion formed, each twin will have: - their own chorion (dichorionic) and therefore each will have its - own placenta and amniotic sac (diamniotic). 2) If cleavage occurs after day 3, the cells that have been set to become the chorion have already been formed, so there is only ONE shared chorion for both twins (monochorionic), and thus ONE placenta that is shared. Can be: A) If cleavage is day 4-8, the twins are *monochorionic diamniotic* ( one chorion, one placenta, each has its own amniotic sac). B) If cleavage is day 8-13, the twins are *monochorionic monoamniotic* (one chorion, placenta, amniotic sac that they share), C) If cleavage is day 13-15, the twins are "conjoined" with a single chorion, placenta and amniotic sac.
# Diagnose Henoch- Schonlein Purpura
The constellation of clinical findings plus blood and urine studies is part of the diagnostic workup. The gold standard for diagnosis is the kidney biopsy!! (will show mesangial deposition of IgA on immunofluorescence.) The urinalysis *will be abnormal*: the urine dip can be *positive for protein and blood*. The microscopic sediment can demonstrate red cells and red cell casts.
# diagnose CO poisoning
The diagnosis is confirmed by co-oximetry, which measures the amount of carboxyhemoglobin (!!!) Smokers can have up to 9-10 percent carboxyhemoglobin saturation chronically. Obtaining a routine arterial blood gas or a pulse oximetry is not enough to diagnose carbon monoxide poisoning: a co-oximetry needs to be ordered. Saturation levels of CO above 40% is considered to be severe exposure. Levels above 55% CO saturation can potentially be fatal.
# Meckel 2's
The five 2's: - 2 inches long 2 feet from ileocecal valve - 2% of population - first 2 years of life - 2 types of ectopic tissue - males 2x more likely
infant first breath
The foramen ovale closes as the result of: • Decreased pulmonary vasculature resistance following neonatal breathing, leading to an increase in left atrial pressure compared to the right. • Reduced blood flow and pressure in the right atrium following placental circulation occlusion. 2. The ductus arteriosus closure is mediated by elevated oxygen levels and decreased prostaglandins. 3. Ductus venosus closes within a week. Note, The foramen ovale is actually patent in 20-30% of adults.!!!!
33. Celiac morphology
The histopathologic picture is characterized by - increased numbers of intraepithelial CD8+ T lymphocytes - with intraepithelial lymphocytosis - crypt hyperplasia - marked villous atrophy (!!!!!) Damage MOSTLY in duodenum (!!!!), vs jejenum and ileum
# TB granuloma
The infection is phagocytosed by *alveolar macrophages* where they proliferate until they are activated by *Th1 lymphocyte*... INF-y and IL-2 mediated *macrophages and cytotoxic T cells* result in *walking off* of TB with *caseating granulomas* !!! .... Which consist of: - activated macrophages - epithelioid cells - Langhans multinucleated giant cells - fibroblasts that synthesize collagen
#chronic viral hepatitis findings
The key features of chronic hepatitis are lymphocytic infiltration (Contrast with the macrophages often seen in acute hepatitis.) and extensive fibrosis leading to cirrhosis.
# where is the most common hamartoma location? (!!!)
The lung, and usually presents as an incidental "coin lesion" on CXR, but must be biopsied to rule out malignancy. In the lung, it contains *hyaline cartilage*, fat, smooth muscle and respiratory epithelium. (!!!)
# HLA/MHC
The major HLA antigens are essential elements for immune function. Different classes have different functions: They function in *antigen presentation to the T-cells* and trigger *T-CELL immunity*!!!!!!
# what is the major characteristic/determinant of the atherosclerotic plaque in a MI ?
The major determinant is the RATE that it occludes the artery. A slow developing occlusion would allow *formation of collaterals* which may prevent MI because it still gives it some oxygen!!! !!! Other factors that promote myocardial necrosis include factors which lead to *decreased plaque stability*
#cardiac tamponade causes
The most common causes of cardiac tamponade include dissection of aortic aneurysm, end-stage lung cancer, heart attack, heart surgery, pericarditis caused by bacterial or viral infections, and wounds to the heart. Patients with hypothyroidism, uremia, or collagen vascular disease (e.g., lupus, rhuematoid arthritis, scleroderma) may have asymptomatic effusions since fluid build-up occurs gradually.
# important AML with cytogenic abnormality
The most important one to know is Acute Promyelocytic Leukemia (APML). The *t(15;17) translocation*n creates a fusion protein with the *retinoic acid receptor (RARα)* and the promyelocytic leukemia protein (PML). This disruption disrupts the ability of cells to mature, so promyelocytes accumulate!! Promyelocytes contain numerous *Auer rods (which are giant cytoplasmic granules* (!!!), which can *activate clotting cascade (low fibrinogen!!), thus there is a risk for DIC !! (medical emergency!) * !!!! Aurer rods stain with PEROIXIDASE!!!! Presents as easy bruising too. Treat via high doses of the Vitamin A derivative all-trans retinoic acid (ATRA)*.... which binds to the PML-RARα protein and acts as an antagonist → accelerates differentiation of promyelocytes to mature into neutrophils.!!
# allopurinol sides
The most serious adverse effect is an allopurinol hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, and worsened renal function Allopurinol is one of the drugs commonly known to cause Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis syndrome (TENS) which is an adverse drug reaction
# Annular pancreas and pancreas embryology
The pancreas forms from the DORSAL + VENTRAL pancreatic buds. The dorsal bud gives rise to the pancreatic tail, body, and most of head!! The ventral bud gives rise to some of head, the uncinated process, and the main pancreatic duct (of Wirsung)!!! In annular pancreas, abnormal migration of the *VENTRAL pancreatic bud* causes the ventral bud to cleave into two poarts, which *forms a ring encircling the descending portion of the duodenum*. This can compress the duodenum, and indants present with symptoms of upper intestinal obstruction. Developmental malformation, pancreas shifts forms ring around duodenum leading to risk of dundenal obstruction
# Tetralogy of Fallot severity
The severity of tetralogy of Fallot is dependent upon the *degree of pulmonic stenosis.* A compensatory mechanism children with tetralogy of Fallot often use involves *crouching down* or *squatting* which *increases systemic vascular resistance* (!!!!), left ventricular pressure/afterload, and *flow from left to right* through the VSD, leading to a *decrease in cyanosis* (ie, kid exercises, gets blue, crouches... it goes away). classic finding is *boot shaped heart* on X-ray (!!!!)
Sides of class III anti-arrhytmics
The side effect of ibutilide is torsades de pointes. (!!!!) • Side effects of sotalol include torsades de pointes and excessive beta blockage. (bradycardia)!!! (!!!) But *Amiodarone* is MUCH LESS likely to cause torsades de pointes!!
# hyperthyroid meds
The three classes are thioamides, anions, and radioactive isotopes.
#neuroblastoma genetics and labs
The* overexpression of N-myc oncogene* is associated with neuroblastomas!!!! Most patients with a neuroblastoma have an inherited deletion of the short arm of Chromosome 2.
# Heomchromatosis treatment (!!!!)
Therapeutic phlebotomy is a procedure that removes blood (and iron) from your body. A needle is inserted into a vein, and your blood flows through an airtight tube into a sterile container or bag. The treatment of choice is therapeutic phlebotomy once weekly initially, then once every 2-6 months indefinitely. If phlebotomy is contraindicated, *deferoxamine (a chelating agent)* is initiated. (!!!!) Remember that *deferoxamine is also the treatment of choice for iron poisoning*. (!!!)
#NMJ blocking agents
There are 2 basic classes of NMJ blockers:* non-depolarizing* and *depolarizing* agents. • Non-depolarizing agents achieve blockade by *functioning as a competitive antagonist). * Depolarizing agents *achieve blockade of the NMJ by over activation of the normal agonist pathway*. The only depolarizing agent currently used in the US is *succinylcholine.*
# Type 2 diabetes meds
There are 5 major oral antidiabetic agents, which can be remembered with the mnemonic STαB Mellitus: Sulfonylureas Thiazolidinediones α-glucosidase inhibitors Biguanides (metformin) Meglitinides.
#Tay-Sachs disease
There is *normal development the first few months of life*.... But then it presents with: -progressive neurodegeneration - developmental delay - weakness/hypotonia - an *abnormal marked startle reflex* !!!! - cherry-red spot on the macula, !!! lysosomes that appear like onion skins (whorled membranes), and there is *no hepatosplenomegaly. *!!!!!!!!!!! • Tay-Sachs Disease has a deficiency in *hexosaminidase A*. This leads to the *accumulation of GM2 gangliosides*, which is NOT converted into GM3 ganglioside. Tay-Sachs Disease is prevalent among Ashkenazi Jews. Note, although it *ALSO has cherry red macula spots*, there is NO hepatosplenomegaly. Patients develop seizures, blindness, spasticity.... And live 2-5 years.
# α1 selective antagonists: (!!!)
These drugs generally end with the suffix -osin. • Prazosin, Terazosin, Doxazosin, Tamsulosin
androgens/estrogens in bones
These hormones are responsible for increased osteoblast activity and synthesis of bone extracellular matrix and the sudden "growth spurt" that occurs during the teenage years. BUT, eventually sex hormones, especially estrogens in both sexes, shut down growth at epiphyseal (growth) plates, causing elongation of the bones to cease. Lengthwise growth of bones typically ends earlier in females than in males due to their higher levels of estrogens.
paramesonephric duct (mullerian duct) !!
They FUSE and form: uterine tubes, uterus, cervix, upper 2/3 of vagina
corticosteroids and neutrophils
They actually cause "demargination" (release from vascular walls) so there is an increase in neutrophils.
Cherry hemangiomsa aka Campbell de morgan spot.
They are SUPERFICIAL and not found on the mucosa. Light microscopty shows proliferation of capillaries and post-capillary venules.
# tension headaches
They are the MOST COMMON recurring headache. Female>male. • Key clinical features of tension headaches include: o Bilateral, non-pulsating headaches often described by patients as a "headband-like" pressing / tightening / squeezing pain around the head. o Only mildly or moderately painful (not disabling) o Not associated with nausea or vomiting o Not aggravated by routine movement (eg, climbing stairs) • Tension headahces respond well to NSAIDs. • Tension headaches are generally associated with either muscular or psychological stressors.
# Beta blockers and RAAS
They decrease everything, Renin, AT1, ATII, aldosterone. Does not affect ACE so it doesn't affect Bradykinin !!!
# osteocytes connections
They have *gap junctions* which allow exchange of nutrients and waste products.
# high oxygen affinity hemoglobin mutations
They have a left shift, decreased P50.... Thus, they have a reduced ability to release oxygen to tissues, leading to renal hypoxia, increased EPI, and compensatory erythrocytosis.
#Extrapyrimidal side effects of typical antipsychotics (!!!!!!_)
They occur due to *dopamine D2 blockade*, which removes dopamine's inhibitory ability, and allows *excess M1 cholinergic actibity* The 4 extrapyramidal symptoms (EPS) occur in 4's: 4 hours → Acute dystonia: *sudden onset sustained involuntary PAINFUL contraction*.... of neck/muscles, tongue and oculogyric crisis (forced elevation of the eyelids!!!!) treat with antihistamines or anticholinergics !!!! 4 days → Akathisia: subjective anxiety and restlessness, nervousness, causes person to be objective fidgetiness . .... *fidgeting like a cat!!!*... Akathisia: treated with propranolol (non-selective beta blocker) 4 weeks → Akinesia: Parkinsonian symptoms (masklike face, cogwheel rigidity, pill-rolling tremor 4 months → Tardive dyskinesia: choreoathetoid (writhing) involuntary movements of mouth and tongue (biting, chewing, grimacing, tounge protrusions). Acute dystonia and akinesia due to *unopposed cholinergic action:* treated with anticholinergics (benztropine or trihexyphenidyl) !!!
# b1 deficiency
Thiamine deficiency may lead to beriberi ("Ber1Ber1") and Wernicke-Korsakoff syndrome. In the United States, thiamine deficiency is most common in alcoholics (due to poor nutrition and that excess alcohol limits the body's ability to absorb and store thiamine.) ... it also caused impaired ATP breakdown and ATP depletion which is *WORSENED by glucose infusion* (!!!!) and *damages highly aerobic tissues* (brain, heart).!!! Note: when you give glucose to a b1 deficient patient you MUST include b1 aka thiamine!!!!!
# Atherosclerosis
Thickening/plaque (mostly cholesterol) of the *INTIMA* which affects blood flow.... primarily large and medium-sized *muscular* arteries are the primary sites of atherosclerosis. endothelial cell damage/dysfunction* results in increased capillary permeability, and *monocytes* and lymphocytes are recruited from blood into the intima. Platelets also bind. (!!!) Growth factors *released by monocytes and platelets (PDGF)* stimulate medial smooth muscle cells to *migrate into the intima*. This all allows LDL entry into intima where it is *oxidized* by accumulating macrophages forming *foam cells* 2. T-cells follow monocytes into the intima where they release cytokines to intensify inflammation, and the T-cell + foam cells form a *fatty streak*. 3. Plaque progression: smooth muscle cell migration from *media*, due to PDGF and produce collagen rich ECM which leads to *fibrous cap* 4. Plaque disruption: hemodynamic stress and degradation of extracellular matrix → fibrous plaque rupture → thrombus formation which can rupture.
stenosis and murmur
Think "sten-O-sis": problem with valve Opening → murmurs secondary to stenosis occur when the involved valve is opening (i.e. mitral/tricuspid value opens in diastole, thus mitral/tricuspid stenosis is a diastolic murmur!!! )
a1 antitrypsin genetics
This condition is inherited in an autosomal "co-dominant" pattern. The most common genotype is PiMM, which is normal. Both M alleles to make alpha- anti trypsin. There are varying genetic patterns of inheritance. If someone has a S or Z allele (PiMS or PiMZ.. *heterozygotes*), they will make *reduced levels* of *alpha-1 antitypsin* (only 1 M allele present) but their bodies still make enough of this protein so that they will not develop symptoms UNLESS they smoke!! (stop smoking!!) Those with PiZZ genotype are at *high risk for the development of panacinar emphysema + liver cirrhosis* because there is *no alpha 1 anti-trypsin* around to *oppose* the enzyme *elastase*. This enzyme basically destroys lung tissue..
# What enzyme performs collagen crosslinking?
This cross-linking action is catalyzed by lysyl oxidase, which requires copper as a cofactor!! . Therefore copper deficiency causes abnormal/weak collagen formation due to lack of cross-linking.
# Where does Wernicke-Korsakoff affect the brain causing memory loss?
This is due to damage of the medial dorsal nucleus of the *thalamus AND the mammillary bodies. (!!!!!)* Results in a phenomenon called "confabulation", where they are unsure of a gap in something, they fill it in with what they believe to be true!! Also anterograde amnesia. These are usually permanent! # what enzyme is diagnostic for Wernicke's encephalopathy and thiamine deficiency? An increase in *erythrocyte transketolase* levels AFTER thiamine infusion.
Common peroneal (fibular) nerve: (!!!)
This is the most commonly injured nerve in the leg due to its superficial location where it courses laterally around the neck of the fibula. Patient is unable to evert or dorsiflex foot and can't extend toes . So foot is held in inversion, plantar flexed position. Foot drop!!!! • There is also a sensory loss in the anterolateral leg and dorsal aspect of foot (!!) • Injury to common peroneal nerve presents with a drop foot • Can be caused by: - a direct blow to the lateral aspect of leg - fibula neck fracture (!!!) - cast that is too tight
# candida defense
Those with T-cell deficiency are susceptible to LOCAL candida infections such as oral thrush, cutateous, vulvovaginitis. NEUTROPHILS prevent hepatogenous spread of candida. So if patients have neutropenia (ie, HIV) they are at risk of disseminated disease Broad spectrum antibiotics suppress the normal bacterial flora and facilitate Candida overgrowth!!!! Other causes include: - contraceptives - systemic corticosteroids
#histologic features of cirrhosis
Three key histologic characteristics define cirrhosis: • Bridging fibrous septa linking portal tracts • Parenchymal nodules • Diffuse fibrosis
bromodeoxyuridine
Thymidine analog, and thymidine is used as a nucleotide for DNA synthesis. A high uptake of it in *brain tumors* means that there are a large number of cells in the S-phase, which indicates it is HIGH GRADE, and thus aggressive (poor prognosis)
lipid lowering therapy
To decrease triglycerides: use Fibrates To decrease LDL: use Statins alone or combination of Statin/Ezetimibe To increase HDL: use Niacin
Diagnose Rheumatic fever
To diagnose Rheumatic fever you must have: - evidence of recent Strep infection (eg, serology (Anti Streptolycin O titer aka ASO titer..... or anti-DNase B titer), and either: ≥ 2 major Jones criteria - or - 1 major Jones criterion and 2+ minor Jones criteria
# treat candidiasis
Topical antifundal medication- Nystatin !!!!! a polyene antifungal. It binds to ergosterol in the fungl membrane causing bores. It is administered orally (swish and swallow)!!!!!
# DNA topoisomerase I vs II
Topoisomerase I makes single stranded nicks to relieve negative supercoiling (only) Topoisomerase II induces transient breaks into both DNA strands simultaneously to relieve BOTH positive and negative supercoiling.
excretion rate
Total filtration- reabsorption Filtration= (inulin clearance) (plasma concentration) Thus: Total filtration = (inulin clearance) (plasma concentration) - (tubular reabsorption)
# metronidazole toxicity
Toxicities of metronidazole include • Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol • Metallic taste • Headache
lithium side effects
Toxicity: Ataxia, memory impairment/confusion, nausea/vomiting, course hand tremors. Can progress to ataxia, incoordination, hyperreflexia, blurred vision as it worsens..... can eventually progress to seizures/coma. General: edema, weight gain (causes hypothyroidism), - nephrogenic diabetes insipidus (causes polyuria, inability to concentrate urine), (!!!) It acts as ADH antagonist!!!! → requires monitoring of kidney function (GFR) and thyroid function (TSH levels) • Requires a close monitoring of serum levels due to narrow therapeutic range and toxic levels can cause altered mental status, convulsions, and death
# warfarin toxicity and reversal
Toxicity: initial paradoxical thrombosis, bleeding, skin/tissue necrosis Reversal: FFP (fresh frozen plasma; contains coagulation factors) vitamin K (but this takes longer).
#barbiturate treatment/toxicity
Toxicity: sedation, respiratory depression, cardiovascular depression • Treatment of toxicity: only supportive measures, there is no antagonist
# Toxoplasma
Toxoplasma gondii is an obligate, intracellular, parasitic protozoa that causes the disease toxoplasmosis. T. gondii is transmitted by *ingestion of infected undercooked meat or cat feces.* • Identification of one or more *ring-enhancing mass lesions* by brain imaging is seen!!!! !!!!!!
Respiratory cell histology layers
Trachea to a main bronchus, then segmental bronchus, then terminal bronchiole, then respiratory bronchiole, then alveoli. Ciliated cells go all the way down to the terminal portion of the respiratory bronchioles!!! (not in alveoli themselves).... Anything below this relies on *alveolar macrophages*. Goblet cells go down as far as the segmental bronchus, they are NOT found in the terminal bronchioles or below. The epithelium is initially pseudostratified ciliated columnar epithelium ..... but by the terminal bronchioles, it is ciliated simple cuboidal.
# transcortical motor aphasia
Transcortical motor aphasia occurs from *damage near Broca's area* producing a nonfluent aphasia where patients are able to comprehend and repeat words after the examiner.
# transition vs transversion mutation
Transition: Purine → Purine OR pyramidine → pyramidine Transversion: Purine → pyramidine or vice versa
# synaptophysin
Transmembrane glycoprotein found in presynaptic vesicles of: - neurons - neuroectodermal - neuroendocrine cells.
# EBV overview
Transmission: saliva ("kissing disease"), classically teens! EBV first infects epithelial cells in the oropharynx/nasopharynx and salivary tissues (giving patient sore throat!!!!!) -then disseminates in the blood and* infects CD-21 B-cells.*!!! EBV also infects the liver!!! (can cause hepatitis) Patient gets: - generalized lymphadenopathy (LAD) - Splenomegaly (speen has white pulp, and it expands... the exact area which expands is the PALS (periarterial lymphatic sheath... very dense blue looking area around vessels)!!!!!! - high white count with ATYPICAL lymphocytes!!!! (CD8+ T-cells)!!!!!!!! EBV infection of the oropharynx may predispose to oral hairy leukoplakia (!!) in susceptible patients (most commonly HIV ones): This is a nontender, adherent (i.e., non-scrapable) whitish(!!) lesion on *lateral tongue* or oral mucosa due to hyperproliferation of lingual epithelial cells The condition does not cause any other symptoms and does not require any treatment. If treatment is required, acyclovir is used
# treat beta blocker overdose (!!!!)
Treat overdose with glucagon !!!!!!!! It acts on cardiac myocytes which *increases intracellular cAMP*., which thus increases release of calcium, thus improving HR and contractivity.
#treat pheochromocytoma
Treat w/surgical excision, BUT before you do surgery, you give *phenoxybenzamine* (irreversable NON selective a-blocker) and a beta-blocker to prevent a hypertensive crisis which could occur from removal of tumor
# treat arsenic poisoning (!!!)
Treat with a chelating agebt, specifically, *dimercaprol*. It displaces arsenic ions from sulfhydryl groups of enzymes and *facilitates its excretion*.
#influenza treatment
Treatment includes *neuraminidase inhibitors* such as zanamivir and oseltamivir *( __ VIR) !!! * Neuraminisase is required for *RELEASE of the virus *from infected cells!!!!
treat nephrogenic diabetes insipidus
Treatment involves adequate hydration, hydrochlorothiazide (thiazide diuretic), indomethacin, or Amiloride (potassium sparing diuretic). Treat with hydrochlorothiazide (paradoxical, but it increases renal Na excretion, → ECF volume contraction → This decreased volume will decrease GFR, and increase proximal tubular reabsorption of water and Na. Therefore, ultimately less water and Na are lost as urine.
# Treat polycythemia vera
Treatment used to reduce red blood cell proliferation (chemotherapy), reduce hematocrit (phlebotomy), and prevent thrombosis (aspirin). Perform phlebotomy (first line treatment), hydroxyurea, or aspirin. Thrombotic complications are a major cause of morbidity and mortality
#treat closed angle glaucoma
Treatments for closed angle glaucoma include immediate laser or surgical iridotomy, in which a hole is made in the iris to reestablish the flow of aqueous humor, thereby relieving intraocular pressure.
# short acting benzos
Tri, Oxa, Alpra Triazolam Oxazolam Alprazolam
# HUS (Hemolytic Uremic Syndrome) (!!!)
Triad of: - microangiopathic hemolytic anemia (fragmented erythrocytes!!) - acute renal failure - thrombocytopenia Most common cause of renal failure in children. b/c of preceding infection with Shiga-like toxin producing- E. coli (!!!!)E. Coli O157:H7 (aka. Enterohemorrhagic E. Coli (EHEC) is usually seen in *undercooked beef !!!!!* *damages endothelial cells and forms PLATELET microthrombi * Since there are NO coagulation factors affected, only *bleeding time is increased* !!!!
# Triple therapy
Triple therapy is used in regions with low resistance rates. It includes: - a proton pump inhibitor (PPI) 2 antibiotics (clarithromycin and amoxicillin)
# Cardiac enzymes
Troponin I, Troponin T - CK- MB -myoglobin - AST
# tuberous sclerosis findings
Tuberous sclerosis findings can be remembered by using the mnemonic HAMARTOMASSS o Hamartomas in the CNS and skin o Angiofibromas of the face, with a butterfly distribution o Mitral regurgitation o Ash-leaf spots (hypopigmented and best identified with a *Wood's lamp*!!! Ash-wood!!!! ) o Rhabdomyoma of the heart o Tuberous sclerosis o Autosomal dOminant inheritance o Mental retardation (autism spectrum disorder diagnoses are common) o Angiomyolipoma of the kidney o Seizures and o Shagreen patches (papules with orange-peel consistency on the trunk) o Subungual or periungual fibromas • Cardiac rhabdomyomas may progress to heart failure. A cardiac rhabdomyoma in a young child is highly suspicious (nearly 100% specific) for tuberous sclerosis. • Angiomyolipomas of the kidney are hamartomatous lesions which can present with abdominal or flank pain and hematuria.
# glioblastoma multiforme histology
Tumor produces a *very large amount of necrosis,* and the living cells around the necrosis form an edge 'lining around it'... called *pseudopalasating necrosis* !!!
# adenocarcinoma in situ of lung (aka bronchioalveolar carcinoma)
Tumor that arises from the alveolar epithelium, it is considered a *preinvasive, malignant neoplasm*. It is characterized by *growth along the intact alveolar septa* but has NOT YET invaded vascular or stroma. Microscopic exam reveals *well differentiated, dysplastic comumnar cells* with or without *mucin*. Tumor tends to spread along the airways, called *aerogenous spread*.
# Volvulus
Twisting of bowel along its mesentary, resulting in obstruction and distribution of blood supply!! Usually happens in *sigmoid colon* (elderly) and *cecum* young) The MIDGUT twists around the SMA
# Type 2 hypersensitivity
Type 2 HSRs (type II (antibody-mediated) hypersensitivity reactions): IgM and/or IgG autoantibodies bind fixed antigens in specific tissues—ie, there are *no circulating immune complexes* !!! ∴ type 2 HSRs are usually tissue-specific instead of systemic (vs. type 3 HSRs which involve circulating immune complexes and are ∴ usually systemic)
# Myasthenia Gravis
Type 2 hypersensitvity. Auto antibodies to postsynaptic Ach receptor at NMJ, which acts like it is *competitive*..... Initially, Ach release is high so we have enough ACH to overcome the competitive inhibition.... However we soon get *myasthenic muscle weakness*.... Which means that with *repeated contractions* we get less and less Ach released (ie, 50, then 40, 30, 20, etc).... So Ach is no longer able to overcome the competitive blockage of the Antibody, and we have very fast fatigue..... with REST, Ach builds up again. The *decreased number of Ach receptors* leads to *reduction on the motor end plate potential*!!!!! Clinical features are muscle weakness that worsens with use, improves with rest.... Clasically involves the eyes, leading to *ptosis* and *diplopia* (double vision) as the most common complaint!!!! Also chewing problems (!!) Anti-cholinesterase WILL improve symptoms.
# serum sickness
Type 3 HS that occus as a reaction to NON-human proteins. Can occur following administration of *monoclonal antibodies* (rituximab, infliximab) OR non-human immunoglobins (venom) OR certain nonprotein drugs. Presents as fever, pruritic rash, and arthralgias that begin 7-14 days after exposure to an antigen. Because of the deposition of IgG of IgM, there is LESS serum C3 !!!!!!
#glycogen storage deficiency 2
Type II (Pompe's): defective lysosomal *α-1,4-glucosidase AKA acid a-glucosidase*→ enzyme is responsible for digesting glycogen → *glycogen deposits accumulate in lysosomes* • Lysosomal α-1,4-glucosidase is responsible for only ~3% of glycogenolysis, so defects *don't cause hypoglycemia * • Organs most affected are those that store glycogen (liver, heart, skeletal muscle) • Left ventricular hypertrophy leads to outflow tract obstruction and cardiac failure • Mortality in infantile form due to cardiac failure from *massive cardiomegaly *→ death before age 2 • *Mnemonic: Pompe's trashes the Pump (heart) *
#glycogen storage deficiency 4
Type IV (Andersen's): defective α-4,6-glucosidase (glycogen branching enzyme) • Inability to form branches → accumulation of long, insoluble glycogen chains → *hepatosplenomegaly and cirrhosis * • Causes infantile cirrhosis, failure to thrive and hypotonia → usually fatal
#glycogen storage deficiency 5
Type V (McArdle's): defective *skeletal muscle glycogen phosphorylase → unable to break down glycogen *→ ↑ glycogen in muscle → muscle cramps/weakness with exercise → can lead to myoglobinuria (myoglobin in urine) • Still form normal glycogen molecules • McArdle's = Muscle phosphorylase
#glycogen storage deficiency 6
Type VI (Hers'): deficient Hepatic glycogen phosphorylase* → gluconeogenesis but no glycogenolysis → fasting hypoglycemia (mild) and hepatomegaly/cirrhosis • Hers' = Hepatic phosphorylase • As with Type V (McArdle's), glycogen structure is normal • Early childhood presentation of hepatomegaly and growth retardation → hepatomegaly may improve with ↑ age
# HTN and aortic dissection
Typically middle-late aged men, with longstanding HTN. In HTN, there is hyaline arterio*lo*sclerosis of the *vasa vasorum* (which are *small vessels* in the *adventitia* which supply oxygen and nutrients to the *outer layers of the thicker vessels*). This decreases blood flow through them, and reduces smooth muscle and weakens the *media* in the aorta
# HIV associated esophagitis
USUALLY candida albicans, but NOT always.
Ulnar nerve injury
Ulnar nerve injury can be caused by: • 1) *Fracture of the medial epicondyle of the distal humerus* due to its superficial location at the elbow (as it courses posterior to the medial epicondyle) • 2) *Cubital tunnel syndrome * • 3) *Fracture of the hook of the hamate* due to its superficial location in the hand (as it passes between the hook of the hamate and the pisiform bone in a fibroosseous tunnel called Guyon's canal) • 4) *Injury during delivery* → Klumpke's palsy, caused by a lesion of the lower roots of the brachial plexus during traumatic vaginal delivery or by excessive traction of an abducted arm during delivery
# Transudate (!!!!)
Ultrafiltrate of plasma, due to increased hydrostatic pressure or decreased serum oncotic pressure. Low protein. Examples include: Nephrotic syndrome or other causes of hypoalbuminemia (decreased oncotic pressure), and congestive heart failure causing pulmonary edema (increased hydrostatic pressure !!!! ). Protein < 30 g/L Serum protein < 0.5 Specific gravity < 1.02 Serum LDH < 0.6 Pleural fluid LDH < 200 U/L
#treat chlamydia
Uncomplicated Chlamydia trachomatis infection can be easily treated with oral azithromycin and doxycycline. • Co-infection with Neisseria gonorhoeae is common, so ceftriaxone (a cephalosporin!!!) MUST also be prescribed to treat gonorrhoea. !!!!!!!!!
treat E-coli
Uncomplicated: Oral Ciprofloxacin Hospitalization: IV Ciprofloxacin
#Classical conditioning stimulus (!!)
Unconditioned stimulus: a stimulus that naturally or automatically produces a response Conditioned stimulus: a stimulus that produces a response following learning Unconditioned response: a natural reflexive behavior that does not have to be learned Conditioned response: a behavior that is learned by an association that is made between the unconditioned stimulus and the conditioned stimulus from the past Ie, 3 year old girl visits her physician for a check up.... But she begins to cry uncontrollably because she remembers previously reveiving an injection and crying uncontrollably. Unconditioned stimulus= injection unconditioned response = crying the first time conditioned stimulus= the clinic/seeing physician conditioned response= crying the second time
# Anaplastic carcinoma thyroid
Undifferentiated malignant tumor of thyroid, usually in elderly (over 65). -< 5% of overall thyroid cancer cases highly malignant cells, 'undifferentiated'/pleomorphic giant cells (!!!!!!!) It is very invasive, so it invades local structures causing recurrent laryngeal nerve palsy and horseness, stridor, dysphasia.
Unstable angina
Unstable angina pectoris is described as chest pain *increasing in severity, frequency, and duration* that *occurs at rest* or that is *not relieved* by the administration of *nitrates*. Unstable angina pectoris is also known as *crescendo angina pectoris* and *pre-infarction angina pectoris*. Unstable angina pectoris episodes are triggered by situations in which there is an *acute plaque rupture * that leads to an *acute thrombosis* with *mural (non-occlusive) thrombus* formation. The decreased ability to perfuse is due to fixed, high grade stenosis of coronary artery due to unstable atherosclerotic plaque. Typically a 90% decrease in luminal area is necessary to cause unstable angina pectoris.... but note, this injury is *still reversible*
# Diagnose duodenal ulcers
Upper GI endoscopy is the gold standard to diagnostic test for PUD. Shows ulcer with *hypertrophy of Brunner glands* (glands in duodenal wall which *produce alkaline mucus like substance*).
ureters and pelvic surgery
Ureters are at risk, especially with hysterectomies, ovarian surgeries.... and could end up causing hydronephrosis if ligated.!!!! (this presents as a distended mass and flank pain)
ureter location
Ureters cross OVER the common/external iliac and UNDER the gonadal vessels. They lie in the TRUE PELVIS where they are *anterolateral* to the internal iliac vessels.
osteoclast activity markers !!)
Urinary deoxypyridinoline is the most reliable. It is released into circulation when bone is absorbed by osteoclasts.
# treat pulmonary hypertension (!!!!!)
Use *Bosentan* which is a *competitive antagonist of endothelin receptors*. It is used for idiopathic pulmonary arterial hypertension. Endothelin is a *potent vasoconstrictor which stimulates endothelial proliferation*.
# Diagnose chronic granulomatous disease
Use 1) *Nitroblue tetrazolium (NBT)* dye reduction test. (!!!!) 2) Dihydrorhodamine (DHR) flow cytometry 1) If NADPH oxidase CAN convert O2 into O2- (superoxide), then *the dye turns blue*, which means the patient does NOT have CGD. If blue inclusions don't develop (the dye remains colorless), the test is NEGATIVE and suggests CGD 2) DHR flow cytometry assess the production of superoxide radicals by measuring the production of DHR to rhodamine, a *fluorescent green* compound. In NADPH oxidase deficiency, there is a *decreased fluorescence* and *less green color*.
# brachial plexus
Use the mnemonic "*Real Texans Drink Cold Beer*" to remember the proximal-to-distal organization of the brachial plexus: *Roots → Trunks → Divisions → Cords → Branches* • 5 Roots: ventral rami of C5, C6, C7, C8, T1 • 3 Trunks: o Superior (upper) trunk (C5, C6) o Middle trunk (C7) o Inferior (lower) trunk (C8,T1) • 6 Divisions: an anterior and posterior division for each of the 3 trunks • 3 Cords (named according to their anatomic relationship to the axillary artery): o Posterior cord → axillary nerve, radial nerve o Lateral cord → raneous nerve, part of median nerve o Medial cord → ulnar nerve, part of median nerve • 5 terminal Branches: axillary, radial, musculocutaneous, median, ulnar nerves
# Right to left shunts mnemonic
Use your hand to illustrate: 1. Truncus arteriosus (because there is one trunk) 2. Transposition of the great vessels (wrap your index finger around your middle finger) 3. Tricuspid atresia (tri = 3 ) 4. Tetralogy of fallot (using four fingers to illustrate the 4 components: a.) VSD b.) overriding aorta that overrides VSD c.) right ventricular outflow stenosis d.) RVH secondary to outflow obstruction) 5. Total Anomalous Pulmonary Venous Return (using all five fingers to recite this 5 word condition) Truncus, transposition and tetralogy (1, 2, 4) are caused by abnormal migration of neural crest cells!!!!
valproic acid
Used as anticonvulsant AND a mood stabilizer!!! Used in Mania!!! It blocks voltage gated sodium channels, and enhances GABA. Used mostly for myoclonic seizures, and tonic-clonic seizures!!!! Valproate increases the risk of neural tube defects!!!!!!!!!!!
# Rifampin use as monotherapy
Used in treatment of bacterial N. Meningitidis AND in mycobacterial infections!!!! Used mostly as prophylaxis for N.Meningitidis!!!
# acetazolamide and mountain climbers
Used prophylactically to to alleviate mountain sickness. Causes metabolic acidosis (to counteract respiratory alkalosis), which results in increased breathing, and higher levels of oxygen in the body.
# IVC filter
Used to "catch an embolism" when patients have contraindication to anticoagulation!
# Winter's formula in metabolic acidosis
Used to *evaluate respiratory compensation* in metabolic acidosis!!! If PaCO2 higher that predicted in metabolic acidosis, there is *concurrent respiratory acidosis*!!!!!!! If PaCO2 is LOWER than predicted in metabolic acidosis (and it should be low), then there is *concurrent respiry ALKALOSIS*!!!!
#lithium
Used to treat acute manic episodes, lowers suicide, prophylaxis of manic and depressive episodes in bipolar disorder, and can be used to treat SIADH (due to side effect profile of nephrogenic diabetes insipidus) Putative mechanism: alters the cellular concentration of the second messenger, inositol triphosphate (IP3) and also shown to alter neuronal sodium transport
capitation
Used under HMO insurance plans. Physicians paid a fixed amount *per enrollee* and NOT per service. They have incentives to contain costs due to a fixed budget allocated to them by the HMO. If they have many patients with chronic diseases, their costs can balloon, so they are motivated to provide more PREVENTATIVE care (ie pap smears, mammograms) They have the greatest financial risk.
# travelers diarrhea
Usually Enterotoxigenic E. Coli (ETEC). Produced heal lable and heat stable enterotoxing.
# Chronic pancreatitis
Usually due to alcohol in adults, cystic fibrosis in children (CF leads to thick secretions from pancreas and harder to drain). Recurrent acute pancreatitis leads to *irreversible destruction/fibrosis of pancreatic parenchyma*, duct flow distortions/obstructions, impaired pancreatic secretions. In later stages, destruction of the endocrine islets can also occur. Pancreatic concretions occur often in alcoholics, and are due to increased protein concentration in the pancreatic fluid. The key difference between acute and chronic pancreatitis is the irreversibility of the damage to pancreatic function in chronic pancreatitis.
# Membranous neopropathy associations
Usually idiopathic, BUT may be associated with: Infectious diseases: - Hepatitis B - Hepatitis C Autoimmune diseases: - *SLE (systemic lupus erythematosus)* (remember most SLE patients actually die from nephr*itic* syndrome, but if they develop nephr*otic* syndrome, it is *membranous nephropathy* !!!! - RA (rheumatoid arthritis) Drugs: - Penicillamine - NSAIDs Malignancies: (!!!!) - Solid tumors—eg, colon carcinoma, lung carcinoma, melanoma - Chronic lymphocytic leukemia
# alcoholic anemia
Usually megaloblastic, due to nutritional deficiency of folate, which impairs synthesis of pruines/pyramidines.
urethral trauma
Usually occur in men because their urethra is longer. Suspect with " -inability to void with a full bladder sensation - high riding boggy prostate Blood at the uretheral meatus Trauma to pelvis can result in posterior urethral injury. Anterior urethra is mostly injured during straddle injuriesl
# Vibrio cholera
V. cholerae is a *oxidase positive, gram negatrive, comma shaped bacilli*, transmitted via a fecal-oral route or from ingestion of *contaminated water, food, and shellfish*. It is common in Asia, but uncommon in the US. Is it very succeptible in *people with low stomach acid!!!!!!* (ie, long term PPI/antacid use.... or gastritis). People with normal • V. cholerae causes *non-inflammatory (no leukocytes) or watery diarrhea sometimes described as "rice water (rice=mucus)." * • • V. cholerae grows flat yellow colonies on TCBS (Thiosulfate Citrate Bile Salts Sucrose) agar.
# Vasopressin V1 vs V2
V1- is Gq.... Increases vascular smooth muscle contraction V2 is Gs.... Increases water permeability and reabsorption in the collecting tubules, release of clotting factors
# SCID labs
VERY low or absent CD3+ T cells Hypogammaglobulinemia.
#polio vaccines
Vaccines that are available include the SalK (killed) and Sabin (live attenuated) vaccines. Killed vaccine (Salk) is the only form used in the US because there is no risk for developing actual disease, as it CANNOT revert to a virulent form! The disadvantage is that it ONLY induces formation of IgG as *mostly a humoral/antibody response!!!*. The live (attenuated) vaccine (Sabin) is taken orally and better at inducing IgA (local intestinal) immunity. It induces *mainly cellular but also humoral* response!!! NOTE: Risk of vaccine-associated paralytic poliomyelitis due to revertant mutants is rare but can be problematic for immunocompromised individuals. !!!
# Vancomycin resistance
Vancomycin binds to *Dlanyl-D-alanine* in the cell wall and *prevents polymerization/formation of peptidoglycan*. Resistance occurs In *Vancomycin Resistane Enterococcus* (VRE) by *substituting of D-lactate* in place of D-alanine*... this prevents it from binding.
# volume distribution
Vd(L)= amount of drug given (mg)/ plasma concentration ECF= 14 liters usually plasma volume normally = 3L Drugs that have a low volume distribution (3-5L) usually remain in the plasma (doesn't go into ECF), they have: - large molecular weight - high binding to plasma proteins - highly charged/hydrophilic
#Serotonin norinephrine reuptake inhibitors
Venlafaxine and Duloxetine: antidepressants of the serotonin-norepinephrine reuptake inhibitor (SNRI) class → duloxetine has a greater effect on NE • Both are used to treat depression • venlafaxine is also used in generalized anxiety disorder • duloxetine can be used for diabetic peripheral neuropathy
third heart sound (S3)
Ventricular gallop which occurs AFTER S2. (Lub-dub-by!!) Heard because of *rapid filling of ventricles in diastole*. It is commonly associated with *increased left ventricular end-systolic volume* because of *left ventricular systolic failure* !!!!! Can be heard by listening at the END of expiration and lieing in the left lateral postion, with the BELL over the apex!!!
# renal oncocytomas
Very rare tumor originating from the *collecting duct* cells. Oncocytes are large, well differentiated neoplasms that contain numerous mitochondria.
# how does hep B cause damage?
Viral HBsAg and HBcAg stimulate HOST CD8+ cells to damage hepatocytes
# Vitamin E
Vitamin E: antioxidant and scavenger of free radicals that protects polyunsaturated fats and fatty acids in cell membranes from lipid peroxidation and protects LDL from oxidation...... Thus, the cells most at risk for damage with deficiency are those with a HIGH FAT content (neurons and ERYTHROCYTES). • Source: abundant in fruits, vegetables, and grains.
# contraction alkalosis
Volume loss (ie, overusing diuretic, )
# alveolar perfusion
We take in 160mmhg air, but it dissipates to like 150mmHG by the trachea. Normal alveolar pO2 is 105mmHG, which is close to midpoint between trachea (150mmHG) and venous blood (40mmHg.) A *perfusion defect* would result in a very high pO2 in the alveoli, close to what it is in the trachea. This can happen in a PE, emphysema, pulmonary fibrosis.
# Wegener granulomatosis in lower respiratory tract (!!)
Wegener granulomatosis in the lower respiratory tract produces symptoms that include hemoptysis, cough, and dyspnea and lesions that include cavitating nodular lesions.
# Wegener granulomatosis in upper respiratory tract (!)
Wegener granulomatosis in the upper respiratory tract produces symptoms that include chronic sinusitis, otitis media, and mastoiditis and lesions that include nasopharynx-saddle nose deformity and collapsed trachea.
coronary steal syndrome
What happens is that in coronary artery disease, collateral vesicles are formed which allow coronary blood flow to occluded areas. But, with a drug such as *dipyridamole* and *adenosine* which are *coronary vasodilators*, decrease flow through the collateral areas, because the ischemic areas are already maximally dilated. So there is LESS blood to ischemic areas, more blood to normal areas.
Creatinine vs GFR!!!
When GFR is normal, large decreases in GFR begin to raise creatinine, but there is a MASSIVE increase in creatinine as GFR is largely decreased!
# Vitamin A eye metaplasia
When Vit A deficient, thin squamous lining of the conjunctiva covering the When Vit A deficient, thin squamous lining of the conjunctiva covering the eye undergoes metaplasia into stratified squamous epithelium, change called keratomalacia (thickening of eye).
# Haldane effect
When deoxygenated blood enters the anveolar capillaries of the lung, the rise in pO2 increases the binding of Oxygen to hemoglobin.... This causes the RELEASE of H+ and CO2 from the hemoglobin (buffering!)
#risk of oxygen in neonatal respiratory distress !!!!
When patients given supplemental oxygen, it increases *free radical injury* risk. This gets into blood and affects *retina* (called *retrolental fibroplasia*(retinopathy of prematurity) induce VEGF and leads to abnormal proliferation of blood vessels.and can also cause blindness. Free radicals can also damage *lung* and cause *bronchopulmonary dysplasia*
# Mast cells and asthma
When re-exposed to *allergen*, there is cross linking of IgE and it *activates mast cell* when then immediately dumps *pre-formed histamine*, which causes histamine induced *vasodilation (arteriole)* and increase permeability (postcapillary venule) Mast cells THEN produce *leukotrienes* C4, D4, E4 to prepetuate inflammation by - vasoconstriction in blood vessels - increase vascular permeability - constrict smooth muscle of broncus
what is the reason large blood transfusions can cause hypocalcemia ?
Whole blood is mixed with *citrate anticoagulant*. Infused citrate can chelate the calcium, causing hypocalcemia, and paresthesias. (tingling in fingers/toes).
# hemiballism
Wild flinging of the *contralateral limb* due to *contralateral injury* in or near the *subthalmic nucleus*!!!! The damage happens most often from a *lacunar stroke* in someone with *longstanding hypetension* !!!
# treat prostate cancer
With local disease, remove prostate via *prostatectomy* In advanced disease, we give continuous *leuprolide* which is a GnRH analogue to shut down HPA and reduce LH/FSH/androgens Or give Androgen receptor inhibitor *flutamide*
treat primary syphilis
With penicillins, which are structural analogs of D-Ala-D-Ala !!!!!!!!
PE and DVT and blood gasses
With risk factors for DVT like prolonged immobility and advancing age, a PE is suspected with things like swollen calf, acute dyspnea. PE causes hypoxemia secondary to a VENTILATION PERFUSION (V/Q) mismatch (redistribution of pulmonary flow). *Hypoxemia* leads to *hyperventilation* and *respiratory ALKALOSIS*!!!! PaO2 will be low PaCO2 will be low (hyperventilation) pH will be high (respiratory alkalosis from hyperventilation)
opioid withdrawl
Withdrawal: - insomnia, yawning - piloerection ("cold turkey"), sweating, - dilated pupils (!!!!!) - *prominent lacrimation* !!!! - "flu-like" symptoms: fever, rhinorrhea, nausea, stomach cramps, diarrhea - anorexia *yawning and lacrimation* are specific for opioid withdrawl !!!!!
#PCP withdrawl and treatment
Withdrawal: recurrence of intoxication symptoms can happen again due to reabsorption of PCP in the duodenum that was previously trapped in the acidic gastric lumen..... sudden onset of severe, random homicidal violence. Depression, anxiety, irritability.... Treat with benzos and rapid acting anti-psychotics to calm them.
total myocardia ischemia
Within seconds, there is transition from aerobic to anaerobic glycolysis. Total ATP levels are fairly normal during the first few minites initially, but within 60 seconds, ATP is rapidly depleted from areas with a *high metabolic demand* (contraction fibers, electrocyte transport pumps). This results in *loss of contractibility within a minute*. IRREVERSIBLE injury occurs after around 30 mins.
#beta blocker drug selectivity (!!!!)
Words that starts with: A-M = Selective (Beta-1 only) N-Z = Non-Selective (Beta-1 and Beta-2) carvedilol and labetalol are exceptions to the A-M, N-Z mnemonic bc they don't have typical -olol suffix !!!!
# cytokine receptor defects SCID
X-linked recessive ....(γ-chain of cytokine receptors → defective signaling of IL-2, IL-4, IL-7, IL-15, and others (.... First Aid says *IL-2R gamma is most common*, but the same gamma chain is used in others)
# fetal erythropoiesis location
Yolk sac (3-8 weeks) During yolk sac fetal hematopoiesis, the hemoglobin formed is embryonic hemoglobin, subunits ζ2ε2. Liver ( 6 weeks-birth) Spleen (10-28 weeks) Bone Marrow (18 weeks - adult)
# Zollinger Ellison syndrome
ZES is caused by gastrin-secreting tumors of (gastrinoma) that are most commonly found in the pancreas OR the small intestine near pancreas (eg, duodenum). The cells that secrete it are actually usually *islet of Langerhans* cells. This excess gastrin leads to excess production of HCl → treatment resistant (!!), recurrent peptic ulcers, duodenal ulcers, maybe jejunum ulcers, chronic watery diarrhea, steatorrhea, vomiting.... Patient worsens with food!! Association with MEN I
metalloproteinases
ZINC containing enzymes that degrade the extracellular matrix. They participate in normal tissue remodeling and tumor invasion through the basement membrane and connective tissues.
# Anti-leukotrienes
Zileuton blocks conversion of arachidonic acid to leukotrienes by inhibiting 5-lipoxygenase (LOX) resulting in decreased production of all leukotrienes. Zafirlukast and Montelukast block leukotriene receptors. (LTD4 (leukotriene) receptor antagonists) • Have a slow onset and are usually used prophylactically for bronchospasm due to exercise, antigen exposure and aspirin.
# What other mineral is needed for strong collagen?
Zinc deficiency- needed for collagenase!!
# pilocytic astrocytoma
a *benign* tumor of astrocytes. *The most common benign AND overall CNS tumor in children*.... Usually arises in the *cerebellum* so it affects balance. (most tumors in children are *beneath the tentorium* !!)!! Presents on imaging as a *cystic lesion*, so think Pilocytic = "pylo-cystic" . They are comprised of *spindle cells with hair-like glial cells associated with microcycts. * Biopsy shows *astrocytes* with *rosenthall fibers* (eosinophilic corkscrew fibers) ..... tumor is also GFAP positive (since astrocytes are glial cells) !!!!
# glioblastoma multiforme
a *malignant, high grade tumor of astrocytes*.... Most common *Malignant* primary brain tumor in adults. Tumor usually arises in the *cerebral hemispheres* and it usually (but NOT always) *crosses the midline corpus callosum* creating a bilateral, symmetrical lesion!!!!!! ("butterfly glioma") Because this tumor is derived from a glial cell, the intermediate filament is GFAP!!! (GFAP= intermediate filament in glial cells).... (Glial fibrillary acidic protein)!!! Very bad prognosis, most patients die within a year.
# Mitral valve prolapse murmur
a *midsystolic* *click* and a mid-to-late systolic murmur is heard.... The murmur DECREASES with squatting.
CMV
a HERPES virus. Most humans are exposed to CMV in their lifetime, but typically only individuals with weakened immune systems become ill from CMV infection. *(immunocompetent may occasionally develop mononucleosis that is monospot negative!!!)*!!! However, serious CMV infections can occur in people with weakened immune systems due to AIDS, organ transplants, bone marrow transplant, chemotherapy, or medicines that suppress the immune system. Common CMV infections affect the *GI tract* •CMV esophagitis (infection of the esophagus) •CMV gastroenteritis (infection of the stomach or intestines... shows multiple erosions/ulcerations!!!!) •CMV retinitis (infection of the eye) •CMV pneumonia (infection of the lung) Histology shows a *MASSIVE OWL EYE* (Giant cells with large nuclei containing centralized prominent basophilic intranuclear inclusion* surrounded by a clear/white halo ("owl's eyes").
# Telomerase
a RNA dependent DNA polymerase, it has *reverse transcriptase enzyme* with intrinsic RNA template that synthesizes *TTAGGG repeats* at the 3' end of linear DNA, in order to prevent shortening during lagging strand template DNA synthesis Very important in *STEM CELLS* !!! Stem cells have LONG TELOMERES.
# Rifampin
a bactericidal antibiotic drug of the rifamycin group. It* inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase. (!!!!!)* The subsequent *absence of mRNA* decreases survival of the bacteria. It is an INDUCER of CYP450!!! "RifAMPin AMP's up"
## strawberry aka superficial hemangioma!!!
a benign and usually self-involuting tumor (swelling or growth) of the endothelial cells that line blood vessels. Commonly presents at birth, enlarge as the child enlarges, but then *often regresses during childhood*. !!!!!! Note: if you pressed on this, it *will blanche* Most often involves skin, but also the liver. (!!!)
# Etoposide
a chemotherapeutic agent used in testicular cancer and small cell lung cancer. It inhibits topoisomerase II, causing chromosomal breaks to accumulate in dividing cells, and ultimately causes cell death.
# Transposition of Great Vessels
a condition in which there is *failure of the aorticopulmonary septum* to *spiral normally* during *separation of the truncus arteriosus* !!! The result is the *aorta originates from the right ventricle* (anterior) and the *pulmonary artery originates from the left ventricle* (posterior), so the *aorta lies to the right of the pulmonary artery*!!! -Associated with *Maternal diabetes*!!! 2 independent circuits formed: RA → RV → aorta and then through systemic circuit, then back to RA!! (circle) LA→LV→ pulmonary, when then flows into LA! (circle) Only way for baby to survive is intravenous prostaglandin E to maintain patency of PDA, which allows for some mixing of arterial and venous blood. Definitive treatment of a transposition of the great vessels involves surgical correction of the transposition. Survival rate is over 90%.
# Progressive multifocal Leukoencephalopathy (!!)
a demyelination/ encephalopathy which involves the *white matter* (oligodendrocytes) at *multiple focci*. Due to *JC virus infection* (John Cunningham) of the *oligodendrocytes* The virus is latent, but is reactivated during *immunosupression* (ie, AIDS, leukemia) increased risk with Natalizumab! Presents with rapidly progressing neurologic signs leading to death
# Reye syndrome
a rare and potentially fatal syndrome seen mostly in children consisting of *mitochondrial dysfunction* . Affects the liver, brain and occasionally kidneys. Fulminant liver failure/encephalopathy in children with viral illness WHO TAKE ASPIRIN - likely mitoc damage of hepatocytes ((decreased Beta-oxidation enzymes). Reye syndrome is characterized by *microvesicular hepatic steatosis (fatty liver)* and severe progressive encephalopathy.!!!!!!!!! progression related to cerebral edema and *↑ ICP (intracranial pressure)*: -Present with hypoglycemia, nausea with vomiting. Children sleepy but do respond. stuporous (daze), seizures.... may progress to coma/death
cystine stones
a rare cause of kidney stones that occur seen in children. They are related to cystinuria. Treatment is hydration and alkalinization of the urine. They may *also form staghorn calculi.*
#omalizumab (!!!)
a recombinant humanized IgG against IgE..... (anti-IgE) Used in (uncontrolled, severed asthma) !!! Mechanism: Blocks the ability of IgE to bind to the Fc receptor on mast cells and basophils. • Over time, omalizumab leads to decreased levels of circulating IgE • Use: Approved for the treatment of allergic asthma in patients who are refractory to corticosteroids. (!!!!) Note: Because of the mechanism of this drug, it is only useful in patients who are proven to have IgE mediated sensitivity.
koliocyte
a sign of infection with human papilloma virus HPV. (!!!) Immature squamous cell with dense, irregularly staining cytoplasm.
#Pseudomembranous Colitis
a type of inflammatory colitis characterized by the *development of pseudomembranes*, frequently caused by Clostridium difficile and usually as a result of antibiotic therapy. Pseudomembranous colitis is classically it is associated with prolonged clindamycin therapy..... however Ampicillin is now becoming more of the leading cause.
#norepinephrine binding and use (!!)
a1>a2>B1 ..... used in hypotension Note: because NE has NO effect on the β2 receptor and therefore it has NO EFFECT ON SMOOTH MUSCLE and cannot elicit the bronchodilatory or vasodilatory effects of β2 receptors, NE cannot be substituted clinically for epinephrine in situations such as anaphylaxis, cardiac arrest, or emergent bronchospasm!! alpha 1 binding leads to *vasoconstriction*,
pH and stone formation
acidic pH is required for - uric acid stones - cysteine stones - calcium oxalate Calcium PHOSPHATE is inhibited in acid!!! Formed at high pH!! Struvite (magnesium ammonium phosphate) also formed at high pH!!!!
# acute adrenal insufficiency (!!!!)
acute classically arises with *Waterhouse-Friderichsen syndrome*- classically in young kids w/ *N.Meningitidis* infection !!! Leads to DIC which leads to a homorrhagic 'sack of blood' necrosis of adrenal glands, leads to acute lack of cortisol. lack of cortisol leads to hypotension.
# lactose tolerance test
administer 50g lactose and measure blood at 0, 60, 120 minutes. If blood glucose increases <20mg/dL and sysptoms occur, lactose intolerance is confirmed. Also there is: Increased stool osmotic gap - increases breath hydrogen - decreased stool pH
Treatment for TCA overdose: (!!)
administration of IV sodium bicarbonate has been shown to be effective for treating metabolic acidosis and cardiovascular complications (narrows QRS complex) !!!!!
# pathoma causes of deaths
adults: 1) CVD 2) cancer 3) cerebrovascular children: 1) accidents 2) cancer 3) congenital
# osmotic diuretics aka Mannitol
affect the *descending limb of look of Henle*. This area is VERY permeable to water, so they act here and REDUCE the reabsorption of water. It is Often used in cases of cerebral edema and increased ICP!! Toxicity: can cause pulmonary edema!!
# Condyloma acuminata
aka *genital warts*, is a *warty neoplasm of vulvar skin*, often large. Most commonly due to HPV 6 or 11, and HPV is characterized by *koilocytic change*..... RARELY progresses to carcinoma, but in rare cases it can. (low risk, not zero risk)
#Hirschsprung's disease
aka Congenital ganglionic megacolon. results from failure of *neural crest cells* to form the *ganglionic plexus'* in the *sigmoid colon and rectum*. It is associated with loss of peristalsis resulting in fecal retention, chronic constipation and abdominal distension. Normally, the bowel wall has Mucosa, submucosa, Muscularis propria, Serosa. Neural crest cells form both the myenteric(auerback) plexis AND the Meissner's!!! Muscularis propria has inner circular layer, outer longitudinal layer. In between then is the *Auerbach/myenteric plexus* which is "essential* for peristalsis and relaxation. Second set of ganglionic cells is called *Meissner's plexus* and it is in the *submucosa*. Helps to regulate *blood flow, secretion, etc* In *Herschsprung's*, you lack *both ganglion* in the *distal parts*... so it is lacking in the *rectum* (always rectum) and MAYBE *sigmoid colon*. (75% of time)
# low molecular weight heparin
aka Enoxaparin It functions like heparin in that it BINDS TO ANTITHROMBIN III.... but *preferentially inhibits Xa* !!!! compared to IIa (thrombin) EnoXaparin → Xa LMWH is given subcutaneously. It is used in DVT prophylaxis and in treatment of established venous thrombosis while bridging with warfarin for long term. No monitoring needed, doesn't ↑ PT, PTT, or INR Not easily reversible
# PCP
aka phencyclidine Mechanism: Works by inhibiting activation of NMDA receptors, thus, increased release of excitatory neurotransmitters. • Intoxication: Hallucinations causes belligerence, dissociativeness, withdrawl at lower doses, then progresses. impulsiveness/ violence towards others vertical & horizontal nystagmus(!!!) ataxia Note, because PCP causes violence, a MAJOR complication of it in users is TRAUMA.
# hypercoagulable state
aka thrombophilia!! balance between pro and anti-coagulant proteins is offset, may be inherited (primary) or acquired (secondary) classic presentation is recurrent DVT's or DVT's at young age, other sites include hepatic and cerebral veins examples: - lack of protein C or protein S - Also: -, factor V Leiden mutation (most common hereditary cause) - lack of anti-thrombin III - anti-phospholipid syndrome -mutant prothrombin - elevated homocysteine
# note on liver and coag factors
all coagulation factors except vWF are synthesized in the liver. Factor VIII is synthesized in sinusoidal endothelial cells and Kupffer cells of the liver as well as tubular epithelial cells in the kidney. Recent research shows that FVIII is actually increased in cirrhosis.
Neonatal respiratory distress
also known as *hyaline membrane disease* is the most common cause of respiratory distress in the newborn. The incidence of NRDS is *inversely proportional to gestational age*. Infants born *<28 weeks* have a 60% likelihood of development. NRDS is due to a *deficiency of pulmonary surfactant* from *type 2 pneumocytes* most commonly stemming from immaturity of the neonatal lungs. A deficiency in surfactant causes *↑ surface tension* in the alveoli and *wide scale atelectasis and decreased lung compliance* with each successive breath. Progressive atelectasis and decreased compliance → *protein-rich exudate* in alveoli, necrotic debris, and the formation of hyaline membranes, which can be found from the respiratory bronchioles to the alveoli.
# Takayasu arteritis
also known as *pulseless disease* is a *granulomatous large vessel vasculitis* involving *aortic arch vessels*. Takayasu arteritis occurs most often in *young Asian women and children* (ie, less than 40). it is basically the same as Giant Cell arteritis, just different location, and affects different groups of people.
# Antiphospholipid antibody syndrome
also known as lupus anticoagulant syndrome) is a commonly tested acquired thrombophilia. (so they have antiphospholipid syndrome PLUS a hypercoaguable state). In the blood stream, *antibodies directly activate platelets and complement → hypercoagulable state* !!! Patients commonly present with a history of recurrent DVT, hepatic, cerebral thrombosis and miscarriages. (!!!!!!!) In vitro, the antibodies interfere with phospholipids (hence antiphospholipid) and inhibit coagulation → ↑ PTT. (!!!!!) Additionally, antiphospholipid antibodies can cause a false positive for syphilis. Patients require *lifelong anticoagulation* (note, even though PTT is increased!!!) This occurs with lupus, but is more commonly a *primary disorder*.
# Werdnig-Hoffmann Disease
an *AR inherited degeneration of anterior motor horn* ... this causes *lower motor neuron lesions* (flaccid weakness, muscle atrophy, fasciculations). Presents as a *floppy baby* with *negative babinski sign* Death occurs a few years after birth
# Aortic regurgitation murmur
an *early diastolic*, "blowing" decrescendo murmur best heard in the "X-area" aka *third left intercostal space* and radiating along the sternal border.
# Pyelonephritis
an *upper* UTI, (pyelo="pelvis"), so it is *infection of the kidney* 1) *Ascending infection* *Vesicoureteral reflux* means incompetent vesicoureteral orifice (b/w *ureter and bladder*) → bacteria can ascend *from the bladder through the ureter to the kidney* !!!!!!! Presents with fever- - flank pain (sensitizes nerves of kidney) - leukocytos *with* WBC casts !!!! (as infection ascents tubule, they cast in shape of the tubule)
# torsades de pointes
an ECG finding during arrhythmia, where there are prolonged QRS complezes that change in amplitude and cycle length during the attacks. It is ALWAYS associated with a prolonged QT interval (due to *decreased K+ efflux!!) which predisposes to torsades de pointes. Thus, treat with magnesium sulfate!!!!
Schizophreniform disorder
an episode of psychosis lasting between 1-6 months!!! It can be considered an "upgrade" from brief psychotic disorder after 1 month has passed. Both it and schizophrenia have at LEAST 2 of delusions, hallucinations, disorganized speech, grossly disorganized/catatonic behavior, and negative symptoms. It MUST last less than 6 months.
Celiac disease overview
an intestinal immune reaction to gluten. Gluten is digested by luminal and brush border enzymes into a 33-amino acid gliadin peptide. Gliadin is deamidated by tissue transglutaminase (tTG) and is then able to interact with HLA-DQ2 (95% of cass) or HLA-DQ8 on antigen-presenting cells and be presented to CD4+ T cells. These T cells produce cytokines that are likely to contribute to the tissue damage and characteristic mucosal histopathology. A characteristic B cell response follows: this includes production of anti-tissue transglutaminase, anti-deamidated gliadin. host factors determine whether disease develops. Among these, HLA proteins seem to be critical, since almost all people with celiac disease carry the class II HLA-DQ2 or HLA-DQ8 alleles. However, the HLA locus accounts for less than half of the genetic component of celiac disease. Other genetic contributors are not fully defined.
# Candida
an opportunistic dimorphic fungus that grows as* budding yeast cells, pseudohyphae, true hyphae, or spores.* • *A positive germ tube test is strongly indicative of C. albicans*. • For most dimorphic fungi, the mnemonic "mold = cold, yeast = heat" applies. C. albicans is unusual because* the mold form grows at 37°C* while the yeast form (pseudohyphae and budding yeasts) predominates at 20°C.
# rituximab (!!!)
anti-CD20 antibody binds CD20 antigen on the surface of B-cells, targeting them for destruction via complement fixation and ADCC (antibody-dependent cell-mediated cytotoxicity) Used in RA, follicular lymphoma !!
pernicious anemia leads to what kind of anemia
anti-IF (intrinsic factor) antibodies bind and thereby prevent IF (produced by parietal cells lining the stomach) from binding with vitamin B12 . Increased levels of gastrin. Decreased levels of gastric acid, secretin, intrinsic factor
Caput medusa
appearance of distended and engorged *paraumbilical veins*, which are seen radiating from the umbilicus across the abdomen to join systemic veins.
Silicosis nodules (!!)
appears as tiny *pale nodules* commonly seen in the upper zones of the lung., as the disease progresses, the nodules turn into *hard collagen-dense *eggshell* scars*. !!!! Microscopically, silicosis is characterized by regions of calcification. *Silica filled macrophages* travel to regional lymph nodes → *fibrosis with eggshell calcification*. (seen on CXR) !!
#negative symptoms schizophrenia
are "subtracted" from a normal person's behavior. They include: • Flattening of affect • Thought blocking (sudden halt in train of thought) • Deficiencies in speech content • Cognitive disturbances • Poor grooming • Lack of motivation • Social withdrawal • Negative symptoms are more treatment-resistant. Additionally, atypical antipsychotics are better suited to treat negative symptoms.
Asbestosis pathophysiology and lung findings
asbestos fibers enter tissue from the airways → *macrophages* attempt phagocytosis. 1. *thickening/Calcification of the pleura* as well as the *domes of the diaphragm* can occur, forming white, calcified "pleural plaques" 2. *Asbestos bodies* are seen on histopathology: asbestos fibers that become coated with an *iron containing* proteinaceous material. Other inorganic materials that becomes coated with the iron-protein substrate are known as *ferruginous bodies*!!!! !! They appear as golden colored rods that have become coated with *ferruginous* (iron rich) protein rich material during the attempted phagocytosis by tissue macrophages.
# fat embolus
associated with bone fractures (long especially) or soft tissue damage (ie, liposuction).... it releases fat into blood stream which then *occludes pulmonary microvessels*... Classic finding is dyspnea (lodged in lung) AND *petechiae on skin overlying the chest* !!!! . They stain with *osmium tetroxide* which turns it black !!!!
# aspirin and gout
at high doses (>3g a day) it prevents tubular resorption of uric acid but at lower doses it competes with uric acid for excretion, so it is contraindicated in gout patients
#projection
attributing an unacceptable internal impulse to an external source. Associated with paranoid symptoms. ie, man who WANTS TO cheat on his wife accuses her of cheating on him. Ie, is angry at his parents for getting a divorce, but he denies this and says he "senses they are mad at him".
# xeroderma pigmentosum
auto recessive *defects in DNA excision repair pathway* where there is a *defective absence of UV-specific endonuclease*. !!!!!! cannot repair pyramidine(thymine) dimers. death can occur by melanoma & squamous cell carcinoma.... Major risk factor in skin cancers
# Galactokinase deficiency:
autosomal recessive *deficiency in galactokinase* which phosphorylates galactose to make galactose-1-phosphate • Accumulation of galactose → galactosemia (blood)→ galactosuria (urine) • Galactosemia → *cataracts (especially in infants) !!!!!!!!!* because the lens of the eye contains aldose reductase, which converts galactose to galactitol, an osmotically active alcohol. It is a *mild condition*
# Glanzmann thrombasthenia (!!!!)
autosomal recessive GPIIb-IIIa deficiency, so neighboring platelets can't form fibrinogen bridges to each other. (platelet AGGREGATION doesn't occur. Remember: ADP causes expression of GPIIb/IIIa, fibrinogen allows crosslinking Note the similarity between the pathogenesis of Glanzmann thrombasthenia and ITP. Ristocetin test shows normal platelet aggregation in response to ristocetin, but it DECREASES with addition of ADP. (!!)
#malignant PKU
autosomal recessive defects in the enzyme *dihydrobiopterin reductase* (called malignant because restricting phenylalanine does NOT correct neurological problems) • Note: in malignant PKU, BH2 is not converted back to BH4 because of a defect in dihydrobiopterin reductase so DOPA needs to be supplemented in these patients
#PKU (phenylketonuria)
autosomal recessive defects in the enzyme phenylalanine hydroxylase (PAH) OR a decrease in tetrahydrobiopterin (BH4), • Phenylalanine can NOT form tyrosine as normal, so phenylalanine accumulates and leads to the following symptoms: - neurologic defects (mental retardation/intellectual disability) - Seizures (!!!) - albinism/hypopigmentation (tyrosine required for melanin synthesis) AND/OR eczema - "musty odor" to their sweat & urine (due to accumulated phenylalanine conversion to phenylketones) • HYPOPIGMENTATION and pallor is shown in parts of the brain on autopsy • Screened for on the 2nd or 3rd day of life due to presence of maternal enzyme at birth
# Classic galactosemia: (!!)
autosomal recessive deficiency in *GALT (galactose-1-phosphate uridyltransferase)* which converts *galactose-1-phosphate, to glucose-1-phosphate and UDP galactose. * • Absence of GALT leads to galactose and galactose-1-phosphate accumulation which are converted to toxic substances such as galactitol, which damages the lens of the eye. • All states mandate neonatal screening because lactose (i.e. milk) is metabolized to glucose and galactose.
# Hereditary fructose intolerance:
autosomal recessive deficiency of *aldolase B*. As a result, *fructose-1-phosphate accumulates as a toxic metabolite, available phosphate levels drop, and glycogenolysis and gluconeogenesis are blocked*, so there is profound hypoclycemia after eating sucrose or fructose!!!! Typically presents once the baby is introduced to baby food and cereals, while taken off breast milk, because breast milk contains glucose and galactose (glucose+lactose). Baby food contains *sucrose* and *fructose*. • Symptoms include vomiting, jaundice, convulsions, and severe cirrhosis. • Treatment is avoiding intake of fructose or sucrose (combination of glucose and fructose).
#Congenital adrenal hyperplasia
autosomal recessive disorder caused by deficiencies in adrenal steroid synthesis enzymes. hyperplasia of BOTH adrenal glands due to congenital defect....21 hydroxylase deficiency is most common cause. The three main enzymatic deficiencies are: - 21-hydroxylase - 11-hydroxylase - 17-hydroxylase All congenital adrenal enzyme deficiencies are characterized by ↓cortisol → ↓ negative feedback on pituitary system → ↑ ACTH release. This persistent stimulation by ACTH causes bilateral hyperplasia of the adrenal glands.
# Essential fructosuria:
autosomal recessive, benign condition resulting from defect in hepatic fructokinase. • Fructose can NOT be phosphorylated into fructose-1-phosphate, so it is unable to be sequestered in the cell and does NOT deplete the cell's phosphate. Fructosuria is an incidential finding (fructose in urine). Fructose is a reducing sugar!!!!!!!!!!! Sugar will NOT be picked up on urine dipstick!!!
#Rotor syndrome
autosomal recessive: Mild, idiopathic direct hyperbilirubinemia. Presents similarly to Dubin-Johnson Syndrome, however there is *no black pigmentation of the liver.* Clinically insignificant - main symptoms is pruritus associated with chronic jaundice
# macrolides
azithromycin, clarithromycin, erythromycin...... "Macro= "ro"mycin.... Acts on the "macro" subunit. *Inhibits protein synthesis* (!!) by blocking translocation by binding to the *50S ribosomal subunit* and blocks transpeptidation and amino-acyl translocation!!!
# Down syndrome and leukemia
before age of 5 is usually Acute megakaryoblastic leukemia after age of 5 is usually ALL (all fall down, eventually)
# Thyroxine binding globulin
binds most T3 or T4 in peripheral blood Only free T3 or T4 is active (!!!) TBG bound T3 or T4 is inactive. Increased *estrogen during pregnancy/HRT/oral contraceptives*.... causes increased TBG* which results in increased TOTAL T3 and T4 levels. However, the FREE T3 and free T4 levels are actually normal (therefore, pregnancy is not a hyperthyroid state).
#Biliary tract obstruction (post hepatic jaundice)
block biliary tract in condicions such as gallstones, pancreatic carcinoma, cholangiocarcinoma) whatever is in bile leaks into blood, so: - CB increases. - Bile salts/acids increase in blood, causing pruritus - cholesterol increases, leading to hypercholesterolemia with xanthomas - cannot put bile in bowel b/c of obstruction, so get pale stools, statorrhea, malabsorption of fat soluble vitamins - dark urine b/c CB (which is water soluble) goes up Summary: - conjugated hyperbilirubinemia - increased urine bilirubin - low urine bilinogen
Gallstones acute pancreatitis
blocks @ ampula decrease pancreatic drainage, premature enzyme activation
# Aldosterone receptor antagonists
blocks aldosterone receptor → limits the transcription/translation of new *Na+ channels* on *principal cells* in the *collecting ducts* → ↓ reuptake of Na AND ↓ efflux of K into the urine (action of aldosterone) Diuresis results as excess Na+ in the lumen of the nephron attracts water, thereby preventing its reabsorption
# What causes vitamin K deficiency??
broad spectrum antibiotics (kills gut flora), warfarin therapy, newborns, fat malabsorption diseases
# protein synthesis inhibitors
buy AT 30, CELL at 50" Aminoglycosides, Tetracyclines (30s subunit inhibitors) Thus, they inhibit INITIATION of protein synthesis.
Class 4 anti-arrhythmics- calcium channel blockers
calcium channel blockers (e.g., Diltiazem, Verapamil), which exert their anti-arrhythmic effect mainly by slowing AV node conduction by inhibiting Ca2+ influx. Additional effects of Class IV agents include: • 1. ↓ SA/AV node automaticity • 2. ↑ effective refractory period • 3. ↑ PR interval Calcium channel blocker toxicity: • CHF • AV block • Facial flushing, headache, gingival hyperplasia
Anion gap metabolic acidosis
can be further broken down into anion gap and non-anion gap metabolic acidosis. • The anion gap allows for determination of the basis of a metabolic acidosis and is represented by the following formula: Anion gap = [Na+] - ([Cl-] + [HCO3-]) • In metabolic acidosis, the value of HCO3- decreases as it is involved in buffering excess fixed acid (H+). (Note, it is NOT excreted, it is being used to buffer)..... In order to maintain electro-neutrality, the level of another anion must increase!!!!! • If the replacement anion is an unmeasured acid (like phosphate, lactate or β-hydroxybutyrate), the serum anion gap will increase. If the replacement anion is Cl-, there is a normal anion gap (also referred to as hyfemic metabolic acidosis).
#hernia repair and infertility
can cause accidential ligation of vas deferens, or scar tissue can obstruct it.
#Surgical neck fracture of humerus
can damage axillary nerve and posterior circumflex humeral aterty. Deltoid is F'ed up so cannot abduct. Loss over deltoid, and lateral aspect of the arm (!!!!)
#digoxin toxicity (!!!)
can lead to hyperkalemia, arrhythmias !!! ! bradycardia which worsens!! blurry/"yellow" vision (!!) nausea/vomiting/diarrhea Fatigue, confusion, weakness.
# dyspnea/wheezing on exertion
caused by interstitial fluid in the lung stimulating juxtacapillary receptors (*J receptors*, innervated by the *vagus nerve*) causing rapid shallow breathing.) Note, can also occur in asthma and COPD
# Clostridium difficile
causes *pseudomembrane colitis and diarrhea*. Disease often arises from nosocomial infection through fecal-oral transmission. *A common risk factor includes antibiotics use (e.g. fluoroquinolones, ampicillin, clindamycin) that alter intestinal flora, allowing C. difficile to flourish*..... * Another risk factor is pneumonia!! * It produces 2 toxins which both *alter cytoskeleton structure disrupting tight junctions* in the mucosa. Toxin A causes more intestinal inflammation and fluid secretion Toxin B is more cytotoxic
Clostridium botulinum
causes adult and infant botulism. The symptoms of botulinum infection include • Flaccid paralysis (floppy baby syndrome) • Dry mouth • Blurry vision (classic signs of ACh blockade) • Death from respiratory failure *C. botulinum spores are unable to germinate in adults' mature intestinal tract. * - Adult botulism occurs only when adults *ingest preformed toxin (foodborne botulinism), often in canned foods!! * - Infant botulinism occurs when*babies ingest spores, often found in honey, *that germinate and subsequently elaborate toxin.
#ethambutol toxicity (!!!)
causes optic neuropathy, either change in acuity or red-green color blindness. !!!
#conversion disorder
causes patients to *suffer from neurological symptoms*!!! , such as *numbness, blindness, paralysis, or fits without a definable organic cause*. It is thought that symptoms arise in response to stressful situations affecting a patient's mental health.
# findings in Irreversible cell injury only
cell membrane rupture (!!!) pyknosis (nuclear condensation) karyolysis (loss of nuclear chromatin) karyorrhexis (nuclear fragmentation) lysosomal rupture ↑ mitochondrial permeability with influx of calcium into the cytoplasm → activation of phospholipases, proteinases, DNAases - mitochondrial vacuolization (!!!)
# G1 phase
cells increase in size and get ready for DNA replication, which occurs in S phase. All proteins are made in G1 phase EXCEPT centioles (S phase)
# central tolerance in thymus
central tolerance in the 1) thymus leads to T-cell (thymocyte) apoptosis or generation of regulatory T-cells. "double negative" stem cells enter the thymus and become *double positive* pro-T-cells meaning they express both CD4+ AND CD8+... they ALSO express a TCR. They then progress to become *single positive* (CD4 OR CD8) and exit the thymus as *naive mature T-cells* *positive selection* means that the *double positive* cells are checked to see if they have a TCR which *can bind self MHC*. If they can recognize self MHC, they progress to become *single positive cells*... if they cannot recognize self MHC, they die via apoptosis. *negative selection* means that the *single positive* cells are checked to see if they can bind *self antigen*. If they *avidly* bind it too tightly, they may cause autoimmunity if not destroyed, thus, they undergo apoptosis.... if they do not, they leave the thymus and proceed. Negative selection binds self antigens on either a *dendritic cell* or a *medullary epithelial cell*
# Abetalipoproteinemia (also known as Bassen-Kornzweig syndrome)
characterized by *microsomal triglyceride transfer protein (MTTP) deficiency*. MTTP is essential for synthesis and secretion of beta-type apolipoproteins (e.g., ApoB-48 and ApoB-100). The inheritance pattern is autosomal recessive. • Due to ineffective MTTP, there is reduced chylomicron and VLDL synthesis and secretion. • Reduced chylomicron and VLDL synthesis leads to *severely reduced absorption of dietary fats and fat-soluble vitamins*. Accumulation of lipids within enterocytes can be seen on intestinal biopsy. (!!!)
# Type III dyslipoproteinemia aka dysbetalipoproteinemia,
characterized by a *mutation in ApoE.* ApoE 3 and 4 are found on chylomicrons and VLDL, and responsible for their binding to hepatocyte receptors. Without them, the liver cannot remove chylomicrons and VLDL from circulation, increasing circulating cholesterol and triglycerides.
#age related macular degeneration
characterized by a loss of central vision due to age-related degeneration of the macula. Can be: Nonexudative ("dry") Exudative ("wet")
# type 2b dislipoproetinemia aka familial combined hyperlipidemia
characterized by decreased LDL receptor and *increased ApoB* (think of it as a negative feecback!!) The inheritance pattern is autosomal dominant. The function of ApoB-100 is to uptake the LDL particle in the liver!! Due to decreased LDL receptor and increased ApoB, the characteristics lab findings are increased serum LDL, VLDL, and triglycerides
# cholestasis
cholestasis is a condition where bile cannot flow from the liver to the duodenum It can be caused by either intrahepatic causes, or extrahepatic causes. Both are *characterized by deposition of bile in the hepatic parenchyma* which leads to *presence of green-brown plugs* in *dilated bile canaliculi*. Reduced bile causes *intestinal malabsorption*, ESPECIALLY *Vitamin A, D, E, K*.
# Cholestyramine and Cholelithiasis
cholesterol lowering agent by binding bile acids and prohibit bile acid recycling... decreased bile acids can lead to Cholelithiasis (gallbladder cholesterol stones) !!! FIBRATES also increase risk of gallstones!!!
# Resins (bile acid sequestrants):
cholestyramine, colestipol, colesevelam • Mechanism: binds bile acids in the intestine, preventing intestinal reabsorption, and thus increased excetion!!! This bile depletion results in an INCREASED bile synthesis from hepatic cholesterol → • LDL ↓↓ • HDL n/c of mild ↑ • Triglycerides n/c or mild ↑ (!!!!!!) • Side effects: GI discomfort (constipation, diarrhea, and flatulence), malabsorption (steatorrhea; decreased absorption of fat soluble vitamins may cause vitamin deficiencies)
# SLE overview
chronic, autoimmune inflammatory disorder that affects multiple body systems, mostly in child bearing females, also in blacks, hispanics, asians. (note, female bias is less profound in children and adults, this makes sense, because children and old adults have less estrogen) Flares and remissions are common.
# Plummer vinson syndrome (!)
classically refers to triad of: (1) esophageal webs in setting of (2) iron-deficiency anemia, with (3) glossitis: (beefy, smooth, shiny red tongue). Be suspicious if a patient presents with symptoms of dysphagia, concurrent anemia, and beefy-red tongue !!
# Campylobacter jejuni
comma-shaped, oxidase positive, gram-negative bacilli. It is the most common cause of gastroenteritis. Patients typically present with inflammatory diarrhea (characterized by WBCs in stool) that is initially watery and ill-smelling that often precede bloody stools. It can be acquired from: 1) domestic animals (cattle, sheep, dogs, chickens) 2) contaminated food such as undercooked chicken and unpasteurized milk
# Secondary hemochromatosis-
complication of transfusion. RBC lysis, and iron overload.
# Wernicke-Korsakoff syndrome
composed of *Wernicke's encephalopathy* and *Korsakoff's psychosis* (memory loss, confabulation and personality change).... This is ususally permanent (!!!!) Alpha-ketoglutarate is NOT able to be converted to succinyl CoA !!!! This enzyme requires B1 as a cofactor!!
# Adrenal medulla
composed of chromaffin cells derived from neural crest!!! Note, they are "modified postganglionic sympathetic neurons, they conain a nicotinic receptor* !!!!
# Psoriasis
condition with well-circumscribed, *salmon colored* plaques with *silvery scale*. Usually present on the *extensor surfaces* and the *scalp*..... (In contrast to eczema, which is usually found on the flexural surfaces of the joints) *pitting of nails* may also occur
# Treatment of Buerger disease
consists of: - smoking cessation (but whatever damage has occurred is permanent) - intravenous iloprost (a prostaglandin analog)
cox-2 inhibitors
coxib". Form of non-steroidal anti-inflammatory drug (NSAID) that directly targets COX-2, an enzyme responsible for inflammation and pain Unlike their traditional NSAID counterparts, selective COX-2 inhibitors may increase the risk of heart attack, thrombosis. They do this by inhibiting only PGI2, aka prostacyclin. Prostacyclin inhibits platelet aggregation (is anti-coagulatory), while TXA2 promotes platelet aggregation (is pro-coagulatory). The "balance" shifts in favor of TXA2, thus, increased risk of clots....
arginine derivatives
creatine, urea, and nitric oxide (!!!!) • Creatine phosphate is a short term energy reservoir primarily used during the early stages of muscular exercise. • NO is an important vasodilator, synthesized from arginine via nitric oxide synthase (NOS). • urea
function of type II pneumocytes
cuboidal and clustered. 2 important functions: 1) regeneration of alveolar lining after injury, and can regenerate themselves and also type I pneumocytes 2) surfactant production
cheyne-stokes breathing
cyclic breathing in which apnea is followed by gradually increasing tidal volumes, then gradually decreasing tidal volumes commonly seen in cardiac disease (congestive heart failure) and neurological disease (stroke, injury, tumors). It indicates a poor prognosis. During start of apnea, PaCO2 levels at lowest (suppressing respiration)... then because of apnea they tend to rise. However, slowed respiratory feedback delays the respiratory response, and PaCO2 rises higher than it should. Basically a period of apnea, followed by hyperventilation (occurs when PaCO2 at highest)
# Neutropenia
decreased number of circulating neutrophils, causes include: -Drugs (ie, chemotherapy, which affects both cancerous and non-cancerous cells, often rapidly dividing cells, including stem cellls) Note: in this case, GM-CSF or G-CSF may be used to boost granulocyte production, including neutrophils !!!!!!!!!! 2. Severe infection- in very severe infections ie gram negative sepsis, neutrophils move into tissues out of circulation
# Rickets/Ostelmalacia
defective mineralization (calcium, phosphate) of osteoid, due to low levels vitamin D (acts on intestine, kidney, bone to resorb calcium and phosphate).
Rickets
defective mineralization with low vitamin D in children. -Pigeon breast deformity (anterior protrusion of the sternum) !!! ! - frontal bossing (prominent forehead) - rachitic rosary (bony prominence at costochondral junctions)!!! - bowing legs (Genu varum, weakened long bones) !! - *Osteoid matrix* is deposited in places
# Chronic bronchitis definition
defined clinically as a *productive cough* for *at least 3 months* (not necessesarily 3 consecutive months)...in *2 consecutive years*. (patients say they cough up cups/buckets of mucus, so much!) Since hypoxia occurs early in the clinical course, patients with chronic bronchitis are referred to as "Blue Bloaters." !!
# GERD
definition of (GERD): symptoms OR mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. due to due to *Gastroesophageal junction incompetence* due to LES incompetence, transient *LES relaxation*, or a hiatal/diaphragmatic hernia.
# what muscles attach to lateral clavicle??
deltoid, traps Deltoid pulls the lateral clavicle inferiolaterally Traps pull the lateral clavicle superiomedially Clavical fracture tends for the distal fragment to be pulled inferiolateral by deltoid. The "medial" aspect of the clavicle in a fracture is pulled UPWARD by the sternocleidomastoid !!! (SCM)
Dementia and Parkinson's
dementia is a very *late complication* of Parksinson's disease...... however, if a patient has *early onset dementia*, it suggests that they have *Lewy body dementia*.... This is characterized by: - Dementia - hallucinations - Parkinsonian like features - *Cortical* Lewy bodies.....
# Prinzmetal angina pectoris aka *variant* angina
described as *intermittent* chest pain *secondary to coronary artery vasospasms*. #often have a history of migraine headaches (!!!!) both conditions are associated with *arterial vasospasms* Prinzmetal angina pectoris is *unrelated to physical activity* and episodes *usually occur at rest*, especially at night and early in the morning. Even though patients presenting with prinzmetal angina pectoris *may* have significant atherosclerosis, the coronary vasospasms causing the episodes are *not related* to atherosclerosis. Is still REVERSIBLE injury.
# Eisenmenger's syndrome !!
describes a condition in which a uncorrected *left-to-right* shunt (VSD, ASD, PDA) *reverses* to become a *right-to-left* shunt in the presence of *progressive pulmonary hypertension* secondary to increased pulmonary circulation and pulmonary artery hypertrophy!!! Right ventricular hypertrophy occurs. Late cyanosis with *clubbing* and *polycythemia* often accompany Eisenmenger's syndrome.
Benzodiazepines
diazepam, lorazepam, midazolam, chlordiazepoxide Benzodiazepines modulate GABA by binding to a specific ALLOSTERIC regulatory site (the benzodiazepine receptor) on the GABA-A receptor: this site is distinct from the GABA binding site but binding of the benzodiazpeine to its site increases the affinity of GABA for the receptor. Note: benzo's, barbs, and alcohol ALL bind to GABA-A. Binding of GABA to its receptor triggers an opening of a Cl- channel which leads to an *increase in Cl- conductance by increasing the frequency of opening,* and thus by increasing the efficiency of GABA, to decrease the excitability of neurons. This reduces the communication between neurons and, therefore, has a calming effect on many of the functions of the brain. NOTE: Since benzo's increase the effectiveness of GABA, they are NOT effective if there is no GABA.
phenytonin teratogen
digital hypoplasia and cleft lip/palate
Posterior urethral valve (PUV)
disorder is an obstructive developmental anomaly in the urethra and genitourinary system of male newborns. A posterior urethral valve is *an obstructing membrane in the posterior male urethra* as a result of abnormal in utero development. It is the most common cause of bladder outlet obstruction in male newborns. !!!! Abdominal ultrasound is of some benefit, but not diagnostic. Features that suggest posterior urethral valves are bilateral hydronephrosis, a thickened bladder wall with thickened smooth muscle trabeculations, and bladder diverticula. Also is *inadequate recanalization of the *ureteropelvic junction* !!!!!!!!!
#memantine toxicity -
dizziness, confusion, hallucinations
# metoclopramide
dopamine-receptor antagonists, It is commonly used to treat nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying due to either diabetes or following surgery, and to help with gastroesophageal reflux disease, do NOT use it with Parkinsons!!!
# Hypercoagulable state in nephrotic syndrome
due to *membranous glomerulopathy* causing preferential *loss of anticoagulants like antithrombin III, protein C and protein S in urine* → ↑ risk of thrombosis (eg, renal vein thrombosis, especially in membranous nephropathy) and ↑ risk of thromboembolic complications !!! Patients present with SUDDEN abdominal/flank pain, and *gross* hematuria. If renal vein thrombosis occurs on the left side in males, this causes a *left sided varicocele*. !!!!!!!!!
# Functional incontinence
due to an inability to reach toilet in time because of impaired health or environmental conditions. Medical etiologies of functional incontinence include: • Weakness • Arthritis • Poor vision • Confusion • Dementia Etiologies of functional incontinence due to environmental conditions include: • Unfamiliar setting • Distant bathroom facilities • Bed rails • Physical restraints
# TB
due to inhalation of *mycobacterium tuberculosis*. .... The droplets are first *phagocytized by alveolar macrophages*, BUT *Sulfatide virulence factors allow intracellular bacterial proliferation* !!!!!!! Serpentine cords that grow in parallel chains correlate with virulence!!!
# Polyarteritis Nodosa S:Sx
due to ischemia and infarction of affected organ: Kidney - renal failure/Hypertension (renal artery) Coronary - ischemic heart disease, acute myocardial infarction GI - abdominal pain, nausea, bloody diarrhea (mesenteric artery) Musculoskeletal - arthritis, myalgia (!!!!) CNS - eye and skin complaints Skin !!!
# Rebound headaches
due to withdrawal of analgesic medications (such as NSAIDs) are often misdiagnosed as chronic migraines, but they will not respond to the normal treatments.
# Paroxysmal nocturnal dyspnea
dyspnea laying over hours because of gradual reabsorption of fluid from the interstitium into the vascular compartment → increases venous return → worsens pulmonary congestion)
# Nitrates
e.g., nitroprusside, nitroglycerin, isosorbide dinitrate Mechanism: forms nitric oxide (NO), a free radical that activates guanylate cyclase → increased cGMP in smooth muscle → vasodilatation . Nnitrates have greater effect on *large veins* and therefore cause *decreased preload, aka left ventricular filling volume* !!!!!! They do this by *reducing venous return* (blood is retained in the venous system).... more so than reducing *afterload*. !! This reduced preload causes *decreased myocardial oxygen consumption*, increases coronary blood flow, improving ischemia. A decrease in preload decreases stroke volume (Frank Starling mechanism), as well as CO, end systolic left ventricle volume, and afterload. Thus, there is a compensatory INCREASE HEART RATE!!!! . NO is normally produced by the endothelial cells of the blood vessel, but the action of NO is on the smooth muscle cells.
# Ehlers Danlos vascular type
easy bruising, aortic dilation and dissection.... *Deficient type 3 collagen*.... characterized by aneurysms and vascular and organ rupture. Retinal detachment is common too.
Maternal AFP levels
elevated in: neural tube defects ventral wall defects (emphalocele, gastroschisis) multiple gestation Low in TS 18 and 21
# tetanus vaccine
elicits humoral response to tetanospasmin bacterial products. Tetanus vaccine is VERY important in develoiping countries, and *especially, pregnant women*, because they will then transfer the IgG to the placenta.
bile salt function
emulsifying fats for digestion Destroy gram negative bacteria by disrupting bacterial outer membranes. Cholestasis permits bacterial overgrowth.
# Detmatomyositis vs polymyositis biopsy
ensheatings the entire group of fassicles is the *epimysium* Muscle fascicle is made up of a bunch of individual fibers. The connective tissue outside the whole fascicle is called the *perimysium*. - while the connective tissue between the fibers is called the *endomysium*... what happens in *dermatomyositis* is *inflammation of the perimesium* , which results in *perifasicular atrophy*, which is at the *edge of the muscle cell* This is necessary to differentiate dermatomyositis from *polymyositis*, which has *endomysial inflammation*!!!
# Liquefactive necrosis
enzymatic lysis leads to liquefaction of necrotic tissue, most often seen in the CNS (Central Nervous System) due to high fat content, where it is caused by interruption of blood supply. - Degradation of lysosomsal enzymes occurs first and THEN there is protein enzymatic degradation. Also common due to *bacterial infections* that stimulate massive leukocyte response. The necrotic cells are completely digested, then leukocytes dye *forming pus*. Pancreatitis- activation of enzymes in pancreas ITSELF, which digest pancreas. (note, there is ALSO fat necrosis in pancreas of peripancreatic fat)
#Phenyalanine hydroxylase
enzyme that converts Phenylalanine to Tyrosine • In this reaction, tetrahydrobiopterin (BH4), the required cofactor, is converted to dihydrobiopterin (BH2) (!!!!!!) • BH2 is converted back to BH4 via the enzyme dihydrobiopterin reductase
#tyrosine hydroxylase
enzyme that converts Tyrosine to Di-hydrOxy-PhenylAlanine (or DOPA) • (BH4) is a necessary co-factor for the enzyme tyrosine hydroxylase. (BH4) is also a co-factor for phenylalanine hydroxylase.
Burr cells
erythrocytes with short, evenly spaced prohjections. They occur as an artifact, OR in association with: uremia pyruvate kinase deficiency Microangiopathic hemolytic anemia mechanican damage
# Tensilon test
exacerbation of myasthenia gravis in those on cholinesterase inhibitors ( - stigmine's) occurs because: 1) Patient is under-treated, so not enough ACh is available for competition with autoantibodies... this is called *myasthenic crisis* administration of *edrophonium*, a short acting cholinesterase inhibitor (*tensillon test*!!!) will improve symptoms. If this happens, we need to increase the "_stigmine" dosage!!! 2) *cholinergic crisis* due to *inappropriately high doses* of Ach esterase inhibitor and there is too much Ach in the cleft. This causes excessive skeletal muscle stimulation which is refractive to future impulses. Administering *edrophonium* will NOT improve symptoms.
# hypertrophied scar
excess production of scar tissue, localized to would. predominately type 1 collagen
# cancer in adults incidence
excluding skin, most common cancers are: Incidence: (!!!) 1) Breast/prostate, 2) Lung, 3) colorectal Mortality 1) Lung 2) Breast/prostate 3) colorectal 4) Pancreatic
: Sildenafil citrate (Viagra) and vardenafil
exploits the pathway downstream of NO (but does NOT increase Nitric Oxide itself, it "enhances" it). NO stimulates guanylate cyclase → ↑ cGMP production → ↑ PKG activity, which leads to ↑ myosin light chain phosphatase activity (relaxing smooth muscle in the corpus cavernosum). *Viagra inhibits the enzyme that degrades cGMP (!!!) (which is PDE-5) !!,* thus, increasing vasodilation and blood flow.
upper 2/3 vagina lymph
external iliac and hypogastric nodes
Esophageal varicies (!!!!!!!!!)
extremely dilated sub-mucosal veins in the lower 1/3 of the esophagus. Note: most of esophagus drains by *azyous vein* into SVC* , but SOME drains *left gastric vein into portal vein*. *Portal hypertension* (commonly due to cirrhosis) causes backup of blood in portal hypertension,* left gastric vein* (!!), and thus dilated sub-mucosal veins. patients with esophageal varices have a strong tendency to rupture, and develop *PAINLESS* bleeding and hematemesis. (this is most common cause of death in *cirrhosis*... cirrhosis patients also cannot synthesize coagulation factors... so here they get bleed, AND inability to seal it.!!!!!!!!!!
# Bartonella henselae
facultative intracellular, pleomorphic, gram-negative bacillus that is part of the oral flora of cats and *causes bacillary angiomatosis and cat-scratch disease in humans. * Transmission of B. henselae occurs via cat bite or scratch to humans. In immunocompromised patients (e.g. AIDS patients) B. henselae infection can present with • *Bacillary angiomatosis • Bacillary peliosis • Culture-negative endocarditis* • Splenitis • Osteomyelitis • Bacteremia • Cat-scratch disease causes localized lymphadenopathy most often in the axillary or cervical lymph nodes along with fever. *• Lymph node biopsy in cat-scratch disease shows stellate granulomas *due to Bartonella presence. Warthin-Starry silver stain will not reveal an abundance of organisms in the immunocompetent patient.
Cleft palate
failure of fusion of the lateral palatine processes ,the nasal septum,and/or the median palatine process......formation of secoundary palate
# diagnose cystic fibrosis
family history, clinical findings, and sweat test showing *↑ chloride ion in the sweat (due to ↓ absorption)* .... Can also actually present with alkalosis and hypokalemia because of renal K+/ H+ wasting!! Also, they are losing chloride and water but NOT bicarbonate.
#21 hydroxylase deficiency presentation
features: SEVERE hyponatremia/ hyperkalemia, and hypovolemia, ALL due to lack of aldosterone *life threatening hypotension* due to lack of cortisol female: ambiguous genitalia/labiosacral fusing and/clitoral enlargement (*females PRESENTS AT BIRTH* from so much extra androgens!! ) Male: *precocious puberty (males)* and excessive growth development due to excess androgens !!!
fever
fever is >38.3. Hyperpyrexia is > 40 degrees!! Severe infection, malignant hyperthermia, neuroleptic malignant syndrome, and heat stroke. Can cause permanent neurological consequnces, convulsions, delirium, coma. A temperature of 43 degrees equals death.
# Hydrocele
fluid collection within the *tunica vaginalis*, which NORMALLY has minimal fluid. Associated with incomplete closure of the *processus vaginalis* in infants, or blockage of lymph drainage in adults. Presents as a boggy scrotal swelling that CAN be *transluminated* since it is mostly fluid.
#Treat benzodiazepine toxicity (!!!)
flumazenil, which is a competitive antagonist at GABA benzodiazepine receptor which has a short half life
# Distinguish follicular hyperplasia from follicular lymphoma
follicle hyperplasia occurs in both immune response (from infection) and follicular lymphoma, so we need to differentiate. In lymphoma, there is disruption of lymph node architecture. In lymphoma, the follicles 'take over' the entire lymph node, whereas in infection, the follicles are present in the cortex. - In normal follicles, there is NO expression of Bcl2 because we WANT apoptosis. If there IS expression, it is follicular lymphoma.
# Tricuspid Atresia
form of congenital heart disease whereby there is a complete absence of the tricuspid valve. Therefore, there is an absence of right atrioventricular connection. This leads to a hypoplastic (undersized) or absent right ventricle. Because of the lack of an A-V connection, an atrial septal defect (ASD) *must* be present to maintain blood flow. Also, since there is a lack of a right ventricle there *must* be a way to pump blood into the pulmonary arteries, and this is accomplished by a ventricular septal defect (VSD)
Diffuse proliferative glomerulonephritis
form of renal lesions in SLE and is also the most common, occurring in 35% to 60% of patients. Most of the glomeruli show endothelial and mesangial proliferation affecting the entire glomerulus, leading to diffuse hypercellularity of the glomeruli, producing in some cases epithelial crescents that fill Bowman's space. When extensive, immune complexes create an overall thickening of the capillary wall, resembling rigid "wire loops" on routine light microscopy. Electron microscopy reveals electron-dense *subendothelial immune complexes (between endothelium and basement membrane)*. Immune complexes can be visualized by staining with fluorescent antibodies directed against immunoglobulins or complement, resulting in a granular fluorescent staining pattern In due course, glomerular injury gives rise to scarring (glomerulosclerosis). Most of these patients have hematuria with moderate to severe proteinuria, hypertension, and renal insufficiency
Churg Strauss
formerly considered a variant of polyarteritis nodosa- it has a presence of *necrotizing granulomas* as well as the *abundance of eosinophils*, which distinguishes this disease from polyarteritis nodosa. Involves multiple organs, especially lungs and heart. * Associated with Asthma!!!!!!!! * Morbidity/mortality often from cardiac and neurologic involvement Patients often develop coronary arteritis or myocarditis - Churg-Strauss syndrome—*p-ANCA (anti-myeloperoxidase antibodies) !!!! * The American College of Rheumatology has 6 diagnostic criteria—presence of 4 of the following 6 is both sensitive (85%) and specific (>99%) for Churg-Strauss: 1. Asthma (wheezing, expiratory rhonchi) 2. Eosinophilia (eosinophil count > 10% on peripheral smear—vs. normal eosinophil count of 1-3%) *3. Mononeuropathy or polyneuropathy (usually peripheral neuropathy causing pain/anesthesia/parathesia in hands and feet... often wrist and/or foot drop)!!!!!!* 4. Migratory pulmonary infiltrates on chest x-ray ("migratory" because these infiltrates may be transient and may appear to move to different locations on serial imaging examinations) 5. Paranasal sinusitis 6. Extravascular accumulations of eosinophils—confirmed on tissue biopsy of skin or nasal polyp
# acute leukemia
from hematopoietic stem cell, myeloblasts or lymphoplasts are formed. Acute leukemia is a neoplastic proliferation of these blasts! Normally these levels are 1-2%, but in acute leukemia, we have a definition (!!!) of >20% blasts in bone marrow. Blasts "crowd out" normal hematopoiesis in bone marrow(!!!), so patients present with 'acute' presentation with *pancytopenia*.... So there is : anemia, thrombocytopenia, neutropenia (RBC's, platelets, WBC's respectively can't be formed.... Clinical findings generally abrupt in onset (!). Fever, bleeding and fatigue are commonly found. (think Doreen suddenly bruising, infection etc!!) Blasts USUALLY enter the blood, resulting in high WBC. They are large, immature cells often with 'punched out' nucleoli on blood smear.
# coccidioides (immitis and posadasii)
fungi responsible for the fungal infection *coccidioidomycosis.* Transmission of Coccidioides spp. occurs mainly via inhalation of spores. The proportion of infections increases with *dust exposure, as occurs during archeological excavations, earthquakes or desert military maneuvers!!* Coccidioides spp are* endemic to the desert regions of the western hemisphere*, including *southern Arizona, the southern and central valleys of California, southwestern New Mexico, and west Texas in the United States... Also Mexico and South America!!!* " Primary infection most frequently manifests as *LUNG disesase like mild community-acquired pneumonia. * cutaneous manifestations include erythema nodosum and erythema multiforme. • Disseminated Coccidiodes infections can lead to lesions in the o Skin or subcutaneous soft tissue o Meninges o Skeleton
#diagnose chediak-Higashi
giant granules in neutrophils in peripheral blood smear
# posterior 1/3 tongue sensation
glossopharyngeal nerve provides *general sensation and taste sensation* to the *posterior 1/3* of the tongue.
# Bernard Soulier syndrome
glycoprotein Ib is absent (autosomal recessive), so platelet adhesion cannot occur as GPIb cannot bind vWF as normal. Note that despite being characterized as a qualitative platelet defect, BSS is associated with mild thrombocytopenia (platelets don't live as long) and giant platelets in the blood. Think St. Bernard (a giant dog) to remember the giant platelets in Bernard-Soulie
# ERB-B2 (HER2/neu) mutation
growth factor receptor, amplified in subset of breast cancers AND cancers of ovary HER2/neu is a 185kd *cell surface growth factor* that also has *intracellular tyrosine kinase* activity...excess HER2/neu, due to *gene amplication* is associated with excess growth and cell and proliferation of tumor. *trastuzumab aka herceptin* is an *antibody against this receptor*!!! HER2/neu stains brown on the surface of cells of cytoplasm, like an "outline of a circle"
hcg subunit similatiries
hCG shares an alpha subunit that is the SAME as TSH, LH, FSH beta subunit of hCG and TSH are very similar.
Cluster B Personality Disorders:
hallmark of emotional, dramatic or erratic behavior (they are "Wild" or Bad to the Bone) • Genetic association with mood disorders and substance abuse
# Cluster C Personality Disorders:
hallmark of fearful or anxious behavior (they are "Worried" or Cowardly, Compulsive, and Clingy) ... includes: Avoidant, Obsessive-compulsive, dependent • Genetic association with anxiety disorders
Cluster A Personality Disorders:
hallmarks of eccentric or odd behavior with fear of social relationships (they are "Weird" or Accusatory, Aloof, and Awkward) Types include: Paranoid, Schizoid, Schizotypal. • *There is NO psychosis* but genetic association with schizophrenia
ammonia magnesium aka struvite stones
happen at high pH >7 are the second most common type of kidney stone. The most common cause is infection with a *urease-positive* organism such as Proteus vulgaris or Klebsiella !!!!!!! These stones *must be removed surgically* to prevent further complications. Also, must treat the organism that caused it.
# mitochondria genome
have their own genetic material, and the machinery to manufacture their own RNAs and proteins.
#erectile dysfunction sides
headache, flushing - dyspepsia - impaired blue-green color vision • Risk of life-threatening hypotension in patients taking nitrates (nitrates increase NO directly)
# Vitamin K excess
hemolytic anemia and jaundice in newborn if mother receives excess vitamin K.
Tonsillar herniation
herniation of the cerebellar tonsils through the foramen magnum, compressing the brainstem, causing cardiopulmonary arrest. Tonsillar herniation can occur if an LP is performed on a patient with unrecognized hydrocephalus or a mass lesion leading to increased ICP.
# sickle cell trait
heterozygous HbS, largely asymptomatic. -<50% HbS (~50% or more HbA) .... ie, maybe 45% HbS and 55% HbA (sickle cell DISEASE has >80% HbS) <50% HbS does not usually result in sickling EXCEPT in renal medulla, due to extreme hypoxia. - patients get microinfarctions. - leads to microscopic hematuria and eventually, decreased ability (!!) to concentrate urine (!!!!!!)
# Sorbitol accumulation:
high blood levels of glucose (or fructose or galactose) lead to osmotic damage from sorbitol accumulation in tissues that lack sorbitol dehydrogenase or express it in insufficient amounts → cataracts, diabetic retinopathy, and peripheral neuropathy. • Liver, ovaries, and seminal vesicles have both aldose reductase and sorbitol dehydrogenase (thus, there is no sorbitol accumulation) Glucose → sorbitol (via aldose reductase) → fructose (via sorbitol dehydrogenase) (!!!!!)
# how to differentiate ACTH secreting pituitary adenoma, from paraneoplastic ACTH secretion
high dose dexamethasone- a cortisol analogue, that will suppress ACTH. If the patient has suppressed cortisol levels in response to low-dose dexamethasone → the patient may look like they have Cushing syndrome, but their ACTH-cortisol axis is probably normal. If the patient has persistently elevated cortisol in response to low-dose dexamethasone, but their cortisol levels are reduced in response to high-dose dexamethasone → *likely an ACTH-secreting pituitary adenoma (Cushing disease)!!! * If the patient fails to suppress cortisol in response to either low-dose or high-dose dexamethasone → *it is cushing syndrome* !!!!! either due to an *ectopic source*!!! either: - Cortisol-producing tumor in the adrenal cortex (high serum cortisol, low serum ACTH) or - Ectopic ACTH-secreting tumor (high serum cortisol, high serum ACTH), most commonly caused by small cell carcinoma of the lung. The ectopic ACTH-secreting tumor will have much higher ACTH levels than the tumor in the adrenal cortex.
# Vitamin A in pregnancy as teratogen
high doses of Vitamin A are highly teratogenic because it is lipid soluble it accumulates.... causes (birth defects include cleft palate, cardiac abnormalities, low IQ scores and extremely high risk for spontaneous abortions)
#lab findings of hemochromatosis
high ferritin (high ferritin means low TIBC), high serum iron, high percent saturation
# Mitral regurgitation murmur
high pitched *holo/pan systolic murmur* at the *apex*, and *radiating to the axilla*. !!!! Louder with squatting (squatting increases afterload so more regurge) and expiration (more blood into LA then LV) Mitral regurgitation is associated with an S3 heart sound!!!
# Pulmonary alterial hypertension (PAH)
high pressure in pulmonary circuit... Normal pulmonary artery pressure = *10-15* mmHg Defined as * > 25 mmHg* pulmonary artery pressure at rest.... or *> 30 mmHg* pulmonary artery pressure during exercise The Coronary sinus (which drains into the RA) is dilated which is SEEN sre as an ABNORMAL finding, as it is NOT normally seen on echo!!!!!
# HPV virus carcinogen (!!!)
high risk subtypes are 16, 18, 31, 33 Squamous cell carcinoma of the cervix AND anogenital region!!! Linked to oral and laryngeal cancers. HPV makes proteins E6 and E7. E6 targets/degrades p53; E7 targets/degrades Rb (a key tumor suppressor) HIV positive people (mostly men) have a high risk of anal carcinoma because of HPV!!!!
chronic bronchitis pathology
highly associated with *smoking*. Underneath *lamina propria* is *submucosa* which contains glands: 1) serous and 2) mucinous Serous gland produces watery fluid to go up above basement membrane to epithelium and humidify air. Mucinous glands produce mucus to line epithelial surface and trap bacteria, etc. Most are multicellular, but *goblet cells* are *single-celled* glands. In smokers, they bring in a *ton of pollutants* so the lung increases amount of mucus to deal with them, so you get *hypertrophy* of the *mucinous* glands. !!!!! The *Reid Index* measures the ratio of *gland thickness* to wall thickness, so in COPD this goes up!! (normal <40%, here maybe 50%+) most mucus is coughed up, but some goes back, and plugs airway which causes trapping and *obstruction* of getting air out. Reid index:= B/A+B+C
homeobox HOX genes
highly conserved genes found in animals, fungi, plants. They modulate *transcription regulators* which control the expression of other genes in the cell. They guide development from earliest stages of embryogenesis to the final differentiation of cells. HoxA-13 is mutated in hand foot genital syndrome clinodactyly, shortened thumbs, small feet, short toes genito-urinary abnormalities.
# Histones
histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. Nucleosome core has 2 molecules EACH of H2A, H2B, H3, H4 H1 histones are NOT part of the nucleosome. They participate in DNA packaging by binding the segment of DNA that lies between nucleosomes, and facilitates the compact packing.
# Labs for Graves
hypertrophy/hyperplasia of follicles with scalloping of colloid (colloid is pink material... scalloping is 'white space' with scalloped appearance ) Lymphocytic infiltrate → germinal centers are common (germinal centers should NOT be in the thyroid ; they are normal in lymph nodes) -Increase total and free T4 - decreased TSH (negative feedback) - hyopcholesterolemia and hyperglycemia
# aplastic anemia bone marrow aspiration
hypocellularity. (an empty, fat marrow) !! (aka *dry tap*)
rubella
icosahedral, enveloped, non-segmented, *positive sense single-stranded RNA (ssRNA) togavirus.* • The rash from rubella infection is usually evident for 3 days. • The common clinical presentation in pregnant women infected with rubella during the first trimester includes a maculopapular rash along with *postauricular and occipital lymphadenopathy. *
# southwestern blot
identifies DNA binding proteins (ie, transcription factors) using labeled oligonucleotide probe
# Thiazide diuretics
ie hydrochlorothiazide, chlorthalidone 1. Inhibits the *NaCl cotransporter* in the *distal convoluted tubule* of the nephron!!!! Leading to *natriuresis (Na+ excretion in the urine)* and *diminished intravascular volume*, and thus to *decreased BP*. Compared with loop diuretics, the thiazide diuretics are *longer lasting but less potent*. 2. Thiazide diuretics also *increase calcium resorption* due to opening of a voltage-gated calcium channel in the DCT, leading to *decreased calcium excretion in the urine* and higher serum levels of calcium !!!!! Decreased calcium in the urine decreases risk for calcium oxalate stones (!!!) ↓ serum levels of: K (hypokalemia) Na (hyponatremia) H+ (cause metabolic alkalosis, ↑ HCO3-) ( due to increased sodium delivery to the distal nephron as well as increased aldosterone) ↑ serum levels of (mnemonic "GLUC") (!!!!) - Glucose (cause hyperglycemia) - Lipids (hyperlipidemia, hypercholesterol !!! ) - Uric acid (hyperuricemia) → may precipitate gout !!! - Ca2+ (hypercalcemia)
# Hemochromatosis biopsy
if suspected, perform liver biopsy. If Brown pigment found in hepatocytes, but may NOT be iron, it may be lipofuscin. Stain this with *Prussian blue*, a stain that *detects intracellular iron*!!! It turns iron in hemosiderin dark blue, but lipofuscin remains brown. Lipofuscin is a brown pigment in hepatocytes (and ALSO in the heart)!!!!! , 'wear and tear' pigment, derrived from breakdown of peroxidized lipids. 'grey hair' of hepatocytes/myocytes.
# Renal artery stenosis
if you have stenosis of renal artery, there is *less blood flow to the glomerulus*.... so *the modified smooth muscles of the JGA responds*!!!! by secreting Renin, etc etc... AT2 formed which: 1) Powerful vasoconstrictor- *Directly contracts arterolar smooth muscle* to *increase peripheral resistance*. 2) promotes adrenal release of aldosterone, which grabs sodium from DCT to expand plasma volume. Renal artery stenosis often involves only 1 kidney, so there is *atrophy of the affected kidney.* !!! Heard by a THRILL!!!!! Causes of stenosis: - Atherosclerosis (usually elderly males), - Fibromuscular dysplasia (usually Young females)
# Type 3 hypersensitivity
immune complex reactions Circulating antigen-antibody complexes deposit on the surface of blood vessels *activating complement that eventually leads to tissue destruction*. !! • Examples include: SLE (systemic lupus erythematosus), PAN (polyarteritis nodosum), PSGN (poststreptococcal glomerulonephritis), serum sickness, Arthus reaction, and hypersensitivity pneumonitis
# Vessels MOST commonly affected by atherosclerosis (!!!)
in order of decreasing frequency: 1. Abdominal aorta (no *vasa vasorum* below the renal arteries (L2 vertebral level) ∴ the infrarenal abdominal aortic wall is more susceptible to ischemic damage than the thoracic aorta) 2. Coronary arteries
# central chemoreceptors
in the MEDULLA are stimulated by decreased pH (increased H+) in the CSF!! H+ itself does NOT diffuse through the blood brain barrier, but CO2 does, and forms H+ in the CSF. THUS, PaCO2 is the MAJOR stimulator of central chemoreceptors!!
# S/Sx of Takayasu arteritis
include an absent/weak upper extremity pulse (!!!!), discrepancy in blood pressure between the arms (>10 mm Hg) night sweats, arthritis, myalgias, skin nodules, visual defects, and stroke. ESR is elevated. Treatment of Takayasu arteritis consists of corticosteroid ASAP!!
Physical exam findings associated with constrictive pericarditis
include elevated jugular venous pressure, which is almost a universal finding. Kussmaul sign, the paradoxical rise in jugular venous pressure (JVP) on inspiration, is another common, but nonspecific finding. • The most common worldwide cause of constrictive pericarditis is tuberculosis. The majority of cases in the US are idiopathic or due to scarring from previous open heart surgery. • Classic image findings associated with constrictive pericarditis include dystrophic calcification on chest x ray in the parietal pericardium.
# Side effects of rosiglitazone/pioglitazone (thiazolidinediones)
include hepatotoxicity (!!!!) and cardiovascular toxicity. Absolute contraindication in pts with liver failure or CHF. Binding to PPAR-γ causes *weight gain from fluid retention*. !!!!!
# thyroid Anions (!!!)
include thiocyanate, perchlorate, pertechnetate, fluoborate, and high levels of iodide. This is different from the Wolff-Chaikoff effect, which is the observation that excess iodine within the thyroid gland will temporarily inhibit thyroid peroxidase, thereby decreasing iodine organification and T3/T4 production. At high levels, iodide (the required precursor for synthesis) exerts strong negative feedback against the release of thyroid hormone. The other anions competitively inhibit iodide transporters into thyroid follicular cells !!!
# Influenza shift vs drift
includes rearrangement of its viral genomic RNA segments; *shifts represent drastic changes and can cause pandemics. * This occurs when virus' with *segmented genomes* exchange segments, resulting in high-frequency transfer of genetic information, and a new virus with a combination of surface antigens that has NEVER been exposed to a human immune system anywhere on the planet. Antigenic/genetic SHIFT cause pandemics!!! "shift in(flu) the pan" Drift includes more minor changes due to mutation of hemagglutinin and/or neuraminidase (ie, H1 N1) , but which the immune response is still able to respond to without major injury. This causes "seasonal flu".
# Duschenes labs and diagnosis
increased CPK and aldolase.... Use western blot and muscle biopsy.
# encephalitis
inflammation of the brain. Viral infections are the most common cause of the condition (HSV-1 in adults, HSV-2 in newborns. Commonly affects the *temporal lobe*. .!!!!!!! Encephalitis can cause flu-like symptoms, such as a fever or severe headache. It can also cause confused thinking, seizures, or problems with senses or movement. However, many cases of encephalitis result in only mild flu-like symptoms or even no symptoms. Diagnosis includes: PCR, especially in early detection of encephalitis Multinucleate giant cells on Tzanck smear of skin lesions Eosinophilic Cowdry intranuclear inclusion bodies
# somatostatinoma
inhibition of gastrin, so patients have achlorhydria (low acid production in stomach) Somatostatin also inhibits CCK, which normally contracts gallbladder, so lack of this leads to cholelithiasis and steatorrhea!!!!! !!!!
# Prolactin (!!)
inhibits GnRH synthesis/release from hypothalamus. This leads to *decreases gonadal hormones* responsible for Amenorrhea and low libido (FSH/LH are indirectly suppressed), IMPOTENCE (it suppresses ALL of GnRH, LH/FSH, test) Long term this *can cause osteoporosis*.
# Inulin vs creatinine on GFR
inulin is filtered, but neither reabsorbed nor secreted by renal tubules. • Renal clearance of inulin is the most accurate method of calculating GFR because inulin is both freely filtered by the renal glomeruli and NOT reabsorbed or secreted in the renal tubules. Because measurement of inulin clearance is difficult and laborious, it is not commonly used clinically. • Clinically, renal clearance of creatinine, an endogenous substance, is the most convenient and most common method of calculating GFR. Use of creatinine clearance to approximate GFR, however, comes with limitations, due to the fact that some creatinine is secreted by the proximal kidney, which may result in a slight overestimation of GFR
# Intussusception
invagination of one portion of the bowel into itself—proximal portion usually dragged into distal portion by peristalsis. As you drag it in, you also drag in blood supply, so this lads to infarction, *currant jelly stools* (contain blood/mucus) Assoc w/a "lead point" - an intraluminal mass that peristalsis can "hook onto" and drag bowel during peristalsis. In *adults*, this is usually a *tumor*.... In children is it usually *lymphoid hyperplasia* after a *viral infection* (ton of peyer's patches)
# Renal cell carcinoma pathogenesis
involves *loss of VHL* from *chromosome 3p*, VHL is a *tumor suppressor gene* Results in *increased IGF-1* (promotes growth) and *increases HIF transcription factor* which in turn increases both *VEGF and PDGF* to promote both *angiogenesis* and *growth of the tumor*!!!!!!!!!!
# Large vessel Vasculitis
involves organ or major branches: 1) temporal (Giant Cell) Arteritis 2) Takayasu Arteritis
# anaplasia (!!!)
irreversible- Anaplasia cells have various sizes and shapes (pleomorphic) and they divide rapidly, producing cells *without any resemblance to the structure or function of the normal cell. * These cells progressively dedifferentiate resembling the undifferentiated cell of their original cell type. - Cells may be fused together creating giant cells (!!!!!) with either single or multiple nuclei and the nuclear cytoplasm ratio may approach 1:1 instead of the normal 1:4 or 1:6.
aspirin
irreversibly inhibits both COX 1 and 2 by* covalent acetylation*, for 3-7 days!! (life of the platelet)....... this decreases symthesis of both Thromboxane A2 .... And also the other prostaglandins, Increased bleeding time until new platelets produced (7 days), but *no effect on PT or PTT*
# The rabies vaccine
is a *killed virus*.... and is one of the few vaccines given after exposure to virus. Works by taking advantage of long incubation period of rabies, by increasing host immunity. Passive immunity: Human Rabies Immune Globulin (HRIG)
# Levofloxacin
is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase iv which is an enzyme necessary to separate replicated DNA, thereby inhibiting cell division
# Tinea versicolor (pityriasis versicolor)
is a common superficial fungal infection caused by* Malassezia* Malessezia, the causative organism in tinea versicolor, is a dimorphic fungus that is part of the normal skin flora and is not contagious. • Tinea versicolor most commonly affects adolescents, young adults, and even children in areas with *hot and humid weather !!!! * • Most cases are reported during the summer, *when the affected areas fail to tan after sun exposure !!! * Tinea versicolor presents with hypopigmented, hyperpigmented, or erythematous macules on the trunk and proximal upper extremities from the degradation of lipids that produces acids that damage melanocytes. Diagnosis is made with *KOH examination of scrapings from lesions..* Both hyphae and yeast cells are evident in a pattern that is described as "spaghetti and meatballs."
Perihepatitis (a.k.a. Fitz-Hugh-Curtis Syndrome)
is a complication of Chlamydia trachomatis or N. gonorrhoeae infection. It is characterized by inflammation of the liver capsule and nearby peritoneum secondary to Pelvic inflammatory disease in 25% of cases of PID. Presents as RIGHT UPPER QUADRANT (liver) pain.
VACTERL syndrome
is a congenital syndrome caused by defective migration of mesoderm-derived cells: congenital syndrome caused by defective migration of mesoderm-derived cells: • Vertebral defect (present in 70% of TEF cases) • Anal atresia (imperforate anus) ± fistula (80%) • Cardiac anomalies, such as VSD, single umbilical artery (53%) • Tracheo-Esophageal fistula ± esophageal atresia (70%) • Renal anomalies (53%) • Limb anomalies such as radial dysplasia, pre-axial polydactyly, and syndactyly (65%) Note: VATER syndrome is a more limited form of the VACTERL syndrome without cardiac or limb defects.
# Total Anomalous Pulmonary Venous Return
is a cyanotic congenital heart condition in which all 4 pulmonary veins drain into the right atrium or the systemic veins (e.g. superior vena cava, coronary sinus, etc). Since there is *no oxygenated blood returning to the left atrium*, an *atrial septal defect* or *ventricular septal defects* are *required* to allow oxygenated blood into the systemic arterial system. TAPVR may result in pulmonary congestion,pulmonary hypertension, failure to thrive, cardiomegaly, and even death.
# Bethanechol !!!!
is a direct cholinergic agonist that stimulates both M2 and M3 receptors. It especially favors M3 activation. • Bethanechol has the following physiologic effects. o Through stimulation of the M3 receptor, bladder detrusor contraction increases with concurrent bladder sphincter relaxation, which promotes urination. o Gut motility also increases as a result of M3 activation. • Bethanechol is usually used to treat postoperative/neurogenic ileus and *bladder atony (urinary retention). * Bethanechol has the following side effects. • Bradycardia • Hypotension • Sweating/flushing • Salivation • Diarrhea • However, there are no effects on the CNS as bethanechol cannot cross the blood-brain-barrier.
# Weber's syndrome (superior alternating hemiplegia)
is a form of stroke characterized by the presence of an *ipsilateral oculomotor nerve palsy and contralateral hemiparesis or hemiplegia.* This lesion is usually unilateral and affects several structures in the midbrain including: substantia nigra contralateral parkinsonism because its dopaminergic projections to the basal ganglia innervate the ipsilateral hemisphere motor field, leading to a movement disorder of the contralateral body. corticospinal fibers contralateral hemiparesis and typical upper motor neuron findings corticobulbar tract difficulty with contralateral lower facial muscles and hypoglossal nerve functions oculomotor nerve fibers ipsilateral oculomotor nerve palsy with a drooping eyelid and fixed wide pupil pointed down and out. This leads to diplopia It is caused by: - midbrain infarction as a result of *occlusion of the paramedian branches of the posterior cerebral artery or of basilar bifurcation perforating arteries*
# Cladribine:
is a purine analog used to treat hairy cell leukemia because of its high rate of success in generating complete remissions. It is resistant to degradatyion by ADENOSIDE DEAMINASE.
Methadone
is a synthetic, orally effective morphine derivative with less efficacy and a *longer duration of action*.... It is indicated for withdrawal from opiate dependence
pulsus paradoxus
is an *abnormally large decrease in systolic blood pressure* DURING INSPIRATION The normal fall in pressure is less than 10 mmHg or 10 torr. When the drop is more than 10mm Hg, it is referred to as pulsus paradoxus. Pulsus paradoxus is a sign that is indicative of several conditions, including *cardiac tamponade*.... pericarditis, chronic sleep apnea, croup, and obstructive lung disease (even asthma!!) a pericardial effusion exerts pressure on the flimsy anterior wall of the right ventricle → ↑ right ventricular pressure, which displaces the interventricular septum to the left, causing ↓ left ventricular volume ∴ ↓ stroke volume ∴ ↓ systolic pressure.
# Omenn Syndrome
is an AR form of SCID that is caused by nonsense mutations in the genes involved in early VDJ recombination (RAG1 or RAG2) → *without VDJ recombination* these patients cannot produce functional lymphocytes
# Baclophen
is an agonist for the GABAB receptors. Its beneficial effects in spasticity result from actions at spinal and supraspinal site. Baclofen is widely used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, spastic diplegia cerebral palsy, multiple sclerosis, amyotrophic lateral sclerosis , peripheral neuropathy and trigeminal and glossopharyngeal neuralgias.
# hartnup disease
is an autosomal-recessive defect in intestinal AND renal transporters for neutral amino acids. This causes tryptophan excretion in urine and leads to pellagra. (dementia, diarrhea, dermititis) Leads to wasting of the* neutral amino acids* except proline, hydroxyproline and arginine!! (differentiate from Fanconi syndrome!!) Patients can develop symptoms of niacin deficiency or pellagra because of wasting of tryptophan!!! Eat more tryptophan/niacin!!!
# Tumor lysis syndrome (TLS) (!!)
is an oncologic emergency caused by *massive tumor cell lysis due to chemotherapy* leading to metabolic abnormalities caused by the release of large amounts of phosphate, potassium, and nucleic acids into the systemic circulation. • TLS usually occurs after the initiation of cytotoxic therapy in certain patients with aggressive lymphomas (i.e. Burkitt lymphoma) and T-cell acute lymphoblastic leukemia (ALL).
# Ventricular septal defect
is an opening in the ventricular septum allowing *left to right* shunting of blood (high pressure in LV to lower in RV). It is the *most common* congenital heart defect... associated with *fetal alcohol syndrome* When blood crosses over, it leads to more blood in pulmonary circuit and pulmonary hypertension... eventually the shunt reverses because the pulmonary pressure is actually higher, so you get blood to shunt right to left, and thus cyanosis.(*Eisenmenger's syndrome*) Small defects often asymptomatic, large defects can lead to Eisenmenger syndrome.
# Hep A
is an unenveloped (naked capsid), single-stranded RNA virus with a cubic (icosahedral) symmetry. # Hep A spread and complications It is commonlt a "anicteric" (subclinical, no jaundice!!) infection in young children!!!! (anti-hepatitis A IgG is present) fecal-oral, uncooked food/seafood, contaminated water. Commonly TRAVELERS. (!!!!!!) (ie, people who travel to shitty/crowded placed). BOILING WATER Kills hep A !!!!!! (not just heating it, it has to be BOILED) Most likely hepatitis to produce Jaundice -most recover, liver damage reversed, no carrier state - produces fever, malaise, nausea, vomiting, etc.
# Brief psychotic disorder
is an unprecedented episode of psychosis lasting more than ONE day but LESS THAN 1 month. (1 day to 1 month). Usually stress related. Has sudden onset, but then full return to premorbid level of functioning.
# Niacin excess
is associated with facial flushing , hyperuricemia, and hyperglycemia. (acanthosis nigricans).... The *insulin resistance* is problematic for diabetics !!!
# type 2 dyslipoproteinemia/ familial hypercholesterolemia
is characterized by an *absence of or a decrease in competent LDL receptors*. The inheritance pattern is autosomal dominant.
# Progressive Multifocal Leukoencephalopathy
is demyelination of the central nervous system due to destruction of oligodendroglia caused by latent John Cunningham (JC) virus in patients with a COMPROMISED immune system. • Progressive multifocal leukoencephalopathy is seen in patients with an HIV infection and is also associated with use of natalizumab and rituximab.
Pericarditis
is inflammation of any of the layers of the pericardium. It often presents with the presence of fluid in the pericardial space. The fluid can be composed of blood, serous fluid, or transudate. Severe and constant middle/left chest pain that radiates to neck/shoulders. Pain increases on inspiration, relieved by sitting up and leaning forward. !!!!!! Physical symptoms of acute pericarditis include a friction rub on auscultation!!! This can best be auscultated with the diaphragm of the stethoscope over the left lower sternal edge or apex during end expiration with the patient sitting up and leaning forward . It may be accompanied by dyspnea/tachypnea in patients with sizable effusions. The pericardial friction rub can be distinguished from a pleural friction rub in that it does not disappear when the patient holds their breath. Pericarditis is worsened by swallowing!!!! Rember, there is a major link with it and SLE!!!!!!
#murphy's sign
is performed by asking the patient to breathe out and then gently placing the hand below the costal margin on the right side at the mid-clavicular line (the approximate location of the gallbladder). The patient is then instructed to inspire (breathe in). Normally, during inspiration, the abdominal contents are pushed downward as the diaphragm moves down (and lungs expand). If the patient stops breathing in (as the gallbladder is tender and, in moving downward, comes in contact with the examiner's fingers) and winces with a 'catch' in breath, the test is considered positive.
Vancomycin
is reserved for serious, multidrug-resistant *gram-positive* organisms including • MRSA • Staphylocossus. epidermidis • sensitive Enterococcus spp. • C. difficile (via oral dose for pseudomembranous colitis)
suprachiasmatic nucleus (!!!)
is the master circadian clock of the nervous system. It synchronizes circadian rhythmicity with the external day-night cycle via light inputs from the retina. Manages release of melatonin (from the pineal gland). This area receives input from *photosensitive ganglionic cells in the retina* via the *tetinohypothalamic tract*. The SCN then takes this info and modulated melatonin/cortisol etc.
# Rhinovirus
is the most primary cause of the *common cold *(the second most common is coronavirus). Transmission occurs via aerosols of respiratory droplets and from contact with contaminated surfaces or fomites, including direct person-to-person contact. • Rhinovirus is *acid-labile, which accounts for lack of gastrointestinal symptoms!!!!! Once the pH drops, the rhinovirus is inactivated in the stomach!!!!!!! * • Rhinovirus preferentially replicates at the cooler 33°C of the nose and upper airways. The warmer temperature of the lungs precludes rhinovirus pneumonia. No vaccine is available due to the variability in surface proteins, which is responsible for the over 100 serotypes.
# GM-CSF (granulocyte-macrophage colony-stimulating factor, sargramostim
is used to stimulate stem cells to produce granulocytes - which are precursors for neutrophils, basophils, and eosinophils, and monocytes.
# Vitamin A uses
isotretinoin (all-trans retinoic acid, acid form of vitamin A), which is a topical medication used for mild acne and psoriasis !!! Vitamin A can be useful in measles !!! All vitamin A medications work by binding to eukaryotic nuclear receptors (retoinoic acid receptors). Then then act as ligand-activated transcription factors.
# plasma protein concentration and renal flow
it does not affect RPF. Has inverse relationship with GFR (ie, high plasma proteins means low GFR.... And thus, low FF)
#acute viral hepatitis findings (!!!!)
key features of acute hepatitis (for ALL virus') are inflammation and hepatocyte degeneration. The main pathological characteristics are listed below: • Ballooning degeneration: Injury causes hepatocytes → necrosis. • Periportal (!!) and bridging necrosis: • Mononuclear inflammatory infiltrate around the portal tracts (!!!!): • Hepatocyte apoptosis (!!!): Caused by CD8+ T cells. The apoptotic hepatocytes are phagocytosed by the infiltrating macrophages. They *form round pink staining acidophilic bodies known as Councilman bodies, aka apoptotic bodies* !!! • Cholestasis with bile plugs: Can cause a brownish staining of the hepatocytes
# There are three serious forms of energy malnutrition:
kwashiorkor, marasmus and mixed marasmus-kwashiorkor. • Kwashiorkor and marasmus are distinguished symptomatically primarily by edema. Patients with kwashiorkor are edematous. Patients with marasmus tend not to have edema.
# klebsiella
lactose-fermenting, growing pink colonies on MacConkey's agar. • K. pneumoniae pneumonia occurs more commonly in people in *long-term healthcare settings (hospital, nursing homes), and in people with impaired immune defenses, especially diabetics and alcoholics (particularly via aspiration)*. K. pneumoniae is uncommon in otherwise healthy people. • K. pneumoniae causes • *Nosocomial and community-acquired pneumonia • Nosocomial urinary tract infections • Liver abscesses* K. pneumoniae pneumonia typically presents with fever, pleuritic chest pain, dyspnea, and "*currant-jelly*" bloody sputum.
# Ischemic stroke necrosis (!!)
leads to *liquefactive necrosis* 1)- earliest finding is *red neurons*!!! Takes about *12 hours*. Present for about 24 hours!!! 2) - After the neurons die, you get inflammation first through neutrophils (last around 1-3 days) . 3) - then macrophages/phagocytosis (*microglial cells* are the 'macrophages of the brain') for days 3-5. 4)... then (1-2 weeks) healing with reactive gliosis from micro glia (!!), and vascular proliferation around the *liquefactive necrotic area*..... and *granulation LIKE tissue forms* after about a week.... 5) Eventually (after like a month) you get a *fluid filled cystic space surrounded by gliosis* (reactive *astrocytes* line the space). !!!!!
# Myocardial infarction
leads to *necrosis* (irreversible) of cardiac myocytes, classically due to *rupture of an atherosclerotic plaque* in a coronary artery, causing with thrombosis and *complete* occlusion of coronary artery, leading to ischemia and infarct. Other causes include coronary artery vasospasm, emboli, and vasculitis (Kawasaki)
#operant conditioning (!!)
learning in which a particular action is elicited BECAUSE it produces a *punishment OR reward*... usually deals with VOLUNTARY responses. Includes: - positive reinforcement - negative reinforcement - punishment - extinction
# Klumpke palsy aka claw hand (!!!)
lesion of the *lower trunk (C8-T1) *of the brachial plexus!!!! ; extremely rare and can be caused by a forceful combination of arm traction and abduction during delivery. Note: Although lower trunk lesions are typically presented as obstetrical complications, adults may sustain the injury *by grasping for a ledge when falling from height!!! * Examples include grasping for the top rung of a ladder when falling or grabbing a tree branch when falling from above.
# p53
like a 'traffic cop'...p53 protein product arrests the cell in G1 phase by inhibiting Cdk4. p53 promotes apoptosis via *activates Bax-Bak,* a pro-apoptotic gene which allows *cyt c to be released from the mitochondria*... it does this by by BLOCKING THE FUNCTION OF BCl-2, thus causing formation of pores in mitochondrial membrane.... remember, BOTH copies of p53 must be knocked out ("two hit hypothesis of tumor supressor genes".
# Clofibrate/fibrates and Cholelithiasis
lipid lowering drug, *increases HMG CoA reductase* !! - also decreases conversion of cholesterol to bile acids by *suppression cholesterol 7a-hydroxylase* ... thus cholesterol is less soluble !!!! • Cholesterol 7α-hydroxylase catalyzes the rate-limiting step of bile synthesis. (!!!!!!!!!!!!!)
# mRNA p-bodies
located in the CYTOPLASM. They contain exonucleases, decapping enzymes, microRNA's, and may even store mRNA.
# symptoms of villous adenomas
lower intestinal bleeding causing guaiac-positive stool (fetal occult blood) and microcytic hypochromic anemia. - partial obstruction (crampy abdominal pain, constipation) -- may secrete *large amounts of mucus* leading to *secretory diarrhea* and secondary electrolyte imbalances!!!! (ie, hypokalemia) !!!
# Superficial inguinal nodes
lower/external vagina and scrotum lymph drainage lower anus
# Lymphangiosarcoma (!!!!)
lymphatic malignancy associated with *persistent lymphedema* that can occur after a *radical mastectomy* for breast cancer.
# macrocytic megaloblastic anemia
macrocytic anemia with hypersegmented neutrophils!! (normally neutrophils have 3-5, >5 is hypersegmented)
# IL-12:
main source is macrophages • Activates NK cells • promotes differentiation of naive T cells into Th1 cells
urogenital sinus males and females
males.... bladder, prostatic urethra, membranous urethra, proximal penile urethra.... NOT the ureter Female.... bladder, lower 1/3 vagina
# Mesothelioma
malignant tumor of the *visceral OR parietal pleura* resulting from long-term exposure to *asbestos*. The development of mesothelioma has a long latency period. Generally occurs *25-45 years after asbestos* exposure. Smoking does NOT increase the risk of mesothelioma in asbestos workers. This is in contrast to the synergistic effect of *smoking and asbestos exposure* on developing *primary bronchogenic lung carcinoma*
Kwashiorkor
malnutrition with inadequate protein ONLY (adequate carbohydrates, calories) • The typical presentation of kwashiorkor is a child with a swollen belly due to ascites (accumulation of fluid in the peritoneal cavity) and an enlarged, fatty liver. Patients may also have normal or near normal height and weight, anasarca, pitting edema of the lower extremities, dry, atrophic, peeling skin, dry hair that falls out easily, and dilated intestinal loops. • In some areas, kwashiorkor presents between ages 1-3 when a child that received enough protein while breastfeeding is displaced by a new child. • Decreased protein consumption leads to decreased protein production. Because of the decreased protein production the capillary oncotic pressure decreases and this leads to tissue edema in kwashiorkor. The following mnemonic might be useful: You need water to wash → kwashiorkor has excess water (edema). • The fatty liver in kwashiorkor is due to decreased apolipoprotein synthesis. Because of decreased apolipoprotein synthesis, fats that would be exported from the liver by apolipoproteins are trapped.
# Manic episode
manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood lasting AT LEAST ONE WEEK. During the mood disturbance, three or more of the following are present. Use the DIG FAST mnemonic: Distractibility Irresponsible and erratic behavior (ie, seeks pleasure without regard to consequences) Grandiosity (inflated self-esteem) Flight of ideas (racing thoughts) Activity is increased and goal directed Sleep (decreased need) Talkativeness or pressured speech
# Aortic dissection presentation
may mimic *myocardial infarction* (both often present with sudden-onset of severe chest pain *radiating to the back)*—however, serum levels of *cardiac enzymes* like CK-MB and troponin I (are normal in aortic dissection*!!!! Unequal pulses in upper extremities are sometimes observed due to (partial) occlusion of the left subclavian artery or brachiocephalic trunk (!!!!!)
# VZV infection clinical course
mild fever prodrome (headache, anorexia, abdominal pain) 24 - 48 hours before onset of a *generalized vesicular asynchronous rash*:
# Cyclothymic disorder:
mild form of bipolar disorder with depressive symptoms lasting at least 2 years. Intermittent hypomanic episodes occur. Many affected patients have relatives with bipolar disorder . Patients do not get either quite as high as bipolar, or as low as major depression. • Cycles between depressive and manic episodes last between 6-9 months and become shorter as the illness progresses • If untreated, a manic episode lasts approximately 3 months • Usual treatment for bipolar disorder is lithium
colostrum
milky fluid that comes from the breasts of humans, cows, and other mammals the first few days after giving birth, before true milk appears. It contains proteins, carbohydrates, fats, vitamins, minerals, and IgA (!!!!!!!) that fight disease-causing agents such as bacteria and viruses.
Amyloid
misfolded protein that deposits in EXTRACELLULAR SPACE (outside of cell), thereby damaging tissues. Not one protein, it is a broad category, multiple proteins can deposit as amyloid. Usually have sinear, non-branching B-pleated sheet configuration. Stains pick up *CONGO RED staining, and reveal APPLE GREEN birefringence when viewed micoscopically under polarized light. * Tends to deposit around blood vessels. Can be deposited systemic (which can be primary, or secondary) or localized.
corticosteroids asthma
molecular mechanisms. 1. Inhibition of phospholipase A2 (mechanism under investigation) causes decreased synthesis of arachidonic acid and its inflammatory metabolites (prostaglandins and leukotrienes). 2. Inactivation of the pro inflammatory transcription factor NF-κB causes decreased production of TNF-alpha and other inflammatory agents • Prostaglandins and leukotrienes are known to contribute to the pathogenesis of bronchospasm. Inhibition of their synthesis is one mechanism by which inhaled corticosteroids help in the treatment of asthma. Corticosteroids also stimulate synthesis of β2 receptors in the lung and nasal mucosa. This is why they are commonly co-administered with long acting β2 agonists, to prevent down regulation of β2 receptors (caused by chronic β2 agonist use).
epinephrine binding and use
more selective to beta receptors than alpha...EXCEPT alpha effects predominate at HIGH doses.... used in: - anaphylaxis - open angle glaucoma - asthma -hypotension At LOW doses, epinephrine DECREASES diastolic blood pressure because of *B2 mediates vasodilation* !! (It also INCREASES systolic pressure because of B1 mediated HR !!) At HIGH doses, it INCREASES diastolic blood pressure because of *a1 mediated vasoconstriction* !!!
# Hashimoto thyroiditis- !!!
most common cause of hypothyroidism in areas of world with sufficient iodine. (!!!!) May initially present as hyperthyroidism (destroy thyroid and some leaks out into blood... but then hypo as cells die) Histologically defined by: - *Lymphocytic infiltrate*/chronic inflammation (!!) and Prominent germinal follicles/centers (!!) - *Atrophic thyroid follicles* lined by *Hürthle cells* (epithelial cells with abundant, granular, deeply eosinophilic cytoplasm... turn pink). Because thyroid follicles are normally lined by low cuboidal epithelium, this is also known as Hürthle cell metaplasia.!!!!
# selective IgA deficiency (!!)
most common inherited B cell defect. (!!) Represents a failure of terminal differentiation of IgA-producing B cells which DO NOT class switch from IgM. → IgA levels are nearly undetectable in serum/plasma. (IgA < 7). Because the defect is specific to IgA-lineage B cells, the other immunoglobulins are normal Increased risk for mucosal infections, especially viral!! IgA deficiency often seen in CELIAC.
# Von Willebrand Disease
most common inherited coagulation disorder. Typically present as: slightly increased bruising -heavier menses Gingival bleeding -nosebleeds and uncontrolled bleeding during MINOR surgeries. (ie, dental extractions)!!! *treat with DDAVP (desmopressin, an ADH analog), which releases vWF from Weibel-Palade bodies of endothelial cells (!!!!) *
# Urothelial (transitional) cell carcinoma
most common tumor of urinary collecting system. Transitional /urotlial epithelium lines the urinary collecting system, which includes the renal calyces, renal pelvis, ureters, bladder ∴ transitional cell carcinoma may arise in any of these locations. Transitional cell carcinoma tends to spread by *direct local extension (invasion) into surrounding tissue*!!!!!! . Contrast this with *renal cell carcinoma*, which *spreads hematogenously.* The most common presenting symptom in bladder cancer is *painless hematuria* !!! Patients often have multiple tumors because the whole area has been hit with carcinogen exposure, and often get recurrance. (called a *field defect*)
# Renal Cell Carcinoma aka *clear cell carcinoma*.
most lethal urologic cancer (40% mortality in RCC vs. 20% mortality in bladder/prostate cancer) All RCCs are *adenocarcinomas* derived from *renal tubular epithelial cells* which are usually from the PROXIMAL TUBULES !!!
hereditary spherocytosis
mostly autosomal dominant inherited defect in one of several RBC cytoskeleton membrane proteins: spectrin & ankyrin are the most commonly affected. Without the structural proteins, the RBC assumes a spherical shape (loses biconcave shape!!!), and creates a high RDW (RBC distribution width)!!! "Normocytic anemia.... *Spherocytes, which are about 2/3 the size of a normal RBC with LOSS of central palor.* !!!
# Anterior shoulder dislocation can also result in (!!!)
musculocutaneous nerve injury. The musculocutaneous nerve courses across the coracobrachialis in front of the shoulder joint, which renders the nerve prone to traction injury. It innervates the biceps and brachialis!!! Musculocutaneous nerve injury presents with anesthesia of the anterolateral forearm and weakness in elbow flexion and forearm supination. !!!!
# JAK2 mutations and conditions
mutation found in polycythemia vera, myelofibrosis, myeloid metaplasia, and essential thrombocythemia.
#Pyloric stenosis
narrowing of the pyloric canal due to *hypertrophy of the smooth musculature*, most commonly in first born males. obstruction (stenosis) → *nonbilious (!!) projectile vomiting* and demands to be re-fed soon *"hungry vomiter"*. (bile enters in duodenum) The pyloric stenosis usually develops between 2-6wks of age.... NOT right at birth! Exam may reveal an *"olive" (the hypertrophic pylorus) * in epigastrium !!! Treat with surgery. Compare to duodenal atresia (distal to bile duct), which features vomiting of bile-stained fluid within 48hrs of birth.
#ach esterase inhibitor toxicity
nausea, dizziness, insomnia
# Wegener Granulomatosis (!!)
necrotizing *medium and small-sized vessel* vasculitis involving nasopharynx (!!!), lung infarctions and glomerulonephritis. In Wegener granulomatosis serum *c-ANCA antibodies* (anti-neutrophil antibodies) correlate erratically with treatment in 90% of the cases.(!!!)
#17 hydroxylase deficiency
needed for pregnenalone to produce glucocorticoids and eventually sex steroids.... 17 hydroxylase deficiency leads to excess mineralcorticoids!!!! With NO glucocorticoids or sex steroids. ↓ In end products *testosterone/DHT AND cortisol (!!)* ↑ In end product aldosterone (!!!) ↑ ACTH, ↑ LH,
# strongyloides stercoralis
nematode (roundworm) that is transmitted by fecal-cutaneous contact. infection clinically presents as *pneumonia and gastroenteritis. * •* Infectious (filariform) larvae penetrate the skin of feet*, causing local itching, eventually entering the bloodstream and is transported to the lungs. The larvae can enter alveoli and ascend toward the trachea, causing respiratory tract inflammation, which can *manifest as pneumonia*. • * Larvae * can pass from the trachea to the pharynx, and when swallowed the larvae mature into adults in the small intestines to invade the mucosa and lay eggs. Larvae from the hatched eggs become embedded within the intestinal wall, causing inflammation that manifests as pain and diarrhea. • Larvae can go through autoinfection, by penetrating the intestinal wall to reenter the bloodstream and repeating the infectious cycle. • *Rhabtidiform larvae can be shed in the feces *to contaminate soil. • Diagnosis can be made by • *Detection of larvae not eggs (as seen in hookworm) in the stool* • Eosinophilia • Swallowing a long string to pull out larvae, also known as the "string test"
# Multiple myeloma and immunoglobulin (!!!!!!)
neoplastic plasma cells produce immunoglobulin, which elevates serum protein, so you test with serum-protein electrophoresis to determine the cause (S-PEP). Normally, there is: - a large albumin band - a1 band - a2 band - b band - gamma band (which is normally wide, not as high as albumin, represents gamma-globulins) In patient with multiple myeloma, since a plasma cell can only produce ONE antibody, there is a very high, sharp spike in the GAMMA region (M-spike) which indicates mono-clonial immunoglobulin, usually IgG (55%), but can be IgA (25%).
# CML- chronic myeloid leukemia
neoplastic proliferation of mature myeloid cells, especially granulocytes (especially basophils). Driven by *Philadelphia chromosome: t(9;22), creating BCR-ABL,* a fusion gene with increased tyrosine kinase activity, which drives overproduction of neoplastic cells. 3 phaes: 1) chronic phase- Splenomegaly is common 2) Accelerated phase (spleen is becoming bigger) 3) transformation to Acute leukemia (AML 2/3 of the time, ALL 1/3 of the time... *patient has mutation in hematopoietic stem cell) Most cases result in blast crisis!!! number of blast forms ↑↑ and behaves like AML (short survival and rapid progression)
# Chronic leukemia
neoplastic prolifferation of MATURE circulating lymphocytes, characterized by high WBC count. General Facts: Insidious in onset when compared to acute leukemias. Characterized by generalized, painless lymphadenopathy. Laboratory findings are similar to acute leukemia, except for blasts which are <10% in chronic leukemia. Clinical course is less devastating, but also less responsive to therapy
# neutrophil rolling
neutrophils hit the SELECTINS which act as 'speed bumps' on endothelial cells as they are expressed. They "roll" on the endothelial vessel. 2 kinds of selectins 1) P-selectin released from Weibel-Palade bodies, mediated by histamine. Weibel-Palade bodies contain 2 important proteins: P-Selectin, and (von) Willebrane factor. 2) E-selectin induced by TNF and IL-1 (!!!). Selectins bind "sialyl Lewis X" (!!) on leukocytes, which results in rolling of neutrophils/leukocytes along the vessel wall.
# Vitamin A deficiency leads to
night blindness - squamous metaplasia leading to skin abnormalities (follicular hyperkeratosis) !!! eye abnormalities (Bitot's spots → buildup of keratin debris in conjuctiva), lung abnormalities (bronchitis, pneumonia) immune suppression
# Changes in heart up to 4hrs after MI
no gross or morphologic changes, but *Ventricular failure* (and subsequent *cardiogenic shock*) is the *most common cause* of death in MI patients during the *in-hospital phase* (ie, after patients have reached the hospital):
# target cell
normal RBC has biconcave shape with central palor (no hemoglobin). Target cells have a bleb of membrane and some hemoglobin in the bleb, which creates a dot of red where there should be central palor. Seen in B-thalassemia !!!!!!
# Postenteric reactive arthritis occurs after an infectious diarrhea and is most commonly associated with:
o Campylobacter o Salmonella o Shigella o Yersina
# Factors associated with a high risk of TLS include:
o High tumor cell proliferation rate o Chemosensitivity of the malignancy o Large tumor burden o High white blood cell count o *High pretreatment serum lactate dehydrogenase (LDH)* Symptoms associated with TLS reflect the *metabolic abnormalities (hypocalcemia, hyperkalemia, hyperphosphatemia, and hyperuricemia) * and include the following: o Diarrhea o Vomiting o Anorexia o Acute kidney injury o Cardiac arrhythmia o Hematuria o Tetany and muscle cramps o Seizures o Sudden death • Acute kidney injury results from hyperuricemia and hyperphosphatemia because uric acid precipitates readily in the presence of calcium phosphate crystals (!!!!!!) Causes *tubular obstruction with urate crystals* !!! • TLS prophylaxis is accomplished with* aggressive IV hydration* and possibly* hypouricemic agents such as rasburicase and allopurinol. * (!!!)
# Effects of acetazolamide toxicity include:
o Hyperchloremic metabolic acidosis (!!!) o Hypokalemia o NH3 toxicity o Neuropathy
# SCID causes (!!!)
o Note that there are several etiologies of SCID: Etiologies: 1) X-linked Cytokine receptor defects- 2) Adenosine deaminase deciciency- 3) MHC II deficiency- (No CD4 Helper T-cells) (Bare lymphocyte syndrome!!! AR inherited) 4) Omenn Syndrome
# Vitamin K deficiency findings
o prolonged (increased) PT and PTT o gastrointestinal bleeding (hemmorhagic disease of newborn!!)
# Asthma
obstructive* lung disease characterized by hyperreactivity of the airways causing *reversible* obstruction and *chronic inflammation*. Often presents in childhood, presents with other atpoic reactions like *eczema* or *allergic rhinitis* 3 types of asthma 1. Atopic asthma- is the most common form. It represents a classic form of *type I hypersensitivity* 2. Non Atopic asthma- characterized by a *lack* of allergen sensitivity. Airway reactivity classically occurs in response to *viral infections*. 3. Drug induced - asthma is due to the effect of *NSAIDs*, which *block the COX* pathway leaving the *unopposed lipoxygenase pathway* which produces *leukotrienes* (potent bronchoconstrictors).
# Duodenal atresia
occlusion of the duodenal lumen secondary to failed recanalization, ends in *blind loop* !! Duodenal atresia is associated with: Polyhydramnios (cannot resorb/digest amniotic fluid) * Bile-containing* vomitus (since the obstruction is distal to the point where bile enters the gut)!!!! *Double bubble appearance* (distention of both *stomach* and *duodenum*) on plain radiographs (!!) Treatment: side-to-side anastomosis (avoids injury to bile and pancreatic duct). 30% assoc w/ Down's (!!!) , 25% w/ isolated cardiac defects
Transcortical sensory aphasia
occurs from damage NEAR Wernicke's area producing an aphasia where patient are able to speak fluently and repeat words after the examiner, but with poor comprehension.
# Wernicke (sensory) aphasia
occurs from damage to posterior part of the *superior temporal gyrus* on the dominant side leading to *receptive, fluent aphasia* (meaning the patient *cannot understand any form of language but is able to verbalize fluently, except the speech lacks any meaning.* Wernicke is wordy!!!! Wernicke aphasia patients are unaware of deficit and show no distress.
# alcohol withdrawl
occurs in the following order: autonomic nervous system hyperactivity (tacycardia, tremors, anxiety) (!!!!!!) ... THEN psychotic symptoms (delusions, hallicinations)... then confusion (!!!!!!!!!!!!) feared complication is Delirium tremens (DT's). Occurs *48-72 hours* after last drink... treat alcohol withdrawl Benzo's for DT's... disulfiram (to condition patient to avoid alcohol)
# anemia of chronic diseases
occurs in the setting of a chronic infectious or inflammatory process (or cancer). It is one of the most common causes of anemia in hospitalized patients. Common causes include: - Chronic infectious processes (TB, osteomyelitis, lung abscess) - Malignancy (breast, lung, renal, HCC, Hodgkin's lymphoma) - Autoimmune disease (SLE, RA)
# Malignant hypertension presentation
occurs most often in young African American males and is accompanied by and *signs and symptoms of end-organ damage* renal failure- with laboratory findings of increased Cr/BUN and hematuria. Also *"flea bitten" kidney* which is *multiple hemorrhages* because of *ruptured arterioles on large swollen kidney* proteinuria, hematuria Change of mental status Chest pain, MI cerebral edema, papilledema.
Serotonin Syndrome
occurs when SSRIs are co-administered with any drug that can increase serotonin levels (e.g. MAOIs, meperidine, stimulants) • Serotonin Syndrome consists of the following triad: 1. Cognitive effects - mental confusion, agitation - hypomania, hallucinations, headache, coma 2. Autonomic effects - shivering, sweating - hyperthermia, hypertension, tachycardia - dilated pupils 3. Somatic effects - myoclonus !!! - hyperreflexia - tremor
# jejunal atreasia aka apple-peel atresia
occurs when the *jejunum fails to vascularize during embryogenesis.* This occurs because *diminished intestinal perfusion (!!!) leads to ischemia of a segment of bowel, with subjequent narrowing/obliteration of the lumen.* !!! If a major vessel is occluded, this results in a proximal blind pouch and a distal twirling (apple peel-like) distal ileum.
Omphalocele
occurs when the midgut loop of herniated intestines *fails to return* to the abdominal cavity. The result is a midline, *shiny peritoneal-covered sac* protruding through the umbilicus and containing abdominal organs . Associated anomalies: Beckwith-Wiedemann syndrome (gigantism, macroglossia, umbilical defect, hypoglycemia), trisomy 13 and 18.
# *coin lesions*
often seen in those under say 40yrs. Could include - granuloma (due to TB, fungus, hystoplasma in midwest!!) - bronchial hamartoma (often calcified)... it is a *benign mass* of *lung tissue and hyaline cartilage* (!!!)
#delusional disorder
one or more delisions for at LEAST one month. Other psychotic symptoms (hallicinations, disorganization) are absent... The patient is not really odd in other facets of life, is not impaired in daily living, just those related to the delusion. can appear similar to schizophrenic delusions. It is characterized by a fixed, non-bizarre delusional system and few if any other thought disorders. An important difference for diagnosis is that individuals with delusional disorder have relatively normal social and occupational functioning. Types include: erutomanic - thinking someone is in love with them Grandiose - thinking they have great talent/achievements Jealous- thinking their partner is unfaithful etc persecutory- believing they are being spied on, poisoned, harassed, etc somatic - believing their own bodily functions/sensations are abnormal
# risk factors for esophageal squamous carcinoma
one word: *irritation* 1. alcohol and tobacco (!!!!) 2. - consumption of Nitroso containing foods (Bezel nut chewing) !!!! - VERY hot tea (high cancer in south China and Iran where they drink hot tea, but this is a secondary cause) - Achalasia (rotting food stuck in esophagus irritates mucosa) - Esophageal webs (rotting food) Assoc w/ lye (strong alkali) ingestion
Opioids receptors
opioid receptors are prominent members of the G protein-coupled receptors. Activation of opioid receptors leads to: 1) inhibition of adenylyl cyclase and a decrease in the concentration of cAMP 2) an increase in K + conductance (increased potassium effux = hyperpolarization)!!!! 3) decrease in Ca 2+ conductance . These actions cause both presynaptic inhibition of neurotransmitter release (SUBSTANCE P) from the central terminations of small-diameter primary afferent fibers and postsynaptic inhibition of membrane depolarization of dorsal horn nociceptive neurons
# Salmonella
oxidase-negative, lactose non-fermenting, gram-negative bacilli. It contains a special capsule called the "Virulence Antigen" which protects it from *opsonization and phagocytosis*. causes Osteomyelitis in *Sickle cell* patients
# Distinguish Churg-Strauss from Microscopic polyangiitis
p-ANCA is positive in both, but: 1. Churg- Strauss has *granulomas* (Microscopic polyangiitis has NO granulomas) 2) Churg- Strauss patients have history of *asthma*.... Microscopic polyangiitis has NO history of asthma (!!!!!!!!!!!) 3) Churg- Strauss patients have peripheral eosinophilia ... Microscopic polyangiitis patients do not
metabolic alkalosis
pH is high. PCO2 is high (indicating hypo-ventilation) !!!!! Bicarbonate is high (think of it as a ton of bicarbonate produced). PaO2 is low
# metabolic acidosis blood values
pH is low. PaCO2 is also low (hyperventilation) Bicarb is low (used to buffer!!) PaO2 is very high (respiration) H2P04 and NH4+ are high!! (buffering!!)
#lymph drainage of gonads
para aortic nodes
# PTT
partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT or APTT) is a performance indicator measuring the efficacy of both the INTRINSIC (now referred to as the contact activation pathway) AND the common coagulation pathways. It monitors heparin, but NOT low molecular weight heparin
# microangiopathic hemolytic anemias
pathologic formation of platelet microthrombi in small vessels. The Thrombi *create shear force on RBC's as they flow past it*....leads to *schistocytes* (fragmented parts of red blood cells, kinda look like a 'helmet' with two pointed ends, thus they are called *helmet cells*).... and also, anemia. Seen in TTP, HUS, DIC, HELP (in pregnant women).
# Nonselective MAO inhibitors (phenelzine) !!!
perform nonselective MAO inhibition (inhibit both MAOA and MAOB) in the presynaptic neuron, thus, inhibition of them leading to increased levels of norepinephrine, dopamine, and serotonin • Not used as first-line agents but can be used to *treat atypical depression* Atypical depression is characterized by: mood reactivity (they improve their mood when positive things happen, majorly depressed people do not really!!!) oversensitivity to rejection, hypersomnia, and increased appetite), • Do not confuse with *selective MAO inhibitors (selegiline and rasagiline)*: they perform selective irreversible MAOB inhibition leading to increased levels of dopamine → used in Parkinson's disease
*pringle maneuver
performed when there is traumatic liver injury, and it is *occluding the hepatoduodenal ligament*. This stops blood to the *portal triad*!!! If it keeps bleeding, then the laceration must be in the *interior vena cava* or *hepatic veins*. !!!!!
#Latent TB
person considered to have latent TB infection (LTBI) if, after assessment the clinician considered that the patient has a high probability of being infected with MTB, and does not have TB disease. They have an immunodiagnostic test which confirms evidence of having the TB organism in their body
#barbiturates
phenobarbital, thiopental, secobarbital) • Potentiates the effect of GABA by increasing the duration (not frequency) of chloride channel opening. Unlike BZDs, these drugs cause direct opening of Cl channels and can thus lead to overdose. • Treats anxiety and seizures • Unlike benzodiazepines, barbiturates induce the cytochrome P450 system ∴ barbiturates are contraindicated in porphyrias: In addition to inducing the cytochrome P450 system, barbiturates also *increase the metabolism of several drugs*, which often *decreases the pharmacological effect of these drugs*
selective alpha 1 agonist
phenylephrine (!!!!) • Clinical applications: hypotension, nasal congestion Causes arterial vasoconstriction. Thus, leads to: - increased systemic vascular resistance and BP - increased BP elicits *baroreceptor mediated increase in vagal tone* which *decreases stroke volume and HR* by SLOWING AV node conduction velocity !!!!!! Decreased pulse pressure
Roc curve
plots true positive rate (sensitivity) against the false positive rate (1-specificity) for different cutoffs of a diagnostic test
# RAS gene mutation
point mutation commonly mutated in MANY cancers. Seen in many carcinomas, lung, colon, pancreas, leukemias ras normally associated with GDP where is is inactive).... but is active when associated with GTP!! Activated Ras then activates MAPk. There is a protein called GAP (GTPase associated protein), this helps ras cleave GTP and turn it off.... GAP mutation causes excess ras cell signalling
# opioid poisoning management
poisoning can be countered with opiate antagonists such as *naloxone,* given IV
# Angiomyolipoma
polyclonal hamartoma consisting of thick-walled blood vessels ("angio"), smooth muscle ("myo"), and adipose ("lipoma") 20-30% of renal angiomyolipomas are found in patients with *TS (tuberous sclerosis)* !!!!!; angiomyolipomas in TS patients are more likely to be bilateral and/or multifocal
# primary hemostasis disorders
present with mucosal and skin bleeding: mucosal- epistaxis (nose bleed, most common), hemoptysis, GI bleed, hematuria Skin: Petechiae- (1-2mm), purpura (2-9mm), ecchymoses (1cm) - easy bruising
# orotic aciduria overview, AKA UMP synthase deficiency!!!!
presentation, treatment Disorder of *pyramidine* metabolism characterized by: - hypochromic megaloblastic anemia. The condition does not improve with vitamin B12 or folic acid administration!!!! - neurologic abnormalities - growth retardation !! - excretion of high levels of orotic acid in the urine. !!!! NO hyperammonia !!!! Treat with *uridine* supplementation. !!!! allows for a source of proper pyrimidine synthesis.
# primary vs secondary hemostasis disorders
primary disorders- skin/mucosal bleeding secondary- deep tissue bleeding into muscles/joints, or rebleeding after surgical procedures (ie, wisdom tooth)
#note primary vs secondatry hyperparathyroidism labs (!!!!)
primary- high PTH, high calcium, low phosphate (all kinda as expected) Secondary- high PTH, but there is high phosphate and low calcium (calcium binds the phosphate). Think of this as PTH is trying to work, but it can't.
# Acute stress disorder
proceeds post traumatic stress disorder, common following a life threatening traumatic event. It lasts LESS than 4 weeks!!!! Ie, nightmares, flashbacks, poor concentration, restlesless..... symptoms MUST cause significant distress or functional impairment.
# GIP (gastric inhibitory peptide or glucose-dependent insulinotropic peptide) produced by what cells?
produced by K cells in duodenum and jejunum.
# Enteropeptidase (aka enterokinase):
produced by duodenum, activates trypsinogen into trypsin. This activates more trypsinogen + other zymogens (positive feedback loop)
# Renal disorders in SLE
proteinuria or cellular casts -*diffuse proliferative glomerulonephritis (nephritic syndrome*) — most common and most severe form of lupus nephritis; most common cause of death (!!!!) characterized by hypertension and hematuria. commonly has "wire-loop" lesions due to prominent subendothelial immune-complex deposits (!!!!) -membranous glomerulonephritis- proetinuria (nephrotic syndrome)... Can get combination of both nephritic and nephrotic.
# PT
prothrombin time (PT) and and international normalized ratio (INR) are measures of the EXTRINSIC pathway of coagulation. "EX PT WAR INR" They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status.
# Keloid
raised scar caused by excessive type III collagen synthesis during tissue repair; common in blacks. Keloids extend beyond the borders of the original wound (vs. hypertrophic scars, which remain limited to the area of the wound) Although there is excessive synthesis of type III collagen early in keloid formation, this type III collagen is slowly converted to type I. Thus, type III collagen predominates early in keloid formation. Examples of causes of keloids: - following skin trauma (classic example: earlobe piercing) - complication of tertiary stage Treponema pertenue (yaws) infection
paroxysmal supraventricular tachycardia (PSVT)
rapid palpitations due to stimulation of atria/AV node. Treat with ADENOSINE to very rapidly slow conduction through the AV node. Side effects of adenosine: - flushing chest burning AV block
# angiosarcoma
rare and aggressive *blood vessel malignancy* that is a prolifferation of endothelial cells (CD31!!!).... *typically occurs* in the head, neck, skin, breast, liver areas.
# Nonexudative ("dry") age related macular degeneration
refers to an atrophy and degeneration of central retinal pigment epithelial layer below the retina, which causes *vision loss through loss of photoreceptors*. It is characterized by an accumulation of an extracellular material known as *drusen deposits (!!!!).* dry usually progresses to wet
# PTH (parathyroid hormone)
released FROM the *chief cells* of the parathyroid gland, when FREE IONIZED Ca2+ is low, acts on: 1) Bone to increase osteoclast activity, but not DIRECTLY...PTH binds to receptor on osteoBLASTS (NOT osteoclasts).... PTH binding causes the blasts to then secrete M-CSF (!!!!), and causes the blasts to both increase their expression of RANK-L and ALSO decrease expression of osteoprotegerin. (!!!!) (Osteoprotegerin NORMALLY binds to RANK-L and acts as a *decoy*, thus it inhibits RANK from binding to it) So, what we have is a combination of increased RANK-L, decreased osteoprotegerin, and thus a "double whammy" allowing MORE RANK and RANK-L binding, which THEN stimulate osteoclasts to break down bone and release calcium.) 2) ↑ Intestinal absorption of Ca2+: , this happens because PTH stimulates 1α-hydroxylase in the kidney → increased 1,25-(OH)2 vitamin D production (calcitriol) 3) Increase renal calcium reabsorption (in DCT), and decrease renal phosphate reabsorption (in PCT)....
#what factors can lead to digoxin toxicity?
renal failure (decreased excretion, *NORMAL AGING* !!!) hypokalemia (increases effect because digoxin competes with K+ ions), hyopmagnesemia, verapamil, amiodarone, quinidine
# Hemostatis overview
repair of damaged vessels 2 forms: 1) Primary- "knee jerk" of blood vessels, mediated by endothelin release, forms weak platelet plug 2) Secondary- stabilizes platelet plug by coagulation cascade
#sublimation
replacing an unacceptable wish with a course of action that is similar to the wish, but does NOT conflict with one's value system ie, using anger against parents, to do well in sports
# Treat follicular lymphoma
reserved for patients who are symptomatic (most aren't). - give low dose chemo, or rituximab.
#Treatment PKU:
restrict phenylalanine and aspartame (contains phenylalanine) in diet - ↑ tyrosine intake (becomes an essential amino acid!)
# Angelman's overview
results from a pathogenic loss (through deletion, inversion, uniparental disomy) *LOSS of the maternal alleles* at 15q11-13. the paternal genes of the homologous chromosome are imprinted in this region (and thus normally silenced), the deletion of the maternal alleles gets rid of the only functional copies of the necessary genes. .... uniparental disomy is 5% of cases Angelman syndrome is characterized by inappropriate laughter, epilepsy/seizures, intellectual disability, ataxic gait. In contrast to Prader-Willi, there is NO obesity in Angelman syndrome.
Conduction aphasia
results from damage to the *arcuate fasciculus* (connection between Wernicke's and Broca's areas). This results in the patient's *inability to repeat words back to someone* but an *intact ability to comprehend* and with *fluent speech. *
marasmus
results from inadequate protein and overall calories. • Marasmus presents with: o "broomstick extremities" due to muscle wasting/breakdown for energy production. o no visible fat and rarely any edema. o A useful memory device for marasmus is: Marasmus causes extreme Muscle wasting. o Patients with marasmus may also present with decreased height and weight for age, thin, dry skin, bradycardia, hypotension, hypothermia, redundant skin folds, and thin, sparse hair.
Prader Willi overview
results from the combination of the normally imprinted and inactive maternal genes in the 15q11-13 region along with a loss (through deletion, inversion, or uniparental disomy) of the PATERNAL homologues in the same region. *Imprinting of the maternal alleles* along with *loss of the same paternal alleles* means there is no functional copy of specific genes in that region, leading to the syndrome. Prader-Willi syndrome is characterized by hypotonia in infancy, obesity and hyperphagia beginning in early childhood, genital hypoplasia, intellectual disability, and small hands and feet.
# Exudative ("wet") age related macular degeneration
results in a sudden visual loss due to leakage of serous fluid into the retina as a result of *abnormal blood vessel formation (neovascularization, hence "wet")* under retinal pigment epithelium. It is less common than dry ARMD.
# Mitral stenosis complications
results in increased left atrium pressures and thus *left atria dilation* (volume overload because all blood in LA cannot be pushed into LV) and thus , pulmonary congestion and pulmonary hypertension, increased pressure in RV and RA. .The increase in left-atrial pressure eventually causes pulmonary vascular congestion, which causes exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea, which are the most common presenting symptoms. Remember, Pulmonary congestion causes- 1) edema etc.... 2) alveolar hemmorage (capillaries rupture, macrophages consume them giving *heart failure cells* (hemosiderin laden macrophages)... hemoptysis can occur. !!! Dilation of the left atria can also *impinge the left recurrent laryngeal nerve* !!!!!!!!
Trochlear nerve palsy (CN IV)
results in the eye being pointed superomedially (up and in) Associated with VERTICAL diplopia (happens when eye looks down at nose, ie, walking down stairs, reading a paper)!!! Compensatory head tilting to the opposite shoulder (Bielschowsky sign) is common for these lesions. Most palsies here are idiopathic OR traumatic.
# vitamin B2 deficiency
riboflavin deficiency causes: - angular cheilitis (cracked angles of the mouth) - glossitis with magenta-colored tongue - corneal vascularization.
# scabies
scabies is an infestation of the skin by the mite Sarcoptes scabiei that results in *pruritic eruption that is usually worse at night. * • The lesions consist of small, erythematous, nondescript papules with a pathognomonic burrow that often appears as a thin, gray/red/brown serpiginous (snake-like) lesions between the fingers. • The distribution of scabies usually spares the back and head, and usually involves the o *Sides and webs of the fingers* o Flexor aspects of the wrists o Extensor aspects of the elbows o Axillary folds o Waist o Posterior aspect of the feet o Extensor surface of the knees o Lower half of the buttocks • Treatment for scabies includes permethrin or oral ivermectin.
# IL-4:
secreted by CD4+ Th2 cells mostly • Further differentiated Th2 cells • IL-4 plays a role in the allergic response by: • - promoting B cell proliferation promoting CLASS SWITCHING from IgM into IgG/IgE !!! also inhibits Th1 while promoting Th2 proliferation
# IFN-γ:
secreted by NK cells (in response to IL-12 from macrophages(!! • Activates macrophages and NK cells, and suppresses Th2 cell activity
# IL-2: (!!!)
secreted by T helper lymphocytes ONLY helps to amplify both the CD4 and CD8 T cell response. (amplify's T cells!!!) IL-2 has anti *renal cell and melanoma* cancer by *increasing both T-cells and NK cells!!* !!!!!
# IL-5:
secreted by Th2 cells mostly • Promotes differentiation of B cells and class IgA production. Also promotes eosinophil production. (!!!!!!!!!!) Involved in allergy/asthma!!!!
# IL-3:
secreted by activated T cells mostly, • Stimulates the proliferation and differentiation of bone marrow stem cells !!!! • Also stimulates growth of mast cells and promotes histamine release.
# IL-6:
secreted by macrophages mostly • induces the production of acute phase reactants (e.g., CRP) by the liver. IL-6 is also a potent pyrogen. • 1. IL -6 STIMULATES OAF (IL-1).... it by itself is NOT OAF... 2. it also promotes the formation of MOTT/FLAME CELLS (from RUssel bodies) in MULTIPLY MYELOMA... IL6 levels are PROGNOSTIC
# IL-1:
secreted by macrophages mostly and osteoblasts • In addition to its role as an endogenous pyrogen (i.e., induces fever), IL-1 performs several important functions: - Stimulates *neutrophil/macrophage migration*, activates endothelial adhesion molecules • - somewhat involved in acute phase reactants - Activates osteoclasts (↑ bone resorption) Aka Osteoclast activating factor!!!
# IL-8:
secreted by macrophages, T lymphocytes • Functions in NEUTROPHIL chemotaxis and PUS formation!!!! (clean up Isle 8) !!!
# IL-10:
secreted by monocytes and to a lesser extent Th2 cells. . It is ANTIINFLAMMATORY and DECREASES expression of cytokines!!! Inhibits macrophages and dendridic cells. !!! IL-10 inhibits IL-2 and IFN-y thus *decreasing cell mediated immunity.* IL-10 enhances IL-4 and IL-5 produced by TH2 cells, thus ENHANCING humoral immunity.
# TNF-α:
secreted mainly by macrophages • Notable functions of TNF-α: - Mediates septic shock !!!!!!!! - Causes vascular leakage, induces leukocyte recruitment - Helps form and maintain granulomas
# CMV Mononucleosis:
seen in sexually active adolescents. Not associated with: + Heterophile antibodies Cervical lymphadenopathy Splenomegaly
mesonephric (Wolffian duct)
seminal vesicles, epididymis, vas deferens, ejaculatory duct in men Gardners duct in women
#derivatives of tryptophan
serotonin (thus, melatonin).... And niacin (thus, NAD+ and NADP+). Serotonin synthesis from tryptophan requires BH4 (tetrahydrobiopterin) and vitamin B6 as cofactors. (!!!!!!) Serotonin is acetylated by acetyl CoA then methylated by S-adenosylmethionine (SAM) to produced melatonin, a hormone in the sleep/wake cycle.
trichomoniasis.
sexually transmitted flagellated protozoa Women infected with T. vaginalis can become an asymptomatic carrier or present with acute vaginitis (burning, pruritis, dysuria, and frequency). Physical exam can reveal a purulent, malodorous, thin discharge. *Punctate hemorrhage may be visible on the vagina and cervix ("strawberry cervix").* Other findings that may be present with T. vaginalis infection, but nondiagnostic, include an *elevated vaginal pH (>4.5).*
# Small cell carcinoma treatment
small cell lung carcinomas are highly mitotic and undifferentiated, they are very sensitive to radiation and chemotherapy treatments. however, due to it's aggressive nature, small cell lung carcinomas are often distantly metastatic at the time of discovery. Even with treatment, prognosis is grim - mean survival after diagnosis is only 1 year. Patients with small cell lung carcinoma are NOT surgical candidates.
# Langerhans cells
specialized dendritic cell (APC!!) found predominately in epidermis!! Derived from bone marrow monocytes and they present antigen to naiive T-cells.
# Spermatocele:
sperm-containing cyst • Dilated epididymal efferent duct containing blocked sperm • Diagnosis by transillumination (translucent!!) and ultrasound
#spironolactone vs eplerenone
spironolactone (relatively non-specific aldosterone receptor antagonist). It also *blocks the androgen receptor* causing the side effects of androgen antagonism such as *gynecomastia* eplerenone (relatively specific aldosterone receptor antagonist ∴ ↓ incidence of anti-androgen side effects (e.g., gynecomastbia) compared to spironolactone)
Prolactin stimulated/inhibited by
stimulated by TRH, PRH (prolactin releasing hormone).. inhibited by dopamine. (!!!)
#GIP (glucose dependent insulinotropic peptide) function
stimulates insulin release, inhibits gastric digestion.
#CCK function
stimulates release of pancreatic juices and bile, inhibits gastric emptying. • Stimuli for secretion: - Small peptides and amino acids in the intestinal lumen - Fatty acids and monoglycerides in the intestinal lumen • Effects: - Contraction of gallbladder - Relaxation of the sphincter of Oddi - ↑ Pancreatic secretion - ↑ Growth of exocrine pancreas - ↓ Gastric emptying Clinical Correlate Since *CCK stimulates contraction of the gallbladder, cholelithiasis will be worsened by fatty meals. *
cavernous sinus
structures that pass through it include: -internal carotid artery - CN's III, IV, V1/V2, VI... so infection is a risk to all of these.
# Granuolmatous inflammation
subtype of chronic inflammation, characterized by granuloma formation, which is a collection of epithelioid hystiocytes (!!), which are macrophages with abundant pink cytoplasm. Surrounded by giant cells and rim of lymphycytes divided into: -noncaseating granulomas -caseating granulomas
# Primary amyloidosis
systemic deposition of AL amyloid (deriged from Ig light chain). Associated with plasma cell dyscrasias (abnormalities of plasma cell) where the light chain can be overproduced, leaks out into blood, can become disfolded and deposit. Also with multiple myeloma and Waldenstrom's macroglobulinemia.
# Acute rheumatic fever
systemic disease affecting the peri-arteriolar connective tissue that can occur 1-4 weeks after an untreated *group A β-hemolytic streptococcal pyogenes* infection. Please also note it is a *pharyngeal infection* (throat). Caused by *molecular mimicry*, where bacteria has *M-proteins* which are antigens which *resemble* human tissues. So, in generating antibodies to fight the M-proteins, the antibodies also attack human tissue.
# uremia and platelets (!!) aka uremic platelet dysfunction
tends to disrupt platelet function, both adhesion and aggregation. This occurs in *those with renal dysfunction*. It can be *improved with dialysis*. The ONLY lab abnormality is bleeding time
# subfalcine herniation
the *cyngulate gyrus* herniates underneath the *falc cerebri*... which then compresses the *anterior cerebral artery*... causing infarction. This may result in paralysis, weakness, and sensory loss of the contralateral foot and leg.
ventromedial hypothalamus
the major satiety center of the hypothalamus, leptin acts here in order to decrease appetite. Destruction of the ventromedial nucleus results in hyperphagia (you cannot decrease hunger). Also, destruction here results in increased aggressiveness.
# Open (wide) angle Glaucoma -
the most common form (90% of cases), which usually affects both eyes & develops slowly so that loss of sight is gradual. There is no pain, redness of the eye or dramatic (sudden) change in vision.
# cutaneous anthrax
the most common form, presents with *rapidly growing papule developing into a painless ulcerous vesicle with a black necrotic eschar/crust*, necrotic center, accompanied by edema of surrounding tissues.
# PPI side effects
the most common side effects are gastrointestinal (nausea, vomiting, abdominal pain). Less common side effects are seen with chronic PPI use: • Hypomagnesemia (due to disruption of intestinal Mg2+ absorption) • Increased risk of hip fractures • Rebound hypersecretion of gastric acid upon discontinuation • Infection (i.e. Clostridium difficile, pneumonia) *hip fractues* occur because insoluble calcium requires an *acidic environment for proper absorption*!!!!!!!
axonal reaction injury aka chromatolysis
the process by which neuronal cell bodies increase protein synthesis after peripheral axonal injury in an attempt to regenerate their axons!!! (Although the process has the potential to enable axonal regeneration, neuronal apoptosis is actually a more frequent outcome.) Histologic features of chromatolysis include • Round swelling of the neuronal cell body • Dispersion of Nissl bodies (rough endoplasmic reticulum and ribosomes) throughout the cytoplasm • Displacement of the nucleus toward the periphery of the cell body
# Sheehan syndrome
there is a high demand of hormones in pregnancy, so the pituitary gland actually doubles in size, but blood supply doesn't increase.... leaves pituitary susceptible to *ischemic necrosis*, especially giving birth and losing blood, causing hypopituitarism... this is Sheehan syndrome. Patients present with poor lactation (low prolactin) - loss of pubic hair (due to loss of LH/androgens) - hypothyroidism - hypocortisolism
#Extra-articular manifestations of ankylosing spondylitis (!!!!)
these are common and include - Uveitis (redness of eye and visual abnormalities such as *blurry vision*, can actually lead to blindness) !!! - aortitis (inflammation of the aorta), results in *weakening of the wall* which can form an *aueurysm*. This would *pull on the aortic valve* , and cause *aortic regurgitation* !!! and *congestive heart failure* - Involvement of thoracic spine can cause costovertebral rigidity and chest pain which leads to a *decreased ability for chest expansion (!!!!!!!) * . This manifests clinically as a nonpulmonary restrictive lung disease (!!!!!) on pulmonary function tests. (Recall that restrictive lung disease can manifest as *hypocapnic respiratory acidosis* due to *hypoventilation* ) !!!!!!
# cricothyrotomy
through 1) skin 2) superficial cervical fascia 3) deep cervical fascia aka pretrachial fascia 4) cricothyroid membrane
# aspirin toxicity (!!!)
tinnitus, gastric ulcers/bleeding, nausea/comiting, acute renal failure.... Can stimulate respiratory center, causing hyperventilation and respiratory alkalosis initially!!!! But THEN many hours later it prevents to metabolic acidosis.
tests for endocarditis
transesophageal echocardiography (TEE). The TEE is more sensitive in detecting vegetations, particularly in prosthetic valves, and in detecting perivalvular disease. also two-dimensional echocardiogram.
# VZV (Varicella-Zoster virus)
transmitted via *respiratory secretions* or *contact w/ varicella vesicles*. (ie, chicken pox!!!) -establishes lifelong latent infection in *ANY sensory ganglia* (i.e., dorsal root ganglia) Varicella is typical during childhood (90% of US population) → reactivation (mostly in elderly) → *herpes zoster* (typically PAINFUL burning rash located unilaterally in a dermatomal distribution)!!!!!!!!!!!! Note, the *varicella IgG antibodies confur immunity againt Chickenpox, NOT herpes zoster!!!!!!!!*
# Wernicke's encephalopathy (!!)
triad of: 1) confusion, apathy, inattentiveness 2) *horizontal* nystagmus, bilateral abducens palsy, complete opthalmoplegia 3) ataxia
# Pancreatic carcinoma location (!!!)
tumor In in head of pancreas- obstructive jaundice, pale stools with palpable/non-tender gallbladder (called Courvoisier sign) !!!! . (tumor *blocks flow of bile in the common bile duct*, bilirubin and conjugated bilirubin leak into blood giving jaundice.... stools become pale b/c bile doesn't leak into duodenum.) Tumor in body/tail of pancreas- can lead to destruction of islet cells which are mostly in body/tail, can lead to secondary mellitus. If thin, diabetic elderly patient, think of pancreatic carcinoma (body/tail)
# Pheochromocytoma
tumor of chromaffin cells of the adrenal medulla and sympathetic chain.... BROWN tumor, produces excess E/NE from chromaffin cells.. It is called the 10% tumor because • 10% are malignant • 10% are found extraadrenal • 10% are bilateral • 10% are not associated with hypertension • 10% calcify • 10% are in children Presents with consequences due to the catecholamine (norepinephrine, epinephrine, dopamine) secreting nature of the tumors. These consequences include: • Hypertension • Paroxysmal (episodic!!!) HTN • increased heart contractility and rate, • increased gluconeogenesis and glycogenolysis, and • intestinal relaxation. • Orthostatic HYPOtension
# VIPoma
tumor that produces vasoactive intestinal peptide. VIP then acts on the gut mucosa to secrete sodium, causing watery diarrhea. VIP also causes the colon to secrete potassium thus, hypokalemia. !!! VIP inhibits gastric acid secretion causing achlorhydria/hypochlorhydria (low gastric acid, thus high pH of stomach). !!!
# connective disorders and aortic dissection
typically *younger patients*: connective tissue disorders affecting the collagen and/or elastic tissue in the wall include: - Marfan syndrome (defect of fibrilin-1- the molecule on which elastic fibers are laid down) - Ehlers-Danlos syndrome - Vitamin C deficiency - Defects in copper metabolism
#defense mechanisms
unconscious means of protecting oneself from painful awareness of feelings, desired to decrease anxiety. Can be immature or mature. immature- ) are maladaptive and seen in children and psychopathy mature (altruism, sublimation, suppression, humor... these are the only ones!!!) are most often used by adults, and are a slightly "healthier" adaptive approach to reality.
Which stones are radiolucent??
uric acid!! all the rest are radiopaque.
# massive proteinurea in nephrotic syndrome
urinary loss of *>3.5 grams of protein per day* (!!!) This is the *hallmark*.
#treat Parkinsons
use the mnemonic "BALSA": • Bromocriptine: dopamine receptor agonist (ergot alkaloid) Note: Newer non-ergot dopamine receptor agonists such as pramipexole and ropinirole are now preferred • Amantadine: • L-DOPA/carbidopa: • Selegiline (MAO inhibitor) + COMT inhibitor (e.g. entacapone or tolcapone) : ↓ dopamine breakdown • Antimuscarinics like Benztropine can also be used to treat Parkinson disease → ↓ tremor and rigidity (mnemonic: Park your Mercedes-Benz)
# gel electrophoresis
uses an electronic field to separate molecules bases on sizes. 1. First, treat the specimin with restriction enzymes, then pipette into a well of agarose gel. Smaller fragments move further than larger ones. Bands of DNA visualized by staining the gel with a fluorescent dye such as ethidium bromide. Then, visualize under UV light.
# lead poisoning causes
usually exposure to paint in kids (old houses!!!) .... In adults environmental (battery, ammunition, radiator, factories)
# Clinical presentation of Hepatitis (!!!)
variable fever, profound malaise (general discomfort), painful hepatomegaly (87% of cases). - Jaundice, Variable finding depending on the type of hepatitis - Increased urine bilirubin and urine urobilogen
# neutrophil margination
vasodilation slows blood flow in post-capillary venue, as as vasodilation occurs, cells marginate from center of vessel to periphery. There is *hemoconcentration* and *decreased wall shear stress*, which inproves contact with the lining.
weak platelet plug
von Willebrand factor binds the EXPOSED collagen (from the endothelial injury) - using GP Ia/IIa this allows platelets to bind to vWF using GP1b on the platelet!!! Note: vast majority of vWF is from Weibel-Palade body of endothelial cell itself, or from a-granules of platelet itself Weibel-Palade body: Mnemonic: W= willebrand, P= P-selectin Step 3: Platelet binding activates them and they DEGRANULATE, and release ADP, Ca2+, serotonin. - ADP promotes expression of GPIIb/IIIa receptor on platelets!!!! Step 4- Gp IIb/IIIa binds FIBRINOGEN as a linking molecule on adjacent platlets to form a WEAK platelet PLUG. Also, Thromboxane A2 is synthesized by membrane enzyme phospholipase A2, which INCREASES platelet aggregation. to strengthen platelet plug, need secondary homostasis (coagulation cascade)
# *paradoxical embolus*
where an embolus that originates on the right side and would normally lodge in pulmonary vasculature, instead it goes a intracardiac or intrapulmonary shunt (patent foramen ovale, ASD, VSD, pulmonary malformation). It occurs commonly when cerebrovascular events (ie stroke, TIA) occur in setting of known thromboembolic disease.!!!
#Schwann cells
while one oligodendrocyte myelinates multiple axons in the CNS, one Schwann cell can only myelinate one axon in the peripheral nervous system. • Derived from neural crest cells • Aid in axonal regeneration • Clinical correlates: 1. Schwann cells can form acoustic neuromas (schwannomas), which are usually unilateral and located at the junction of the cerebellum and the pons ∴ mass effects of the tumor may cause cerebellopontine angle syndrome. 2. ~90% of bilateral schwannomas are associated with NF2 (neurofibromatosis type 2)
radial nerve injury presentation
wrist drop (loss of elbow, wrist and finger extension) , - decreased grip strength (because wrist EXTENSION) is necessary for maximal force of flexors. Without the ability to hold the wrist in extension, the flexors in the anterior forearm (flexor pollicis longus, flexor digitorum profundus, flexor digitorum superficialis) are not adequately stretched → excessive overlap of actin and myosin filaments → suboptimal power generation leads to ↓ grip strength. NOTE: with *nursemaid's elbow* there is NO loss of sensation beause it only damages the DEEP BRANCH of the radial nerve, but NOT the superficial branch (sensory sensation)!!!!
# Medullary thyroid Carcinoma
~5% of thyroid cancer cases. Parafollicular (C-cells) are malignant → ↑ calcitonin production, and thus hypocalcemia. (!!!!) - nests of polygonal cells that stain *positive for amyloid with Congo red * !!!!!!!!!!!! calcium deposited in it. "Malignant *spindle shaped* cells (!!!!) secreting calcitonin in an amyloid stroma." - Classically associated with MEN 2A and MEN 2B (Multiple Endocrine Neoplasia) syndromes due to inherited *activating mutation of RET proto-oncogene* !!!! although ~70% of cases are caused by sporadic mutation. If there IS a RET mutation, can have option of prophylactic thyroidectomy.
# Hyperlipidemia and hypercholesterolemia in nephrotic syndrome (!!!)
—as a result of ↑ hepatic synthetic activity, including synthesis of albumin and lipoprotein synthesis: ↑ VLDL → IDL → ↑ LDL ∴ ↑ cholesterol Think of it as we are *losing so much protein*, the liver *ramps up* synthesis of albumin and lipoproteins. (!!!!) We also experience *lipiduria* !!!!!
# HSV-1
• *Gingivostomatitis in the mouth*!!!!!! is the most common. • *Lesions of the oral mucosa* • *Keratoconjunctivities on the cornea, typically presenting as a branching "dendritic ulcer."* • Esophagitis with ulcers that appear well-circumscribed and have a "volcano-like" appearance. Often seen in immunocompromised individuals (ie. organ and bone marrow transplant recipients). HSV-1 can spread via cranial nerves to the brain and *cause focal necrotic lesion in the temporal lobe, causing inflammation and encephalitis.* HSV-1 is the *most common cause of sporadic encephalitis*, and can present with Altered mental status Seizures Aphasia
C. albicans overgrowth can lead to:
• *Oral thrush *of the mouth that appears as a white exudate on mucous membranes. • Vaginitis that presents with itching, copious secretion, and "cottage cheese" appearing clumps. • *Cutaneous candidiasis* can present as a beefy red rash with satellite pustular lesions in moist intertriginous areas (where two skin areas touch) such as under the breasts, axilla of the arm, or anogenital region. • Vaginitis from C. albicans typically presents with a normal vaginal pH less than 4.5 versus bacterial vaginosis or trichomonal vaginitis, where vaginal pH may be higher than 4.5. • Oral thrush presents as white plaques that can be removed or scraped away!!! Very associated with HIV/immunosuppression !!!!!!!!!!!!! Contrast this with hairy leukoplakia, a manifestation of EBV also present in AIDS patients, which presents as white plaques on the side of the tongue that CANNOT be scraped off.
# actinomyces israelii
• *abscess in the mouth, lungs, GI tract, and GU tract*. Abscesses in the mouth can produce cervicofacial mycetoma, which manifests as a hard lump, often in the jaw, commonly known as *"lumpy jaw." !!!!!!!! * • Sinus tracts classically have yellow sulfur granules surrounded by purulence and neutrophils, but there is no sulfur actually present. A. israelli is transmitted during the event of* personal injury or trauma*. • A. israelli is part of the normal flora of the oral cavity, GI tract, and the female GU tract. • In women, *intrauterine devices are a risk factor for A. israelli infection. * • In the setting of trauma/surgery, disruption of the mucosal barrier causes local infection and inflammation. Slow expansion can spread to other tissues, forming sinus tracts and possible hematogenous spread to other sites.
# causes of primary gout
• 1. Alcoholism → ↑ turnover of adenine nucleotides (ie, ATP) during the conversion of acetate to acetyl-CoA → ↑ urate production 2. Protein-rich diets: red meat, seafood, beer 3. Unknown enzyme defects Primary gout may also occur secondary to ↓ excretion of uric acid. For example: 1. Thiazide diuretics 2. Lead poisoning → interstitial nephritis → ↓ urate excretion 3. Alcoholism → ↑ production of lactate, which is an antiuricosuric agent because lactate competes with urate for the same renal excretion sites → ↓ urate excretion • [Note: Alcohol can cause hyperuricemia by both increasing urate production and by decreasing urate excretion, as describe above]
# Sarcomeres
• A muscle fiber (cell) is an elongated multinucleate cell containing many myofibrils. Muscle fibers are surrounded by a connective tissue called endomysium. • A myofibril consists of many sarcomeres. Each sarcomere is composed of many myofilaments (e.g., actin, myosin, titin).
blood testes barrier
• A physical barrier in the testis between blood vessels and the seminiferous tubules - avoids autoimmune response • TIGHT JUNCTIONS (!!!) between Sertoli cells form the blood-testis barrier
# Causes of hydronephrosis
• Acquired (Adults): - Stones (most common) - Benign Prostatic Hypertrophy (BPH) - Tumors in pelvic area (e.g., cervical tumors)
# Migraine headaches
• Affects females> males. Often *associated with family history*. !! Mnemonic: POUND Pounding (pulsatile), phonophobia, photophobia !!! • One-day duration • Unilateral • Nausea/vomiting • Disabling due to excruciating pain (ie, so painful that it limits routine activities) Migraines can be accompanied by an aura (!!!!) which is a constellation of neurological symptoms which can affect the auditory, visual or olfactory system. - photophobia - nause
# Adverse effects of Tetracyclines:
• Brown Teeth discoloration in children, also bone growth impairment.... contraindicated in children and pregnant and breastfeeding women • Photosensitivity
# Femoral nerve:
• Can be caused by a pelvic fracture which presents with *inability to flex the hip or extend the knee * • There is also a *sensory loss in the anterior thigh and medial leg*
#Neurologic manifestations of rheumatoid arthritis (RA) include:
• Carpal tunnel syndrome • Atlantoaxial joint subluxation • Ischemic stroke
#cholelithiasis / gallstone presentation
• Causes RUQ inflammation → inflammation affects phrenic nerve of the diaphragm → pain radiating to the shoulder. • Charcot's triad of cholangitis: fever, jaundice, RUQ pain. Reynold's pentad: addition of hypotension and MS Δ (mental status changes), indicating sepsis. • Pancreatic duct obstruction: pancreatitis. Remember that pancreatic duct joins CBD near the ampulla.
# Vitamin D deficiency and toxicity (!!)
• Deficiency: o rickets in children (imperfect calcification, softening, and distortion of the bones classically resulting in bowed legs) o osteomalacia in adults (soft bones and bone pain). o hypocalcemic tetany (decreased extracellular calcium levels cause increased excitability of voltage gated sodium channels, leading to increased muscle contractions) o Chvostek's sign (tapping facial nerve produces facial spasms on same side) • Toxicity (taking megadoses of vitamin D or medical causes such as sarcoidosis): o Hypercalcemia, hypercalciuria o renal calcium stones o nausea and vomiting o loss of appetite (!!!!) o confusion/stupor
#positive symptoms schizophrenia
• Delusions • Hallucinations • Disorganized speech (e.g., loose associations) • Disorganized or catatonic behavior (ie blank expression)
#amantadine
• Designed as an antivital influenza agent. • Known to have dopaminergic activity and possibly anticholinergic activity as well. • Can cause dry mouth, nausea, comiting, blurring of vision, hallucinations, etc...
#diagnose/treat 5-AR deficiency
• Diagnosis of 5α-reductase deficiency is done by karyotyping, abdominopelvic ultrasound for presence of female or male internal structures, and lab studies. The hallmark diagnosis is an elevated serum ratio of testosterone:DHT. Testosterone/estrogen are normal.... LH is normal or maybe slightly increased. • Treatment of 5α-reductase deficiency initially involves gender assignment. Following assignment, hormone replacement therapy can be tailored to the chosen sex.
carbidopa
• Dopamine is converted to dopamine in CNS → L-DOPA can cross blood-brain barrier; carbidopa is a *peripheral decarboxylase inhibitor* that increases the bioavailability of L-DOPA to the brain. • Note, peripheral conversion to dopamine is largely responsible for side effects of L-dopa such as nausea and vomiting.
# Adjustment Disorder
• Emotional symptoms, social, school, or work impairment that occurs *within 3 months of a stressful life event*!!!!. They are considered excessive for a human experience (i.e.: divorce, moving, serious illness) There are NO flashbacks and nightmares. • It usually lasts less than 6 months !!!! • Treatment involves psychotherapy and group therapy
# Histoplasma capsulatum
• Endemic to the Ohio, Missouri, and Mississippi River valleys. Lives in *soil near bird and bat droppings. *Transmitted by inhalation. Histoplasma causes *pulmonary histoplasmosis which is characterized by non-specific respiratory symptoms, often cough or flu-like,* esp. in immunocompromised hosts. It is very similar to tuberculosis. The fungus is *ingested by macrophages and seen on light microscopt and small intracellular oval bodies*!!!!! Severely immunocompromised patients with defective cell-mediated immunity (eg, AIDS) cannot form granulomas. The *splenic and liver calcifications* can be seen on abdominal imaging and are generally a sign of a more serious disseminated disease which can be found in the bone marrow, blood, and skin.
#male vs female chlamydia presentation
• Female patients typically present with mucopurulent vaginal discharge in cervicitis; abdominopelvic pain in pelvic inflammatory disease; and dysuria in dysuria-pyuria syndrome. • Male patients present with watery or mucous discharge. (!!!!) In addition they may present with dysuria in urethritis, and may have unilateral testicular pain in epididymitis. (!!!!!)
#Benzo use
• First line agents to treat alcohol withdrawal—known as Delirium Tremens (DTs) if the withdrawal is severe • First line agents for status epilepticus (!!!!) - anxiety, night terrors, insomnia, sleep walking Muscle relaxant
# Influenza causes:
• Flu • Croup in children • Secondary bacterial pneumonia • Replication occurs within the nucleus, which is unique to RNA viruses. (!!!) Orthomyxoviruses and retroviruses are the only RNA viruses that replicate within the nucleus. *H. Influenzae requires X factor (hematin) and V factor (NAD+) to grow!! Its presence depends on an antiphagocytic polysaccharide CAPSULE!!! * *Older patients with influenze are likely to get secondary bacterial pneumonia: - Streptococcus pneumonia - staph aurea -H. Influenzae*
#glycogen storage diseases
• Glycogen accumulation in hepatocytes → foreign body reaction and hepatocyte injury → progressive cirrhosis 7 types. Mnemonic: *Von Gierke Put Coors And McDonalds in Her Taurus*. (Imagine Von Gierke loading up his girlfriend's Ford Taurus with Coors and McDonalds for a picnic) • Type 1: Von Gierke • Type 2: Pompe • Type 3: Cori • Type 4: Andersen • Type 5: McArdle • Type 6: Hers • Type 7: Tarui
# First Generation Antihistamines: "ramine" !! !
• Hydroxyzine • promethazine • diphenhydramine • chlorpheniramine • brompheniramine. • Mechanism: H1-receptor inverse agonists - bind to the histamine receptor and produce an effect opposite to that of histamine binding --> thus reducing itching, rhinorrhea and sneezing. • Adverse Effects: Because first generation antihistamines are lipophilic they can easily cross the blood-brain barrier and thus cause significant sedation.!!! (do NOT give with benzos!!!) Also has mild anticholinergic effects. !!! (red as a beat, dry as a bone, mad as a hatter, hot as a hair, etc...)
# Respiratory acidosis
• Hypoventilation (from anesthetics or morphine) • Airway obstruction • Sleep apnea • Restrictive lung diseases • COPD Ph is low. PaCO2 is high, thus it is respiratory acidosis. Bicarb is high (renal compensation, normally only slightly high at first, takes 3+ days to become fully compensated)
# Depolarizing agents work in 2 phases: depolarizing phase and desensitizing phase.
• In *phase I block* (depolarizing phase), succinylcholine binds the receptor and depolarizes the membrane, which causes an *INITIAL DISCHARGE* that produces fasciculations followed by a *flaccid paralysis.* Because succinylcholine is metabolized slowly, the membrane becomes unresponsive to further impulses. • In *phase II block (desensitizing phase)*, the membrane eventually repolarizes, however it remains unresponsive because it is desensitized. During later phase II, desensitizing agents are susceptible to reversal by ACh esterase inhibitors.
#Alpha-1 antitypsin deficiency adults vs children (!!!)
• In adults, AAT deficiency causes the combination of liver disease and COPD (!!!). It should be suspected as a diagnosis if a non-smoker has COPD and liver disease and/or a family history of either. • In infants/children, it can cause neonatal jaundice, hepatitis or even liver failure. It is the leading cause of liver transplantation in children.
Zone III liver damage
• In the liver, blood flows from the portal vein and hepatic artery toward the central vein. Therefore, the cells in zone III near the central vein, which are last to be perfused, have the highest risk for damage due to ischemia. Also sensitive to: ALCOHOLIC hepatitis (has cyp450) Metabolic toxins
#polymyalgia rheumatic labs
• Increased erythrocyte sedimentation rate (ESR) • Increased C-reactive protein • Normal creatinine kinase (CK), due to no myositis
# Amphetamines and Cocaine intoxication and withdrawl
• Intoxication: - pupillary dilatation, hypertension, tachycardia, cardiac arrhythmias - psychomotor agitation, impaired judgment - euphoria, prolonged wakefulness and attention • Withdrawal— post-use "crash" including: - depression, lethargy, hypersomnolence - headache, stomach cramps, hunger
#Barbiturates sides
• Intoxication: respiratory depression and low safety margin • Withdrawal: anxiety, seizures, delirium, and life-threatening cardiovascular collapse
# Clopidogrel, ticlopidine
• Irreversibly *bind/antagonize ADP receptors* → prevents ADP induced GPIIb/IIIa activation → ↓ platelet aggregation • Indications: coronary stents, thrombotic stroke, *antiplatelet therapy in post-stroke and post-TIA patients A recent study found that adding clopidogrel to aspirin in patients who already suffered a stroke or transient ischemic attack reduces the chance of further cerebrovascular events compared to aspirin alone. • Toxicity: ticlopidine - can cause neutropenia!!! Presents with fever and mouth ulcers!!!!! Must monitor closely on ticlopidine!! Clopidogrel It can be used for *angina in those that are aspirin allergic!!!!*
# tibial nerve injury
• Knee trauma-Knee dislocation • Can't invert or plantarflex (can't stand on toes) the foot ( so the right foot is stuck in dorsiflexion) !!! cannot flex (curl) the toes due to loss of innervation to the interossei muscles. • Sensory loss on the sole (plantar surface) of the foot !!!!
# legionella
• L. pneumophila grows on *charcoal yeast extract with iron and cysteine.* Transmission of L. pneumophila occurs via aerosols from *environmental water sources such as air conditioning systems and hot water tanks. * L. pneumophila causes *severe, atypical pneumonia termed Legionnaire's disease* or self-limiting Pontiac fever that presents with a *mild flu-like illness (high fever, chills, fatigue, malaise, and headache) without respiratory symptoms. * • In addition to a prominent nonproductive cough, severe Legionella pneumonia can be accompanied by confusion, diarrhea, and signs of kidney damage: proteinuria, microscopic hematuria. Diagnosis of L. pneumophila infection is made via the *presence of antigen in urine.* • *Hyponatremia is an important, distinguishing feature of Legionella pneumonia.*!!!!!! This may be related to inappropriate ADH secretion and/or renal tubulointerstitial disease impairing sodium reabsorption.
Status epilepticus
• Life threatening, persistent seizure activity in the brain • Treatment: First line anti-seizure drugs are benzodiazepines, such as diazepam. First line drug for prophylaxis is phenytoin to increase seizure threshold
# metronidazole
• Metronidazole treats anaerobic organisms generally below the diaphragm. Contrast this with the indication for clindamycin, which is used to treat anaerobic infections above the diaphragm. Used for: • Trichomonas • Gardnerella vaginalis • Anaerobes (Bacteroides, C. difficile)
# Echinococcus granulosus
• Most common cause of *hydatid cysts* !!! It usually occur from ingestion of *eggs usually found in dog feces*. Also Echinococcosis is common in sheepherders who acquired the tapeworm from *sheep dog feces. Sheep dogs become infected after eating raw sheep meat. * hydatid cysts form in liver, lung, or brain. Cysts grow, divide, and expand causing organ displacement and dysfunction. Release of antigenic cyst contents can *lead to SEVERE ANAPHYLAXIS* and spread of infection
#retinoblastoma (!!)
• Most common primary ocular malignancy of childhood (generally found in children under age 6) • Retina location, unilateral or bilateral • Commonly discovered on fundoscopic exam, which reveals leukocoria: instead of seeing a red reflex, the examiner will see a white mass. !!!! • Linked to homozygous deletion or inactivation of Rb gene (chromosome 13)
#treat heroin users (!!)
• Naloxone competitively inhibits opioids at the Mu receptor, and are used in cases of acute overdose !!!! Naltrexone is also a pure opioid antagonist, and is used for management of long term opioid dependance. • Methadone which is a *long acting oral opiate* is used for heroin detoxification or long term maintenance (!!) It has a *long, but moderate* withdrawl.
Neisseria gonorrhae
• Neisseria are diplococcic gram negative, with flattened sides sometimes referred to as kidney bean-shaped. !!! Note: Pilli are requires for infection!!!!!! The Pilli undergo antigenic variation!!! • Patients with urethritis and cervicitis from gonorrhea can present with pain or discomfort while urinating or pain during sexual intercourse, as well as a yellow/white thick mucopurulent discharge from the urethra or vagina. Contrast this with the clear/watery discharge seen in chlamydial infections. • N. gonorrhoeae is the most common cause of septic arthritis in sexually active people, usually affecting the knee. Gonorrhoeae infection does NOT result in lasting immunity because these bacteria *modify their outer membrane via antigenic variation*!!!! The antibodies produced during infection are VERY SPECIFIC to the strain. Treat gonorrhea with a cephalosporin!!!!!
atropine toxicity
• Overdosage can produce an anticholinergic toxidrome (hot as a hare, blind as a bat, dry as a bone, red as a beet, and mad as a hatter) Hyperthermia from decreased sweating, so there is dry, flushed skin disorientation and altered mental status. - tacycardia extreme thirst. Beware: can cause: - acute angle closure glaucoma (!!!) - urinary retention in men with prostatic hyperplasia !!!!!!
#Guillain Barre presentation
• Paresthesia in the fingertips or toes (distally), .that ascends proximally (!!!) • Ascending muscle weakness and paralysis that begins in the distal / lower extremities. • Disappearance of reflexes (areflexia) • Autonomic dysfunction including hypertension, orthostatic hypotension, paroxysmal hypertension, facial flushing and brady/tachycardia. • Bells Palsy can result • Burning or shock-like pain the lower extremities • Death from *paralysis of respiratory muscles*
# How can change in gene sequence alter a protein?
• Point mutation: One base substituted for another o Silent: Base substitution often in 3rd position of protein , but it still makes the SAME amino acid acid due to tRNA wobble) (!!!!!!!!!!!!!!!!!!) o Missense: Changed amino acid (conservative; new amino acid is similar in structure) o Nonsense: SUBSTITUTION (not a deletion!!!) Change resulting in altered protein (codon changed to stop codon) o Frameshift: truncated proteins!!! (gene stops working!!!) (misreading of all nucleotides downstream). "deletion or addition of any number of nucleotides NOT divisible by 3, that causes all downstream codons to change/ o Splice site mutation: may lead to intron-exon skipping, the protein is larger and often nonfunctional (but still detected by antibodies)
positive inotrop
• Positive inotropic agents result in a shift of the curve to a higher cardiac output and a correspondingly lower right atrial pressure. • Stroke volume increases leading to decreased right atrial pressure because more blood is ejected with each beat. • Negative inotropic agents or pathological conditions such as heart failure lead to decreased cardiac output and a higher right atrial pressure.
# Vitamin B6 deficiency/toxicity
• Pyridoxine deficiency causes: o peripheral neuropathy and convulsions (due to its role in neurotransmitter synthesis (serotonin, E, NE, dopamine, GABA)). !!!!!!!!!!!!! o sideroblastic anemias due to defective heme synthesis and resulting iron excess. • Pyridoxine toxicity is associated with peripheral neuropathy, presenting with burning, numbness and tingling of the hands and feet
Autoimmune diseases caused by S. pyogenes include
• Rheumatic fever (a Type II hypersensitivity reaction)!!! • Post-streptococcal glomerulonephritis (a Type III hypersensitivity reaction)!!!!! • Pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS) syndrome *Protein M is the major virulence factor!!! • S. pyogenes is pyrrolidonyl arylamidase (PYR) test positive, a rapid test used for the presumptive identification of S. pyogenes and Enterococci. *!!!!
# Risk factors for Cholelithiasis
• Risk factors are the 4 F's: fat, female, fertile, forty (more than 40 years old) Estrogen- Crohn's disease (damage terminal ileum, damage reuptake of bile salts/acids) - Cirrhosis - (decrease production of bile salts from hepatocytes) - Prolonged TPN
staph aures causes
• S. aureus is the most common cause of: • Hospital-acquired bacterial pneumonia • Ventilator-associated bacterial pneumonia (Pseudomonas aeruginosa is the 2nd most common cause) • Cellulitis • Osteomyelitis • Impetigo • Acute infective endocarditis POSE w/ your staff Pneumonia (bacterial in hospital) Osteomyelitis Skin -impetigo (bullous) cellulitis Endocarditis -acute infective
# Streptococcus pyogenes (Grp A Strep, GAS)
• S. pyogenes is the most common bacterial cause of sore throat. Patients may present with *fever, malaise, sore throat or enlarged cervical lymph nodes.* Also *facial puffiness and dark urine* if it cause PSGN!!!! • Patients with skin infections from S. pyogenes may present with *pustular lesions and honeycomb-like GOLDEN YELLOW crusts known as non-bullous impetigo !!!!!!!!!!!!!* at the site of inoculation. S. aureus, however, is the most common cause of both non-bullous and bullous impetigo.
staph saprophyticus
• S. saprophyticus is novobiocin resistant. Contrast this with S. epidermidis, which is novobiocin sensitive. • S. saprophyticus causes urinary tract infections and cystitis. S. saprophyticus infections spread via bodily fluids and often occurs in sexually active young women. S. saprophyticus is nitrate reductase negative, so a dipstick test will produce a false-negative result.
#Turner syndrome presentation
• Short stature (<5 feet) • "Streak gonads" (ovarian dysgenesis) with infertility • "Menopause before menarche" • Broad chest with widely-spaced nipples (!!!!) • Webbing of the back/*posterior triangle* of the neck (cystic hygroma), due to *lymphatic defects*.... with a low hairline • Lymphedema in the hands and feet (impaird lymph)!!! !!! • Abnormal development of female secondary sex characteristics
#fibrates sides
• Side effects: - Myositis—fibrates are especially *myotoxic when used in combination with statin*!!!! - Fibrates combined with statins can lead to rhabdomylosis → ATN (!!!) - ↑ LFTs (liver function tests) — i.e., ↑ serum levels of liver enzymes: ↑ AST, ↑ ALT - Small risk of cholelithiasis (!!!) They do this by DECREASING 7a-hydroxylase. This reduces conversion of cholesterol into bile acids, thus bile is supersaturated with cholesterol.
SNRI side effects
• Side effects: stimulant effects (tachycardia, ↑ BP), nausea, constipation, sedation, and if suddenly stopped can cause SNRI discontinuation syndrome (flulike symptoms and electric-like shocks) • Both medications can result in persistent pulmonary hypertension (PPHN)
# Hypomanic Episode
• Similar to manic episode except the mood disturbance is not severe enough to cause marked impairment in social and/or occupational functioning or to necessitate hospitalization; there are no psychotic features Lasts for at LEAST 4 DAYS
# watershed zones of intestines
• The 2 most commonly affected watershed zones in the GI tract are: 1) the splenic flexure (between the SMA and IMA) 2) the sigmoid colon (between the IMA and pudendal artery). • Watershed zone infarctions are typically transmural.
# type 1 dyslipoproteinemia manifestations
• The clinical findings include chylomicron-induced acute pancreatitis, hepatosplenomegaly, and eruptive/pruritic skin xanthomas • There is *no increased risk of atherosclerosis*. !!!!!
scrofula
• The most common extrapulmonary manifestion of tuberculosis is *mycobacterial cervical lymphadenitis*, also known as scrofula. This is a lymphadenitis of the cervical lymph nodes and usually appears as a chronic, painless mass in the neck.
#androgen insensitivity presentation
• The typical presentation of androgen insensitivity is of a *patient who phenotypically appears as a woman, and presents with primary amenorrhea*. She will also present with *no axillary or pubic hair, no uterus, and rudimentary vagina. Testes are present, usually within the labia majora or abdomen.* • Methods for diagnosis of androgen insensitivity: • Karyotyping • Androgen receptor mutation analysis • Lab studies that reveal: increased levels of testosterone, LH, and estrogen • Treatment for androgen insensitivity syndrome involves: • Hormone replacement therapy • Psychological support • Orchidectomy (to reduce the risk of malignancy)
treat ARMD
• Treatment options for wet ARMD include intraocular injections of *anti-VEGF antibodies (ranibizumab and bevacizumab)* in order to decrease the rate of neovascularization.
# treat migraines (!!!)
• Triptans such as sumatriptan are the first line agent for migraine abortive therapy. They are *5HT agonist* which act by STIMULATING serotonin uptake post-synaptically. This acts by: - inhibiting the release of Vasoactive peptides (Substance P, CGRP) . Substance P/CGRP give a headache because they *vasodilate*.... So Triptans promoting vasoconstriction -
#mitochondrial disorders
• Upon fusion of sperm and egg, the egg supplies the mitochondria of the newly formed zygote → mitochondrial diseases are inherited through the mother!!! • When the zygote and other stem cells divide, there is *random distribution of mitochondria to daughter cells*. Thus, there is a potential for uneven distribution of mutated mitochondria. As a result, some tissues have normal mitochondria whereas others may have diseased mitochondria. This principle is known as *heteroplasmy.* The result is a large variety of affected tissues, disease severity, and subsequent clinical presentations.
# Acute rejection: (!!)
• Usually occurs a week to less than 6 months after transplantation because the *T cells take time to differentiate (cell-mediated immunity)* There is a *dense lymphocytic infiltarion* where *Host Cytotoxic T cells* react against a mis-matched *Graft HLA antigen or MHCs*. characterized by: *neutrophillic/lymphocytic infiltrate,* necrotizing vasculitis/endothelitis !!!! • Treated with steroids and various immunosuppressants (!!!!), including tacrolimus, cyclosporine, and mycophenolate mofetil.
#vitamin E deficiency (!!!)
• Vitamin E deficiency is rare and primarily occurs in: o children with cystic fibrosis (due to fat malabsorption secondary to decreased bile salts and pancreatic insufficiency)!!!! o abetalipoproteinemia (fat malabsorption) Signs are: hemolytic anemia peripheral neuropathy (!!!) posterior column/spinocerebellar degeneration (!!!!) (ataxia!!!) retinal degeneration myopathy. Vitamin E deficiency signs can *MIMIC those of vitamin B12 deficiency*, but *vitamin E deficiency is WITHOUT increased methylmalonic acid levels or megaloblastic anemia. *
# Acute cholecystitis-
• acute inflammation of gallbladder wall due to stone in CYSTIC DUCT, pressure builds up, decreases gallbladder blood supply and it becomes ischemic, leads to bacterial overgrowth. E. coli (most common) • Klebsiella • Enterococcus
#Klinefelter's clinical presentation
• clinical presentation of Klinefelter's syndrome is variable, but includes: • Elongated Body (very tall, long limbs, increase in length between soles of the feet and pubic bone) !!! • Testicular atrophy causing infertility(!!!) • Eunuchoid appearance (wide hips and gynecomastia) !!! • Female distribution of body hair • Lack of male secondary sex characteristics (deep voice, beard, male pubic hair distribution) Klinefelter's syndrome patients often have complications including: • Increased incidence of type II diabetes mellitus and metabolic syndrome • Mitral valve prolapse • Osteoporosis/Bone Fractures • Testicular cancers
# Down syndrome findings
• congenital heart disease (often ASD or VSD, due to *failure of endocardial cushion fusion*!!) !!! "• Flat nasal bridge, • Oblique eye fissures • prominent epicanthal folds - Excessive skin at the neck. • Single palmar fold (""simian crease"") • Hirschsprung disease, duodenal atresia
#closed angle glaucoma and risks
• is characterized by an occlusion of flow between the iris and lens, resulting in rapid increase in IOPIt is an ophthalmologic emergency that leads to irreversible vision loss within hours if left untreated. • Symptoms of closed angle glaucoma include a *red and very painful eye, blurry vision or seeing "halos" !!!!!) a rock-hard eye, a dilated and non-reactive pupil, and a severe frontal headache with nausea and vomiting. (!!!!) • Risk factors for closed angle glaucoma include Asian or Inuit race, eye trauma, and intraocular infection.
# anthrax inhalation
• resents with nonspecific myalgias, fever, chest pain, and cough due to hemorrhage of thoracic lymph nodes, hemorrhagic mediastinitis, and necrotizing pneumonia. This is followed by bacteremia and meningitis in a fatal fulminant phase. • Alimentary tract anthrax presents with abdominal pain, dysentery, and necrotic ulcers of the oral and gastrointestinal tract. • *Widening of the mediastinum is a classic finding of inhalation anthrax (!!!!!!!)*, due to the hemorrhagic mediastinitis. This is a nonspecific finding.
# PTT deficiency is caused by what factors? (!!!)
↑ PTT is caused by deficiency of all factors except VII and XIII (factor XIII only delays bleeding , NOT PT or PTT)
# Labs in primary hyperparathyroidism
↑ serum PTH/ AND Ca (as expected) ↓ serum phosphate (as expected) ↑ urinary cAMP!! (PTH binding coupled to Gs protein) ↑ serum alkaline phosphatase (b/c PTH actually activates osteoBLASTS)
# sickle cell splenectomy increases risk for what encapsulated bacteria
→ increased risk of Salmonella typhi osteomyslitis (!!!!)
# Potassium sparing diuretic side effects
→ overdose or supratherapeutic levels of K sparing diuretics can lead to *hyperkalemia* (vs. loops and thiazides, which can cause *hypokalemia* Thus, although relatively weak in terms of their diuretic effect, K sparing diuretics are commonly co-administered with loops and/or thiazides to dampen the K wasting effect of these more powerful diuretics. Hyperkalemia toxicity causes nausea, comiting, diarrhea, areflexia, weakness, paresthesia
# features in reversible (AND irreversible) cell injury
↓ ATP synthesis (causes decreased action of Na+ / K+ pumps in the cell membranes, leading to increased Na+ and water within the cell (cell swelling). membrane blebbing mitochondrial swelling dilatation and degranulation of the rough endoplasmic reticulum fatty changes, glycogen depletion autophagocytosis • The swelling of the cell leads to the loss of microvilli, due to stretching of the plasma membrane, and membrane blebbing (pinched-off segments of the cell), which is visible on microscopic exams. • The ribosomes dissociate from the rough endoplasmic reticulum (RER) due to its swelling leading to decreased protein synthesis. • During cellular injury, the cell must rely on anaerobic glycolysis for energy leading to decreased glycogen levels and lactic acid buildup. • The lactic acid decreases the pH leading the clumping of the nuclear chromatin!!!!!!!!!