Step Uno Notes

What are the Celiac trunk branches?

Additional Notes: - The short gastric artery (a branch of the splenic artery) has very poor anastomoses, and the tissue supplied by them is vulnerable to ischemic injury following splenic artery blockage

What does mitochondrial DNA code for?

- 14 proteins (some involved in oxidative metabolic pathway), and the Ribosomal RNA and transfer RNA needed for mitochondrial protein synthesis

What are 2 histology findings of photoaging?

- Photoaging is d/t UVA (A=Aging) - it is characterized by epidermal atrophy with flattening of rete ridges (epithelial extensions that project down into the underlying dermis

What is Akathisia?

- Subjective restlessness with inability to sit still (can be an Extrapyramidal side effect of antipsychotics - dopamine antagonist meds)

What are some characterizations of Bulemia Nervosa?

-Recurrent episodes of binge eating and compnesatory behavior (vomiting, exercise, laxitives, etc.) to prevent weight gain (at least 1x per week for 3 months) -Excessive worry about body shape and weight -Maintains normal body weight (so they will not experience the signs of malnutrition and starvation that an anorexic patient would) --- This differs from anorexia because someone with anorexia will have a BMI under 18.5 --- This differs from binge-eating disorder, because patients with binge-eating disorder do not use inappropriate compensatory behavior

What are 3 ways to calculate Cardiac output?

CO = SV x HR CO = rate of O2 consumption / arteriovenous O2 content difference CO = Mean arterial pressure / total peripheral resistance

Sucrose gets broken down into what?

Glucose + Fructose

Where is Iron absorbed?

The Duodenum

Where is Vitamin B12 absorbed?

The Ileum (it must be combined with intrinsic factor to be absorbed)

Forms of candida at 20, and 37 degrees:

-20 = pseudohyphae with budding yeast (blastoconidia) -37 = germ tubes

What is the glutamate-glutamine cycle? and how does hyperammonemia affect it?

-Glutamate-glutamine cycle is a cycle where astrocytes take up glutamate in the synapse to prevent excessive excitatory stimulation. Via glutamine synthase, the glutamate i converted to (non-active) glutamine with Ammonia as an additional substrate. Glutamine can then be sent back to neurotransmitters, to be converted back to glutamate, and used again. -Hyperammonemia will cause excess glutamine to accumulate in astrocytes, which increases the intracellular osmolarity of the astrocyte, and causes it to swell, which impairs glutamine release. Therefore, the hyperammonemia will decrease the amount of glutamine avaliable for conversion to glutamate in neurons, and disrupt excitatory neurotransmission NOTE: Gutamine = (Glutamate+NH3)

A-a gradient equation, normal range, and causes for an increased gradient:

A-a gradient = PAO2 - PaO2 Normal = 5-15 A high gradient could be seen in hypoxemia: causes include shunting (R-->L), V/Q mismatch, and fibrosis (impaired diffusion) NOTE: If the pt is hypoxic, with a normal A-a gradient, then think: high altitude or hypoventilation

What is Acute Dystonia?

-Sustained muscle contractions, frequently causing twitching, repetitive movements or abnormal postures (typically in neck, mouth, tongue, or eye muscles) (can be an Extrapyramidal side effect of antipsychotics - dopamine antagonist meds... will usually occur within the first few days of recieving this med)

What artery provides the majority of blood to the femoral head and neck?

-The medial femoral circumflex artery and its branches provide the majority of blood supply to the femoral head and neck. -Injury to these vessels d/t a displaced femoral neck fracture can cause osteonecrosis of the femoral head

What is the karyotype of Klinefelter syndrome? And, what are common manifestations?

47, XXY - primary testicular failure (small, firm testes, and azoospermia), eunuchoid body habitus, tall, gyenocomastia, sparse body hair, decreased muscle mass, possible mild intellectual disability

What nerves mediate the Gag Reflex?

Glossopharyngeal nerve (CN IX) - mediates the afferent limb (general sensory) Vagus nerve (CN X) - mediates the efferent limb

Lactose gets broken down into what?

Glucose + Galactose

What is the location of Cryptococcus Neoformans primary infection?

The lungs (it's usually asymptomatic) (with severe immunocompromise, they can then spread through the blood to other organs - mainly the CNS)

What is Phenylketonuria

- Autosomal recesive disorder caused by a deficiency of the enzyme *phenylalanine hydrozylase* (or less commonly d/t its cofactor: Tetrahydrobiopterin (BH4))... Thus, Phenylalanine cannot be converted to Tyrosine - The deficiency causes an accumulation of phenylalanine (and phenyl keotnes) in body fluids and in the CNS. - Homozygous infants are normal at birth, but gradually develop severe intellectual disability and seizures if left untreated - Hypopigmentation of skin, hair, eyes, and catecholaminergic brain nuclei is also frequently seen - Also pt's commonly have a *musty body odor* (becuase phenyl functional group is aromatic)

What is the pathogenesis of Wilson Disease?

- Autosomal recessive mutation of ATP7B gene - an ATP-mediated hepatocyte copper transport. This leads to lack of copper transport into bile, and lack of copper incorporation into ceruloplasmin (the key molecule that carries copper in blood). Excess copper can cause damage by binding to sulfhydryl groups of cellular proteins - Signs: Liver injury (elevated transaminases), Psych symptoms, tremor/parkinsonian symptoms (d/t copper deposition in the basal ganglia), Kayser-Fleischer rings - Labs: elevated transaminases (showing liver injury), low serum ceruloplasmin, also will likely see low total Cu in serum but high free Cu in serum - Treatment: D-Panicillamine (copper chelator)

Describe the embryo/physio of Septate Uterus, Bicornate Uterus, and Uterus didelphys

-Incomplete lateral fusion of paramesonephric ducts can result in various anomalies ---Incomplete lateral fusion of the upper segments can result in a bicornate uterus ----Complete lack of fusion can lead to a uterine didelphys -Failed involution of the paramesonephric ducts can result in a longitudinal uterine septum

Anion Gap equation and normal range?

Anion Gap = Sodium - (Bicarb+Chloride) Normal = 8-16

Describe the process of Base excision repair:

Base excision repair repairs various non-bulky DNA base alterations. - First: specific Glycosylases recgonize the abnormal base and cleave it, leaving an empty sugar/phosphate site (AP site). - Second: Endonuclease cleaves the 5' and of the AP site, and Lyase cleaves the 3' end - Third: DNA polymerase fills the gap, and the final nick is sealed with Ligase

Complete Mole vs. Partial Mole chromosome #

Complete Mole = 46 Partial Mole = 69 Note: Complete mole has the swollen grape like villi

What is the most common organism that causes bacteremia in sickle cell patients?

First is Strep Pneumo, and H. Influenza is second Note: it is recommended that all asplenic patients recieve penicillin prophylaxis, and the pneumococcal vaccine

What two things are secreted by parietal cells?

Gastric Acid, and Intrinsic Factor

Light microscopy findings of Post-Strep Glomerulonephritis: Immunoflourescence microscopy findings: Electron microscopy findings:

Light microscopy = hypercellular glomeruli d/t leukicyte infiltration and mesangial/endothelial cell proliferation Immuno = Granular deposits of IgG, IgM, and C3 (immune complex deposition) EM = Subepithelial humps, representing Ab-Ag complex deposition

What is a major side effect of TMP-SMX?

Trimethoprim (TMP) and Sulfamethoxazole (SMX) inhibit different enzymes in the formation of tetrahydrofolic acid, which contribute to purine/pyrimidine synthesis Thus, TMP-SMX is associate with bone marrow suppression

What is the primary histologic feature in patients with cushing syndrome?

hyperPLASIA of the zona fasciculata (NOT hypertrophy... This may occur, but it is not the primary finding!)

What are the presenting symptoms of inflammatory breast carcinoma? And what is the underlying cause of these specific symptoms?

- Inflammatory carcinoma in characterized by carcinoma in the dermal lymphatics - Clinically you see an inflamed, swollen boob, with a rash (peau d'orange) that is often itchy, but usually with no discrete mass (it is often mistaken for acute mastitis) - The swelling and inflammation is d/t the tumor being in the lymphatics (lymphatic obstruction) and causing a back up

What is Annular Pancreas, and what happened embryologically to cause it?

-Annular pancreas is when there is pancreatic tissue encircling the descending duodenum -It is due to a failure of the ventral pancreatic bud (which is to the right of the duodenum in the embryo) to properly migrate towards the the dorsal bud (which is to the left of the duodenum in the embryo) during the 7th/8th week of fetal development NOTE: This is not due to an incomplete fusion of the ventral and dorsal buds. When the two buds dont fuse, it is called Pancreas divisum

What are the levels of CRH, ACTH, and Cortisol, in a patient on chronic glucocorticoids?

- CRH = LOW - ACTH = LOW - Cortisol = LOW - Glucocorticoids suppress the synthesis and release of CRH from the hypothalamus, and also block its ACTH stimulatory effect on the anterior pituitary

Describe the pathway that CSF flows:

- CSF is formed by 4 choroid plexuses found in each of the ventricles - CSF flows from the lateral ventricles to the third ventricle via the interventricular foramina of Monro - It then circulates to the fourth ventricle via the cerebral aqueduct (of Sylvius) - CSF exits the fourth ventricle and enters the subarachnoid space via one of 3 foramina: the 2 lateral foramina of Luschka and the single midline foramen of Magendie - CSF then gets returned to venous circulation via the arachnoid villi (granulations)

What is the main function of Cytochrome P450 Monooxygenase?

- CYP450 monooxygenase metabolizes steroids, alcohol, toxins, and other foreign substances by rendering them soluble and easier to excrete - Unfortunately, many pro-carcinogens are converted into active metabolites by the CYP450 system

In skeletal muscle, what does Ca bind to in order to initiate contraction?

- Ca is released from the sarcoplasmic reticulum, and binds to troponin, which shifts tropomyosin, and exposes the myosin binding groove on actin filaments

What junctions are cadherins in? And, what junctions are connexon in?

- Cadherins are involved in Adherens junctions (also in desmosomes) - Connexons are involved in Gap junctions NOTE: A connexon is a cylinder with a central channel composed of 6 connexin proteins

What is "chloride shift" and how does it contribute to the high RBC chloride content in venous blood?

- Carbonic anhydrase activity within erythrocytes forms bicarbonate from CO2 and water. - Many of the bicarb. ions diffuse out of the RBC into the plasma. To maintain the electrical neutrality, chloride ions diffuse into the RBC to take their place. This process is called "chloride shift" and is the principal cause of high RBC chloride content in venous blood

How does Carcinoid syndrome present? And what is the treatment?

- Carcinoid tumors (most commonly ileal tumors) secrete a number of biologically active substances including serotonin, and can cause symptoms (Carcinoid syndrome) when they metastasize outside of the gut (so the secreted substances avoid first pass metabolism) - Common manifestations of Carcinoid syndrome are: flushing, asthma-like symptoms, diarrhea, and syncope (d/t low BP). Long standing carcinoid syndrome can cause right-sided valvular disease - The most definitive treatment for carcinoid syndrome is surgical excision - Octreotide can be given to control symptoms - it is a somatostatin analog, and acts on somatostatin receptors to inhibit secretion of many hormones and hormone-like substances

What causes Carcinoid Syndrome? And, what are some manifestations? How is it diagnosed?

- Carcinoid tumors most frequently arise from the enterochromaffin (endocrine) cells of the intestinal mucosa, and can create a number of vasoactive substances (serotonin, bradykinin, prostaglandins) - Carcinoid tumors confined to the intestine do not cause carcinoid syndrome as their secretory products are metabolized by the liver before entering systemic circulation - Intestinal carcinoid tumors that metastasize to the liver and/or extraintestinal carcinoids (like bronchial carcinoid), release vasoactive substances that avoid the first-pass metabolism and results in carcinoid syndrome (flushing, diarrhea, asthma-like symptoms)

What heard issue would result in a patient with Cardiac Amyloidosis? And how does this present on histology?

- Cardiac amyloidosis can cause a restrictive cardiomyopathy, and often results in diastolic heart failure d/t ventricular hypertrophy with impaired ventricular filling - Histology of cardiac amyloidosis would show: Normal cardiac cells with other areas of myocardium infiltrated by an *amorphous and acellular pink material* - Congo Red Stain would show Apple-green birefringence under polarized light microscopy

What are some cardiovascular manifestations of SLE? And, what is Verrucous (Libman-Sacks) Endocarditis?

- Cardiovascular manifestations of SLE include accelerated atherosclerosis, small-vessel necrotizing vasculitis (with fibrinoid necrosis), pericarditis, and Leibman-Sacks endocarditis - Leibman-Sacks Endocarditis is characterized by thickened valve leaflets (typically mitral and/or aortic) with multiple small vegetations on BOTH leaflets (Normal endocarditis will usually have vegetations on only one side)

What results from a carnitine deficiency? And, how does this manifest clinically?

- Carnitine is necessary for the transport of fatty acids from the cytoplasm into the mitochondrial matrix - This is necessary for the B-oxidation of fatty acids into acetyl CoA, which is needed to feed into the TCA cycle or be used to form ketone bodies - As a result, cardiac and skeletal myocytes cannot generate ATP from fatty acids and the liver is unable to synthesize ketone bodies when glucose is low - Patients with this typically have myopathy (elevated creatine kinase, and weakness), cardiomyopathy, hypoketotic hypoglycemia, and elevated muscle triglycerides

What is the effect of Diphtheria exotoxin?

- Catalyzes the ADP-ribosylation of host cell elongation factor-2

What is the most common location for a cavernous hemangioma in the brain?

- Cavernous hemangiomas are vascular malformations that most commonly occur in the brain parenchyma; they can carry an increased risk of intracerebral hemorrhage and seizure

What are the 3 Antibodies that can be seen in a pt with Celiac disease? And, where should you biopsy to establish a definite diagnosis?

- Celiac is a disease caused by immune mediated damage of the small bowel villi d/t gluten exposure (and its most pathogenic component: gliadin) - It can present with bloating, diarrhea, flatulence, and possibly short stature and weight loss - Serum test could show elevated IgA endomysium, IgA Tissue transglutaminase, or IgA gladin - Duodenal biopsy is confirmatory, because the damage is most prominent in the duodenum, and is characterized by villous flattening, crypt hyperplasia, and intraepithelial lymphocyte infiltration

What drug should be given to a patient post-Subarachnoid hemorrhage to prevent cerebral vasospasm?

- Cerebral vasospasm can occur between 3-8 days following a subarachnoid, and are thought to be d/t the degradation of subarachnoid blood clots - It manifests as AMS and focal neuro deficits 3-8d post Subarachnoid - Nimodipine (a Ca-channel blocker) has been shown to reduce morbidity and mortality d/t cerebral vasospasm post-Subarachnoid... It is a cerebral selective drug

What are the 2 Chiari malformations? And, how do they manifest?

- Chiari type 1 = characterized by low lying cerebellar tonsils that extend below the foramen magnum into the vertebral canal... It presents in adolescent/adulthood with paroxysmal occipital headaches, and cerebellar dysfunction (dizziness, ataxia) - Chiari type 2 = characterized by downward displacement of the cerebellum (vermis, tonsils) and medulla, through the foramen magnum... Compression of the medulla may result in dysphagia, stridor, and apnea. Non-communicating hydrocephalus almost always occurs d/t aqueductal stenosis. Pts also commonly have an associated lumbar myelomeningocele

What is a Cholesteatoma?

- Cholesteatomas are collections of squamous cell debris that form a mass behind the tympanic membrane - They ca be congenital or may occur as an acquired primary lesion or following infection, trauma, or surgery - They can cause hearing loss d/t erosion into the auditory ossicles

A choriocarcinoma in males is a malignant tumor of what? And what is usually elevated?

- Choriocarcinoma is a malignant tumor of syncytiotrophoblasts (which makes B-HCG) and cytotrophoblasts - B-HCG is characteristically elevated in these - B-HCG has an alpha subunit that is similar to FSH, LH, and TSH... its beta subunit is very similar to TSH, and this allows HCG to bing and activate the TSH receptor (with a very low affinity), which can lead to a paraneoplastic hyperthyroidism

Name 9 important inducers of CYP450

- Chronic alcohol use - St. Johns Wart - *Phenytoin* (anti-epileptic) - *Phenobarbitol* (anti-epileptic) - Nevirapine (Non-Nucleoside Reverse Transcriptase Inhibitor) - *Rifampin* (Abx) - *Griseofulvin* (Anti-Fungal) - *Carbamazepine* (anti-epileptic) "Chronic alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs" (Also Modafinil and Cyclophosphamide via UWORLD) NOTE: CYP450 inducers will REDUCE the effect of Warfarin (decrease its efficacy)

Describe the respiratory tree histology in the 4 levels of the conducting zone, and the 2 levels of the respiratory zone:

- Ciliated cells persist up-to/through the proximal portions of the respiratory bronchioles. - The presence of cilia beyond the most distal mucus-producing cells (goblet cells, which end by the larger bronchioles) is important because it prevents bronchiolar mucus accumulation and airflow obstruction NOTE: in 2017 first aid, the Terminal bronchioles are ciliated cuboidal, NOT ciliated columnar

What receptors does Verapamil block? And, what does this result in within pacemaker cells?

- Class IV antiarrhythmics block L-type Ca channels UWORLD says: This blockage causes slowing of BOTH phase 4 (spontaneous depolarization) AND phase 0 (upstroke) - it slows phase 4 b/c "as the pacemaker cell approaches threshold, L-type Ca channels begin to open, which further increases Ca influx and significantly decreases the time until threshold is reached" ... So Verapamil would then stop this, and then increase the time it takes to reach threshold (as seen in the picture, the L-type Ca channels start to open before spontaneous depolarization)

What are symptoms of gas gangrene? What is the most common organism that causes it? and what is the treatment?

- Clostridium Perfringens causes 95% of gas gangrene. Its spores are in the soil, and can inoculate penetrating injury sites. - Symptoms of gas gangrene are severe pain, swelling, crepitus (gas under tissue, which can also be seen on Xray, which can help distinguish this from other narcotizing infections) - Treatment is Abx with emergent debridement NOTE: C. Perfringens can also cause a late-onset food poisoning with watery diarrhea. This is d/t toxin formed when large quantities of clostridial spores are ingested, germinate, and release toxin.

What is a Clue cell?

- Clue cells are seen in Pap smears in the setting of bacterial vaginosis (which involves a change in vaginal flora from lactobacilli to anaerobic gram-negative rods like Gardnerella Vaginalis) - Clue cells are squamous cells covered with rods to obscure normal epithelial margins

What is the cofactor needed for the conversion of Phenylalanine to Tyrosine? And, what is the name of the enzyme that regenerates this cofactor?

- Cofactor = *Tetrahydrobiopteron (BH4)* - *Dihydropteridine Reductase* regenerates BH4 from BH2 - A deficiency in either of these could be mistaken for classic phenylketonuria d/t deficient Phenylalanine reductase... But although phenylalanine levels can be corrected with dietary restriction, if the deficiency is d/t one of these two, downstream deficiencies of dopamine, norepinephrine, epinephrine, and serotonin lead to progressive neurologic deterioration

What is Colchicine used for? And, what is its mechanism? And, what are some side effects?

- Colchicine is used to treat acute gouty arthritis in patiets who cannot take an NSAID - It binds tubulin and inhibits its polymerization into microtubules... This, in turn, disrupts cytoskeletal-dependent functions such as chemotaxis and phagocytosis - It also reduces the formation of leukotriene B4 (which is involved in neutrophil chemotaxis) - SE = Nausea, abdominal pain, diarrhea, and very rarely agranulocytosis

What are common presenting symptoms of Epithelial Ovarian Cancer (EOC)? And, what are some risk factors and protective factors?

- Common manifestations include abdominal distention, ascites, pleural effusion, bowel obstruction, decreased appetite, weight loss, and ovarian mass - Cancer antigen-125 can be used as a serum marker to monitor treatment and screen for re-ocurrance (but very non-specific) - Risk factors: Fam history, infertility, nulliparity, polycystic ovarian syndrome, endometriosis, BRCA1 or BRCA2 mutations, Lynch syndrome, Postmenopausal hormone therapy -Protective factors: Combined oral contraceptive, multiparity, breastfeeding, salpingo-oophorectomy

State the common manifestations of Turner syndrome:

- Common manifestations of Turner syndrome that are observable on inspection = include primary amenorrhea, short stature, high arched palate, low hairline, webbed neck and widely speced nipples. - Primary amenorrhea also occurs in these patients d/t in utero degeneration of the ovarian follicles (gonadal dysgenesis) - The ovaries usually appear underdeveloped and atrophic ("streak gonads") d/t in utero degeneration of the ovarian follicles with replacement by fibrotic tissues... And since menstruation and breast development are estrogen-dependent processes, they do not occur b/d the ovaries are not functional

What is the cause of Thoracic outlet syndrome and what is its presentation?

- Compression of the lower trunk of the brachial plexus can cause upper extremity numbness, tingling, weakness - Compression of the subclavian artery can cause exertional arm pain - Compression of the subclavian vein can cause upper extremity swelling - It most commonly occurs within the *Scalene Triangle* which is formed by the anterior and middle scalene and the first rib - The brachial plexus trunks and subclavian arteries pass between the anterior and middle Scalenes, within the triangle, while the subclavian vein runs anteromedial to the triangle

What type of overload can cause concentric left ventricular hypertrophy, and, which type causes eccentric left ventricular hypertrophy?

- Concentric left ventricular hypertrophy can result from *Pressure Overload* (like chronic HTN or aortic stenosis) - Eccentric left ventricular hypertrophy can result from *Volume Overload* (like chronic aortic/mitral regurg., MI, or dilated cardiomyopathy)

What is Congenital Long QT syndrome? What is the most common cause? And, what can it result in?

- Congenital long QT syndrome is most often caused by genetic mutations in a K+ channel protein that contributes to the outward-rectifying potassium channel - A decrease in the outward K+ current leads to prolongation of action potential duration and QT interval - This prolongation predisposes to the development of life-threatening ventricular arrhythmias (ex: torsades de pointes)

What is the most common and persistent opioid side effect?

- Constipation - This and Miosis are NOT affected by tolerance

9 things that can cause a rash on Palms and Soles:

- Coxsackie (Hand, foot, mouth) - Rocky Mountain Spotted Fever (Rickettsia Rickettsii) - Syphilis (secondary stage) - Janeway Lesions of bacterial endocarditis (cutaneous evidence of septic emboli) - Kawasaki disease - Measles (starts on face and moves down - usually a confluent rash) - Toxic shock syndrome - Reactive Arthritis (rare small hard nodules called keratoderma blennorrhagicum) - Meningococcemia

What is the embryologic origin of an Craniopharyngoma? And, what are characteristics of it on gross inspection?

- Craniopharyngiomas are suprasellar tumors found in children and composed of *calcified cysts containing cholesterol crystals* - They arise from surface ectoderm, specifically remnants of Rathke's pouch, an embryonic precursor of the anterior pituitary

How does Crohns increase Calcium Oxalate renal stones?

- Crohns classically involves the terminal ileum. The terminal ileum is where bile acids usually get reabsorbed. So with ileum inflammation, bile acids are lost in the feces. Loss of bile acids impairs fat absorption. The excess lipids in the bowel then bind to calcium ions, and these soap complexes are excreted with feces. - Normally, dietary calcium binds dietary oxalate, producing an insoluble complex of calcium oxalate, which gets excreted - this process promotes oxalate excretion. However, *in Crohns, the calcium bound to lipids is unable to bind to oxalate. Because of this, oxalate absorption is increased, promoting the formation of oxalate kidney stones*

How can Crohns disease lead to bleeding problems?

- Crohns disease typically involves the terminal Ileum - Bile Acids are re-absorbed in the Terminal ileum... So when the terminal ileum is inflamed or resected, bile acids are lost with feces... - Loss of bile acids causes fat malabsorption, which may lead to deficiencies in Fat-soluble vitamins... Like Vitamin K - Vitamin K deficiency will lead to a coagulation disorder, which typically results in easy bruising, large hematoma formation in deep tissues and joints (hemarthrosis) after minor trauma, and prolonged bleeding after surgery

What are the symptoms of cyanide poisoning? And what is the Antidote?

- Cyanide inhibits cytochrome c oxidase (complex 4) in mitochondria, which lowers peripheral tissue Oxygen consumption - Arterial oxygen tension (PaO2), Arterial Saturation (SaO2), and Total blood oxygen content (CaO2) remain unchanged, but venous oxygen content rises and the arterial-venous oxygen gradient falls - Cyanide poisoning presents with reddish skin discoloration, tachypnea, headache, and tachycardia, often accompanied by N/V, confusion, and weakness.. Can progress to seizures and cardiovascular collapse - Antidote = Inhaled amyl nitrite, which oxides Fe2+ (ferrous) to Fe3+ (ferric), generating Methemoglobin. Methemoglobin is incapable of carrying O2, but has a high affinity for Cyanide. So it binds the cyanide in the blood, freeing it from complex 4 - Other antidotes are Hydroxycobalamin (B12 precursor, which can bind to intracellular cyanide) and sodium thiosulfate

What does the immunohistochemical marker, Cytokeratin, indicate?

- Cytokeratin is a commonly used immunohistochemical marker of epithelial-derived tumors (such as breast cancer) - Cytokeratins are proteins that help form the keratin-containing intermediate filaments that makes up the cytoskeleton of almost all epithelial cells

What is McCune-Albright Syndrome?

- D/t an activating mutation in the G protein/CAMP/Adenylate cyclase signaling pathway - Triad of: --- *Fibrous dysplasia of the bone* (multiple osteolytic-appearing lesions of the hip and pelvis) --- *Endocrine abnormalities* (usually precocious puberty) --- *Cafe-au-lait spots* (d/t increased G-protein stimulation of melanocytes)

What type of virus causes Dengue fever? And how does primary and secondary infections manifest?

- Dengue viruses are trasnmitted by the Aedes mosquito and are ssRNA (Flavivirus), with 4 different serotypes - First infection can be asymptomatic, or cause a self-limited disease in most adults with symptoms: high-grade fever, headache, retro-orbital pain, bleeding (epistaxis, petechiae/purpura), diffuse macular rash, muscle and joint pain ("break bone fever"), leukopenia, thrombocytopenia, and elevated liver enzymes - Primary infection can lead to lifelong immunity against the same serotype, but individuals ca be infected with a different serotype, and this typicall causes a more severe illness - Dengue hemorrhagic fever, which can be a more serious manifestation of secondary infection, is d/t increased capillary permeability and can be manifested by marked thrombocytopenia, prolonged fever, respiratory/circulatory failure, and shock, which patients also developing significant hemorrhagic tendencies and spontaneous bleeding

How long must symptoms be present to fit criteria for Major Depressive Disorder?

- Depressed mood must be present most of the day, almost every day for >2 weeks... and the patient must have at least 5/9 of SIG E CAPS symptoms

In diastolic heart failure, what is the Left Ventricular ejection fraction, LV end-diastolic volume, and elevated LV filling pressure?

- Diastolic heart failure is caused by decreased ventricular compliance and is characterized by: *Normal left ventricular ejection fraction* *Normal left ventricular end-diastolic volume* *Elevated left ventricular filling pressures*

How does Digoxin decrease heart rate?

- Digoxin stimulates the vagus nerve, and increases parasympathetic vagal tone, which decreases AV nodal conduction (mechanism is unclear) NOTE: The primary effect of Digoxin is inhibition of Na/K ATPase, which indirectly inhibits the Na/Ca exchanger, which leaves more Ca in the cell to increase contractility (positive inotropy)

What are some signs of digoxin toxicity?

- Digoxin typically presents with cardiac arrhythmias and nonspecific GI (nausea, vomiting), neurological (confusion, weakness), and visual symptoms (blurry yellow vision) - Elevated potassium is another sign of Digoxin toxicity and is caused by inhibition of Na-K-ATPase pumps (FIRST AID PG. 307)

What type of drugs are Diphenoxylate, and Loperamide? And, what are they used for?

- Diphenoxylate and Loperamide are both opioid agonists that bind to the Mu-opioid receptor in the GI tract and slow motility - They are used to treat diarrhea (not caused by toxin-producing or invasive organisms) - Side effects = rebound constipation and mild sedation

How does Adult Dry Beriberi manifest? And, what vitamin is deficient?

- Dry beriberi is characterized by peripheral neuropathy in distal extremities, with resulting sensory and motor impairments, and symmetrical muscle wasting - It is caused by a Thiamine (B1) deficiency NOTE: Wet beriberi has these symptoms, with the addition of cardiac involvement (cardiomyopathy, high-output CHF, peripheral edema, tachycardia)

What are 3 random symptoms that indicate Phrenic nerve irritation?

- Dyspnea - Hiccups (diaphragmatic irritation) - Referred pain to shoulder (area innervated by supraclavicular nerve originating from C3 & C4) Phrenic nerve palsy would show elevation of the affected hemidiaphragm

What is dystrophic calcification?

- Dystrophic calcification is considered a hallmark of cell injury and death, occurring in all types of necrosis in the setting of normal calcium levels - Dystrophic calcification occurs in damaged or necrotic tissue in the setting of normal calcium levels - On H&E stain, these appear as dark-purple, sharp-edged aggregates. Deposits that develop lamellated outer layers are described as psammoma bodies NOTE: Metastatic calcification occurs in normal tissue in the setting of hypercalcemia

What is the most common cause of coronary sinus dilation?

- Elevated right sided heart pressure secondary to pulmonary HTN - B/c the coronary sinus communicates freely with the right atrium, it will become dilated by any factor that causes dilation of the right atrium

In what medical circumstances can a minor consent to their own care?

- Emergent care - Sexually Transmitted Infection - Substance abuse (most states) - Pregnancy/Prenatal care (most states) - Contraception NOTE: 2/3 of states require parental consent prior to abortion; 1/3 require parental notification, but not consent

In what way can end stage renal disease cause a coagulopathy?

- End stage renal disease leads to an accumulation of uremic toxins in the circulation - causing "Uremic platelet dysfunction" - These uremic toxins can impair platelet aggregation and adhesion and result in a QUALITATIVE platelet disorder, characterized by prolonged bleeding time with normal platelet count, PT and PTT.

What role does platelets play in the formation of an Atherosclerotic plaque?

- Endothelial dysfunction promotes platelet adhesion, aggregation, and release of growth factors and cytokines - Platelet-derived growth factor (PDGF) is released by locally adherent platelets, dysfunctional endothelial cells, and infiltrating macrophages, and promotes the migration of smooth muscle cells from the media to the intima & its subsequent proliferation - Platelets also release Transforming growth factor beta (TGF-B), which is chemotactic for smooth muscle cells and induces interstitial collagen production

What vasoconstrictive substance is typically found in high levels in patients with Pulmonary Arterial Hypertension (also known as Primary Pulmonary Hypertension)?

- Endothelin - Endothelin is a potent vasoconstrictor that also promotes smooth muscle proliferation - Endothelin receptor antagonists (Bosentan, Ambirsentan) inhibit this pulmonary arteriolar smooth muscle proliferation and alleviate vasoconstriction to lower pulmonary arterial pressure and improve the dyspnea in patients with Primary Pulmonary Arterial Hypertension NOTE: Primary arterial hypertension is suspected when the patient has an elevated mean pulmonary arterial pressure (>25mmHg), but a normal pulmonary capillary wedge pressure (which is a measurement of the pressure in the left atrium... Normally under 12)

What are the histology findings of an Ependymoma (children)

- Ependymal peri-vascular rosettes with Rod-shaped blepharoplasts (basal ciliary bodies) found near the nucleus - Can be glial fibrillary acidic protein (GFAP+) positive - Commonly found in the 4th ventricle

What is the Epidermal growth factor receptor pathway?

- Epidermal growth factor receptor (EGFR) is stimulated in a paracrine or autocrine fashion by its ligands - This then leads to downstream activation of KRAS, a membrane-bound GTP-binding protein that stimulates cellular growth and proliferation - Many cancers leverage this system to drive unchecked cellular growth by over-expressing EGFR or by developing constitutive activating mutations in the KRAS proto-oncogene - Tumors harboring activating KRAS mutations are resistant to treatment with Anti-EGFR drugs (eg. Cetuximab, Panitumumab)

What 2 body tissues cannot use Ketone bodies for energy?

- Erythrocytes (because they lack mitochondria) - Liver (because it lacks the enzyme, thiophorase, which is required to convert acetoacetate to acetoacetyl-CoA, which can then get converted to Acetyl-CoA and enters the TCA cycle) NOTE: The brain preferentially uses glucose, but will use ketones for most of its energy during prolonged starvation

How does pregnancy changes lead to gallstones?

- Estrogen influences increased cholesterol synthesis by upregulating hepatic HMG-CoA reductase activity, which causes the bile to become supersaturated with cholesterol - Progesterone reduces bile acid secretion and slows gallbladder emptying

How does measuring a waste-to-hip ratio help in the diagnosis of type 2 diabetes?

- Excess *Visceral fat* (surrounding internal organs) correlates very strongly with insulin resistance than does SubQ fat - Measuring Waist circumference or waist to hip ratio is an effective indirect measurement of visceral fat, especially in patients with only mild elevations in total BMI - *An elevated waste circumference is associated with a higher risk of insulin resistance, diabetes, and coronary artery disease*

What are some clinical manifestations of hyperaldosteronism?

- Excess Aldosterone will cause Na retention, and excess K and H secretion, resulting in hypertension, hypokalemia, and metabolic alkalosis - These electrolyte abnormalities can manifest clinically as parasthesia and muscle weakness

What is the "latent period" discrepancy in stats?

- Exposure to risk modifiers must occur continuously over extended periods before disease outcome is affected EX: Antioxidant in stroke prevention... you need to take the antioxidant for a long time to see benefit... i.e. "The discrepancy can be explained if reduction in stroke risk through antioxidant use is associated with a long latent period"

What is Factor V Leiden? And, what are these patients at increased risk for?

- Factor V Leiden is a mutant version of coagulation Factor V, which is resistant to the degradation of activated protein C... This leads to a hypercoaguable state - Patients are at risk for DVT, cerebral vein thrombosis, and recurrent pregnancy loss

Describe Familial dysbetalipoproteinemia (type 3 hyperlipoproteinemia):

- Familial dysbetalipoproteinemia is an autosomal recessive disorder characterized by elevated cholesterol and triglyceride levels - It is d/t defects in ApoE3 and ApoE4, which leads to decreased clearance of Chylomicron and VLDL remnants by the liver, resulting in elevations in cholesterol and triglyceride levels - Pts typically develop Premature atherosclerosis, and eruptive & palmar xanthomas

What is Saltatory conduction?

- Fast conduction made possible by the presence of myelin - The myelin sheath serves as an electrical insulator that results in the impulse "jumping" between 2 adjacent nodes (*Saltatory conduction*)

What is the drug of choice to reduce blood pressure in hypertensive emergency?

- Fenlodopam is a selective peripheral dopamine-1 receptor agonist - It is given IV to lower BP during hypertensive emergency, especially in patients with renal insufficiency - Fenlodopam causes arteriolar dilation, and increases renal profusion (which promotes diuresis and natriuresis)

Name the main enzyme that Fibrates upregulate, and another enzyme that they inhibit: What does this result in?

- Fibrates work through *Peroxisome Proliferator-Activated Receptor-alpha (PPAR-a)* - Their primary mechanism is up-regulation of lipoprotein lipase, which hydrolyzes triglycerides in chylomicrons and VLDL to release free fatty acids, which results in increased oxidation of fatty acids, leading to increased clearance of VLDL and Triglycerides - Another direct effect of activation of PPAR-a is decreased VLDL production by the liver - They severely drop triglyceride levels, and are first line in treatment of hypertriglyceridemia - Fibrates can also inhibit cholesterol-7a-hydroxylase, which catalyzes the rate limiting step in the synthesis of bile acids... This reduced bile acid production results in decreased cholesterol solubility in bile and favors formation of cholesterol stones

What is a common but benign event that can occur after administration of a fibrinolytic (like tPA) in a pt with an acute MI?

- Fibrinolytics may cause a reperfusion arrhythmia after clot lysis and restoration of blood flow... These arrhythmias are usually benign Accelerated idioventricular rhythm is a common reperfusion arrhythmia

What is the equation for Filtration Fraction?

- Filtration Fraction is the fraction of plasma flowing through the glomeruli that is filtered across the glomerular capillaries FF = GFR/RPF - Renal Plasma Flow (RPF) is used to calculate FF rather than Renal Blood Flow (RBF) because RBF includes the volume of blood that is occupied by erythrocytes, which is unable to be filtered across the glomerulus capillaries -RPF = RBF * (1 - Hematocrit)

In what state can ACE inhibitors cause most significant first-dose hypotension?

- First-dose hypotension can be most serious is patients with volume depletion (ex: from diuretic use)

State what is in each region of the lymph node: - Follice - Paracortex - Medullary Cords - Medullary Sinuses

- Follicle - Site of B cell localization and proliferation (center = germinal center) - Paracortex - Site of T cells. Also has high endothelial venules, which T cell and B cels enter from blood - Medullary Cord - Has closely packed lymphocytes and plasma cells - Medullary Sinus - Has Macrophages and reticular cells (these communicate with the efferent lymphatics - leaving the node)

How does follicular lymphoma present? What translocation is it associated with? How does it look on histology?

- Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in adults, and the second most common overall - It has a long, waxing and waning clinical course, and most often presents in middle-aged patients with painless lymph node enlargement or abdominal discomfort from an abdominal mass - It is associated with a t(14:18) translocation, which swaps BCL-2 gene (18) and the IG heavy chain gene (14) - This leads to over expression of BCL-2, which inhibits apoptosis (because the function of BCL-2 is to stabilize the mitochondrial membrane, and prevent cytochrome c from leaking into the cytoplasm... because this would then lead to apoptosis) - The histology grossly looks like follicle-like nodules diffusely throughout the lymph node - which has disrupted the normal lymph node architecture. More closely, you can see a mixture of cleaved and non-cleaved follicle center cells in a nodular pattern. There are also no tingible body macrophages in germinal centers (no empty white spaces, indicating no apoptosis) NOTE: Pathoma page 61

What is the only GLUT transporter that is responsive to insulin? And, what tissues is it in?

- GLUT-4 is the only glucose transporter that is responsive to insulin - GLUT-4 is only expressed in skeletal muscle and adipocytes

The two main disorders of Galactose metabolism are: Galactokinase deficiency and Classic Galactosemia... Describe them:

- Galactokinase deficiency - Autosomal Recessive. Deficiency causes a buildup of Galactitol. Mild condition - Classic galactosemia - Autosomal recessive. Absence of Galactose-1-phosphate uridyltransferase. More severe. Note: The more severe disease leads to Phosphate depletion, because it is being used up to make the Galactose-1-Phosphate

What is the pathogenesis of Gallstone Ileus?

- Gallstone ileus is a mechanical bowel obstruction caused when a large gallstone erodes into the intestinal lumen through a Cholecystenteric fistula - Air in the biliary tract (Pneumobilia) is a common finding and is d/t retrograde passage of intestinal gas through the fistula - Sx = crampy pain, vomiting, bloating - Ex = signs of small bowel obstruction (abdominal distension, tenderness, and high-pitched bowel sounds)

What are the 2 basal long-acting insulin formulations?

- Glargine - Detemir

How do Giloblastomas present histologically?

- Glioblastoma is a highly aggressive primary tumor (in adults) - Commonly occurs in the Frontotemporal lobe, and grows across the corpus callosum - Consists of: bizarre-looking glial cells with multiple mitotoc figures, *pseudopalasading cells border areas of necrosis*, and abundant neovascularization and hemorrhage - *GFAP+*

What 2 factors are required for growth of H. Influenzae?

- H. Influenzae requires V (NAD+) and X (Hematin) - This can be accomplished by growing H. Influenzae in the presence of Staph Aureus and demonstrating the "satellite phenomenon", whereby H. Influenzae grow only near the B-hemolytic Staph Aureus colonies that produce the needed X and V factors

What is the pathogenesis of a gastric ulcer vs. duodenal ulcer d/t H. pylori?

- H. pylori colonization of the *Gastric Antrum* leads to depletion of somatostatin-producing Delta cells (which are mostly in the antrum), which will lead to increased gastrin levels & increased acid secretion by parietal cells. H. Pylori also releases cytotoxins that inhibit duodenal bicarb production. These combined effects lead to increased acid load emptying into the duodenum, leading to *duodenal ulcers* - H. Pylori colonization of the *gastric body* will lead to *gastric ulcer* formation d/t the direct mucosal damage caused by bacterial products (ammonia & cytotoxins) and the resultant inflammatory response... Note that the Delta cells will not be destroyed here b/c they are located in the antrum, which is not affected

How can Desmopressin treat Hemophilia A and/or VonWillebrand disease?

- Hemophilia A tx - Desmopressin increases circulating factor VIII levels (which is produced by endothelial cells) - Von Willebrand tx - Desmopressin stimulates vonWillebrand factor secretion from endothelial cells NOTE: This can NOT be used to treat Hemophilia B (which must be treated with Factor IX replacement)

What carcinogens is Hepatic angiosarcoma associated with? And, what marker do the tumor cells express?

- Hepatic angiosarcoma is very rare - It is associated with exposure to carcinogens such as: Arsenic, Thorotrast, and Polyvinyl Chloride - The tumor cells express CD 31+ (an endothelial cell marker)

What molecule plays a primary role in regulating iron storage and release by other cells involved in iron homeostasis?

- Hepcidin - Hepcidin can bind to Ferroportin (a transmembrane protein which transferrs iron in enterocytes into circulation), and cause it to be internalized and degraded... Thus decreasing intestinal absorption of iron - Hepcidin also can inhibit the release of iron by macrophages NOTE: High iron levels and inflammatory conditions increase the synthesis of hepcidin by hepatic parenchymal cells

What does a C1 (complement) inhibitor deficiency result in?

- Hereditary angioedema - C1 inhibitor deficiency causes increased cleavage of C2 to C4 and results in inappropriate activation of the complement cascade - C1 inhibitor also blocks Kallikrein-induced conversion of Kininogen to Bradykinin, a potent vasodilator associated with angioedema... so without the inhibitor there will be increased Bradykinin and this can lead to angioedema - ACE inhibitors are absolutely contradicted in these patients!!

What causes Hereditary angioedema? And, what drug class is contraindicated in these patients?

- Hereditary angioedema is d/t deficient C1 esterase inhibitor (Autosomal Dominant) - C1 esterase inhibitor normally suppresses activation of C1, and therefore suppresses the rest of the classical compliment pathway - C1 esterase also inactivates Kallikrein, which normally catalyzes Kininogen to Bradykinin... Thus, in hereditary angioedema, both active kallikrein and bradykinin levels are increased - Bradykinin, C3a, and C5a mediate angioedema by increasing vasodilation and vascular permeability - ACE inhibitors are contraindicated in patients with hereditary angioedema... This is because ACE converts bradykinin to its inactive metabolites. So ACE inhibitors can lead to increased bradykinin levels... This, on top of the already increased levels of bradykinin and a pt with hereditary angioedema, is NO bueno!

What is heteroplasmy (genetics)

- Heteroplasmy describes the condition of having different mitochondrial genomes within a single cell - The severity of mitochondrial diseases is often directly related to the proportion of abnormal to normal mitochondria within a patient's cells

What does hormone-sensitive lipase do?

- Hormone-sensitive lipase (HSL) is found in adipose tissue where if functions to drive the breakdown of stored triglycerides into free fatty acids and glycerol... Which can be used for gluconeogenesis and and ketone body formation NOTE: Lipoprotein lipase has a similar function to HSL, but it is found in endothelial cells where it degrades triglycerides found in chylomicrons and VLDL, to form free fatty acids that are then transported into adipocytes storage or used by tissues for energy

What is the mnemonic for Anti-muscarinic toxicity?

- Hot as a hare (decreased sweating) - Dry as a bone (decreased sweating) - Red as a beet (compensatory cutaneous vasodilation d/t inhibition of eccrine sweat glands) - Blind as a bat (increased pupil dilation) - Mad as a hatter

What are the 4 meds that are used to treat HTN in a preggo?

- Hydralazine (Dilates arterioles > veins) - Methyldopa (alpha-2 agonist - pre-synaptic so negative feedback to inhibit sympathetic output) - Labetalol (nonselective a & B antagonist) - Nifedipine (Ca Channel blocker) "Hypertensive Moms Love Nifedipine"

What is the mechanism of Hydralizine? And what is a common side effect?

- Hydralizine is a *direct vasodilator* (artery>vein) by increasing cGMP, which lowers BP - The lowered BP can trigger a reflex sympathetic activation and stimulate the renin-angiotensin-aldosterone axis, which can result in a tachycardia, and fluid retention/edema -This drug can also produce Lupus-like syndrome

What are symptoms of hypercalcemia? How can a granulomatous dz (like TB or sarcoidosis) cause this?

- Hypercalcemia can cause impaired depolarization of neuromuscular membranes (causing weakness, constipation, and confusion), Impaired urine concentration in the distal tubule (leading to polyruia/polydipsia), and renal stone formation and bone demineralization with bone pain. -Activated macrophage, as seen in granulomatous diseases, can express 1-alpha-hydroxylase, which converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol - the active form). Activated Vitamin D will upregulate calcium and phosphate absorption in the small intestines, and increase calcium and phosphate reabsorption in the kidneys... 1-alpha-hydroxylase is usually only functional in the kidney

What are 2 ways that Beta-Blockers can help with hyperthydoidism

- Hyperthyroidism causes an upregulation of B-adrenergic receptor expression, leading to increased catecholamine effects... and Beta-blockers can help blunt these adrenergic manifestations - In addition, lipid-soluble B-blockers (like Proranolol) reduce conversion of T4 to T3 in peripheral tissue by inhibiting 5'-Monodeiodinase NOTE: peripheral conversion is also decreased by Glucocorticoids and Propylthioruacil

What is the main chemotactic factor for Neutrophils?

- IL-8 is a chemokine produced by macrophages that induces chemotaxis and phagocytosis in neutrophils "Clean up on isle 8" - Neutrophils are recruited by IL-8 to Clear infections NOTE: Other significant chemotactic agents include n-formylated peptides, leukotriene B4, 5-HETE, and complement C5a

What is a rare concern when given IV acyclovir?

- IV acyclovir can cause crystalline nephropathy (5-10% of pts) if adequate hydration is not also provided - This occurs because a high concentration of acyclovir in the collecting duct can exceed its solubility, and it can crystalize and damage the renal tubule

If Giant cell arteritis is suspected (aside from administrating steroids), what diagnostic test should be done immediately?

- If GSA is suspected, a *C-reactive protein* or *erythrocyte sedimentation rate* should be determined promptly These are non-specific, but highly sensitive and are almost always elevated in pt with GSA ... if these are elevated, then the pt should undergo Temporal Artery Biopsy (to confirm diagnosis)

What is the first step if there is suspicion for child abuse?

- If there is suspicion for abuse, the first step is to ask permission to interview the child alone, and conduct a full evaluation - Following the full evaluation, physicians should contact Child Protective Services immediately with any child abuse concerns NOTE: This is the same for elder abuse... If there is suspect of abuse, the patient should be interviewed alone to avoid intimidation by possible abusers... After the history and physical, if there is still concern for abuse, then it must be reported

Drug: Omalizumab

- IgG1 monoclonal antibody that binds with IgE to inhibit the action of IgE with its receptor on mast cells and basophils - effective and acceptable add-on therapy for patients with severe allergic asthma... It has been shown to be effective in reducing dependency on both oral and inhaled steroids

Describe the pathogenesis of the Sertoli and Leydig cells in Klinefelter syndrome:

- In Kleinfelter, there is progressive destruction and hyalinization of the seminiferous tubules, which causes the tests to be small and firm - *Sertoli cell damage* causes *decreased serum inhibin* - *Leydig dysfunction* causes *reduced testosterone* - The loss of negative feedback via Inhibin and Testosterone will lead to elevated FSH and LH

What is one way to differentiate Membranous Nephropathy from Membranoproliferative Glomerulonephritis on light microscopy?

- In Membranoproliferative Glomerulonephritis, light microscopy shows large hypercellular glomeruli (hence "proliferative") - In Membranous Nephropathy, diffuse thickening of the capillary wall is seen without an increase in the cellularity

In a patient with pancreatitis, what other findings would help prove that it is due to alcohol consumption?

- In Pancreatitis d/t alcohol abuse the pt will likely have >2 AST:ALT ration - Gallstones would be absent (ruling out this as a cause) - The patient may have a isolated macrocytosis (MCV >100)... This is seen even in the absence of anemia, and is likely related to poor nutrition (ex: folate deficiency), liver disease, and/or direct toxicity of alcohol in the marrow NOTE: Gallstones are the most common cause of acute pancreatitis, and alcohol abuse is the second most common cause

In addition to the MCP and PIP joints of the hand, where else can Rheumatoid Arthritis affect?

- In addition to the MCP and PIP joints of the hand, RA may also involve wrists, elbows, knees, ankles, and Cervical spine. - Cervical spine involvement can be common with longstanding disease, and may lead to severe pain and disability d/t spinal instability and potential radiculopathy/cord compression NOTE: DIP joints are spared!! also, hips and lumbosacral joints are also usually spared

What uterine specimen findings would you expect during an Ectopic Pregnancy?

- In an ectopic pregnancy, a uterine specimen would reveal decidualized endometrium only - dilated, coiled endometrial glands and vascularized edematous stroma. These are the changes that occur dueing the Luteal / Secretory phase of the menstural cycle, under the influence of progesterone, as the endometrium prepares for implantation. Embryonic and trophoblastic tissue will be absent from the uterus (you will NOT see villi)

What is the primary cell in Gliosis (after irreversible neuronal injury)?

- In irreversible neuronal damage/death, *astrocytes* proliferate at the site of injury in a process called gliosis (or astrocytosis) - Proliferating astrocytes are enlarged and contain a large number of fibrils and glycogen granules. Their nuclei are large, vesicular and display prominent nucleoli. Proliferated astrocytes replace lost neurons and compensate for their volume loss. Later, after the neuronal death, astrocytic processes form a closely connected firm meshwork, called a gliotic scar

What are 6 compensatory changes that contribute to long-term high altitude acclimatization?

- Increased 2,3-BPG - Increased Hb production (via erythropoeitin production) - Increased pulmonary diffusion capacity - Vascular endotheilial growth factor-induced angiogenesis - Increase in cellular mitochondria counts - Hemoconcentration (d/t HCO3 diuresis and fluid shift)

How does an increase in cGMP cause SMOOTH muscle relaxation?

- Increased cGMP activates myosin light chain phosphatase (and reduces the activity of myosin light-chain kinase) - Myosin light chain phosphatase dephosphorylates the myosin light chain, and this causes smooth muscle relaxation NOTE: Smooth muscle lacks a troponin complex --- Phosphorylated myosin light chain = contraction (phosphorylation allows myosin to bind to actin) --- Dephosphorylated myosin light chain = relaxation NOTE: First aid pg. 434

Whats the pathogenesis of how Increased intracranial pressure can cause vision disturbance?

- Increased intracranial pressure compresses the optic nerves, resulting in impaired axoplasmic flow and optic disc edema

What are the side effects of PPIs?

- Increased risk for osteoporotic fractures is d/t decreased Calcium absorption in the GI tract... B/c insoluble calcium requires an acidic environment for proper absorption

What is the mechanism of Isoniazid?

- Inhibition of mycolic acid synthesis by M. Tuberculosis. - The mechanism is not totally understood, but Isoniazid must be processed by mycobacterial catalase peroxidase (encoded by KatG) for the drug to be activated within the bacteria - Isoniazid also requires a specific protein sequence in its enzyme target

What 2 classes of drugs should be given for Status Epilepticus? And, what is the mechanism for both?

- Initial treatment includes IV lorazepam and Phenytoin given concurrently - Benzo mechanism = bind to ligand-gated chloride channel of the GABA(a) receptor, and enhance the inhibitory effect of GABA by increasing post-synaptic chloride influx (and hyper-polarization of the cell) - Phenytoin is a long-acting anticonvulsant that inhibits neuronal high-frequency firing by reducing the ability of Na channels to recover from inactivation

What do these findings indicate if there is a history of pelvic fracture: Inability to void with a full bladder sensation, a high-riding boggy prostate, and blood at the urethral meatus,

- Injury to the posterior urethra is associated with pelvic fractures, and the anterior urethra is most commonly damaged in straddle injuries - The membranous segment of the posterior urethra (distal to the prostate) is most susceptible to injury because it doesn't have the protection of the prostate around it - Inability to void with a full bladder sensation, a high-riding boggy prostate (caused by hematoma formation below the gland), and blood at the urethral meatus are suggestive of urethral injury, particularly in the setting of a pelvic fracture - If urethral injury is suspected, placement of a foley catheter is contraindicated

How does Arsenic poisoning present? and what is the antidote?

- Insecticides and contaminated water are common sources of arsenic - Arsenic poisoning impairs cellular respiration, by inhibiting pyruvate dehydrogenase, and presents with abdominal pain, vomiting, diarrhea, hypotension, QT prolongation, and a GARLIC odor of the breath - Treatment is Dimercaprol (a chelating agent)

What is malingering?

- Intentional falsification of symptoms for personal gain (financial benefits, time off work, etc.) - they are working for an obvious reward

What do Interferon alpha and beta do?

- Interferon alpha and beta are produced by most human cells in response to viral infections. The production of alpha and beta interferons helps suppress viral replication by halting protein synthesis and promoting apoptosis of infected cells, limiting the ability of viruses to spread through tissues - Interferon alpha and beta can be secreted and bind to type I interferon receptors found on infected and neighboring cells (autocrine/paracrine)

How does interstitial lung disease affect radial traction on the airways?

- Interstitial lung disease is associated with decreased lung volumes and increased lung elastic recoil caused by fibrotic interstitial tissue - The increased fibrotic tissue (& elastic recoil) results in *increased radial traction (outward pulling) on the airways*, leading to increased expiratory flow rates when corrected for the low lung volume *This is why the FEV1/FEV ratio is high in patients with restrictive lung disease* (d/t airway widening relative to the low lung volumes)

What is the underlying cause of an Atresia of the Jejunum/Iluem?

- Intestinal atresia DISTAL to the duodenum are the result of *vascular accidents* in utero (like vascular occlusion) - The result of these are a blind end Jejunum or Ileum, with a length of absent bowel or mesentery, and then a terminal ileum spiraled around an ileocolic vessel NOTE: Duodenal atresia is d/t failure to re-canalize

How does Timolol work in Glaucoma treatment?

- It decreases the secretion of aqueous humor by the ciliary epithelium (Note: *Acetazolamide*, a carbonic anhydrase inhibitor, and *Alpha-2-agonists*, also decreases the secretion of aqueous humor by the ciliary epithelium)

Dermatitis herperiformis (small, herpes-like vesicles) is associated with what GI condition? And, why does it occur?

- It is associated with Celiac Disease - It occurs b/c IgA antibodies against Gliadin can cross-react with epidermal transglutaminase, and can cause IgA deposition at the tips of dermal papillae - Histologically, Dermatitis Herpetiformis is characterized by micro abscesses containing fibrin and neutrophils at the dermal papillae tips

What is Granuloma Inguinale (Donovanosis)? And, what causes it?

- It is caused by Klebsiella Granulomatis - It initially manifests as a painless genital papule that eventually ulcerates, with NO lymphadenopathy - The base may have granulation like tissue - Diagnostic = "Deeply staining gram negative intracytoplasmic cysts (Donovan Bodies)" - If untreated, it can lead to severe lymph obstruction and lymphedema (elephantiasis)

What is the mechanism of Malignant hyperthermia (after anesthesia)

- It is caused by a defect Ryanodine receptor (Autosomal Dominant) - Pt presents w/ diffuse muscle rigidity, followed by hyperthermia and possible myoglobinuria - Abnormal Ryanodine receptors release a large amount of Ca after exposure to the anesthetic... this excess free Ca in the cytoplasm stimulates ATP-dependant reuptake by the sarcoplasmic reticulum. The excessive consumption of ATP generates heat... Together, loss of ATP and heat can further cause muscle damage - Rhabdomyolysis leads to release of potassium, myoglobin, and creating kinase into circulation

What is the inheritance of Achondroplasia?

- It is inherited as *Autosomal Dominant* - A person with Achondroplasia is most likely Heterozygous, b/c most homozygotes die shortly after birth NOTE: 85% of cases appear as a sporadic mutation d/t advanced paternal age, while 15% of cases are inherited from a parent... But regardless of how the person got it, it is still passed on in an autosomal dominant fashion

How does a Glioblastoma Multiforme appear on gross examination?

- It is typically located within the cerebral hemisphere . and may gross the midline - they grossly contain areas of necrosis and hemorrhage

How does parvovirus manifest in an adult?

- It will usually be a teacher because there can be school outbreaks - Sx = acute symmetric arthralgia/arthritis involving hands, wrists, knees, and/or feet, with or without rash

What cells in the kidney secrete Renin?

- JG (Juxtaglomerular) cells are modified smooth muscle cells located in the wall of the afferent arteriole, and contain renin zymogen granules NOTE: The macula densa cells are located in the distal tubule and monitor salt content and tubular flow rate... They transmit this info to the the JG cells

What is Kartagener Syndrome?

- Kartagener Syndrome is Autosomal Recessive, and is a form of primary ciliary dyskinesia (PCD), which are caused by a variety of mutations that impair ciliary structure and function - Primary ciliary dyskinesia can be d/t defective dynein arms, b/c dynein arms have ATPase which generates energy to slide microtubules past each other, producing movement - Patients with PCD can have recurrent respiratory infections (d/t impaired mucociliary clearance), situs inversus (d/t defect in Left-Right Dynein, and impaired ciliary movement during embryogenesis), and infertility in men and women (d/t immotile sperm and immobility of fallopian tube cilia)

What is diagnostic for Diabetes Nephropathy?

- Kimmelstiel-Wilson nodules - Diagnostic for nodular glomerularsclerosis - These are always in the peripheral of the mesangium - In DM Nephropathy... It starts with selective loss of albumin with no casts... But then can progress to overt nephrotic syndrome

What are the 3 bacteria that are (fast) fermenters of lactose and will shot up as pink on MacConkey?

- Klebsiella (3A: Alcoholics, Abscesses, Aspiration PNA) - E. Coli - Enterobacter Note: The slow fermenters are Citrobacter, and Serratia

What is a Koilocyte (cell)?

- Koilocytosis is a hallmark sign of HPV infection. Koilocytes are pyknotic, superficial or immature squamous cells with a dense, irregularly staining cytoplasm and perinuclear halo-like clearing - Koilocytes can be seen on a Pap smear and indicate an HPV infection - Koilocytes are pathognomonic for HPV

What is the treatment for hyperammonemia in Hepatic Encephalopathy?

- Lactulose is metabolized by GI bacteria, which makes an acidic environment. This converts absorbable Ammonia (NH3) into non-absorbable Ammonium (NH4), which gets pooped out - Abx - kill GI bacteria that form NH3

What are Lacunes? And, what causes Lacunar Infarcts?

- Lacunes are small (<15mm) cavitary infarcts located within the basal ganglia, posterior limb of the internal capsule, pons, and cerebellum (i.e. the deep brain structures) - Lacunar infarctions are the result of small vessel occlusion in the penetrating vessels supplying the deep brain structures (such as: occlusion of lenticulostriate arteries) - The most common cause of these occlusions are Lipohyalinosis (hyaline thickening of the vascular wall secondary to leakage of plasma proteins), Microatheromas (atherosclerotic accumulation of lipid-laden macrophages in the intimal layer), and hypertensive arteriolar sclerosis (hardening/thickening of the vessel wall).... These all predispose to thrombotic vessel occlusion

Hypothalamic nuclei and functions (Lateral, Ventromedial, Anterior, Posterior, Arcuate, Paraventricular, Supraoptic, and Suprachiasmatic)

- Lateral - Mediates hunger (makes you hungry) - stimulated by ghrelin (lateral makes you grow lateral) - Ventromedial - Mediates satiety (makes you full) stimulated by leptin (medial makes you more medial - skinny) - Anterior - Mediates heat dissipation (makes you cool off - parasympathetic) (A/C: Anterior = cooling) - Posterior - Mediates heat conservation (makes you hot - sympathetic) - Arcuate - secretes dopamine (inhibits prolactin), growth hormone-releasing hormone (GHRH), and gonadotropin-releasing hormone (GnRH) - Paraventricular - secretes ADH, corticotropin-releasing hormone (CRH), oxytocin, thyrotropin-releasing hormone (TRH) - Supraoptic - secretes ADH and oxytocin - Suprachiasmatic - circadian rhythm regulation and pineal gland function (you need sleep to be charismatic)

What is the best way to listen to Left ventricular gallops (S3 & S4)?

- Left ventricular gallops (S3 and/or S4) are best heard with the bell of the stethoscope over the cardiac apex while the patient is in the left lateral decubitus position at the end of expiration (because the decreased lung volume brings the heart closer to the chest wall)

Which antibiotic can precipitate serotonin syndrome if combined with an SSRI?

- Linezolid has MAO inhibitory activity, and can therefore precipitate serotonin syndrome when used concomitantly with an SSRI - Serotonin syndrome is characterized by the triad of autonomic instability, altered mental status, and neuromuscular irritability/hyperactivity

What type of necrosis occurs in the CNS after ischemia?

- Liquefactive necrosis - this occurs here d/t lack of substantive supporting stroma - The infarcted CNS tissue is eventually replaced with a cystic astroglial scar NOTE: In other organs, lethal ischemic injury results in coagulative necrosis

What 4 bacteria are resistant to Cephalosporins?

- Listeria monocytogenes (tx w/ Ampicillin) - MRSA (tx w/ vancomycin) - Enterococci (tx w/ Linezolid or Tigecycline) - Atypicals (mycoplasma, Chlamydia) (tx w/ Macrolides)

What are the side effects of Lithium?

- Lithium is used for the treatment of Bipolar disorder, and unipolar depression - SE = Tremor, Diabetes Insipitus, Hypothyroidism (weight gain, dry skin, hair loss, constipation, goiter), and Ebstein Anomaly of the tricuspid valve if used during pregnancy LiTHIUM: - L&T = Low Thyroid - H = Heart (Ebstein Anomaly) - I = Insipidus (nephrogenic diabetes insipidus) - U&M = Unwanted Movements

How does locked-in syndrome present? And, what causes it?

- Locked in syndrome is d/t a *Pontine hemorrhage*... Usually d/t a *basilar artery stroke* (Basilar artery stroke can affect Pons, Medulla, and lower midbrain) - It is characterized by spastic quadriplegia, paralysis of most cranial nerves, but preserved eye movement and consciousness

What drugs are the first line therapy for psychomotor agitation associated with alcohol withdrawl?

- Long acting benzos such as diazepam of chlordiazepoxide (or lorazepam) - if the pt has liver disease, then pick a benzo that does not undergo metabolism in the liver and has no active metabolites (lorazepam, oxazepam, temazepam)

What are the staining characteristics of Nocarida?

Branching filamentous bacilli - gram POSITIVE And partially acid fast

After the onset of ischemia, how long does it take for there to be loss of cardiomyocyte contractility? And, how long for there to be irreversible injury?

- Loss of cardiomyocyte contractility = after 60 seconds - Irreversible ischemic injury = after 30 minutes

What is conversion disorder?

- Loss of sensory or motor function (ex: paralysis, blindness, mutism), often following an acute stressor - Patients may be aware but seem indifferent towards their symptoms ("la belle indifference) - so they are not super super anxious about it - Also called *functional Neurologic symptom disorder*

What is the inheritance pattern of Lynch syndrome? And what defects cause it?

- Lynch syndrome is autosomal dominant - It is d/t abnormal nucleotide mismatch repair, typically d/t mutations in MSH2 and/or MLH1 which code for MutS and MutL - It is associated with colorectal cancer, endometrial cancer, ovarian cancer, and skin cancer

What product of fatty acid synthesis inhibits fatty acid degradation?

- Malonyl-CoA - The conversion of Acetyl-CoA to malonyl-CoA is the rate-limiting step of de novo fatty acid synthesis - Malonyl-CoA inhibits carnitine acyltransferase (which is used in the carnitine shuttle in fatty acid degradation), preventing the transfer of Acyl groups into the mitochondria... This occurs to prevent the breakdown of newly synthesized fatty acids

What is deficient in Maple Syurp Urine Disease? And, what are some clinical manifestations?

- Maple Syrup Urine Disease is autosomal recessive, and d/t Branched-Chain a-Ketoacid dehydrogenase complex (BCKDC) deficiency - BCKDC normally allows for the breakdown of Leucine, Isoleucine, and Valine, into substrates that enter the TCA cycle - Thus a deficient BCKDC leads to elevated levels of branched-chain amino acids, and is neurotoxic primarily d/t elevated Leucine - It manifests in infants with irritability, poor feeding, lethargy, increased muscle tone, and the urine has a sweet "maple syrup" odor. - Treatment is dietary restriction of branched chain amino acids

What are characteristics of dissociative identity disorder?

- Marked discontinuity in identity & loss of personal agency with fragmentation into *>2 distinct personality states* - Associated with severe trauma/abuse

What cells secrete Pepsinogen/pepsin? Where are these cells? What do this enzyme do?

Chief cells in the stomach secrete pepsinogen, which gets converted to pepsin in the presence of acid. Pepsin initiates protein digestion

Signs of Common peroneal nerve injury

Common peroneal nerve injury is common and typically results from trauma to the leg near the head of the fibula. Signs include foot drop (d/t inability to dorsiflex) and characteristic "steppage gait". Damage also causes loss of sensation to the anterolateral leg and dorsum of the foot. NOTE: common peroneal nerve is also called common fibular nerve

McArdle disease (Glycogen storage disease type V): - What enzyme is deficient? - What is the pathogenesis? - What are classic symptoms?

- McArdle disease is d/t a deficiency in myophosphorylase (an isoenzyme of glycogen phosphorylase present in muscles) - During glycogenolysis, glycogen phosphorylase shortens glycogen chains by cleaving a-1, 4-glycosidic linkages between glucose molecules, liberating glucose-1-phosphate, which can then be converted to glucose-6-phosphate, and proceed to glycolysis - A myophosphorylase deficiency causes failure of muscle glycogenolysis, resulting in decreased exercise tolerance, muscle pain and cramping, and myoglobinuria with physical activity

What is the mechanism & main side effects of the DM drugs: Thiazolidinediones (Pioglitazone, Rosiglitazone)

- Mechanism: Increase insulin sensitivity in peripheral tissue by binding to PPAR-g nuclear transcription regulator - Main SE = *Fluid retention* d/t increased Na reabsorption, which can lead to *water weight gain*, *peripheral edema*, and *decompensation of underlying CHF*... Can also cause 8adipose weight gain*

What is a typical presentation of Acute Myelogenous Leukemia?

- Median age of onset = 65 - Most pts present with complications of pancytopenia (fatigue from anemia, bruising from thrombocytopenia, infection from possible functional neurtopenia despite leukocytosis) - Median WBC count is 15,000 at the time of diagnosis, and there is > 20% myeloblasts in the bone marrow

What are the histological characteristics of Medullary Carcinoma?

- Medullary thyroid cancer is a neuroendocrine tumor that arises from parafollicular calcitonin secreting C cells - It is characterized by *nests or sheets of polygonal polygonal or spindle-shaped cells with amyloid deposits derived from calcitonin* NOTE: Amyloid deposits stain with Congo red stain

What is the filtration, secretion, and re-absorption pattern of Creatinine and Inulin?

Creatinine is filtered, with an insignificant amount also being secreted into the renal tubules, and none of it is Reabsorbed. Inulin is filtered, not secreted at all, and not reabsorbed at all NOTE: Inulin clearance can be used to estimate GFR because of these properties

What mutation is seen in familial medullary thyroid cancer?

- Medullary thyroid cancers are tumors of the parafollicular calcitonin-secreting C-cells - Germline mutations of the RET proto-oncogene are present in more than 95% of patients with familial medullary thyroid cancer - RET proto-oncogene mutations are also commonly found in sporadic medullary thyroid cancers - RET is associated with MEN 2A and MEN2b (both which include medullary thyroid cancer) NOTE: - RAS mutations are common in follicular thyroid cancer - Inactivation of p53 is fairly common in anaplastic thyroid cancer

Types of exocrine glands: - Merocrine - Apocrine - Holocrine

- Merocrine - release a watery secretory product via exocytosis with no loss of cell membrane (ex: salivary gland, eccring sweat gland) - Apocrine - release membrane-bound vesicles containing the secretory product (ex: mammary glands) - Holocrine - release the entire content of cells via cell lysis (ex: sebaceous glands, meibomian glands)

Name 7 drugs that can cause Drug Induced Lupus:

- Methyldopa - alpha-2 agonist (used to treat HTN in preggo) - Sulfa drugs - Hydralazine - arteriole vasodilator (for severe HTN and HTN in preggo) - Isoniazid - Abx for TB - Procainamide - Class 1A antiarrhythmic - Phenytoin - Anti-epileptic (blocks Na channels for Status Epilepticus prophylaxis) - Etanercept - TNF-a inhibitor THE BIG DOGS ARE: *HYDRALAZINE, PROCAINAMIDE, & ISONIAZID*

What is Methylmalonic acidemia?

- Methylmalonic acidemia is an organic acidemia d/t complete or partial deficiency of methylmalonyl-COA mutase - Complete deficiency classically presents with lethargy, vomiting, and tachypnea in a newborn. - Labs = hyperammonemia, ketotic hypoglycemia, and metabolic acidosis - Dx via elevated urine methylmalonic acid and propionic acid

Describe the Metyrapone test in evaluating adrenal insuffieiency (& Hypothalamus-Pituitary-Adrenal Axis integrity)

- Metyrapone blocks Cortisol synthesis via inhibition of 11B-hydroxylase, thus causing an build up of 11-deoxycortisol - 11-deoxycortisol lacks glucocorticoid activity, and thus does not inhibit pituitary ACTH secretion - So as a result, the reduction of cortisol levels following Metyrapone administration cause an increase in pituitary ACTH secretion, which will further increase the 11-deoxycortisol production - 11-deoxycortisol gets metabolized in the liver to 17-hydroxycorticosteroids, which accumulate in the urine - SO, if the HPA axis is intact, you will see a rise in serum 11-deoxycortisol and urinary 17-hydroxycorticosteroids - If these fail to rise, then it implies a primary or secondary adrenal insufficiency (which can then be distinguished based on plasma ACTH levels)

What are the clinical manifestations of Trisomy 18?

- Micrognathia (small jaw) - Low-set ears - Prominent occiput - Rocker bottom feet - Hypertonia - Clenched hands - Overlapping fingers - Cardiac abnormalities

What are the clinical manifestations of Trisomy 13?

- Midline facial defects (holoprosencephaly, Cleft lip/palate) - Polydactyly (more than 5 fingers or toes) - GI abnormalities (omphalocele, umbilical hernia)

What major disease should be suspected if you see migratory thrombophlebitis?

- Migratory thrombophlebitis should raise suspicion for cancer - Hypercoagulability is a very common paraneoplastic syndrome seen most frequently in visceral adenocarcinomas of the pancreas, colon, and lung - Hypercoagulability develops because adenocarcinomas produce a thromboplastin-like substance capable of causing chronic intravascular coagulations that can disseminate and tend to migrate NOTE: Migratory superficial thrombophlebitis is known as Trousseau sign

These 3 drugs are used for pregnancy termination.. what is the mechanism of each? - Misoprostol - Mifepristone - Methotrexate

- Misoprostol - Prostaglandin E1 agonist - causes cervical softening and uterine contractions leading to expulsion of the pregnancy - Mifepristone - Progesterone antagonist - that results in apoptosis and necrosis of the uterine decidua - Methotrexate - Folic acid antagonist - inhibit trophoblast division

What is the inheritance pattern of a mitochondrial dysfunction? And, how do they usually present?

- Mitochondrial dysfunction usually presents with myopathy, nervous system dysfunction, lactic acidosis, and ragged red fibers on muscle biopsy - Mitochondrial myopathies d/t mtDNA mutations are inherited from mother to all children (maternal inheritance) NOTE: mtDNA can also be referred to as "extranuclear DNA"

What retroperitoneal structure is at risk of being accidentally injured during hysterectomy?

- The ureter can be injured during hysterectomy d/t its close proximity to the uterine structures - The distal ureter may be severed during ligation of the uterine vessels b/c the ureter passes inferior and lateral to the uterine artery at the level of the internal cervical os prior to entering the bladder ("water under the bridge") - A ureteral obstruction d/t a suture leads to flank pain d/t distention of the proximal ureter with urine - A transection injury of the ureter causes localized leakage of urine as well as flank pain NOTE: Since it is usually only one ureter injured, the patient is able to urinate normally

What stimulates Theca cells, and what stimulates Granulosa cells?

- Theca cells are stimulated by LH - Granulosa cells are stimulated by FSH

What do Matrix Metalloproteinases do?

- Their primary function in the *degradation of collagen and other proteins in the extracellular matrix* - Their activity is important in wound healing, as it encourages both myofibroblast accumulation at the wound edges and scar tissue remodeling (They also participate in a tumor cell invading the basement membrane b/c they can beak up the connective tissue)

What is Chvostek and Trousseau sign and what do they indicate?

- They indicate low blood Ca (leading to neuromuscular excitability) - Chvostek = tapping facial nerve elicits twitching of the nose and lips - Trousseau = Inflation of a blood pressure cuff leads to carpal tunnel spasm

What 3 drugs can impair lithium clearance and lead to toxicity?

- Thiazide diuretics, ACE inhibitors, and NSAIDs

What diuretic is indicated in patients with recurrent calcium-based nephrolithiasis?

- Thiazides increase calcium reabsorption from the nephron (one of the side effects to thiazides is they cause hypercalcemia) - This will decrease the calcium in the urine, and help prevent stone formation NOTE: Thiazides are contraindicated in the setting of hypercalcemia

What is the most common location for Avascular Necrosis (Osteonecrosis)? What are risk factors for this? And how does it present?

- Most common location = Femoral head Causes = Thrombotic/embolic occlusion (sickle cell, decompression sickness), Glucocorticoids, Vascular inflammation/injury (vasculitis, radiation), Alcohol abuse, traumatic fracture - Presentation = Pain on weight bearing and at rest, Decreased passive range of motion - PE = restricted range of motion in the affected joint, no swelling, erythema, or warmth - There can be a wedge shaped zone or geographic zone of necrosis, and on microscopy this will show dead bony trabeculae (empty lacunae) and fat necrosis

What is the mechanism & result of Thiazolidinediones (Pioglitazone, Rosiglitazone) in pt's with DM?

- Thiazolidinediones exert their glucose-lowering affects by decreasing insulin resistance - *They activate peroxisome-proliferator activated receptor-gamma*, a nuclear receptor that alters the transcription of genes involved in glucose and lipid metabolism (GLUT4 & Adiponectin)

What tumors are associated with Multiple endocrine neoplasia type 1?

- Multiple endocrine neoplasia type 1 is caused by mutations in the MEN1 (menin) tumor suppressor gene - it is characterized by the 3 Ps: *Parathyroid adenomas*, *Pituitary tumors*, and *Pancreatic endocrine tumors* (usually gastrinoma) - Primary hyperparathyroidism is often the initial manifestation and usually presents with asymptomatic hypercalcemia or renal stones - Entero-pancreatic neuroendocrine tumors, like Gastrinoma (leading to Zollinger-Ellison syndrome), insulinoma, and non-functional, are often metastatic and are a frequent cause of tumor-related death in MEN1

What are some muscle manifestations of hypothyroid (*Hypothyroid Myopathy*)

- Muscle pain, cramps, and weakness involving the proximal muscles - Delayed tendon reflexes & myoedema (focal muscle contraction at the site of percussion - d/t impaired Ca uptake by the sarcoplasmic reticulum) - Elevated Creatine Kinase - Other typical features of hypothyroid (fatigue, weight gain, bradycardia, and brittle nails)

What is the underlying cause of the Increased iron in Primary Hemochromatosis?

- Mutation in HFE gene (C282Y) - This mutation causes *increased intestinal Iron absorption* b/c the HFE protein normally interacts with the transferrin receptor to form a complex that senses iron stores... So inactivating mutations of the HFE protein cause enterocytes and hepatocytes to detect falsely low iron levels Labs = high Ferratin, low TIBC, high serum iron, high %saturation

Neuroblastoma (in children)... What is it? and what is its presentation?

- This is a tumor arising from neural crest cell usually in the adrenal medulla (but can be in the sympathetic chain/ganglia) - Usually presents in a child < 4 years old, with Abdominal distension, a firm/irregular abdominal mass, and possible Opsoclonus-myoclonus (nonrhythmic conjugate eye movements and involuntary jerking movements) - Bone marrow can cause anemia/pancytopenia, and orbital mets can cause periorbital ecchymoses - Urine typically has elevated catecholamine breakdown products (HVA, VMA) - Biopsy = *small round blue cells and Homer Wright Rosettes*, NSE+

Crohns Disease: What is a common mutated gene, and how does it contribute to the pathogenesis?

- Mutations in the NOD2 gene have shown strong association with Crohn disease - NOD2 is expressed in epithelial cells and macrophages and helps regulate innate immunity. It encodes an intracellular microbial receptor that recognizes bacterial lipopolysaccharides and subsequently activates the NF-kB pathway. NF-kB is a pro-inflammatory transcription factor that increases cytokine production. In Crohn disease, mutations in NOD2 result in decreased activity of NF-kB, which impairs the innate immune response of the intestinal mucosa (ex: antimicrobial peptide synthesis, mucin secretion). The loss of this natural battier defense allows luminal bacteria to penetrate submucosal tissues, causing an exaggerated response by the adaptive immune system that results in chronic GI inflammation

What is Length time bias?

- This occurs when subjects with a rapidly progressive form of a disease are less likely to be detected by screening compared to those with slowly progressive disease *do not get this confused with Lead-time bias*

What is the action of topoisomerase 1 and topoisomerase 2?

- Topoisomerase 1 - makes single stranded nicks to relieve supercoiling - Topoisomerase 2 - makes transient breaks in both strands of DNA simultaneously to relieve both negative and positive supercoiling Both of these are capable of re-sealing the breaks that they create

Which organ has the highest amount of oxygen extraction from blood?

- Myocardial oxygen extraction exceeds that of any other tissue or organ in the body - D/t the high degree of oxygen extraction, increases in myocardial oxygen demand can only be met by an increase in coronary blood flow NOTE: Since the myocardial oxygen extraction is so high, then the cardiac venous blood in the coronary sinus is the most deoxygenated blood in the body

What are the characteristics of a Myoclonic Seizure? And, what is first line treatment?

- Myoclonic seizures are characterized by: brief, involuntary jerking movements involving both upper extremities with preservation of consciousness - First line treatment = Broad-Spectrum anticonvulsants (*Valproic Acid*, Lamotrigine, Levetiracetam, Topiramate)

What 2 ions are lost in sweat in a pt with Cystic Fibrosis?

- Na and Cl - Because a normal CFTR protein will reabsorb Cl in the eccrine duct, and then Na and H2O will follow. So, CFTR facilitates the production of hypotonic sweat. - Patients with Cystic Fibrosis are unable to reabsorb Cl, and therefore they cannot reabsorb Na, and thus secrete sweat with high Cl and Na levels NOTE: This is for SWEAT!!! This is not the same as respiratory epithelium!!!!

Drug: Carbamazepine

- Na+ channel blocker - For: Partial (focal) seizures, 1st line for Trigeminal Neuralgia , & Bipolar Disorder - BAD SE = Agranulocytosis, Aplastic Anemia, SIADH, Liver toxicity, teratogen, & Cytochrome P450 inducer

What 2 findings indicate a Glucagonoma?

- Necrolytic migratory erythema (erythematous papules/plaques on face, perineum & extremities) - Diabetes Mellitus / Hyperglycemia

What is the difference between Tourette disorder and Chronic Tic disorder

- Tourette disorder: must have *multiple motor ticks and at least 1 vocal tick* (but they dont have to be concurrent) - Chronic tic disorder: involves *one or more motor or verbal ticks, but NOT both* - For both, they need to have these symptoms for over 1 year (Tourette onset must be before age 18)

What is a transamination reaction? And, what vitamin is essential for these?

- Transamination reactions typically occur between an amino acid and an a-keto acid. The amino group from the amino acid is transfered to the a-keto acid, and the a-keto acid in turn becomes an amino acid. - Pyridoxal Phosphate (active B6) is a cofactor in amino acid transamination and also in decarboxylation reactions.

What are the neurologic symptoms of Vitamin E deficiency?

- Neuro symptoms of Vitmain E deficiency closely mimic Friedreich Ataxia and include Ataxia (d/t degeneration of the spinocerebellar tracts), loss of position and vibration sense (d/t degeneration of the dorsal columns), and loss of deep tendon reflexes (d/t peripheral nerve degeneration) NOTE: Vit B12 deficiency can also present similarly d/t subacute combined degeneration of the dorsal and lateral spinal columns (but B12 deficiency will also have a megaloblastic anemia)

What amino acid can be converted into Niacin?

- Niacin (Vit B3) can be synthesized endogenously from Tryptophan - Niacin is an essential component of NAP and NADP - Niacin deficiency results in Pellagra: dermatitis, diarrhea, and dementia

What 3 reactions in the TCA cycle require Niacin?

- Niacin is a precursor for NAD+ and NADP+ So all reactions/enzymes of the TCA cycle that use NAD, therefore require Niacin: - *Isocitrate dehydrogenase* - *a-ketoglutarate dehydrogenase complex* - *malate dehydrogenase* Also: *Pyruvate dehydrogenase complex* requires NAD+

What type of transport is required to bring glucose into most cells?

- Transport of glucose into the cells of most tissues occurs by means of *facilitated diffusion* - glucose cannot passively diffuse across the cell membrane in any significant way, and requires *carrier proteins* (Transmembrane glucose transporter proteins - GLUT) - This transport *does not require energy* because glucose is moving down its concentration gradient

What is the most important mediator of coronary vascular dilation in large arteries and pre-arteriolar vessels?

- Nitric Oxide is the most important mediator of coronary vascular dilation in large arteries and pre-arteriolar vessels - thus, it is most responsible for controlling coronary blood flow within the zone of auto-regulation - NO causes vascular smooth muscle relaxation by a guanylate cyclase-mediated cGMP secondary messenger system - NOTE: Adenosine, a product of ATP metabolism, acts as a vasodilatory element in the small coronary arteries

What is the most common cause of viral gastroenteritis in developed countries?

- Norovirus is the most common cause of viral gastroenteritis - Symptoms include: acute onset diarrhea, vomiting, fever, malaise, and headache... The diarrhea is typically watery without blood d/t lack of small bowel inflammation

What travels through the superior orbital fissure?

- Oculomotor nerve (CN III) - Trochlear nerve (CN IV) - Ophthalmic branch of Trigeminal (CN V1) - Abducens nerve (CN VI) - Superior ophthalmic vein NOTE: - Ophthalmic canal = Optic nerve & Ophthalmic artery - CN V2, Infraorbital vessels, and branches from the sphenopalatine ganglion pass through the inferior orbital fissure, but do not enter the orbit

What anti-HTN drug can cause (an initial) increase in Creatinine and Potassium?

- One effect of ACE inhibitors ("-pril) is preventing efferent arteriole constriction and thus decreasing GFR - It is expected for GFR to decrease initially - and is not seen as a major "side effect" - This decrease in GFR can cause an increase in serum Creatinine, and also an increased serum potassium (also d/t decreased aldosterone and decreased K secretion)

What is an adverse effect of mu opioid analgesics on the gallbladder?

- Opioid analgesics can cause contraction of smooth muscles in the sphincter of Oddi, leading to increased pressures in the common bile duct and the gallbladder and can cause biliary colic

Where is the transport of glucose going AGAINST its concentration gradient?

- Transpot of glucose against the concentration gradient occurs via the *Na/Glucose* symporter, which is found in the *intestinal and renal tubular epithelium* and used to transfer glucose intracellularly from the lumen

How do you differentiate leukoplakia from candida? And, what are common causes for both?

- Oral thrush from candida CAN easily be scraped off, while leukoplakia CANNOT be easily scraped off - When oral thrush is scraped off, it reveals an erythematous mucosal surface underneath - Oral thrush is associated with wearing dentures, diabetes mellitus, immunosuppressed patients, and patients receiving steroids, Abx, or chemo... Unexplained oral thrush in an otherwise healthy individual suggests the possibility of HIV - Tobacco use can cause leukoplakia, which is pre-cancerous

What is Trastuzumab? And, what is it used for?

- Trastuzumab is a monoclonal Ab used in patients with HER2 (Human Epidermal Growth Factor Receptor) positive breast cancer - Trastuzumab binds the extracellular domain of HER2 and prevents activation of a transmembrane tyrosine kinase, which downregulates cellular proliferation and promotes apoptosis

What is Orotic Aciduria? What is defective? How does it present? And, what should be given for treatment?

- Orotic aciduria is a rare autosomal recessive disorder of de novo pyrimidine synthesis that occurs d/t a defect in UMP Synthase. - Children present with physical and mental retardation, megaloblastic anemia, and large amounts of urinary orotic acid - Uridine supplementation can improve symptoms as Uridine is converted to UMP via nucleoside kinases NOTE: there is NO hyperammonemia (this is to distinguish it from ornithine transcarbamylase deficiency (a urea cycle disorder), which also has increased urinary orotic acid, but also has hyperammonemia) - Also can rule out B12 or folate deficiency since the megaloblastic deficiency does not respond to supplementation with these

What are the names of the 2 phases of the ovarian cycle and uterine cycle?

Ovarian cycle: Follicular phase, and Luteal phase Uterine cycle: Proliferative phase, and secretory phase

What is a severe toxicity of aggressive osmotic diuretic therapy (like Mannitol)?

Pulmonary edema - d/t rapid rise in volume of the vessels, which can also increase the overall hydrostatic pressure in the vasculature

What step of gluconeogenesis requires Biotin (B7) as a cofactor? And what does biotin do as a cofactor?

Pyruvate --> Oxaloacetate (via the enzyme Pyruvate carboxylase) -Biotin acts as a CO2 carrier on the surface of carboxylase enzymes

What is Osteitis Fibrosa Cystica?

- Osteitis Fibrosa Cystica is the most characteristic skeletal manifestation of primary hyperparathyroidism - The skeletal findings in hyperparathyroidism most commonly involve cortical (compact) bones in the appendicular skeleton. Subperiosteal thinning is a characteristic feature and appears radiologically as subperiostral erosions in phalanges of the hand, a granular "salt-and-pepper" skull, and osteolytic cysts in the long bones (osteitis fibrosa cystica) - Pathoma: Osteitis Fibrosa Cystica = "Fibrosis and cystic spaces" - FA: Osteitis Fibrosa Cystica = "Cystic bone spaces filled with brown fibrous tissue" NOTE: Primary hyperparathyroidism is usually caused by a benign parathyroid adenoma, and classic symptoms include: bone pain, renal stones, GI disturbance, Psych probs. ("bones, stones, abdominal groans, psych moans")

What are the 2 most important factors for osteoclast differentiation?

- Osteoclasts originate from the mononuclear phagocytic cell lineage and are ultimately formed when several precursor cells fuse to create a multinucleated mature cell (normally 2-5 nuclei) - The 2 most important factors for osteoclastic differentiation are produced by osteoblasts and bone marrow stromal cells, and are: Macrophage colony-stimulating factor (M-CSF), and receptor for activated nuclear factor kappa-B ligand (RANK-L) - Osteoprotegerin (OPG) is a physiologic decoy receptor that decreases binding of RANK-L to RANK NOTE: In Pagets disease, osteoclasts are typically very large and can have up to 100 nuclei

What is Osteogenesis Imperfecta? What is the cause/pathogenesis? And, how does it present?

- Osteogenesis Imperfecta results from defective synthesis of Type 1 collagen by Osteoblasts - It is typically inherited as Autosomal Dominant - Type 1 collagen is the predominant collagen in Osteoid (the organic portion of the bone matirx)... This is what allows bone to be somewhat flexible while still maintaining strength - Clinical manifestations include: history of fractures only after minimal trauma, blue sclera (d/t thinning of scleral collagen and revealing underlying choroidal veins), small/malformed teeth (dentinogenesis imperfecta)... Hearing loss (d/t abnormal ossicle bones), lax joints, and easy bruising can also be seen NOTE: Type 1 collagen = bONE

What are the 3 criteria for Polycystic Ovarian Syndrome (PCOS)?

- PCOS is characterized by at least 2 of the 3 following: --- Hyperandrogenism --- Irregular periods --- Polycystic ovaries on Ultrasound NOTE: Disruption of intra-ovarian steroidogenesis causes anovulatory cycles, and results in chronic estrogen stimulation with decreased progesterone secretion, placing PCOS patients at risk for endometrial hyperplasia/carcinoma

What is Pancreas Divisum?

- Pancreas divisum occurs when the ventral and dorsal pancreatic buds fail to fuse - and the pancreatic secretions are drained via two separate duct systems

What is paraneoplastic cerebellar degeneration?

- Paraneoplastic syndrome most commonly associated with small cell lung cancer - d/t immune response against tumor cells that cross-react with Purkinje neuron antigens, leading to acute-onset rapid degeneration of the cerebellum

What are symptoms of paranoid personality disorder?

- Paranoid personality disorder is classified in Cluster A ("weird") - Pt's exhibit a lifelong pattern of pervasive suspicion and distrust - "Pervasive distrust and suspiciousness of others and a profoundly cynical view of the world" - However, unlike patients with psychotic disorders, they do not have fixed delusions and other psychotic symptoms

What is a major side effect of Trazodone?

- Trazodone is a highly sedating antidepressant - It is a serotonin modulator (antagonizes postsynaptic serotinin receptors and inhibits serotonin reuptake), and has minimal efects on NE and dopamine. It additionally has some alpha blocker effect, and histamine H1 receptor antagonism - Side effects = sedation, nausea, postural hypotension - Severe side effect = Priapism TraZZZoBONE!!!!

What is the characteristic triad of Wiskott-Aldrich syndrome?

- Triad = Thrombocytopenia, Eczema, and Recurrent infections (Usually infections by encapsulated organisms d/t defective humoral and cellular immunity) - There is defective antigen presentation since these cells are unable to re-organize their cytoskeleton (See FA 2017) - X-Linked... D/t mutation in WASP gene (WATER: Wiskott-Aldrich = Thrombocytopenia, Eczema, and Recurrent infections)

Histology characteristics of true vocal cord vs false vocal cord:

- True Vocal Cords: covered with stratified squamous epithelium, because the folds undergo frequent friction and abrasion, and stratified squamous epithelium is protective - False Vocal Cords (ventricular folds) - folds in mucus membrane lined with respiratory epithelium (ciliated, pseudostratified, columnar, mucus-secreting epithelium, with goblet cells). The false vocal cords are adjacent to the true vocal cords and help to lubricate the true vocal cords with mucus and protect the airway from foreign bodies.

True diverticulum vs. False diverticulum

- True diverticulum is when there is an outpouching of all 3 layers - False diverticulum is where there is an outpouching of the mucosa and submucosa through the muscularis layer NOTE: In diverticulosis (colonic diverticula), which usually is seen in the sigmoid, the pathogenesis involves "Pulsion", or increased intraluminal pressure created during straining bowel movements

What amino acid can get converted to Serotonin?

- Tryptophan can get converted to Serotonin (with BH4, and Vit B6 as cofactors) NOTE: Serotonin can further get converted to melatonin

What is the most important prognostic indicator for bladder carcinoma?

- Tumor penetration of the bladder wall is the major determinant of prognosis NOTE: most bladder carcinomas are urothelial (transitional) carcinoma, and painless gross hematuria is the most common presenting sign

What type of collagen is seen in the final stage of healing after an MI?

- Type 1 collagen - Type 1 collagen is the most abundant type, and is found in most interstitial connective tissues (and bone) where it provides strength and support NOTE: Granulation tissue is composed primarily of type 3 collagen. This is seen 1 week after MI, but is eventually replaced with type 1 collagen as the infarct matures

What is the function of the ubiquitin proteasome pathway in the immune response?

- Ubiquitin ligases recognizes specific protein substrates and attach a ubiquitin tag, which marks the proteins to be degraded by proteasomes - If this protein substrate was a foreign intracellular protein, then the protein gets broken down to a specific size, and coupled with the major histocompatibility 1 protein complex in the endoplasmic reticulum - These then get presented on the cell surface for recognition by CD8+ lymphocytes

What 2 blood coag. lab values are increased with unfractionated Heparin administration?

- Unfractionated heparin binds to antithrombin and causes inactivation of several coag. factors, most significantly Thrombin (factor IIa) and factor Xa - This causes the PTT and TT to be prolonged -PTT is prolonged with meds that inhibit the intrinsic pathway - TT (thrombin time) is prolonged with meds that directly or indirectly prolong thrombin NOTE: PT time should theoretically be prolonged by the action of Heparin on the final common pathway, in practice, the PT reagent contains heparin neutralizers that minimize its effect

What is the lymph drainage pattern of the Rectum/Anus?

- Upper rectum = Inferior mesenteric - Lower rectum to the anal canal above the pectinate line = Internal iliac - Anal canal below the pectinate line = Superficial inguinal FA pg. 93

What class of drug should be used for urge incontinence (overactive bladder syndrome)?

- Urge incontinence is d/t uninhibited bladder contractions - If behavioral therapy alone is unsuccessful, pharm management with an antimuscarinic (targeting M3 receptors - like Oxybutynin) can help improve symptoms.

At what part of the nephron do uric acid stones form and why?

- Uric acid is soluble at physiologic pH, but it can precipitate in the normally acidic environment of distal tubules and collecting duct (since the lowest pH along the nephron is found in the distal tubules and collecting ducts) - Ways to prevent uric acid crystal formation (which can be the result of tumor lysis syndrome) include: urine alkalinization and hydration, as high urine flow and high pH along the nephron prevents crystallization and precipitation of uric acid

In renal development, what does the Ureteric bud, and the Metanephric mesenchyme give rise to?

- Urteric bud - Forms the collecting ducts to the ureter (so the collecting ducts, minor/major calyces, pelvises, and ureter) - Metanephric mesenchyme - Forms the glomerulus to the Distal convoluted tubule NOTE: - The Ureteric bud is also called the metanephric diverticulum - The Metanephric mesenchyme is also called the metanephric blastema or metanephric mesoderm

How does homocystinuria present? And, what should be given for treatment?

- Usually presents around age 3-10 - Sx = *Dislocated lens, Intellectual disability, Marfanoid habitus* - Large risk for: *Cardiovascular events* (ex: thromboembolic occlusions of both large and small vessels, especially in brain, heart, and kidneys) - 50% of the time it is d/t an autosomal recessive deficiency in Cystathione synthase, which requires Pyridoxine (B6)... 50% of these patients respond well to *high dose Pyridoxine (B6)*, which improves residual enzyme activity

What are VIPomas and how do they present?

- VIPoma is a pancreatic islet cell tumor that hypersecretes Vasoactive intestinal peptide (VIP), which increases intestinal chloride loss into the stool and causes excess losses of the accompanying water, sodium, and potassium - VIP also inhibits gastric acid secretion - Somatostatin inhibits the secretion of many GI hormones, including VIP, and is used to treat the symptoms of the VIPoma - Octreotide is a synthetic analog of somatostatin used to inhibit the secretory diarrhea in VIPoma NOTE: WDHA syndrome is d/t a VIPoma and stands for: Watery Diarrhea, Hypokalemia, and Achlorhydria (absence of HCl in gastric secretions)

3 drugs mentioned in UWorld that lead to higher chance of Neural Tube defect:

- Valproate (for Bipolar or Epilepsy) b/c it impaired folate metabolism - Folate antagonists like Methotrexate and TMP-SMX

What is paroxysmal nocturnal hemoglobinuria (PNH)? And, how does it present?

- Paroxysmal nocturnal hemoglobinuria (PNH) is d/t a mutated PIGA gene, which is involved in the synthesis of Glycosylphosphatidylinositol (GPI) anchor, which is necessary for the attachment of several cell-surface proteins - RBCs will not have CD55 (decay-accelerating factor) or CD59 (MAC inhibitory protein) on them... These proteins help inactivate complement and prevent the MAC from forming on normal cells - Absence of the GBI anchor results in CD55 and CD59 deficiency and complement-mediated hemolysis (which occurs more often at night b/c complement activity is during sleep with decreased pH) - The classic triad = hemolytic anemia (hemoglobinuria), pancytopenia (d/t stem cell injury), and thrombosis at atypical sited (d/t release of prothrombotic factors from lysed RBCs and platelets) - This is Coombs negative because the RBCs do not have Antibodies bound directly to them - Chronic hemolysis can also end up causing iron deposition in the kidney (hemosiderosis) - Treat with Eculizumab (a terminal complement inhibitor)

What is the first line seizure drug for: - Partial (focal) seizures - Tonic-clinic seizures - Absence Seizures - Status Epilepticus (both acute and prophylaxis)

- Partial (focal) seizure = Carbamazepine - Tonic-clonic seizure = Valproic Acid (also possible phenytoin, fosphenytoin) - Absenze seizure = Ethosuximide - Status Epilepticus (acute) = Benzodiazepam - Status Epilepticus (prophylaxis) = Phenytoin or fosphenytoin

What is Factitious disorder?

- Patients deceptively produce signs and symptoms of a medical or psychiatric illness or induce injury to obtain attention and recieve protracted care *to assume the "sick role"* - more likely in women and health care workers

What are the symptoms of an Adrenal crisis? And, what is the treatment?

- Patients with adrenal insufficiency are not able to increase glucocorticoid production in response to acute stress (illness, surgery, etc.) - Adrenal crisis is characterized by severe hypotension, abdominal pain, vomiting, weakness, and fever - In addition to aggressive fluid resuscitation, treatment requires immediate glucocorticoid supplementation

What is the mechanism of Penicillins and Cephalosporins?

- Penicillins and Cephalosporins are both B-lactams and irrereversibly bing to penicillin-binding proteins such as transpeptidases - Blocking transpeptidase prevents cross-linking of peptidoglycan cell wall

What is seen on peripheral blood smear and bone marrow smear in a pt with lead poisoning?

- Peripheral smear may show: Basophilic Stipping (d/t inability to degrade RNA d/t inhibition of a nucleotidase by lead) (Seen in picture) - Ring sideroblasts can be seen in the bone marrow NOTE: Basophilic stippling is nonspecific and can be seen in the thalassemias and myelodysplastic syndrome

What is the best way to prevent wrong-site surgery?

"dual identifiers" (usually a nurse and physician) - who independently confirm that they have the correct patient, site, and procedure - checks must be truly *independent* to ensure patient safety

What percentage correlates with 1 standard deviation, 2, and 3...

*68-95-99.7 rule*

Stimulation of what adrenergic receptor stimulates JG cells to secrete renin?

*Beta 1*

Pseudogout is d/t the deposition of what? And what is seen on synovial fluid stain?

*Calcium pyrophosphate* - Synovial fluid shows *rhomboid-shaped crystals* with weakly *positive birefringence under polarized light*

What is needed in the media to grow Mycoplasma?

*Cholesterol* - It requires cholesterol to grow b/c their cell membrane is composed of a single cholesterol-rich phospholipid bilayer

What is the triad of Congenital Toxoplasmosis?

*Chorioretinitis, Hydrocephalus, & Intracranial calcifications*

What medication/class forms the cornerstone of chronic therapy for patients with persistent asthma?

*Corticosteroids* - Fluticasone & Budesonide

What is the specific adverse effect of Doxorubicin on the heart?

*Dilated Cardiomyopathy* - The most effective method of preventing this is administration of *Dexrazoxane*

Hawthorne effect vs. Pygmalion effect

*Hawthorne bias* - a type of "Measurement bias" - it is the tendency of study subjects to change their behavior as a result of their awareness that they are being studied *Pygmalion effect* - a type of "Observer-Expectancy bias" - describes the fact that a researchers beliefs in the efficacy of treatment can potentially affect the outcome

Immediately at the onset of Anaphylaxis, what 2 things are secreted by *Mast Cells*

*Histamine & Tryptase* - Histamine - a vasoactive amine - Tryptase - a marker of mast cell activation

How do the Calyces present in Hydronephrosis vs. Chronic Pyelonephritis?

*Hydronephrosis* = Distended/dilated renal pelvis/calyces *Chronic pyelonephritis* = Blunted calyces (Vesicoureteral reflux predisposes to both)

An agar containing: Chocolate sheep blood, vancomycin, Colistin (Polymyxin), Trimethoprim, and Nystain, is used to isolate what organism?

*Neisseria* species - This is Thayer-Martin medium

What is the most notable side effect of Ethambutol?

*Optic Neuropathy* "*EYE*thambutol"

What can happen if you correct hyponatremia too quickly?

*Osmotic demyelination syndrome* - Demyelination of the axons in the central part of the pons... causes *spastic quadriplegia and pseudobulbar pasly*

How do you treat rabies?

*Postexposure prophylaxis* - Rabies immune globulin + inactivated vaccine

What anterior pituitary hormone is capable of suppressing GnRH

*Prolactin* NOTE: This is significant in a prolactinoma tumor because the large levels of prolactin can suppress GnRH, leading to decreased LH secretion (which can impair testosterone production in a male and estrogen in a female)

Describe the balance between Prostacyclin and Thromboxane A2:

*Prostacyclin (Prostaglandin I2) - inhibits platelet aggregation and vasodilates*, (it also inhibits platelet adhesion to vascular endothelium, increases vascular permeability, and stimulates leukocyte chemotaxis *Thromboxane A2 - enhances platelet aggregation and causes vasoconstriction* - These together are in a balance and maintain capillary patency and normal blood flow

Somatic Mosaicism vs. Gonadal Mosaicism:

*Somatic Mosaicism* - affects cells forming the body, causing disease manifestation to develop in affected individuals *Germline Mosaicism* - affects cells that give rise to gametes, allowing the affected genes to pass to the offspring

What 2 vitamins are not present in adequate amounts in breast milk?

*Vitamin K* - this is supplemented as an IM injection at delivery *Vitamin D* - should be provided in supplementation to exclusively breast fed infants to prevent Rickets NOTE: There is also not much Iron in breast milk. But the minimal amount is sufficient enough until 4 months of age, then after 4 months, infants that are exclusively breast fed should get Vitamin D supplementation, until solid food intake begins

An ulcer in the distal duodenum (beyond the duodenal bulb) suggests what?

*Zollinger-Ellison Syndrome*

What stage of meiosis are a womans eggs arrested in during childhood?

*prophase of meiosis I* These germ cells are called primary oocytes at this stage *prOOOphase 1 until OOOvulation*

What are the 2 main *Incretins*? And what is their function?

- *Glucagon-like peptide-1 (GLP-1)* - *Glucose-dependent insulinotropic peptide (GIP)* Incretins are GI hormones produced by the gut mucosa that stimulate pancreatic insulin secretion in response to sugar-containing meals -This is the reason why blood insulin levels will increase more after an oral dose of glucose vs. a IV dose of glucose

What are the 2 main concerns regarding *BK Virus*

- *Post-transplant Nephropathy* (typically when the latent virus is reactivated) - *hemorrhagic cystitis* (in immunocompromised)

What is the timeframe of Schizophereniform disorder?

- 1 month - 6 months - it has the same symptoms as schizophrenia, but functional decline is not required d

What is the perineal body (anatomy)?

- A fibromuscular tissue between the urogenital and anal triangle (called the central tendon of perineum in the picture) - A midline episiotomy is a vertical incision from the posterior vaginal opening to the perineal body

What 4 drugs classes are contraindicated in a patient taking a benzo?

- Benzos should be excluded from use in conjunction with alcohol, barbiturates, neuroleptics (1st-gen Antipsychotics), and/or 1st-gen Anti-histamines, d/t the synergistic CNS sedation

How many manic episodes are required to meet criteria for the diagnosis of Bipolar Type 1?

- Bipolar 1 is is defined by the presence of at least 1 manic episode - Manic episodes have a very elevated, expansive, or irritable mood, with abnormally and persistently increased activity or energy lasting at least 1 week (Characterized by DIG FAST)

Drug: Entacapone?

- COMT inhibitor that increases the bioavaliability of levodopa by inhibiting its peripheral methylation - This allows for more dopamine to enter the brain

Between cardiac tissue, vascular smooth muscle, and renal juxtaglomerular cells (that secrete renin)... Which has B1 and which has B2 receptors?

- Cardiac tissue: B1 & B2 - Vascular smooth muscle: B2 - JG cells: B1 - The Beta receptors are G protein-coupled receptors associated with Gs, which increases intracellular cAMP via adenylyl cyclase NOTE: B-blockers "A"-"M" block only B1, and B-blockers "N"-"T" block B1 & B2

What is chancroid? And, what causes it?

- Chancroid is caused by Haemophilus Ducreyi - Multiple painful red papules that erode and become deep tender ulcers... The base may have a yellow exudate - Regional lymph nodes may swell, and become chronic ulcers - Organisms often clump in long parallel strands ("school of fish") *YOU DO CRY, WITH DUCREYI* - painful

Why would a patient with polycystic ovarian syndrome (PCOS) take the drug: Clomiphene?

- Clomiphene is a estrogen receptor modulator that decreases the negative feedback inhibition on the hypothalamus by the circulating estrogen, resulting in increased gonadotropin production (FSH and LH) and ovulation - This can be given to patients with PCOS who desire to become pregnant NOTE: Many patients with PCOS have irregular mensural cycles and have difficulty with fertility d/t the excess androgen levels

What are the expected *PTH* and *1,25-(OH)2* (Active Vit D) levels in a patient with *Sarcoidosis*

- Decreased *PTH* - Elevated *1,25-(OH)2* (Active Vit D) - This is b/c of increased 1α-hydroxylase-mediated vitamin D activation in macrophages (of the granulomas), which will increase levels of active Vitamin D, and cause blood Calcium levels to be high, which will result in negative feedback to PTH

Describe some normal changes associated with cardiac aging:

- Decreased left ventricular chamber apex-to-base dimension - Development of a sigmoid-shaped ventricular septum - Myocardial atrophy with increased collagen deposition - Accumulation of cytoplasmic lipofuscin pigment (yellow-brown) within cardiomyocytes

What nerve and arteries/veins are in the anterior leg compartment?

- Deep peroneal (fibular) nerve - Anterior tibial artery & veins

What are the cofactors required for all dehydrogenase enzyme complexes

- Dehydrogenase complexes need 5 cofactors: Thiamine (B1), Lipoate, Coenzyme A (B5), FAD (B2), NAD (B3) "Tender Loving Care For Nancy" Ex: Branched-chain a-ketoacid dehydrogenase, pyruvate dehydrogenase, a-ketoglutarate dehydrogenase

For schizophrenia to be diagnosed, the patient needs over 2 of a list of symptoms, and 1 of those needs to be one of these 3... (what are the 3)

- Delusions - Hallucinations - Disorganized speech (the other 2 are disorganized behavior, and negative symptoms) - The total illness duration (i.e. the decline in functioning) must be over 6 months (which includes the prodrome & residual symptoms) with >1 month of ACTIVE diagnosis required symptoms

What is the preferred medication (class) for Restless Leg Syndrome?

- Dopamine agonists are the preferred medication for treatment of restless leg syndrome (ex: ropinirole, pramipexole)

What growth characteristics help distinguish an Enterococcal infection?

- Enterococcus are capable of growing in hypertonic saline and bile - They are also, gamma-hemolytic, catalase-negative, and pyrrolidonyl arylamidase-positive NOTE: Genitourinary instrumentation or catheterization have been associated with Enterococcal endocarditis

What is the Liver path finding of "eosinophilic globules" indicate?

- Esoinophilic globules in the liver indicate "councilman bodies", which represents the hepatocyte undergoing apoptosis, where they form very acidophilic bodies - This is typically seen in viral hepatitis and yellow fever

Describe the pathogenesis of autoimmune gastritis/pernicious anemia... And the relevant levels of gastrin, gastric ph, and parietal cell mass:

- Pernicious anemia occurs as a result of CD4+ cell-mediated immune response against parietal cells found in the body and fundus of the stomach - Destruction of parietal cells leads to decreased intrinsic factor secretion, which impairs B12 absorption in the terminal ileum... this results in B12 deficiency and development of megaloblastic anemia - Destruction of parietal cells also leads to decreased HCl secretion, which leads to an elevated intraluminal pH, and this stimulates gastrin secretion by G cells

Describe the regulation of Fructose-2,6-bisphosphate on glycolysis and gluconeogenesis in the fed and fasting state:

- Phosphofructokinase-2 increases F2,6BP levels in response to insulin - Fructose 2,6-bisphosphatase decreases F2,6BP levels in response to glucagon - Fructose 2,6-bisphosphate (F2,6BP) activates phosphofructokinase-1 (increasing glycolysis) and inhibits fructose 1,6-bisphosphatase (decreasing gluconeogenesis)

What do glucocorticoids up-regulate in the liver?

- Glucocorticoids increase hepatic gluconeogenesis and glycogenesis - Aside from in the liver, glucocorticoids are primarily catabolic (favor breakdown of things)

What is the major amino acid in the blood?

- Glutamine (Glutamate-NH3) is the major amino acid in the blood b/c it transports excess ammonia from peripheral tissues to the kidney. - In the nephron, the amide nitrogen is hydrolyzed by glutaminase to regenerate glutamate and a free ammonium ion, which can then be excreted in the urine NOTE: I think this also carries the NH3 into the urea cycle (?) (but it does get converted to Alanine-NH3 to enter the liver, and then gets converted back to Glutamate-NH3) FA Page 78

How do mitochondrial myopathies look on microscopy?

- Gomori trichome stain = "blotchy red muscle fibers" - Electron microscopy = increased number of enlarged, abnormally shaped mitochondria

What are some distinguishing factors of an Enterococcus UTI?

- Gram-positive cocci in pairs and chains - Gamma hemolysis (none) - Unable to convert nitrates to nitrites - Able to grow on 6.5% hypertonic saline - Able to grow in bile (via hydrolyzation of esculin) -

What is the breath test associated with lactase deficiency and the breath test associated with H. Pylori?

- Lactase deficiency = *Hydrogen breath test* - H. Pylori = *Urea breath test* (pt. swallows radio-labeled urea and the H. pylori is able to split this, and the pt breaths off CO2 with the radio-label)

What are the qualities of methadone? And, how does it work for heroin detox?

- Methodone is a potent, full Mu-Opioid receptor agonist - It has a long half-life with sustained effects after chronic dosing and suppresses cravings and withdrawal symptoms for >24hrs. - It has a high affinity to the opioid receptor, which blocks the euphoric effects of other opoids NOTE: Buprenorphine is a sublingual, partial agonist, that is used for maintenance therapy

What are the main side effects of Methotrexate?

- Methotrexates ability to inhibit rapidly growing cells can lead to toxicity in cells with rapid turn over, like: Oral/GI mucosa (*ulcers*), hair follicles (*alopecia*), and bone marrow (*pancytopenia*) - *Hepatotoxicity* - *Pulmonary fibrosis* - Folate deficiency (*Megaloblastic anemia*, and *teratogenic*)

What is hibernating myocardium?

- Myocardial hibernation refers to a state of chronic myocardial ischemia in which both myocardial metabolism and function are reduced to match a concomitant reduction in coronary blood flow. This new equilibrium prevents myocardial necrosis - These changes lead to decreased contractility and LV systolic dysfunction - But, revascularization and subsequent restoration of blood flow to hibernating myocardium improves contractility and LV function

What hypothalamic nuclei produces Oxytocin and Vasopressin

- Oxytocin = paraventricular nuclei of hypothalamus - Vasopressin = supraoptic nuclei of hypothalamus

What are the characteristics of a PDA murmur?

- PDA is characterized by a continuous murmur heard best at the left infraclavicular region with meximal intensity at S2 - A smal PDA is often asymptomatic and is usually detected incidentally during routene cardiac auscultation - It occurs most commonly in patients born prematurely and those with cyanotic congenital heart disease

Healthcare payment: Capitation

- Physicians receive a set amount per patient assigned to them per period of time, regardless of how much the patient uses the healthcare system (used by some HMOs)

What 4 hormones have a structurally similar alpha subunit?

- TSH - LH - FSH - HCG

In embryonic development, what does the Allantois become?

- The Allantois becomes the Urachus, which is a duct between the fetal bladder and umbilicus - Total failure of the Urachus to obliterate can lead to a patent Urachus (urine from the umbilicus)

A tumor in what location is the most common cause of superior vena cava syndrome

- The SVC is most easily compressed by *mediastinal masses* - Lung cancer, followed by non-hodgkin lymphoma, is the most common cause of SVC syndrome

What is Complete Atrioventricular (AV) canal defect?

- The most common type of cardiac defect in patients with Downs Syndrome - Failure of endocardial cushion fusion results in an ostium primem atrial septal defect, a ventricular septal defect, and a single AV valve

What is Pica?

- Pica is the compulsive consumption of a nonfood and/or non-staple food. - Ice is the most commonly ingested substance, and more than 1/3 women with Pica will ingest more than 1 substance - It is common in pregnancy and often seen with iron deficiency anemia - Pregnancy patients should be assessed throughout the pregnancy for the presence of Pica, especially if they experience unexplained weight loss

How can Pilocytic astrocytoma be distinguished from Medulloblastoma on CT?

- Pilocytic astrocytoma is the most common brain tumor in children, while a medulloblastoma is the most common malignant brain tumor in children - They both commonly present in the cerebellum - *Pilocytic astrocytoma is usually a well-demarcated lesion with cystic and solid components* - *Medulloblastoma imaging will reveal a solid lesion*

In Herpes Simplex virus Encephalitis, what brain region typically shows edema?

- There is typically *temporal lobe edema* on MRI b/c the virus enters the brain via the olfactory tract and travels to the olfactory cortex (in the medial temporal lobe) - Hemorrhagic inflammation of the temporal lobe also usually causes elevated erythrocytes in the CSF

Childhood, Pilocytic astrocytoma vs. Medulloblastoma vs. histology:

- These both arise in the cerebellum... Pilocytic astrocytoma is the most common brain neoplasm in childhood, & Medulloblastoma is the second most common *Pilocytic astrocytoma* - Pilocytic astrocytes & Rosenthal fibers (low-grade) *Medulloblastoma* - sheets of small cells with deeply basophilic nuclei and scant cytoplasm (small, round, blue cells), and abundant mitoses

The lateral horns (intermediolateral cell columns) can be seen at what spinal levels and serves what purpose?

- They are seen at the thoracic and early lumbar (T1-L2) spinal levels - They are made up of sympathetic preganglionic neurons

What it Platelet-Activating Factor?

- Platelet activating factor is released by endothelium, platelets, and immune cells, and is involved in leukocyte function (endothelium attachment, phagocytosis, degranulation), platelet stimulation, and changes in vascular tone and permeability

What is the Triad of Normal Pressure Hydrocephalus?

- Urinary incontinence (*WET*) - Gait Apraxia - "Magnetic gait" (*WOBBLY*) - Cognitive dysfunction (*WACKY*) - It is a communicating hydrocephalus caused by decreased CSF reabsorption by the arachnoid granulations

What vessels are spared in Polyarteritis Nodosa? And what is a major unusual risk factor?

- Polyarteritis Nodosa is a segmental, transmural, necroziting inflammation (fibrinoid necrosis) of medium to small vessels in any organ, BUT typically spares the lungs! - Polyarteritis Nodosa is usually idiopathic, but is associated with Hepatitis B in 30% of cases NOTE: Segmental, transmural inflammation of the arterial wall with fibrinoid necrosis is characteristic of Polyarteritis Nodosa

How does ADH affect how the kidney handles urea excretion?

- Vasopressin (ADH) produces a V2 receptor-mediated increase in water permeability within the cortical and medullary collecting ducts. As water leaves the tubular fluid, urea concentration greatly increases in these tubular segments. Although the cortical collecting duct is impermeable to urea, ADH activates urea transporters in the medullary collecting duct, increasing urea reabsorption and decreasing renal urea clearance. - This passive reabsorption of urea into the medullary interstitium, in the presence of ADH, significantly increases the medullary osmotic gradient, allowing the production of maximally concentrated urine

What is the reason for why the pain with appendicitis moves from a dull periumbilical pain to a localized pain at McBurney point?

- Visceral pain (d/t inflammation of the organ and visceral peritoneum) is dull and not localized - Somatic pain (d/t inflammation of the parietal peritoneum) is severe and well localized - Appendicitis causes dull visceral pain at the umbilicus d/t afferent pain fibers entering the T10 level in the spinal cord. Progressive inflammation of the appendix irritates the parietal peritoneum and abdominal wall to cause more severe pain shifting from the umbilicus to McBurney point

What are some features of Vitamin A deficiency? And, what are some potential causes of deficiency?

- Vitamin A deficiency can manifest as Night blindness, severe eye dryness and corneal ulceration/degeneration, hyperkeratosis (dry, scaly, skin), and growth retardation - Some potential causes of this could include things that lead to malabsorption of fat-soluble vitamins, such as: Biliary obstruction, exocrine pancreatic insufficiency, or small bowel resection (Crohns, Bariatric surgery)

What are vitamin A's effects on epithelia?

- Vitamin A maintains orderly differentiation of specialized epithelia, including mucus-secreting columnar epithelia of the ocular conjunctiva, resipratory and urinary tracts, and the pancreatic and other exocrine ducts. - Low Vit A can cause squamous metaplasia of such epithelia to a keratinizing epithelia

Where does H. Pylori colonize to form duodenal ulcers and gastric ulcers?

- When H. pylori colonizes the *Gastric Antrum*, it causes duodenal ulcers - When H. Pylori colonizes the *Gastric body* (corpus), it causes gastric ulcers

HAART therapy for HIV is associated with fat redistribution, how does this manifest in a patient?

- lipoatrophy involving the face and extremities (mostly seen with NRTI and protease inhibitors) - Central fat accumulation in the trunk and viscera (can look like Cushings)

What Abx should be given to treat Pelvic inflammatory disease?

- treatment for PID must cover both Gonorrhoeae and Chlamydia - Treatment = Ceftriaxone + Azythromycin or Doxycycline NOTE: - Ceftriaxone = Gonorrhoeae - Azythromycin or Doxycycline = Chlamydia

What are the 2 mechanisms for Polyhydraminos? And, what are some examples of each

- Polyhydraminos can be d/t decreased fetal swallowing or increased fetal urination - Anencephaly is a neural-tube defect, where disruption of the cranial end of the tube results in absence of the skull and some of the brain (forebrain)... This results in Polyhydraminos because there is an absence of the swallowing centers in the brain, so the baby wont swallow the amniotic fluid - Maternal diabetes and multiple gestations can also cause a polyhydraminos, but it tends to be more mild - Increased fetal urination can be d/t high cardiac output d/t anemia or other reasons (this makes sense because higher heart rate --> more blood taken from mom --> more peepee) NOTE: - Basically the fluid in the fetus needs to be in equilibrium with the fluid outside (amniotic fluid). The fetus gets blood from the mom, some blood gets filtered by kidneys and gets peed out. The fetus swallows some of the pee, and this maintains an equilibrium. When any of these mechanisms are disturbed, then oligohydraminos or polyhydraminos can occur

GI Drug: Sucralfate

- Pormotes peptic ulcer healing by binding to the base of mucosal ulcers and provide physical protection against gastric acid

Why do Spider Angiomatas develop in hyperestrogenic states (liver cirrhosis, pregnancy)?

- Possibly d/t Estrogens effects on arteriolar dilation (the # and size of these skin lesions generally correlate with the severity of liver disease)

What deletion causes Prader-Willi and what are some common manifestations

- Prader-Willi is due to a a microdeletion affecting the paternal chromosome 15q11-13 critical region - Signs are short stature, hypotonia, intellectual disability, hyperphagia, and obesity

What causes Wernicke encephalopathy? And, what is the classic presentation?

- Presentation = Confusion, Ataxia, Nystagmus, Ophthalmoplegia (*CAN 'O beer*) - If it progressed to Korsakoff psychosis, then add symptoms: anterograde/retrograde amnesia, apathy, lack of insight, and confabulation - it is d/t *thiamine deficiency (B1)* (usually in alcoholics) - The brain structure that most frequently undergoes necrosis in the setting of thiamine deficiency is the *mammillary body* - Alcoholics or malnourished patients should receive IV thiamine supplementation before IV dextrose administration, because giving dextrose without any prior thiamine can precipitate Wernicke encephalopathy

*Maple Syrup Urine disease*: Key presentation. What is deficient. How is it treated.

- Presentation = vomiting, poor feeding, and urine smells like maple syrup... Can cause CNS defect, intellectual disability, and death - Blocked degradation of Branched chain AAs (*Isoleucine, Laucine, Valine*) d/t deficient *a-ketoacid dehydrogenase* - Dehydrogenase complexes need 5 cofactors: Thiamine (B1), Lipoate, Coenzyme A (B5), FAD (B2), NAD (B3) - Treat with restriction of branched chain AAs in diet, and *Thiamine supplementation* *I* *L*ove *V*ermont Maple Syrup, from maple tree *B1*ranches

What is primary ciliary dyskinesia?

- Primary ciliary dyskinesia is d/t an Autosomal Recessive mutation in the proteins responsible for normal flagellar and ciliary structure/function (dynein, assembly proteins, etc.) Clinical manifestations: --- *Impaired mucociliary clearance* (predisposes to respiratory tract infections- cough, chronic sinusitis, otitis media, bronchiectasis) --- *Randomization of left-right body asymmetry* (half of patients have sinus inversus) --- *Infertility* d/t impaired sperm flagella or immobility of fallopian tube cilia

What 3 autoantibodies are commonly seen in SLE?

-ANA (sensitive but not specific) -Anti-dsDNA (highly specific, but not sensitive) -Anti-snRNPs (Anti-Smith) (highly specific, but not sensitive)

What is the protein that is defective in Hemochromatosis? What is its normal function? And, how does a change in this lead to hemochromatosis?

- Primary hemochromatosis is d/t mutations affecting the *HFE Protein* - HFE normally interacts with the transferrin receptor to form a complex that functions as a sensor of iron stores... So, *inactivating HFE protein mutations cause enterocytes and hepatocytes to detect falsely low levels of iron* - Thus, Enterocytes start absorbing more iron, and Hepatocytes decrease Hepcidin synthesis, which results in increased ferroportin on enterocytes to allow more iron to enter the blood

What is the presentation of an acute hemorrhage of the pituitary (Pituitary Apoplexy)

- Prior to the hemorrhage, patients usually have chronic symptoms associated with the underlying pituitary tumor

What 3 drugs are linked to drug-induced lupus?

- Procainamide - Hydralazine - Isonaizid - These drugs are metabolized by N-acetylation in the liver, and genetically predisposed individuals who are slow acetylators are at greater risk for developing Drug-induced Lupus erythematosus NOTE: Anti-histone antibodies indicate Drug-induced lupus

What is used for immediate heparin reversal?

- Protamine Sulfate (binds heparin and forms a complex with no anti-coag activity) NOTE: Heparin increases the effect of naturally occurring anticoagulant anti-thrombin III

What are the adverse effects of HIV Protease inhibitors and Integrase inhibitors?

- Protease inhibitors end in "-navir", and can cause metabolic complications (lipodystrophy, dyslipidemia, and insulin resistance) - Integrase inhibitors end in "-gravir", and can cause myopathy

What are characteristics of Panic Disorder?

- Pt has recurrent, unexpected panic attacks (with physical symptoms), which are followed by persistent concern about additional attacks - One key feature is that some of the attacks need to be spontaneous with no obvious trigger (to rule out another disorder that is related to and limited to specific situations) NOTE: This is different than generalized anxiety disorder, because in GAD, the pt has chronic multiple worries, anxiety, and tension... But they do not have recurrent, unexpected, panic attacks

In what 3 instances are nitrates contraindicated?

- Pt with hypertrophic cardiomyopathy (the decreased left ventricular end diastolic volume can increase outflow tract obstruction) - Right ventricular infarction (d/t reduced preload, impairing cardiac output) - Pts on Phosphodiesterase inhibitors (synergism increases the risk of severe hypotension)

How does cauda equina syndrome present?

- Pt's with cauda equina syndrome present with severe bilateral radicular pain, saddle anasthesia, and hyporeflexia... Bowel/bladder incontinence are late manifestations of cauda equina syndrome

What are some signs of Biotin deficiency?

- Pts present with non-specific symptoms, including changes in mental status, myalgias, anorexia, and chronic dermatologic changes (like macular dermatitis) - Pts an also develop metabolic acidosis as a result of increased conversion of pyruvate to lactic acid

What type of tumor is a patient at risk for if they have Familial Retinoblastoma?

- Pts with familial retinoblastoma have an increased risk for *Sarcomas* later in life, especially *Osteosarcoma*

What effect does the Pufferfish toxin have?

- Pufferfish tetrodotoxin binds to voltage-gated Na channels in nerve and cardiac tissues, preventing Na influx and depolarization Sx = Dizziness, weakness, loss of reflexes, paresthesia of the face and extremities, nausea, vomiting, and diarrhea

What 3 enzymes is Thiamine an important co-factor for?

- Pyruvate dehydrogenase (links glycolysis to TCA cycle: Pyruvate --> Acetyl CoA) - a-ketoglutarate dehydrogenase (in the TCA cycle: a-ketoglutarate --> Succinyl-CoA) - Transketolase (in the HMP shunt) NOTE: Thiamine = B1

What is Li-Fraumeni syndrome?

- Rare, Autosomal dominant - Germline mutation in the tumor suppressor gene - p53 - which causes impaired regulation of apoptosis - Multiple malignancies at early age, aka, SBLA cancer syndrome: *S*arcoma, *B*reast, *L*eukemia, *A*drenal gland

How long does renal compensation take to stabilize alkalosis? (ex: in the setting of high-altitude sickness)

- Real compensation takes 24-48 hours - Altitude sickness is causes a hypobaric hypoxia (from decreased pO2 in the air).. The resulting tissue hypoxia stimulates peripheral chemoreceptors, causing hyperventilation to improve oxygen. This results in dumping of CO2, and thus increased blood pH (respiratory alkalosis)... Renal bicarb excretion compensates for the alkalosis, stabilizing the pH toward the normal range within 48 hours (NOTE: but even after this time, the pO2 in the arterial blood gas will likely still be low)

Describe the liver histology findings in a patient with Alpha-1-Antitrypsin deficiency:

- Reddish-pink, periodic acid-Schiff-positive granules of unsecreted, polymerized AAT in the periportal hepatocytes

What characteristic signs indicate mesothelioma?

- Related to asbestos exposure (insulation, shipbuilding) - *Hemorrhagic pleural effusions and pleural thickening are characteristic* - The tumor encases the lung

What is the process of Liquefactive necrosis in the brain?

- Release of lysosomal enzymes from the ischemia neurons results in degradation of the tissue in the ischemic region - Phagocytic cells migrate to the area and remove necrotic tissue leaving a cavity, and astrocytes proliferate around the necrotic area with the formation of a scar (gliosis) (Complete digestion of necrotic tissue with the formation of a cavity is known as liquefactive necrosis)

What is Renal Ammoniagenesis?

- Renal Ammoniagenesis is a process by which renal tubular cells metabolize Glutamine to Glutamate, and generate ammonium that is excreted in the urine and Bicarb that is absorbed into the blood - This process is responsible for the vast majority of renal acid excretion in chronic acidotic states

What is the most common location for Renal Cell carcinoma to metastasize to?

- Renal cell carcinoma can widely metastases to the lungs as the most common site, with pulmonary metastases found in about half of all cases of disseminated disease NOTE: The most common subtype of Renal Cell Carcinoma is Clear cell carcinoma, which has rounded/polygonal cells with abundant clear cytoplasm

How does renal papillary necrosis present? And, what are 4 common causes?

- Renal papillary necrosis classically presents with gross hematuria, acute flank pain, and passage of tissue fragments in urine (sloughed papillae) - Grey/yellow necrosis can be seen in the distal 2/3 of the renal pyramids, and coagulation necrosis can be seen microscopically - Causes include: --- Sickle cell disease or trait (sickled cells cause obstruction of small kidney vessels, predisposing to ischemia) --- Analgesic use (NSAIDs block prostaglandin synthesis, which causes constriction of afferent arteriole, which can cause ischemia in patients predisposed to renal hypoperfusion) --- Diabetes Mellitus (Nonenzymatic glycosylation can cause changes in vascular walls, leading to renal vasculopathy and subsequent hypoperfusion) --- Pyelonephritis and/or Urniary tract obstruction ( edematous interstitium of the pyelonephritic kidney compresses the medullary vasculature, leading to ischemia)

What is Tardive Dyskinesia?

- Repetitive, rhythmic, involuntary movements of the tongue, lips, face, trunk, and extremities (Orofacial dyskinesias are most common: facial grimacing, tongue movements, lip smacking, and puckering) - Older age and exposure to first-generation antipsychotics (dopamine antagonist) increase the risk of developing TD

What is Reye Syndrome?

- Reye Syndrome occurs in children with febrile illness treated with salicylates (*Aspirin*) - the underlying cause is unknown but there is usually some mitochondrial dysfunction - It consists of hepatic failure and encephalopathy (d/t hepatic dysfunction and the toxic effect of hyperamonemia in the CNS) - The characteristic histo finding in the liver = Microvascular steatosis of hepatocytes (the presence of small fat vacuoles in the cytoplasm of hepatocytes) without inflammation or necrosis

What 2 antibodies are seen in Rheumatoid arthritis?

- Rheumatoid Factor - an *IgM autoantibody against the Fc portion of IgG* - *Anti-Citrullinated protein antibody* (ACPA or Anti-CCP) (bind to self proteins) - ANTI-CITRULLINATED PROTEIN ANTIBODY IS MORE SPECIFIC!!!!!

How does riboflavin deficiency manifest? What is the function of riboflavin in general and in the TCA cycle?

- Riboflavin = Vit B2 - Deficiency manifests with Cheilosis (inflammation of lips, scaling and fissures at the corner of the mouth), and corneal vascularization. Also can see glossitis, and seborrheic dermatitis. - Riboflavin is a component of FAD and FMN, which are co-factors used in redox reactions (they get converted into reduced FMNH2 and FADH2). FMN is a component of complex 1, and FAD is a component of complex 2 in the electron transport chain. NOTE: Complex 2 is succinate dehydrogenase. This participates in the electron transport chain, and the TCA cycle. In the TCA cycle, Succinate is converted to Fumarate via Succinate dehydrogenase (and during this process, FAD gets reduced to FADH2).

What is a Robertsonian translocation? And, what can it cause?

- Robertsonian translocations occur between 2 acrecentric, non-homologous chromosomes (like 14 and 21), and results in the fusion of the 2 long arms and 2 short arms - A parent with this will remain a symptomatic, but if it is passed down, the resultant fetus will have an unbalanced Robertsonian translocation with 46 chromosomes, but 3 effective copies of chromosome 21 [46,XX t(14;21)]... This results in Translocation Downs Syndrome - This is much less common to the meiotic non-disjunction form NOTE: Dysmorphic features of Downs Syndrome include: Epicanthal folds (eyes), upslanting palpebral fissure (eye), protruding tongue, and excessive skin at the nape (back) of the neck... Birth weight and length are often below average, and hypotonia and a weak startle (Moro) reflex are characteristic. In addition, cardiac defects are present in >50% of cases

What are the characteristics of Syndrome of Inappropriate Antidiuretic hormone secretion (SIADH)

- SIADH is characterized by low plasma sodium and osmolality, inappropriately concentrated urine, and clinically normal volume status (Euvolemic hyponatremia) - The Euvolemic hyponatremia occurs b/c there is first a subclinical hypervolemia, which suppresses the RAAS system, and stimulates release of natriuretic peptides, leading to excretion of Na in the urine. So d/t these mechanisms, the body water becomes normal, but blood Na becomes low. - An important cause of SIADH is a paraneoplastic effect secondary to small cell lung carcinoma

What is the normal function of Secretin? And, what does it do if the patient has Zollinger-Ellison Syndrome?

- Secretin is a hormone released from (S cells in) the duodenum in response to acid and fat - It increases pancreatic bicarb secretion, increases bile secretion, and inhibits the release of gastrin from normal gastric G cells - BUT! Secretin paradoxically stimulates release gastrin from a Gastrinoma - this can help differentiate Zollinger-Ellison syndrome from other causes of hypergastrinemia

If a person becomes unconscious d/t hypoglycemia, what is the proper way to handle this, in a NON-medical setting?

- Severe hypoglycemia with loss of consciousness is typically treated with intramuscular glucagon in the non-medical setting - It is then treated with IV dextrose in the medical setting

In HIV drugs, what is the naming trend for NRTIs, Protease inhibitors, and Integrase inhibitors?

-NRTIs have many different names, but 3 of them ed in: "-vudine" (ex: Zidovudine) - Protease inhibitors: "-navir" (ex: Atazanavir) (Navir tease a protease) - Integrase inhibitors: "-tegravir" (ex: Raltegravir) (inTEGRase = "-TEGRavir")

What is Sheehan Syndrome (post-partum)

- Sheehan syndrome is d/t *ischemic necrosis of the pituitary gland* leading to panhypopituitarism (with failure of lactation, central hypothyroidism, and adrenal insufficiency) - It occurs b/c the pituitary enlarges during pregnancy d/t estrogen-induced hyperplasia of lactotrophs; however, the blood supply does not increase proportionally... This makes the pituitary vulnerable to ischemia, especially in the case of systemic hypotension d/t peripartum hemorrhage

What is the mechanism of Shiga and Shiga-like toxin?

- Shiga and Shiga-like toxins inactivate the 60s robosomal subunit in human cells, leading to an inhibition of protein synthesis and eventual cell death

What are the 2 most classic findings of a pancoast tumor (superior sulcus tumor)?

- Shoulder pain & Horners syndrome

How does irreversible neuronal injury manifest?

- Shrinkage of the neuronal body, deep eosinophilia of the cytoplasm, pyknosis of the nucleus and loss of Nissl substance *Red Neuron*

What is the common ending of the Dihydropyridine Ca channel blockers?

-dipine

What is the mechanism behind Sirolimus?

- Sirolimus is an immunosuppressant - it binds to the FK-506 binding protein in the cytoplasm, and forms a complex that binds, and inhibits mTOR - Inhibition of mTOR signaling blocks IL-2 signal transduction and prevents cell cycle progression and lymphocyte proliferation

What areas of the body are most commonly affected by Graft-vs-host dz?

- Skin, Liver, and GI tract - Histo of liver = lymphocytic infiltration and destruction of small intrahepatic bile ducts (looks similar to Primary Biliary Cholangitis)

What 5 vitamins/minerals will be decreased, and what 2 vitamins/minerals will be increased in Small Intestinal Bacterial Overgrowth:

- Small intestinal bacterial overgrowth will result in deficiency of most vitamins (B12, A, D, E) and iron, but increased production of folic acid and vitamin K (because the enteric bacteria can produce these)

If a drug is given by continuous infusion IV, and is metabolized by first-order kinetics, how many half lives must pass to reach steady state concentration?

4-5 hours

What is the most common lung cancer in nonsmokers?

Adenocarcinoma

What nerve supplies sensory innervation to the posterior arm and posterior forearm and posterior hand

All of these are supplied by the *radial nerve*

Name 12 important inhibitors of CYP450

- Sodium Valproate (tx seizures and bipolar) - *Isoniazid* (TB Abx) - *Cimetidine* (H2 blocker for GERD) - Ketocon*azole* (Anti-fungal) - Flucon*azole* (Anti-fungal) - Acute alcohol abuse - Chloramphenicol (Abx) - *Erythromycin* (macrolide) - Sulfonamide (Abx) - *Ciprofloxacin* (Abx) - Omeprazole (PPI) - Metronidazol (Abx) "SICKFACES.COM" (Also: Amiodarone (class 3 anti-arrhythmic), *Ritonavir* (protease inhibitor), and *Grapefruit Juice*)

Somatic symptoms disorder vs. Illness anxiety disorder?

- Somatic symptom disorder = Excessive anxiety and preoccupation with 1 or more unexplained symptoms (so they have symptoms) - Illness anxiety disorder - Fear of having a serious illness despite few or no symptoms & consistently negative evaluations

What are 3 important tests before starting Amiodarone treatment?

Amiodarone (Class 3 antiarrhythmic - K channel blocker) - 3 main SE = *Pulmonary fibrosis, Hepatotoxicity, Hypo/Hyperthyroidism* (also QT prolongation) - Before treatment, check: *PFT, LFT, TFT* (pulmonary function test, liver function test, thyroid function test) --- am*IOD*erone is 40% IODine by weight ---

What is the most common cause of spontaneous lobar hemorrhage in the elderly?

Amyloid angiopathy - Amyloid angiopathy is a consequence of B-amyloid deposition in the walls of small- to mediul-sized cerebral arteries, resulting in vessel wall weakening and predisposition to rupture. They are not associated with systemic amyloidosis - Spontaneous lobar hemorrhage tends to be recurrent and most often involves the occipital and parietal lobes

What substance is detected by a southwestern blot? And, what type of probe is used?

- Southwestern blot detects Proteins that bind DNA, such as transcription factors, nucleases, and histones - A dsDNA is used as the probe NOTE: c-Jun, and c-Fos are nuclear transcription factors that can be detected by this (they are proto-oncogenes)

What is Rheumatoid Factor?

An IgM auto-antibody directed against the Fc portion of IgG

What is something that is almost always required for the progression of a Lower UTI to acute pyelonephritis?

An anatomic of functional *vesicoureteral reflux* is almost always necessary for the development of acute pyelonephritis "Without vesicoureteral reflux, the ascent of pathogens to the kidneys is very unlikely, and pyelonphritis does not occur"

What are typical symptoms of spinal stenosis? And, what postural change can improve these?

- Spinal Stenosis is d/t an abnormal narrowing of the spinal canal, usually in the lumbar region causing compression of nerve roots, which leads to lower extremity pain, numbness/parasthesia, and weakness - Symptoms are posture-dependant, where extension of the lumbar spine will further narrow the spinal canal and worsen the symptoms, but lumbar flexion can relieve the pain (like walking uphill, leaning on a shopping cart, etc.) NOTE: The most common cause of spinal stenosis is d/t degenerative arthritis of the spine, which results in narrowing of the spinal canal d/t intervertebral disc herniation, ligamentum flavum hypertrophy, and osteophyte formation.

A spontaneous deep intracerebral hemorrhage is typically caused by rupture of what artery?

- Spontaneous deep intracerebral hemorrhage is typically caused by a hypertensive vasculopathy involving the penetrating branches of the major cerebral arteries. - Chronic hypertension leads to the formation of *Charcot-Bouchard aneurysms*, which ultimately rupture and bleed within the deep brain structures - The most frequently affected locations include the basal ganglia (putamen), cerebellar nuclei, thalamus, and pons Of these, the basal ganglia and internal capsule are the most common locations, and these are supplied by the lenticulostriate arteries, which are small vessel branches off of the middle cerebral artery

What receptors does Phentolamine work on?

Antagonist at a1 & a2

What is the embryologic origin of the Anterior and posterior pituitary?

Anterior pituitary = Surface ectoderm (from Rathke Pouch) Posterior pituitary = neural tube

What path does prostate cancer take to spread to the spine?

- Spread to the skeletal system is usually via hematogenous spread - The vertebral venous plexus communicates with many venous networks, including the prostatic venous plexus (which receives the blood supply from the prostate, penis, and bladder) NOTE: The vertebral venous plexus runs up the entire spinal column, and connects with the venous supply of the brain via a valveless system

What is stimulus control in the setting of treating insomnia?

- Stimulus control focuses on eliminating stimulating bedroom activities and getting into bed only when sleepy

Describe the lifecycle of Strongyloides Stercoralis and how is it diagnosed?

- Strongyloides Stercoralis infection begins following skin penetration by Filariform (infectious) larva and can be diagnosed by finding Rhabditiform (non-infectious) larvae in the stool - The Rhabditiform larvae can mature into filariform larva in the human GI tract, precipitating an autoinfection cycle that occurs entirely within the affected individual (Strong Guy in bottom right corner) FA PAGE 155

What histological finding is characteristic of Acute myeloid leukemia

Auer Rods

What is a rare, but severe complication of the Measles virus?

- Subacute sclerosing panencephalitis (SSPE) is a rare complication of measles that occurs in children or young adults several years after the initial infection - Oligoclonal bands of measles virus Ab are found in the CSF of these patients NOTE: Measles virus has hemagglutinin (mediates cell surface adhesion), and matrix protein (important for viral assembly)

Subarachnoid hemorrhage is most commonly caused by what?

- Subarachnoid hemorrhage usually occurs d/t rupture of *saccular (berry) aneurysms* or arteriovenous malformaations. - Berry aneurysms usually occur at the circle of Willis, usually in the anterior communicating artery - Berry aneurysms are associated with Ehlers-Danlos syndrome and autosomal dominant polycystic kidney disease

What is the name of the Prodrug to 6-Mercaptopurine?

Azathioprine

What is the most common vitamin deficiency seen in alcoholics?

B1 - Thiamine

What are some key signs of Abusive head trauma in an infant (shaken baby syndrome)?

- Subdural hemorrhage (rupture of bridging veins) - Retinal hemorrhages

What are the 3 main veins that go into the portal system?

- Superior mesenteric vein - Inferior mesenteric vein - Splenic vein

t(8:14) translocation is associated with what disease and produce what product?

Burkitt Lymphoma - C-MYC overexpression (translocation of C-MYC from chromosome 8 to the Ig heavy chain locus on chromosome 14)

What is the classic triad of congenital Toxoplasmosis

Chorioretinitis, Hydrocephalus, intracranial calcificatons

What are the common symptoms of Lead poisoning?

- Symptoms of lead poisoning include colicky abdominal pain, constipation, lead lines on the gum (blue pigmentation), peripheral neuropathy, and anemia - In a child, it can present with initially normal development, and then later development regression (like a child was meting language milestones, but then regressed at later visits)

What is in the white pulp of the spleen?

- T cells are found in the periarteriolar lymphatic sheath (PALS) within the white pulp - B cells are found in follicles within the white pulp.

What immune cells defend against local (superficial) Candida? What immune cells defend against disseminated Candidiasis?

- T cells are important in prevention of superficial Candida (ex: oral/esophageal) - HIV can therefore increase the risk for this - Neutrophils prevent the hematogenous spread of Candida (Disseminated candidiasis like Candidemia or Endocarditis) - pts that are neutropenic or immunocompromised (like cancer w/ chemo) are at risk for this

What neuroendocrine marker is positive in most small cell lung carcinomas?

Chromogranin (this is can also be positive in carcinoid tumors!)

t(9:22) translocation is associated with what disease and produce what product?

Chronic Myelogenous Leukemia (Philadelphia chromosome) - BCR-ABL hybrid

What is Kallmann syndrome?

Classic presentation = hypogonadism + asomnia (cant smell) (they usually have delayed puberty)

In what step of the TCA cycle is GDP converted to GTP? In what step of gluconeogenesis is GTP consumed and converted to GDP

- TCA: The conversion Succinyl-CoA to Succinate (via Succinyl-CoA synthase - also called Succinate thiokinase) converts a GDP to a GTP - Gluconeogenesis: The conversion the oxaloacetate to phosphoenolpyruvate (via phosphoenolpyruvate carboxykinase) utelizes GTP

What is Tamoxifen used for? What are some side effects?

- Tamoxifen is a selective estrogen receptor modulator (SERM), which has agonist or antagonist activity depending on the tissue - In boobs, Tamoxifen has anti-estrogenic effect, and is used as an adjuvant treatment of estrogen receptor-positive breast cancer - In endometrial tissue, tamoxifen has a stimulatory effect, which can lead to endometrial hyperplasia and endometrial cancer - Other side effects include hot flashes and venous thromboembolism NOTE: Raloxifene is also a (SERM), and does not have a stimulatory effect on the endometrium

Describe what you know about Ovarian Teratomas:

- Teratomas are the most common subtype of germ cell tumor - They occur most frequently in females aged 10-30 - They are divided into mature and immature types - Mature types have cell lines of >1 germ layer, commonly including hair follicles, teeth, bones, and skin NOTE: On histo, look for abnormal things. Such as a random circle of darker staining cells (could indicate a hair follicle), or the presence of dermis/epidermis surrounding the area, etc.

What is the underlying cause of Xeroderma Pigmentosum?

Defective nucleotide excision repair

Dihtheria toxin vs. Shiga Toxin

Diphtheria toxin - Inactivates elongation factor (EF-2) Shiga toxin - Inactivates 60S ribosome by removing adenine from rRNA

What cellular process is the BRCA1 & BRCA2 genes involved in?

Double stranded DNA break repair - These are inherited in an autosomal dominant fashion and are associated with breast and ovarian cancer

What is the most common cause of Congenital intellectual disability?

Down Syndrome - Fragile X is 2nd most common cause

Burkitt Lymphoma is associated with what infectious agent?

EBV

What 2 viruses is Ribavirin used for?

Hep C and RSV

What hormone is responsible for the increased insulin resistance in pregnancy (specifically during the 2nd and 3rd trimester) ?

Human placental lactogen (hPL) - This is secreted by Syncytiotrophoblasts - It ensures a readily available supply of glucose and amino acids to the fetus

how does CO2 affect cerebral arteries?

Hypocapnia causes cerebral vasoCONSTRICTION - thus, low CO2 in blood will cause decreased cerebral blood flow

What main cytokines are secreted by TH1 cells?

INF-g - And also IL-2, IL-3 (which are secreted by all T cells)

IL-4 enhances class switching to what?

IgE & IgG

What are the 3 main actions of Cholecystokinin?

Increase pancreatic secretion, Increase gallbladder contraction, and Decrease gastric emptying

Hemochromatosis can lead to what type of heart failure?

It can lead to both dilated and restrictive cardiomyopathy, but DILATED is more common!!!

Lymphatic drainage of the lower extremity: Medial vs. Lateral

Lesions on the medial foot will cause inguinal lymphadenopathy, whereas lateral lesions are more likely to cause lymphadenopathy in both the popliteal and inguinal areas

What are the 2 exclusive ketogenic acids?

Leucine (Leu) Lysine (Lys)

What are the 4 key mediators that attract and activate Neutrophils?

Leukotriene B4 C5a IL-8 Bacterial products

Whate are the 2 most common areas of spread of prostate cancer?

Lumbar spine & Pelvis

Name 3 sets of reactions that occur in miotchondria, and 3 that occur in the cytosol:

Mitochondria: B-oxidation of Fatty Acids, TCA cycle, Carboxylation of Pyruvate (into oxaloacetate for gluconeogenesis) Cytosol: Glycolysis, Fatty Acid Synthesis, Pentose Phosphate Pathway

What is grown on Thayer-Martin VCN medium?

Neisseria species - It is a heated blood agar (or chocolate) that is supplemented with Vancomycin, Polymyxin (Colistin), and Nystatin (VCN)

In what sex can Posterior urethral valves occur?

ONLY MALES - it is d/t a malformation of the Wolffian (Mesonephric) duct

What does this enzyme do: Phosphoribosyl Pyrophosphate (PRPP) synthase

PRPP synthetase is the enzyme responsible for the production of the activated ribose necessary de novo synthesis of purine and pyrimidine nucleotides

Is it ever okay to challenge a parent about their childs care?

Parents authority to make medical decisions for their children can be challenged in cases in which a child is at significant risk for harm Physicians are justified in obtaining a court injunction to proceed with life-saving medical treatment of the child

Healthcare payment: Global payment

Patient (or insurer) pays for all expenses associated with a single incident of care with a single payment - usually used during elective surgeries, as it covers the cost of surgery as well as the necessary pre- and postoperative visits

What bursa is at the medial knee?

Pes Anserine bursa

Tetralogy of Fallot: - What embryological problem causes it? - What are the 4 abnormalities? - What is a typical patient presentation?

- Tetralogy of Fallot is caused by abnormal neural crest migration leading to an anterior and cephalad deviation of the infundibular septum - The 4 abnormalities are: --- Ventricular septal defect --- Overriding aorta (over the right and left ventricles) --- Right ventricular outflow tract obstruction (Pulmonary infundibular stenosis) --- Right ventricular hypertrophy - A typical presentation is cyanotic spells ("tet spells" often caused by crying, fever, exercise d/t exacerbated RV outflow obstruction), Prominent right ventricular impulse, systolic murmur: -The cyanotic spells improve with squatting d/t increased systemic venous return which decreases the right to left shunt, and mainly d/t increased afterload while squatting, which decreases the right to left shunt - The murmur is a harsh, systolic ejection murmur over the mid-to-left upper sternal border d/t the presence of pulmonary stenosis

What antifungals work at the fungal cell wall?

- The *Echinocandins* block glucan synthesis, and therefore suppress fungal cell wall synthesis - Echinocandins = *-"fungin"

What muscles are targeted with Kegel Exercises (pelvic floor strengthening)

- The *Levator Ani Muscles* (iliococcygeous, pubococcygeus, puborectalis) - These muscles form a U-shaped sling around the pelvic viscera & hold the bladder and urethra in the appropriate anatomic position

Antimitochondrial Ab indicates what?

Primary Biliary Cirrhosis

What is the most common pituitary adenoma?

Prolactinoma

What supplies the blood to the proximal and distal ureter?

Proximal ureter = renal artery Distal ureter = superior vesical artery (a branch of the anterior trunk of the internal iliac)

What are 2 meds that can be used to treat Enterobius Vermicularis?

Pyrantel Pamoate (preferred in preggos) Albendazole (first-line)

What are the 2 branches of the common peroneal (fibular) nerve? And, what do they innervate?

- The 2 branches are the deep peroneal nerve, and the superficial peroneal nerve - The deep peroneal nerve - innervates the anterior compartment muscles of the leg, which dorsiflex the foot and toes... This nerve also provides sensation over the webspaces between the first and second toes - The superficial peroneal nerve - Innervates the lateral compartment muscles, which evert the foot... This nerve also provides sensation to the dorsum of the foot and lateral shin NOTE: The common peroneal nerve is susceptible to injury at the neck of the fibula d/t its superficial location... Injury to the common peroneal Nerve will result in weakness on foot dorsiflexion and eversion, and impaired sensation over the lateral shin and dorsal foot, and between the first and second toes

What is the most common type of thyroid carcinoma? And, what distinguishes it from the other types?

- The 4 main types of thyroid carcinoma are papillary, follicular, medullary (derived from parafollicular calcitonin-secreting C cells), and anaplastic - The most common type is: Papillary carcinoma - Characteristic finings on histopathology are: large cells with overlapping nuclei containing finely dispersed chromatin, giving an empty or ground-glass appearance (Orphan Annie Eye), and intranuclear inclusions or grooves (d/t invagination of the nuclear membrane)... Psammoma bodies may also be found within the tumor

The majority of the hearts anterior order is the:

Right ventricle

What receptors does Phenylephrine work on?

Selective alpha-adrenergic agonist

What are the 2 most significant risk factors for the development of esophageal squamous cell carcinoma?

Smoking tobacco and drinking alcohol

What is the most important environmental risk factor for pancreatic cancer?

Smoking!

What are the 4 major dopaminergic pathways in the brain?

- The 4 major dopaminergic pathways in the brain are: - 1&2 - Mesolimbic & Mesocortical pathways - regulate cognition and behavior (hyperactivity in mesolimbic pathway = positive symptoms of schizophrenia) - 3 - Nigrostriatal pathway - regulates coordination and voluntary movements - 4 - Tuberoinfundibular pathway - connects the hypothalamus to the pituitary and is responsible for the inhibition of prolactin secretion

What is a severe side effect of *Lamotrigine*

Stevens-Johnson Syndrome (must titrate slowly)

What is the vector for Dengue fever and Chikungunya? And how do each classically manifest?

- The Aedes Aegypti mosquito transmit the viruses that cause both Dengue fever and Chikungunya - Dengue fever = acute fever, headache, retro-orbital pain, joint/muscle pain - Chikungunya = fever, flu-like symptoms, prominent polyarthralgia, diffuse macular rash NOTE: The Aedes Aegypti mosquito also transmits the virus that causes yellow fever

What type of channel is the Cystic Fibrosis Transmembrane Regulator (CFTR) protein?

- The CFTR protein is a transmembrane *ATP-gated* chloride channel

The gene HER2 codes for what gene product?

- The HER2 oncogene encodes for a transmembrane glycoprotein with intrinsic tyrosine kinase activity in the intracellular domain - This tyrosine kinase is a member of the family of epidermal growth factor receptors - and thus plays a role in the activation of transduction pathways that control epithelial growth and differentiation - Epithelial cell carcinomas that over-express HER2 demonstrate increased proliferation and resistance to apoptosis NOTE: Over-expression of this protein is associated with a worse prognosis and increased risk of disease reoccurrence - Trastuzumab (Herceptin) is a monoclonal Ab against HER2

Why/How is Hep B required for Hep D infection?

- The Hep B surface antigen must coat the Hep D antigen of the Hep D virus before it can infect hepatocytes (then it can multiple and do everything on its own) NOTE: Superinfection is a worse prognosis

What has a higher diastolic pressure, Right Ventricle or Pulmonary Artery?

The right ventricular diastolic pressure is similar to right atrial/central venous pressure (1-6mmHg), where as pulmonary artery diastolic pressure is slightly higher (6-12mmHg) d/t resistance to flow in the pulmonary circulation

What is the peak time for RSV virus?

Winter

Describe the process by which vasoactive substances are released from Mast cells & Basophils in Anaphylaxis:

- The IgE receptor on Mast cells & Basophils binds to the Fc portion of IgE - A cross-linking of multiple membrane-bound IgE antibodies by a multivalent antigen results in aggregation of the IgE receptors, which causes a degranulation and release of preformed mediators NOTE: The binding of IgE to the IgE receptor is NOT covalent

What is the major virulence factor on E. Coli strains that can cause neonatal meningitis?

- The K1 capsular antigen is present on 20%-40% of intestinal E. Coli isolates and is the major virulence factor among E. Coli strains that cause neonatal meningitis - The K1 capsule allows the bacteria to survive in the bloodstream and establish meningeal infection NOTE: E. coli is a frequent cause of neonatal meningitis, second only to group B Strep

Where is the principal site for norepinephrine synthesis in the brain?

- The Locus Ceruleus is a paired brainstem nucleus located in the posterior rostral pons near the lateral floor of the fourth ventricle, and functions as the principal site for norepinephrine synthesis in the brain - It projects to virtually all parts of the CNS and helps control mood, arousal, sleep-wake, cognition, and autonomic function

What is the main source of NADPH? And, what cells are very dependent on NADPH?

- The Pentose Phosphate Pathway (or HMP shunt) is the main source of NADPH (first step is catalyzed by G6PD) - This is very active in: --- Cells experiencing high oxidative stress (like erythrocytes), which use NADPH to regenerate reduced glutathione --- Organs such as the liver and adrenal cortex that are involved in reductive biosynthesis (synthesis of fatty acids, cholesterol, and steroids) and P450 metabolism --- Phagocytic cells generating a respiratory burst via NADPH oxidase NOTE: in contrast to NADH which can reduce ADP to ATP, NADPH cannot do this!

What is the order of increasing conduction speed by the different tissues in the heart?

- The Purkinje is the fastest because this ensures that the ventricles contract in a bottom-up fashion

What is some weird test that can help differentiate Strep Pyogenes (since the bacitracin susceptibility test is not very specific)

- The Pyrrolidonyl Arylamidase (PYR) test - S. Pyogenes is: PYR-POSITIVE

Where are serotonergic (serotonin-releasing) neurons found?

- The Raphe nuclei of the brain stem - The Raphe nuclei are located in the medulla, pons, and midbrain, and the axons from these cell bodies project widely throughout the CNS to synapse on various structures - These neurons play a role in the sleep-wake cycle, anxiety, mood, psychosis, sexuality, eating behavior, and impulsivity (*Ralph at vista was a happy guy b/c he was full of serotonin*)

What is the Ristocetin aggregation test?

- The Ristocetin aggregation test measures in vitro von-Willebrand factor (vWF) dependent platelet aggregation - Ristocetin activates GP-1b receptors on platelets and makes them available for vWF binding - So, if the vWF is decreased (in vWF deficiency), there will be poor platelet aggregation, even in the presence of added ristoceitin... (However, normal platelet aggregation will occur if normal plasma (which contains vWF) is added to a solution of a patients platelets with vWF deficiency) NOTE: Both Von-Willebrand factor deficiency and Bernard-Soulier syndrome (deficiency of GP-1b receptors) will have failure of aggregation with addition of ristoceitin... But Bernard-Soulier syndrome will not be corrected after addition of normal serum

Where does the ventral posterior lateral nucleus of the thalamus, and the ventral posterior medial nucleus of the thalamus receive inputs from?

- The Ventral Posterior Lateral Nucleus of the Thalamus receives input from the Spinothalamic tract (Fast pain and temperature) and the Dorsal Columns-Medial Lemniscus (touch, 2-pt discrimination, vibration, proprioception) - The Ventral Posterior Medial Nucleus of the Thalamus receives input from the Trigeminal pathway - These 2 nuclei then send somatosensory projections to the cortex via thalamocortical fibers - If these 2 nuclei are damaged (i.e. the entire posterior Thalamus), it results in complete contralateral sensory loss

What is another name for the Vitelline duct?

- The Vitelline duct is also called the Omphalomesenteric duct, which connects the yolk sac to the midgut lumen - A vitelline fistula occurs when the duct fails to close - Mickels diverticulum occurs when the duct partially closes

What secondary messenger system is activated with stimulation of the adrenergic receptors?

- The adrenergic receptor are a Gs protein-coupled receptor that activates adenylyl cyclase and increases intracellular cAMP concentrations - This all ultimately leads to the effects seen, such as relaxation of bronchial smooth muscle (if Beta2)... etc.

Gerstmann syndrome is d/t damage to the angular gyrus of the dominant parietal lobe... How does damage here manifest?

- The angular gyrus of the dominant parietal lobe lobe (supplied by the MCA) , is part of the parietal association cortex, which integrates multi-sensory (visual, tactile, verbal...) info to comprehend events and solve problems. It is specifically important in semantic processing, word reading and comprehension, and number processing - Damage to this area results in Gerstmann syndrome: --- *Agraphia* (inability to write) --- *Acalculia* (inability to carry out math) --- *Finger agnosia* (inability to identify individual fingers on the hand) --- *Left-right disorientation* - In addition, damage to the angular gyrus can be associated with alexia (inability to read), and aphasia (impaired speech)

How does an Axillary nerve injury present?

- The axillary nerve originates from the posterior cord of the brachial plexus and carries fibers from C5 and C6 - It provides motor to the deltoid muscle and the teres minor - It provides sensory to the skin over the lateral shoulder - Axillary nerve injury most commonly occurs in the setting of shoulder trauma (ex: anterior dislocation, proximal humeral fracture)... Patients usually have sensory loss over the upper lateral arm and weakness on shoulder abduction d/t denervation of the deltoid muscle

What type of collagen is deficient in the most common type of Ehler-Dhanlos syndrome?

- The classical type (joint and skin symptoms) is caused by a mutation in type V collagen - The vascular type (vascular and organ rupture) is caused by deficient type III (this is called type 4 Ehler-Danlos)

What is the anatomical course of the Femoral nerve? And, how does a femoral nerve injury present?

- The femoral nerve is derived from nerve roots L2-L4. It descends through fibers of the psoas major muscle, and emerges laterally between the psoas and iliacus muscle, and then runs beneath the inguinal ligament to the thigh - Patients with femoral nerve neuropathy develop weakness involving the quadriceps muscle group (impaired thigh flexion, and leg extension), have a diminished patellar reflex, and have sensory loss over the anterior thigh, medial thigh, and medial leg.

What is the wobble hypothesis?

- The first 2 nucleotide positions on the mRNA codon require traditional base pairing, whereas the third "wobble" nucleotide position may undergo less stringent base pairing - This allows for the genetic code to be degenerate b/c more than 1 codon can code for a particular amino acid

How can Diabetes Insipidus be differentiated by Primary Polydipsia?

- The first step is to look at the plasma osmolality Note: Many times in Primary polydipsia, if the Vasopressin is given late in the water deprivation test, the urine osmolality will not change much because the patient has maximal endogenous ADH effect

What is the best treatment method for Rheumatoid arthritis, both short and long term?

- The foundation of management of RA is disease-modifying antirheumatic drugs (DMARDS) - Methotrexate (first-line), sulfasalazine, hydroxychloroquine, minocycline, and TNF-a inhibitors... These can alleviate pain/inflammation, and reduce long-term joint destruction - DMARDS take weeks to work, so when starting these, you can give systemic and intra-articular glucocorticoids or NSAIDS, to provide rapid/temporary relief

What area of the brain is first damaged during global cerebral ischemia?

- The hippocampus is the first area damaged during global cerebral ischemia NOTE: The cells most susceptible to ischemia are the pyramidal cells of the hippocampus, and the Purkinje cells of the cerebellum

List the steps in the pupillary light reflex

- The impulse of the light flows through the Optic nerve, optic chiasma, and then the optic tract - The pupillary constriction is mediated by *Parasympathetic fibers from the Edinger-Westphal nucleus, that run with the oculomotor nerve* and innervate the Sphincter pupillae (These fibers run on the outside of CN III) - The nasal portion of the retina contributes more input to the pretectal nucleus than the temporal portion of the retina

How does the lipophilicity of a drug determine where it is metabolized and eliminated?

- The kidney is the primary site for elimination of most drugs, while the liver is the main site of biotransformation of these agents in preparation for elimination - Drugs that are more lipophilic (high Vd, good penetration into CNS) are preferentially processed by the liver into more polar compounds for easier elimination in the bile and urine

What portion of the heart forms the majority of the posterior surface

- The left atrium - An enlarged Left atrium can cause dysphagia by pressing on the esophagus

How is the Lepromin skin test used to differentiate between Tuberculoid and Lepromatous forms?

- The lepromin skin test will be positive in patients with tuberculoid leprosy as they exhibit a strong CD4+ TH1 cell-mediated immune response - The lepromin skin test will be negative in patients with lepromatous leprosy d/t their weak TH1 cell-mediated response NOTE: - Tuberculoid form is more mild b/c the pt mounts a primarilly cell-mediated response leading to activated macrophages that can kill M. Leprae - Lepromatous is more severe/disseminated and characteried by an innate inability to recognize and mount a cellular immune response... So they have more of a humoral response

How far superior does the lung pleura extend to?

- The lung apices and cervical pleura extend *above the clavicle and first rib* through the superior thoracic aperture

What is the main distinguishing characteristic of *Atypical Depression*

- The main distinguishing characteristic of Atypical depression is *mood reactivity* (i.e. feeling better in response to positive events) - Other hallmarks of atypical depression are: increased appetite and sleep, leaden paralysis (heavy arms and legs), and rejection sensitivity

How can a Tricyclic antidepressant lead to Torsades?

- The main mechanism of Tricyclics is to inhibit reuptake of NE and serotonin BUT... Tricyclics also can *inhibit fast sodium channel conduction*, which can slow dow the myocardial depolarization and lead to cardiac arrhythmia (which is the most common cause of death for patients on Tricyclics) In addition to this, Tricyclics have some a1 antagonist effects, which can cause hypotension. Which can be exacerbated if the pt also has decreased cardiac output

What does the urine copper reduction test for?

nonspecifically detects the presence of a reducing sugar

What is the major determinant of whether or not a coronary artery plaque will cause ischemic myocardial injury?

- The major determinant of whether or not a coronary plaque will cause ischemic myocardial injury is the rate at which it occludes the involved artery - A slowly developing occlusion would allow for the formation of collaterals that could prevent myocardial necrosis

What are the weakest plates of bone in the orbit?

- The medial and inferior wall (orbital floor) - Medial wall is composed of the thin ethmoid and lacrimal bones which separate it from the ethmoid air cells - Inferior wall (orbital floor) is composed of thin bone (maxilla bone) that separates it from the maxillary sinus

What 2 muscles does the median nerve run in-between in the forearm?

- The median nerve courses between the humeral and ulnar heads of the pronator teres and then travels between the flexor digitorum superficialis and the flexor digitorum profundus before entering the wrist within the flexor retinaculum

What does the *Minimal Alveolar Concentration* measure regarding inhaled anesthetics?

- The minimal alveolar concentration (MAC) is a measure of *potency* of an inhaled anesthetic - It is the concentration of the anesthetic in the alveoli that renders 50% of patients unresponsive to painful stimuli (ED50) - Potency and MAC are inversely proportional - The lower the MAC - The more potent the anesthetic

What is the most common cause of unilateral fetal hydronephrosis?

- The most common cause of unilateral fetal hydronephrosis is an *inadequate canalization of the ureteropelvic junction* - which is the connection site between the kidney and ureter

What is the most common congenital heart defect? What is the most common cause of childhood cyanosis?

- The most common congenital heart defect is a ventricular septal defect (note: The murmur for VSD may not be detected at birth, but becomes audible 4-10 days later as the pulmonary vascular resistance continues to decline) - The most common cause of childhood cyanosis is Tetralogy of Fallot

What cytogenic abnormality is seen with Acute promyelocytic leukemia?

t(15:17)

Fractures of what are the most common manifestation of osteoporosis?

vertebral fractures

What are the major side effects of Amphotericin B?

- The most dangerous adverse affect of Amphotericin B is its nephrotoxicity - Nephrotoxicity can lead to anemia (decreased erythropoietin production), and electrolyte abnormalities (hypokalemia and hypomagnesemia) (d/t an increase in the membrane permeability of the distal tubule) - Hypokalemia can cause weakness and arrhythmias. ECG findings of hypokalemia include T wave flattening, ST depression, prominent U waves, and PACs / PVCs.

What occurs during the 3 Stages of Acute tubular necrosis?

- The most important complication during the recovery phase is hypokalemia

How can you identify a nondepolarizing NMJ blocker by the name?

"-*CUR*-"

Where are ribosomoal RNA sequences transcribed?

- The nucleolus contains ribosomal DNA coding for the 28S, 5.8S, and 18S ribosomal RNA components, as well as newly transcribed rRNA in association with ribosomal proteins that are translated in the cytoplasm from mRNA - The main function of the nucleolus is the synthesis and assembly of immature 60S and 40S ribosomal subunits that are exported from the nuclues to fully mature in the cytoplasm. - All ribosomal RNA, except 5S rRNA, is transcribed in the nucleolus.

What causes an S3?

"S3 is commonly associated with increased ventricular end-systolic volume" - S3 frequently occurs in the setting of mitral regurg. and systolic heart failure (dilated cardiomyopathy)

What phrase is used to identify Blastomyces Dermatitidis on stain?

"Thick wall and *Broad-Based Budding*" - Dont confuse with Cryptococcus Neoformans which can be described as Heavily encapsulated, and budding.. but it is "narrow budding"

What is a feature that occurs in Thromboangiitis Obliterans (Buerger's Disease), but not other vasculitis?

"This segmental thrombosing vasculitis often extends into contiguous veins and nerves (a feature rarely seen in other types of vasculitis)" - "The inflammatory process may eventually encase all three structures (arteries, veins, and nerves) in fibrous tissue

What is the anatomical path of the obturator nerve? And, what does it innervate?

- The obturator nerve arises from the lumbar plexus (L2-L4), and descends posteriomedial to the iliopsoas and then descends through the obturator canal, to enter the medial thigh region - It supplies the obturator externus muscle, and then divides into anterior and posterior branches to supply the thigh adductor muscles - The anterior division also gives off a terminal cutaneous branch that provides sensation over the distal medial thigh

What is a cross-sectional study?

"snap-shot" in time (absence of a time period)

What are the #1 and #2 cause of multiple ring-enhancing lesions with mass effect in a patient with HIV?

#1 = Toxoplasmosis #2 = Primary Central Nervous System L ymphoma (but this is commonly a large, solitary lesion)... This is a diffuse, large-cell non-Hodgkin lymphoma of B-cell origin that usually occurs as a late complication of HIV infection. Epstein-Barr virus is identified in almost all cases

What is the name of a an anti-viral that is for the Herpes virus family, that DOES NOT require phosphorylation by viral kinase?

(Note: Foscarnet also does not require kinase activation)

What is Systemic Mastocytosis?

(Probably Low Yield) - A clonal mast cell proliferation in the bone marrow, skin, and other organs - Usually d/t mutation in the KIT receptor tyrosine kinase - Excessive histamine release from degranulation of mast cells, which mediates symptoms like: Syncope, flushing, hypotension, pruritis, and urticaria - Also, the excess histamine can induce gastric acid secretion

What is the gram nature of Bordetella pertussis?

* Gram negative coccobacillus*

How long after the onset of CNS Ischemia does it take for microglia cells to come? And how do they appear on microscopy?

*3-5 days* - they phagocytize the fragments of neurons, myelin, and necrotic debris... and therefore will have an abundance of lipids inside them d/t the phagocytosis of myelin breakdown products

What 2 things are produced by sarcoid granulomas?

*ACE* *1,25-dihydroxy-cholecalciferol (active vitamin D)* (d/t increased a-hydroxylase activity in the granuloma macrophages) - These are the reason why sarcoidosis patients usually have elevated ACE and hypercalcemia

How does Lateral pontine syndrome present?

*AICA STROKE* - Spinothalamic tract affected - loss of contralateral pain/temp - Sympathetic tract - Horners syndrome - CN 5 - loss of ipsilateral face pain/temp - CN 7 - Ipsilateral face droop, and loss of corneal reflex - CN 8 Vestibular nuclei = nystagmus, vertigo, N/V... Cochlear nuclei = deafness

Hereditary inherited mutation in *APC* gene is associated with what disorder?

*APC is a tumor suppressor gene* - *Autosomal dominant* inherited mutation is associated with *Familial Adenomatous Polyposis*

How does medial medullary syndrome present?

*ASA STROKE* - Corticaospinal tract - contralateral hemiparesis - Medial Lemniscus - contralateral loss of proprioception/vibration - CN 12 - tongue deviation to side of lesion

What happens to the ciliary mm. and lens when you look at something close to you?

*Accommodation* Ciliary mm. contract, zonules (fibers) relax, and the lens becomes round (The ciliary muscle is innervated by parasympathetic fibers)

The large difference in Isoniazid half-lifes seen in people is d/t fast vs. slow _________________?

*Acetylation* - Isoniazid is metabolized by acetylation - Slow acetylators are at risk of adverse side effects

What is Actinic Keratosis? And, what cancer can this turn into?

*Actinic Keratosis* = small, scaly, erythematous lesions with a sandpaper texture occurring on sun exposed areas - It is characterized by *hyperkeratosis* (hyperplasia of the stratum corneum), *parakaratosis* (retention of nuclei in the stratum corneus), and *atypical keratinocytes* (with pleomophic nuclei and multiple mitosis) - Some Actinic Keratosis can eventually invade the dermis and become *invasive squamous cell carcinoma*

What is bound to RAS in its active state? And, in its inactive state?

*Active = RAS-GTP* *Inactive = RAS-GDP* - RAS becomes active when a growth factor ligand binds to a receptor tyrosine kinase and this triggers binding of adapter proteins that interact with RAS, promoting GDP removal and GTP binding - RAS proteins have intrinsic GTPase activity that allows them to hydrolyze GTP; this mechanism prevents accumulation of active RAS (GTP-bound) in the absence of hormone signaling

What 2 types of blood cancer are pts with Downs syndrome pre-disposed to?

*Acute Lymphoblastic leukemia* *Acute myelogenous leukemia*

How can hemorrhagic cystitis due to Cyclophosphamide be prevented?

*Aggressive hydration and co-administration of Mesna* - *Mesna binds and inactivates the toxic metabolites* (acrolein) of Cyclophosphamide that damage the uroepithelial cells & cause death/necrosis of the cells

What is the name of the stain used in the acid fast stain, and what does it stain?

*Alanine Dye (Carbolfuchsin)* - detects *Mycolic acid*

Which category of receptor/messenger does: Alpha adrenergic, Beta adrenergic, Muscarinic (M1, M2, M3), and Nicotinic, receptor act on?

*Alpha 1* - secondary messenger - Inositol Triphosphate (IP3) pathway *B1 & B2* - secondary messenger - Receptor acitvates Adenylate cyclase, which generates cAMP to activate Protein Kinase A *M1 & M3* - secondary messenger - Inositol Triphosphate (IP3) pathway *M2* - secondary messenger - cAMP system (but it DECREASES cAMP) *Nicotinic* - ligand-gated ion channels that open after ACh binding to allow Na & Ca influx, and K outflux

What adrenergic receptor is responsible for eye dilation?

*Alpha 1* - stimulation of this will constrict the pupillary dilator muscle, and dilate the pupil - Phenylephrine is an ophtho drug that does this before exam

What is: Amniotic fluid embolism?

*Amniotic fluid embolism (AFE)* is a rare and catastrophic pregnancy complication that results from amniotic fluid entering the maternal circulation - Common signs of AFE include hypoxia, hypotensive shock, and DIC - Fetal squamous cells are seen in the pulmonary vasculature during histo evaluation (on autopsy)

What are the major side effects of Chloramphenicol?

*Anemia, Leukopenia, thrombocytopenia, aplastic anemia* - Chloramphenical suppresses bacterial protein synthesis by binding to the ribosomal 50s subunit and inhibiting the peptidyl transferase enzyme

What is injured in a radial head subluxation (nursemaids elbow)?

*Annular ligament* This injury usually results from a sharp pull on the hand while the forearm is pronated and elbow extended - Affected children will have their arm held close to them, with elbow extended, and forearm pronated

What 2 antibodies are seen in Sjogren syndrome?

*Anti-Ribonucleoprotein* = Anti-Ro/SSA & Anti-La/SSB

What is the antibody of Antiphospholipid syndrome that can cause false positive VDRL/RPR?

*Anti-cardiolipin* (but note: "lupus anticoagulant" is what is the cause of the paradoxically elevated PTT)

What antibody is sensitive for drug induced lupus?

*Anti-histone antibody*

What is the most common cause of Candida Vaginitis?

*Antibiotic use is the most common cause of Candida Vaginitis d/t reduction of the lactobacilli population, which facilitates Candida overgrowth* - Other potential causes = Pregnancy, systemic Corticosteroid use, Diabetes Mellitus, and Immunosuppression

What 3 antibodies are usually seen in Lupus?

*Antinuclear Antibody* (ANA) *Anti-dsDNA Antibody* *Anti-Smith Antibody* (Anti-sm)

What parts of the nervous system would result in a upper motor neuron lesion?

*Any part of the pyramidal system* - Corticospinal tract in the spinal cord, medulla, pons, midbrain, internal capsule, and precentral gyrus (primary motor cortex)

What cellular process is responsible for the bleeding seen after progesterone withdrawl?

*Apoptosis* - When the endometrium is no longer exposed to progesterone, prostaglandin synthesis increases, leading to vasoconstriction of the spiral arteries... Progesterone withdrawal also leads to secretion of metalloproteases by endometrial stromal cells and apoptosis of the endometrial epithelium

What type of Leukemia do Auer Rods suggest?

*Aucte Myelogenous Leukemia*

What is the inheritance of Hypertrophic Cardiomyopathy? And, what are the 2 most common genes affected?

*Autosomal Dominant* - Affects the sarcomere genes: *Cardiac beta-myosin heavy chain gene*, & *myosin-binding protein C gene*

What changes are seen in the neuronal body after an axon has been severed?

*Axonal reaction or Chromatolysis* describe the changes in the body of a neuron that occur after an axon has been severed... These processes reflect increased protein synthesis that facilitates axonal repair - *Enlarged, rounded cells with peripherally located nuclei, and dispersed finely granular Nissl substance are seen*

What med is an initial treatment in the ED for acute coronary syndrome (possible CAD + Tachy + Chest pain)? And, what can be an adverse effect of this?

*B-Blockers* - The B1 block decreases HR, BUT the B2 block can cause bronchoconstriction and wheezing (which can be exacerbated if the pt has asthma or COPD) - "B-blockers reduce BP and cardiac work, which is beneficial in the acute treatment of Myocardial Ischemia"

What drugs have been shown to improve long-term survival in patients with heart failure d/t left ventricular systolic dysfunction?

*B-blockers*, ACE inhibitors, Angiotensin II receptor blockers, and Aldosterone antagonists

What autonomic receptor is capable of relaxing the uterus?

*Beta 2* - Ritodrine and Terbutaline are B2 agonists and are used in OB to defer premature labor

What are the 2 sympathetic receptors located on Pancreatic Beta Cells? And, what do they do?

*Beta2 & Alpha2* - Stimulation of Beta2 increases insulin secretion - Stimulation of Alpha2 inhibits insulin secretion -

What is the classic cause of Potters Sequence in a baby?

*Bilateral renal agenesis* - It can also be d/t other lesions like posterior urethral valves or Autosomal recessive polycystic kidney disease Potter Sequence = Pulmonary hypoplasia with facial and lower limb deformities

What class of lipid lowering agents can cause increased levels of triglycerides?

*Bile acid binding resins* ("Chole....")

What is the mechanism of the anti-HIV drug *Enfuvirtide*?

*Binds gp41, inhibiting viral entry* en*FU*virtide inhibits *FU*sion

What are the blood levels of Homocysteine and Methylmalonic acid, in B12 deficiency?

*Both Homocysteine and Methylmalonic acid are elevated* - This can help differentiate from folate deficiency, where only Homocysteine is elevated, and Methylmalonic acid is normal

In the GI anatomy: What are Brunners glands? And, where are they located?

*Brunners (Submucosal) glands* - secrete copious amounts of alkaline mucus into the duodenum. They are most numerous at the pylorus, but may be found intermittently up to the ampulla of Vater

What is a common risk factor for Placenta acreta/increta/percreta?

*C-Secton* Also: inflammation, or placenta previa ... Basically anything that can complicate the integrity of the decidua basalis

What is the mechanism is which Carbon Tetrachloride (CCl4) damages the liver?

*CCl4 causes free radical injury* CCl4 gets oxidized by the P450 system, which forms a free radical (CCl3), which reacts with structural lipids and causes lipid degradation and H2O2 formation (lipid peroxidation) - The end result is swelling of the Endoplasmic Reticulum, Destruction of Mitochondria, Increased permeability of cell membranes, and ultimately *Hepatocyte Necrosis*

What 2 receptors are necessary for HIV entry into cells?

*CD4* - primary receptor *CCR5* or *CXCR4* - co-receptor - HIV virus gp120 binds both CD4 and CCR5 on T-cells or macrophages, and after binding to BOTH, fusion of cell membranes and entry can occur NOTE: A small amount of CD4 and CCR5 are on macrophages, and this is how HIV can also infect macrophages NOTE: HIV can also use CXCR4 on T-cells as a co-receptor (later in infection)

CN lesions... which way does it deviate? CN 4 - head tilt CN 5 - jaw deviation CN 10 - Uvula CN 11 - Shoulder & head turn CN 12 - Tongue

*CN 4 (Trochlear)* - *Head tilt AWAY form affected side* (b/c the superior oblique intorts the eye, so without this, the eye is extorted... so turning your head away serves to manually intort) *CN 5 (Trigeminal)* - *Jaw deviates TOWARD affected side* (b/c the pterygoid mm. on opposite side pull the jaw anterior, which will cause it to rotate and deviate on the other side *CN 10 (Vagus)* - *Uvula deviates AWAY from the affected side* (b/c the weak side of the palate collapses, and this pushes the uvula away) *CN 11 (Accessory)* - Shoulder droop on SAME side of lesion and weakness turning head AWAY* (d/t weak trapezius and sternocleidomastoid) *CN 12 (hypoglossal)* - tongue deviates TOWARD affected side (think that the muscles push the tongue toward midline, so when one gets knocked out, the other keeps pushing it toward that side)

What passes through the Jugular foramen?

*CN IX* - Glossopharyngeal *CN X* - Vagus *CN XI* - Spinal Accessory nerve *Jugular Vein*

What is the name of the Active Vitamin D that can be given to a patient with transient or post-op hypoparathyroidism?

*Calcitriol* (1,25-(OH2)D3

What is the first line treatment for Trigeminal Neuralgia?

*Carbamazepine* - A neuroleptic med that inhibits neuronal high-frequency firing by reducing the ability of Na channels to recover from inactivation - Carbamazepine can cause bone marrow suppression

What intracellular molecules get activated and mediate apoptosis?

*Caspases* - "*Apoptosis is mediated by caspases that activate proteases and endonucleases*... Proteases break down cytoskeleton and Endonucleases break down DNA"

Compare the *Central Chemoreceptors* vs. *Peripheral Chemoreceptors*

*Central Chemoreceptors* - located *in the medulla* & stimulated by decreased pH in the surrounding CSF... The blood brain barrier is mostly impermeable to H+, so blood pH has little effect on these chemoreceptors, BUT, CO2 readily diffuses through the blood-brain barrier and forms H+ in the CSF... Thus, *increased PaCO2 is the major stimulator of central chemoreceptors* *Peripheral Chemoreceptors* - located *in the carotid body and aortic body* & are the primary sites for *sensing arterial PaO2 and are stimulated by hypoxemia*... They are also stimulated by increased PaCO2 levels and blood H+ concentration, but central chemoreceptors are far more important for the increased respiratory response to hypercapnia

What does the Cerebellar Vermis modulate? And, what does a lesion to this area result in?

*Cerebellar Vermis* - modulates axial/truncal posture and coronations via connections with the medial descending motor systems - Acute lesions result in *truncal ataxia* with a wide-based, unsteady gait (Pts may also develop vertigo/nystagmus d/t involvement of the inferior vermis & flocculonodular lobe)

What area of the brain is responsible for vomiting after Chemo treatment? And, where is this?

*Chemoreceptor Trigger zone* - Located on the dorsal surface of the medulla and caudal end of the 4th ventricle (area postrema - which samples chemicals in circulating blood)

Describe why these 4 malaria meds are used: Choloquine, Mefloquine, Atovaquone/Proguanil, and Primaquine

*Chloroquine* - first line for resistant strains *Mefloquine* or *Atovaquone/Proguanil* - if the strains are resistant to Chloroquine *Primaquine* - must be added to the treatment if the causative agent is P. Vivax or P. Ovale to completely eliminate liver hypnozoites (and prevent from relapses) NOTE: The 3 malaria species are: P. falciparum, P. ovale, P. vivax

What 2 markers are typically positive in small cell lung carcinoma?

*Chromogranin* *Synaptophysin*

What is the mechanism of Cilostazol?

*Cilostazol* is a phosphodiesterase inhibitor that inhibits platelet aggregation and acts as a direct vasodilator - Agents that increase intra-platelet cAMP levels decrease platelet aggregation by preventing platelet shape change and granule release... Thus, Cilostazol reduces platelet aggregation by inhibiting platelet phosphodiesterase (the enzyme responsible for breakdown of cAMP) NOTE: *Dipyridamole* has this same mechanism and effect

What class of anti-arrhythmic preferentially binds to rapidly depolarizing ischemic myocardial tissues, and has minimal effect on normal tissues?

*Class 1B - Lidocaine, Mexiletine* - These preferentially bind Na channels in the inactivated state... Ischemic myocardium has higher than normal (less negative) resting membrane potential, which delays recovery of Na channels from the inactivated state, which allows increased binding of Class 1B blockers *Thus, they are effective at suppressing ventricular tachyarrhythmias induced by rapidly depolarizing and ischemic myocardium*

What are Cold Agglutinins? And what bacteria can cause them?

*Cold agglutinins* - IgM antibodies that bind red blood cells and cause clumping/agglutinations at *low body temperature* - They can be d/t *Mycoplasma Pneumoniae* b/c their surface antigen (I-antigen) is also present on the plasma membrane of erythrocytes, so cross-reactive IgM can develop which can bind to RBCs, activate complement, and lyse the cells (can also be d/t infectious mononucleosis and certain hematologic malignancies)

What 3 extracellular proteins can integrins bind to?

*Collagen, Fibronectin, Laminin* - The interaction of these extracellular proteins with integrin creates the adhesion of cells to the extracellular matrix (Increased expression of laminin in cancer allows the tumor to adhere to the basement membrane and eventually invade via secretion of proteolytic enzymes)

Communicating hydeocephalus vs non-communicating hydrocephalus

*Communicating Hydrocephalus* - There is no obstruction of CSF flow from the ventriculi to the subarachnoid space - It usually occurs secondary to *dysfunction of the subarachnoid villi* (after meningitis or subarachnoid hemorrhage, etc.) - ALL ventriculi are symmetrically enlarged *Non-communicating Hydrocephalus* - The flow of CSF to the subarachnoid space is disrupted by an *obstruction* - Ventriculi above the obstruction are enlarged, while those below the obstruction are normal

How would a stroke at the subthalamic nucleus manifest?

*Contralateral Hemiballisum* - wild, involuntary, large-amplitude, flinging movements of the proximal limbs on one side of the body - This is because the Subthalamic nucleus plays a role in inhibiting the Thalamus to prevent movement... So damage to the subthalamic nucleus would cause this inhibitory signal to disappear and then uncontrolled motion could occur

Nitroprusside can cause what type of Toxicity?

*Cyanide Toxicity* (it releases cyanide) - Nitroprusside is metabolized in the body to release Nitric Oxide and Cyanide

What amino acid is essential in a patient with homocystinuria d/t Cystathione synthase?

*Cysteine*

What agar is used to culture Corynebacterium Diphtheriae?

*Cysteine-Tellurite agar* - the colonies grow black - C. Diphtheriae can also be cultured in Loefflers medium

What is the Bacillus Anthracis capsule made of?

*D-glutamate*

What are the manifestations of Tabes Dorsalis?

*D/t degeneration of nerve fibers in the dorsal column of the spinal cord and dorsal nerve roots* - Common Manifestations: --- *Sensory Ataxia* (wide-based gait and loss of equilibrium when the patients eyes are closed - d/t damaged lower extremity proprioception) --- *Absent deep tendon reflexes* (d/t damaged dorsal nerve roots) --- *Lancinating pains* - sharp, stabbing pains that may last minutes or hours; unknown cause

In prokaryotes, during DNA replication, what enzyme is responsible for removing the RNA primer

*DNA Pol I* It has 5-3 polymerase activity, 3-5 exonuclease activity, and 5-3 exonucleae activity (this also removes the RNA primer)

Decorticate vs. Decerebrate:

*Decorticate* - (Flexor posturing) - flexion of upper extremities and extension of lower extremities --- D/t lesion above the red nucleus causing a loss of descending inhibition of the red nucleus and subsequent hyperactivity of upper limb flexors *Decerebrate* - (Extensor posturing) - extension of upper and lower extremities --- D/t lesion at or below the red nucleus causing a loss of descending excitation to the upper limb flexors, and thus a predominance of extensors NOTE: The red nucleus is in the midbrain tegmentum / Pons

What is the most characteristic biochemical change seen in Huntingtons?

*Decreased GABA* d/t loss of GABA-containing neurons

What is the main thing that is defective in Rickets? and what is it due to?

*Defective mineralization of osteoid due to Vitamin D deficiency*

What is the characteristic finding on the mitral valve of someone who has Rheumatic mitral valve stenosis?

*Diffuse fibrous thickening and distortion of the mitral valve leaflets along with commissural fusion at the leaflet edges*

What 2 substances will accumulate when methotrexate is used?

*Dihydrofolate (DHF)* and also normal *Folic Acid*

Of the common blood pressure medications, which class can cause peripheral edema as a side effect?

*Dihydropyridine Ca Channel blockers* (-pine) - The side effects of these are: headache, flushing, dizziness, and *peripheral edema* - They cause peripheral edema because they preferentially dilate the precapillary vessels (arteriolar dilation), which leads to increased capillary hydrostatic pressure and fluid extravasation into the interstitium (Note this can be balanced by addition of an ACE inhibitor or ARB because these cause post capillary vasodilation)

What is the pathogenesis in the formation of a Zenker Diverticulum?

*Diminished relaxation of the cricopharyngeal muscles* during swallowing results in increased intraluminal pressure in the oropharynx. This may eventually cause the mucosa to herniate through a zone of muscle weakness in the posterior hypopharynx, forming a *Zenker (false) diverticulum* - This presents in elderly patients with oropharyngeal dysphagia, halitosis, regurgitation, and recurrent aspiration

Psych terms: Displacement vs. Transference:

*Displacement* - A person expresses unacceptable feelings meant for *someone in their present life toward a different, "safer" person* *Transference* - Shifting of emotions/desires associated with a *person from the past to another person in the present*

Psych phrases: Displacement vs. Projection

*Displacement* - Redirection of emotions or impulses to a neutral person or object (Man who gets yelled at by his boss, doesn't confront his boss, but instead yells at his wife) *Projection* - Attributing ones internal feelings to others (ex: guy who wants to cheat on his wife, then accuses his wife of cheating) (ex: Kid who is mad at his parents for getting divorced, starts to act different and says that his parents are mad at him)

Dysplasia vs. Metaplasia vs. Anaplasia vs Neoplasia:

*Dysplasia* - disordered, non-neoplastic growth *Metaplasia* - switching from one differentiated cell type to another *Anaplasia* - complete lack of differentiation of cells in a malignant neoplasm *Neoplasia* - uncontrolled, clonal proliferation of cells (can be malignant or benign)

What can cause an elevated B-HCG in preggo and what can cause a low HCG?

*Elevated HCG* = Multiple gestations, Hydatidiform mole, choriocarcinoma, Down Syndrome *Low HCG* = ectopic/failing pregnancy, Edwards syndrome, Patau Syndrome

How does septic shock lead to lactic acidosis?

*End-organ hypoperfusion* in septic shock impairs tissue oxygenation and *decreases oxidative phosphorylation*, leading to a buildup of NADH and shunting of pyruvate to lactate following glycolysis

Aqueous humor is produced by______________?

*Epithelial cells of the Ciliary Body*

What does Amphotericin B bind to in fungus?

*Ergosterol* of fungal cell membranes - It can also bind to cholesterol in humans to a lesser degree and cuase toxicity in human tissue - The most important side effects = Nephrotoxicity, Hypokalemia, Hypomagnesemia

Where does Parvovirus B19 replicate?

*Erythrocyte precursors* in the bone marrow (Not other bone marrow precursors!!!)

Baby girl with ambiguous genitalia and clitoromegaly, with a mom who had voice deepening and facial hair growth during pregnancy, indicates what?

*Fetal-Placental Aromatase deficiency* - Maternal virilization occurs d/t transfer of excess androgen into maternal circulation - You can also rule out 21-hydroxylase and 11B-hydroxylase b/c there are no salt/fluid abnormalities

What is the liver microscopy findings of Hepatitis B?

*Finely granular, diffusely homogenous, pale eosinophilic cytoplasm ("ground-glass" hepatocytes)*

In the setting of Left ventricular heart failure, why does transudated fluid in the lungs cause dyspnea?

*Fluid accumulation in the lung interstitium results in decreased compliance* - "The presence of fluid in pulmonary interstitium causes distortion (swelling) of the affected tissue, increasing resistance to movement (decreased lung compliance)" - "Dilution of surfactant by edematous fluid increases surface tension, reducing compliance and making alveoli more prone to collapse"

What are the histology findings of a Juvenile pilocytic astrocytoma?

*GFAP+* - Spindle cells with hair-like glial processes, mixed with Rosenthal fibers (eosinophilic corkscrew fibers) and granular eosinophilic bodies - This tumor is the most common in childhood... It can arise in the cerebellum, brainstem, hypothalamic region, or optic pathways - It is commonly seen as a cystic tumor in the cerebellum

What glucose transporter is regulated by insulin, and where it it located?

*GLUT-4* - This is in the cytoplasm, but in response to insulin, will translocate to the plasma membrane It is on muscle and adipose tissue (it allows for uptake of glucose into these tissues in response to insulin - think for energy storage)

What is Biliary sludge and what causes it to form?

*Gallbladder hypomotility* causes bile to become concentrated, promoting precipitation and accumulation of particulate material - This forms a *viscous biliary sludge* that can cause transient bile duct obstruction (biliary colic) and promote cholesterol gall stone formation

What type of reaction occurs in the activation of factors II, VII, IX, and X, in which Vitamin K is a cofactor?

*Gamma-carboxylation* - Vitamin K is an essential cofactor for gamma-glutamyl carboxylase, which carboxylates factors II, VII, IX, X

Summarize the 2 types of Gastric adenocarcinoma in 1 sentence each:

*Gastric Adenocarcinoma* - *Intestinal type* - forms a solid mass that projects into the stomach lumen and is composed of glandular-forming cuboidal or columnar cells - *Diffuse type* - infiltrates the stomach wall and displays signet-ring cells on light microscopy

Where in the respiratory epithelium do Goblet cells end and Club cells start?

*Goblet cells* - mucus-secreting cells from the trachea to the larger bronchioles *Club cells* - surfactant-like fluid secreting cells from the proximal bronchioles to the respiratory bronchioles

What system acts as a negative feedback to regulate and maintain muscle tension (during contraction)? And what system monitors muscle length (during stretch)?

*Golgi tendon system* - is a feedback system that monitors and maintains muscle force (during active contraction *Muscle spindle system* - is a feedback system that monitors muscle length (during stretch) (this is commonly tested via testing deep tendon reflexes)

What is another name for Wegner Granulomatosis ?

*Granulomatosis with Polyangiitis* ("C disease = weCner")

What 4 conditions can cause target cells?

*H*bC disease, *A*splenia, *L*iver disease, *T*halassemia "*HALT* said the hunter to his target"

What drug can be given to an elderly person with infection related delirium to improve her agitation and psychosis associated with Delirium?

*Haloperidol* - A low dose of a high-potency antipsychotic is the medication of choice to treat the behavioral and psychotic manifestations of delirium *Dont use a benzo!!!* - they can worsen confusional states, especially in an elderly person

What is a Hamartoma? And, what is the most common type?

*Hamartoma* is an excessive growth of a tissue type native to the organ of involvement - The lung is the most common location - *Lung hamartomas* often contain islands of mature hyaline cartilage, fat, smooth muscle and clefts lined by respiratory epithelium - Lung Hamartomas usually present as asymptomatic, peripherally located "coin lesions" in patients 50-60 years old

What is Haptoglobin?

*Haptoglobin* is a serum protein that binds to free Hemoglobin and promotes its uptake by the reticuloendothelial system - Haptoglobin levels decrease when significant quantities of Hemoglobin are released into circulation, as occurs with intravascular hemolysis - *Decreased serum Haptoglobin* level will be seen in conditions that cause *intravascular hemolysis* - Binding of Haptoglobin to circulating hemoglobin reduces renal excretion of free hemoglobin, which can help prevent tubular injury NOTE: this is NOT Hepcidin... Hepcidin is an acute phase reactant that decreases iron absorption and iron release in anemia of chronic disease

What is the only virus that gets it envelope from the host cell nuclear membrane (as opposed to the plasma membrane)?

*Herpesvirus family*

If someone is deficient in Fructokinase, what enzyme is able to take over and work in the metabolism of Fructose?

*Hexokinase* - In fructokinase deficiency, hexokinase takes over the role of fructose metabolism, converting dietary fructose into fructose-6-phosphate

What are the 3 high potency 1st gen Antipsychotics, and what are the 2 low potency?... What side effects are more pronounced in each?

*High Potency* = *Trifluoperazine, Fluphenazine, Haloperidol* ("Try Fly High") --- SE: More Neuro (extrapyramidal) *Low Potency* = *Chlorpromazine, Thioridazine* --- SE: More Anticholinergic (dry mouth), antihistamine (sedation), a1-block (orthostatic hypotension)

Describe the concept of blood/gas partition coefficient in relation of gaseous drugs

- The onset of action of a gas anesthetic depends on its solubility (blood/gas partition coefficient) - Drugs with high blood/gas partition coefficient are more soluble in the blood, demonstrate slower equilibration with the brain, and have longer onset times NOTE: In pic: Nitrous oxide has a low blood/gas partition coefficient, and Drug A has a high blood/gas partition coefficient

What is a severe side effect of Halothane?

*Highly fatal fulminant hepatitis* - This may not be noticed until days after use with gradual deterioration - Causes a hepatocellular pattern of injury - widespread centrilobular necrosis and inflammation of the portal tracts and parenchyma (it is indistinguishable from viral hepatitis) - Typically presents with a fever, anorexia, nausea, myalgias, arthralgias, and a rash... but tender hepatomegaly and jaundice can be seen if there is widespread liver inflammation - Labs = elevated serum Aminotransferase, prolonged prothrombin time, leukocytosis, and eosinophilia (the prolonged PT is d/t failure of synthesis of factor VII) - Decreased albumin most likely will NOT be seen b/c the half life of albumin is 20 days

What do patients with adult-type coarctation of the aorta commonly die from?

*Hypertension-associated complications* (including left ventricular failure, ruptured dissecting aortic aneurysm, and intracranial hemorrhage) - These pts are at risk for ruptured intracranial aneurysms b/c the increased incidence of congenital berry aneurysms of the Circle of Willis as well as aortic arch HTN

Narcolepsy (with cataplexy) is usually caused by a deficiency in what peptides?

*Hypocretin-1 & Hypocretin-2* - These are produced in the lateral hypothalamus, and function to promote wakefulness and inhibit REM sleep-related phenomena

What is a major adverse effect of Sulfonylureas? (and what are the names of these drugs!!!)

*Hypoglycemia* - b/c they increase insulin secretion by B-cells independent of blood glucose concentration

What are the classic electrolyte lab findings for Primary Adrenal Insufficiency?

*Hyponatremia* *Hyperkalemia* *Non-anion gap metabolic acidosis* (d/t decreased H secretion) *Hyperchloremia* (this is to maintain the extracellular electrical neutrality d/t the decrease in bicarb, which is low d/t the elevated H+)

What receptor does the drug *Abciximab* bind to?

*II*b times *III*a equals "ab*SIX*imab

What cytokine is important in Giant cell (temporal) arteritis?

*IL-6* - Cell mediated immunity is the primary mechanism underlying giant cell arteritis (because it is a granulomatous vasculitis) - IL-6 is an important driver of this process and closely correlates with severity of symptoms

What 2 cytokines activate NK cells?

*INF-g* - secreted by Th1 cells *IL-12* - secreted by macrophages NOTE: NK cells are CD56+

How does a confidence interval help conclude if a study is statistically significant or not?

*If the confidence interval does NOT include the null value, then the result is statistically significant* - If it crosses the null value, then the result is not statistically significant - For odds ratio and relative risk, the null value is 1 b/c these stats are ratios (ie, RR = 1, represents no difference in risk between groups) - If the parameter is a difference (like the difference in blood pressure between 2 groups) then the null value is 0

What are the 2 most important opsonins?

*IgG & C3B* NOTE: Although IgM can be a potent stimulator of C3b opsonization via activation of the complement cascade, there are no receptors on macrophages for the Fc portion of IgM and it does not directly enhance phagocytosis

What class of Antibody is in Anti-Rh(D) immune globulin?

*IgG* NOTE: Administration of Anti-Rh(D) IgG antibodies during pregnancy does NOT cause significant transplacental fetal hemolysis b/c the quantity of Anti-Rh(D) administered is very small compared to that produced in a typical immunologic reaction

First line treatment for CML w/ the Philadelphia chromosome is?

*Imatinib* - is a potent inhibitor of the BCR/ABL protein tyrosine kinase

What is another name for Type 1 hypersensitivity?

*Immediate Hypersensitivity* - Although this is technically Antibody mediated... the term "Antibody-mediated hypersensitivity" refers to a Type 2 hypersensitivity (like a hyperacute transplant rejection).... at least according to Uworld?

In-frame deletion vs. frame shift deletion

*In-frame deletion* = one or more complete codons (triplets) are removed, which does not affect the reading frame of subsequent codons *Frame shift deletion* = deletion of a number of bases that is not divisible by 3

What is the underlying cause of Albinism?

*Inability to produce melanin*

How does a Thiazide diuretic influence blood Calcium?

*Increase blood calcium* How I think about it: Thiazides block Na/Cl transporter in the distal convoluted tubule. So since the body cannot reabsorb Na here, it messes up and reabrorbs Ca instead

What type of epithelia is in the ovary?

- The ovary has simple cuboidal epithelium, which is able to rapidly proliferate to repair ovulatory surface defects (such as, from ovulation)

What can cause an increased AFP in pregnancy and what can cause a low AFP?

*Increased AFP* = Dating error, anencephaly, Open neural tube defects (except spina bifida will have normal AFP) *Low AFP* = Downs Syndrome & other Chromosome abnormalities

What 3 stains can be used for *Cryptococcus Neoformans*? And, what is 1 more diagnostic test?

*India ink Stain* - for CSF sample... ("Budding yeast with peripheral clearing / "halo") *Mucicarmine* (Red) / *Methenamine* (Silver) - from bronchoalveolar lavage... ("Budding yeast with thick capsule") - ALSO - *Latex agglutination* (in serum or CSF) can be used to dx Crypto

Describe the position of the groin hernias: Femoral, Indirect, Direct:

*Indirect* - Contents protrude through the deep inguinal ring & travel LATERAL to the inferior epigastric vessels *Direct* - Contents protrude through Hesselbach triangle & travels MEDIAL to the inferior epigastric vessels *Femoral* - Contents protrude through the femoral ring & Travels inferior to the inguinal ligament and MEDIAL to the FEMORAL vessels

3 Groin hernias: Indirect, Direct, Femoral... Pathophys and anatomy of each:

*Indirect* - d/t *Patent Processus Vaginalis* (Content protrudes through the deep inguinal ring, and travels *lateral to inferior epigastric vessels*) *Direct* - d/t *Weakness of transversalis fascia* (Content protrudes through hesselbach triangle and travels *medial to inferior epigastric vessels*) *Femoral* - d/t *weakness of the proximal femoral canal* (Contents protrude through the femoral ring, and travels *inferior to the inguinal ligament*) NOTE: The Rectus Abdominus muscle is the medial border of Hesselbachs triangle, while the transversalis fascia forms the floor of the triangle - Direct hernias are only covered by external spermatic fascia (b/c they only pass through the superficial inguinal ring) - Indirect hernias are covered by all 3 spermatic fascia layers

What test can be used to distinguish E. Coli from Enterobacter Cloacae?

*Indole test* - E. Coli is *Indole Positive* - Enterobacter is *Indole Negative* (Enterobacter is another lactose-fermenting gram-negative rod that is a common cause of UTIs in women)

What is the mechanism of the Cholesterol lowering drug: Ezetimibe?

*Inhibits CHOLESTEROL absorption at the brush border of the small intestine* - Thus, the amount of dietary cholesterol reaching the liver decreases... To compensate, the liver increases LDL receptor expression, which draws cholesterol out of the circulation

What is the mechanism of Ribavirin?

*Interferes with the duplication of viral genetic material* - Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase

What are the 2 renal conditions that can be associated to NSAIDs?

*Interstitial nephritis* (this can be acute or chronic) --- Acute = acute drug-induced hypersensitivity --- Chronic = d/t NSAIDS concentrating in the renal medulla and papillae, uncoupling oxidative phosphorylation, and damaging tubular/vascular endothelial cells *Papillary Necrosis* - necrosis of renal papillae (from decreased prostaglandin synthesis and constriction of the medullary vasa recta)

What is the most likely cause of a patient with prolonged neutropenia presenting with a fever, chest pain, cough, dyspnea, and hemoptysis, that is not responsive to Abx - and grows a mold on culture?

*Invasive pulmonary aspergillosis*

What is Isolated systolic hypertension? And, what is the most common cause?

*Isolated systolic HTN (ISH)* = Systolic BP > 140, with a diastolic BP < 90 It is d/t age-related stiffness and decrease in compliance of the aorta and major peripheral arteries NOTE: ISH is responsible for 60%-80% of the HTN cases in ppl > 60 years old

What are the Prostaglandins used to treat Open-Angle glaucoma? And, how do they work?

*Latanoprost & Bimatoprost* (anything that ends in "-prost") - These decrease the collagen content in the uveoscleral outflow pathway and *increase outflow* of aqueous humor

What is the measure that is used to assess fetal lung maturity?

*Lecithin/Sphingomyelin (L/S) ratio* - By 35 weeks gestation, the L/S ratio averages 2:1 or higher - which indicates lung maturity NOTE: Another name for Lecithin is Phosphatidylcholine

What should be given to reverse Methotrexate toxicity?

*Leucovorin (Folinic Acid)* - this serves as a reduced form of folic acid that does not require the action of dihydrofolate reductase

What 2 things can be seen on liver biopsy as "yellow-brown accumulations"? And, how can they be distinguished?

*Lipofuscin* - a brown pigment that is the byproduct of the turnover of peroxidized lipids ("wear and tear") that is commonly present in hepatocytes *Hemosiderin* - an iron-storage complex inside macrophages of the reticuloendothelial system that appears yellow-brown (usually seen in Kupffer cells in the liver) - Prussian-blue stain can identify Hemosiderin (and iron) and stain it blue

What specific cells does Shigella Invade?

*M (microfold) cells* that overlie the Peyers Patches - These are the cells that are at the base of mucosal villi within a Peyer Patch, and sample gut lumen contents and transfer antigens to their basal lamina to present the antigen to macrophages and lymphocytes - Shigella invades the M cell via endocytosis, lyses the endosome it was contained in, multiplies, and then spreads laterally into other epithelial cells

Multiple Myeloma is d/t a malignant proliferation of what? And, what are some classic clinical features?

*Malignant proliferation of plasma cells in the bone marrow* - a bone marrow sample of greater than 30% plasma cells is diagnostic for multiple myeloma - Clinical features: --- *Normocytic and normochromic anemia* (d/t bone marrow infiltration and replacement by malignant cells) --- *Bone pain w/ hypercalcemia* (d/t activated osteoclasts) --- *Elevated serum protein* --- *Increased risk of infection* (monoclonal antibodies lack antigenic diversity) --- *Primary AL amyloidosis* (d/t accumulation of immunoglobulin light chains) --- *Proteinuria leading to renal failure*

If someone has "cystic medial degeneration" what condition should you think of?

*Marfans Syndrome* Cystic medial degeneration - consists of Myxomatous changes with pooling of proteoglycans in the media layer of large arteries (Myxomatous changes = pathologic weakening of connective tissue)

What type of acid/base imbalance does vomiting cause?

*Metabolic alkalosis* d/t net loss of gastric acid

What stage of meiosis are a womans eggs arrested in at ovulation (prior to fertilization)?

*Metaphase of meiosis II* These cells are called secondary oocytes They remain in metaphase II until fertilization occurs *an egg MET a sperm*

What is the most common malignant neoplasm of the adult liver?

*Metastasis* are the most common malignant neoplasms of the adult liver (20x more common than hepatocellular carcinoma) - Patients with liver mets typically have multiple nodules, often resulting in hepatomegaly

What landmark in the pons does the Trigeminal nerve exit?

*Mid-pons* at the level of the *Middle cerebellar peduncle*

During delivery, what is cut during a *Midline Episiotomy* and during a *Mediolateral episiotomy*

*Midline Episiotomy* - vertical incision from the posterior vaginal opening to the *perineal body* *Mediolateral episiotomy* - cuts the transverse perineal muscle

What diuretic can improve survival in patients with CHF and decreased ejection fraction?

*Mineralocorticoid receptor antagonists (Spironolactone & Eplerenone)* - These drugs block aldosterone binding in the cortical collecting tubule *AND* they are able to block the deleterious effect on aldosterone on the heart - causing regression of myocardial fibrosis and improvement in ventricular remodeling - THUS, they improve survival in patients with CHF and decreased ejection fraction

What is the most common Nephrotic syndrome in children?

*Minimal change disease* d/t T-cell dysfunction which produces glomerular permeability factor, which causes podocyte fusion and decreases the anionic properties for the glomerular basement membrane - No change on light microscopy - Effacement of foot processes on electron microscopy

What is the most common predisposing condition for native valve infective endocarditis (IE) in developed nations?

*Mitral valve prolapse with regurgitation* - NOTE: Rheumatic heart disease remains a frequent cause of Infective endocarditis in developing nations

What drug is first line in the treatment of Narcolepsy?

*Modafinil* - a non-amphetamine stimulant - 1st line b/c it is well tolerated, effective, and drug abuse is rare --- Amphetamines are second line ---

What would be found in the stool of a person infected with Vibrio cholerae or Enterotoxigenic E. Coli?

*Mucus and some sloughed epithelial cells, but NO fecal leukocytes or red cells* Both Vibrio Cholerae and Enterotoxigenic E. Coli cause a purely toxin-mediated watery diarrhea (they do NOT invade the mucosa or cause enterocyte death) - The toxins secreted by these organisms modify electrolyte handling by enterocytes, but do not cuase cell death, so no erythrocytes or leukocytes will be noted on school microscopy

How can multiple myeloma manifest in the kidney?

*Myeloma cast nephropathy* - d/t excess excretion of free light chains (Bence Jones Proteins)... These proteins are filtered by the glomerulus in small amounts and then reabsorbed in the tubules. When levels exceed reabsorptive capacity, light chains precipitate and form casts that cause tubular obstruction and epithelial injury, leading to impaired renal function - On light microscopy, numerous large, glassy casts that stain intensely eosinophilic can be seen

What is the most common complication of Statin use?

*Myopathy* - Also beware of hepatitis

What is the main mechanism of Phencyclidine (PCP)?

*N-methyl-D-aspartate* receptor antagonist

What type of acid/base imbalance does diarrhea cause?

*NORMAL anion gap metabolic acidosis*

In primary osteoperosis (not due to another medical condition), what are the lab findings for serum calcium, phosphate, PTH, and Alk Phos?

*NORMAL!!!!* - This is how you can distinguish osteoporosis from osteomalacia (defective mineralization of osteoid d/t vit D deficiency) b/c osteomalacia would have low calcium, low phosphate, and high PTH and high Alk phos

What are Neurophysins?

*Neurophysins* are carrier proteins for Oxytocin and Vasopressin - they act as chaperone molecules as Oxytocin and Vasopressin are shuttled toward the nerve terminals in the posterior pituitary NOTE: Point mutations in Neurophysin II underlie most cases of hereditary hypothalamic Diabetes Insipidus, d/t insufficient AHD release

A CBC w/ diff will show increased level of what cell in a pt taking high-dose prednisone?

*Neutrophils* - Corticosteroids decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation

What reaction does this enzyme catalyze: *Phenylethanolamine-N-Methyltransferase*

*Norepinephrine --> Epinephrine* This is upregulated by *cortisol* and occurs in the *adrenal medulla*

What conditions present with elevated prenatal AFP levels?

*Omphalocele, & Gastroschisis* *Neural tube defects* (except spina bifida where AFP is normal)

What is the most common cause of lung abscesses? And, what are some risk factors for this occurrence?

*Oropharyngeal aspiration* is the most common cause of lung abscess - Risk factors include conditions associated with *loss of consciousness* or *dysphagia*, such as: alcoholism, drug overdose, seizure disorder, prolonged anesthesia, and severe neuro diseases

osteoblastic vs. osteolytic bone metastases

*Osteoblastic (Sclerotic)* = D/t osteoblasts, indicates a more indolent course *Osteolytic (lucent)* = D/t osteoclast stimulation, tend to represent aggressive cancer

What is the most important virulence factor in E. Coli with regards to it establishing a UTI?

*P Fimbriae* - because it allows adhesion to uroepithelium

What 5 tumors can have Psammoma Bodies?

*P*apillary carcinoma of thyroid *S*erous papillary cystdenocarcinoma of ovary & endometrium *M*eningioma Malignant *M*esothelioma *PS*a*MM*oma

How does lateral medullary syndrome present?

*PICA STROKE* - Spinothalamic - contralateral pain/temp - Sympathetic - Horners syndrome - Nucleus Ambiguus (CN IX, X) - hoarseness, dysphagia - Also has parts of CN 5 & 8 --- CN 5 - loss of ipsilateral pain/temp --- CN 8 nystagmus/vertigo, N/V

When determining alveolar ventilation status, what is the most important indicator?

*PaCO2* So this means, that *when determining if a person is breathing fast or slow, you should pay most attention to PaCO2* (not oxygen, because other things can affect oxygen loading/unloading, and oxygen can become diffusion limited in disease states like fibrosis/emphysemia etc.) ----FROM ANOTHER QUESTION---- - Also, it is very rare for CO2 to ever be diffusion limited... This is because the diffusion capacity of CO2 across the respiratory membrane is 20x greater than O2. So CO2 levels are not nearly as affected as O2 in diffusion limited states (like pulmonary fibrosis or emphysemia)... *So think of CO2 as always being perfusion limited, and never diffusion limited*

Between Parasympathetic/Sympathetic, which deals with Accommodation?

*Parasympathetic* - The ciliary muscle contracts, which reduces tension on zonular fibers, and allows the lens to become more spherical (allowing someone to see close objects) - The ciliary muscle is under *Parasympathetic control* from the Edinger-Westphal nucleus / ciliary ganglion

Parathyroid cells vs. Parafollicular cells

*Parathyroid cells* - from the 3rd (inferior parathyroid) and 4th (superior parathyroid) branchial pouch --- *Secretes PTH* *Parafollicular Cells* - from the Neural Crest --- Secretes Calcitonin (which puts Ca back into bone and lowers blood Ca)

What molecule can be produced by squamous cell lung carcinoma?

*Parathyroid hormone-related peptide (PTHrP)* - This closely resembles PTH, and acts similar to PTH, and increases bone resorption and decreased renal excretion - This leads to the condition known as *Humoral Hypercalcemia of malignancy* - Serum will show high PTHrP, but low PTH NOTE: Other tumors that can produce PTHrP are: Renal & Bladder, and Breast & Ovarian

Describe the clinical course of Parvovirus B19 vs. Roseola Infantum (HHV-6)

*Parvovirus B19:* - 1. nonspecific prodrome... - 2. "slapped-check rash" after the prodrome symptoms have resolved... - 3. lacy, reticular rash follows, spreading over the trunk and extremities *Roseola Infantum (HHV-6):* - 1. Very high fever for 4 days - 2. Diffuse lacy body rash that spares the face after the fever has subsided (rash usually starts at trunk and spreads to face & extremities) (Usually infects children 6months - 2 years old)

Which is more common: Patent foramen ovale or Atrial septal defect?? And, what process causes each?

*Patent foramen ovale is more common than atrial septal defect* (the ovale can be patent in 25% of adults) - Patent foramen ovale is caused by incomplete fusion of the septum primum and septum secundum (after delivery) - ASD is caused by aplasia of the septum primum or septum secundum (secundum defects are more common)

How is the mechanism of action different for Vancomycin and Penacillins?

*Penacillins* - D-Ala-D-Ala structural analog that binds penicillin-binding proteins (transpeptidases) and *block transpeptidase cross-linking of peptidoglycan in cell wall* *Vancomycin* - *Inhibits cell wall peptidoglycan formation* by binding D-Ala-D-Ala portion of cell wall precursors

How does ventilation and perfusion change from the apex to the base of the lung

*Perfusion greatly increases from the apex of the lung to the base; ventilation increases slightly from the apex to the base* - for this reason, the ventilation/perfusion ratio decreases . in the lung from apex to base

What are the characteristic findings of *diffuse esophageal spasm* on esophageal manometric study?

*Periodic, simultaneous, and non-peristaltic contractions of the esophagus d/t impaired inhibitory innervation within the esophageal myenteric plexus* - Pts typically present with liquid/solid dysphagia and chest pain d/t inefficient propulsion of food into the stomach

Where does the oxidation of very long chain fatty acids take place?

*Peroxisomes* - Very long chain fatty acids & certain branched-chain fatty acids cannot undergo mitochondrial Beta-oxidation, and are thus metabolized in peroxisomes

What is Phenoxybenzamine? And, what is it used for?

*Phenoxybenzamine* is an irrereversible alpha1 and alpha2 receptor antagonist - It is used in the treatment of pheochromocytoma to block the norepinephrine stimulated vasoconstriction (It is good for this since it is an IRREVERSIBLE antagonist... so even very high concentrations of norepinephrine cannot overcome its effects)

Drug: Phentolamine

*Phentolamine* is a reversible, competitive alpha antagonist used in the management of a catecholamine-induced hypertensive crisis (like pheochromocytoma, MAO inhibitor toxicity, cocaine intoxication) NOTE: But, since it is reversible, high doses of Norepi can overcome its effects!!!

What enzyme is upregulated by cortisol to increase epinephrine synthesis?

*Phenylethanolamine-N-Methyltransferase*

In addition to headache, scalp tenderness, jaw claudication, and sudden vision loss... What is one other manifestation of Temporal arteritis that presents in more than 50% of patients?

*Polymyalgia rheumatica* occurs in more than half of patients with temporal arteritis... - It is characterized by neck, torso, shoulder, and pelvic girdle pain and morning stifness... Fatigue, fever, and weight loss may also occur

What does Periodic Acid-Schiff stain for?

*Polysaccharides*, mucosubstances, basement membrane, and *glycogen* (when combined with Diastase) - it is specifically used for the glycoprotein cell wall of Tropheryma Wippelii

What is *Porcelain gallbladder*? And, a pt with this is at increased risk for what cancer?

*Porcelain gallbladder* is a potential manifestation of chronic cholecystitis and is often found in association with multiple gallstones. It is d/t dystrophic intramural deposition of calcium salts in the setting of chronic inflammation. - Porcelain gallbladder is associated with an increased risk of *Adenocarcinoma* of the gallbladder

T-cell development... Positive vs. Negative Selection:

*Positive Selection* - Only T cells expressing a TCR that is able to bind self MHC are allowed to survive & those cells expressing a TCR that is not specific for self MHC are signaled for elimination by apoptosis --- Occurs in the thymic cortex, and involves interaction of T cells with Thymic cortical epithelial cells *Negative Selection* - (Occurs after positive selection) The process by which T cells possessing TCRs that bind with high affinity to self antigen or self MHC class I or II are eliminated by apoptosis... this serves to eliminate T cells that may be overly autoreactive against self antigens --- Occurs in the thymic medulla and involves interaction of the developing T cells with thymic medullary epithelial and dendritic cells

What is the most common location for an anal fissure?

*Posterior midline distal to the dentate line* - likely d/t decreased blood flow to this area

What is the power of a study?

- The power of a study is its ability to detect a difference between groups when such a difference truly exists - Power is related to type II error (B), which is the probability of concluding there is no difference between groups when one truly exists - Power = 1 - B (type II error)

Post-MI Pericarditis: *Postinfarction fibrinous pericarditis* vs. *Dressler's syndrome*

*Postinfarction fibrinous pericarditis* - Occurs 1-4 days after an MI, and is d/t inflammation from the transmural necrosis, affecting the adjacent visceral and parietal pericardium (usually the inflammation is localized to the region of the pericardium overlying the necrotic myocardial segment) *Dressler's syndrome* - "Late-onset post-MI pericarditis" - Occurs several weeks after an MI, and is d/t autoimmune polyserositis provoked by antigens exposed or created by infarction of cardiac muscle (so pericardium is usually diffusely inflammed) - BOTH of these typically respond to Aspirin, or NSAIDS/glucocorticoids

What bursitis is associated with repetitive anterior knee trauma (ex: kneeling a lot)

*Prepatellar bursitis* - Usually associated with anterior knee pain - The prepatellar bursa is located between the patella and the overlying skin - Bursitis will have painful & possible decreased active range of motion, but normal PASSIVE range of motion (b/c there is less pressure being put on the bursa)

What is the pathogenesis to Creutzfeldt-Jakob disease?

*Prion protein (PrP)* is normally found in neurons and has an a-helical structure. It the conversion of a-helix into B-pleated sheet occurs, the protein becomes resistant to proteases - Accumulation of this abnormal protein in grey matter is thought to cause prion disease - Affected grey matter undergoes *Spongiform change*. Vacuoles form within the cytoplasm of neurons and neutrophils. Later, they grow bigger and form cysts, involving larger areas of brain tissue

What accounts for the fast-onset and rapid-recovery of Propofol when given IV?

*Propofol is highly lipophilic* - Following bolus infusion, it is rapidly cleared by the plasma and preferentially distributed to organs receiving high blood flow (like the brain). This initial distribution accounts for the rapid onset of sedation seen with its administration. - Over time, Propofol is redistributed to organs receiving less blood flow (fat, muscles, etc.). Because the site of Propofol is the brain, redistribution accounts for the rapid termination of the drug

What is the virulence factor of Strep Pyogenes that is responsible for inhibiting Phagocytosis & complement activation?

*Protein M*

What class of drug (and names) block the final common pathway of gastric acid secretion from parietal cells?

*Proton Pump Inhibitors* - these block the H/K-ATPase proton pump at the apical membrane of the parietal cell - PPIs end in "*-prazole*" (Omeprazole, Lansoprazole) - Since these drugs block the final common pathway, they inhibit acid secretion no matter the stimulus (Vagus, Histamine, Gastrin)

What 2 portions of the nephron are most susceptible to ischemic damage in Acute tubular necrosis?

*Proximal Tubule* & *Medullary segment of the thick ascending limb* - This is b/c they participate in active (ATP-consuming) transport of ions and have high oxygen demand

How does Glioblastoma Multiforme present histologically?

*Pseudopalisading tumor cells around areas of necrosis and hemorrhage*

Psych Phrases: Reaction formation vs. Sublimation

*Reaction formation* - Replacing a (subconscious) warded-off idea/feeling with emphasis on its opposite (ex: guy who has lustful thoughts enters a monastery)(ex: Woman who cares for the child of her husbands and his ex-wife, resents having to care for the child, but acts like she loves him so much) *Sublimation* - Replacing an unacceptable wish with a course of action that is similar to the wish but socially acceptable (Teenager is mad and has aggressive urges towards his parents, but channels it into excelling in sports)

What is the most notorious side effect of Amphotericin B?

*Renal Toxicity* - Amphotericin B can cause renal vasoconstriction, and reduce GFR... It can also act as a direct toxin on renal epithelial cells, leading to acute tubular necrosis, renal tubular acidosis, and electrolyte disturbances *Severe hypokalemia and hypomagnesemia* can occur - with many patients needing supplementation

What is detected by Reverse Transcription PCR?

*Reverse Transcription PCR is used to detect and quantify levels of mRNA in a sample* It uses reverse transcription to create a complementary DNA template that is then amplified using the standard PCR procedure

How does Rifiximin, and Lactulose, each work in treating hepatic encephalopathy?

*Rifiximin* - A nonabsorbable abx - Alters GI flora to *decrease intestinal production and absorption of Ammonia* *Lactulose* - gets catabolized by intestinal bacteria to short chain fatty acids, which lower the intestinal pH and *increase conversion of ammonia to ammonium*

Right-sided vs. Left-sided colon cancer presentation:

*Right Sided* - tend to grow as large, bulky masses that protrude into the colonic lumen d/t the relatively large caliber of the ascending colon. They are more likely to bleed, and more likely to cause Iron deficiency anemia *Left Sided* - tend to be smaller. Often infiltrate the wall of the colon, encircling it and narrowing the lumen - and are therefore more likely to cause obstruction, and patients generally have altered bowel habits

How does the location of a colon cancer (adenocarcinoma) differ its clinical presentation?

*Right sided cancer* - usually presents with occult bleeding and symptoms of iron deficiency anemia (fatigue, pallor), and other non-specific symptoms... Patients usually dont develop intestinal obstruction b/c the ascending colon has a larger caliber lumen than the descending colon and stool in the proximal colon is more liquid *Left sided cancer* - tends to infiltrate the intestinal wall and encircle the lumen, causing constipation and symptoms of intestinal obstruction *Rectosigmoid* - often causes hematochezia (fresh blood) *Rectal* - Tenesmus (ineffective/painful straining on defecation) and small-caliber stools

Anatomically, where is the SA and AV nodes located?

*SA node* - the junction of the right atrium and superior vena cava *AV node* - in the right atrium near the septal cusp of the tricuspid valve

Between Salmonella and Shigella... Which can produce H2S when grown on Triple sugar iron (Hektoen) agar, and which cannot?

*Salmonella* - YES H2S production - grows as a black colony *Shigella* - NO H2S production - grows as a green colony

What are 2 important *S-100* tumors?

*Schwannoma* &*Melanoma* - These are both of Neural crest origin (Also in *Langerhan cell histiocytosis*)

What is the major component of adaptive immunity against Giardia Lamblia infection?

*Secretory IgA* - Secretory IgA impairs adherence of Giardia to the intestinal brush border, and is the major component of adaptive immunity against Giardia *Conditions causing IgA deficiency predisposes patients to chronic Giardiasis (ex: IgA deficiency, X-linked agammaglobulinemia, and Common variable immune deficiency)

Describe what each iron lab test means: Serum Iron TIBC % Saturation Serum Ferritin ALSO: Ferroportin and Hepcidin

*Serum Iron* - Measure of iron in the blood *TIBC* - Indirect number of total transferrin ions in blood *% saturation* - percent of transferrin molecules that are bound by iron *Ferritin* - Reflects iron stores in macrophages and liver (Whenever Ferritin is low, the liver will recgonize this and make more transferrin molecules to go to find more iron... So any time ferritin decreases, the TIBC (aka transferrin) will increase) *Ferroportin* - The transporter that transports iron form enterocytes to the blood *Hepcidin* - Molecule released by the liver (in response to inflammation) - decreases iron absorption by degrading ferroportin, and decreases iron release from macrophages to erythroid precursors

How can Chlorthalidone cause muscle weakness & cramps?

*Significant hypokalemia can lead to muscle weakness, cramps, and possible rhabdomyolysis*

What is used to improve visualization of Liegonella? And what is required for its growth?

*Silver stain* improves Legionella Culture must be performed on buffered *charcoal yeast extract* (BCYE) agar supplemented with *L-cysteine and iron*

What cells are responsible for synthesizing the fibrous cap in an Atheroma?

*Smooth Muscle Cells* - 1st - endothelial injury, leading to expression of Surface Vascular Cell-Adhesion Molecules (VCAM) - 2nd - VCAMs allow monocytes and T-lymphocytes into the intima, where they release cytokines - 3rd - The released cytokines promote migration & proliferation of Vascular Smooth Muscle Cells - 4th - Vascular Smooth Muscle Cells then also synthesize extracellular matrix proteins (collagen, elastin, proteoglycans) that form the fibrous cap *Vascular smooth muscle cells are the only cells within the atherosclerotic plaque that is capable of synthesizing structurally important collagen and other matrix components*

What is the primary mechanism for how Nitrates relieve angina?

- The primary anti-ischemic effect of nitrates is mediated by venodilation with a decrease in left ventricular end-diastolic volume and wall stress (d/t decreased preload), resulting in decreased myocardial oxygen demand and relief of angina symptoms NOTE: nitrates do slightly cause artery dilation, but nitrates dilate the large epicardial arteries more than the small resistance vessels... Furthermore, coronary arteries in an area of flow-limited stenosis are typically dilated maximally to maintain resting blood flow, limiting the ability of nitrated to significantly increase blood flow in stenotic coronary arteries

Stress vs. Urge vs. Overflow incontinence

*Stress* - d/t decreased urethral sphincter tone and urethral hypermobility --- Sx = Leakage with coughing, lifting, or sneezing *Urge* - d/t detrusor hyperactivity --- Sx = sudden overwhelming urge to urinate *Overflow* - d/t impaired detrusor contractility and/or bladder outlet obstruction --- Sx = incomplete emptying & persistent involuntary dribbling NOTE FOR URGE: Regions in the pons and cerebral cortex partially inhibit the micturition reflex and also regulate contraction/relaxation of the external sphincter. Spinal cord lesions above the sacral region can cause a loss of higher center control of micturition and lead to detrusor hyperreflexia and urge incontinence --- This is how patients with Multiple Sclerosis can get urge incontinence

Superficial (strawberry) hemangioma vs. Cherry hemangioma

*Superficial (strawberry) hemangioma* - appears during the first weeks of life. Initially grows rapidly, then frequently regresses spontaneously by late childhood *Cherry Hemangioma* - small, red, cutaneous papules common in aging adults

What action/sensation is innervated by the Superficial peroneal nerve and Deep peroneal nerve?

*Superficial Peroneal nerve*: --- Motor = Foot eversion --- Sensory = lateral leg & dorsal/lateral foot *Deep Peroneal nerve*: --- Motor = Ankle dorsiflexion & toe extension --- Sensory = small area between the big toe and the second toe

What are the MAO inhibitors?

*T*ranylcypromine, *P*henelzine, *I*socarboxazid, *S*elegiline (MAO Takes Pride In Shanghai)

In an elderly woman with hypertension and osteoporosis, what diuretic could be most useful?

*THIAZIDE* - because they *increase calcium absorption in the distal convoluted tubule*

What nerve innervates the Stapedius muscle?

*The Stapedius Nerve (A branch of the Facial Nerve: CN VII)* - Paralysis of the stapedius muscle results in hyperacusis (increased sensitivity to sound)

What is the best location to hear an S4 heart sound? (and what is S4 associated with?)

*The apex* - It is associated with ventricular non-compliance (like *Left ventricular hypertrophy*).... The Left atrium is pushing against a stiff ventricular wall - The louder the sound, the more likely it is d/t a stiff left ventricle

What is the biggest determinant of symptom severity in a pt with Tetralogy of Fallot?

*The degree of right ventricular outflow tract obstruction* - Because this is what determines how much deoxygenated blood is being shunted from right to left, and delivered to the systemic circulation

What nerve is in close proximity to the Superior thyroid artery? What nerve is in close proximity to the Inferior thyroid artery?

*The external branch of the superior laryngeal nerve* is in close proximity to the Superior Thyroid artery (this nerve supplies the cricothyroid muscle) *The recurrent laryngeal nerve* is in close proximity to the Inferior Thyroid artery (this nerve supplies the intrinsic muscles of the larynx - except the cricothyroid)

Overuse of which of these 2 diuretics would cause Hyponatremia: Loop vs. Thiazide?

*Thiazide* - this is b/c pts taking thiazides have a normal corticomedullary concentration gradient and are better able to retain free water in response to increased ADH levels... This retention of free water, but decreased Na absorption at the distal convoluted tubule, can cause the Hyponatremia

What is the primary concern in this presentation: Fever & sore throat in pt with Graves on medication?

*Thionamide-Induced Agranulocytosis* - Thionamides = Methimazole and Propylthiouracil - These both have a rare complication of agranulocytosis - If this is suspected, the drug should be discontinued immediately, and a white blood cell count with differential obtained to confirm diagnosis

What is the main contributor to muscle wasting in a pt with a tumor/infection/underlying systemic disease?

*Tumor necrosis factor-a* - It causes appetite suppression via the hypothalamus and also increases metabolic weight

What type of hypersensitivity is an *Acute hemolytic Transfusion reaction*

*Type 2 (Antibody-mediated)* hypersensitivity - These occur minutes-hours of starting a blood transfusion and are most often d/t ABO incompatibility between the donor and recipient... Anti-ABO Abs bing to the corresponding antigens on transfused donor erythrocytes, leading to complement activation - Anaphylatoxins (C3a and C5a) cause vasodilation and symptoms of shock - Formation of the MAC leads to complement-mediated cell lysis

What single Hypersensitivity type does, "Antibody-mediated hypersensitivity" refer to?

*Type 2* (according to Uworld) - Like in a hyper-acute transplant rejection (pre-existing antibodies react to donor antigen) NOTE: Type 1, 2, and 3, however, all utilize antibodies

What enzyme is deficient in Porphyria Cutanea Tarda?

*U*roporphyrinogen *D*ecarboxylase =*U*n*D*ersized (AllAsianPeoplesUnfortunatelyUndersizedCocksFail) NOTE: Late step derangements (following Porphobilinogen (PBG) conversion) cause photosensitivity, which is thought to be d/t the accumulation of porphyrinogens that react with oxygen on excitation with UV (sun) light

What is the difference in action/effect of Unfractionated Heparin vs. Low Molecular Weight Heparin (LMWH)?

*Unfractionated Heparin* - has equal activity against Factor Xa & Thrombin (IIa) *LMWH* - has greater activity against Factor Xa, than thrombin

How would a mainstem bronchus obstruction present on X-ray?

*Unilateral pulmonary opacification and deviation of the trachea and mediastinum TOWARD the opacified lung* - An obstructive lesion in the mainstem bronchus (ex: central lung tumor in chronic smoker) can prevent ventilation of an entire lung, leading to obstructive atelectasis (alveolar collapse) and complete lung collapse.... This will pull the trachea and mediastinum structures towards it

What are the 2 substances that drive angiogenesis?

*Vascular endothelial growth factor (VEGF)* *Fibroblast growth factor (FGF)*

How does gross liver histology differ in Von Gierke dz vs. Cori dz?

*Von Gierke dz* - d/t Glycogen phosphorylase deficiency --- "Hepatic steatosis is a cardinal manifestation" *Cori Dz* - d/t debranching enzyme (a-1,6-glucosidase) deficiency --- "Hepatic fibrosis is common, but fatty infiltration is rarely seen

What type of casts are seen in Acute Pyelonephritis?

*WBC Casts* - "WBC casts are pathognomonic for pyelonephritis in the setting of UTI"

Regarding multi-compartment drug metabolism, what tissues make up the "well-vascularized peripheral compartment" and what makes up the "poorly-vascularized peripheral compartment"?

*Well vascularized peripheral compartment* = Brain, liver, kidneys, lungs *Poorly vascularized peripheral compartment* = Skeletal muscle, fat, bone - First a highly lipophilic drug will be rapidly distributed to organs with high blood flow, then over time it will redistribute to the poorly vascularized peripheral compartment (which has the highest volume of distribution for lipophilic agents)

What is a Xanthoma?

*Xanthoma* - plaque or nodule composed of lipid-laden histiocytes in skin, especially eyelids (xanthelasma) - These are indicators of hyperlipidemia REMEBER!!! - Cholestatic conditions, like obstructive biliary lesions and primary biliary cirrhosis, can result in subsequent hypercholesterolemia, and lead to formation of Xanthelasmas in the eyelids!!!

What is the most common benign liver tumor?

*cavernous hemangioma* - Microscopically = cavernous, blood-filled vascular spaces of variable size lined by a single epithelial layer - Excellent prognosis with surgical resection - Biopsy is contraindicated d/t potential hemorrhage

What is the fasting insulin level typically in a patient with polycystic ovarian syndrome?

*elevated*

What is the microscopic path findings of: Primary Biliary Cirrhosis

*extensive lymphocytic infiltration, and granulomatous destruction of interlobular bile ducts*

What is the first thing that should be considered in an elderly person to reduce falls?

*medication review* - Medication related falls are a common problem in elderly nursing home patients... Optimal management should include a careful mediation review and discontinuation of agents associated with increased falls

What type of drug is Phentolamine?

*non-selective alpha-blocker*

What antibody is seen in Churg-Strauss Syndrome?

*p-ANCA* (also called *Myeloperoxidase*-ANCA) Churg Ctrauss Syndrome = Eosinophilic granulomatosis w/ polyangiitis

What heart manifestations are pathognomonic of Carcinoid syndrome?

*plaque-like deposits of fibrous tissue on the right-sided endocardium* - This can lead to tricuspid regurg. and right-sided heart failure - Endocardial fibrosis and thickening are generally limited to the right heart as vasoactive products are inactivated distally by pulmonary vascular endothelial Monoamine Oxidase

What is the proper prophylaxis for Osteoporosis in an old lady?

*regular weight bearing exercise and adequate Ca and Vit. D intake throughout adulthood*

What is *stress-related mucosal disease*

*stress-related mucosal disease* is usually caused by local ischemia in the setting of severe physiologic stress (shock, extensive burns, sepsis, severe trauma) - Ulcers arising in the setting of severe trauma/burns = *Curling ulcers* - Ulcers arising from intracranial injury are caused by direct vagal stimulation = *Cushing ulcers*

A patient with a lung mass, low serum sodium, and low serum osmolality, suggests what?

*syndrome of inappropriate antidiuretic hormone secretion* (SIADH) - Small cell lung carcinoma (a tumor of neuroendocrine origin) can release ADH independent of feedback inhibition

What translocation is common in Burkitt Lymphoma? And, what does this result in?

*t(8:14)* - translocation of c-myc (8) to the Ig heavy chain locus on 14 - This results in *overexpression of c-myc, which is an oncogene that functions as a transcription activator* - Histology = numerous mitotic figures and apoptotic bodies ("stary sky appearance")

What translocation is associated with Chronic Myeloid Leukemia?

*t(9:22)* - The Philadelphia Chromosome - This generates a BCR-ABL fusion protein with increased Tyrosine Kinase activity

In the setting of an elevated Alk Phos, what enzyme should be studied next to differentiate between bone and liver?

*y-glutamyl transpeptidase (GGTP)* - This is b/c GGTP is not present to a significant extent in bone and is therefore useful in determining whether an elevated Alk Phos is of hepatic or bony origin

How does the chest X-ray look in Mycoplasma Pneumoniae infection?

- "A classic sign is a chest x-ray revealing findings that are much worse than the clinical appearance"

What is the liver histology of Hepatitis A?

- "Spotty necrosis" with ballooning degeneration (hepatocyte swelling with wispy/clear cytoplasm) - Councilman bodies (eosinophilic apoptotic hepatocytes) - Mononuclear cell infiltrates

Describe Hereditary Spherocytosis: What causes it to occur? What does it look like on blood smear? How is it diagnosed and treated?

- (Usually) Autosomal dominant defect in cytoskeleton-membrane tethering proteins (ankyrin, spectrin, or band 3) - D/t the loss of these proteins, membrane blebs are formed and lost over time, which causes the cells to become round - These round cells are less mobile in the spleen and get eaten by splenic macrophages - Dx = Osmotic fragility test becuase the round cells cannot expand, so they have increased fragility - Tx = Splenectomy

When is the best situation to use each of these anti-emetics: - 5-HT3 antagonist - Antahistamine - Anticholinergic - Dopamine

- *5-HT3 antagonist* - visceral nausea (gastroenteritis, chemotherapy, post-anesthesia) - *Antahistamine* - vestibular nausea - *Anticholinergic* - vestibular nausea - *Dopamine* - nausea associated with migraine

What does an Aldolase B deficiency result in?

- *Aldolase B deficiency causes hereditary fructose intolerance* (Autosomal Recessive) - The disease manifests after introduction of fructose into the diet with vomiting and hypoglycemia 20-30min after fructose ingestion. These infants can present with failure to thrive, jaundice, and hepatomegaly (d/t *toxic accumulation of fructose-1-phosphate in the liver*) NOTE: Formation of Fructose-1-P, causes depleted phosphate, which results in inhibition of glycogenolysis and gluconeogenesis

What 3 antibodies are specific to Scleroderma (Diffuse & Limited)

- *Anti-topoisomerase I (anti-Scl-70)* - more in diffuse scleroderma - *Anti-centromere* - more in limited scleroderma / CREST syndrome - *Anti-RNA Polymerase III*

What antibodies are associated with Lupus?

- *Antinuclear Antibodies* (ANA) - *Anti-dsDNA* (specific, poor prognosis) - *Anti-Smith* (directed against snRNPs) (specific, but not prognostic) (Anti-histone is specific to drug induced lupus)

What is the inheritance of Neurofibromatosis type 1? And, what are its characteristic symptoms?

- *Autosomal Dominant* mutation in NF1 tumor suppressor on Chromosome 17 - *Cafe-au-lait spots* - hyperpigmented lesions with either smooth or irregular borders - *Neurofibromas* - Short, sessile or pedunculated lesions that vary in size and are commonly multiple & distributed throughout the body - *Optic Glioma* - can cause visual loss - *Lisch Nodule* - Pigmented, asymptomatic hamartomas of the iris - *Various bony abnormalities* - pesudoarthritis, scoliosis, etc. - other associated *tumors* = Meningioma, astrocytoma, glioma, pheochromocytoma NOTE: Neurofibromatosis type 1 is also called: von Recklinghausen disease

What does the prostatic plexus innervate?

- The prostatic plexus lies within the fascia of the prostate and innervates the corpus cavernosa of the penis, which facilitates BONERS - So, a prostatectomy or injury to the prostatic plexus can cause BONER problems

What EKG changes can be seen after B-blocker infusion?

- *B-bockers will prolong the PR interval* - The PR interval is the period from the beginning of atrial depolarization (start of P wave) to the beginning of ventricular depolarization (start of QRS complex) - The longer the PR interval, the longer it takes for an electrical stimulus to travel from the SA node to the ventricles via the AV node, bundle of His, and fascicular branches - So since B-blockers slow AV nodal conduction, they will prolong the PR interval

What is one of the earliest signs of coagulative necrosis in cardiac myocytes on light microscopy? And, how long does it take for this to develop?

- *Cytoplasmic Hypereosinophilia* is one of the earliest signs of coagulative necrosis of cardiac myocytes - It begins 4 hours after the onset of lethal ischemia

GI ulcers in what location are very rarely malignant, and do not require biopsy to r/o malignancy?

- *Duodenal Ulcers* are not associated with an increased risk of carcinoma in the same location - Gastric ulcers caused by H. pylori are associated with an increased risk of gastric cancer, but duodenal ulcers related to this infection do not lead to a higher risk of duodenal carcinoma

What is one very common side effect of Phenytoin use? And what are signs of Phenytoin toxicity?

- *Gingival hyperplasia* is a common side effect of phenytoin (seen in 50% of patients that take it) - Phenytoin toxicity mainly affects the cerebellum and vestibular system, causing *ataxia and nystagmus* NOTE: Phenytoin has a ton of side effects, induces P450, and is also contraindicated in pregnancy (teratogenic and also disrupts folic acid metabolism)

How can you distinguish Hemophilia from von Willebrand disease?

- *Hemophilia* will usually present with deep tissue, joint, or delayed & prolonged postsurgical bleed... Hemophilia A&B are also X-linked recessive, so they are typically in men - *vWF disease* will usually present with mild mucosal and skin bleeding and bruising (prolonged bleeding during dental procedures or heavy menstrual periods)... vWF disease is Autosomal Dominant, so it affects both sexes equally

If cholecystectomy is refused, what medical therapy can be given to a patient with a gallstone?

- *Hydrophilic bile acid supplements* (ex: Ursodeoxycholic acid) improve cholesterol solubility by reducing the amount of cholesterol secreted into the bile and increasing biliary bile acid concentration

What state does the Rb protein need to be in to allow for the transition of G1 to S phase?

- *Hyperphosphorylated Rb is inactive*, and allows cells to transition unchecked from the G1 phase to the S phase NOTE: Proliferation signals activate CDK4 (cyclin-dependant kinase 4), whih results in the hyperphosphorylation of the Rb protein

What is the course of the pudendal nerve? And, what does it innervate?

- The pudendal nerve originates from S2-S4. It exits the pelvis through the greater sciatic foramen and then re-enters the pelvis through the lesser sciatic foramen - Sensory branches provide sensation to the external genitalia as well as the anus and perineum - Motor branches innervate the pelvic floor muscles, and the external urethral and anal sphincters NOTE: it provides the sensory for external hemorrhoids (via its inferior rectal branch)

What does the hormone, Human placental lactogen, do?

- *Increases insulin resistance* during the 2nd and 3rd trimester to ensure a readily available supple of glucose and amino acids to the fetus - It *increases maternal lipolysis* - with the resulting free fatty acids and ketones providing energy to the mother (preserving glucose and amino acids for the fetus)... These can also provide the fetus with energy during times of maternal malnutrition - *It stimulates pancreatic Beta cell insulin production* NOTE: Gestational diabetes results when pancreatic function is not sufficient to overcome the pregnancy-related increase in insulin resistance

How can you determine if Central DI is d/t the posterior pituitary or the hypothalamus?

- *Isolated posterior/infundibular injury* may cause *transient central DI* as the hypothalamic nuclei are still intact and axonal regeneration and hypertrophy can allow adequate ADH release into the circulation - *Damage to the hypothalamic nuclei* results in loss of vasopressinergic neurons, which often leads to *permanent central DI*

How will LV-End Diastolic Pressure, Peripheral venous capacitance, and systemic vascular resistance change with an IV infusion of nitroglycerin?

- *LV-End Diastolic Pressure* - lower b/c less preload - *Peripheral venous capacitance* - increase d/t Nitros vasodilatory effect - *systemic vascular resistance* - decrease (b/c nitro still has a modest effect on arteriolar dilation and this can be seen more in higher doses, such as IV)

In ovulation induction therapy, a short course of Menotropins is given, followed by a single injection of HCG... What is the purpose of both of these?

- *Menotropins* - mimics FSH and triggers formation of a dominant ovarian follicle - *HCG* - is administered when the follicle appears mature, and it's alpha subunit is structurally similar to LH, so this is given to mimic the LH surge and induce ovulation

What is Primary Myelofibrosis?

- *Myelofibrosis* Is one of the Myeloproliferative disorders - It is d/t a proliferation of mature myeloid cells (usually megakaryocytes) - It commonly is d/t a *mutated JAK2* - The Megakaryocytes produce excess platelet-derived growth factor (PDGF), which causes *bone marrow fibrosis* - As the disease progresses, pancytopenia can be seen - Pts usually have hepatomegaly and splenomegaly d/t extramedullary hematopoesis - Tear-drop RBCs, nucleated RBCs, and immature granulocytes are seen on blood smear (Tear-drop cells b/c the few RBCs that are produced in the marrow squeeze out of the fibrosis and get that shape... Immature cells b/c the spleen is bad at preventing immature cells from leaving)

What is the liver biopsy finding in Primary Biliary Cholangitis?

- *Patchy Lymphocytic inflammation with destruction of intrahepatic bile ducts* NOTE: these findings look similar to that in Graft-vs-host dz... which highlights the immunologic etiology of Primary Biliary Cholangitis

What enzyme is responsible for activating glycogen phosphorylase?

- *Phosphorylase kinase (PK)* phosphorylates Glycogen phosphorylase, which then promotes the breakdown of glycogen - In the muscle, Increased intracellular calcium is the most potent activator of Phosphorylase kinase, and can also be activated by epinephrine NOTE: In the liver, PK is activated via the binding of epinephrine and glucagon

Aside from the common hyperthyroid symptoms, what 2 signs are specific to Graves disease?

- *Pretibial Myxedema* - *Graves ophthalmopathy* - These occur because the TSH receptor is also on fibroblasts, adipocytes, and other tissues - Pretibial Myxedema occurs b/c - fibroblasts are stimulated by Thyrotropin Receptor Antibodies (TRAb) which also activates T-cells, and these then lead to excess production of glycosaminoglycans and adipogenesis - Graves ophthalmopathy occurs in a similar manner, with the activation of orbital fibroblasts and adipocytes, and expansion of the retro-orbital tissues displacing the globe forward NOTE: Administration of a B-blocker for symptom control will manage the classic symptoms of hyperthyroid (those which are d/t thyroid hormone stimulation and increased B-adrenergic receptor expression and stimulation), but it will NOT have any effect on the Pretibial Myxedema and Graves Ophthalmopathy b/c these are a direct effect of the Antibody (not the thyroid hormone)

What electrolyte findings are seen in Primary hyperaldosteronism? And what is the "Aldosterone escape"?

- *Primary hyperaldosteronism* causes increased renal Na reabsorption, leading to HTN, hypokalemia, and metabolic alkalosis (d/t increased excretion of H+ and increased HCO3- reabsorption stimulated by aldosterone at the alpha -intercalated cells) - Despite increased Na absorption, hypernatremia and pedal edema are rarely observed d/t *aldosterone escape*. The increased intravascular volume causes increased renal blood flow (w/ resulting pressure natriuresis) and augmented release of Atrial Natriuretic Peptide. This limits sodium retention and prevents the development of overt volume overload and significant hypernatremia. Lab findings, assuming intact aldosterone escape = *Normal Sodium, Low Potassium, High Bicarbonate, Metabolic Alkalosis*

What are the characteristic genital lesions that appear at Primary, Secondary, and Tertiary syphilis?

- *Primary* = *Chancre* - painless ulceration with raised, indurated borders, at the site of inoculation (usually penis or vulva) - *Secondary* = *Condyloma lata* - large grey wart-like growth typically appearing in the genital/perineal region - *Tertiary* = *Gumma* - begins as a painless, indurated granulomatous lesions that progress to white-grey rubbery lesions that may ulcerate

What are the 2 descriptions of a neoplastic colonic polyp?

- *Serrated* - *Adenomatous (Villous > Tubular)* (Villous is a Villain!!) - Sessile growth is worse than Pedunculated in these - The greatest risk for progressing from adenoma to carcinoma = >2cm, sessile growth, villous histology (NON-neoplastic = Hyperplastic, Inflammatory, Juvenile, Lymphoid)

What are the 2 main modes of transmission of Hep B?

- *Sexual* - *Percutaneous* (IV drugs, Needle stick accident, blood transfusion) (NOTE: The risk of sexual transmission of Hep C is LOW!!!... So if a person is doing lots of sex things, they will more likely get Hep B)

What are 3 different potential manifestations of a pancoast tumor that invaded/compressed surrounding structures?

- *Shoulder Pain* radiating to the axilla and scapula (most common presenting symptom) - occurs d/t involvement of the lower brachial plexus. Also can see parasthesias, weakness, and muscle atrophy - *Horner Syndrome* - Ipsilateral ptosis, miosis, and anhydrosis - occurs d/t involvement of the cervical sympathetic ganglia - *Spinal Cord Compression* & paraplegia - can result from tumor extension into the intervertebral foramina

What enzyme is deficient in Niemann-Pick disease? And, what are its clinical manifestations?

- *Sphingomyelinase* is deficient in Neimann-Pick... Thus, Sphingomyelin builds up in cells, which become "large lipid-laden foam cells" - The clinical manifestations are d/t the build up of these foam cells in the liver and spleen (*hepatosplenomegaly*) and CNS (*Hypotonia, neurodegeneration*), and retina (*Cherry-red spot* on macula) "You need your 'sphinger' to pick your nose" (AUTOSOMAL RECESSIVE)

What are the 2 main "watershead" areas of the colon?

- *Splenic flexure* (border between SMA and IMA) - *rectosigmoid junction* (border between sigmoid artery and superior rectal artery)

What 4 areas/organ-systems are affected by Henoch-Schonlein Purpura?

- 1 - *GI tract* - Abd pain, GI bleed - 2 - *Kidneys* - IgA nephropathy (IgA immune complex deposition in the mesangium) - episodic gross or microscopic hematuria - 3 - *Skin* - Palpable purpura on the butt and lower extremities - 4 - *Joints* - self-limited migratory arthralgia usually in the large joints of the lower extremities

Describe the Acid-Base abnormalities that occur with *Acute Salicylate intoxication*

- 1 - *Respiratory Alkalosis* - b/c salicylates directly stimulate the medullary respiratory center, resulting in increased ventilation and loss of CO2 in the expired air - 2 - *Anion gap metabolic acidosis* - starts to develop after 12 hours, because high concentrations of salicylates increase lipolysis, uncouple oxidative phosphorylation, and inhibit the citric acid cycle... This results in the accumulation of organic acids in the blood (eg. ketoacids, lactate, pyruvate), which bind to bicarbonate, thereby increasing the calculated anion gap

By which 2 mechanisms does therapeutic ionizing radiation cause cell death?

- 1 - DNA double-strand breaks - 2 - Free radical formation (reactive oxygen species are formed by ionization of water) NOTE: Exposure to UV radiation (a NON-ionizing radiation leads to formation of pyrimidine-pyrimidine dimers: thymine dimers)

What are the 4 main functions of the facial nerve?

- 1 - Motor output to the facial muscles - 2 - Parasympathetic innervation to the lacrimal, submandibular, and sublingual glands - 3 - Special afferent fibers for taste from the anterior 2/3 of the tongue - 4 - Somatic afferents from the pinna and external auditory canal

What are the 2 main defense functions of eosinophils?

- 1 - Parasite defense... IL-5 produced by TH2 and Mast cells activates eosinophil proliferation during parasite infection. When a parasite is coated by IgG and IgE, these Abs can bind to the Fc receptor on the Eosinophil cell surface. This triggers eosinophil degranulation and release of cytotoxic proteins (like major basic protein) and reactive oxygen intermediates. This mechanism is an example of Antibody-dependent cell-mediated cytotoxicity - 2- Type-1-hypersensitivity reactions... Eosinophils also synthesize prostaglandins, leukotrienes, and cytokines that contribute to the inflammation seen in late-phase type 1 hypersensitivity and chronic allergic reactions

Hoe many calories are generated by: - 1g of protein - 1g of carbs - 1g of fat

- 1g of protein = 4 calories - 1g of carbs = 4 calories - 1g of fat = 9 calories

What cranial nerves are associated with the 1st, 2nd, 3rd, 4th, and 6th, branchial (pharyngeal) arches?

- 1st = Trigeminal (CN V - specifically V2/V3) - 2nd = Facial (CN VII) - 3rd = Glossopharyngeal (CN IX) - 4th = Superior laryngeal branch of Vagus (CN X) - for swallowing - 6th = Recurrent laryngeal branch of Vagus (CN X) - for speaking NOTE: it goes: 5, 7, 9, 10

What are the 2 different Pneumococcal vaccines? And what is the benefit of each?

- 23-valent polysaccharide vaccine protects against a wider range of serotypes, but Ab levels decline over 5 years, and it is also not immunogenic in pts under 2 year old d/t their poor humoral Ab response - 13-valent conjugate vaccine contains a nontoxic diphtheria protein conjugated to the polysaccharide that boosts the immune response through T cell recruitment.. Therefore, it allows for the development of memory B cells, higher and longer-lasting Ab levels, and less mucosal carriage (herd immunity)

What are the names of the 3 thiazide diuretics? And what are their side effects?

- 3 Thiazide diuretics = Hydrochlorothiazide, Chlorthalidone, and Metolazone - Thiazide diuretics raise serum glucose, cholesterol/triglycerides, uric acid, and calcium (HyperGLUC) - Thiazide diuretics lower serum sodium, potassium, and magnesium

What are classic symptoms of Neuroleptic Malignant Syndrome? And, what are differentiating symptoms from serotonin syndrome?

- 4 primary features of NMS = hyperthermia, severe generalized rigidity, autonomic instability, and AMS - Serotonin has: neuromuscular hyperactivity (shivering, clonus, and hyperreflexia), as opposed to the diffuse rigidity and bradyreflexia seen in NMS (serotonin syndrome can also have sweating, N/V/D, while this is not commonly seen in NMS)

What does 5a-reductase do? And, what is the clinical presentation if it is deficient?

- 5a-reductase converts testosterone to DHT - DHT is responsible for the development of male external genetalia - So in the male fetus, the internal genitalia develop normally under the influence of testosterone, but the external genitalia do not develop properly d/t the lack of DHT, and this results in male pseudohermaphroditism... These patients will typically masculinize at puberty d/t high levels of testosterone - Small phallus (penis) and hypospadias are commonly seen

What is Etanercept?

- A *TNF-alpha inhibitor* that can be added to methotrexate to treat moderate-severe RA - It is a fusion protein linking a soluble TNF-alpha receptor to the Fc component to human IgG1... thus, *it reduces the biological activity of TNF-alpha by acting as a decoy receptor*

What is a Cystoscopy?

- A Cystoscopy is an endoscopy of the bladder via the urethra

What is a Krukenberg Tumor?

- A Krukenberg tumor is a tumor formed in the ovary when a primary gastric cancer (Diffuse type) has metastasized to the ovary - The histo finding is: Nests of signet ring cells (a mucin filled cell with a peripheral nuclei)

What vision changes would occur with occlusion of the posterior cerebral artery?

- A PCA occlusion would produce a Contralateral homonymous hemianopia WITH macular sparing - Macular sparing occurs because collateral blood is supplied by the middle cerebral artery to the occipital pole, which processes central visual information NOTE: A MCA occlusion would produce a homonymous hemianopia with macular involvement (it also would typically have motor and sensory deficits) NOTE: Lateral geniculate nucleus is in the thalamus NOTE: Meyers loop is in the temporal lobe NOTE: Dorsal optic radiation is in the parietal lobe

What is a pericardial knock?

- A brief, high frequency, precordial sound heard in early diastole (shortly after S2) in patients with *CHRONIC constrictive pericarditis*. It occurs earlier than an S3 ventricular gallop, and may be confused with the opening snap of mitral stenosis

When performing a Cricothyrotomy, what anatomical structures does the scalpel pierce?

- A cricothyrotomy establishes an airway through the placement of a tube between the thyroid cartilage (superior) and cricoid cartilage (inferior) - The incision will go through: --- Skin --- Superficial cervical fascia (including fat and platysma muscle) --- Investing and pretracheal layers of the deep cervical fascia --- Cricothyroid membrane

What are the characteristic histo findings in Celiac disease? And what 2 antibodies could be seen in serology?

- A duodenal biopsy would show crypt hyperplasia, villous atrophy, and intraepithelial lymphocytic infiltration - Screening is with serology and tests for elevated IgA anti-endomysial and Anti-Tissue transglutaminase Ab NOTE: Celiac is d/t a hypersensitivity to gluten. Specifically, Gliadin (a breakdown product of gluten) triggers an immune response

Antibodies directed against what are responsible for the major adaptive immunization against Influenza?

- A humoral response with antibodies directed against hemagglutinin is generally the most important source of protection to prevent reinfection with the influenza virus - Anti-Hemagglutinin Abs can neutralize the virus and primarily block its binding to the host cell

What is a Cross-sectional study?

- A prevalence study that simultaneously measures exposures and outcomes... A "snapshot" - Can show a risk factor association, but cannot always establish causality

How does allergic bronchopulmonary aspergillosis (ABPA) manifest?

- ABPA occurs in 5%-10% of corticosteroid-dependant asthmatics - Pt with ABPA has very high serum IgE levels, eosinophilia, and IgE plus IgG Ab to Aspergillus. - There is intense airway inflammation and mucus plugging with exacerbations and remissions - Repeated exacerbations may produce transient pulmonary infiltrates and proximal bronchiectasis

Where is ADH produced, and where is it secreted?

- ADH is produced in neurons of the peraventricular and supraoptic nuclei of the *hypothalamus* - ADH is secreted from the *posterior pituitary* into the hypophysial vein to then enter systemic circulation NOTE: Oxytocin is produced and secreted in this same manner!

What are the radial nerve branches? And, what do these innervate?

- The radial nerve divides into the Superficial and Deep branches after passing the lateral epicondyle - The *superficial branch* provides pure sensory to the radial half of the dorsal hand - The *deep branch* innervates the extensor compartment muscles of the forearm... It then passes through the supinator canal (between the superficial and deep parts of the supinator muscle), and becomes the *posterior interosseous nerve*, which innervates the muscles involved in finger and thumb extension

What is the pathogenesis of Acute Respiratory Distress Syndrome?

- ARDS is d/t a variety of disease processes (such as pancreatitis)... Activation of neutrophils induce protease and free radical-mediated damage of type 1 and 2 pneumocytes - ARDS is characterized by diffuse injury to the pulmonary microvascular endothelium and alveolar epithelium, resulting in increased permeability and leaky alveolocapillary membrane - Leakage of protein-rich fluid leads to edema that combines with necrotic epithelial cells to form hyaline membranes in the alveoli... This all ultimately results in a non-cardiogenic pulmonary edema with normal pulmonary capillary wedge pressure, - It ultimately leads to decreased lung compliance, increased work of breathing, and worsened V/Q mismatching.

How to pulmonary vascular complications arise as a consequence of Atrial Septal Defect?

- ASD creates a left-right shunt because of the high pressure in the left atrium - The muscular pulmonary arteries can develop laminated medial hypertrophy as a result of the increased blood flow through the pulmonary vasculature... and this can eventually become so severe over time that the pulmonary vascular resistance can rise above the total systemic vascular resistance - This can result in Eisenmenger syndrome: late-onset reversal of a left-right shunt (to become right-left) d/t pulmonary vascular sclerosis resulting from pulmonary hypertension... This manifests as late-onset cyanosis, with clubbing and polycythemia

What is Acanthosis Nigricans? And, what is it associated with?

- Acanthosis Nigricans are hyperkeratotic, hyperpigmented plaques with a classic "velvity" texture. It usually occurs in flexural areas (axillae, posterior neck, and groin), but can occur on other areas of the body - Benign Acanthosis Nigricans is associated with Insulin resistance (diabetes mellitus, acromegaly, and obesity)... Increased insulin levels and insulin-like growth factor stimulate the epidermal and dermal proliferation - Malignant Acanthosis Nigricans is associated with underlying neoplasms, especially GI and GU tracts (gastric adenocarcinoma is the most common cause of malignant Acanthosis Nigricans)... The sudden appearance of these could suggest underlying malignancy

What is the characteristic stain for *Acute Lymphoblastic Leukemia* and the stain for *Acute Myeloid Leukemia*?

- Acute Lymphoblastic Leukemia (ALL) = *Terminal deoxynucleotidyl transferase (TdT)* - Acute Myeloid Leukemia (AML) = *Myeloperoxidase* (or just "*peroxidase*") NOTE: - ALL mainly affects children - AML has the characteristic "Auer Rods"

Describe parotitis:

- Acute bacterial parotitis is an acute bacterial or viral infection of the parotid gland - It occurs more commonly in elderly post-op patients who are intubated and dehydrated. - Staph Aureus is the most common bacterial etology - It presents as acute onset of firm erythematous pre/postauricular swelling that extends to the mandible... and patents can also develop trismus, dysphagia, and systemic findings - Since the parotid gland secretes amylase, suppurative parotitis can present with elevated serum amylase (pts will have normal serum lipase b/c pancreas is not involved)

What is the Pentose phosphate pathway (HMP shunt)? What is the rate limiting step and what enzyme catalyzes it?

- The rate limiting step is: glucose-6-phosphate --> 6-phosphogluconolactone (which is subsequently converted to 6-phosphogluconate) - The pentose phosphate pathway is the only mechanism for RBCs to generate NADPH (which is needed to reduce oxidized Glutathione via Glutathione reductase) NOTE: G6PD deficiency is X-linked recessive

How do blood levels of Reticulocytes, Hemoglobin, and Erythrocytes, change when a pt with pernicious anemia is treated with B12?

- The reticulocyte count increases dramatically once B12 replacement is initiated, and then Hemoglobin and Erythrocyte count levels rise more gradually and take up to 8 weeks to normalize

What nerve roots make up the sciatic nerve?

- The sciatic nerve is derived from nerve roots L4-S3 - Compression most often occurs at the level of L5 or S1 - L4 compression will result in absent patellar reflex - S1 compression will result in absent ankle jerk reflex

What is Acute intermittent Porphyria: How does it manifest? What causes it? How is it treated?

- Acute intermittent porphyria is *Autosomal dominant*, and characterized by a *deficiency in Prophobilinogen (PBG) deaminase* - Symptoms are usually seen when there is a combination of this deficiency, in combination with something that happened to upregulate Aminolevulinate (ALA) synthase (such as drugs or alcohol) - Symptoms of the Porphyrias occur d/t the accumulation of porphyrin precursors in blood, tissues, and urine - Acute intermittent porphyria attacks are d/t the accumulation of ALA (aminolevulinic acid) and PBG (porphobilinogen) - Symptoms are: Painful abdomen, Port wine-colored urine, Polyneuropathy, and Psychological disturbances - The red urine darkens on exposure to light and air d/t oxidation of the excess PBG - Treatment = infusion of glucose or hemin, which inhibit ALA synthase (to prevent the buildup of the porphyrin precursors) FA Page 403

How does the stool pH change in a patient with Lactase deficiency?

- The stool pH will *DECREASE* - Lactase deficiency results in incomplete hydrolysis of lactose into monosaccharides glucose and galactose. The fermentation of undigested lactose by gut bacteria leads to increased production of short-chain fatty acids, which acidify the stool (Also during this time, Hydrogen gas is produced, which is the cause for the increased breath hydrogen in patients with lactase deficiency)

What portion of the nephron is NEVER permeable water?

- The thin and thick ASCENDING limbs of Henle are NEVER permeable to water

What nerve innervates the Latissimus Dorsi?

- The thoracodorsal nerve innervates the Latissimus Dorsi - It originates from the posterior cord of the brachial plexus and carries fibers from C6, C7, and C8

Describe the anatomical thyroid developmental path, and what can occur if there are errors in this development?

- The thyroid gland is formed from evagination of the pharyngeal epithelium and descends to the lower neck - D/t failure of migration, the thyroid can reside anywhere along the thyroglossal duct's usual path, including the tongue (lingual thyroid - the most common site of ectopic thyroid tissue)

What is the translocation associated with Acute Promyelocytic Leukemia (APML)? And, what pathology results from this translocation?

- The translocation is t(15:17), which swaps the promyelocytic leukemia gene (PML) on chromome 15 with the retinoic acid receptor alpha (RARA) gene on chromosome 17 - This translocation results in inhibition of myeloblast differentiation and results in the development of APML NOTE: - DIC can be seen in this leukemia - Treatment is with All-trans retinoic acid (a vitamin A derivative)

What is the most common malignancy of childhood?

- Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood - The neoplastic cells of ALL arise from lymphocytic precursors that are of either pre-B or pre-T lineage - B-cell ALL is responsible for 70-80% of cases, while T-cell ALL accounts for 15-17% of cases. - Both lineages contain TdT (an antigen of lymphocyte precursors) - The best way to differentiate is via cell surface markers: --- pre-B lymphoblasts = CD10+, CD19+, CD20+ --- pre-T lymphoblasts = CD2+, CD3+, CD4+, CD5+, CD7+, CD8+ NOTE: T-cell ALL often presents as a mediastinal mass that can cause respiratory symptoms, dysphagia, or SVC syndrome (impaired blood drainage from head)

What is the time frame of Acute Stress Disorder vs. PTSD?

- Acute stress disorder requires symptoms that last from *3 days to 1 month* - PTSD requires symptoms that last *over 1 month*

What are the histo findings of Lung Adenocarcinoma in situ, and is it considered malignant or benign?

- Adenocarcinoma in situ arises from the alveolar epithelium and is located at the periphery of the lung - It is "pre-invasive" with growth along the alveolar septa without stromal invasion. - Histo shows well differentiated dysplastic columnar cells with or without intracellular mucin - Despite not presenting as invasive it is considered malignant! - It has the tendency to undergo aerogenous spread (along the airways) and can progress to invasive if not resected

What 2 regions of the brain have the most pronounced atrophy in Alzheimers?

- Advanced Alzheimers is associated with diffuse brain atrophy - Atrophy is MOST pronounced in the temporoparietal lobes and hippocampus - Hippocampal atrophy is evident even in early stages of the disease, and can be detected with MRI

In the Cahill cycle, Alanine can get converted to pyruvate and then to glucose. What is the reaction that takes place to allow this to occur / What molecule is the (NH3) group of Alanine transferred to?

- Alanine is the major amino acid responsible for transferring nitrogen to the liver for disposal - During the catabolism of proteins, *amino groups are transferred to a-ketoglutarate to form glutamate*... Glutamate is then processed in the liver to form urea

Describe the Polyol pathway (glucose-sorbitol): - What is the first enzyme and product, and what is the second enzyme and product? - What cells do not have this first enzyme?

- Aldose reductase converts glucose to sorbitol - Sorbitol can be slowly metabolized to fructose by sorbitol dehydrogenase - Tissue with low/no sorbitol dehydrogenase = Lens (has some), Retina, Kidney, Schwann cells This pathway accelerates cataract development in diabetics, and contributes to the pathogenesis of diabetic retinopathy, neuropathy, and nephropathy

When do you see an *Allergic transfusion reaction*?

- Allergic transfusion reactions are *IgE-mediated (Type 1)* hypersensitivity reactions against plasma proteins found in the transfused blood - It can be mild (urticaria, itching) or result in severe anaphylaxis (most common in IgA-deficient patients with anti-IgA antibodies)

Describe the interaction of Allopurional and Azathioprine/6-MP:

- Allopurinol inhibits Xanthine Oxidase - Xanthine Oxidase inhibits Azathioprine/6-MP - So, if you use Allopurinol, and block Xanthine Oxidase, then Azathiopeine/6-MP levels will rise - This can be bad if unexpected, and lead to bone marrow suppression and decreased leukocyte production - It can be used, if monitored, to increase Azathioprine/6-MP levels

What molecules can get converted into Propionyl-CoA, and eventually enter the TCA cycle as Succinyl-CoA?

- Amino Acids = Valine, Isoleucine, Methionine, Threonine - Lipids = Odd-chain fatty acids, cholesterol - Pyrimidines = Thymidine and Uracil

How may amylin play a role in the pathogenesis of type 2 diabetes?

- Amylin is stored in insulin secretory granules and is co-secreted with insulin from pancreatic beta-cells - Deposits of Amylin are universally seen in the pancreatic islets of patients with type 2 diabetes... And therefore may play a role in the beta cell apoptosis and defective insulin secretion

What is reverse T3 (rT3)?

- An inactive form of T3 - T4 is converted in peripheral tissue to T3 (active form) and reverse T3 (inactive form)

How does Estrogen influence T4 and T3 levels?

- An increase in estrogen activity, as seen in pregnancy or post-menopausal estrogen replacement therapy (for hot flashes), increases the levels of Thyroxine-binding globulin (TBG) - This increase in TBG causes a corresponding drop in free T4 and T3, but in patients with a normal hypothalamic-pituitary-thyroid axis, this reduction will result in a transient increase in thyroid hormone production until the additional quantity of TBG gets saturated, and normal free T4 and T3 levels are restored (so the patient remains euthyroid)

Name 3 aromatase inhibitors, Describe their function and clinical use:

- Anastrozole, Letrozole, and Exemestane - Inhibit peripheral conversion of androgens to estrogen - Used in the treatment of Estrogen Receptor positive breast cancer in postmenopausal women

What are the 2 branches of the external Iliac? And where do they go?

- The two branches are the inferior epigastric artery, and the deep circumflex iliac artery - The inferior epigastric artery branches just proximal to the inguinal ligament and runs superior/medial to provide blood to the lower anterior abdominal wall - The deep circumflex iliac artery branches more laterally, and also supplies blood to the lower abdominal wall NOTE: The external iliac becomes the common femoral artery once it passes the inguinal ligament

What are some characteristics of Ankylosing Spondylitis? And, what is one thing that is important to monitor in these patients?

- Ankylosing Spondylitis is a chronic inflammatory condition associated with the HLA-B27 serotype - It is characterized by stiffness and fusion (ankylosis) of the axial joints ("bamboo spine"), and also inflammation at the site of insertion of tendons into bone (enthesitis) - Some other symptoms include systemic symptoms, acute anterior uveitis, and aortitis (leading to aortic regurgitation) - Involvement of the thoracic spine and costovertebral and costosternal junctions can limit chest wall expansion, leading to hypoventilation... SO it is very important to monitor chest expansion regularly in patients with Ankylosing Spondylitis

How does anorexia lead to amenorrhea?

- Anorexics have diminished adipose tissue stores. This leads to decreased circulating leptin, which inhibits pulsatile GnRH release from the hypothalamus, causing decreased pituitary LH and FSH secretion, causing low estrogen levels, and amenorrhea (and bone loss)

Describe the characteristics of Aortic regurg.

- Aortic regurg causes a high pitched, blowing decrescendo diastolic murmur that begins immediately after closure of the aortic valve - The peak intensity of AR occurs immediately after the aortic valve closes, when the pressure gradient between the aorta and left ventricle is maximum - It is heard best along the left sternal border at the third and fourth intercostal spaces while the patient is sitting up and leaning forward with the breath held in expiration

What are the 3 post-prandial short acting insulin formulations?

- Aspart - Lispro - Glulisine *A*lways *L*owers *G*lucose

How large must a coronary atherosclerotic plaque be to start producing symptoms?

- Atherosclerotic plaques do not produce an imbalance of myocardial oxygen supply and demand sufficient to cause angina until they *obstruct 75% or more* of the luminal cross sectional area

What is the inheritance of Hereditary nonpolyposis colon cancer (Lynch Syndrome)? And, what is defective?

- Autosomal Dominant - Inherited mutation in one of the genes responsible for DNA mismatch repair (MSH2, MLH1)

What is defective in Ataxia-Telangiectasia? And, what are common symptoms?

- Autosomal Recessive mutation of the ATM gene (A=Ataxia, T=Telangiectasia, M=Mutated) - This gene is responsible for double strand DNA break repair, and is defective in this disease... Thus, these patients DNA is very sensitive to Ionizing radiation - The classic symptoms are cerebellar ataxia, telangiectasia, and increased risk of sinopulmonary infections (d/t immune deficiency primarily manifesting as an IgA deficiency)

What is the disorder: Myotonic Muscular dystrophy?

- Autosomal disorder d/t *CTG* trinucelotide repeats in the DMPK gene - This causes abnormal expression of myotonin protein kinase - Microscopy shows = Atrophy of muscle fibers (Type 1 fibers > Type 2 fibers), but NO muscle fiber necrosis - Classic symptoms of *myotonia* are difficulty loosening ones grip after a handshake or inability to release the doorknob - Other common symptoms = muscle wasting, cataracts, testicular atrophy, frontal balding *CTG = Cataracts, Toupee (male balding), Gonadal Atrophy*

What is the cause of cystinuria? And, what do cystine stones look like?

- Autosomal recessive defect in the sodium-independant dibasic amino acid transporter, which is on the apical membrane of intestinal and proximal renal tubules - The stones precipitate at low pH... so treatment is increasing hydration and urine alkalization NOTE: This transporter is responsible for the transport of: lysine, arginine, orithine, and cysteine (*COLA*)

Mutation of what oncogene is highly associated with melanoma?

- BRAF - BRAF is a protein kinase involved in signaling pathways in melanocytes - BRAF mutation (V600E) is seen in 40%-60% of patients with melanoma NOTE: BRAF mutations can also be seen in Non-Hodgkin lymphoma, and papillary thyroid cancer FA Page 218

How can aspirin help in reducing someones risk for developing colon adenocarcinoma?

- Because increased COX-2 expression has been found in many forms of colon adenocarcinoma & it is part of the Adenoma-to-Carcinoma sequence - Aspirin can inhibit COX to prevent this COX-2 expression

What are 3 other findings that are associated to Autosomal Dominant Polycystic Kidney Disease

- Berry aneurysm - Hepatic cysts - Mitral valve prolapse

What is the mechanism of the diabetes drugs: "-glitazone"

- Bind PPAR-y - an intracellular nuclear receptor that acts as a transcriptional regulator of many genes involved in glucose and lipid metabolism

What affect does binding of the Mu receptor (by opioids) have on the pre synaptic and post synaptic spinal afferent neurons?

- Binding Mu on the pre-synaptic neuron causes closure of voltage gated Ca channels, reducing Ca influx, and decreased excitatory neurotransmitter release - Binding Mu on the post-synaptic neuron, causes opening of Potassium channels, leading to K efflux and membrane hyperpolarization

In skeletal muscle contraction, what does binding of a new ATP molecule do?

- Binding of a new ATP molecule causes detachment of the myosin head from the actin filament - Hydrolysis of this ATP molecule (to ADP & Pi, which remains on the myosin head) causes the myosin head to adopt a high-energy position ("cocked back"), ready for the next contraction cycle

What is the definition of bioavailability (F)? And, how can it be calculated/determined?

- Bioavailability (F) refers to the fraction of administered drug that reaches the systemic circulation in a chemically unchanged form. - Generally, an IV administered drug has 100% bioavalability (F = 1) - Bioavailability for a drug administered by a non-IV route is always less than 1 - Bioavailability can be determined by examining a graph of plasma concentration versus time, and then applying the following formula: F = (AUC oral x dose IV)/(AUC IV x dose oral) - The area under the oral administration curve simply represents the total amount of drug that was absorbed by the body and made available in systemic circulation from the time of administration to the time of complete elimination

How do Schwannomas present Histologically?

- Biphasic pattern of cellularity (high cellularity mixed with myxoid regions of low cellularity) - *S-100+*

What are signs of *Norepinephrine (NE) Extravasation*? And, how is this treated?

- Blanching of a vein into which Norepinephrine is being transfused, with induration and pallor of the tissues surrounding the IV site, are signs of Norepinephrine Extravasation - The NE leak from the IV, causes intense Alpha-1 receptor mediated vasoconstriction, which can lead to local tissue necrosis - Necrosis can be prevented with infiltration of solution containing Phentolamine - an Alpha-receptor BLOCKER... This will lead to vasodilation and counteract the Alpha-1 vasoconstriction of NE

Portosystemic anastomoses between which 2 veins is responsible for esophageal varices?

- Blood in the left gastric vein backs up d/t portal hypertension, and this leads to dilation of the portosystemic anastomoses between the left gastric vein and the esophageal vein - This then results in dilation of the esophageal veins - esophageal varices

What should be ruled out first in a postmenopausal woman or man over 50, who shows signs of Iron deficiency anemia?

- Blood loss, especially occult loss from the GI tract, must be ruled out in a patient with iron-deficiency anemia - GI blood loss is often occult, so the lack of dark or bright red stools in a patient should not rule out GI bleed

What drug is a competitive antagonist of endothelin receptors used to treat idiopathic pulmonary arterial HTN?

- Bosentan is a competitive antagonist of endothelin receptors used for treatment of idiopathic pulmonary arterial hypertension

Whats the difference between a Lacunar infarct and an Intraparenhymal hemorrhage?

- Both lacunar infarcts and intraparenchymal hemorrhages most commonly involve the same small penetrating arterioles and typically affect the basal ganglia/internal capsule/striatum - The difference is that Lacunar infarcts is an ischemic stroke while intraparenchymal hemorrhages are hemorrhagic strokes... They have different underlying etiologies as to why they occur - Intraparenchymal hemorrhages are typically d/t small rupture of Charcot-Bouchard aneurysms - Lacunar infarcts are most often d/t lipohyalinosis, microatheroma formation, and hardening/thickening of a vessel wall (hypertensive arteriolar sclerosis) - Remember, a hemorrhage will appear acutely on a CT as a HYPERdensity... While an ischemic strokes may not immediately reveal the expected HYPOdensity

How can you clinically differentiate: Severe Combined Immunodeficiency vs. X-linked Agammaglobulinemia

- Both present early in childhood, but X-linked agammaglobulinemia occurs around 6 months because moms antibodies is protective & baby has a functional cell-mediated response *SCID* - deficient T and B cells. So the patient will have *fungal & viral infections* (d/t deficient T cells), and *bacterial and protozoa infections* (d/t deficient B cells and no immunoglobulin) --- Thymic hypoplasia/aplasia can also be seen d/t severe T cell deficiency *X-linked Agammaglobulinemia* - B cells cannot mature do there is no immunoglobulin. So the patient will have *bacterial & protozoa infections* (d/t no immunoglobulin), but Cell-mediated immunity is intact so they will not have increased risk of fungal and viral infections

What is a major side effect of Bupropion?

- Bupropion an an antidepressant with similar structure to amphetamines, and inhibits the reuptake of NE and dopamine - It is sometimes preferred to an SSRI because it does not cause the weight gain and sexual side effects - Its major side effect is increased seizure risk (at high doses) - Bupropion is contraindicated in patients with seizure disorders, anorexia, and bulimia nervosa

How do ACE inhibitors cause hyperkalemia?

- By blocking conversion to Angiotensin II, ACE inhibitors therefore decrease the amount of aldosterone... This can cause potassium retention (because aldosterone is responsible for Na reabsorption and K&H secretion at distal tubule) NOTE: significant hyperkalemia is not common in patients with normal renal function and who are not on other drugs that can raise K

What are the 2 main nerves that innervate cutaneous sensation to the auditory meatus/canal?

- CN V3 (mandibular) - carries sensation form the majority of the external auditory meatus including the Tympanic Membrane, except the posterior wall - CN X (vagus) - provides cutaneous sensation to the posterior external auditory canal via its small auricular branch - Stimulation of the Vagus nn. can cause vasovagal syncope

What are the effects of Carbon Monoxide on the oxygen-carrying capacity, oxygen content, and dissolved oxygen in blood?

- CO binds to Hgb at a higher affinity than Oxygen... By decreasing the fraction of Hgb available for oxygen binding, CO decreases the oxygen-carrying capacity and oxygen content of blood, but does not decrease the amount of oxygen dissolved in plasma (reflected by the partial pressure of oxygen: paO2)

What 2 enzymes does lead inhibit heme synthesis

ferrochelatase and ALA dehydratase

What protein on HIV binds to the CD4 receptor?

gp120 - The polyprotein product of the env gene is glycosylated to become gp160, and then cleaved to form gp120 and gp41 - gp120 mediates viral attachment by binding to the CD4 receptor - gp41 anchors gp120, and mediates fusion and entry

How does a dorsal midbrain (Parinaud syndrome) present?

it is d/t a *lesion of the posterior midbrain* (superior colliculus and pretectal area) - Sx = *vertical gaze palsy (cant look up)*, pupillary light-near dissociation, *lid retraction*, convergence-retraction nystagmus, and *can cause cerebral aqueduct obstruction* and lead to non-communicating hydrocephalus - This can *often be caused by a Pineal gland mass* (with tho most common pineal gland mass being a germinoma)

In a cardaic biventricular pacemaker with 3 leads, where does each lead go?

lead 1 - right atrium lead 2 - right ventricle lead 3 - courses through the coronary sinus (in the atrioventricular groove on the posterior aspect of the heart) into a lateral venous tributary in to obtain left ventricular pacing

Are down syndrome cases usually d/t maternal non-disjunction of meiosis 1 or 2

meiosis 1 - When this occurs, they receive BOTH of their moms different chromosome 21 copies - When it occurs during meiosis 2, the kid receives 2 copies of one of the moms chromosome 21

Exposure to what compound creates methemoglobin?

nitrites

Remember if doing a genetic calculation, if it says the disease "affects X many people", then you will have to do Hardy-Weinberg.... So, what are the equations?

p+q = 1 P^2 + 2pq + q^2 = 1

Is the internal iliac and external iliac in the peritoneal cavity or retroperitoneal?

retroperitoneal

Lambert-Eaton Myasthenic Syndrome is associated with what cancer?

small-cell lung cancer

What is Encephalomalacia?

softening or loss of brain tissue after cerebral infarction

What is the equation for half life?

t1/2 = (.7 x Vd) / (CL) Vd = Volume of distribution CL = Clearance rate

What 2 molecules would you expect to be elevated in the serum of a patient with a B12 deficiency?

- Vitamin B12 (Hydroxocobalamin) deficiency presents with megaloblastic anemia (d/t impaired DNA synthesis) and neurological deficits (impaired myelin synthesis) - Vitamin B12 serves as a cofactor for Methylmalonyl-CoA mutase (converts methylmalonyl-CoA to Succinate-CoA), which is important in fatty acid metabolism - Vitamin B12 also serves as a cofactor for Methionine synthase (converts homocysteine to Methionine) - B12 deficiency therefore results in elevated levels of serum Methylmalonic acid and Homocysteine - The elevated methylmalonic acid can disrupt myelin synthesis and result in subacute combined degeneration of the dorsal columns (loss of priprioception/vibration) and lateral corticospinal tract (spastic muscle weakness, hyperreflexia, ataxic gait) NOTE: Folate deficiency will also show an elevated serum homocysteine, so the elevated methylmalonic acid is specific to B12!!!

What causes Wolf-Parkinson-White syndrome? And, what are the characteristic EKG findings?

- WPW is d/t an *Atrioventricular accessory pathway* (bundle of kent)... This allows electrical impulses to bypass the AV node and causes early excitation of the ventricles ECG triad: --- *Short PR wave* --- *Wide QRS* --- *Delta wave (slurred/broad upstroke of the QRS)* NOTE: WPW is usually asymptomatic, but can be associated with a variety of cardiac arrhythmias d/t re-entry of electrical impulses through the aberrant conduction pathway

What is Wallerian degeneration?

- Wallerian degeneration refers to the process that occurs when the axon is damaged, resulting in axonal degeneration and breakdown of the myelin sheath distal to the site of injury, and axonal retraction proximally - In the PNS - the axon can be regenerated - In the CNS - axonal regeneration does not occur d/t the persistence of myelin debris, secretion of neuronal inhibitory factors, and development of dense glial scarring (as seen in the picture)

What drugs are used in the treatment of Wet Macular Degeneration?

- Wet age-related macular degeneration is characterized by retinal neovascularization d/t increased vascular endothelial growth factor (VEGF) levels. - Patients typically have acute vision loss (days to weeks), and metamorphopsia with funduscopy showing a grayish-green subretinal membrane and/or subretinal hemorrhage - Treatment includes smoking cessation and VEGF inhibitor therapy with Ranibizumab or Bevacizumab NOTE: Patients with dry or wet age-related macular degeneration benefit from antioxidant vitamins and zinc

What is Placenta Accreta?

- When the placenta attaches to the myometrium without penetrating it - It is usually detected on Ultrasound - Presents: No separation of placenta after delivery (i.e. the placenta has to be removed manually), this causes post-partum hemorrhage, that resists uterotonic medications Prior *C-section* is a risk factor d/t previous disruption of decidual layer

How can you tell a 21-hydroxylase deficiency vs. a 11B-hydroxylase deficiency in a female?

- With both of these, androgen synthesis will be increased in the girl, and she will have ambiguous genitalia - *21-hydroxylase deficiency will have hypotension and hyperkalemia* (b/c there is no action of aldosterone or other viable precursors) - *11B-hydroxylase deficiency will have hypertension and hypokalemia* (this is because the precursor: 11-deoxycorticosterone is a weak mineralocorticoid... This will be produced in large amounts because cortisol is not producing negative feedback on ACTH)

What is Lesch-Nyhan syndrome?

- X-linked recessive - deficiency in *HGPRT* (Hypoxanthine Guanine Phosphoribosyltransferase), which leads to impaired purine salvage, and increased uric acid production & de novo purine synthesis Clinically = gout, poor muscle control, intellectual disability, writhing or repetitive involuntary movements, and self-mutilating behaviors Tx = Allopurinol (or Febuxostat 2nd line) *H* - Hyperuricemia *G* - Gout *P* - Pissed off (aggression, self-mutilation) *R* - Retardation *T* - dysTonia

What is Xeroderma Pigmentosum? How does it present? And, What is defective in this disorder?

- Xeroderma Pigmentosum presents as children with severe photosensitivity, hyperpigmentation in sun exposed areas, and a greatly increased risk of skin cancer - Xeroderma Pigmentosum is an autosomal recessive disorder characterized by *defective nucleotide excision repair* often caused by a deficiency in UV-specific endonuclease - UV rays can damage DNA, leading to formation of thymine dimers between 2 adjacent thymine residues... These thymine dimers normally get repaired by UV-specific endonuclease

What 2 things do you give to reverse warfarin-induced anticoagulation? And, which has more rapid effects?

- You give both Fresh Frozen plasma and Vitamin k - Fresh frozen plasma RAPIDLY reverses warfarin effects (because it contains all the clotting factors)... Whereas vitamin K requires time for clotting factor re-synthesis

What is *Nonbacterial thrombotic endocarditis*?

- a form of noninfectious endocarditis characterized by deposition of sterile platelet thrombi on cardiac valves - It is commonly associated with advanced malignancy and can also occur with chronic inflammatory disorders (antiphospholipid syndrome, SLE) and sepsis

What is the PI3K/Akt/mTOR pathway?

- an intracellular signaling pathway important for anti-apoptosis, cellular proliferation, and angiogenesis - Mutations in this pathway can contribute to cancer pathogenesis - STEPS = growth factor binds to the tyrosine kinase, which autophosphoylates itself. This activates Phosphoinositide 3-kinase (PI3K), which then phosphorylates PIP2 to PIP3. This activates Akt (or protein kinase B). This activates mTOR, which translocates to the nucleus to induce genes involved in cell survival, anti-apoptosis, and angiogenesis

What is a *Benign glomus tumor (glomangioma)*?

- can be a very tender, small, red-blue lesion under the nail bed - The tumor originates from the modified smooth muscle cells that control the thermoregulatory functions of dermal glomus bodies (Differential diagnosis for a colored neoplasm under the nail = subungual melanoma)

What is the drug: Infiximab?

- chimeric (human/murine) IgG1 antibody to TNF-alpha

How does total systemic vascular resistance change during exercise?

- exercise DECREASES total systemic vascular resistance - this is d/t the vasodilation within active skeletal muscles, which is mediated by the local release of adenosine, potassium ions, ATP, CO2, and lactate - NOTE: There is a rise in mean arterial pressure, however, d/t the contraction of arterioles in all other tissues (aside from the actively working muscles - b/c the blood then gets shunted here)

What are the side effects of Erythropoiesis-stimulating agents (ESAs) used to treat anemia d/t chronic kidney disease?

- increased risk of *thromboembolic events* and *hypertension* - ESAs = Erythropoietin & Darbepoietin alpha

How does the topical cream *Capsaicin* help with neuropathic pain?

- it causes a defunctionalization of afferent pain fibers and depletes substance P

What is Streptococcus Bovis (S. Gallolyticus) associated with?

- it colonizes the gut, and can cause bacteremia and subacute endocarditis and is associated with colon cancer

What is a typical presentation of Churg-Strauss Syndrome?

- late onset asthma, rinosinusitis, and eosinophilia are classic... but it can affect many other organs too - Can also see asymmetric neuropathy d/t the vasculitis affecting epineural vessels (the small vessels that supply peripheral nerves) - P-ANCA (MPO ANCA)

What is the treatment for a pregnant mother who is positive for group B strep?

- rectal and vaginal screening at 35-37 weeks. If positive, or if the mother had a previous child affected with GBS, then give intrapartum antibiotic prophylaxis - Penicillin is first line, but ampicillin is an acceptable alternative NOTE: treating the mother earlier, at like 30 weeks does not help, because it will get rid of the bacteria for a few weeks, but she is at risk of getting colonized again before giving birth

What are the histology findings of Medulloblastoma (children)?

- small, poorly differentiated cells with scant cytoplasm and little stroma... Homor-Wright rosettes and small blue cells - Usually in the cerebellum and can compress the 4th ventricle

What is at the 3' end of tRNA?

- tRNA has a CCA sequence at its 3'-end that is used as a recognition sequence by proteins The 3' terminal hydroxyl group of the CCA tail serves as the amino acid binding site

How does the confidence interval change with increasing sample size?

- the confidence interval gets smaller (i.e. more precise) with increasing study sample size MATH: - Standard Deviation = SD - Standard Error (SE) = SD / (square root number in the sample) - 95% Confidence interval = x +- 1.96 (SE) - So with a large sample number, the # standard error will decrease leading to a smaller (more precise) confidence interval - with a decreased width

What is the Infundibulopelvic (IP) ligament (in women)?

- the infundibulopelvic (IP) ligament is also called the suspensory ligament of the ovary... and it houses the ovarian nerve plexus, and ovarian artery, ovarian vein, and lymphatic vessels NOTE: An ovarian torsion typically involves twisting of the infundibulopelvic ligament, usualy d/t the weight of a large adnexal pass... The resulting occlusion of blood and nerve supply to the ovary results in severe, acute pelvic pain and ovarian ischemia

What composes the portal triad, which runs through the hepatoduodenal ligament?

- the portal triad runs through the hepatoduodenal ligament and is composed of the hepatic artery, portal vein, and common bile duct - The Pringle maneuver is a surgical technique, where the portal triad is occluded, in order to distinguish the source of right upper quadrant bleeding. If hepatic bleeding persists, then the IVC or hepatic veins are likely to be injured NOTE: The cystic artery is a branch off of the right hepatic artery

What nerve is particularly prone to injury in the posterior triangle of the neck?

- the spinal accessory nerve (CN X1) is a pure motor nerve that passes superficially through the posterior triangle of the neck, and provides innervation to the sternocleidomastoid and trapezius - Injury to this nerve will result in trapezius weakness (and possibly sternocleidomastoid weakness if the injury is proximal) - Trapezius weakness manifests as drooping of the shoulder, impaired abduction of the arm above horizontal (d/t weakness in rotating the glenoid upward), and winging of the scapula

What mutations causes von-Hippel-Lindau? And what are some manifestations/complications?

- von-Hippel Lindau is caused by a deletion of the VHL gene on chromosome 3p (it is Autosomal Dominant) - Characterized by many tumors, both malignant and benign - HARP: Hemangioblastoma (in retina, brain stem, cerebellum, and spine), Angiomatosis, Renal cell carcinoma (clear cell), and Pheochromocytoma

What hemoglobins are seen in alpha thalassemia intermedia and major?

- α-thalassemia intermedia (3 gene deletion) = "HbH" = β chains form tetramers ( β4) - α-thalassemia major (4 gene deletion) = "Hb Barts" = lethal in utero, γ chains form tetramers (γ4)

The presence of what is a main indicator to the severity of a mitral regurg. murmur?

-*The presence of an audible S3 gallop* S3 is generated by sudden cessation of blood flow into the left ventricle during the passive filling phase of diastole (rapid ventricular filling phase). A higher volume of blood flow or a more dilated left ventricle is more likely to produce an S3... So in patients with MR, an S3 is the best indicator of severe MR with left-sided volume overload (absence of an S3 can be used to exclude severe chronic MR)

What is the vaginal pH change in: --- Bacterial vaginosis --- Trichomoniasis --- Candida vaginitis

--- Bacterial vaginosis = *pH > 4.5* --- Trichomoniasis = *pH > 4.5* --- Candida vaginitis = *Normal pH (3.8-4.5)*

Describe the process and findings of both Acute Interstitial Pancreatitis, and Acute necrotic pancreatitis:

--- Pancreatitis is a continuum and begins as Acute intersitial pancreatits and can progress to Acute necrotic pancreatitis--- *Acute Interstitial Pancreatitis:* - Duct obstruction leads to stasis of secretions and digestion of adipose cells by lipase. This results in formation of fatty acids, that bind to calcium, and precipitate as calcium salt. Areas of focal necrosis and calcium precipitation induce an inflammatory reaction - The pancreas looks edematous, and on light microscopy, interstitial edema, focal fat necrosis, and Ca deposits are seen *Acute Necrotic Pancreatitis* - The inflammatory process continues, and the edema causes decreased blood flow to the acini. Ischemia damages acini, which causes abnormal activation of trypsin. Trypsin then can activate other enzymes, which autodigest pancreatic tissue, and also can destroy blood vessels causing hemorrhage into necrotic areas. - Black areas of hemorrhage are seen on gross exam, along with areas of white chalky fat necrosis are visible in the pancreatic tissue, and these can spread to mesentery, omentum, and other parts of the abdominal cavity.

What are 3 different Alzheimers treatments?

----------AD therapies---------- - 1 - Enhanced cholinergic neurotransmission (b/c patients with AD have decreased Ach) --- Donepezil, Galantamine, Rivastigmine, Tacrine - AChE inhibitors - 2- Neuroprotection via antioxidants (may slow functional loss) --- Vitamin E (a-tocopherol) - neuroprotective agent that may slow functional loss - 3- NMDA receptor antagonism (helps prevent excitotoxicity (mediated by Ca) --- Memantine - NMDA receptor antagonist

What class of hypertensive medication should be used in caution in a patient with renal artery sclerosis?

-ACE Inhibitors (-pril) (and angiotensin receptor blockers: - sartan) - Patients with renal artery sclerosis will have reduced renal blood flow, and this will decrease GFR... To maintain GFR, the RAAS system is stimulated, and Angiotensin II will constrict the efferent arteriole - ACE inhibitors or Angiotensin II receptor blockers cause efferent arteriolar vasodilation that causes the GFR to fall and may lead to the development of acute renal failure NOTE: This is most worrisome if the patient has bilateral renal artery sclerosis because in unilateral, the normal kidney can compensate for the decreased GFR... But if bilateral, this compensation cannot occur

What is the mechanism of the -azoles? And, what is a main side effect?

-Azoles inhibit 14-a-demethylase, which converts lanosterol into ergosterol, which is an essential component of the fungal cell membrane - Side effects are: --- testosterone synthesis inhibition (gyneocomastia) --- liver dysfunction (d/t P450 inhibition) --- drug-drug interactions (because 14-a-demethylase is a cytochrome P450 enzyme, so -azoles can inhibit cytochrome p450, which could cause other drugs to have increased toxicity) NOTE: Ketoconazole blocks several stpes in steroid synthesis and can therefore be used to treat Cushing syndrome if surgery is not an option

What is the most common mutation in Cystic Fibrosis? And, what does this result in?

-CF is most commonly d/t a 3-base pair deletion of phenylalanine in the CF transmembrane conductance regulator (CFTR) gene at amino acid position 508 (F508) - This mutation impairs post-translational processing of CFTR, resulting in shunting of CFTR toward the proteasome, with complete absence of the protein on the cell surface

What is the difference between Confounding Bias vs. Effect modification?

-Confounding bias - there is a 3rd factor, but when this factor is taken away, there is NO real effect on outcome --- EX: Drug A seems to increase lung cancer rates... BUT only smokers take drug A. So if we eliminate smoking, we see that Drug A really has no effect... If we were to break down the data into smokers and non-smokers, we would find that Drug A has no effect on cancer -Effect modification - There is a real effect, but the effect requires a 3rd variable --- EX: Drug A seems to increase lung cancer rates... But when looked at further, this only occurs in patients positive for Gene X. So if we break it down into Gene X positive, and Gene X negative, we will see that Drug A does have an effect, but it requires Gene X as its effect modifier - Effect modification is NOT a bias NOTE: - A stratified analysis can help distinguish these (this is where you further break the study into 2 groups (i.e. smokers vs. non-smokers, or pts with a gene vs. pts without a gene))... - A stratified analysis will eliminate the confounding bias (the risk ratio will go away in both groups once it is split into 2 sub groups)... - However, in effect modification, the risk will be seen in one group and not in the other, and this will mean that the one group has an effect modifier

Role of Sertoli and Leydig cells in male development

-First SRY gene on Y chromosome produces testes determining factor, and the testes form -Leydig (interstitial cells) - secrete testosterone which promotes male internal genitalia (via mesonephric (Wolffain) duct) and external genitalia -Sertoli (cells inside the testicle) - secrete Mullerian inhibitory factor (MIF) which suppress development of the paramesonephric (Mullerian) duct, which suppresses internal female genitalia... Sertoli cells also produce androgen-binding protein, which concentrates testosterone in the seminiferous tubules to enable spermatogenesis

What does IL-10 do?

-IL-10 is anti-inflammatory and has immunomodulatory roles. It attenuates the immune response through inhibition of TH1 cytokines (IL-2 and IFN-y), reduction of MHC-II expression, and suppression of activated macrophages and dendritic cells NOTE: TGF-B is also anti-inflammatory

What interleukins induce the differentiation into TH1 cells, and which induce TH2 cells?

-IL-12 is secreted by macrophages and stimulates the differentiation into TH1 - IL-4 is released by other types of antigen-presenting cells and facilitates differentiation into the TH2 subset

What are some clinical features of IgA deficiency?

-Its usually asymptomatic -Can get recurrent sinus/pulmonary infections and GI infections -Concomitant autoimmune diseases are common -Anaphylaxis during transfusions can occur (this is b/c if the patient has very severe IgA deficiency, their body may make IgE antibodies directed against IgA... So when transfused with blood products that may contain a small amount of IgA, the patient will possibly develop anaphylaxis)

Layers of the gastric mucosa:

-Simple columnar epithelial cells (contains cells that secrete mucus) -Upper glandular layer (contains parietal cells which are pale/pink, round, plate-like cells) -Deeper aspect of gastric glands (mostly small, basophilic, granular chief cells that make and secrete pepsinogen) -Muscularis Mucosae -Submucosa (contains well-vascularized connective tissue)

What is the rate limiting step in glycolysis? And, what non-glucose monosaccharide (galactose, mannose, fructose) bypasses this step?

-The rate limiting step is the conversion of Fructose-6-P to Fructose-1,6-BP... which is catalyzed by Phosphofructokinase-1 - Dietary fructose is phosphorylated in the livver to Fructose-1-P and is rapidly metabolized because it bypasses PFK-1 (Fructose eventually enters glycolysis as Glyceraldehyde-3-P)

What are the 5 steps of Neutrophil arrival and function, and what happens during each step?

1 - *Margination* - vasodilation slows blood flow and the neutrophils can move from the center to the periphery of the vessel 2 - *Rolling* - Neutrophils roll on the endothelium and the *Sialyl Lewis X* on the Neutrophils comes in contact with *E-Selecting & P-selectin* on the Endothelial cell... this slows down the neutrophils 3 - *Activation* - The Neutrophil Integrins are upregulated by chemokines (C5a & LTB4) 4 - *Tight Adhesion / Crawling* - Neutrophils firmly attach to the endothelium via *binding of CD 18* (Beta 2 integrin) to ICAM-1* (Intercellular adhesion molecule-1) on endothelial cells 5 - *Transmigration* - Neutrophils squeeze between cells *via integrin attachments and adherence to PECAM-1* (platelet endothelial cell adhesion molecule-1)

What are 3 (genetic) ways in which Down Syndrome can arise?

1 - *Meiotic nondisjunction* 2 - *Unbalanced translocation* 3 - *Mosaicism* - Affected individuals have 2 distinct cell lines as a result of nondisjunction during mitosis: one with a normal genotype and one with trisomy 21. The proportion of affected cells determines the severity of the DS features

Steps of the GI adenoma to carcinoma sequence:

1 - Progression from normal mucosa to a small adenomatous polyp - *APC inactivation* 2 - Increase in size of the adenoma - *KRAS activation* 3 - Malignant transformation of adenoma to carcinoma - *inactivation of TP53* (And increased expression of COX)

By what 2 mechanisms can Beta blockers reduce blood pressure?

1 - reduce myocardial contractility and heart rate 2 - decrease renin release by the kidney (which is mediated in part by sympathetic stimulation of B1 receptors)

What are the Percentages associated with 1, 2, and 3 standard deviations?

1 SD = 68% 2 SD = 95% 3 SD = 99%

How many brachiocephalic arteries are there? And, how many brachiocephalic veins are there?

1 brachiocephalic artery (right) 2 brachiocephalic veins (left and right)

What are 3 lab tests that indicate poor prognosis in a pt with cirrhosis?

1&2 - Tests that indicate impaired biosynthetic capacity = Elevated PT, and hypoalbuminemia 3 - Test that indicates impaired transport & metabolic capacity = elevated bilirubin

Describe the GI Adenoma-Carcinoma sequence:

1) - APC mutation (inactivation) - increases risk of polyp formation 2) - KRAS mutation (activating: RAS-GTP bound) - leads to formation of polyp 3) - p53 mutation (inactivation) - allows for progression to carcinoma (COX also increases progression to carcinoma, so Aspirin can impede progression)

Describe the stepwise mechanism of Digoxin:

1. Digoxin directly inhibits the Na/K ATPase. This then initially increases the Na concentration inside the myocardial cell 2. The increased Na inside the cell will slow the action of the Na/Ca exchanger (which brings Na in, and Ca out) because it will not want more Na inside the cell - This therefore leads to increased Ca inside the cell 3. Increased intracellular Ca stimulates binding of Ca to Troponin, causing improved myocyte contractility

What 3 things are used in the treatment of Diphtheria, and put them in order of importance:

1. Diphtheria antitoxin 2. Penicillin or Erythromycin 3. DPT vaccine

What is the first and second leading cause of death in a Marfans patient?

1st - *Aortic Dissection* d/t cystic medial degeneration 2nd - *Cardiac failure* secondary to mitral valve prolapse and/or aortic regurgitation

Quick hints for Branchial arch derivatives:

1st - CN 5 - MMMM 2nd - CN 7 - SSSS (and S for Seven - CN7) 3rd - CN 9 - "_pharynge_" 4&6 - CN 10 - ACCCT

How long does renal compensation for Alkalosis or Acidosis take?

24-48hrs

What is normal osmolarity of plasma?

300 mOsm/L - Therefore this is the same osmolarity as the proximal tubule

What numbers are the shortcut to calculate rate on an ECG?

300, 150, 100, 75, 60, 50

What is a normal, healthy, A-a gradient?

5-15 mmHg - Hypoxemia in the setting of a normal A-a gradient indicates that both the alveolar and the arterial partial pressure of oxygen are low

What is a normal FEV1/FVC ratio?

80

What is the most common genetic make-up of a complete mole?

90% of times, a complete mole most results from the fertilization of an ovum what has no maternal chromosomes... The haploid 23X sperm is then duplicated, forming diploid *46,XX* tissue that contains *only paternal DNA* NOTE: 46, YY moles from the duplication of 23Y sperm have not been observed as a zygote without an X chromosome will not survive - Less commonly, 2 sperm can fertilize an empty ovum and create 46, XY tissue

What is the statistical power?

= 1 - Beta Beta = the probability of committing a Type II error (stating that there is NOT a difference when there really is one) "B = Blindly let a guilty man free"

What is the equation for a 95% and 99% confidence interval?

= Mean +/- [z-score for confidence interval] x SE - Standard Error = SD/√n - Z for 95% = 1.96 - Z for 99% = 2.58

What is the equation for physiologic dead space?

= Tidal Volume x ([PaCO2 - PeCO2]/PaCO2) - PaCO2 = arterial partial pressure of CO2 - PeCO2 = partial pressure of CO2 in the expired air

What is *Fat Embolism Syndrome*?

A condition affecting >10% of patients with severe skeletal injuries - characterized by: *pulmonary insufficiency, diffuse neurological impairment, petechiae, thrombocytopenia, and anemia* - Fat globules dislodge from bone marrow and enter the marrow vascular sinusoids, and then occlude pulmonary microvessels - Microvascular occlusion of the cerebral white matter, brain stem, and spinal cord cause the neuro manifestations - The multiple fat emboli can stain black with *Osmium Tetroxide*

What is the effect of urinary citrate and stone formation?

A high urinary citrate concentration has stone-preventing effects as citrate binds to free (ionized) calcium, preventing its precipitation and facilitating its excretion - Potassium Citrate can be prescribed to prevent recurrent calcium stones in adults when dietary modifications are unsuccessful

What is the strongest single risk factor for suicide?

A history of previous suicide attempt

An old man w/ back pain at night, that is not relieved by rest or analgesics, suggests what?

A malignant cause of back pain - Common malignancies with a propensity for bony metastasis include: Protate, Breast, Kidney, Thyroid, Lung (PB/KTL - Lead Kettle) (it is not osteoarthritis is b/c it doesnt get better with rest, it is worse at night, and not relieved with analgesics)

What is Calcineurin?

A protein phosphatase inside T-cells. When activated upon by receptor stimulation, it dephosphorylates Nuclear Factor of Activated T-cells (NFAT), which allows NFAT to go in the nucleus, and bind IL-2 promoter (IL-2 stimulates growth and differentiation of T-cells) Cyclosporine and Tacrolimus - 2 immunosuppressants used in transplant patients that inhibit Calcineurin activation

In a statistically significant study. What parameter must the confidence interval show, and what must the corresponding p-value be?

A result is considered statistically significant if the 95% confidence interval does not cross the null value, which corresponds to a p-value <0.05 EXAMPLE: if a RR is 1.4, with a 95% confidence interval of 1.02-1.85... Then since the RR > 1, we say that there is a risk, and we can say it is statistically significant because the 95% confidence interval does not contain the null value (of 1.0 for relative risk and odds ratio)... And therefore the p-value would be <0.05

Regarding capillary pressure and lymphatic drainage, when does edema start to occur?

A rise in central venous pressure (d/t right heart failure), leads to a rise in capillary hydrostatic pressure, which will increase net plasma filtration (into the interstitium), and increase interstitial fluid pressure - As the interstitial fluid pressure increases, so does lymphatic drainage, which can compensate for moderate central venous pressure elevations and prevent the development of clinically apparent edema - However, large central venous pressure elevations can overwhelm lymphatic reabsorptive capacity, leading to development of overt edema

What is an ecological study?

A study using populations not individuals

What is *Lipofuscin*

A yellow-brown *"wear and tear"* pigment associated with normal aging - It is an insoluble pigment composed of lipid polymers and protein-complexed phospholipids - It is the product of free radical injury and *lipid peroxidation* - Autopsy of an elderly person will reveal deposits in heart, colon, liver, kidney, eye, and other organs

How does a-fib cause systemic hypotension in a patient with pre-existing chronic aortic stenosis / LV hypertrophy?

A-fib causes a loss of the atrial contraction, which is especially important for patients with LV hypertrophy / aortic stenosis... This loss of atrial contraction can reduce left ventricular preload and cardiac output sufficiently to cause systemic hypotension

What class of anti-hypertension medications is most recommended in all patients with systolic heart failure?

ACE-inhibitors / Angiotensin II receptor blockers (-pril, & -sartan) - In addition to improving hemodynamics (improved blood pressure control), these agents inhibit the chronic angiotensin II-mediated adverse cardiac remodeling that occurs with heart failure, providing an additional mortality benefit

What displacement does the ACL and PCL prevent?

ACL - Prevents ANTERIOR displacement PCL - Prevents POSTERIOR displacement

What 3 substances are derived from POMC (Pro-opio-melano-cortin)?

ACTH, MSH (Melanotropin), and Endorphins

Name 4 antibodies that are seen in Polymyositis and Dermatomyositis (1 is most important):

ANA Anti-Jo-1 (Anti-Histidyl tRNA Synthase) (most important) Anti-SRP Anti-Mi-2

What binds to Potassium channels in Pancreatic beta cells to close them and cause depolarization?

ATP

In what direction does the trachea deviate in a pneumothorax and pleural effusion?

AWAY from the affected lung - This is b/c the excess air or fluid in the pleural space will push against the mediastinal structures

What HIV drug is contraindicated if the patient has a HLA-B*57:01 mutation?

Abcavir (a Nucleoside reverse transcriptase inhibitor)

What is "myotonia"?

Abnormally slow reaction of muscles

What is the primary cause for the formation of a lung abscess in the setting of a bacterial infection?

Abscess formation is largely driven by neutrophil recruitment and activation leading to the release of cytotoxic granules that kill bacteria but also cause liquefying necrosis of surrounding tissue

A Ventricular septal defect & a persistent *Truncus Arteriosus* can be the result of what embryologic absence?

Absent ectodermal neural crest cells

What is the typical presentation of *Acute Acalculous cholecystitis*?

Acalculous cholecustitis is an acute inflammation of the gallbladder in the absence of gallstones - It typically occurs in critically ill patients (eg. those with sepsis, severe burns, trauma, immunosupression) d/t gallbladder stasis and ischemia - Clinical findings may be subtle, and include fever, RUQ pain, and leukocytosis

What are the 3 ketone bodies created?

Acetone Acetoacetate B-hydroxybutyrate

Release of what neurotransmitter is inhibited in Botulinum infection?

Acetylcholine

What should you do when dealing with a mother who is answering all of her kid/teenagers questions?

Acknowledge the mothers concerns and ask to speak with the patient alone *In situations where a parent's presence may interfere with obtaining honest answers from an adolescent, physicians should politely ask the parent to wait outside and interview the patient privately* - This is also important when discussing drugs, alcohol, tobacco, and sexual activity with teenagers

What clotting factors does protein C work on?

Activated Protein C cleaves and inactivates *Va* and *VIIIa* NOTE: Factor V Leiden mutation produces a factor V resistant to inhibition by activated Protein C (Factor V leiden is the most common cause of hypercoagulability in Caucasians)

What state is RB active? And, what does this prevent?

Active = DEPHOSPHORYLATED-RB - This prevents the cell from proceeding from G1 to S stage of the cell cycle

What are some symptoms of Vitamin A overdose?

Acute = nausea, vomiting, vertigo, blurred vision Chronic = alopecia, dry skin, hyperlipidemia, hepatotoxicity, hepatosplenomegaly, and visual difficulties, and possible benign intracranial hypertension (pseudotumor cerebri) Teratogenic = microcephaly, cardiac abnormalities, fetal death (in first trimester)

What blood cancer has "Auer Rods"

Acute Myeloid Leukemia

What is the mechanism of Acyclovir?

Acyclovir is a Nucleoside (Guanosine) analog that gets incorporated into newly replicating viral DNA to ultimately terminate DNA chain synthesis - A Virus encoded Thymidine Kinase converts acyclovir into acyclovir monophosphate, and then later converted into acyclovir triphosphate, which competes with deoxyguanosine triphosphate for viral DNA polymerase

What do these symptoms suggest: Enlarged/non-tender gallbladder, weight loss, obstructive jaundice?

Adenocarcinoma at the head of the pancreas compressing the common bile duct

Dermatomyositis has a strong association with malignancy... specifically which ones?

Adenocarcinomas - Especially lung, colorectal, and ovarian

What is Adenomyosis and what are some common symptoms?

Adenomyosis is the presence of endometrial glandular tissue within the myometrium - Symptoms are Menorrhagia (heavy menstrual bleeding) (d/t increased endometrial surface), and dysmenorrhea (d/t endometrial tissue growth in the confined myometrial space), and a uniformly enlarged uterus on physical exam

What nerves mediate the Cough Reflex?

Afferent limb of the cough reflex is mediated by the internal laryngeal nerve (a branch of the superior laryngeal nerve, off of CN X). Internal laryngeal nerve contains only sensory and autonomic fibers. It is located directly behind the piriform recesses, which lie on either side of the laryngeal orifice.

What accounts for larger RBCs with bluish discoloration in a patient who was started on iron supplementation for Iron deficiency anemia?

After iron supplementation, hemoglobin levels increase as well as enhanced erythropoiesis, which results in a release of both mature RBCs and some reticulocytes (which are larger than mature RBCs) - The reticulocyte does not have a nucleus, but has retained a network of *ribosomal RNA*, which appears blue on Wright-Giemsa stain

What are the normal physiologic changes in lung aging?

Aging is associates with a steady decrease in chest wall compliance, but increase in lung compliance (d/t loss of elastic recoil). This results in no net change of total lung capacity, but there is a marked increase in residual volume, and a decrease in forced vital capacity.

What is the pathogenesis of Alcoholic hepatic steatosis (fatty liver)?

Alcohol metabolism generates excess NADH... This excess NADH decreases free fatty acid oxidation (so a build up of fats in the liver) - Also, contributing pathogenetic factors include impaired lipoprotein assembly and secretion, and an increase in peripheral fat catabolism

"urine that turns black on standing"

Alkaptonuria

Describe the changes in GFR, RPF, and FF (Filtration Fraction) in: - Afferent arteriole constriction - Efferent arteriole constriction

Also note: - FF = GFR/RPF - Prostaglandins preferentially dilate the AFFERENT arteriole (causing increased GFR, increased RPF, but no net change in FF) - Angiotensin II preferentially constricts the EFFERENT arteriole (causing increased GFR, decreased RPF, and increased FF) [NOTE: RPF = RBF * (1 - hematocrit)]

What is the main resistance mechanism for Aminoglycosides?

Aminoglycoside resistance is most commonly d/t *antibiotic-modifying enzymes* - These enzymes add chemical groups to the antibiotic, which diminishes the ability to bing to the 16S ribosomal RNA within the 30S ribosomal subunit

What enzyme is deficient in the congenital form of Sideroblastic anemia?

Aminolevulinic acid synthase (ALA synthase) - This is X-LINKED!!! (AAPUUCF)

What class 3 antiarrhythmic has a lower chance of causing Torsades?

Amiodarone

What are the names of the 4 class III Anti-arrhythmics?

Amiodarone Ibutilide Doftilide Sotalol

What is a subluxation?

An incomplete or partial dislocation of a joint

What is the pathogenesis of Anovulation?

Anovulation is common in the first several years after menarche and the last few years before menopause... It manifests with marked menstrual cycle variability - In the absence of ovulation, the ovarian follicle does not degenerate and become a corpus luteum. As a result, no progesterone is produced and estrogen levels remain particularly high, causing the endometrium to remain in the proliferative phase. Chronically proliferative endometrium becomes disorganized and fragile with unstable venous capillaries, resulting in irregular periods of stromal breakdown with variable, but often heavy, bleeding.

What are symptoms of Anterior dislocation of the humerus?

Anterior dislocations of the humerus are the most common, and most commonly occurs with a blow to an externally rotated / abducted arm (throwing a football) - They present with flattening of the deltoid prominence, protrusion of the acromion, and anterior axillary fullness (b/c the humeral head has moved here) - The axillary nerve is commonly damaged, which innervates the deltoid and teres minor, and provides sensation to the skin overlying the lateral shoulder

What 2 drugs should be given for a pt with Cholinesterase poisoning?

Antidote = *Atropine* (competitive inhibitor of ACh receptors) & *Pralidoxime* (regenerates AChEsterase if given early) NOTE: Cholinesterase poisoning is usually d/t organophosphates, that irreversibly inhibit AChE... Sx = Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle & CNS, Sweating, and Salivation

What antibody is typically positive in Primary Biliary Cirrhosis? Who is the most common person it presents in?

Antimitochondrial Ab - Usually in middle-age woman

What is Antiphospholipid Antibody syndrome?

Antiphospholipid Antibody syndrome is a primary or secondary autoimmune disorder characterized by the presence of Antiphospholipid antibodies in the setting of venous or arterial thromboembolism and/or recurrent pregnancy loss - It is frequently secondary to SLE, where up to 30% of patients with SLE have Antiphospholipid Antibodies - The Antiphospholipid Antibodies cause a paradoxical PTT prolongation... because in vivo, they actually produce a hypercoaguable state d/t the activation of phospholipid-dependent coagulation pathways - These antibodies also cause False-positive results on Nontreponemal Syphilis tests by reacting with Cardiolipin

What are the 2 diastolic murmurs:

Aortic Regurgitation Mitral Stenosis (Atrial septal defect can cause a diastolic murmur d/t increased blood flow across the tricuspid valve, but this is best detected with fixed split inspiration)

The terms, "Bounding femoral pulses", "carotid pulsations", and "head bobbing", indicate what murmur?

Aortic regurgitation - Aortic regurg causes an increase in total stroke volume with abrupt distention and rapid falloff of peripheral arterial pulses, resulting in a wide pulse pressure. This leads to bounding peripheral pulses, and head bobbing with each heartbeat.

How does amyloid stain under Congo-Red?

Apple-Green Birefringence

Key Stroke: ASA (spine)

Area = Anterior Spine Key finding = Loss of motor, pain, temp sensation below the lesion... but vibration and proprioception are spared

Key Stroke: PICA

Area = Lateral Medulla Key Finding = Dysphagia, hoarseness

Key Stroke: AICA lesion

Area = Lateral pons Key finding = Facial droop, hearing loss

Key Stroke: ASA (medulla)

Area = Medial Medulla Key finding = Contralateral motor loss, tongue deviation (to the side of the lesion)

Key Stroke: Basilar Artery

Area = Ventral Pons Key finding = "Locked in" - quadriplegia, but the pt can blink

What amino acid is used to synthesize Nitric Oxide?

Arginine

"ash-leaf spots" is a buzzword for what neurocutaneous disorder?

Ash-leaf spots are HYPOpigmented

Jimson weed causes what type of poisoning?

Atropine / Muscarinic Antagonist poisoning! - Treat with Physostigmine

What type of depression is a MAO inhibitor useful in?

Atypical depression and treatment-resistant depression - It is still NOT first line for these because of its risk profile

*Anti-smooth muscle* is associated with what disease?

Autoimmune hepatitis type 1

What is the inheritance of Adult Polycystic Kidney disease?

Autosomal Dominant

What is the inheritance of von Willebrand dz?

Autosomal Dominant

BRCA1 and BRCA 2 are inherited in what fashion and are associated with what cancers?

Autosomal Dominant - Associated with breast and ovarian cancer - the BRCA1 & BRCA2 genes are normally involved in double-stranded DNA break repair

What is Inclusion cell (I-cell) disease?

Autosomal recessive lysosomal storage disorder - d/t failure of the Golgi to phosphorylate mannose residues on glycoproteins... This results in proteins being secreted extracellularly instead of delivered to the lysosome - Clinical features = coarse facial features, gingival hyperplasia, clouded corneas, restricted joint movements, claw hand deformities, kyphoscoliosis, and high plasma levels of lysosomal enzymes - Usually fatal in childhood

What is Hartnup Disease?

Autosomal recessive metabolic disorder, with inactivating mutations affecting neutral amino acid transporters (like tryptophan). Thus, Tryptophan cannot be absorbed in the small intestine and kidney. Tryptophan gets converted to Niacin (with B2 - Riboflavin, and B6 - Pyridoxine as cofactors). Low Niacin causes Pellagra (Diarrhea, Dementia, and Dermatitis, and hyperpigmentation of sun-exposed skin). You can also see cerebellar ataxia early in childhood in pt with Hartnup dz. Dx: via detection of high levels of neutral amino acids in the urine. Tx: High protein diet, and daily niacin or nicotinamide supplementation.

How does normal pressure hydrocephalus cause urinary incontinence?

B/c of distortion of the white matter - Bladder control is influenced by descending cortical fibers that run in the distended paraventricular area - Later, loss of cortical inhibition on the sacral micturition center causes the development of urge incontinence

What receptors does Dobutamine stimulate? And, what it its main uses?

B1 > B2 > a1 - Main effects = Positive inotropy (contractility) and chronotropy (heart rate) (Inotropy > chronotropy)... And mild vasodilation - Use = management of refractory heart failure associated with left ventricular systolic dysfunction and cardiogenic shock

The Ixodes tick can transmit what 2 infectious things

Babesia - causes Babesiosis Borrelia Burgdoferi - causes Lyme dz

Intraerythrocytic inclusions of "Rings and/or Maltese Crosses" is suggestive of infection by what?

Babesia species (Plasmodium (malaria) also can cause rings, but not crosses)

Someone that works in "Wool Processing" is suggestive of what microbio bug?

Bacillus Anthracis

What is the mechanism of Baclofen? And, what is it used for?

Baclofen is an agonist at the GABA-B receptor, which induces muscle relaxation - It is effective as monotherapy for the treatment of spasticity secondary to both brain and spinal cord disease (including multiple sclerosis)

What are the 2 most common organisms isolated from a general intraabdominal infection?

Bacteroides Fragilis & E. Coli (Bacteroides is a Gram negative part of the Enteric normal flora)

Where in the brain is the most common site of Copper deposition in a patient with Wilsons disease?

Basal Ganglia - atrophy of the basal ganglia ensues d/t generation of free radicals

What is becks triad? And what does it indicate?

Becks triad = JVD, Hypotension, Diminished heart sounds It indicates - Cardiac Tamponade

What is the best drug of choice for an old person with Insomnia

Benzos, Antihistamines, and sedating anti-depressants should be avoided in treatment of insomnia in the elderly d/t their adverse effects

If someone has a coarctation of the aorta, what else should you be suspicious for?

Berry Aneurysm - Makes sense b/c if someone has an abnormal aorta, then it is possible for them to have other vessel problems, like in the brain

In terms of insulin release from the pancreas, Stimulation of alpha 2 and stimulation of beta 2 on the pancreas will do what?

Beta 2 - *promotes* insulin release Alpha 2 - *inhibits* insulin release (The alpha-2 effect is prominent, causing sympathetic stimulation to lead to overall inhibition of insulin secretion)

Why would a patient with Beta Thalassemia trait and Diabetes have a falsely low HbA1c?

Beta thalassemia has an elevated HbA2 level to compensate for the beta globin chain underproduction - But these cells with HbA2 are more prone to hemolysis - ie. increased red cell turnover - *HbA1c levels are affected by alterations in red blood cell survival - conditions that increase red blood cell turnover, can cause falsely low HbA1c levels*

What is the normal age (range) of Puberty in boys and girls?

Between the ages of *8 and 13 for girls* and *9 and 14 for boys*

Bile soluble vs. bile insoluble. Which can grow in bile?

Bile INSOLUBLE = able to grow in bile (Hence the boots in Sketchy - showing that they stay solid in bile and are able to grow)

Describe the pathogenesis of how Crohns can lead to gallstones:

Bile acids are secreted into the duodenum, where they emulsify fat - Since bile acids are charged, they need transporters to be re-absorbed... These *transporters are located in the ileum* - The terminal ileum is the most common site of Crohns involvement, and therefore bile acids are lost in the feces when the terminal ileum is inflamed - There will therefore be a lower bile acid in the bile, so the ratio of cholesterol/bile acids increases & supersaturation of the bile with cholesterol can lead to gallstones

Haptoglobin does what?

Binds free Hemoglobin (like after hemolysis)

What kidney disease is associated with "spike & dome" appearance on electron microscopy (or methenamine silver stain)

Biopsy shows - uniform, diffuse thickening of the glomerular capillary wall on light microscopy without an increase in cellularity

What characteristics does E. Coli have when grown on each of these Agars: Blood, MacConkey, Eosin Methylene Blue (EMB)?

Blood - most strains are B-hemolytic MacConkey - Pink Eosin Methylene Blue (EMB) - green metallic scheen

What antibodies are present in people with blood group A, B, AB, and O... And what type of antibodies are these (IgA, IgM, IgG, I,D)?

Blood group A: has Anti-B (IgM) Blood group B: has Anti-A (IgM) Blood group AB: has no antibodies Blood group O: has Anti-A and Anti-B (usually IgG)

Borderline personality disorder:

Borderline personality disorder is characterized by a persistent pattern of unstable relationships, mood lability, and impulsivity - Individuals with borderline personality disorder may exhibit suicidal ideation or behavior in the context of an interpersonal crisis in which they feel rejected of abandoned

Brown vs. Black gallstones:

Both Brown/Black pigmented gallstones arise from conditions that increase the amount of *unconjugated bilirubin* in bile *Brown gallstones* - associated with biliary tract infections (microbes producing B-glucuronidases) *Black gallstones* - occur w/ chronic hemolytic anemia (sickle cell) and/or increased enterohepatic cycling of bilirubin (Crohn dz)

Whats the difference between the Antibody binding site for complement and phagocytic cells?

Both bind the Fc portion, but the binding site for complement is closer to the hinge region than the binding site for phagocytes

What immune response is most common in chronic transplant rejection?

Both cellular and humoral (Type II and IV)

Where do both, Chromaffin cells of the Adrenal Medulla and Parafollicular C cells of the Thyroid, originate from?

Both the Chromaffin cells of the Adrenal Medulla and the Parafollicular C cells of the Thyroid originate from embryonic neural crest tissue (part of the ectoderm) NOTE: - The adrenal cortex is from the mesoderm - The thyroid follicular cells are endoderm

Sensation to the lateral forearm is supplied by what nerve?

Branches of the Musculocutaneous nerve called the: lateral cutaneous nerve of the forearm

What type of aphasia does damage to Brocas, Wernickes, and Arcuate fasciculus, cause?

Brocas - expressive aphasia with broken speech but good comprehension ("Broken Boca") Wernickes - receptive aphasia with poor comprehension, but fluent meaningless speech ("Wernicke is Wordy") Arcuate fasciculus - conduction aphasia with poor repetition (unable to repeat a sentence back) but appropriate comprehension and fluent, if sometimes paraphasic, speech

What are 3 dopamine agonists?

Bromocriptine (ergot) Pramipexole (non-ergot) Ropinirole (non-ergot) - These are useful in the tx of parkinsons - Bromocriptine can also treat prolactinemia (d/t the inhibitory effect dopamine has on prolactin secretion)

How does chronic transplant rejection manifest in the lungs?

Bronchiolitis Obliterans - lymphocytic inflammation, fibrosis, and, ultimately, destruction of the bronchioles

What is the pathogenesis of a Brown pigment stone

Brown pigment stones typically arise secondary to bacterial or helminthic infections of the biliary tract, which results in release of B-glucuronidase by injured hepatocytes and bacteria - B-glucuronidase converts conjugated bilirubin to the unconjugated form

What is used to culture Legionella Pneumophila?

Buffered Charcol Yeast Extract (BCYE) agar

How does the drug Buprenorphine act on the mu-receptor?

Buprenorphine is a partial opioid receptor agonist that binds with high affinity, but has low intrinsic activity

What is another way to say: C-ANCA and P-ANCA?

C-ANCA = PR3-ANCA (proteinase-3) P-ANCA = MPO-ANCA (myeloperoxidase)

A baby with poor feeding, weakness, and loss of muscle tone, who has been fed formula, juice, and honey.... What does he have?

C. BOTULINUM!!!! - *Honey* is always contaminated with Botulinum spores on USMLE! - there are in vitro (& stool) tests for organism and toxin

What nerve roots mediate the bicep and brachioradialis reflex?

C5-C6 spinal nerves

What nerve roots mediate the tricep reflex?

C7, C8

What 2 CD markers are on Macrophages?

CD14 CD40

What 3 cells are responsible for a type 4 hypersensitivity reaction?

CD4, CD8, and Macrophages - Macrophages present antigen to CD4, the CD4 then secrete cytokines that recruit CD8... CD4 and CD8 both produce IFN-g, which stimulates macrophage phagocytosis - Type 4 does NOT use antibody!!!

What are 3 ways you can distinguish Chronic Myeloid Leukemia from a Leukemoid reaction?

CML will have: - *Negative Leukocyte Alkaline Phosphatase stain* (LAP is an enzyme in the secondary granules of granulocytes & since the neoplastic cells have no intent to fight an infection, they do not care to make this) - *Increased Basophils* - *t(9:22)* - Philadelphia chromosome leading to BCR-ABL fusion with increased tyrosine kinase activity (NOTE: Leukemoid reaction is reactive neutrophilic leukocytosis like something d/t an infection)

Where is each cranial nerve nucleus located?

CN 1 and 2 are terminal nerves Midbrain: 3 and 4 Pons: 5, 6, 7, 8, Medulla: 9, 10, 11, 12

CN III (oculomotor) courses by what artery that makes it susceptible to injury if this artery has an aneurysm?

CN III is particularly susceptible to injury from ipsilateral posterior communicating artery aneurysms - An aneurysmal compression of CN III produces mydriasis (d/t superficial parasympathetic fiber damage) with diplopia, pitosis... and if the somatic efferent fibers are damaged as well, it can be down and out - This all occurs on the ipsilateral side

*Conjugate gaze anatomy*

CN VI (6), PPRF, and MLF are all in the *PONS* CN III (3) is in the midbrain

What is CREST syndrome?

CREST syndrome is variant of limited scleroderma (confined to face, forearm, fingers) *C* - Calcinosis *R* - Raynaud Phenomenon *E* - Esophageal dysmotility (d/t fibrous replacement of the muscularis) *S* - Sclerodactyly (thick/tight skin) *T* - Telangiectasia - The pathogenesis is chronic autoimmune inflammation, vascular endothelial injury resulting in chronic ischemic tissue damage, and excessive activation of fibroblasts leading to progressive tissue fibrosis - Both types of systemic sclerosis can also lead to pulmonary hypertension d/t increased collagen deposition in the pulmonary arterioles

What is the first line treatment of Trigeminal Neuralgia?

Carbamazepine

This triad suggests what: muffled heart sounds, JVD, and hypotension?

Cardiac Tamponade - This is Becks Triad

In short, what general effect do volatile anesthetics have on: Cardiovascular, Respiratory, Brain, Kidneys, Liver?

Cardio - myocardial depression and decreased cardiac output leading to low blood pressure Respiratory - respiratory depressant - decrease minute ventilation and cause hypercapnia Brain - decrease vascular resistance and increase cerebral blood flow, which increases ICP (undesired effect) Kidney - decrease GFR and increase renal vascular resistance decreasing renal plasma flow Liver - decrease liver blood flow

What type of Beta blocker is best post-MI?

Cardioseletive Beta-Blockers - with predominant action on B1 receptors Ex = Atenolol, Bisoprolol, Metroprolol

Carotid body vs. Carotid sinus

Carotid body = chemoreceptor for O2 Carotid sinus = baroreceptor sensitive to blood pressure

Describe how the *Carotid Sinus Massage* works

Carotid sinus massage puts pressure on the baroreceptors making them think that BP is elevated - This leads to increased afferent firing from the carotid sinus (via a branch of the glossopharyngeal nerve - CN IX), which in turn increases efferent vagal (CN X) parasympathetic tone - The increased parasympathetic tone slows conduction through the AV node and prolongs the AV node refractory period, helping to terminate a re-entrant tachycardia like SVT

What nerves mediate the afferent and efferent limbs of the reflex for the Carotid Sinus and Aortic arch baroreceptors?

Carotid sinus: --- Afferent limb - Glossopharyngeal (CN IX) --- Efferent limb - Vaugs (CN X) Aortic arch baroreceptor: --- Both Afferent & Efferent - Vagus

What does a Chi-Square test look at?

Categorical = Yes or no Ex: they either have high blood pressure or normal blood pressure... It does NOT compare the actual numerical value of each blood pressure

Celecoxib

Celecoxib is a selective COX-2 inhibitor. COX-2 is an inducible enzyme upregulated during inflammation by IL-1 and TNF-a. COX-2 inhibitors decrease inflammation by inhibiting COX-2 production of pro-inflammatory arachidonic acid metabolites. They do not affect COX-1, thus they have minimal gastroduodenal activity

Which immune response is most common in acute transplant rejection?

Cell Mediated (type IV hypersensitivity) - but sometimes it is humoral

How to Meningiomas present on histology?

Cells in lobules or whorls, and may have psammoma bodies

Name 4 characteristics that could cause a drug to be trapped in the plasma compartment:

Characteristics such as high molecular weight, high plasma protein binding, high charge, and hydrophilicity tend to trap the drug in the plasma compartment (resulting in a low Volume of Distribution, typically between 3-5L)

What is Cheyne-Strokes breathing?

Cheyne-Strokes breathing describes cyclic breathing in which apnea is followed by gradually increasing then decreasing tidal volumes until the next apneic period - It is seen in *Advanced heart failure*

Organophosphates (Insecticides) cause what type of poisoning?

Cholinesterase inhibitor poisoning (i.e. d/t an Acetylcholinesterase inhibitor) - Treat with Atropine!

What are the eye manifestations of congenital CMV?

Chorioretinitis

What is one way that Crohns lead to a bowel Obstruction?

Chrohns can cause *Strictures* - as a result of bowel wall edema, fibrosis, and hypertrophy (thickening) of the muscularis mucosae, which narrows the intestinal lumen. This can then progress to bowel obstruction

What is the mnemonic for the TCA cycle?

Citrate Is Krebs Starting Substrate For Making Oxaloacetate Sitrate, Isocitrate, a-Ketoglutarate, Succinyl-CoA, Succinate, Fumarate, Malate, Oxaloacetate __, N, N, G, F, __, N

What is "clasp-knife" Spasticity indicate?

Clasp-Knife spasticity = initial resistance to passive extension followed by a sudden release of resistance - This form of spasticity is seen with *upper motor neuron lesions* d/t lack of upper motor neuron inhibition of the spinal stretch reflex arc

What classes of anti-arrhythmics can cause Torsades?

Class 1A - Quinidine, Procainamide, Disopyramide Class III - Amiodarone, Ibutilide, Dofetilide, Sotalol

What class of Anti-arrhythmic can have an increased effect at faster heart-rates?

Class 1C Anti-arrhythmics - Flecainide & Propafenone - These are Na channel blockers that have increased effect at faster heart rate (use-dependent)... They can prolong QRS duration at higher heart rates

What are the names of the Class 3 anti-arrhythmics and how do they work?

Class 3 = AIDS: *Amiodarone, Ibutilide, Dofetilide, Sotalol* - They are potassium channel blockers, and inhibit the outward repolarizing current of the cardiomyocyts action potential - These drugs therefore increase action potential duration, refractory period, and QT interval - Serious adverse effect of QT interval = Torsades (Sotalol is particularly dangerous for this b/c it also has B blocking)

What is the classic population that gets Lupus?

Classically arises in middle-aged females, especially African American and Hispanic women

What is the equation to find the renal clearance (C) of any substance?

Clearance = ([urine concentration of S]x[urine flow rate])/(plasma concentration of S)

What is the best antibiotic to treat pulmonary abscesses involving combinations of anaerobic flora?

Clindamycin (remember, Clindamycin is for anaerobic infections ABOVE the diaphragm and Metronidazole is for anaerobic infections BELOW the diaphragm)

What medication should be used for prevention of cardiovascular vascular events in a patient with stable angina if Aspirin is not tolerated?

Clopidogrel - it is "as effective as aspirin for prevention of cardiovascular events and should be sued in patients with aspirin allergy"

What bacteria has a toxin that acts as a Lecithinase?

Clostridium Perfringens Toxin A acts as a Lecithinase, which cleaves Lecthin (a phospholipid), which damages cell membranes, and leads to myonecrosis and hemolysis

When is Colchicine used? And what are its side effects?

Colchicine is used in acute gout attacks - It is usually used second-line to NSAIDs, but it is first-line if the patient has mild-moderate renal failure, peptic ulcer disease, or other contraindications to NSAIDs - Side effects are GI issues b/c Colchicine also disrupts microtubule formation in the GI mucosa

At what portion of the nephron is there the LOWEST osmolarity if ADH levels are low

Collecting duct

What is the most common type of cardiac defect in patients with Downs Syndrome?

Complete Atrioventricular (AV) canal defect

On MMSE, how do you test Comprehension, Concentration, Short-term memory, Visual-spatial, and Executive function?

Comprehension - follow multistep command Concentration - Recite months of the year backwards Short-term memory - Recall 3 unrelated words after 5 min Visual-spatial - Draw intersecting pentagons Executive function - Draw a clock oriented to the time requested

Describe the 4 steps of lobar pneumonia: Congestion, red hepatization, gray hepatization, resolution

Congestion - Day 0-2 - Neutrophils respond and release cytokines to increase pulmonary capillary endothelium, which leads to the accumulation of erythrocytes and proteinaceous fluid in the alveolar space, resulting in the affected lobe becoming heavy and red Red Hepatization - Day 2-4 - The proteinaceous fluic transforms into fibrin strands, resulting in a confluent exudate of fibrin, neutrophils, and erythrocytes. The lobe appears liver-like (red, firm, airless) on gross exam Gray Hepatization - Day 4-7 - red cell disintegration along with increased leukocyte infiltration causes the lung to appear gray rather than red. Neutrophils begin to be replaced by macrophages that begin the repair process Resolution - >7 days - Macrophages secrete digestive enzymes that liquefy the fibrinous exudate, which is reabsorbed, expectorated, or phagocytized by macrophages... The lung parenchyma regains its normal appearance by 3 weeks

What is the Mycobacterium Tuberculosis "Cord Factor"? And what does it do?

Cord factor is a surface glycolipid, that makes MTB grow in long, serpentine cords - It is a primary virulence factor for MTB - it prevents macrophages from being bactericidal d/t the inhibition of phagolysosome acidification and also leads to the formation of caseating granulomas (b/c it forms a highly toxic crystalline monolayer on hydrophobic surfaces) *Strains that lack cord factor are not virulent*

How do Corticosteroids cause Neutrophilia?

Corticosteroids cause neutrophilia (despite causing eosinopenia and lymphopenia) - Corticosteroids decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation

What is Cortisols effect on Insulin/glucose?

Cortisol increases Insulin resistance (diabetogenic) Cortisol increases Gluconeogenesis, lipolysis, and proteolysis (decreases glucose utilization) - So low cortisol, leads to less insulin resistance... Like if a pt has diabetes and Addisons (leading to low cortisol), then they will need less insulin than would a person with just diabetes

What bacteria "contains metachromatic granules that stain with alanine dyes"?

Corynebacterium Diphtheria

"cobblestone" appearance is seen in what inflammatory bowel disease?

Crohn Disease - Cobblestone" appearance = wavy depressed ulcerations that separate elevated islands of healthy tissue

What inflammatory bowel disease has Noncaseating granulomas?

Crohns Disease

Cushing syndrome vs. Cushing disease

Cushing Syndrome - the umbrella term Cushing Disease - ACTH-secreting pituitary adenoma

How would a neurocysticercosis bran lesion appear on CT?

Cyst with minimal enhancement and no edema - Note - these patients usually have sezures and are from central/south america

What is the first line treatment for Wilsons dz?

D-Penicillamine This contains a free sulfhydryl group and functions as a copper chelator

What is the purpose of a D-xylose test?

D-xylose is a monosaccharide whose absorption is not affected by exocrine pancreatic insufficiency, and can be used to differentiate between pancreatic vs. mucosal causes of malabsorption

What is the receptor binding trend of Dopamine?

D1 > B1 >a1 NOTE: Dopamine stimulates the specific D1 receptors in the renal vasculature and tubules

What type of DNA repair is defective in Lynch syndrome (Hereditary nonpolyposis colorectal cancer)

DNA mismatch repair

What are two HLA's that are associated with Diabetes Mellitus Type 1?

DR3 and DR4

What is DRESS syndrome?

DRESS = Drug Reaction with Eosinophilia and Systemic Symptoms - typically occurs 2-8 weeks after exposure to high-risk drugs such as: Anticonvulsants, allopurinol, Sulfonamides, and Antibiotics - Patients typically develop fever, generalized lymphadenopathy, facial edema, diffuse skin rash, eosinophilia, and internal organ dysfunction

How is post-op malignant hyperthermia treated

Dantrolene This is a muscle relaxant that works on the Ryanodine receptor and prevents further release of Ca into the cytoplasm of muscle fibers

What med should be given to a patient in Neurolrptic Malignant Syndrome?

Dantrolene (A muscle relaxant - Prevents release of Ca2+ from the sarcoplasmic reticulum of skeletal muscle by binding to the ryanodine receptor)

What is Pulsus Paradoxus? What conditions does it occur in? And why does it occur - mechanism?

Decrease in amplitude of systolic BP by > 10mmHg during inspiration. Seen in cardiac tamponade, asthma, COPD, obstructive sleep apnea, hypovolemic shock, pericarditis, and croup (NOTE: Asthma and COPD exacerbation are the most frequent causes of pulsus paradoxus in the absence of pericardial disease) It occurs because 1. inspiration causes blood to pool in the pulmonary vessels and decrease pulmonary venous return to the L side of the heart, 2. inspiration causes increased venous return to Right side of heart, which will expand the right side, and then the right side will somewhat compress the left side - causing decreased LV end diastolic volume and stroke volume (this is more extreme in tamponade when the pressures are getting equalized between all the chambers of the heart) Other Explanation = Inspiration causes in increase in systemic venous return, resulting in increased right heart volume. Normally, this results in expansion of the right ventricle into the pericardial space with little impact on the left side of the heart. BUT, in conditions that impair expansion into the pericardial space (like in acute cardiac tamponade), the increased right ventricular volume occurring with inspiration leads to bowing of the interventricular septum toward the left ventricle. This leads to a decrease in left ventricular end-diastolic volume and stroke volume, with a resultant decrease in systolic pressure during inspiration.

What are the 2 potential causes of Phenylketonuria?

Decreased *phenylalanine hydroxylase* Decreased *Tetrahydrobiopterin*

The deep inguinal ring is an opening in what fascia? The superficial inguinal ring is an opening in what fascia?

Deep inguinal ring = opening in the *transversalis fascia* Superficial inguinal ring = opening in the *external oblique muscle aponeurosis*

What is deficient in *Cori Disease*, and what accumulates in the cytosol?

Deficiency in *Debranching enzyme (a-1,6-glucosidase)* - There is an accumulation of *limit dextrin-like structures* in the cytosol NOTE: Classic presentation = hypoglycemia, hepatomegaly, and muscle weakness/hypotonia (this can help distinguish from Von Gierke dz. because there is no muscle involvement in Von Gierke)

What are the 3 Non-nucleoside reverse transcriptase inhibitors?

Delavirdine Efavirenz Nevirapine -*VIR*- (beware of "Enfuvirtide", which is a fusion inhibitor)

Delusional disorder vs. Paranoid personality disorder?

Delusional disorder - the pt has 1 or more fixed delusions, but apart from this their functioning is not really impaired (ex: believing that they are being cheated on or poisoned) Paranoid personality disorder - the paranoid features and distrust extends across a wide range of situations (this person would have more of a distrust of many many people, not just a delusion about a specific thing)

What causes a Diaphragmatic hernia in an newborn/infant? And what side is the hernia usually on?

Diaphragmatic hernia is when Abd structures enter the thorax - Can be d/t defect of pleuroperitoneal membrane, or d/t trauma - Most commonly a hiatal hernia when the stomach herniates upward through the esophageal hiatus of the diaphragm - Commonly occurs on left side d/t the liver blocking the right

How can a decreased Calcium diet increase the risk of kidney stones?

Dietary Ca helps bind Oxalate in the gut to form unabsorbable Calcium Oxalate. Low-Calcium diets allow increased amounts of free Oxalate to be absorbed and then excreted in the kidney, thereby causing hyperoxaluria

What 3 drugs used for different reasons inhibit Dihydrofolate reductase?

Dihydrofolate converts Folic acid (B9) into Tetrahydrofolate (THF) - Methotrexate - used in humans to target rapidly proliferating human cells by preventing synthesis of purine and thymidylic acid (used in DNA synthesis) - Trimethoprim - restricts bacterial growth - Pyrimethamine - used for parasites: Plasmodium (malaria) and Toxoplasma (in combo with sulfonamide)

Name 2 First-gen H1-histamine antagonists. And, what is the most common side effect to this medication?

Diphenhydramine Chlorpheniramine - First-gen H1-receptor antagonists can cause significant sedation - This sedation is exacerbated when used with other drugs that cause CNS depression (ex: benzos)

What 2 bacteria produce a toxin that inactivates elongation factor (EF-2)

Diphtheria & Pseudomonas

What type of vaccination is the vaccine for C. Diphtheriae

Diphtheria toxin inhibits protein synthesis through ADP-ribosylation of Elongation Factor-2 The Diphtheria-Pertussis-Tetanus vaccine contains diphtheria toxoid, which stimulates the production of neutralizing antibodies (IgG) against the binding component (B subunit) of the diphtheria endotoxin

What are the classic 4 Ds of Botulism toxin symptoms?

Diplopia, Dysphagia, Dyarthria, Dyspnea

Direct Coombs test vs. Indirect coombs test:

Direct Coombs test—detects antibodies attached directly to the RBC surface. Indirect Coombs test—detects presence of unbound antibodies in the serum

Pathway of Stimulation/Inhibition in Direct pathway:

Direct pathway - goal is to create movement (*D1*) - Striatum (Putamen + Caudate) inhibits Globus Pallidus Internus and Pars Reticulata - GPi and Pars Reticulata STOP inhibiting the Thalamus - Thalamus is free to activate the cortex

What is the adverse effect of using Doxycycline in a preggo woman?

Discolored/stained teeth

What is the common presentation of septic arthritis d/t Neisseria?

Disseminated Gonococcal infection is one of the most common causes of septic arthritis in young, sexually active individuals & is usually d/t the spread of Neisseria Gonorrhoeae from a (usually asymptomatic) GU infection into systemic circulation - Typical presentation = *Purulent arthritis or the triad of polyarthralgia, vesiculopustular skin rash, and tenosynovitis* (inflammation of the tendon sheath)

At what portion of the nephron is there the LOWEST osmolarity if ADH levels are high

Distal convoluted tubule - osmolarity approaches 100 mOsm/L

What is the mechanism of the drug Disulfiram?

Disulfiram inhibits aldehyde dehydrogenase, and has an adverse mechanism of action when alcohol is ingested - It does not reduce craving, and is only used in abstinent patients with strong motivation to maintain abstinence

What receptors does Dobutamine stimulate? And what effects result?

Dobutamine stimulates Beta receptors (B1>B2) Thus, it increases heart rate and contractility while exerting little effect on peripheral vascular resistance

3 things to remember with Echinococcus Granulosus:

Dog feces, hydatid liver cyst, anaphylaxis

Homovanillic Acid is the primary metabolite of what?

Dompmine

What innervates the Rhomboids and Levator scapulae?

Dorsal scapular nerve (C5)

What drugs induce Cytochrome P-450?

Drugs that induce P450 will REDUCE the effectiveness of Warfarin

In Dry macular degeneration, where are the Drusen particles found?

Drusen are yellow extracelluar materials - In Dry MD, they are found inbetween Bruches membrane and the Retinal pigment epithelium Bruchs Membrane is the innermost layer of the choroid, which comes in contact with the retinal epithelium (FROM BB)

How does Ductal Breast carcinoma in-situ present on histology?

Ducts distended by pleomorphic cells with prominent central necrosis (with calcification) without extension beyond the ductal basement membrane - These tumors are usually identified on mammography as Microcalcifications

What is the most common GI abnormality associated with Down Syndrome?

Duodenal Atresia

Which type of ulcer has the strongest correlation to H. Pylori?

Duodenal ulcer (90% of the time is d/t H. pylori) (in contrast, 70% of gastric ulcers are d/t H. pylori)

In simple terms, what does an ELISA measure?

ELISA = Enzyme-linked Immunosorbent assay - a test commonly employed to measure the amount of protein in body fluids

What is the FIRST step in the development of atherosclerosis?

ENDOTHELIAL CELL INJURY

What does the ESR test?

ESR = Erythrocyte Sedimentation rate - ESR is increased in the presence of acute phase reactants (c-reactive protein, fibrinogen) - Chronic inflammation is associated with increased circulating pro-inflammatory cytokines (IL-1, IL-6, TNF-a), which stimulates the liver to release acute phase reactants NOTE: ESR is *Erythrocyte* sedimentation!! it has nothing to do with Platelet activation and aggregation

What is used to treat Lyme Dz in early and late stage

Early (eruption of erythema migrans) = Doxycycline Late (Manifestations weeks/months after eruption of erythema migrans) = Ceftriaxone

What 3 mutation sites are associated with early-onset (<60 y/o) familial Alzheimers? and what is associated with late-onset familial Alzheimers?

Early Onset: --- Amyloid precursor protein (APP) gene on chromosome 21 --- Presenilin 1 gene on chromosome 14 --- Presenilin 2 gene on chromosome 1 ---NOTE: These all promote the production of A-B Amyloid Late onset: --- Associated with the e4 allele of Apolipoprotein E (unclear mechanism) (ApoE4 increases risk of sporadic form) --- ApoE2 decreases risk of sporadic form

What are some complications of vericose veins?

Edema, stasis dermatitis, skin ulcerations, poor wound healing, and infections

Efficacy vs. Potency?

Efficacy - measure of the maximum pharmacodynamic effect achievable with a drug Potency - dose of the drug that is required to produce a given effect (Drugs that bind their receptors with a higher affinity or are better to gain access to their target tissues will have greater potency (lower ED50))

When dealing with a hopeless patient, what is the first best thing to do?

Empathizing with the patients frustration over past treatment failures can help build the physician-patient relationship Always empathize first!!!!

How is the uterus grossly different in Endometriosis vs. Adenomyosis?

Endometriosis - The uterus is usually *normal sized* (because the ectopic endometrial tissue is outside of the uterus), and it can also be retroverted (in contact with rectum) if there are implants/adhesions involving the urterosacral ligmaent - Adenomyosis - the uterus is *usually enlarged* (because the ectopic tissue is inside the uterine myometrium)

How does Kaposi Sarcoma (HHV-8) present in the GI tract?

Endoscopy = lesions which range from reddish/violet flat maculopapular lesions to raised hemorrhagic nodules Biopsy = spindle cells, neovascularization, and extravasated red blood cells NOTE: Kaposi sarcoma causes vascular proliferation & dysregulates vascular endothelial growth factor (VEGF), leading to aberrant angiogenesis

How do Enhancer sequences mechanistically increase the transcription rate?

Enhancer sequences can bind activator proteins that facilitate bending of DNA... DNA bending then allows the activator protein to interact with general transcription factors and RNA pol II at the promoter, increasing the rate of transcription (Enhancers can be located upstream or downstream, and may be near or far)

What does Enteropeptidase do, and how would a dysfunction manifest?

Enteropeptidase is a duodenal brush border enzyme that converts trypsinogen to trypsin. Trypsin degrades complex polypepties to dipeptides, tripeptides, and amino acids, while also activating other pancreatic enzymes. Enteropeptidase deficiency leads to both protein and fat malabsorption as trypsin is required to activate both enzymes required for both lipid and protein digestion. This disease causes diarrhea, failure to thrive, and edema (d/t hypoproteinemia)

Rule of thumb: enzymes in the early steps of porphyrin synthesis cause what symptoms, and enzymes in the later steps cause what symptoms?

Enzyme deficiencies in the early steps of porphyrin synthesis cause neurovisceral symptoms (acute porphyrias), while deficiencies in the latter steps (after condensation of PBG to HMB) result in photosensitivity (cutaneous porphyrias)

What is Spongiosis (skin microscopy finding)?

Epidermal accumulation of edematous fluid in intercellular spaces - Seen in Eczema (Eczematous dermatitis)

What is Acanthosis?

Epidermal hyperplasia (increased spinosum layer) - seen in Acanthosis Nigricans

What virus is identified in approximately 50% of systemic B-cell lymphomas and almost all primary CNS lymphomas occurring in the setting of HIV infection?

Epstein-Barr Virus

What is the appearance of Erythema Multiforme? And, why does it occur?

Erythema multiforme is an acute inflamatory disorder that can involve the skin, and also oral mucosa if severe... It appears as *erythematous, round papules that evolve into target lesions with a dark red inflammatory zone surrounded by a pale ring* - It represents a cell-mediated immune process, with an inflammatory infiltrate predominated by cytotoxic CD8+ lymphocytes... It is most frequently associated with infections (Herpes, mycoplasma) and may be d/t an immune response against antigens deposited in the skin

In Barrett Esophagus, the cells change from what to what?

Esophageal *squamous epithelium* is replaced by *intestinal columnar epithelium*

Lots of oxylate crystals in the tubular lumen in a homeless person indicates what?

Ethylene Glycol - Which can cause Nephrotoxic acute tubular necrosis

The effect of Ethylene glycol ingestion on the kidney:

Ethylene glycol (in antifreeze) ingestion leads to *toxic, acute tubular necrosis* with vacuolar degeneration and ballooning of the proximal tubular cells - Typical findings include high anion gap metabolic Acidosis, increased osmolar gap, and *Calcium oxalate crystals in the urine*

Erythroid percursors in the liver and spleen are indicative of what?

Extramedullary hematopoiesis - Extramedullary hematopoiesis is most frequently caused by severe chronic hemolytic anemias (like B-thalassemia)

How does hypertrophic cardiomyopathy present on Histology?

Extreme myofiber disarray with interstitial fibrosis

What activates the extrinsic and intrinsic coag pathways?

Extrinsic = Tissue Thromboplastin (tissue factor) Intrinsic = Subendothelial collagen

What enzyme is deficient in Fabry Disease? And, how does it present?

Fabry disease is X-linked recessive, and is d/t a deficiency of a-galactosidase A - Early manifestations are neuropathic pain, telangiectasias, hypohydrosis, and angiokeratomas (dark-red, non-blanching macules and papules that typically occur in clusters over the butt, groin, and umbilicus - Complications that develop in adulthood include: glomerular (proteinuria, renal failure), cardiac (LVH), and cerebrovascular (TIA, stroke)... With cerebrovascular and cardiac being the most common causes of death

What is decreased in hemophilia B?

Factor IX (9) - X-linked recessive - Will have prolonged PTT

What is deficient in Hemophilia B?

Factor IX deficiency

What clotting factor is bound to vonWillebrand factor?

Factor VIII (8)

What is decreased in hemophilia A?

Factor VIII (8) - X-linked recessive - Will have prolonged PTT

What 4 clotting factors are synthesized by the liver?

Factors 2, 7, 9, 10 NOTE: Factor 7 has the shortest half life of them all NOTE: Liver dysfunction/Alcoholism can lead to a deficiency of these

Accessory nipples are d/t what? (embryo)

Failure of involution of the mammary ridge

Metronidazole side effects:

Feel like shiiiiit if you drink booze!

What is the composition of normal hemoglobins (fetal, adult, and adult 2)

Fetal = α2γ2 Adult = α2β2 Adult A2 = α2δ2 (2-3% of Hb in a healthy adult)

What is the Teratogenic effect of ACE inhibitors & ARBs?

Fetal Renal Malformation - Can lead to Oligohydramnios & Potter Sequence *Angiotensin II is required for normal renal development*

What fetal parts synthesize AFP?

Fetal liver, GI tract, & Yolk Sac (in early gestation only)... the levels increase with increasing gestational age

What lipid drug is the most effective for the treatment of hypertriglyceridemia?

Fibrates

How do fibroadenomas of the breast present histologically?

Fibroadenomas of the breast are the most common benign tumor of the breast - Histo = cellular or myxoid stroma that encircles and sometimes compresses epithelium-lined glandular and cystic spaces

Aside from histamine, what other receptors can be blocked by first-generation Antihistamines?

First-gen antihistamines = *Chlorpheniramine, Dimenhydrinate, Diphenhydramine* - They can also block alpha-adrenergic, serotonergic, and cholinergic

What is the blood flow equation, and what is significant about the variables?

Flow (Q) = [(pressure difference)/(viscosity x length)] x radius^4 This shows how important the radius is with regard to blood flow... as *blood flow is directly proportional to the vessel radius raised to the 4th power* - so if an artery has flow decreased by a factor of 16, then you can conclude that the radius has decreased by a factor of 2 aka 50%... since 2^4 = 16 - or visa versa, so a radius reduction by a factor of 2 will reduce blood flow by a factor of 16

What are the findings of Hydrops Fetalis?

Fluid accumulation in multiple compartments of the fetus Uwrold: "Pleural effusion with secondary pulmonary hypoplasia and ascites"

What is the mechanism of Flutamide in the treatment of prostate cancer?

Flutamide is a nonsteroidal agent that acts as a competitive testosterone receptor inhibitor. Prevention of androgen-receptor binding blocks the stimulatory effect of androgens on the primary tumor and metastasis and leads to a reduction in their size (this occurs b/c prostate cancer is testosterone-dependant)

What kidney syndrome is associated with HIV and Heroin use?

Focal segmental glomerulosclerosis - This is a NEPHROTIC syndrome

What are 3 causes of Megaloblastic anemia?

Folate deficiency B12 deficiency Orotic Aciduria

t(14;18) translocation is associated with what disease and produce what product?

Follicular lymphoma - BCL-2 overproduction (BCL-2 proto-oncogene is moved from chromosome 18 to chromosome 14, near the site of the Ig heavy chain)

What prognosis time-frame is required for hospice?

For hospice, the physician must substantiate a prognosis of equal to or under 6 months with documentation of irreversible decline in clinical and functional status

What are side effects of Foscarnet (for treatment of CMV)?

Foscarnet is used to treat gancyclovir resistant CMV Side effects = hypocalcemia, hypomagnesemia, which can cause seizures (this is b/c Foscarnet can chelate calcium, and can also promote nephrotoxic renal magnesium wasting)

Where do proteins go that are made by free ribosomes and ribosomes on the rough ER?

Free Ribosome = translate proteins found within the cytosol, nucleosol, peroxisome matrix, and nuclear-encoded mitochondrial proteins Attached ribosomes = translate most secretory proteins, integral membrane proteins of the nucleus and cell membrane, and proteins within the ER, Golgi, and Lysosomes

What is the frontal lobe responsible for and how does damage here manifest? And, Left vs. Right manifestations?

Frontal lobe - responsible for *executive function* and *personality* - Executive function = perform complex tasks, motivation, organization, planning, purposful action - Left sided frontal lobe lesions have an association with apathy and depression - Right sided frontal lobe lesions have an association with disinhibited behavior

What are the names of the 3 normal loop diuretics, and the 1 that is non-sulfide:

Furosemide, Bumetanide, Torsemide Non-sulfa = Ethacrynic acid

What messenger system is used by Beta-1 & Beta-2 receptors?

G protein activation of adenylate cyclase - Increase in cAMP

What are Heinz Bodies seen in?

G6PD - when the Hb gets oxidized, it precipitates as a Heinz body... This body can get Phagocytosed in the spleen and lead to a "Bite Cell"

How does a GI bleed lead to hyperammonemia in someone with liver cirrhosis?

GI bleeding causes increased nitrogen delivery to the gut in the form of hemoglobin, which is then converted to ammonia (by the gut bacteria) and absorbed into the bloodstream

What is the pathogenesis of *Gallstone Ileus*?

Gallstone Ileus results from passage of a large gallstone through a cholecystenteric fistula into the small bowel, where it ultimately causes obstruction at the ileum - Pts typically present with symptoms/signs of small bowel obstruction, and an abdominal x-ray may reveal gas within the gallbladder and biliary tree

What are major adverse effects of Ganciclovir?

Ganciclovir interferes with human host cell DNA synthesis (to a greater extent than does ancyclovir) Major adverse effects of ganciclovir include neutropenia, anemia, thrombocytopenia, and impaired renal function NOTE: Gancyclovir is used to treat CMV, and is therefore commonly administered to pts with advanced HIV

Gancyclovir vs. Foscarnet

Gancyclovir - Guanine nucleoside analogue similar to acyclovir, that requires intracellular conversion by virally encoded kinase and then by cellular kinase Foscarnet - Does not require intracellular activation... It directly inhibits DNA polymerase in herpesvirus and reverse transcriptase in HIV

What type of connection connects Osteocytes in bone?

Gap Junctions - A gap junction is made of channel proteins (called connexons), which premit electrical and chemical communication between cells - This type of connection is important, because it allows it allows for the osteocytes to communicate by sending signals, and exchanging nutrients and waste products NOTE: Osteocytes serve to maintain the structure of the mineralized matrix and control the short-term release and deposition of Calcium

How does Gardos Channel Blockers work in the treatment of Sickle Cell?

Gardos Channel blockers hinder the efflux of potassium and water from the cell, preventing dehydration of erythrocytes and reducing the polymerization of HbS

What 3 molecules stimulate Gastric acid secretion? What 4 molecules inhibit Gastric acid secretion?

Gastric acid is stimulated by: *Histamine, ACh, and Gastrin* Gastric acid is inhibited by: *Somatostatin, Glucose-dependant Insulinotropic peptide (GIP), Prostaglandin, and Secretin*

What are the characteristic cell seen in Gaucher disease?

Gaucher cells - Lipid-laden macrophages that look like "wrinkled tissue paper" that can be seen in the liver, bone marrow, and lymph tissue - They form b/c of the accumulation of Glucocerebroside - which is a glycolipid component of leukocyte and erythrocyte membranes

Describe the receptor/pathway responsible for Glucagons effect on glycogen breakdown:

Glucagon acts through the G-protein/adenylate cyclase second messenger system... Protein Kinase A is the primary intracellular effector enzyme in this pathway Protein Kinase A activates Glycogen phosphorylase kinase which then activates glycogen phosphorylase - the enzyme responsible for glycogen breakdown REMEMBER: Glucagon phosphorylates, which activates glycogen phosphorylase (which breaks down glycogen)

What is the most abundant excitatory Neurotransmitter?

Glutamate

The inferior gluteal nerve innervates what muscle?

Gluteus maximus

What is the typical Amino Acid sequence of Collagen?

Gly-X-Y (X and Y are Proline and Lysine) Glycine is needed in every 3rd position because it is so small, it is the only amino acid that can fit into the confined space between individual alpha chains

Tetanus toxin prevents the release of what 2 neurotransmitters?

Glycine & Gamma-Aminobutyric acid (GABA) - these are both inhibitory neurotransmitters

What is the gram nature & morphology of Moraxella Catarrhalis?

Gram negative diplococci - Can distinguish from Neisseria b/c it does not ferment maltose

What color does E. coli grow on Eosin Methylene Blue (EMB) agar?

Green-metallic

What is the function of Histone H1?

H1 histone is located outside the histone core and helps package nucleosomes into more compact structures by binding and linking the DNA between adjacent nucleosomes NOTE: The histone core is made of 2 of each: H2A, H2B, H3, H4

What are some characteristics of reversible and irreversible injury?

HALLMARK OF REVERSIBLE: --- Cytosol swelling --- Swelling of the rough ER --- Disaggregation of granular/fibrillar elements of the nucleus & nuclear clumping HALLMARK OF IRREVERSIBLE: --- Plasma membrane damage --- Mitochondrial membrane damage --- Lysosome membrane damage

How does hand grip affect Hypertrophic cardiomyopathy and Ventricular septal defect murmur intensity ?

HCM - decrease intensity - b/c it impedes forward blood flow, increasing left ventricular volume, and decreasing murmur intensity d/t reduced outflow tract obstruction VSD - increase intensity - b/c the increased systemic vascular resistance will impede forward blood flow, which will increase the flow across the VSD

Over expression of what marker is most likely associated with aggressive breast cancer?

HER2 - Tx = Traszuzumab (anti-HER2 antibody)

What 2 viruses is Acyclovir affective against?

HSV & VZV - Acyclovir gets phosphorylated by HSV/VZV thymidine kinase (little to no activity against EBV & CMV)

Haptoglobin vs. Hepcidin:

Haptoglobin - a serum protein that binds to free hemoglobin and promotes uptake by the reticuloendothelial system Hepcidin - acute phase reactant that decreases iron absorption and iron release in anemia of chronic disease

What is HbA2?

HbA2 = α2δ2 (2-3% of Hb in a healthy adult) - This is elevated in Beta Thalassemia

When does fetal hemoglobin start to dissappear?

HbF (α2γ2) is the predominant Hb in the second an third trimester of pregnancy, and during the first few months after birth - Hb F comprises about 60-80% of all Hb in a term infant

What is a Heinz body? And, what condition is it usually seen in?

Heinz Bodies - dark, intracelllular inclusions that stain with supravital stain and represent hemoglobin that has denatured/precipitated from oxidative stress - Heinz bodies are strongly associated with G6PD deficiency

What is deficient in Hemophilia A? And how does this present?

Hemophilia A = factor VIII deficiency - Both Hemophilia A and B present with prolonged bleeding after trauma/bleeding, and deep tissue or joint bleeding - prolonged PTT *X-linked recessive* - so you usually see it in males

What type of virus is Hep *E* ? How is it transmitted? And what is the major concern?

Hep E = non-enveloped, ssRNA - Spread: Fecal-Oral - Most concerning feature is the high mortality rate observed in infected pregnant women

What is the main mechanism for copper removal from the body?

Hepatic excretion into bile

Aflatoxin is associated with what cancer?

Hepatocellular Carcinoma - Aflatoxin can induce mutations in p53

What 2 cancers can show with an elevated AFP?

Hepatocellular carcinoma

Lysing of blood cells when incubated in hypotonic saline with glycerol is the diagnostic test for what?

Hereditary spherocytosos (*Positive acidified glycerol lysis test*)

What is the most common cause of Fatal sporadic encephalitis in a normal person?

Herpes Simplex Virus - 1 - Brain exam will show *edema & hemorrhagic necrosis of the temporal lobe* - which can cause aphasia and personality changes

What is the most common cause of sporadic Encephalitis?

Herpes simplex virus (HSV) type 1 - There is typically *temporal lobe edema* on MRI b/c the virus enters the brain via the olfactory tract and travels to the olfactory cortex (in the medial temporal lobe) - Hemorrhagic inflammation of the temporal lobe also usually causes elevated erythrocytes in the CSF

What virus causing encephalitis can cause *edema and hemorrhagic necrosis of the temporal lobe*

Herpes simplex virus - 1

What are the serum levels of B-HCG, AFP, and Estriol, seen in trisomy 21?

High B-HCG Low AFP Low Estriol

A high level of Fructose-2,6-Bisphosphate will stimulate what pathway?

High F-2,6,-BP = Glycolysis is ON!!!

What is the difference between High-grade cervical intraepithelial neoplasia (CIN) vs. Low-grade CIN?

High grade CIN = the atypical cells have invaded beyond the lower 1/3 of the cervical epithelium Low grade = the cells have not invaded past the lower 1/3 of the cervical epithelium

What 2 components reduce the risk of cholesterol stones in the gallbaldder?

High level of bile salts and phosphatidylcholine increase cholesterol solubility and decrease the risk of gallstones. - water soluble cholesterol can be rendered soluble in small amounts by the detergent action of amphipathic bile salts and phosphatidylcholine (a phospholipid)

What is a Cardiac Myxoma?

Histology = composed of scattered cells within a mucopolysaccharide stroma, abnormal blood vessels, and hemorrhaging

What does histone acetylation promote?

Histone acetylation promotes the *formation of Euchromatin* - Euchromatin (loosely arranged chromatin) has very high levels of transcriptional activity

What is the mechanism of Hydroxyurea in the treatment of Sickle Cell dz?

Hydroxyurea *increases Fetal Hemoglobin (HB F)* by an unknown mechanism... It is reserved for patients with frequent pain crisis - An increase in HbF can confer protection against the polymerization of sickle cells

What is the biopsy findings of a patient with post-strep glomerulonephritis?

Hypercellular, inflamed glomeruli NOTE: to differentiate: Rapidly progressive glomerulonephritis has crescents in Bowmans space

What are the official criteria for diagnosis of Preeclampsia?

Hypertension onset after 20 weeks gestation plus proteinuria OR signs of end-organ damage - End-organ damage is d/t endothelial damage secondary to the release of inflammatory factors from abnormal placentation

What should you expect in a patient with recurrent pancreatitis, but no gallstones, and no alcohol use?

Hypertriglyceridemia!!! (NOT hypercholesterol! - this possibly can cause cholesterol stones, but the patient doesnt have stones!)

Hypoxia vs. Hypoxemia:

Hypoxia = the reduction of oxygen supply at the tissue level Hypoxemia = Arterial oxygen tension or partial pressure of oxygen is low

What 3 pro-inflammatory cytokines are seen in chronic inflammation that influence the liver to secrete acute-phase reactants?

IL-1 IL-6 TNF-a

What main cytokines are secreted by macrophages?

IL-1 IL-6 IL-8 IL-12 TNF-a

What main cytokines are secreted by TH2 cells?

IL-4 IL-5 IL-10 - And also IL-2, IL-3 (which are secreted by all T cells)

What messenger system is used by Alpha-1 receptors?

IP3 (Phosphatidylinositol 2nd messenger system)

A patient with normal PaO2 and SaO2, but low total blood oxygen, indicates what?

If PaO2 and SaO2 are both normal, the lower total blood content is most likely secondary to *lower Hemoglobin concentration*

Where does bile get reabsorbed?

Ileum (So this process can get F-ed up in Crohns disease)

What inflammatory cell is characteristically seen and indicative of sarcoidosis in a bronchoalveolar lavage?

In pulmonary sarcoidosis, accumulation of *CD4+ cells* in areas of active disease drives granuloma formation - This is detectable as a *high CD4+/CD8+ ratio* (2>1) in bronchoalveoler lavage fluid

What is a Syringomyelia?

In syringomyelia, a central cystic dilation in the cervical spinal cord (a syrinx) slowly enlarges, usually causing damage to the anterior white commissure and anterior horns... Usually at the level of C8-T1 - If this further expands, is can produce lower extremity weakness and hyperreflexia (UMN sign) by affecting the lateral corticospinal tract and can also lead to loss of position and vibration senses in the feet d/t involvement of the posterior columns *The combination of fixed segmental loss of upper extremity pain and temperature sensations, upper extremity lower motor neuron signs, and/or lower extremity upper motor neuron signs in the sitting of scoliosis suggests syringomyelia*

How do glucocorticoids promote osteoporosis?

Increase osteoclast differentiation and activity, decrease osteoblast activity and synthesis of bone matrix, and inhibit intestinal calcium absorption

How is pyruvate dehydrogenase complex deficiency treated?

Increased intake of Ketogenic nutrients (high fat, low carb, and ketogenic AAs: Leucine & Lysine) - In pyruvate dehydrogenase deficiency, patients are unable to convert pyruvate to Acetyl-CoA, which results in shunting of Pyruvate to Lactic acid... So treatment is aimed at decreasing glucogenic components, and increasing ketogenic components to provide energy in the form of Acetyl-CoA without increasing lactate production

Hyperkeratosis

Increased thickness of the stratum corneum - seen in psoriasis and calluses

What effect will increased vagal tone have on the AV node?

Increased vagal tone will result in inhibition of pacemaker activity of the SA node, *slowed conduction through the AV node*, and decreased myocardial contractility

Pathway of Stimulation/Inhibition in Indirect pathway:

Indirect pathway - goal is to further inhibit movement (*D2*) - Striatum (Putamen + Caudate) inhibits Globus Pallidus Externus - Globus Pallidus Externus then stops inhibiting the Subthalamic nucleus - Subthalamic nucleus stimulates Globus Pallidus Internus - Globus Pallidus further inhibits Thalamus *Nigrostriatal degeneration in Parkinsons is d/t excessive excitation of the Globus Pallidus Internus by the Subthalamic nucleus... which causes excessive excitation of the thalamus* - Thus high-frequency stimulation treatment at either of these 2 locations can inhibit firing from these 2 locations and improve mobility

What is one major side effect of the Halogenated inhaled anesthetics (ex: Desflurane)

Inhaled anesthetics are metabolized by the hepatic cytochrome P450 system, by which they are converted into reactive intermediates that can cause hepatocellular damage (*"Halothane Hepatits"*)... Pts will present with acute hepatitis days after medication exposure, and liver biopsy may show centrilobular hepatic necrosis NOTE: The inhaled anesthetics end in *"-ane"*

What is the mechanism of the Anti-fungal Terbinafine?

Inhibits the fungal enzyme squalene epoxidase

Describe the receptor/pathway responsible for insulins effect on glycogen synthesis:

Insulin acts via receptor tyrosine kinase signaling (it interacts with a tyrosine kinase receptor with an intrinsic kinase domain) Tyrosine Kinase / PI3 Kinase is stimulated by insulin, and promotes glycogen synthesis by activating protein phosphatase - and enzyme that DEphosphorylates (and ACTIVATES) glycogen synthase REMEMBER: Insulin deposphorylates, which activates glycogen synthase (to create glycogen)

What is the treatment of choice for DKA?

Insulin and Saline - These therapies will: --- Increase serum bicarb (by allowing glucose utilization and stopping production of ketone bodies) --- Increase serum sodium (from the saline... b/c Na was lost d/t osmotic diuresis from high blood sugar) --- Decrease serum glucose (via insulin) --- decrease serum osmolarity (via decreasing glucose) --- decrease serum potassium (b/c the insulin will drive the K back into cells)

How does elevated free fatty acid levels contribute to insulin resistance?

Insulin resistance in adipose cells hinders the anti-lipolytic effects of insulin, leading to lipolysis and release of Free Fatty Acids. - In turn, chronically elevated Free Fatty acid levels contribute to insulin resistance by impairing insulin-dependent glucose uptake and increasing hepatic gluconeogenesis

Why would someone with type 2 diabetes have elevated Free Fatty Acid in their serum?

Insulin resistance in adipose cells hinders the anti-lipolytic effects of insulin, leading to lipolysis and release of Free Fatty Acids. - In turn, chronically elevated Free Fatty acid levels contribute to insulin resistance by impairing insulin-dependent glucose uptake and increasing hepatic gluconeogenesis

What serves as the trigger for hepatocellular carcinoma d/t Hep B infection?

Integration of viral DNA into the genome of host hepatocytes triggers neoplastic changes

What is internuclear ophthalmoplegia?

Internuclear ophthalmoplegia is a disorder of conjugate gaze in which the affected eye (ipsliateral to the lesion) is unable to adduct and the contralateral eye abducts with nystagmus. Convergence and the pupillary light reflex are preserved. This typically occurs with damage to the *medial longitudinal fasciculus* (which would occur in the dorsal pons) NOTE: -The paramedian pontine reticular foramen and the Abducens nucleus (CN6) are in the Pons -The oculomotor nucleus (CN3) is in the midbrain

What does Prussian blue stain detect?

Intracellular *iron* - it turns blue - "Golden cytoplasmic granules in macrophages that turn blue with Prussian blue stain" is consistent with Hemosiderin laden macrophages

What type of receptor possesses a zinc finger?

Intracellular receptors, which can act directly as transcription factors - These receptors bing lipid-soluble hormones which can diffuse across the cell membrane (steroids (eg. estrogen, aldosterone, cortisol), thyroid hormone, and fat soluble vitamin receptors)

What is the most common type of breast cancer?

Invasive ductal carcinoma (the precursor to this is Ductal Carcinoma in situ)

What anticholinergic drug is used in preventing bronchoconstriction?

Ipratropium - Ipratropium blocks the action of acetylcholine at muscarinic receptors, preventing bronchoconstriction and reducing parasympathetic stimulation of tracheobronchial submucosal glands in the lungs - Note: the effects usually take about 60-90 minutes to occur "IPRAAAAY I can breathe again"

What unintentional nerve block commonly occurs with interscalene nerve block aimed at anesthetizing the brachial plexus as it passes through the scalene triangle (between middle and anterior scalenes)?

Ipsilateral diaphragmatic paralysis d/t accidental anesthetization of the roots of the phrenic nerve (C3-C5) as they pass through the interscalene sheath (it descends with the internal jugular vein, on the anterior scalene)

Being a vegetarian can make you deficient in what 2 things that can lead to anemia?

Iron B12 (but B12 stores take a long time to get depleted, so they need to be a vegetarian for a long time)

What receptors does Isoproterenol stimulate? And, what effect does this have?

Isoproterenol is a non-selective Beta agonist It decreases peripheral vascular resistance (B2) and diastolic BP (B2), and increases the cardiac rate (B1) and output (B1) NOTE: These effects lead to a very wide pulse pressure

What does impaired excitation-contraction coupling mean in terms of muscles?

It implies that an action potential occurs but the muscle is unable to contract (ex: if there is impaired actin and myosin binding...)

How does Desmopressin work in treating von Willebrand Disease?

It increases vWF release from Weibel-Palade bodies of the endothelial cells

What type of receptor is the insulin receptor?

It is a receptor with intrinsic tyrosine kinase ability, which then leads to downstream signaling

What is Vitiligo? And, what causes it?

It is caused by a loss of epidermal melanocytes

How does diabetic mononeuropathy of CN III present?

It is caused by central ischemia, which affects the somatic nerve fibers but spares peripheral parasympathetic fibers. Symptoms include ptosis, down an out gaze, but normal light and accommodation reflex

What is the calculation for RISK (not relative risk)?

It is just the # of people who developed something divided by the total # of people in the study = a/(a+b) ... Basically it is just the numerator in Relative Risk calcuation

In performing a Suprapubic cytoscopy, what layers are pierced?

It would pierce superficial fat/fascia (camper fascia & scarpa fascia), the aponeurosis of the abdominal muscles, the transversalis fascia, extraperitoneal fat, and the bladder wall

What are Janeway lesions?

Janeway lesions are a sign of Infective endocarditis - they are PAINLESS, macular, and erythematous lesions typically located on the palms and soles - They are the result of septic embolization from valvular vegetations and are composed of bacteria, neutrophils (microabscesses), necrotic material, and subcutaneous hemorrhage

Describe the JAK-STAT pathway:

Janus Kinase (JAK) is a nonreceptor (cytoplasmic) tyrosine kinase STAT = signal transducer and activator of transcription Some molecules that use the JAK-STAT pathway are Growth hormone, cytokines (ex: interferon), and hematopoietic growth factor (ex: erythropoietin!!!!!!, thrombopoietin, G-CSF) NOTE: Growth hormone promotes growth by acting on the cell surface receptors that stimulation production of insulin-like growth factor-1 (IGF-1 or Somatomedin C), primarily in the liver NOTE: Virtually all patients with polycythemia vera have a mutation in JAK2 that causes constitutive activation of its kinase domain, resulting in clonal proliferation of myeloid cells

How does Congenital CMV present?

Jaundice, hepatosplenomegaly, sensorineural hearing loss, ventriculomegaly, intracranial calcifications NOTE - most newborns with CMV infection are asymptomatic

What does DNA ligase do?

Joins Okazaki fragments

What is Kallikrein?

Kallikrein converts kininogen into bradykinin

What is the characteristic histology of a squamous cell lung cancer?

Keratin pearls or intracellular bridges

What is the triad of Wernicke encephalopathy? And what are additional symptoms of Korsakoff?

Korsakoff syndrome is a complication of Wernicke encephalopathy, the hallmarks of which are permanent memory loss and confabulation

A herniated disc between L2 & L3 will affect which nerve root?

L3

What hemisphere of the brain is usually dominant?

LEFT

What side is the dominant brain lobe usually?

LEFT

What is the toxic component of Lipopolysaccharide?

LIPID A

What type of vaccine is the Measles, Mumps, Rubella vaccine?

LIVE VACCINE

What receptors does Labetalol work at?

Labetalol is a reversible, competitive antagonist at Alpha1, and Beta 1&2 receptors... It has partial Beta2 agonist activity - it is used in HTN treatment

What part of Type II pneumocytes secreted surfactant

Lamellar Bodies

The Femoral nerve, artery, and vein all travel within the Femoral triangle, as well as deep inguinal nodes/lymph vessels... What is the order of their location from Lateral to Medial

Lat to Med: - Femoral Nerve - Femoral Artery - Femoral Vein - Deep inguinal nodes/lymph vessels *NAV*

What is Lead Time Bias?

Lead-time bias can occur when a test detects or diagnoses the disease at an earlier stage than another test without impacting the natural history of the disease EX: A studying comparing disease survival times may then erroneously conclude that using the earlier-detection test prolongs survival, when in actuality the increased survival time is due solely to earlier detection of the disease *Do not get this confused with "Length-time bias*

Recurrent skin and mucosal infections with the absence of purulence, is suggestive of what?

Leukocyte Adhesion Deficiency (LAD) - LAD is autosomal recessive, and characterized by the absence of CD18 antigens (LFA-1 integrin), which are essential for leukocyte adhesion to endothelial surfaces and migration to peripheral tissue - LAD findings are: recurrent skin and mucosal infections, and periodontal disease. The infections lack purulence d/t absence of leukocytes in peripheral tissue. Wound healing is also impaired, including late separation of the umbilical cord (b/c neutrophils cannot adhere and enter to destroy the tissue). Persistent leukocytosis is a common finding d/t leukocytes not being able to migrate out of blood vessels

What is Leukotriene B4?

Leukotriene B4 is a metabolite of the arachidonic acid pathway. Its main function is to stimulate neutrophil migration to the site of inflammation *"Neutrophils arrive 'B4' others"*

What are the Class 1B antiarrhythmics? and when are they usually used?

Lidocaine & Mexiletine - These are usually used post-MI "1*B* = *B*est post-MI"

Describe the Phosphatidylinositol 2nd messenger system (G-protein and Phospholipase C)

Ligand (like phenylephrine) binds to the G-protein coupled receptor and activates phospholipase C. Membrane phospholipids are broken down into diacylglycerol (DAG) and inositol triphosphate (IP3). Protein kinase C is subsequently acitvated by DAG and Calcium (which is released from the endoplasmic reticulum under the influence of IP3) *Alpha-1 Adrenergic Receptors & Muscarinic M1 and M3 use this pathway*, also so does V1 vasopressin, H1 (histamine), oxytocin, angiotensin II, TRH, GnRH

What do CNS ependymal cells do?

Line the ventricles (make up the choroid plexus) and make CSF

How does Lipid A release cause shock?

Lipid A is the toxic component of LPS - It causes activation of macrophages leading to widespread release of IL-1 and TNF-alpha, which can cause the signs of shock (fever, hypotension, diarrhea, oliguria, vascular compromise, and DIC)

What bacteria is this: Gram + Rod that produces a very narrow zone of B-hemolysis on blood agar, that is motile at low temperature?

Listeria Monocytogenes

What innervates Serratus anterior?

Long Thoracic nerve (C5-C7 nerve roots) Injury to this nerve can occur during axillary lymph node dissection or chest tube insertion

What type of diuretic should be given IV in a patient with heart failure exacerbation and significant volume overload?

Loop Diuretic (Furosemide, Torsemide, Bumetanide)

Why does primary adrenal insufficiency cause hyperpigmentation?

Loss of cortisols negative feedback on the pituitary gland leads to increased release of ACTH and MSH (Melanocyte stimulating hormone)... The increased MSH causes hyperpigmentation

What type of drug should be used if anticoagulation is needed in a pregnant woman?

Low Molecular Weight Heparins *Enoxaparin* or *Dalteparin*

What 2 arteries develop the highest burden of Atherosclerosis?

Lower abdominal aorta & Coronary arteries

What is Lymphogranuloma Venereum? And, what is it caused by?

Lymphogranuloma Venereum is caused by Chlamydia Trachomatis (serotypes L1-L3) - 1st - Small shallow ulcers (not painful) - Weeks Later - Large painful coalesced inguinal lymph nodes - Lesion cell scraping will show: "Intracytoplasmic chlamydial inclusion bodies in epithelial cells & leukocytes" with mixed granulomatous and neutrophilic inflammation

What is the liver microscopy findings of Hepatitis C?

Lymphoid aggregates with focal areas of macrovesicular steatosis

How does Myasthenia Gravis affect Motor end plate potential?

MG decreases the numbers of functional ACh receptors - b/c the Ab blocks the receptors, causes receptor internalization and degredation, and damages the motor end plate d/t complement activation from the antibody binding - Less receptors results in a reduction of the number of postsynaptic cation channels that can open in response to ACh, which *reduces the amplitude of motor end plate potential and prevents muscle fiber depolarization*

What structures compose MCH 1 and MHC 2 molecules?

MHC 1 = Heavy chain & B2-microglobulin MHC 2 = Alpha and Beta polypeptide chains

Tongue innervation: 1- Motor innervation 2- General sensory 3 - Gustatory innervation (taste buds)

MOTOR: - The hypoglossal nerve provides the motor to all of the tongue, except the palatoglossus muscle which is innervated by the vagus nerve (CN X) GENERAL SENSORY (pain, temperature, pressure): - Anterior 2/3 = Mandibular branch of Trigeminal nerve (CN V3) - Posterior 1/3 = Glossopharyngeal nerve (CN IX) - Posterior area of tongue root = Vagus (CN X) GUSTATORY INNERVATION (teste) - Anterior 2/3 = chorda tympani branch of facial n. (CN VII) - Posterior 1/2 = glossopharyngeal n. (CN IX) - Posterior area of the tongue root and taste buds of the larynx and upper esophagus = Vagus n. (CN X)

If you suspect osteomyelitis, what test should you order?

MRI (and blood cultures) - MRI is the most sensitive sensitive imaging method for diagnosing vertebral osteomyelitis

Malignant infiltration of breast carcinoma to what location would cause dimpling over the skin?

Malignant infiltration of *suspensory ligaments* of the breast causes dimpling of the overlying skin

What is the structure most affected in patients with Wernicke encephalopathy?

Mammillary body - the Mammillary body is part of the Papez circuit, which is a neuro pathway of the limbic system that is involved in the cortical control of emotion and memory

A coagulopathy & abnormal bleeding d/t Rat poison ingestion should be treated how?

Many rat poisons have a long acting derivative of Warfarin in them... and thus a coagulopathy/abnormal bleeding d/t rat poison should be treated similar to Warfarin toxicity - *Immediate treatment with Fresh Frozen Plasma, in addition to Vitamin K*

2 systemic disorders that are associated with Ectopia Lentis (dislocation of the lens of the eye)

Marfan - most common!!! Homocysteinuria (Cystathionine B deficiency)

Heparin is naturally present in what type of cell?

Mast Cells

Anaphylaxis is the result of widespread degranulation of what 2 cells?

Mast cells & Basophils

What does the process of "matching" attempt to eliminate in a study?

Matching is a method used in case-control studies to control *confounding* - First, matching involves selecting variables that could be confounders (age, race)... Cases and control are then selected based on the matching variables so that both groups have a similar distribution in accordance with the variables

How can uncontrolled maternal diabetes lead to an infant who is hypoglycemic?

Maternal hyperglycemia causes increased transplacental glucose delivery to the infant, fetal hyperglycemia, and ultimately, Beta cell hyperplasia - The resulting hyperinsulinemia caused by islet cell hyperplasia is associated with fetal macrosomia (large weight) and hypoglycemia after delivery

Who is covered by Medicare vs. Who is covered by medicaid?

Medicare - Patients over 65 who have worked and paid taxes, and younger individuals with disabilities, and those with end-stage renal disease Medicaid - homeless, undocumented immigrants, pregnant women, and low-income families

What is the most common malignant brain tumor in childhood?

Medulloblastoma - This typically arises in the cerebellum

What is the most common MALIGNANT tumor in children?

Medulloblastoma - This is the second most common tumor overall in children, behind Pilocytic astrocytoma

What 2 childhood tumors are characterized by Homor-Wright rosettes?

Medulloblastoma (usually in the cerebellum) Neuroblastoma (usually in the adrenal medulla)

If a MCV is > 110, what does this suggest?

Megaloblastic anemia! - Macrocytic anemia is > 100. But severe macrocytosis ( >110) is usually d/t megaloblastic anemia

What is the mechanism of the Anti-DM drug class: Meglitinides?

Meglitinides (ex: Repaglinide, and Nateglinide) are short acting glucose-lowering meds that are used in patients with significant post-prandial elevated glucose levels - They bind to, and close the ATP-dependant K channel on pancreatic B-cells, inducing depolarization and L-type Ca channel opening, which stimulated Insulin release... They are functionally similar to the sulfonylureas ("gli-" drugs)

What is the cause for albinism?

Melanocytes that do not produce melanin (b/c of absent or *defective tyrosinase*)

Junctional Nevi vs. Compound Nevi vs. Intradermal nevi

Melanocytic nevi are benign neoplasms composed of round, uniform melanocytes that are mitotically inactive - *Junctional Nevi* - aggregates of nevus cells limited to the dermoepidermal junction. Appear as flat, black-brown pigmented macules with a darker center than periphery - *Compound Nevi* - aggregates of nevus cells that extend into the dermis. Appear as raised papules with uniform brown/tan pigmentation - *Intradermal Nevi* - the epidermal nests of nevus have been lost and the remaining cells in the dermis do not produce pigment. Appear as skin-tan colored, dome-shape, and sometimes pedunculated

What kidney syndrome is associated with Hep B/C?

Membranoproliferative glomerulosclerosis (Type 1) - This is a NEPHROTIC syndrome

What causes Meniere disease? And, what are common symptoms?

Meniere disease is a disorder of the inner ear and characterized by *increased volume and pressure of endolymph* It is characterized by a triad: --- *Tinnitus* --- *Vertigo* (commonly associated with N/V) --- *Sensorineural hearing loss* (Weber louder in normal eaer) - The symptoms are commonly episodic

Mesonephros vs. Metanephros:

Mesonephros - interm kidney for 1st trimester, then becomes internal male genital system Metanephros - permanent kidney development (ureteric bud and metanephric mesenchyme)

What can be secreted by macrophages in the intima of an atherosclerotic plaque that can decrease the plaques stability?

Metalloprotieinases (these degrade extracellular matrix proteins - like collagen)

What is the most common cause of intracranial tumor in adult?

Metastases - These are usually well-circumscribed masses along the grey-white junction

What drug is given for the bronchoprovocation test in determining asthma?

Methacholine This is a muscarinic agonist that causes bronchoconstriction and increases airway secretions... A decrease in FEV1 after *methacholine challenge* indicates bronchial asthma

What stain is used for Pneumocystis?

Methenamine *Silver Stain* - Shows "Disc-shaped yeast-like cells" NOTE: this can also be used for: Other fungi, Leigonella, H. Pylori

What is the preferred first-line disease-modifying treatment for most patients with moderate to severe RA?

Methotrexate

Which turns DNA off and which turns DNA on... Methylation and Acetylation?

Methylation - turns DNA off (M = Mute) Acetylation - turns DNA on (A = Active)

What is the treatment of choice for Giardia?

Metronidazole NOTE: Giardia can be visualized in 2 ways: The trophozoite AND cyst form

What 3 drugs can you use to treat C. Diff?

Metronidazole Oral Vancomycin Fidaxomicin

Name 4 antimicrobials with good activity against anaerobic bacteria:

Metronidazole, Carbapenems, Clindamycin, & Piperacillin-Tazobactam

What is the characteristic histopath finding in HIV-associated dementia?

Microglial nodules, groups of activated macrophages/microglial cells formed around small areas of necrosis that may fuse to form multinucleated giant cells

Why are mature erythrocytes not able to produce heme?

Mitochondria are necessary for the first and final 3 steps of heme synthesis... Thus, mature erythrocytes lose their ability to synthesize heme when they lose their mitochondria

How can a hoarse voice result from mitral stenosis?

Mitral stenosis leads to left atrial dilation, and this can be sufficient enough to impinge on the left recurrent laryngeal nerve

What 2 structures cause the outflow tract obstruction seen in Hypertrophic cardiomyopathy?

Mitral valve leaflet and interventricular septum

What are the 2 most common causes of Severe Combined Immunodeficiency?

Most common = X-linked IL-2R gamma-chain deficiency Second most common = Adenosine deaminase deficiency (leads to a buildup of dATP which is toxic to lymphocytes)

What are the major side effects to Isoniazid?

Most important = Hepatotoxicity

What are the symptoms of digoxin toxicity? And what is the most serious?

Most serious = the development of potentially fatal cardiac arrhythmia (of virtually any type)

What makes up the crescents in Rapidly progressive Glomerulonephritis?

Mostly *Fibrin and Macrophages* "the crescents in RPGN consist of proliferated glomerular parietal cells, monocytes, and macrophages that have migrated to Bowmans space, as well as abundant fibrin between cellular layers of the crescents

What are the 2 main serious side effects of Statins?

Muscle and liver toxicity (myopathy and hepatitis) - Hepatic transaminases should be checked prior to initiating therapy and repeated if symptoms occur

Rouleaux formation of RBCs on blood smear is seen in what?

Mutliple Myeloma (the increased serum protein concentration (from immunoglobulin) decreases the charge between RBCs so they can stick together - and dont repel eachother)

What other organ abnormalities are commonly seen in patients with Myasthenia Gravis?

Myasthenia gravis is associated with abnormalities of the thymus (ex: thymoma, thymic hyperplasia)

"Tear drop RBCs" on peripheral stain are seen in what?

Myelofibrosis (Megakaryocytes produce excess platelet-derived growth factor (PDGF) causing marrow fibrosis)

Myopia vs. Hyperopia

Myopia = Nearsightedness (pt cannot see far) Hyperopia = Farsightedness (pt cannot see near)

If a patient wants to go on a date with you, what do you do?

NEVER DO IT!!!! - its always unethical

What is the equation for Number Needed to harm?

NNH = 1 / (Attributable risk) (Attributable risk is the difference between exposed and unexposed groups) EXAMPLE: -Risk of lung cancer in smokers is 21%. Risk in non-smokers is 1%.. Attributable risk = 20% -NNH = 1/.2 = 5

Does Amyotrophic lateral sclerosis cause sensory loss?

NO!!!!! - it is a progressive degeneration of upper and lower motor neurons

Ischemic brain disease

NOTE: - Nissl body/substance is a large granular body found in neurons. They are of rough ER, with rosettes of free ribosomes, and are the site of protein synthesis

What are the main arteries derived from the 1st, 3rd, 4th, and 6th Aortic arches?

NOTE: 1st arch - the middle meningeal artery branches off of the maxillary artery (for epidermal hematoma question)

What is Abetalipoproteinemia?

NOTE: Lipids absorbed in the small intestine cannot be transported into the blood and accumulate in the intestinal epithelium, resulting in enterocytes with clear of foamy cytoplasm

What drug causes "Yellow-tinged" vision?

NOTE: Old people tend to have worse kidneys, so beware of the dose of Digoxin in an old person

What is synthesized by RNA Pol 1, RNA Pol 2, and RNA Pol 3?

NOTE: Since RNA Polymerase 1 functions to transcribe ribosomal RNA components, its site of action is therefore in the nucleolus.. Since the nucleolus is the site of ribosomal subunit maturation and assembly

What ions are moving in each of the 3 phases of Pacemaker action potential (phase 0, phase 3, and phase 4)?

NOTE: This is much different than what happens in myocardial action potentials (FA page 280/281)

Passive vs active immunity:

NOTE: passive is NOT only mother to child!!! (dont make that mistake again you moron!)

According to UWORLD, what is the second most common cause of a single duodenal ulcer?

NSAIDS!!!! - it said, that Gastrinomas would usually manifest with multiple ulcers, and if they had Multiple Endocrine Neoplasia type 1, then they would have other symptoms

For each of these ions, state if they are mostly found intracellular or extracellular: - Na - K - Cl - Ca

Na = extracellular K = Intracellular Cl = extracellular Ca = extracellular Since Cl is at a higher concentration outside of the cell, this extracellular gradient drives Cl into the cell, which would make the membrane potential more negative

What 3 ions are regulated by aldosterone?

Na, K, H Brings Na into the cell Dumps K and H into the tubular lumen

What is the first line drug to reduce alcohol craving in a patient that wants to quit?

Naltrexone - this blocks the Mu-opoid receptors, and therefore blocks the rewarding and reinfocring effects of alcohol, and has been shows to reduce the craving for it

*Modafinil* is a drug for:

Narcolepsy (it is a daytime stimulant)

What is Necrotizing Enterocolitis (in a newborn)

Necrotizing Enterocolitis is one of the most frequent GI emergencies affecting newborns. It occurs predominantly in pre term infants secondary to GI and immunologic immaturity. Upon initiation of enteral feeding, bacteria are introduced into the bowel where they proliferate excessively d/t compromised immune clearance. Impaired mucosal barrier function allows the bacteria to invade the bowel wall, causing inflammation and ischemic necrosis of the terminal ileum and colon. As the disease progresses, the bowel becomes congested and gangrenous with the formation of intramural gas collections *An infant with abdominal distension, bloody stools, and pneumatosis intestinalis (air in the bowel wall) is diagnostic for Necrotizing Enterocolitis*

The most common cause of Neonatal intraventricular hemorrhage is bleeding from where?

Neonatal intraventricular hemorrhage usually occurs in the fragile *germinal matrix*, and increases in frequency with decreasing age and birth weight It is a common complication of prematurity (The germinal matrix is a highly cellular and vascular layer in the subventricular zone from which neurons and glial cells migrate out during brain development.... it becomes less prominent and its cellularity/vascularity decreases between 24-32 weeks gestation)

What is the equation for Net Excretion rate of a substance/drug?

Net excretion rate = (GFR)(Plasma concentration of drug) - (tubular reabsorption of drug) NOTE: Inulin can be used to estimate GFR

What teratogenic manifestation is seen with Valproate?

Neural Tube Defects - Try to switch the patient to Levetiracetam (a non-teratogenic medication)

What is the most common extra-cranial neoplasm in kids?

Neuroblastoma - tumor of the adrenal medulla

What is Conversion disorder?

Neurologic symptom incompatible with any known neurologic disease; often acute onset associated with stress

What are the two major side effects to Tehophylline?

Neurotoxicity (*seizures*) Cardiotoxicity (*tachy-arrhythmias*)

What Lipid-lowering med can lead to GOUT?

Niacin - b/c it decreases renal excretion of uric acid

What disease results from Niacin deficiency? And, what are the symptoms?

Niacin (B3) deficiency results in *Pellagra* Sx = *Diarrhea, Dementia, and Dermatitis*, you can also see hyperpigmentation of sun exposed skin - The rash can seem similar to lupus, but it is commonly on the face, and around the neck

What is the main side effect of Niacin? And, what mediates this?

Niacin causes cutaneous *flushing*, warmth, and itching These effects are mediated by prostaglandins (PGD2 & PGE2) - These effects can be diminished by the pretreatment with aspirin

What type of receptor is at the Neuromuscular junction?

Nicotinic - Specifically *Nm* - a *ligand gated ion channel* that opens after ACh binding - causing *immediate* influx of Na and Ca, and outflux of K

What are Nissl Bodies?

Nissl bodies are the rough ER in neurons - they synthesize peptide neurotransmitters for secretion

What does Nitroprusside do?

Nitroprusside = short-acing balanced venous and arterial vasodilator - So it will decrease Left ventricular pre-load and afterload

How does Berylliosis present on histology?

Noncaseating epitheloid granulomas (usually in the lung, hilar lymph nodes, and can be in systemic organs) without obvious associated particles (this sounds like Sarcoidosis, but its not)

What specifically do these test for: - Nontreponemal - RPR, VDRL - Treponemal - FTA-ABS

Nontreponemal (RPR, VLDL) - tests for *Antibody to cardiolipin-cholesterol-letithin antigen* Treponemal (FTA-ABS) - tests for *Antibody to treponemal antigens*

What are the 5 major causes of hypoxemia?

Normal A-a gradient: High altitude, Hypoventilation Elevated A-a gradient: V/Q mismatch, Diffusion limitation (fibrosis), Right to left Shunt

In a currently asymptomatic patient with asthma, how would her chest X-ray look?

Normal!

How can severe *hypertriglyceridemia* cause pancreatitis?

Normally small amounts of pancreatic lipase enters the pancreatic capillaries, where they can metabolize triglycerides to free fatty acids... But excess free fatty acids can be toxic to the pancreatic tissue, and cause pancreatitis (via direct tissue toxicity)

What are the clinical findings of aplastic anemia?

Note: The absence of splenomegaly is key in diagnosing aplastic anemia

How does Salmonella Typhi infection present?

Note: Treat with fluoroquinolone (-floxacin)

What 2 modifiable factor have a positive influence on peak bone mass

Nutritional status (Calcium and Vit D intake) Physical activity - Most of the variation, however, it genetically determined

What gives sputum its "greenish" color during infections?

Nutrophil MYELOPEROXIDASE - Myeloperoxidase is a blue-green heme-based pigment molecule thats inside neutrophil granules and catalyzes the production of hyperchlorous acid (HOCl) via the reaction: H2O2 + Cl --> HOCl- (bleach), which is the last step of oxidative burst

Drug: Octreotide

Octreotide - a long acting somatostatin analog - inhibits secretion of various vasodilatory hormones Used for: Acute variceal bleeds, acromegaly (overproduction of growth hormone), VIPoma, Carcinoid tumors

What cranial nerves carry parasympathetic fibers?

Oculomotor (CN III) Facial (CN VII) Glossopharyngeal (CN IX) Vagus (CN X)

Antagonists at what 2 receptors are most effective in treating bronchospasm in asthma?

Only *Leukotrienes* (LTC4, LTD4, and LTE4) and *Acetylcholine* produce bronchospasm that is relieved by *antagonists*.. So anti-leukotrienes (Montelukast, Zafirlukast) and Muscarinic antagonists (Fluticasone, Budesonide), are receptor ANTAGONISTS that can help in asthma bronchospasm treatment NOTE: Things like corticosteroids & B-agonists can relieve bronchospasm, but these are not receptor ANTAGONISTS

What causes Open-angle Glaucoma? And how does it present?

Open-angle glaucoma is characterized by increased intraocular pressure d/t increased secretion or decreased outflow of aqueous humor - It presents with an older person, who has painless peripheral vision loss... Then on fundoscopic exam you see *"cupping"* (Thinning of the outer rim of the optic nerve)

Is Strep Pneumo Optochin sensitive or resistant? And is it bile soluble or insoluble

Optochin sensitive (helmet not covering his chin) Bile soluble (not able to grow in bile) (horse has muddy feet) UWORLD: "Autolysin produced by S pneumo is activated by bile, resulting in cell lysis"

Name 4 families of viruses that have a segmented genome? (note: 2 are irrelevant)

Orthomyxovirus (ex: Influenza = -ssRNA) Reovirus (ex: Rotavirus = dsRNA) Bunyavirus Arenavirus (BOAR) NOTE: segmented viruses have a greater potential to undergo rapid genetic shifts through reassortment of their segmented genomes

What are Osler nodes?

Osler nodes are a sign of Infective endocarditis - They are PAINFUL, violet colored, nodules typically located in the pulp of fingers and toes - They are d/t immune-complex deposition in the skin

What cancer is associated with *CA-125*

Ovarian epithelial cancer (Serous Cystadenocarcinoma, Mucinous Cystadenocarcinoma)

How can renal stenosis lead to renal atrophy?

Over time, stenosis can cause renal atrophy d/t oxygen and nutrient deprivation NOTE: The most common cause of renal artery stenosis is obstruction by an erythematous plaque

What is the filtration, secretion, and re-absorption pattern of Para-aminohippuric acid (PAH)?

PAH is filtered and actively secreted into the tubular lumen. It is NOT re-absorbed. Thus, between filtration and secretion, there is nearly 100% excretion of PAH that enters the kidney PAH clearance can be used to calculate effective renal plasma flow (eRPF) *PAH is freely filtered by the glomerulus into Bowmans space, however, the majority is secreted by the proximal tubule via carrier-mediated active transport*

How do the lipid lowering drugs, PCSK9 inhibitors, work?

PCSK9 inhibitors block the action of PCSK9 (which normally degrades LDL receptors), resulting in *increased availability of LDL receptors on hepatocyte membranes* and subsequently increased clearance of LDL from the blood

What are the PTH, Ca, Phosphate, and Calcitriol levels in Chronic kidney disease?

PTH = Elevated Ca = Low Phosphate = Elevated Calcitriol = Low

What is the mechanism of activating osteoclasts via PTH?

PTH causes osteoBLASTS to increase the production of RANK-ligand and monocyte colony-stimulating factor (M-CSF)... These two stimulate osteoclastic precursors to differentiate into bone-resorbing, mature osteoclasts

What is the most common cause of isolated elevated Alkaline Phosphatase in patients > 40 years old

Pagets disease of the bone - Because at the end stage of this, osteoblasts are laying down a ton of bone, and produce Alk Phos to create an alkaline environment in order to mineralize the bone

This bone histology finding is indicative of what: "mosaic pattern of lamellar bone with prominent cement lines

Pagets disease of the bone NOTE the cement lines in the picture and it looks like a mosaic

Tumor marker: *CA 19-9* is associated with what?

Pancreatic cancer

Lupus can lead to what type of low blood counts?

Pancytopenia (decreased erythrocytes, leukocytes, and platelets) - *Decreased erythrocytes* d/t formation of IgG against erythrocytes (Type II hypersensitivity) - *Thrombocytopenia* - d/t antibodies against platelets (Type II hypersensitivity) - *Leukopenia* - primarily d/t antibody-mediated destruction of neutrophils (Type II hypersensitivity)... but this is less common

Papilledema vs Elevated intraocular pressure:

Papilledema - indicates edema of the optic disc (optic nerve)... Which ultimately indicates increased intracranial pressure --- Fundoscopy = elevated optic disc with blurred margins Elevated intraocular pressure - what is seen in glaucoma --- Fundoscopy = optic disc cupping

What does the parietal lobe process? And how does damage here manifest? And, Right vs. Left symptoms?

Parietal lobes process and interpret visual, auditory, and motor signals received from other parts of the brain - Parietal lobe damage results in difficulties with spatial and visual perception - Non-Dominant (usually right side) parietal lobe lesion = hemi-neglect, constructional apraxia (inability to copy drawings or 3D constructions - like a clock), and denial of the problem - Dominant lesions (commonly left side) = Gerstmann syndrome - Right and left confustion, difficulty with writing and mathematics

What is the most common infectious agent that can cause Hydrops Fetalis?

Parvovirus

Patau Syndrome vs. Edwards syndrome:

Patau = Trisomy 13 --- major symptoms are d/t the defect of prechordal mesoderm fusion leading to midline defects: --- Holoprosendephaly (brain has one hemisphere) --- Microcephaly (small head) --- Cleft lip/palate --- Omphalocele (stomach contents outside in a sac) --- Cutis Aplasia (skin defect of the scalp) Edwards = Trisomy 18 --- growth retardation --- hypertonia --- micrognathia (small jaw) --- heart defects --- clenched hands w/ overlapping fingers --- Meckel diverticulum --- Malrotation

Differential clubbing and cyanosis without blood pressure or pulse discrepancy are pathognomonic for what?

Patent Ductus Arteriosus complicated by Eisenmenger syndrome (reversal of shunt from left-to-right to right-to-left) (coarctation can also cause specific lower extremity cyanosis, but this will also have blood pressure and pulse delay between the upper and lower extremities)

Patients exposed to Silica (which gets inhaled) are at increased risk for what? And why?

Patients with Silicosis have *fibrotic nodules in the upper lobes* of the lung, calcified hilar lymph nodes (*eggshell calcifications*), and *birefringent particles surrounded by fibrosis* on biopsy - Pts have *increased risk for TB* b/c silica impairs phagolysosome formation by macrophages

Bullous pemphigoid vs. Pemphigus vulgaris... which one will you see "erosions"?

Pemphigus vulgaris b/c the bullae are very weak and often rupture prior to presentation with only erosions remaining NOTE: These bullae will spread laterally when pressure is applied on top (Asboe-Hansen sign), and new blisters may for with gentile traction on rubbing (Nikolsky)

Penicillins are structurally similar to what molecule in the cell wall? And, inhibit what enzyme?

Penicillins are a structural analog to *D-Ala-D-Ala* - They bind *Transpeptidases* and block cross-linking

What stain is used for Tropheryma Whipplei

Periodic Acid-Schiff - It stains the glycoprotein in their cell walls (See foamy macrophages in intestinal lamina propria)

What is the pharm term: Permissiveness?

Permissiveness is when the presence of substance A is required for the full effect of substance B. EX: Cortisol increases vascular and bronchial smooth muscle reactivity to Catecholamines (by upregulating a receptors on arterioles) and increases glucose release by the liver in response to glucagon

What are the characteristics of Depersonalization/derealization disorder?

Persistent/recurrent experiences of one or both: - Depersonalization (feeling of detachment from or being an outside observer of ones self) - Derealization (experiencing surroundings as unreal) - Reality testing is intact (i.e. an individual may feel detached from his or her body, but knows this is not true)

What is phenotypic mixing?

Phenotypic mixing refers to coinfection of a host cell by 2 viral strains, resulting in progeny virions that contain nucleocapsid proteins from one strain and the unchanged parental genome of the other strain. Since there is no change in the underlying viral genomes (no genetic exchange), the next generation of virions revert to their original, unmixed phenotypes This is different than reassortment because reassortment refers to changes in genomic composition that occur when a host cell is coinfected with 2 segmented viruses that exchange whole genome segments.

What is the order of catecholamine synthesis starting with Phenylalanine?

Phenylalanine Tyrosine DOPA Dopamine Norepinephrine Epinephrine

What receptors does Phenylephrine work at? And, what are the effects of this?

Phenylephrine is a selective alpha-1 adrenergic receptor agonist - It causes marked arterial vasoconstriction - Which increases systemic vascular resistance and blood pressure The increased blood pressure induces a compensatory increased vagal tone, which causes a decreased stroke volume (decreased pulse pressure) and decreased heart rate

"infant with a musty body odor"

Phenylketonuria

Irritation of what nerve can cause hiccups?

Phrenic nerve - Phrenic nerve can cause hiccups d/t spasmodic diaphragmatic contraction pulling air against a closed larynx

What is the most common childhood tumor?

Pilocytic Astrocytoma (it is benign with a good prognosis)

What is Pleiotrophy?

Pleotrophy - instances where multiple phenotypic manifestations result from a single gene mutation - Most syndromic genetic illnesses exhibit pleiotropy

What is the most common cause of Hirsutism in a woman?

Polycystic ovarian syndrome - Often associated with elevated androgen levels - Treat w/ Combo oral contraceptive - work by suppressing LH secretion from the pituitary, thereby decreasing ovarian androgen production... (They also increase sex-hormone-binding globulin synthesis by the liver, decreasing free testosterone)

What is Polycythemia Vera?

Polycythemia Vera is a clonal myeloproliferative disease of pluripotent hematopoietic stem cells - Characteristic features = increased RBC mass, increased plasma volume, and low erythropoietin levels - The majority of patients have a JAK2 mutation, rendering hematopoietic stem cells more sensitive to growth factors

What is Polyploidy?

Polyploidy occurs when more than 2 complete sets of homologous chromosomes exist within an organism or cell EX: partial hydatidiform more (69, XXX)

What is the polysaccharide capsule of Haemophilus Influenzae type b (Hib) composed of?

Polyribosylribitol phosphate

When are women at high risk for development of Myasthenia Gravis?

Post-partum period

What coronary blood vessel supplies the AV node?

Posterior Descending Artery - The PDA has a branch to the AV node (the AV nodal artery) - This can arise off of the right coronary artery or the left circumflex depending on the dominant circulation

What one "-statin" drug is not metabolized by CYP450

Pravastatin - So, if a patient is on an agent that inhibits CYP450, then Pravastatin is the statin of choice (because a CYP450 inhibitor would increase the concentration of other statins, which would increase the chance of statin induced myopathy, rhabdomyolysis, and subsequent renal failure) - Beware of Erythromycin (CYP450 inhibitor)

Genetic term: Heteroplasmy

Presence of both normal and mutated mtDNA, resulting in variable expression in mitochondria inherited diseases - This occurs b/c, during mitosis, mitochondria are randomly distributed between daughter cells. As a result, some cells contain mitochondria with mostly damaged mtDNA, while some contain mostly normal mtDNA

What do Anti-mitochondrial Antibodies indicate?

Primary Biliary Cirrhosis

What part of the lungs is infected in primary TB and what part in secondary (reactivation) TB

Primary TB = lower lobe Secondary TB = upper lobes NOTE: Ghon complex refers to the initial areas of infection (lower lobe & ipsliateral hilar lymph node)

Which endocrine hormones utilize intracellular receptors?

Progesterone, Estrogen, Testosterone, Cortisol, Aldosterone, T3/T4, Vitamin D *PET CAT* on *TV*

What are the functions of prokaryotic DNA Pol I and DNA Pol III?

Prokaryotes have 3 DNA Polymerases (I, II, and III) - *DNA Pol I* = 5-3 polymerase activity, 3-5 exonuclease activity, and 5-3 exonucleae activity (this also removes the RNA primer) - *DNA Pol III* = 5-3 polymerase activity, and 3-5 exonuclease activity NOTE: This 5-3 exonuclease activity, specific to DNA Pol III, is important to remove the RNA primer and further repair missed damages

What is the proper protocol to prevent neonatal tetanus? And, what is the treatment for neonatal teatnus?

Proper prophylaxis = Vaccinate women who are pregnant or may become pregnant with the inactivated tetanus toxin, so the woman can provide transplacental IgG to the fetus. Treatment = Give Tetanus Immune Globulin to neutralize unbound toxin, and give Abx to kill C. tetani

What should be given to an AIDS patient for prophylaxis against Mycobacterium Avium? And, what should be given for treatment if infected?

Prophylaxis = weekly *Azythromycin* (or Clarithromycin) Treatment = Azythromycin or Clarithromycin + Ethambutol (can add Rifampin) NOTE: M. Avium liked to grow at high temperatures!!!!

What substance is secreted from the vascular endothelium to inhibit platelet aggregation?

Prostacyclin (Prostaglandin I2)

What post translational modification occurs in the Golgi to tag proteins that are suppose to go to the lysosome?

Proteins targeted for lysosomes have their mannose residue phosphorylated by a Phosphotransferase enzyme in the Golgi - These proteins are then transported to the lysosome where they can serve as catalysts for degradation of cellular components

How does congenital hypothyroidism present?

Pt is initially normal at birth, but symptoms can develop once maternal T4 wanes Sx = Lethargy, Enlarged Fontanelle, Protruding tongue, Umbilical hernia, Poor feeding, Constipation, Dry Skin, Jaundice Dx = High TSH, Low T4... Newborn screening Tx = Levothyroxine - Early diagnosis is necessary b/c T4 is essential for normal brain development and myelination during early life, and infants are at risk for severe and irreversible intellectual disability

What would be the Ca, Phos., and PTH, levels in a pt w/ Vit. D deficiency?

Pt w/ vit. D deficiency would have: - Low Calcium (d/t low Vit D) - Low Phosphate (d/t low Vit D, and increased PTH) - High PTH (in response to low Calcium - secondary hyperparathyroidism)

What would be the Ca, Phos, and PTH levels in a pt with chronic renal failure?

Pt with chronic renal failure would have: - Elevated phosphate (d/t sick kidneys that cant excrete) - Low calcium (d/t high phosphate in blood binding to Calcium, and d/t decreased conversion of Vit D to active form, d/t sick kidneys - leading to less calcium from GI and bone) - Elevated PTH (d/t low Ca and high Phos)

What are Howell-Jolly Bodies seen in?

Pts with functional hyposplenia or asplenia - They are basophilic nuclear remnants found in RBCs, that are normally removed by a functioning spleen

Why might a patient have a megaloblastic anemia?

Pts with sickle cell dz and other hemolytic anemias have an *increased folic acid requirement* d/t increased erythrocyte turnover - As such, they are prone to developing relative folic acid deficiency and megaloblastic anemia

What pulmonary complication can be seen in both types of systemic sclerosis?

Pulmonary hypertension - this is d/t increased deposition of collagen in the pulmonary arterioles.... Microvascular injury of the pulmonary arterioles leads to narrowing of the lumen and increased pressure in pulmonary circulation

When is the pulmonary vascular resistance at its lowest? And, why?

Pulmonary vascular resistance (PVR) is lowest at the functional residual capacity. Increasing lung volumes increase peripheral vascular resistance d/t the longitudinal stretching of alveolar capillaries (but reduction in diameter) by the expanding alveoli Decreasing lung volumes also increase pulmonary vascular resistance d/t decreased radial traction from adjacent tissues on the large extra-alveoler vessels & compression by the positive intrathoracic pressure

How does an internal capsule stroke present?

Pure motor weakness affecting the contralateral arm, leg, and lower face - Contralateral spasticity or increased tone, hyperreflexia, and a positive babinski are also present (because it is upper motor neuron lesion!)

What is Pure Red Cell Aplasia?

Pure red cell aplasia is a rare form of marrow failure characterized by severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thrombopoiesis - It is associated with thymoma, lymphocytic leukemias, and parvovirus B19 (SEEMS LOW YIELD)

What are the 4 fates of pyruate, and what enzymes catalyze these steps?

Pyruvate gets converted to Acteyl-CoA (via pyruvate dehydrogenase) to enter the TCA-cycle (this ocurrs in aerobic conditions) Pyruvate gets converted to Lactic acid (via lactate dehydrogenase). This regenerates some NAD+ from the NADH, allowing for limited ATP production via anaerobic glycolysis (this occurs in anaerobic conditions) Pyruvate gets converted to Oxaloacetate (via pyruvate carboxylase, +biotin, ATP, CO2) to regenerate glucose in gluconeogenesis Lastly, Pyruvate can be converted to Alanine (via alanine transaminase) to enter the Cahill cycle and allow amino groups and carbons to be transported from muscle to the liver (NOT IMPORTANT!!!!)

What is the equation for Renal Blood Flow, using PAH?

RBF = (PAH clearance) / (1-HCT) (PAH clearance = RPF)

Sudden onset L-sided flank pain, hematuria, and a left-sided varicocele suggests what?

RENAL VEIN THROMBOSIS

What type of virus is West Nile? And, what are its serious manifestations?

RNA Flavivirus - +ssRNA - Mild sx = fever + rash + arthralgia - Severe sx = Meningitis, encephalitis, flaccid paralysis

Amatoxins, in wild mushrooms, inhibit what?

RNA polymerase II (halting mRNA synthesis)

What is the Renal Plasma Flow (RPF) equation, using PAH?

RPF = PAH clearance = (urine[PAH] x urine flow rate)/(plasma[PAH]) (Think of PAH clearance as the proportion of PAH that goes out into the urine compared to the amount that stays in the blood)

Avoiding the use of unsafe abbreviations and trailing zeros in medication orders can help reduce the incidence of medication errors

Random fact.

Psych Term: Rationalization vs. Suppression:

Rationalization - making excuses for unacceptable feelings or situations Suppression - mature defense mechanism involving a conscious choice not to dwell on a particular thought or feeling

A granuloma seen a few weeks after a sutured repair of a laceration is suggestive of what?

Reaction to a foreign body (a retained suture)

How is cholesterol taken up by cells?

Receptor-mediated endocytosis (mediated by the LDL receptor)

Recombination vs. Reassortment:

Recombination - gene exchange that occurs through the crossing over of 2 double-stranded DNA molecules (crossing over at homologous regions) Reassortment - mixing of genome segments in segmented viruses that infect the same host cell

What are the main side-effects of Nitrates?

Reflex tachycardia, hypotension, flushing, headache

A very dehydrated patient will re-absorb most of his water in what portion of the kidney?

Regardless of hydration status, the majority of water reabsorption in the nephron occurs in the *Proximal Tubule* passively with the reabsorption of solutes - *The proximal tubule reabsorbs >60% of the water filtered by the glomeruli regardless of the patients hydration status*

What is the Reid Index with regards to Chronic bronchitis?

Reid index = ratio of the thickness of the mucous gland layer to the thickness of the wall between the epithelium and the cartilage Normal = 40%

How does obesity affect respiratory compliance?

Respiratory compliance is diminished both by a reduction in chest wall compliance from increased weight, and by a reduction in lung compliance d/t microatelectasis - Ultimately, morbid central obesity can cause a pattern of extrinsic restrictive pulmonary function tests... The largest changes are a reduction in expiratory reserve volume and functional residual capacity

Parakeratosis

Retention of nuclei in the stratum Corneum - seen in Psoriasis

Describe Retrograde vs. Anterograde axonal transport:

Retrograde - Moves from synapse to the nucleus (mediated by Dynein-Dynactin complex) Anterograde - Moves from nucleus to synapse (mediated by kinesin) NOTE: - In microtubule: Dynein is retrograde (+ --> -), and Kinesin is anterograde (- --> +) - The plus end of microtubules typically lie at sites distant from the nucleus (think + because this is the side where the microtubule is adding more stuff - aka getting longer here)

What is Rett Syndrome?

Rett syndrome is a neurodevelopment disorder seen almost exclusively in girls (males die in utero) - Normal development until 5-18 months, then loss of motor and language skills, stereotypic hand movements, and also deceleration of head growth (it is thought to be X-linked dominant, with a majority of cases d/t de novo mutations in MECP2 gene)

What pathology does this finding indicate: *Diffuse fibrous thickening and distortion of the mitral valve leaflets along with commissural fusion at the leaflet edges*

Rheumatic Mitral valve stenosis

What is a characteristic finding of Aortic stenosis d/t Rheumatic valve disease?

Rheumatic Valve disease causing Aortic Stenosis is characterized by *fusion of valve commissures d/t repetitive inflammation*

*Anti-cyclic citrullinated peptide antibody* (Anti-CCP) is associated with what?

Rheumatoid arthritis - This is THE MOST specific antibody for rheumatoid arthritis

A child with frontal bossing and bowing of his legs has what disease?

Rickets - which is d/t defective mineralization of osteoid d/t vitamin D deficiency

In what directions do the left/right frontal eye fields generate movement

Right eye field - generates conjugate gaze to the left Left eye field - generates conjugate gaze to the right Think of these and both pushing the eye... Pushing from the right side will force it left, and visa versa... So then a lesion will cause both eyes to be deviated *toward the side of the lesion*

What drug is a monoclonal antibody used in lymphoma treatment that targets CD20?

Rituximab

A patient with polycystic kidney disease has a headache & nuchal rigidity... what do they have?

SUBARACHNOID HEMORRHAGE - b/c intracranial berry aneurysms of the Circle of Willis are often seen in patients with ADPCKD

What do these mean: SaO2, PaO2, CaO2?

SaO2 = % Oxygen saturation PaO2 = Arterial Oxygen tension CaO2 = Total blood oxygen content

What diagnostic test is used to Identify Trichomonas Vaginalis?

Saline microscopy (wet mount)

What is the general level of infectious dose needed to cause gastroenteritis for Salmonella vs. Shigella?

Salmonella - high infectious dose Shigella - very low infectious dose

Osteomyelitis in a sickle cell patient should raise suspicion for what 2 bacteria?

Salmonella and Staph Aureus - Salmonella Typhi has the"Vi" capsule - Staph Aureus doesnt have a capsule, but it is the most common in all patients, so it remains high on the differential)

How will the biopsy look in a patient with Giant cell (temporal) arteritis?

Scattered, focal *granulomatous inflammation* centered on the media with *intimal thickening/fibrosis*, *elastic lamina fragmentation*, and *giant cell formation* (without distinct granulomas)

What is the pathogenesis of secondary lactose intolerance?

Secondary lactase deficiency can occur after inflammatory (celiac dz) or infectious (Giardiasas) processes damage the microvilli of the small intestines. The damaged cells slough off, and are replaced by immature cells with low lactase concentrations

What class-switching does IL-5 induce?

Secreted by TH2 cells, and enhances class switching to IgA - Also stimulates growth and differentiation of Eosinophils

What class-switching does IL-4 induce?

Secreted by TH2 cells, and enhances class switching to IgE and IgG

What does IL-3 do?

Secreted by all T cells... Stimulates the growth and differentiation of bone marrow stem cells (functions like GM-CSF)

What is seen on light microscopy in Guillain-Barre syndrome?

Segmental demyelination of the peripheral nerves and an endoneural infiltrate

What is Acantholysis (skin microscopy finding)?

Separation of epidermal cells - seen in Pemphigus vulgaris

What are the 2 most common organisms for a septic abortion?

Septic abortion typically presents with fever, abdominal pain, uterine tenderness, and/or foul-smelling discharge and pregnancy termination Common offending pathogens include Staph. Aureus, and E. Coli, d/t seeing of the uterine cavity during instrumentation

5-hydroxyindoleacetic acid (5-HIAA) is the metabolic product of what neurotransmitter?

Serotonin

What are the two types of ovarian epithelial cancers?

Serous Cystadenocarcinoma (most common, usually bilateral, psammoma bodies) Mucinous Cystadenocarcinoma (pseudomyxoma peritonei, mucin-producing epithelial cells) - These are associated with cancer antigen *CA-125*

What stimulates Sertoli cells, and what does it produce as negative feedback? What stimulates Leydig cells, and what does it produce as negative feedback?

Sertoli = Stimulated by FSH, Produces Inhibin Leydig = Stimulated by LH, Produces Testosterone

What rare ovarian tumor can cause virilization (Hirsutism, clitoromegaly, deeper voice) and amenorrhea?

Sertoli-Leydig Tumor - Virilization is d/t increased testosterone secretion - Pts are usually young women - Histo = hollow or solid tubules lined by round Sertoli cells and surrounded by a fibrous stroma

What lab need to be checked before giving metformin?

Serum Creatinine - to assess liver function - b/c a side effect of metformin is lactic acidosis, which is a bigger risk in those with hepatic or renal dysfunction

Describe Serum Sickness:

Serum sickness is a type III hypersensitivity reaction to nonhuman proteins characterized by vasculitis resulting from tissue deposition or circulating immune complexes. It usually manifests 7-14 days after exposure to antigen. Clinical findings include fever, pruritic skin rash, arthralgias, and low serum C3 and C4 (d/t deposition of IgG and IgM, which are compliment-fixing antibodies) Note: It can occur after administration of heterologous proteins such as Chimeric monoclonal Abs (-mab drugs), non-human immunoglobulins (like antitoxin), and even some drugs (penicliin, cefaclor, TMP-SMX)

4 organisms with very low infectious doses that cause GI problems

Shigella spp. Campylobacter Jejuni Entamoeba histolytica Giardia lamblia

When prescribing a Benzo to a patient during the initiation period for an SSRI, what duration benzo should you prescribe?

Short or Intermediate acting TIPS to remember duration: - Triazolam - you just want to try it shortly - Oxazepam - quick and strong like an ox - Midazolam - short and dazzling -Diazepam - so long youll die - Chlordiazepoxide - longest name - Flurazepam - Lasts so long youll spend all day on the floor

What would the spleen look like in someone with sickle cell?

Sickle cell dz is characterized by repeated splenic infarctions that ultimately result in *splenic atrophy and necrosis* - This process is usually complete by late childhood/adolescence

What are the 5 causes of Microcytic anemias?

Sideroblastic anemia Anemia of Chronic Disease Lead Poisoning Thalassemias Iron Deficiency (late) 'SALTI"

What can be used to better visualize a Kayser-Fleischer ring in a patient with Wilsons Disease?

Slit Lamp

Slow twitch (type 1) muscle vs. Fast twitch (type 2) muscle:

Slow twitch (type 1) - perform actions requiring low-level sustained force --- Function via aerobic metabolism, thus have high myoglobin and mitochondria --- They have very red muscle fibers --- Ex: Paraspinal muscles ---(Think: A Slow Red Ox - slow twitch, red fibers, oxidative phosphorylation) Fast Twitch (type 2) - specialized for generating rapid forceful pulses of movement --- Type 2b generate ATP from anaerobic glycogenolysis and subsequent glycolysis --- Type 2a are intermediate between Type 1 and Type 2b, and generate ATP via aerobic metabolism

Lambert-Eaton syndrome is classically associated with what malignancy?

Small cell lung cancer

What is the cause/pathogenesis of centriacinar emphysema associated with chronic smoking?

Smoke causes oxidative injury, and alveolar macrophages get activated... Neutrophils are then recruited. Activated macrophages and neutrophils release proteases (especially elastase) that degrade the extracellular matrix This results in a *protease-antiprotease imbalance* - which leads to acinar wall destruction and irreversible airspace dilation to the terminal bronchioles

Where in the cell does steroid hormone synthesis occur?

Smooth ER (this is also where drug detox occurs)

When triglycerides are being metabolized, they are broken down into Glycerol and Fatty acids... What pathways do these then go into?

So of these substances, only glycerol can feed directly into gluconeogenesis

What should be given for a Tricyclic overdose presenting with long QT

Sodium Bicarb (NaHCO3)

What are the names of the 3 K+ sparing diuretics

Spirnolactone Triamterene Amiloride ("The K STAys")

This combination of symptoms suggests what: left shoulder pain, hypotension, tachycardia?

Splenic laceration and hemoperitoneum - The shoulder pain represents referred pain d/t peritoneal irritation "Any abdominal process (ex: ruptured spleen, peritonitis, hemoperitoneum) irritating the sensory fibers around the diaphragm can cause referred pain via the phrenic nerve to the C3-C5 shoulder region

What sequences are targeted by spliceosomes?

Spliceosomes remove introns containing GU at the 5' splice site and AG at the 3' splice site

What is "standard error" and how is it calculated?

Standard error (SE) is used to show how closely sample means are related to population means SE = SD/(square root of the sample size) - Example: "Investigators would be 95% confident that the true mean folate level in the underlying population lies within the mean +/- d SE

What is the equation of standard error?

Standard error is estimated considering both the SD and the size of the sample (n) = SD/√n

What are the 3 most common pathogens for post-flu pneumonia?

Staph Aureus, Strep Pneumo, Haemophilus influenzae

Daily treatment of Penicillin in a sickle cell patient is meant to protect against what?

Strep Pneumo

What brain space contains CSF?

Subarachnoid space

What is a cross-over study?

Subjects are randomly allocated to a sequence of 2 or more treatments given consecutively - A washout (no treatment) period is often added between treatment intervals to limit the confounding effects of prior treatment

A sudden upward jerking of the arm can cause injury to what part of the brachial plexus? And, how would this manifest?

Sudden upward jerking of the arm can cause injury to the *lower trunk* of the brachial plexus - The lower trunk carries fibers from C8-T1, and contributes to both the median and ulnar nerves... Together, these nerves innervate all of the intrinsic hand muscles, so damage here would cause paralysis or weakness of the hand muscles

What nerve innervates the gluteus medius?

Superior gluteal nerve

Of the Ectoderm derivatives, what comes from the surface ectoderm, neural tube ("neuroectoderm"), and neural crest?

Surface ectoderm - skin (epidermis), eyes, etc. Neural Tube (Neruoectoderm) - CNS Neural Crest - PNS, and non-neural structures nearby (melanocytes, bones of skull, endocardial cushions, etc.)

What statistical method compares the means of 2 groups? And what compares the means of 3 or more groups?

T-test = 2 groups Analysis of Variance (ANOVA) = 3+ groups (T = Tea is meant for 2) ("Analysis of variance" is 3 words)

What do T-tubules in skeletal and cardiac muscle essentially do/ensure?

T-tubules allow the depolarization impulse to rapidly propagate through the interior of the muscle fiber - This ensures Ca release from the sarcoplasmic reticulum occurs uniformly throughout the fiber, and allows *synchronized contraction of myofibrils* in each muscle cell

What are the 2 promoters of transcription in eukaryotic cells?

TATA (25 bases upstream) and CAAT (75 bases upstream) boxes - They promote the initiation of transcription by serving as binding sites for transcription factors and RNA Pol II

What are the relative hemoglobin values, reticulocyte counts, and RBC indices (like MCV) for a person with Sickle Cell TRAIT?

THEY ARE ALL NORMAL! - *Patients with sickle cell trait are usually asymptomatic with normal hemoglobin level, reticulocyte count, and RBC indices*

What are the 3 main cytokines responsible for inducing the systemic inflammatory response, and can mediate sepsis?

TNF-a IL-1 IL-6 (all secreted by macrophages) FA page 104

What cytokine induces and maintains granulomas?

TNF-alpha NOTE: IFN-y also activates macrophages, and can contribute to granulomas

A frontal eye field lesion will produce gaze deviation in what direction?

TOWARDS the lesion/bleed the FEF are in the frontal lobe (Think: b/c these push away, so loosing it on one side will have unopposed action pushing it to that side)

What enzyme is decreased in Thrombocytopenic purpura (TTP)

TTP is d/t decreased *ADAMTS13*, which is an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degredation - Large uncleaved multimers lead to abnormal platelet adhesion, resulting in microthrombi (which then can cause the microangiopathic hemolytic anemia and formation of RBC schistocytes)

What med can be given that can reduce the risk of Gynecomastia in men with prostate cancer who receive androgen-deprivation therapy,

Tamoxifen

What does telomerase do? And, where is it most active?

Telomerase is a reverse transcriptase (RNA-dependant DNA polymerase) that lengthens telomeres by adding TTAGGG repeats to the 3' end of chromosomes *Stem cells have long telomeres d/t high telomerase activity*, allowing them to proliferate indefinitely in a controlled manner

How does temporal lobe damage manifest? And, right vs. left symptoms?

Temporal lobe injury can cause disturbances in language, sensory interpretation, and impaired memory. Pts can also exhibit behavioral changes (hyperorality and hypersexuality) - Non-dominant (usually right side) lesions can affect nonverbal memory, including musical ability - Dominant (usually left side) lesions can affect verbal memory, such as word recognition fora

In what way to these muscles rotate the arm: Teres major and Teres minor?

Teres Major = Internal rotation Teres Minor = External rotation (In pic. green = teres minor, and the muscle below it is the teres major)

At what portion of the respiratory tree does the primary mode of removing inhaled particles switch from ciliated cells (mucociliary clearance) to macrophages?

Terminal bronchioles and proximal = *Ciliated cells* Distal to the terminal bronchioles (respiratory bronchioles and alveoli) = *Alveolar macrophages*

What are some various, multi-system (cardio, derm, GU, boob) effects of androgenic steroid abuse?

Testosterone stimulates RBC production, which accounts for the higher hematocrit in normal males compared to normal females... And this effect is exaggerated in exogenous androgen abuse, which will increase hematocrit in a dose dependent manner

What nerve is at risk of injury during thyroidectomy, and what does it innervate?

The *External branch of the superior laryngeal nerve* is at risk of injury during thyroidectomy d/t its proximity to the superior thyroid artery and vein - It innervates the *cricothyroid* muscle

What is the name of the ligament that contains the *Ovarian artery, vein, lymphatics, and nerves*

The *Suspensory ligament of the ovary* (or *Infundibulopelvic ligament*) NOT THE "OVARIAN LIGAMENT" - this is what attaches the ovary to the side of the uterus

What is another name for the Flexor retinaculum?

The *Transverse Carpal Ligament* - It attaches to the hamate and pisiform on the ulnar side, and the trapezium and scaphoid on the radial side

How do androgens promote acne development?

The 4 major elements that underline acne development are: - 1) Follicular epidermal hyperproliferation - 2) Excessive sebum production - 3) Inflammation - 4) Propionibacterium acnes - Androgens promote both follicular epidermal hyperproliferation, and excessive sebum production NOTE: Drugs that can cause acne eruptions are: Anabolic steroids (methyltestosterone), Epidermal growth factor receptor inhibitors, and Lithium

Where is the AV node located in the heart?

The AV node is located on the endocardial surface of the right atrium , near the insertion of the septal leaflet of the tricuspid valve and the orifice of the coronary sinus - It is in the inter-atrial septum

How many days after fertilization until the embryo implants? When can you see blood B-HCG, and when can you see urine B-HCG?

The Blastocyst implants 6 days after fertilization The syncytiotrophoblast invades the endometrium 6-7 days after fertilization, and starts secreting B-HCG... So it can be detected in serum then It cannot be detected in urine until it reaches 20 IU/L, which usually occurs 14 days after fertilization

The sporadic form of Burkitt lymphoma usually presents in what area of the body?

The abdomen

What does the arteriovenous concentration gradient reflect in an inhaled anesthetic?

The arteriovenous concentration gradient reflects the overall tissue solubility of an anesthetic *Anesthetics with high tissue solubility are characterized by large arteriovenous concentration gradients and slower onset of action* - To make sense of this - Higher peripheral tissue solubility means more anesthetic is extracted from the arterial blood. This increases the arteriovenous concentration gradient, meaning that more anesthetic must be absorbed to saturate the blood & then the brain

The binding of *Programmed death receptor (PD-1)* on Cytotoxic T cells to its ligand *PD-L1* on other cells, results in what?

The binding of PD-1 to its ligand PD-L1 *downregulates the immune response* against cells by inhibiting Cytotoxic T cells - Many cancers evade the immune system by increasing expression of PD-L1

Difference between: optic nerve, optic track, and optic chiasm

The black circle at the end of the optic track = *Lateral Geniculate body* (which is in the thalamus) *Dorsal optic radiation* is in the parietal lobe *Meyers loop* is in the temporal lobe

Where is the bladder relative to the visceral/parietal peritoneum?

The bladder is under the peritoneum. Thus the superior border of the bladder is covered with peritoneum the bladder is therefore *Extraperitoneal*

What step in the urea cycle creates urea?

The conversion of Arginine to regenerate Ornithine and create Urea... this is catalyzed by Arginase NOTE: And Arginase deficiency can present with spastic diplegia, growth delay, and abnormal movements NOTE: Arginine is also a precursor for Nitric oxide

In a patient with Alzheimers, where is loss of ACh most apparent?

The decline in ACh levels is most notable in the *Basal nucleus of Meynert*, which participates in memory and cognition - It is also notable in the Hippocampus, who's major function is the formation of new memories

What nerve and artery run together along the posterior aspect of the humerus?

The deep brachial artery and the radial nerve NOTE: Midshaft fractures of the humerus risk injury to these structures

What portion of the Kidney does renal cell carcinoma most commonly arise from?

The epithelium of the *proximal renal tubule*

What cranial nerve passes through the parotid gland? And compression of this nerve by a parotid tumor can cause what?

The facial nerve courses through the parotid gland The facial nerve innervates the muscles of facial expression, thus, compression can cause an ipsilateral facial droop

What innervation comes from the inferior hypogastric plexus?

The inferior hypogastric plexus, which has both sympathetic and parasympathetic components, innervates the internal pelvic viscera (this would provide innervation to internal hemorrhoids above the dentate line)

What is the Endoneurium?

The innermost layer of connective tissue that surrounds a nerve axon and its corresponding blood vessel

An anterior displacement of the posterior portion of the 12th rib would penetrate which organ?

The kidney

Branches of the Musculocutaneous nerve supply sensation to where?

The lateral forearm

Draw the Neuro visual pathway:

The lateral geniculate body is in the Thalamus Meyers loop is in the temporal lobe Dorsal optic radiation is in the parietal lobe (think because it is the more dorsally located of the two radiations)

Describe the pathway of fetal circulation:

The most highly oxygenated blood in the fetus is carried by the umbilical vein, which (mostly) empties directly into the inferior vena cava via the ductus venosus FA Page 270

What does the paramesonephric duct become?

The paramesonephric (Mullerian) duct becomes the internal female genetalia: *Falopian tubes, uterus, proximal vagina*

What level is ideal for a Thoracentesis, at the midclavicular, midaxillary, and paravertebral lines?

The parietal pleura extends 2 rib levels below the visceral pluera... So to extract fluid via thoracocentesis, you should put it in this space: - Midclavicular - 6th-8th rib - Midaxillary - 8th-10th rib - Paravertebral - 10th-12th rib (therefore you can also tell that the lowest margin of the lung is at rib 6, 8, and 10 at these lines)

What/where is the perineal membrane?

The perineal membrane is the inferior fascia of the urogenital diaphragm

What posterior rib level is the spleen located?

The posterior left *9th, 10th, and 11th* ribs overlie the spleen

Where is the prostate relative to the bladder?

The prostate is in contact with the bottom posterior part of the bladder

Where is 2/3 of the filtered K reabsorbed in the kidney?

The proximal tubule Then the thick ascending loop of henle reabsorbs about 25%-30% more

How does the rabies virus infect & gain access to a human?

The rabies virus has a bullet shaped envelope with knob-like glycoproteins that can bind *Nicotinic ACh receptors* - The virus uses these receptors to enter muscle, where it replicates for days-weeks, and then spreads in a retrograde fashion through the peripheral nerve axon to the CNS

What motor and sensory is provided by the Radial nerve?

The radial nerve provides: - Sensory innervation to the skin of the posterior arm, forearm, and dorsal lateral hand - Motor innervation to all of the extensor muscles of the upper limb below the shoulder (triceps and wrist/finger extensors) - Motor signal for contraction in the tricep reflex (C6/C7) runs through the radial nerve NOTE: Damage to the proximal radial nerve (at the axilla or midshaft humerus) may result in wrist drop NOTE: The radial nerve has a superficial course within the axilla, predisposing it to injury ("crutch injury" or "saturday night palsy"

What is the Rare disease assumption?

The rare disease assumption stats that the odds ratio approximates relative risk when disease incidence is low (<10%)

Where does the coronary sinus drain into?

The right atrium (between the IVC and tricuspid valve) - Most of the venous drainage from the myocardium traverses the coronary sinus, which delivers deoxygenated blood to the right atrium

In what organelle does the hydroxylation of proline and lysine residues of collagen occur?

The rough ER

What accounts for the rubbery property of elastin?

The rubber property of elastin is d/t extensive *cross-linking* between elastin monomers - The cross linking is facilitated by *lysyl oxidase* which deaminates some *lysine residues* of tropoelastin allowing the cross-links to form between neighboring peptides

blockage of what vein will cause gastric varices only in the fundus of the stomach?

The splenic vein (or sort gastric vein) - The short gastric vein drains the fundus of the stomach, and drains into the splenic vein - The splenic vein can get thrombosed d/t chronic pancreatitis, pancreatic cancer, or abdominal tumors... b/c the splenic vein runs along the posterior surface of the pancreas and can develop a blood clot from pancreatic inflammation

What does the Tensor tympani muscle do? And what innervates it?

The tensor tympani contracts the tympanic membrane medially, thereby increasing its tension and dampening sound transmission - it is innervated by the mandibular banch of the trigeminal nerve (CN V3)

What 3 molecules form the thin filament in muscle? And, to which one does calcium bind?

The thin filament is made up of Actin, Troponin, and Tropomyosin Calcium Binds to Troponin (The calcium binding to troponin causes a conformational change in the troponin complex, causing it to displace tropomyosin and expose the myosin binding site on the actin filaments)

Describe the pattern of Airway resistance along the bronchial tree:

The upper respiratory tract (mouth/nose through larynx) accounts for about half of the total resistance, and then the remainder is derived form the lower respiratory tract, starting with the trachea - *Resistance is highest in the medium-sized bronchi because of high turbulent flow* *Remember resistance is very dependent on the TOTAL diameter... so the diameter of the bronchioles is small individually, but since there are so many, the summated cross-sectional area is very big*

What does it mean if the urine is positive for reducing substances?

There is sugar in the urine (glucose, fructose, galactose, or one of their similar compounds)

How does the diffusion capacity for Carbon Monoxide change in emphysemia?

There will be a *decreased diffusion capacity* - this is d/t destruction of alveoli and adjoning capillary beds (diffusion capacity is also decreased in pulmonary fibrosis, but this is d/t the fibrosis and larger diffusion area)

What would a deficient Galactokinase enzyme cause?

There will be build up of galactose, which will get converted to Galactitol, which is an osmotic agent that can cause cataracts - There are no serious systemic manifestations in GALK deficiency, and cataracts may be the only manifestation

Describe the activation cascade that occurs with stimulation of glucagon receptor, TSH receptor, or PTH receptor.

These all work through G-coupled protein receptors using adenylate cyclase second messenger system. The alpha subunit of the G-protein is bound to GDP, which inactivated it. When the receptor is activated, the alpha subunit changes shape, releases GDP, and binds to GTP, which then allows the Alpha subunit to dissociate from the G protein complex. The specific alpha subunit used in these receptor-signaling complexes is called: Gs. Free Gs (with GTP bound) activates adenylate cyclase, which converts ATP to cAMP, which then activates protein kinase A. Protein kinase A then phosphorylates specific serine/threonine residues in various enzymes, leading to their activation or deactivation. It can also phosphorylate proteins that bind to regulatory regions of genes on DNA. NOTE: other hormones that use this same pathway (but dont have the same alpha subunit) are: ACTH, and ADH

How do TNF-alpha, Catecholamines, Glucocorticoids, and Glucagon, lead to insulin resistance (i.e. decreased insulin-mediated glucose uptake)

They *phosphorylate Serine* and Threonine residues of insulin receptor and the insulin receptor substrate via Serine Kinase, which then leads to insulin resistance (d/t decreased activity of the insulin receptor which normally has tyrosine kinase activity)

At what spinal level are both the Gracile and Cuneate Fasciculi present?

They are both present above T7, whereas only Gracile fasciculus is present below this level

What is the mechanism of Bisphosphonates?

They are taken up by osteoclasts, and decrease osteoclast activity, induce osteoclast apoptisis, and decrease development/recruitment of osteoclast precursor cells The drugs end in "-dronate"

The intercostal vein, artery, and nerve lie ____________ relative to the rib?

They lie in the subcostal groove on the *lower border of the rib*

What do caspases do?

They mediate apoptosis Activation of caspases leads to activation of proteases (which break down cytoskeleton) and endonucleases (which break down DNA)

Where is the most common location for an anterior nose bleed?

They most commonly occur within the vascular watershead area of the nasal septum at Kiesselbach plexus (an anastomosis of the anterior ethmoidal artery, sphenopalatine artery, and superior labial artery)

Thiazide vs. Loop diuretic... which increases and which decreases Ca reabsorption?

Thiazide = INCREASES CA REABSORPTION Loop = DECREASES CA REABSORPTION

How does the Human Multidrug resistance (MDR1) gene work to become resistant to cancer therapy?

This gene codes for P-glycoprotein, which is a *transmembrane ATP-dependent efflux pump protein* that has a broad specificity to hydrophobic compounds and can reduce the influx of drugs and can increase the efflux of drugs from the cytosol

What innervates the Latissimus Dorsi?

Thoracodorsal nerve (C6-C8)

"hypersensitivity to intradermal injections of tobacco extract" suggests what?

Thromboangiitis Obliterans (Buerger's Disease)

What are the functions of Thyroid peroxidase?

Thyroid peroxidase is multi-functional: --- catalyzes the oxidation of iodide (I- to I2), the iodination of thyroglobulin, and coupling between 2 iodized tyrosine residues NOTE: 90% of Hashimoto thyroiditis patients have antibodies against Thyroid peroxidase

What does the QT interval represent?

Time required for depolarization and repolarization

What is Varenicline used for?

Tobacco cessation - it is a partial agonist of nicotinic ACh receptors... And can therefore reduce nicotine withdrawal cravings and reduce the reward feeling of nicotine

Describe the distribution of body mass and body water:

Total body water = 60% of total body mass Non-water mass = 40% of total body mass Intracellular fluid is 2/3 of the total body water, and extracellular fluid is 1/3 of the total body water (this comes out to 40% of the total body mass and 20% of the total body mass respectively) Interstitial fluid is 3/4 of the total extracellular fluid, and plasma is 1/4 of the total extracellular fluid

What is *Toxic Megacolon*

Toxic Megacolon is a well-recgonized complication of Ulcerative colitis (and less commonly Crohns & C. Diff) - It is d/t severe inflammation causing release of inflammatory mediators, bacterial products, and increased nitric oxide, which contribute to smooth muscle paralysis. The colon gets distended, and there is thinning of the intestinal wall, making ti prone to perforation - *Presentation* = abdominal pain/distension, bloody diarrhea, fever, and signs of shock - *Plain X-ray is the preferred imaging study* (Barium contrast study and colonoscopy are contraindicated d/t rupture risk)

What translocation is associated with Chronic Myelogenous Leukemia? and what does this form? and how does it affect a receptor?

Translocation = 9:22 - This forms a fusion protein of ABL proto-oncogene (chromosome 9) and the BCR gene (chromosome 22) - The resulting oncogene, *BCR-ABL*, codes for a fusion protein with *constitutive tyrosine kinase activity*

What is the first line for treatment of PTSD?

Trauma-focused *cognitive-behavioral therapy* and antidepressant medication (*SSRI* preferred or SNRI)

What is Plummer-Vinson Syndrome?

Triad of *D*ysphagia, *I*ron deficiency anemia, and *E*sophageal webs - Koilonychia (*spoon-shaped nails*) and *Shiny red tongue* can also be seen d/t the iron deficiency anemia - Most symptoms resolve after supplementation with Iron

What is the mechanism for "Triptan" drugs?

Triptans are used as abortive therapy during an acute migraine - They are *Serotonin 5-HT agonists* that directly counter the pathophysiologic mechanism of migraine headaches by inhibiting the release of vasoactive peptides, promoting vasoconstriction, and blocking pain pathways in the brainstem - Significant elevations in blood pressure and cardiac events have been reported with triptans and their use should be avoided in patients with cardiac or cerebrovascular disease

Patau syndrome

Trisomy 13 *P* = *P*atau = *P*uberty age = 13

Edwards syndrome

Trisomy 18 *E* = *E*dward = *E*lection age = 18

Bilateral Renal Angiomyolipomas are associated with what condition?

Tuberous Sclerosis

What does *linkage disequilibrium* mean?

Two allele loci are said to be in linkage disequilibrium when a pair of alleles are inherited together in the same gamete (haplotype) more often or less often than would be expected given random pairing - This most often occurs when the genes are in close physical proximity on the same chromosome

What are the 3 stop codons?

UAA, UAG, UGA - These DO NOT code for an amino acid, so the last amino acid added comes from the 3 codon sequence before this

Compare the inflammatory pattern of Ulcerative Colitis vs. Crohns:

UC - *continuous superficial inflammation* affecting the mucosa and submucosa with crypt abscesses (neutrophil collections with glandular lumen) and crypt atrophy. NO granulomas. Crohns - *Patchy transmural inflammation* (skip lesions) involving the entire thickness of the intestinal wall, *noncaseating granulomas* (a hallmark of crohns!!!), distortion of normal mucosal architecture, and panneth cell metaplasia.

What is Ubiquitin?

Ubiquitin is a protein that undergoes ATP-dependant attachment to other proteins labeling them for degradation - These misfolded proteins enter the proteasome and are degraded into small peptides - Impairment of the ubiquitin-proteasome system can contribute to the development of neurodegenerative disorders, including Parkinsons and Alzheimers

What nerve supplies most of the intrinsic nerves of the hand?

Ulnar nerve - Intrinsic muscles of the hand are responsible for finger abduction/adduction

In embryonic development, the bodies veins fall into 3 mian groups: umbilical, vitelline, and cardinal veins... What do these later become?

Umbilical - This eventually degenerates Vitelline - Forms the portal system Cardinal - Forms constituents of the systemic venous circulation (such as the IVC, etc.)

What is a classic finding in a Uncal Herniation?

Uncal herniation often *compresses the ipsilateral CN III* as it exits the midbrain, resulting an *oculommotor nerve palsy with a fixed dilated pupil* (eg. d/t preganglionic parasympathetic fiber damage) NOTE: if the ipsilateral Posterior cerebral artery is compressed, it can lead to a contralateral homonymous hemianopsia with macular sparing

What food item is most associated with E. Coli 0157:H7 (enterohemorrhagic E. Coli)

Undercooked ground beef

How does a pancreatic pseudocyst differ from a true cyst?

Unlike true cysts, *pseudocysts are not lined by epithelium* - the walls of a pseudocyst consist of granulation tissue and fibrosis Pathogenesis = The proteolytic enzymes may disrupt the walls of the pancreatic ducts and cause leakage of pancreatic secretions into the peripancreatic space. This fluid has a high pancreatic enzyme content and induces an inflammatory reaction in the walls of the surrounding organs. Granulation tissue forms, encapsulating the fluid collection and forming a pseudocyst

What is the normal timeframe for Acute transplant rejection?

Usually 1-4 weeks following transplantation (First aid says "weeks to months")

What is the main mode of transmission of Hep C?

Usually IV drug use (Sexual transmission of Hep C is VERY RARE!!!)

What is the most common cause of Post-partum hemorrhage?

Uterine Atony - failure of the uterus to contract adequately after delivery (which usually contracts to compress the placental blood vessels) This usually responds to uterotonic agents

What is the resistance mechanism for Mycobacterial organisms to *Isoniazid*

Via *decreased activity of Catalaze-Peroxidase* Mycobacterial catalase-peroxidase is required for the initial enzymatic conversion of Isoniazid to its active metabolite within the mycobacterial cells

What is the most common side effect of the chemo drug: Vincristine?

Vincristine inhibits microtubule polymerization, which prevents synthesis of the mitotic spindle in dividing cells. - This also interferes with microtubule formation in the nerve axons, and can thus cause neurotoxicity... Which can manifest clinically as peripheral neuropathy NOTE: Other chemo microtubule inhibitors are: Paclitaxel, and Vinblastine

What is Virchow Triad?

Virchow Triad described 3 things that contribute to the development of thrombosis (DVT/PE): - Stasis - Hypercoaguability (Cancer, Factor V leiden, etc.) - Endothelial damage

What is the most likely adherence site for Viridans Streptococci

Viridans strep can adhere to *Fibrin-Platelet aggregates* d/t their ability to produce dextrans - fibrin and platelets are deposited at sites of endothelial trauma, providing a site for bacterial adherence and colonization during bacteremia... In pt with pre-existing valvular lesions, Viridans strep can adhere to the affected valve and establish infection leading to endocarditis

What vitamin must be given with Isoniazid, and why?

Vitamin B6 (Pyridoxine) - this is b/c Isoniazid is structurally similar to pyridoxine, so it increases urinary excretion of pyridoxine - This can result as a Vitamin B6 deficiency which manifests as a peripheral neuropathy

What co-factor is needed for the hydroxylation of Proline and Lysine, in collagen synthesis ?

Vitamin C (Ascorbic Acid)

What does Vitamin C do in collagen synthesis?

Vitamin C is required for the hydroxylation of proline and lysine residues in pro-collagen

What is Neonatal Vitamin K deficiency?

Vitamin K is a necessary cofactor for gamma-carboxylation of coagulation factors: II, VII, IX, X - Newborns who do not receive a prophylactic supplementation of vitamin K are at risk for Bleeding complications - A Vit K shot is necessary b/c there are low Vitamin K stores at birth, and the neonatal liver cannot use Vitamin K efficiently NOTE: this is especially a risk for Pts with Cystic Fibrosis because they are at additional risk for Vitamin K d/t poor absorption of fat-soluble vitamins

How does Acetyl-CoA help regulate glycolysis/gluconeogenesis?

When Acteyl-CoA is high, it will upregulate Pyruvate carboxylase, and downregulate Pyruvate dehydrogenase, which will promote gluconeogenesis - When Acetyl-CoA is low, then pyruvate will be diverted to pyruvate dehydrogenase, to prevent the cell from being energy starved

during what daily actions is a CN 4 nerve palsy most noticeable?

When the affected eye needs to look down and toward the eye (b/c it cannot do this motion well w/o the superior oblique muscle) - therefore it is noticeable while walking down stairs, or reading, etc.

Selection Bias:

When your sample is not representative of the general or target population

If a question talks about "cystic degeneration of the putamen" what should you keep in mind?

Wilsons disease (UWorld said this is a common association on USMLE)

what genetic abnormality is the cause of Fragile X?

X-linked disorder caused by a loss-of-function mutation in the fragile X mental retardation (FMR1) gene on the long arm of X chromosome

Does T3 produce negative feedback on Hypothalamus (TRH) and Anterior Pituitary (TSH)?

YES!!!! - in the normal state, most of the circulating thyroid hormone is in the form of T4, which provides most of the feedback suppression of TSH release. However, T3 also suppresses TSH

What is a case series study?

a descriptive study that tracks patients with a known condition to document the natural history or response to treatment - These cannot quantify statistical significance

What receptors does Norepinephrine act on?

a1, a2, B1

What receptors does Isoproterenol work on?

agonist at B1 & B2

What receptors does Epinephrine work on?

agonist at B1 = B2 > a1

Why might it take a while for a diabetic pt to see the effects of Pioglitazone?

b/c the glucose-lowering effects of Thiazolidinediones requires alterations in gene transcription and protein synthesis, it takes several days to weeks after starting the therapy to observe a significant reduction in glucose levels

Why does someone with primary adrenal insufficiency have hyperpigmentation?

because very high ACTH (from lack of cortisol negative feedback) stimulates melanocytes NOTE: This only happens in primary adrenal insufficiency. It does not happen in secondary adrenal insufficiency because the pituitary does not secrete the high ACTH

What 2 enzymes in heme synthesis are inhibited in Lead?

d-Aminolevulinic acid (ALA) dehydratase Ferrochelatase

Why are patients with Nephrotic syndrome at a hypercoaguable state?

d/t loss of anticoagulant factors, especially antithrombin III