UWorld

When is FADH2 produced?

produced from FAD in the TCA cycle Via the conversion of succinate to fumarate by succinate dehydrogenase

Where is vWF synthesized? How about Factor VIII?

vWF = made in endothelial cells Factor VIII = made by liver sinusoidal endothelial cells both are increased by Desmopressin (DDAVP)

Uric Acid crystal shape

yellow/brown diamond/rhombus

Common Robertsonian translocation causes of Downs?

t(14;21) and t(21;22)

Where are bile acids reabsorbed? What disease can lead to impaired bile acid reabsorption?

terminal ileum Crohn's disease loves the terminal ileum, can lead to decreased bile acid reabsorption and wasting of bile acids into feces

Ramelteon MOA

melatonin agonist in suprachiasmatic nucleus Used for insomnia in the elderly

What is Charcot Marie Tooth Disease?

mutation on myelin protein gene (neural form of muscular atrophy) Foot drop seen due to involvement of *DEEP PERONEAL NERVE*

What causes Ehlers-Dalos exactly?

hereditary disorder due to a deficiency in procollagen peptidase, the enzyme responsible for cleaving terminal propeptides from procollagen in the extracellular space! Symptoms due to the formation of soluble collagen that does not properly crosslink!

How do accessory nipples form?

ie. extra nipples Due to failure of involution of the mammary ridge. Usually anywhere along milkline from axilla to perineum. Usually asymptomatic, but can swell or become tender during menses, pregnancy, and lactation (just like regular nipples)

Describe the Adenoma to Carcinoma sequence. What OTC drug is useful for reducing the risk of this progression?

"AK-53" Aspirin is protective (due to COX-2 over expression)

What enzymes are impaired in thiamine deficiency?

"ATP" -alpha- keotglutarate dehydrogenase -Transketolase -Pyruvate Dehydrogenase

Name of sarcomere region where its only actin? myosin?

"An Interesting Zoo Must Have Mammals!" Actin in the I-band attaches to Z-line Myosin in the H-band attaches to M-line

Picture of Sarcomere

"HIZ" shrinkage

DAG and IP3. Which stars in PM? Which goes to ER to release Ca?

DAG stays in PM IP3 goes to ER to release Ca

What is breast milk made up of sugar-wise?

Lactose! (glucose + galactose) & maltose (glucose + glucose)

Where does elastase come from in the lungs?

Macrophage lysosomes and neutrophil primary granules

Where do optic tract fibers project to?

Mainly to the Lateral Geniculate Nucleus (LGN = "light") Superior Colliculus (reflex gaze) Pretectal Area (light reflex) Suprachiasmatic nucleus (circadian rhythms) (F = Meyer's Loop)

What is released from eosinophils that functions to kill helminths?

Major basic protein

Which nerve provides sensory innervation to the TMJ and middle ear?

Mandibular nerve (V3) --- damaged in Temporomandibular disorder

Majority of cause of Downs syndrome?

Meiotic Nondisjunction in Meiosis I of the ovum

Describe normal brain development

PMR TDMMM

Schistosoma- how do they infect us? Which species infect where?

larvae penetrate skin, travel to liver. Adult worms travels to different places: S. japonicum and S. mansoni = mesenteric venules of intestines S. haematobium = urinary bladder venous plexus

What AA becomes essential in PKU?

Tyrosine

What si the other 22q11 deletion syndrome that is similar to DiGeorge syndrome? What does it entail?

Velocardiofacial syndrome--- palate, facial, and cardiac defects in addition to the "CATCH"

MOA of Cilostazol

cAMP activates PKA, which causes inhibition of platelet aggregation. Cilostazol is a phosphodiesterase inhibitor, leading to less breakdown of cAMP, and further inhibition of platelet aggregation. Also causes arterial vasodilation (may cause coronary steal syndrome) Used in claudication

Pathognomonic term for hepatic schistosomiasis?

eggs that settle into pre sinusoidal radicals of the portal vein can cause PERIPORTAL "PIPESTREAM" FIBROSIS

Calcium phosphate crystal shape

elongated wedge shaped that form rosettes --- looks like pen CaPS!

Describe the hemoglobinopathy electrophoresis patterns seen for HbS and HbC and all the mixes/traits/diseases

HbS: glutamic acid (negative) --> valine (non polar) HbC: glutamic acid --> lysine (basic =positive ***Speed= HbA>HbS>HbC

What is Carnitine synthesized from? What does it need? What is its purpose?

Synthesized from lysine and methionine, requires Vitamin C Responsible for the transport of fatty acids into the mitochondria for beta oxidation

Where does Secondary TB reactivate in the lungs? Why?

Upper lungs, particularly the apex---probably due to decreased lymphatic flow or increased oxygen tension Causes extensive cavitation!

What does the ureteric bud give rise to? What does the metanephric blastema/mesenchyme give rise to?

Ureteric Bud: Collecting system of the kidney (collecting tubules/ducts--> ureters) Metanephric Mesenchyme: glomeruli, Bowman's space, PCT, loop of henle, and DCT!

Where do uric acid crystals normally form? Why?

Uric acid is an acid (duh) so its precipitates in acidic environment (HA). Most acidic environments of the kidney are the *distal tubules and cortical collecting duct*

How to prevent neonatal tetanus?

Vaccinating women who are pregnant or may become pregnant with inactivate tetanus toxin (tetanus toxoid). These omg will give to babies tranplacentally via IgG

Tx for paroxysmal supraventricular tachycardia?

Valsalva Maneuver (increases vagal tone) If unsuccessful, then IV Adenosine

Components of Chocolate agar (Thayer-Martin)? What do they inhibit?

Vancomycin - inhibits gram positives Colistin (polymyxin) - Gram negs other than neisseria Nystatin (VCN) - yeast sometimes trimethoprim is added to inhibit Proteus species

What typical causes black versus brown pigmented gall stones?

Black = intravascular hemolysis Brown = Biliary infection

features of symptomatic hypokalemia?

Muscle weakness, cramps, rhabdomyolysis and cardiac arrhythmias

Explain Laron Dwarfism

Mutated GH receptors resulting in decreased linear growth Pts will have high serum GH concentrations and low levels of IGH-1

Treatment for Chagas Disease?

Nifurtimox caused by trypanosoma cruzi

How do arteries vasodilate? (the entire reaction)

Besides picture, know that increased cGMP leads to activation of PKG, which reduces intracellular Ca2+ levels in smooth muscle cells, leading to relaxation/vasodilation

Drugs with negative cardiac chronotropic effects?

Beta blockers and calcium channel blockers

What does epinephrine stimulate more at low dose?? high dose?

low dose = Beta-2 (vasodilator skeletal muscle) High dose = Alpha-1

ACE-inhibitor effects on the kidney?

Blocks ATII's vasoconstrictive effect on the efferent arteriole. *Will cause a DECREASE in GFR, which may be noticed by an increase in creatinine

How do beta-1 blockers decrease bp?

Blocks Beta-1 Receptors in heart, decreasing contractility and HR Also inhibits Renin release

Best Tx for preventing reactivation of HCV-2 infection?

Daily oral acyclovir, valcyclovir, or famciclovir Can surprise further multiplication as soon as reactivation occurs

Chronic Granulomatous Disease: heritance? whats wrong here?

X-linked, phagocytes can't synthesize NADPH oxidase Super susceptible to Catalase positive organisms

Carbamazepine: -MOA? -Side Effects?

Blocks voltage gated *Na-channels* in cortical neurons Side effects: 1. *Bone Marrow Suppression* (CBCs done regularly) 2. *Hepatotoxic* (monitor LFTs) 3. *SIADH* due to increased ADH secretion

Symptoms of diabetic retinopathy? What is seen on fundoycopic exam?

Blurry vision, black spots, floaters, and decreased *PERIPHERAL* vision

What are some things that affect the MAC in inhaled anesthetics?

Body temperature and decreases with increasing patient age!

Catalase positive organisms?

"CATs Need PLACESS to Belch their Hairballs" Catalase + Nocardia Pseudomonas Listeria Aspergillus Candida E coli Staphylococci Serratia Burkholder cepacia H pylori

Common findings of multiple myeloma

"CRAB" --- secreting a ton of protein hyperCalcemia Renal involvement (Bence jones proteins= Ig light chains) Anemia Bone lytic lesions/Back pain *Monoclonal M protein spike of IgG *Plasma cells secreting a ton of monoclonal immunoglobulin or immunoglobulin fragments

What is Plummer-Vinson Syndrome?

"DIE" Dysphagia, Iron deficiency anemia, and esophageal webs (fragile mucousal folds that cause solid food dysphagia, usually in the mid to lower esophagus)

Why does pregnancy and the use of OCP's lead to increased risk of cholelithiasis?

"Fat, Fertile, Female and Forty" Estrogen increases cholesterol synthesis by up regulating hepatic HMG CoA reductase activity, causing the bile to become supersaturated with cholesterol Progesterone reduces bile acid secretion and slows gallbladder emptying.

Short acting benzodiazepines that are safe in people with liver problems? Why?

"LOT" Lorazepam Oxazapam Temazapam They undergo glucourondiation directly and are not dependent on liver enzymes for their metabolism *Lorazepam is most often prescribed

What is the order from fastest to slowest of the cardiac tissue conduction velocity of: SA node, AV node, Bundle of His, and Purkinje fibers?

"Park At Venture Avenue!!!!!!!"

What is a neuron called that is reacting to acute irreversible cell damage? What causes this to happen? What happens to the neuron?

"Red Neuron" Due to Transient ischemia, hypoxia, toxicity or hypoglycemia Neuronal cell body becomes shrunken and separated from surrounding tissue. Cytoplasm stains deeply eosinophilic (opposite of normally staining basophilic Nissl Bodies AKA the neuron's RER). Nucleus becomes pyknotic (shrunken and basophilic). Nucleolus and Nissl substance (RER) disappear. Occurs 12-24 hrs after injury, followed by death of neuron. Remnants are phagocityzed by microglia. Astrocytes proliferate over site of injury and form GLIAL SCAR.

What are causes of ARDS? What happens in ARDS? What about the PCWP?

"SPARTAS" Sepsis Pancreatitis/Pneumonia Aspiration uRemia Trauma Amniotic fluid embolism Shock Endothelial damage -->INC ALVEOLAR CAPILLARY PERMEABILITY/leakage --> protein-rich leakage into alveoli --> diffuse alveolar damage *Will see NONCARDIOGENIC pulmonary Edema. PCWP will be NORMAL since this has nothing to do with heart failure

What can precipitate a DIC attack?

"STOP Making New Thrombi" Sepsis (gram negative) Trauma Obstetric complications Pancreatitis (acute) Malignancy Nephrotic Syndrome Transfusions

Where do cranial nerves V1, V2, and V3 exit?

"Standing Room Only!" V1 = Superior Orbital Fissure (along with SO4, LR6,R3) V2 = Foramen rotundum V3 = Foramen ovale

What causes beriberi? What are the 2 kinds? Describe each

"ber1ber1" --- Vit B1/thiamine deficiency

Side effects of isotretinoin?

"iso-threat-inoin"

What is primary sclerosing cholangitis?

"onion skin" bile duct fibrosis-- beading of INTRA and EXTRA HEPATIC bile ducts ***Associated with Ulcerative Colitis (so its pyoderma gangrenosum)

Describe what is seen in an MI after different time periods on microscopy

***1st thing seen is after 4 hours --> early coagulation necrosis (cytoplasmic eosinophilia and nuclear pyknosis)

What characterizes diastolic heart failure? What can cause it?

***DUE TO DECREASED LV COMPLIANCE! Normal LV ejection fraction and LVEDV in the setting of INCREASING LV FILLING PRESSURES! Due to conditions that decrease LV compliance, such as impaired myocardial relaxation (ischemia) or increased intrinsic ventricular wall stiffness (amyloid deposition). These can both happen from long standing HTN causing LV wall hypertrophy, which impairs myocardial relaxation and increases intrinsic wall stiffness.

Describe the PI3K/Akt/mTOR pathway

***Inhibited by PTEN!

Histological changes seen over the course of time in an ischemic stroke

**Nothing is seen histologically before 12 hours!

Cause of Hypertrophic Cardiomyopathy?

*AD mutation of Beta-myosin heavy chain or cardiac myosin-binding protein C gene*--- causes disproportionate thickening of the ventricular septum compared to LV free wall (symmetrical septal hypertrophy)--> causes building of the septal muscle into the LV outflow tract during systole (dynamic obstruction). The LV size is also reduced Histologically: Extreme myofiber disarray with interstitial fibrosis

Picture showing where Cranial nerves emerge from the brainstem

*Always start with Cranial nerve 6!

Describe findings of Freidrich's Ataxia: What else can look like it?

*Autosomal Recessive Ataxia (degeneration of spinocerebellar tract) Loss of position and vibration sense (due to degeneration of dorsal columns and dorsal root ganglia) Loss of DTRs (peripheral nerve degeneration) Spastic muscle weakness and positive Babinski (Lateral corticospinal tract involvement) *Similar to Vitamin E deficiency

VEGF inhibitor? Used for?

*Bevacizumab* Used to treat some metastatic cancers (eg. colon, lung)

Phenylketonuria: Pathyophys? Clinical features? Diagnosis? Treatment?

*Brain damage due to phenylalanine metabolites *Hypopigmentation involving the skin, hair, eyes, and catecholaminergic brain nuclei (which produce a dark pigment known as neuromelanin) results from the inhibitory effect of excess phenylalanine on melanin synthesis

Drugs that are mood stabilizers? Indications? Side effects?

*Carbamazepine = CYP 450 inducer *Lamotrigine is actually more effective in preventing depression rather than mania

What are some features of cystic fibrosis?

*Congenital Bilateral absence of the vas deferens (CBAVD) most likely because CFTR mutation causes abnormal development of Wolffian structures

Treatment for serotonin syndrome? MOA?

*Cyproheptadine* 1st generation histamine antagonist with non-specific 5-HT1 and 5-HT2 receptor antagonistic properties

What is Restrictive Cardiomyopathy? What causes it?

*Decreased compliance* of ventricular endomyocardium leads to restriction filling in DIASTOLE! Caused by amyloidosis, sarcoidosis, radiation, endocardial fibroelastosis, Loftier syndrome (endomyocardial fibrosis with a prominent eosinophilic infiltrate), and hemochromatosis (although it more commonly causes dilated cardiomyopathy)

Describe the classic location/histology of silicosis

*Eggshell* calcifications of hilar lymph nodes, affects upper lobes! (comes from base/earth, affects the roof) ~Silicone breast implants like like eggs have been added to a woman's breast!

Describe the courses of the laryngeal nerve around the neck. What does each branch into? What is innervated by what?

*Exception = Cricothyroid muscle (C**T muscle). Its innervated bye sternal laryngeal nerve while all the others are innervated by the recurrent laryngeal nerve!

How do keloids occur?

*Excessive collagen formation Excessive TGF-beta causes excessive differentiation of fibroblasts into myofibroblasts, causing keloids to extend BEYOND the borders of the original wound. Can be raised, painful, and pruritic Affect Asians and Africans more often

What gene is mutated in associated with maturity-onset diabetes of the young (MODY)?

*Glucokinase!* Glucokinase has lower glucose affinity than other hexokinases. This allows it to function as a glucose sensor in ß-cells by varying the rate of glucose entry into the glycolytic pathway based on blood glucose levels. Heterozygous mutations of glucokinase causes a decrease in ß-cell metabolism of glucose, causing less ATP formation, and diminished insulin secretion! This produces MODY, which is characterized by mild, non progressive hyperglycemia that often *worsens with pregnancy induced insulin resistance*. Homozygous mutations lead to fetal growth retardation and severe hyperglycemia at birth!

What are some of the negative effects of androgen abuse?

*Increased hematocrit (erythrocytosis), testicular atrophy, and acne are key

Is darkening of the skin upon UV exposure due to increase melanocyte cell proliferation of increased melanin production?

*Increased melanin production!*

Voltage gated sodium channel toxins (4)? How do they work?

*Inhibit Na channels, prevent depolarization: -Tetrodotoxin (puffer fish) -Saxitoxin (dinoflaggelates in "red tide") *Open Na channels, causing persistent depolarization: -Ciguatoxin (exotic fish, Moray eel) -Batrachotoxin (South American Frogs)

Common complications of prematurity?

*Intraventricular hemorrhage usually due to hemorrhage from the fragile germinal matrix (very vascular)

Landmark for pudendal nerve block?

*Ischial Spine* (divides greater and lesser sciatic foramen) and *sacrospinous ligament* Palpate ischial spines intravaginally, and inject medially in very close proximity to the ischial spine through the sacrospinous ligament!

Describe the classic location/histology of asbestosis

*Ivory White* calcified, supradiaphragmatic and pleural plaques that affect the *lower lobes* (come from room, but affects the base) *increased risk of pleural effusions*

Epistaxis is most commonly caused by disruption of what plexus? Where? What makes up this plexus?

*Kiesselbach's plexus* in the anteroinferior part of the *Nasal Septum* (aka Anterior Nose bleeds) 1. Septal branch of the *Anterior Ethmoidal Artery* 2. Lateral nasal branch of the *Sphenopalantine Artery* (posteriolateral branches are injured in posterior nosebleeds) 3. Septal branch of the *superior labial artery* (branch of facial artery) ("ASS")

What are the 3 treatment for cyanide poisoning?

*Know this cold! Remember, nitroprusside can induce cyanide poisoning!

Does chronic alcohol abuse cause a macro or mictocytosis?

*MACROCYTOSIS!* Even in the absence of anemia, macrocytosis (MCV>100) is often seen and is likely due to poor nutrition (eg. folate deficiency), liver disease, and/or direct toxicity of alcohol on bone marrow.

Artery that is the main supply to the femoral head? What can happen if its injured?

*MEDIAL* femoral circumflex artery Osteonecrosis of the femoral head

What can cause caudal regression syndrome? What is it? How does it present?

*Maternal Diabetes* Genesis of the sacrum and occasionally the umber spine. Can range in severity from anal atresia to sirenomelia Presents with flaccid paralysis of the legs, dorsiflexed contractors of the feet, and urinary incontinence

What are the DMARDS used to treat RA and their side effects?

*Methotrexate (1st line)*- chemo related (stomatitis, bone marrow suppression alopecia) plus hepatotoxicity Sulfasalazine Hydrochloroquine- irreversible retinopathy Minocycline (its a tetracycline) - photosensitivity dermatitis TNF-alpha inhibitors

Compare/contrast myasthenia gravis versus Lambert-Eaton syndrome

*Note- Lambert-Eaton syndrome usually is a paraneoplastic disorder, usually with small cell lung cancer

Describe the Multiple endocrine neoplasias

*Note: Parathyroid tumors cause hypercalcemia. Medullary thyroid cancers secrete calcitonin, leading to hypocalcemia!

What parts of the external auditory ear canal does the vagus nerve innervate? What can happen if this is accidentally irritated during exploration?

*Posterior part of the external auditory canal*, as well as the concavity and posterior eminentia of the concha. (most of the external auditory canal is innervated by CN V3) *Can induce *vasovagal syncope* after stimulation of the posterior external auditory canal by an otoscope. Parasympathetic outflow via the vagus nerve leads to decreased heart rate and blood pressure!

3 types of glial cells? origin? function?

*Proliferation of astrocytes in an area or neuron degeneration = gloss (formation of a glial scar)

How does loss of estrogen in a female lead to osteoporosis?

*RANK-L* (nuclear factor kappa B ligand)= promotes osteoclast differentiation *Osteoprotegerin (OPG)* = Decoy receptor for RANK0 binds it and shuts it down ***The ratio of OPG:RANK-L determines if osteoclasts are activated or not Estrogen maintains bone mass by inducing production of OPG and decreases RANK expression on osteoclast precursors, decreasing osteoclast formation ***Loss of estrogen effect causes a decrease in OPG to RANK-L ratio, causing increased osteoclast activity and bone turnover

What is a diagnostic test you can use to detect cystine in the urine? How do you treat these types of stones?

*Sodium Cyanide-nitroprusside Test* helps detect presence of cystine in the urine (screening test) Cyanide is initially added to the urine, converting any cystine into cysteine. Afterward, nitroprusside is added and reacts with the sulfahydryl group on free cysteine, causing a red-purple discoloration (positive test) Tx = Hydration and urinary alkalinizatoin (acetazolamide)

What types of injuries can lead to nerve compression of CN III?

*Transtentorial (uncal) herniation* Neoplasms Aneurysms of the PCA (ie. Berry Aneurysm) Will see pupillary dysfunction since it is compressing the outer portion of the nerve, leading to loss of parasympathetic component

Pompey Disease: enzyme deficiency? symptoms?

lysosomal enzyme alpha 1,4-glucosidase (aka acid maltase), helps break down glycogen Presents with cardiomyopathy and hypotonia

Monoclonal Ab for Her2/neu positive breast cancer? How does it work? What if the cancer metastasizes to bone?

*Trastuzumab* Binds to extraceullar portion of HER2 and prevent activation of transmembrane *Tyrosine Kinase*, thereby down regulating cell proliferation and promoting apoptosis Can use *Denosumab* , a Monoclonal Ab against RANKL (functions similar to osteoprotegerin, OPG) if it metastasizes to bone in order to reduce skeletal related events

Describe the secondary structure of tRNA

*also contains chemically modified bases, such as dihydrouridine, ribothymidine, pseudouridine, etc.

Function of COMT? MAO?

*both break down NE and epinephrine COMT: -epinephrine to metanephrine -norepinephrine to normetanephrine MAO: -metanephrine and normetanephrine to vanillylmandelic acid

Describe germline versus somatic mosaicism genetics

*consider germline mosaicism whenever a genetic mutation is identified in the offspring but not the parents!

Important URI in children?

*note: dyspnea associated with acute laryngotracheitis (croup) occurs when inflamed subglottic tissue obstructs the upper airway

Compare/contrast pemphigus vulgaris versus bulors pemphigoid

*pemphigus vulgarus = stratum spinosum

Describe PKU

*seizures*, *intellectual disability*, *MUSTY BODY ODOR*

What are some example of unmyelinated nerve fibers (group C nerve fibers)?

-Autonomic postganglionic nerves -afferent nerves that conduct heat sensation -afferent neurons that transmit slow-onset dull. burning or visceral pain -First order bipolar sensory neurons of olfaction

Distribution of: -Coccidiomycoses -Blastomycoses -Histoplasmosis

-Coccidiomycoses = New mexico (southwest US) -Blastomycosis = Great lakes + ohio river valley (where the civil war was fought, so also the east coast) -Histoplasmosis = midwestern and central US (Mississippi and Ohio River valley)

Functions of the HMP shunt??

-Creates NADPH, a reducing equivalent in the cytosol -Produces ribose-5-P, needed for the synthesis of nucleotides!

Explain the cardiac changes associated with normal changes

-Decreased LV chamber size (especially in the apex-to-base dimension) -->leads t ventricular septum becoming sigmoid shaped -Atrophy of myocardium causes increased interstitial connective tissue (often with extracellular amyloid deposition). -Lipofuscin pigment in cardiomyocytes

Pathophysiology of Polycythemia vera? Blood manifestations? Clinical symptoms? Treatment?

-Due to a JAK2 mutation of hematopoietic stem cells, which makes them more susceptible to growth factors! -Thrombotic events (from blood hyper viscosity), peptic ulceration pruritus (due to histamine release from basophils), and gouty arthritis (from increased cell turnover) -Ruddy face with splenomegaly seen -Treatment = phlebotomy to keep the hematocrit below 45%

Whom does Medicare cover?

-Elderly (>65) -Younger individuals with disabilities, ESR disease, or ALS

MOA of Ribavirin? S/E? Used for?

-Induces lethal hypermutation -Inhibits RNAP and Inosine monophosphate dehydrogenase (depleting GTP) -causes defective 5' cap formation on viral mRNA transcripts -modulates a more effective immune response (inhibits TH2 and stimulates TH1 response) Used in RSV and HCV S/E: Hemolytic anemia and teratogen

Common causes of gynecomastia in men? Tx?

-Obesity (increased aromatase conversion of testosterone to estrogen) -Hyperthyroidism (increased LH secretion and estrogen production) -Cirrhosis (increased aromatase activity, decreased clearance of estrogens) -Chronic Kidney Disease (decreased testosterone production) -Androgen Deprivation therapy for prostate cancer Tx = Tamoxifen (SERM)

Classic manifestations of a pineal mass?

-Obstructive hydrocephalus from aqueduct stenosis (papilledema, headache, and vomitting) -Dorsal midbrain (Parinaud) Syndrome (paralysis of upward gaze, ptosis, and pupillary abnormalities) due to direct compression of the pretectal region of the midbrain! *Usually a germinoma, a midline malignant tumors arising from germ cells.

Symptoms of polyps/adenomas in the colon?

-Occult or visible bleeding (can lead to iron deficiency anemia) -Large polyps can cause obstruction (pain, constipation, abdominal distention) -***Villous adenomas can secrete large quantities of watery mucous, leading to secretory diarrhea, hypovolemia, and electrolyte abnormalities!

How to diagnose Cystic Fibrosis? MCC of death?

1. Elevated sweat chloride levels -If ambiguous, go to #2 2. Measurement of nasal transepithelial potential difference and genetic testing for CFTR mutations should be done to confirm the diagnosis! MCC of death = pneumonia, bronchiectasis, and cor pulmonale

Describe what the glossopharyngeal nerve innervates: Somatic motor? Parasympathetic? General sensory? Special sensory?

-Somatic motor: Stylpharyngeaus muscle (elevates larynx when swallowing) -parasympathetic: inferior salivary nucleus --> CN IX--> otic ganglion --> travels along auriculotemporal nerve (CN V) --> parotid gland secretion General sensory: inner surface of tympani membrane, eustachian tube, post. 1/3 tongue, upper pharynx (afferent portion of the gag reflex), carotid body and sinus special sensory: taste to post 1/3 of tongue

Significance of Duodenum: 1st part? 2nd part? 3rd part? 4th part?

1 = horizontal, only part of duo NOT retroperitoneal 2 = travels inferiorly with head of pancreas; where ampulla of Vater enters 3 = horizontal with uncinate process of pancreas near SMA 4 = travels superiorly, once it passes ligament of Treitz it becomes jejunum

What is it called if someone has 1 allele of Sickle Cell? Both alleles?

1 allele = Sickle Cell TRAIT 2 allele = Sickle Cell DISEASE

Treatment options for Alzheimers Disease?

1. Enhancement of cholinergic neurotransmission: i -ie. Donepezil-- Cholinesterase inhibitor 2. Neuroprotection via antioxidants -Vitamin E (alpha-tocopherol) 3. NMDA Receptor Antagonism -Memantine (its believed that glutamate overstimulation of NMDA receptors may contribute to AD symptoms)

What 2 ways are excess cholesterol removed from the body?

1. Excretion of free cholesterol into the bile 2. Conversion of cholesterol into bile acids

Describe how atherosclerosis develops

1. *Endothelial injury/dysfunction* causing increased vascular permeability and enhanced leukocyte adhesion 2. Accumulation of lipoproteins (LDL) within the vessel wall 3. *Monocyte adhesion* to the endothelium, followed by migration and transformation into lipid-laden *macrophages (foam cells)*. 4. Release of growth factors (ie. PDGF, TGF-ß) by adherent platelets, activated macrophages, and endothelial cells all due to endothelial dysfunction. 5 Recruitment of T cells and *smooth muscle cell proliferation* from the media to the intima, which leads to extracellular matrix production! ***With advancing age, the chronic inflammatory process initiated by endothelial cell injury transitions from fatty streaks within the intimate (composed mainly of lipid-laden foam cells) into atherosclerotic plaques, such as fibrous cap atheromas and fibrous plaques.

Three post-transcriptional processing events?

1. 5' capping (7-methyl guanosine) 2. Polyadenylation of 3' end: AAUAAA sequence signals Poly-A signal to be added after it. This protects the mRNA from degradation in the cytoplasm 3. Splicing: Initial pre-mRNA (hnRNA) splices out introns, retains exons to become mature mRNA

Components of a triple test?

1. Alpha-fetoprotein (AFP): synthesized by fetal liver, GI tract, and yolk sac (early gestation only). Maternal serum AFP levels increase with gestational age. 2. Estriol levels reflect both placental and fetal function, as both are necessary for its synthesis. 3. Human chorionic gonadotropin (hCG) is synthesized by trophoblastic tissue.

4 major causes of hypoxemia (low PaO2)? Which his a normal A-a gradient?

1. Alveolar hypoventilation (normal A-a gradient) 2. V/Q mismatch 3. Diffusion impairment 4. Right-to-left shunting

How can you diagnose DM?

1. Fasting Blood Glucose >126 2. Random glucose >200 3. HbA1C >6.5% *Note-- Osmotic symptoms (polyuria, polydipsia, blurred vision) suggest the blood glucose levels are >180

2 main virulence factors for B. anthracis? What do they do?

1. Antiphagocytic Poly-gamma-D-glutamic acid capsule 2. Anthrax exotoxin, a trimeric toxin composed of protective antigen, edema factor, and lethal factor ---Protective antigen functions to translocate edema and lethal factor into the cytosol ---Edema factor acts as a calmodulin-dependent adenylate cyclase that increases cAMP, causing accumulation of fluid w/in and btw cells, and also causes suppression of neutrophil/macrophage function

Main indications for Diazepam?

1. Anxiolytic for GAD and panic attacks 2. Sedative-hypnotic for short term insomnia 3. Anticonvulsant for status epilectus and for tx of alcohol withdrawal induced seizures (along with chlordiazepoxide) 4. Muscle relaxant for spasticity caused by UMN disorders and tetanus

Most common cause of death in Marfans Syndrome? 2nd MCC? Typical symptoms?

1. Aortic Dissection due to untreated aneurysm from *cystic medial degeneration/necrosis* of the aorta (will also see MVP) 2. Cardiac failure secondary to MVP and/or aortic regurg ** MVP, lens displacement, aortic root dilation and aortic dissection

Inherited Disorders caused by deficient DNA-Repair Enzymes (5)

1. Ataxia-Telangiectasia (radiation susceptibility) 2. Xeroderma Pigmentosum (UV radiation = melanoma and SCC) 3. Fanconi Anemia (susceptibility to DNA cross-linking agents) 4. Bloom Syndrome (generalized chromosome instability) 5. HNPCC (defect in DNA mismatch repair enzymes)

What are 2 causes of Renal Artery Stenosis? How would this patient present?

1. Atherosclerosis of the renal artery in elderly 2. Fibromuscular Dysplasia in women 20-30. Narrowing of multiple segments of renal artery occurs ("string of beads"). *Pt presents in either case with HTN and abdominal bruit

Treatment for TIA?

1. BP control 2. Statin therapy 3. Low-dose aspirin

Acute treatment for Status epilepticus?

1. Benzodiazepines (ie. *Lorazepam*) in order to stop the INITIAL seizure (benzos work w/in minutes) 2. *Phenytoin* also administered to prevent the RECURRENCE of seizures (reduces ability of sodium channels to recover from inactivation)

Describe the orthostatic hypotension from standing reflex

1. Blood pools in veins below heart --> decreased Venous Return to heart 2. Dec. ventricular filling and drop in C.O. 3. Drop in BP evokes compensatory baroreceptor reflex 4. Inc sympathetic tone that increases peripheral vascular resistance (alpha-1 Receptors) as well as HR and contractility (Beta-1 Receptors)

Common side effects of Phenytoin?

1. CNS manifestations due to effects on cerebellum (ataxia) and vestibular system (nystagmus) 2, Gingival hyperplasia (due to increased PDGF from macrophages) 3. Interferes with the metabolism of folic acid = megaloblastic anemia 4. Cyt P450 Inducer 5. Teratogen = fetal hydantoin syndrome (cleft lip/palate)

3 main types of immunosuppressive agents?

1. Calcineurin inhibitors (Cyclosporine and Tacrolimus) = Inhibits NFAT, and NF-kß, decreasing IL-2 synthesis 2. mTOR inhibitors (Sirolimus/Rapamycin) = Decrease IL-2R signaling 3. de nono Purine Synthesis Inhibitors/T-lymphocyte proliferation inhibitors (Azathioprine and Mycophenolate) = inhibit DNA replication 4. Glucocorticoids

What 3 things regulate the medullary respiratory center?

1. Central chemoreceptors in medulla are stimulated by a decrease in pH (CO2 can cross the BBB and form H+ in the CSF). Therefore, *PaCO2 is the MAJOR stimulator of central chemoreceptors!* 2. Peripheral chemoreceptors in the carotid and aortic bodies are the primary site for sensing *PaO2* and are stimulated by hypoxemia! 3. Pulmonary stretch receptors include myelinated and unmyelinated C fibers in the lungs/airways. These receptors regulate the duration of inspiration depending on the degree of lung dissension (Hering-Breuer Reflex)--- protects lung from overinflation

3 phases that regulate gastric acid secretion?

1. Cephalic- cholinergic/vagal mechanisms stimulate this by sight, smell etc. 2. Gastric: mediated by presence of gastrin (stimulates histamine secretion and therefore acid secretion) and it triggered by the chemical stimulus of food in stomach 3. Intestinal: down regulates gastric acid secretion after a meal. Ileum/colon release peptide YY, which binds to receptors on the endocrine, histamine-containing cells called enterochromaffin-like cells (ECLs). This inhibits gastrin-stimulated histamine release from ECLs. Also inhibited by somatostatin and PGs.

How does therapeutic ionizing radiation (eg. gamma rays, x-rays) used inc cancer treatment cause cell death?

1. DNA DOUBLE-strand breakage 2. Free-radical formation

2 ways Tb can gain resistance to INH? When can INH be used as mono therapy?

1. Decreased bacterial expression of catalase peroxidase enzyme (Kat G) which is required for INH activated once INH enters the Tb cell 2. Modification of the protein target binding site for INH (mycolic acid production) *Can be used as mono therapy for a positive PPD and a negative CXR

Describe the histology seen inside active/acute plaques of multiple sclerosis

1. Demyelination with relative preservation of axons (decreased saltatory conduction) 2. Accumulation of lipid-laden macrophages (containing the products of myelin breakdown) 3. Astrocytosis (proliferation in response to injury) 4. Infiltration by lymphocytes and mononuclear cells Note- Chronic MS plaques lead to loss of axons, neurons, and oligodendricytes

What is pellagra? What can it be seen in?

1. Dermatitis -- B/L and symmetric on sun exposed areas of the body and is characterized by rough, thick, scaly skin 2. Diarrhea -- due to atrophy (and occasional ulceration) of the columnar epithelium of the GI tract 3. Dementia due to neuronal degeneration in the brain and spinal cord, with lesions similar to those associated with pernicious anemia *Can be seen in those with decreased Niacin (Vit B3) or tryptophan, carcinoid syndrome, prolonged INH use, or Hartnup disease

Treatment for acute C. diptheriae infection?

1. Diphtheria Antitoxin- important to give this first because it is ineffective against toxin that has already entered heart or CNS tissue! 2. Penicillin/erythromycin 3. DPT vaccine

How is Campylobacter jejuni transmitted?

1. Domestic animals (cattle, sheep, dogs and chickens). Seen in farm and lab workers 2. Contaminated food such as undercooked poultry or unpasteurized milk

Non fusion of the urethral folds in male? female?

male = hypospadias female = normal, makes the vestibule of the vagina

2 drugs/supplements you give to lower Triglyceride levels

1. Fibrates: Activates PPAR-alpha, which leads to decreased hepatic VLDL production and increased LPL, which hydrolyzes Triglycerides in chylomicrons and VLDL into free fatty acids! 2. Fish oil (omega-3 fatty acids): decrease VLDL production, and inhibit the synthesis of Apolipoprotein B

What 3 conditions can an S3 heart sound be heard in?

1. Forceful, rapid filling of a ventricle that has normal or elevated compliance 2. Normal or even decreased filling rate when ventricular compliance is low 3. Blood flowing into an overfilled ventricle with high end-systolic volume

3 Physiologic causes of nausea? Drugs to treat each of the 3?

1. GI tract mechanical/chemical irritants: -chronic irritation causes increased mucous serotonin release and activation of 5-HT3 receptors on vagal and spinal afferents, which relay impulses to the medullary vomiting center. -*5-HT3 Receptor antagonists (eg. ONDANSETRON)* = treatment of choice 2. Vestibular System (motion sickness and vertigo): -Tx= 1st generation H1 receptor antagonists (diphenhydramine, meclizine) and Muscarinic ACh receptor antagonists (*scopolamine*) 3. Central nausea (chemoceptor trigger zone activates the D2 receptor in the area postrema): -Tx= Dopamine receptor antagonists (metoclopramide, promethazine)

Describe how differentiation of the reproductive system takes place:

1. Gonadal Stage: The primordial germ cells originate near the yolk sac and move towards the genital ridge, forming primitive gonads consisting of germ cells, supporting cels and steroidogenic cells. Under the influence of the SRY gene on the Y chromosome, male gonads begin to secrete testosterone (from Leydig cells) and MIF (from sertoli cells) 2. Ductal Stage: In the male embryo, MIF causes the Paramesonephric (mullerian) ducts to regress, while the mesonephric ducts develop into the epididymis, ductus deferens, and seminal vesicles. In the female embryo, testosterone and MIF are not produced. The Mullerian (paramesonephric) ducts give rise to the uterine tubes, uterus, cervix, and upper vagina under the influence of maternal estrogen and the mesonephric duct regresses. 3. Genital Stage: The genital tubercle gives rise to the glans penis in males and the glans clitoris in females. The urogenital folds transform into the ventral aspect of the penis in males and the labia minora in females. The genital swellings become the scrotum in males and the labia majora in females. The urogenital sinus gives rise to the bladder, urethra, prostate, and bulbourethral glands in the males. In females it develops into the bladder, urethra, lower vagina, and Bartholin glands

You have a substance in your body that you want to get rid of via dialysis. What are 3 ways to increase the rate of drug removal?

1. High molecular concentration GRADIENTS 2. Larger membrane surface areas! 3. Increased solubility of the diffusing substance

What 3 things stimulate gastric acid secretion in the funds/body of stomach from parietal cells?

1. Histamine (H2)-- increases cAMP 2. ACh (M3 muscarinic receptors)-- increases calcium 3. Gastrin (cholecystokinin B receptor) -- increases calcium. Also stimulates histamine synthesis/release from enterochromaffin-like cells in stomach

What are the 3 orders of neurons of the sympathetic chain as it projects to the eye (as seen in Horner's syndrome)

1. Hypothalamus down to T1-T2 where they synapse in intermediolateral horn. 2. Exit spinal cord through anterior nerve roots and white communicating rami to reach 3rd order neurons located in the superior cervical ganglion (C2). 3. Postganglionic fibers travel along carotid arteries to reach target tissues in face/head

Precipitating factors for G6PD anemia?

1. Infections 2. Drugs: Dapsone, antimalarials, sulfonamide abxs (TMP-SMX) 3. Diabetic Ketoacidosis 4. Fauvism (ingestion of fava beans)

Why exactly does aspirin increase risk of upper DI bleed?

1. Inhibition of platelet aggregation 2. Impairment of Prostaglandin-depedent GI mucous protection

By what 2 ways do thiazides increase calcium reabsorption?

1. Inhibition of the apical Na/Cl cotransporter 2. Inducing hypovolemia causes increased Na and H2O absorption in the PCT, leading to passive increase in paracellular Ca reabsorption

Describe the 3 phases of Acute Tubular Necrosis

1. Initiation phase: original ischemic or nephrotoxic insult. lasts about 36 hours, no real changes yet 2. Maintenance phase: tubular damage is fully established and pts commonly have oliguria, fluid overload, and electrolyte abnormalities (hyperkalemia, metabolic acidosis). usually lasts about 2 weeks, during which the GFR stabilizes at a significantly lower level, with a rise in serum creatinine. Hits = light microscopy will show tubular epithelial necrosis, denudation of the tubular BM, and casts (muddy brown) 3. Recovery phase: *Repithelialization of tubules* is characteristic. GFR recovers quickly when the debris/casts are cleared. However, the tubular cells recover more gradually, resulting in transient polyuria and loss of electrolytes due to impaired tubular resorption and decreased renal concentrating ability!

Pathogenesis of acne

1. Keratinization of hair follicle with formation of keratin plug which blocks release of sebum 2. Hypertrophy of sebaceous glands with excess sebum production 3. Colonization of glands with P. acnes 4. Bacterial hydrolysis of TGs in sebum and release of inflammatory FAs

What are 3 examples of diseases caused by heteroplasmy?

1. Leber hereditary optic neuropathy = leads to bilateral vision loss 2. Myoclonic epilepsy with ragged red fibers = myoclonic seizures and myopathy associated with exercise. Skeletal muscle biopsy shows irregularly shaped muscle fibers (ragged red fibers) 3. Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) = its in the name bro

MCC of SCIDS? 2nd MCC (pathogenesis of this guy)

1st = IL-2R defect 2nd = Adenosine Deaminase Deficiency (normally responsible for elimination of excess adenosine within cells) -Excess adenosine accumulate within lymphocytes, leading to lymphocyte cell death

When are melatonin levels the highest/lowest? cortisol?

melatonin: -highest = Night Lowest = day Cortisol: -Highest = Morning -Lowest = night

What 4 things does the facial nerve innervate? Besides unilateral facial paralysis, what else can patients with Bell's palsy present with?

1. Motor Output to the facial muscles 2. Parasympathetic innervation to lacrimal, submandibular, and sublingual salivary glands 3. Special afferent fibers for taste from anterior 2/3 of tongue 4 .Somatic afferents from pinna and external auditory canal Pts with Bell's palsy can also present with decreased tearing, hyperacusis, and/or loss of taste of ant 2/3 of tongue

What 3 drugs can be used to help treat alcoholism? When can you give each? MOA?

1. Naltrexone: blocks the mu-opioid receptor (its narcan) and can be initiated when pts are STILL DRINKING. It blocks the rewarding and reinforcing effects of alcohol 2. Disulfiram: Inhibits aldehyde hydrogenase, causing an aversion. Can only be used in abstinent pts 3. Acamprosate: modulates glutamate neurotransmission at the NDMA receptor. Can only be used once abstinence has been achieved

Describe the neurogenic (autonomic) and neuroglycopenic symptoms of hypoglycemia:

1. Neurogenic symptoms: -caused by sympathoadrenal activation and are mediated via norepi/epi and ACh released by sympathetic postganglionic fibers. Symptoms of norepi/epi release include tremulousness, palpitations, and anxiety/arousal, whereas cholinergic symptoms include sweating, hunger, and paresthesias 2. Neuroglycopenic: -symptoms include behavioral changes, confusion, visual disturbances, stupor, and seizures

What usually causes lung abscesses?

1. Oropharyngeal Aspiration (MC): Contains mixed aerobic and anaerobic oral flora (peptostreptococcus, prevotella, bacterioides, fusobacterium). Risk factors include loss of consciousness or dysphagia (such as seizures, alcoholism, drug overdoses, prolonged anesthesia, and server neurologic disease) 2. Complication of Bacterial Pneumonia: Usually due to immunosuppression, old age, chronic lung disease. Necrotizing pneumonias are usually nosocomially caused by Staph aureus, E coli, Klebsiella, and Pseudomonas. 3. Hematogenous spread via septicemia or endocarditis: Usually multiple and mono microbial (usually Staph or strep)

Function of Thyroid Peroxidase enzyme? What disease has Abs against it?

1. Oxidation of Iodide to Iodine (I2). 2. Iodination of thyroglobulin tyrosine residues 3. Iodotyrosine coupling reaction that forms T3 and T4 *Abs are made against TPO in Hashimotos Thyroiditis

Branches of the splenic artery (3)? Which is most susceptible to damage from ischemia?

1. Pancreatic branches: run posterior to the upper border of the pancreas, supplying its BODY and TAIL 2. Left Gastroepiploic Artery 3. Short Gastric branches: supplies the upper part of the greater curvature of the stomach! *Shot gastric arteries have very poor anastomoses, making them very vulnerable to ischemic injury!

What are the 2 types of pneumococcal vaccines? How do they work? Who are they given to?

1. Polysaccharide Vaccine (PPSV23-- PREVNAR): Protects against 23 strains, but Abs levels decline after 5 years. Also not immunogenic in children <2 due to immature humoral Ab response. -Recommended for all adults >65 or those 2-64 with certain medical conditions (diabetes, COPD, CV disease) 2. Conjugate Vaccine (PCV13-- PREVNAR) Protects against 13 strains; its a polysaccharide vaccine conjugated to a nontoxic diphtheria protein, which boosts immune response through *T cell recruitment*! Strongly immunogenic, causes memory B cells to develop. Part of all routine childhood vaccinations, adults >65, and those <65 with certain medical conditions ***The PROTEIN component allows T Cell recruitment!!!

5 stages of behavioral change? (ie. alcoholics)

1. Precontemplation (denial) 2. Contemplation (acceptance) 3. Preparation (planning to make change) 4. Action 5. Maintenance

Describe how the embryonic kidneys develop

1. Pronephros forms, non functional, goes away at week 4 2. Mesonephros: 1st functional kidney. Persists in males as Wolffian Duct system, regresses in females to form the vestigial Gartner's Dcuts. 3. Metanephros: first, the metanephric diverticulum (aka the Ureteric Bud), which sprouts off the caudal portion of the mesonephric duct, penetrates into the metanephric mesoderm (metanephric blastema). The interaction of these two structures drives the formation of the true kidney!

What parts of the brain are most susceptible to ischemic injury?

1. Pyramidal cells of the Hippocampus (1st area affected) 2. Purkinje cells of the cerebellum 3. Watershed zones (btw ACA/MCA and MCA/PCA)

For gluconeogenesis, what 3 enzymes of glycolysis must be bypasses? How does gluconeogenesis go about doing this?

1. Pyruvate Kinase: mitochondrial *Pyruvate carboxylase*converts pyruvate into oxaloacetate. Oxaloacetate transforms into malate so it can exit the mitochondria, gets converted back into oxaloacetate, and in the cytosol gets converted into PEP by *PEPCK*. 2. Phosphofructokinase-1 (PFK-1): *Fructose 1,6-bisphosphatase* 3. Hexokinase: *Glucose-6-phosphatase

How do you diagnose syphilis? Which test do you do first? Second? How do they work?

1. Rapid plasma Reagin test: (screening) -Patient's serum mixed with solution of cardiolipin, cholesterol, and lecithin. Aggregation ("flocculation") of sample demonstrates presence of ANTI-CARDIOLIPIN Abs in patients serum. -Anti-cardiolipin abs since T. pallidum causes cell destruction, releasing human cellular lipids into blood stream, allowing anti-cardiolopin abs to be formed against them -Non specific test bc other species of T. pallidum can cause yaws, pinta or bejel which can all cause anti-cardiolipin abs -Can also do a *VDRL* since both are easy and inexpensive -***Can be used to follow disease progression and therapeutic response to treatment 2. FTA-ABS (confirmatory test): -Detects Antibodies directed against Treponema. -Mixes patients serum with whole killed T. pallidum, and the Anti-Treponema Abs can be visualized through indirect immunofluorescence.

What metabolic changes are seen in someone who overdoses on aspirin?

1. Respiratory Alkalosis: first disturbance to occur, as sialicylates directly stimulate the medullary respiratory center. The resulting increase in ventilation leads to increased loss of CO2 in the expired air (< 3 hours) 2. Anion Gap Metabolic Acidosis: begins shortly after, as high concentrations of salicylates increase lipolysis, uncouple oxidative phosphorylation, and inhibit the TCA cycle. This results in the accumulation of organic acids in the blood (ketoacids, lactate, and pyruvate) So it starts as respiratory alkalosis, then progresses to ma mixed metabolic acidosis/respiratory alkalosis

What are the manifestations of each stage of alcohol withdrawal? At what time frame do they occur? What is the first symptom to occur? Most severe?

1st = tremulousness (6-24 hrs) Most severe = delirium tremens (48-96 hours)

Which 3 centers regulate the micturition reflex?

1. Sacral micturition center-- located in S2-S4 level and responsible for bladder contraction. Parasympathetic fibers travel from S2-S4 white matter within pelvic nerves and stimulate cholinergic receptors in the bladder wall! 2. Pontine Micturition Center --- located in the pontine reticular formation. It coordinates relaxation of the external urethral sphincter with bladder contraction during voiding 3. Cerebral cortex -- inhibits the sacral micturition center!

What 2 things help prevent the premature activation of trypsinogen in the pancreas? Why can result if either of these are lost?

1. Serine peptidase inhibitor Kazal type 1 (SPINK1) is a trypsin inhibitor. It impedes any prematurely activated trypsin molecules 2. Trypsin itself can serve as its own inhibitor as well by cleaving other trypsin molecules (rendering them inactive) *Hereditary pancreatitis can occur if either are lost = recurrent acute pancreatitis attacks!

MCC of hematogenous osteomyelitis? 2nd MCC?

1. Staph aureus 2. Strep pyogenes

Too much acid in stomach causes bicarb to be secreted from where? How are they stimulated?

1. Submucosal (Brunner) Glands: -Located mainly in 1st part of duodenum near pylorus, but can extend all the way to ampulla of vater -terminate in the crypts of Lieberkuhn *stimulated by tactile or increased parasympathetics *Also too much acid in duodenum causes release of SECRETIN from S-cells of duodenum which increase bicarb release 2. Epithelial cells of pancreatic ducts: -watery secretions that are high in bicarb *Stimulated by SECRETIN

What are the 2 ways host defenses help fight candida infections?

1. T-lymphocytes (helper T cells) are important for the prevention of SUPERFICIAL candida infections (oral/esophageal candidiasis, cutaneous candidiasis, cutaneous, and vulvulovaginitis candidiasis). Conditions such as *HIV* (low T-cell count) increase risk for superficial candidiasis 2. Neutrophils prevent the HEMATOGENOUS spread of candida. Disseminated candidiasis is more likely in patients who are neutropenic or immunocompromised (cancer with chemotherapy) and those with inherited impairments of phagocytosis

What are the 3 hormones that predominantly influence sexual development?

1. Testosterone: develops male internal geneitalia, spermatogenesis, male sexual differentiation at puberty (muscle mass, libido) 2. DHT: Develops male external genitalia, growth of prostate, male pattern hair growth. Also amplifies effects of testosterone due to high affinity for testosterone receptor 3. Estrogen: endometrial proliferation, devilment of ovarian granuloma cells, breast development

Most common cause of ring-enhancing lesions with mass effect in patient with HIV? 2nd MCC?

1. Toxoplasma gondii 2. Primary Central Nervous System Lymphoma (PCNSL) -Its a diffuse, large-cell Non-hodgkin Lymphoma of B cell origin due to EBV!

What 3 drugs inhibit dihydrofolate reductase?

1. Trimethoprim: bacteriostatic when alone, bactericidal with sulfamethoxazole 2. Methotrexate: S-phase specific for rapidly dividing cells 3. Pyrimethamine: antimalarial and tx against toxoplasmosis

In early embryonic development, what are the 3 main types of veins that develop? What do they become?

1. Umbilical Vein -- degenerates 2. Vitteline Veins -- Portal venous system 3. Cardinal veins --- form veins of systemic circulation

What drugs should be avoided in patients with Hypertrophic cardiomyopathy?

1. Vasodilators (Dihydropyridine calcium channel blockers, nitroglycerine, and ACE inhibitors) decrease SVR, leading to decreased afterload and lower LV volumes, leading to worsening of blockage! 2. Diuretics decrease LV venous filling (preload) and also result in greater outflow obstruction

What enzymes is thiamine a cofactor for? What happens in thiamine deficiency? How do you treat?

1. alpha-ketoglutarate dehydrogenase (TCA cycle) and branched-chain alpha-ketoacid dehydrogenase 2. Transketolase-- enzyme in HMP shunt that helps convert ribulose-5-P (from glucose) to glycolysis intermediates (such as glyceraldehyde-3-P) 3. Pyruvate Dehydrogenase-- converts pyruvate (from glycolysis) into Acetyl-CoA (enter TCA cycle) Alcoholics can get Wernicke Encephalopathy (opthalamoplegia, taxi, and confusion) due to severe thiamine deficiency, leading to a foci of hemorrhage and necrosis in the maxillary bodies and periaqueductal grey matter. This is due to decreased glucose utilization, leading to problems in tissues with high aerobic demand (CNS and heart). Diagnosis = low erythrocyte transketolase activity that increases with thiamine administration Tx: Give both glucose and thiamine

How does the respiratory tract clear particles based on size: -10-15 micrometers? -2.5-10 micrometers? -<2 micrometers?

10-15 (large) = Trapped in upper respiratory tract 2.5-10 (medium) = enter trachea/bronchi and are cleared by mucociliary transport <2.5 (small) = reach terminal bronchiole and alveoli- phagocytized by macrophages

MOA of Metryapone?

11ß-hydroxyalse inhibitor-- blocks synthesis of cortisol in adrenals

Major breakdown product seen in androgen-secreting adrenal tumors?

17-ketosteroids (eg, androstenedione, androsterone), which are the breakdown products of a number of steroid hormones, especially androgens.

1st line tx for PCOS? What if they want to get pregnant?

1st line = Weight reduction, followed by OCPs If trying to get pregnant = Clomiphene (antagonist at estrogen receptors at hypothalamus, disrupting normal negative feedback, allowing more FSH and LH release, stimulating ovulation)

What holds the 2 heavy chains of an Ab together?

2 disulfide bonds just before the huge region

Name some diseases caused by genetic mutations on chromosome: 7 16 20 22

7: Cystic Fibrosis, Ehlers Danlos, and Osteogenesis Imperfecta 16: Polycystic Kidney Disease and Tuberous Sclerosis 20: Maturity Onset diabetes of the young type 1 (MODY) 22: DiGeorge Syndrome

Why does fetal hemoglobin (HbF) not actively bind to 2,3-BPG?

2,3-BPG is NEGATIVELY CHARGED, and HbF has no beta chain (so no positively charged histidine residue to bind it!) The gamma chain of HbF has serine in place of histidine.

Equation for maintenance dose?

note- IV drugs have a bioavailability fraction of 1

Elevated 17-hydroxyprogesterone?

21-Hydroxylase Deficiency (Adrenal cortical hyperplasia)

Function of Transketolase?

2nd enzyme in the Pentose Phosphate pathway, occurs in cytoplasm (#6 in diagram, requires thiamine)

Why do 3rd generation cephalosporins have greater activity against gram negative bacteria compared to 1st and 2nd generation cephalosporins?

3rd generation cephalosporins have combinations of chemical groups around the ß-lactam ring that prevent ß-lactamase access, so they are ß-lactamase resistant!

What does the 3rd pharyngeal pouch give rise to? 4th?

3rd: Dorsal = inferior parathyroid glands Ventral = Thymus 4th: Dorsal = Superior Parathyroid glands Ventral = Parafollicular (C) cells of thyroid

What mutation causes cystic fibrosis? Why?

3-base pair deletion causes removal of phenylalanine at position 508 (∆F508). "Fenylalanine" on chromosome *7* This results in impaired postTRANSLATIONAL processing (improper folding/glycosylation), which is detected by the ER. Therefore the ER sends it for degradation by the proteasome instead of to the cell surface!

What is missing in DiGeorge Syndrome? What are they at increased risk of infections of? What about blood serum concentration levels?

3rd and 4th Pharyngeal Pouches Viral and Fungal Infections (no thymus) No Parathyroids causes hypocalcemia (tetany)

Cephalosporins with activity against pseudomonas?

3rd gen = Ceftazidime 4th gen = Cefepime

What weeks of development does differentiation and development of external genitalia occur?

8-15 weeks

What is Turner Syndrome? What are some clinical features?

45 (X,O) -Loss of *PATERNAL* X Chromosome. Streak ovaries, primary amenorrhea, increased risk for ovarian dysgerminoma. no barr bodies Webbed neck due to CYSTIC HYGROMA, which are dilated lymphatic channels. Its a mass composed of cystic spaces separated by connective tissue, impairs lymphatic drainage/outflow. Also causes lymphedema of hands and feet. Heart problems: Coarctation of Aorta (diminished femoral pulses) and Bicuspid Aortic valve Shield chest, widely spaced nipples Cubitus valgus (increased carrying angle of arms) Horseshoe Kidney Short stature (deletion of 2nd SHOX gene located on X chromosome) "Knuckle-Knuckle-Dimple-Sign"

What is a normal A-a gradient? Why does an A-a gradient even exist in the first place?

5-15 mmHg Blood entering the lungs initially gets hit with the exact same PO2 as the alveoli, but it gets lowered by the addition of deoxygenated blood from: -Bronchial circulation (drains into left atrium) -Intrapulmonary AV anastomoses -Thesbian veins of the heart (drain into left atrium and ventricles)

Which rRNA is transcribed outside of the nucleolus?

5S rRNA is located outside of the nucleolus Transcribed by RNAPIII, along with tRNA

When does the blastocyst implant? When can ß-hCG be detected in serum? urine?

6 days after fertilization. Serum = 8 days (<5 IU/L) Urine = 14 days (20 IU/L)

C. diff enterotoxin A? Enterotoxin B?

A = Watery Diarrhea B = colonic epithelial cell necrosis and fibrin deposition (colitis)

Why is the macula spared in a PCA infarct?

A PCA infarct knocks out the occipital lobe, which contains the primary visual cortex (striate) The macula is spared because collateral blood is supplied by the MCA to the occipital lobe, which possesses central visual information.

Inheritance of hemophilia A, B, and C?

A and B = XR (ABs are "X-Rated") C = AR

What isa glomangioma made of? What are its functions normally?

A benign glomus tumor (glomangioma) can produce a very tender, small red-BLUE lesion under the nail bed. This type of tumor originates from the modified smooth muscle cells that control the *thermoregulatory* functions of the dermal glomus bodies!

What determines the ventricular contraction rate in A fib?

A fib is initiated by aberrant electrical impulses that arise within regions of heightened atrial excitability (most often the pulmonary veins). Once triggered, AF leads to electrical remodeling of the atria with development of shortened refractory periods and increased conductivity. This facilitates the creation and persistence of multiple ectopic foci and re-entrant impulses within the atria, increasing the risk and chronicity of subsequent episodes (A-fib causes A-fib!) Ventricular response in A-fib is *dependent on the transmission of abnormal atrial impulses through the AV node*. Each time the AV node is excited, it enters a refractory period during which additional atrial impulses are not able to be transmitted o the ventricles; therefore, the majority of atrial impulses never reach the ventricles!

What is progressive supra nuclear palsy? How does it present? What does brain biopsy show?

A form of parkinsonism from neurodegeneration of the midbrain and frontal subcortical white matter Presents with rapidly progressive gait dysfunction and falls, executive function loss, and vertical gaze palsy Brain biopsy shows deposits of abnormally phosphorylated tau proteins

What structures are incised in an episiotomy? What connects to the latter of the two?

A midline episiotomy is a vertical incision from the posterior vaginal opening to the perineal body. Structures anchored to the perineal body: -Bulbospongiosus muscle -External Anal Sphincter -Superficial and deep transverse perineal muscles -Fibers from the external urethral sphincter, levator ani, and muscular coat of the rectum

Explain the actual cause for why hydroceles occur:

A patent processus vaginalis allows for communication of the peritoneal cavity with the scrotum. This allow fluid to accumulate within the Tunica vaginalis! ***WILL transluminate!

What hormone causes gestational diabetes? Why does this occur?

A physiologic increase in insulin resistance occurs during the 2nd and 3rd trimesters due to shunting of carbohydrate metabolism toward supplying glucose and AAs to the fetus. Insulin resistance is primarily due to the action of human placental lactogen (*hPL*), also known as chronic somatomammotropin, a peptide hormone secrete day the syncytiotrophoblasts. Insulin resistance leads to increased glucose levels in maternal circulation;glucose crosses freely into the fetus and is continuously consumed for fetal energy. Maternal lipolysis and proteolysis are also increased by hPL, with the resulting FFAs and ketones providing energy to the mother. In cases of maternal malnutrition, the increased ketones can also provide the fetus with energy. hPL also stimulated *pancreatic ß-cell insulin production*. Gestational DM results when pancreatic function is not sufficient to overcome the pregnancy-related increase in insulin resistance. There average levels of hPL rise with increasing gestational age and pleated at term, reflecting the increasing energy requirements of the growing fetus. Testing for gestational DM is therefore more accurate in the 3rd trimester and is done with an oral glucose challenge and a measurement of serum glucose levels after 1 hour!

Describe a Marcus Gunn pupil in the context of the pupillary light reflex

A relative afferent pupillary defect (Marcus Gunn Pupil) often occurs with lesions involving the optic nerve, such as optic neuritis in multiple sclerosis Optic tract lesions can also cause a relative afferent pupillary defect in the pupil contralateral to the tract lesion, as the nasal portion of the retina contributes more input to the pretectal nucleus! This defect can be observed during the *swinging flashlight test* because the patient's pupils constrict less (and therefore appear to dilate) when a bright light is swung to the pupil contralateral to the tract lesion!

What is CREST syndrome?

A variant of systemic sclerosis with skin disease. Calcinosis Raynaud Phenomenon Esophageal Dysmotility Sclerodactyly Telangiectasia

Which serotypes of Chlamydia trachomatis cause what diseases?

A-C = Occular infection (trachoma) in children ("C with your eyes!") D-K = Urogenital (STD) infections and inclusion conjunctivitis ("DicK")-- can progress to PID. Children can get neonatal conjunctivitis and pneumonia ("staccato" cough 1-2 weeks after birth) L1-L3 = Lymphogranuloma venereum (LGV)

Which type of antibodies are seen in ABO blood groups? D antigens in newborns?

ABO = IgM D (Rh antigen) = IgG

Acute Pericarditis: What causes it? Why does leaning forward help?

Decreases pressure on the parietal pericardium Usually due to myocardial infarction, Rheumatic fever, uremia, or viral infection

Main difference between 21-hydroxylase deficiency and Aromatase deficiency?

Aromatase deficiency presents with Maternal visualization. In 21-hydroxyalse deficiency, maternal visualization does not occur due to intact placental aromatase activity

What 3 therapies reduce morbidity and improve survival and should be started in a patient with CHF or decreased ejection fraction?

ACE Inhibitors ß-Blockers Spironolactone-- Blocks the deleterious effects of aldosterone on the heart (myocardial fibrosis and ventricular remodeling/left ventricular hypertrophy)

What 2 things are elevated in sarcoidosis? why?

ACE and Calcium! Macros in the granulomas express high levels of ACE and 1-alpha hydroxylase

MOA of bordetella toxin? Stages?

AB exotoxin that ribosylates Gi, causing increased cAMP. This leads to insulin production, leukocyte and neutrophil dysfunction, and increased sensitivity to histamine. Catarrhal stage (mild URI symptoms), paroxysmal (whooping cough) and convalescent stage

Causes of Dilated Cardiomyopathy?

ABCCCD Alcohol abuse wet Beriberi Coxsackie B viral myocarditis Chronic Cocaine Use Chagas Disease Doxorubicin toxicity others= hemochromatosis, sarcoidosis

What 3 molecules are produced from POMC?

ACTH, MSH, and ß-endorphins (endogenous opioid, helps suppress pain) The fact that ACTH and an endogenous opioid are produced from the same precursor molecule (POMC) suggests a close relationship between the stress axis and the opioid system!

Where is each synthesized: ACh Dopamine GABA NE Serotonin

ACh = Basal Nucleus of Meynert (dorsal pons) Dopamine = Ventral Tegmentum and SNpc GABA = Nucleus Accumbens NE = Locus Ceruleus (Pons) Serotonin = Raphe Nucleus (brainstem)-- Raphe = Rave, increases serotonin levels!

What is Von-Hippel Lindau Disease?

AD

What is hereditary spherocytosis? What are seen on labs?

AD defect in RBC structural proteins (spectrin, ankyrin, or protein 4.1) Characterized by increased RBC osmotic fragility and MCHC (mean corpuscular Hb concentration) increased above 36 g/dL

Achondroplasia -- inheritance? gene messed up? What does the patient look like?

AD gain of function point mutation in FGFR3, which normally inhibits cartilage proliferation especially in the long bones. Endochondral ossification is inhibited, while membranous ossification is fine. 90% are due to new mutations (usually paternal allele). Will also have a severe doral kyphosis, and increased lumbar lordosis, which essentially put the patient's lower back in hyperextension, causing spinal stenosis!

What is hereditary spherocytosis?

AD hemolytic anemia due to a RBC membrane defect, usually PM scaffolding proteins SPECTRIN and ANKYRIN. W/o this scaffolding, spherocytes are less deformable and are prone to accelerated destruction in the spleen! *RBCs lack central pallor!

What causes malignant hyperthermia? How does it occur? How do you treat it?

AD hypersensitivity of skeletal muscle to inhaled anesthetics (especially halothane) and succinylcholine (muscle relaxant) Abnormal ryanodine receptors release large amount of Ca into cytosol in response to anesthetic. This stimulates the ATP-dependent reuptake of Ca back into SR. Excessive consumption of ATP generates heat; loss of ATP with high temp induces muscle damage. Rhabdomyolysis leads to release of potassium, myoglobin, and creatine kinase into circulation. Tx = Dantrolene, binds ryanodine receptor on SR and prevents further release of Ca

Describe tuberous sclerosis:

AD mutation ion the tumor suppressor gene TSC1 (hamartin) and TSC2 (tuberin), cutaneous angiofibromas (adenoma sebaceum) seizures, and mental retardation, CNS hamartomas, renal/vascular cysts, CARDIAC RHABDOMYOMAS and RENAL ANGIOMYOLIPOMAS!!!

Describe neurofibromatosis type 2 (NF-2)

AD nervous system tumor syndrome in which patients commonly develop bilateral CN VIII schwannomas and multiple meningiomas

Amniotic fluid of NT defects will show increased levels of what?

AFP and AChEsterase

What is the most important prognostic factor for patients infected with PSGN?

AGE! Children do much better than adults!

Acute treatment for Acute intermittent Porphyria

AIP is due to deficiency of PBG deaminase. Want to stop the pathway. *Glucose or Heme will inhibit ALA synthase*, shutting down the heme pathway and reducing symptoms. Dextrose (glucose) is given IV, which inhibits Peroxisome proliferator-activated receptor gamma, a transcription factor that induces synthesis of ALA synthase. Do NOT give Cyp P450 inducers, which actually up regulate ALA synthase and would make this worse!

What is a negative thing that increased activity of microsomal monooxygenase can cause?

AKA Cytochrome P450 Unfortunately activates inactivated pro-carcinogens into carcinogens. An example is benzo(o)pyrene causing lung cancer

Describe inflammatory breast cancer

AKA Peau d'orange Its in invasive breast cancer causing dermal lymphocyte invasion where the neoplastic cells block lymphatic drainage, causing edema and erythematous rash with firm/coarse skin resembling an orange peel

Describe the Paramesonephric duct

AKA the Mullein Duct Estrogen from ovaries stimulates this to form the "ducts" of the female repro tract! Forms the fallopian tubes, uterus, and upper portion of vagina (lower 2/3s from urogenital sinus) Remnant in males = appendix testis

Describe the Mesonephric duct

AKA the Wolfian Duct Testosterone from testis stimulates this to form the "ducts" of the male repro tract! Forms the seminal vesicles, epididymis, ejaculatory duct, and ductus deferens (SEED) ***NOT THE PROSTATE OR TESTIS Remnant in females = Gartner duct

Type of Amyloidosis in Multiple Myeloma?

AL Amyloidosis. Amyloid protein is derived from monoclonal Ig Light chains, deposits in kidneys, heart, tongue, and nervous system

What drugs can induce mania?

ALL ANTIDEPRESSANTS CAN INDUCE MANIA in susceptible pts. Especially pts who present as depressed, you treat them with antidepressant, and they come back weeks later in mania. Tx them with mood stabilizers (aka pts with UNRECOGNIZED BIPOLAR DISORDER, especially bipolar I)

What do the Superficial Inguinal Lymph nodes drain?

ALL skin below the umbilicus including the anus (below dentate/pectinate line) with the exception of: Testes, glans penis, and Posterior calf (these drain to Deep Inguinal Lymph node)

Difference between ANOVA/t-test and chi-squared?

ANOVA/t-Test compare the MEANS Chi-square compares 2 categorical variables

What murmur are you listening for when you listen between the 3rd/4th intercostal spaces on the right and the patient sits up, leans forward and exhales and holds their breath?

AORTIC REGURGITATION

What causes the esophageal dysmotility in CREST syndrome?

Result of atrophy and fibrous replacement of the muscular in the lower esophagus. The esophageal body and LES become atonic and dilated, leading to GERD

What Leukemia can be treated with a vitamin? Why does this work? Common problem in this disease

APL (M3 variant of AML) can be treated with ATRA (high dose Vitamin A) Retinoid acid receptor-alpha (RAR-alpa) on chromosome 17 is translocated to chromosome 15 where it fuses with PML gene to form new gene called PML/RAR-alpha). AKA t(15;17). This now abnormal RAR-alpha cannot signal for differentiation of myeloid precursors at physiological doses of retinoid acid. ATRA overcomes this. DIC commonly seen in APL *Auer Rods* seen: These are azurophilic, needle-shaped cytoplasmic inclusions of MPO formed by the fusion of primary granules found in myeloblasts and promyelocytes!

You run a gel, and you see DNA fragments in multiples of 180 base pairs. What does this usually indicate?

APOPTOSIS! This phenomenon is known as *DNA Laddering*. This occurs through the action of specific endonucleases during karyorrhexis. These endonucleases cleave DNA at internucleosomal linker regions, which occur at 180 base pair intervals in the genome!

Inheritance of Sickle cell anemia?

AR

Which types of diseases tend to be autosomal recessive? How about autosomal dominant?

AR = Enzyme defieincies (ie. Classical galactosemia) AD = Defective non-catalytic proteins

What is the pathogenesis of hereditary hemochromatosis?

AR Missense mutation in *HFE* gene, a cell membrane protein that interacts with transferrin molecules to endocytose the iron-transferrin complex. A mutated HFE leads to reduced iron uptake into cells, so the hepatocytes/intestinal cells sense falsely low iron levels. It increases iron accumulation via: 1. Enterocytes increase apical expression of Divalent metal transporter 1 (*DMT1*), *increasing intestinal iron absorption in the lumen* 2. Hepatocytes *decrease hepcidin* synthesis, which increases ferroportin expression on basolateral surface of enterocytes and promotes iron secretion into circulation!

Most common genetic cause of Cystic Fibrosis?

AR Phenylalanine deletion (F508)

What causes Orotic Acuduria? Presentation? Tx? What does this present similar to?

AR deficiency in UMP synthase, the enzyme that converts orotic acid into UMP in the de novo pyrimidine synthesis pathway. Increased urinary orotic acid and megaloblastic anemia refractory to folate/B12 tx. Children present with psychical and mental retardation. Tx = UMP (uridine) to bypass the enzymatic defect Increased urinary orotic acid is also seen in ornithine transcarbamaylase deficiency, but OTC deficient patients will also have hyperammonemia encephalopathy in the first few weeks due to impaired urea synthesis!

Describe the pathogenesis of methylmalonic acidemia

AR deficiency of methylmalonyl-CoA mutase Buildup of methylmalonic acid and propionic acid leads to metabolic acidosis, hypoglycemia, production of ketones, and hyperammonemia. Diagnose via increased elevated urine methylmalonic acid and propionic acid

Describe Fructokinase deficiency (aka benign/essential fructosuria)

AR disorder causing fructose to be excreted unchanged in urine. Hexokinase takes over the role of fructose metabolism, converted fructose into fructose-6-P (instead of fructokinase converted it into fructose-1-P!). Fructose-6-P can then be metabolized in glycolysis, converted to glucose-6-P (PPP) or glucose-1-P (glycogen synthesis)

What is medium-chain Acyl-Coa dehydrogenase deficiency? Describe it

AR disorder of fatty acid ß-oxidation (forming ketones). Patients have a decreased ability to break down fatty acids into Acetyl-CoA, leading to accumulation of 8-10 carbon fatty acyl carnitines in the blood and hypoketotic hypoglycemia. Patients present with lethargy, vomiting, and confusion.

Ataxia-Telangiectasia: Cause? Presentation?

AR mutation in ATM gene causing defects in DNA double strand break repair. Its VERY susceptible to *X-ray Radiation*, high risk of cancer Cerebellar defects (ataxia) Spider Angiomas Repeated Sinopulmonary infections (IgA deficiency) Oculocutaneous telangiectasia later in life Inc AFP

Wilson Disease: -Pathophysiology?

AR mutation in ATP7B hinders intracellular hepatocyte copper transport, causing reduced formation/secretion of ceruloplasmin (the major extracellular copper transport protein) and *decreased secretion of copper into the biliary system*! Copper forms free radicals that cause hepatocellular injury, and it can also leak into blood and become deposited in various tissues (basal ganglia, cornea). If pt has neurological deficits, they will have *Kayser-Fleischer Rings* on *split-lamp examination*! Confirm diagnosis with *low serum cerruloplasmin* and increased urinary copper excretion, and elevated hepatic copper content on liver biopsy! Tx = Penicillamine

What causes Abetalipoproteinemia? Clinical symptoms? What is seen on blood smear?

AR mutation in MTP gene, which is responsible for the normal folding of the apoB protein and also helps transfer lipids into the forming chylomicrons/VLDLs. Clinical signs include malabsorption, decreased vitamins ADEK, et. ***Will see ACANTHOCYTES, which are RBCs with abnormal thorny projections due to messed up PM from cholesterol dysregulation!

What causes Bloom syndrome? Clinical features?

AR mutation in the BLM gene (encodes DNA HELICASE) Chromosomal instability and breakage cause: Growth retardation, facial anomalies (ex: microcephaly), and photosensitive rash, and immunodeficiency (i.e. recurrent infections)

Cystinuria pathogenesis?

AR mutation in transporter shared by the dibasic AA's cysteine, ornithine, lysine, and arginine (COLA) that is in intestinal lumen and kidney tubular lumen at PCT.

What is Hartnup Disease? Tx?

AR, causes deficiency of neutral AA transports (like tryptophan, needed to make niacin) in proximal renal tubular cells and enterocytes. Leads to tryptophan deficiency from decreased absorption from gut and peeing out too much. Decreased tryptophan causes niacin deficiency-- pellagra (tryptophan is also a precursor for melatonin and serotonin, think carcinoid). Urinary excretion of proline, hydroxyproline, and arginine remains unchanged, and this important finding differentiates Hartnup disease from other causes of generalized aminoaciduria such as Fanconi syndrome! Tx with high protein diet and Nicotinic Acid

What is the action of ATII on the plasma flow through the glomerulus? What happens over time?

ATII constricts the efferent arteriole, increasing the glomerulus capillary hydrostatic pressure leading to an increase in GFR. Over time however, there will also be an increase in glomerulus capillary oncotic pressure, which opposes and eventually overwhelms the increase in glomerular capillary hydrostatic pressure, leading to a decrease in GFR!!!

What are the effects of AV shunts on the cardiovascular system? What happens to the heart? What happens to the afterload?

AV shunts bypass the arterioles, the major source of resistance in the CV system. Blood under arterial pressure directly empties into veins, causing an *increased preload!* Total peripheral resistance is decreased since blood is bypassing the arterioles, thus *decreasing afterload!*

Examples of NRTIs? MOA?

Abacavir Tenofovir (nucleoTide - doesn't need to be P) Emtricitabine Didanosine Stavudine *Lamivudine *Zidovudine (prophylaxis and pregnancy) haVE YOU DINED (vudine) with my NUCLEAR (nucleo-side) family? Competitively inhibits Reverse Transcriptase

Symptoms of opioid withdrawal? Which are pretty specific? Is this life threatening?

Abdominal pain, N/V/D, piloerection, mydriasis, diaphoresis and LACRIMATION/YAWNING NOT life threatening and does not result in seizures like withdrawal from alcohol or benzodiazepines

What is a Zener Diverticulum? How does it occur?

Abnormal spasm/diminished relaxation of the *cricopharyngeal* muscles during swallowing. Increased intraluminal pressure eventually results in herniation of the pharyngeal mucousa through a zone of muscle weakness (false diverticulum- no muscularis involved) in the posterior hypo pharynx (aka *Killian Triangle*).

What is myotonia? Describe myotonic dystrophy

Abnormally slow relaxation of muscles (sustained grab on doorknob usually) Preferential atrophy of Type I muscle fibers (1 slow red ox)

If a heart were to become ischemic, how soon would the myocardium stop contracting? What is myocardial stunning? When is damage irreversible?

About 60 seconds! The major early biochemical consequence of totally myocardial ischemia is cessation of aerobic glycolysis and initiation of anaerobic glycolysis. This transition occurs within seconds and results in inadequate production of high energy phosphates (ATP, creatine phosphate) and the accumulation of deleterious metabolites (lactate). Although ATP levels remain relatively normal during the first few minutes of ischemia, ATP is rapidly depleted from areas of the cell with high metabolic demand, such as the cytosol surrounding the contraction fibers and electrolyte pumps. The depletion of ATP in critical cellular areas and the accumulation of toxins results in the loss of contractility within about 60 seconds of total myocardial ischemia! As ischemia persists, ATP levels within the affected cardiac myocytes continue to fall while lactate levels continue to rise. When ischemia lasts less than 30 minutes, loss of contractile function is still reversible . However, on restoration of blood flow, full myocardial contractility is not immediately restored. Instead, there is prolonged dysfunction of the myocardium ("Myocardial stunning"), with contractility gradually returning to normal over the next several hours to days, Increasing durations of ischemia prolongs the time that the myocardium remains stunned. Under hypoxic conditions, ATP within cardiomyocytes is degraded to ADP. AMP, and eventually adenosine. Adenosine is able to cross the cell membrane and act as a vasodilator when the coronary blood flow if insufficient to meet myocardial demand. However, persistent ischemia can lead to depletion of massive amounts of adenosine. After 30 minutes of total myocardial ischemia, about half of the adenosine stores are lost. At this point, failure of cellular homeostasis is inevitable and ischemic injury becomes irreversible!

Where are gracile and cuneate fasiculi present?

Above T7, both are present. Below T7, only the gracile fasciculi is present (ONLY LEGS!)

Do you insert a needle above or below a rib in a thoracocentesis?

Above! Picture a "VAN" driving under the rib!

Classic histology of psoriasis?

Absent Stratum Granulosum Overlapping parakeratosis Hyperplastic epidermal thickening (acanthosis) with prolonged downward thickenings between the dermal papillae ("rete ridges")

Zellweger Syndrome: pathogenesis?

Absent peroxisomes, VLCFAs accumulate in tissues. Infants can't form myelin in CNS (neuronal defects)

Explain the normal metabolism of fructose:

Absorbed via GLUT5. Phosphorylated by fructokinase in liver, yielding fructose-1-P, which is converted by Aldolase B into DHAP and glyceraldehyde. Both these molecules are then converted into glyceraldehyde-3-P, which can then enter glycolysis!

How do bacteria normally gain antibiotic resistance? How about gaining the ability to make a toxin?

Abx resistance: conjugation (via sex pillus) Ability to make toxin: Lysogenization (bacteriophage infects bacteria with genome, and then that genome integrates into the host bacteria's genome)

Use of Dapsone? Side effects of Dapsone?

Abx used for leprosy, 2nd line in Pneumocystis Jiroveci Pneumonia and Toxoplasmosis Can cause fever, rash, methemoglobinemia, and hemolytic anemia on G6PD patients (puts oxidative stress on the body)

What is seen histologically in iron overload? How do you treat?

Accumulated ferritin stores in Kupffer cells (macros of RES system) is called hemosiderin, which is a brown or yellowish-brown pigment visualized via a Prussian-Blue stain. Treat with iron chelation therapy to prevent "Bronze diabetes" (deposition of excess iron in liver, myocardium, skin and pancreas)

Explain the histology seen in Prion diseases

Accumulation of ß-pleated sheets resistance to proteases (PrPSC) accumulates in grey matter. 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 the brain tissue

Drugs that lead to liver NECROSIS?

Acetaminophen and halothane

What 2 diseases cause absent esophageal peristaltic movements?

Achalais Systemic Sclerosis (will see atrophy of the muscular with collagenous fibrosis)

Difference between achrondoplasia and HG deficiency?

Achondroplasia = Only long bones affected (endochrondral ossification). Intramembranous ossification is unaffected GH Deficiency = Both Long and flat bones are affected (Defective endochrondral and interosseous ossification are not functional)

Is hypocitraturia associated with an acidic or basic pH?

Acidic! (weird)

Intranuclear acidophilic inclusions? Basophilic?

Acidophilic = Herpes simplex Basophilic = cytomegalovirus

What tumor can arise in the cerebellopontine angle?

Acoustic Schwanzoma If B/L = NF-2

What causes Paroxysmal Nocturnal Hemoglobinuria (PNH)? Clinical symptoms?

Acquired mutation of the PIGA gene within a clonal population of multipoint hematopoietic stem cells. PIGA is involved in the synthesis of *GPI*, which is an anchor for CD55 (Decay Accelerating Factor, DAF) and CD59 (MAC inhibitory protein). These proteins help inactivate complement and prevent the MAC from forming on normal cells. Absence of the GPI anchor leads to CD55/59 deficiency and *complement mediated hemolysis*. Pts also develop *thrombotic complications* (i.e. Budd Chiari Syndrome) likely due to a release of free Hb and other prothrombotic factors from lysed RBCs and platelets. Also, since PNH is a stem cell, it as often associated with *pancytopenia* and *aplastic anemia*, and hemosiderosis (iron deposition in kidney due to chronic hemolysis--- can interfere with PCT function and cause interstitial scarring/cortical infarcts)

What are P-bodies? Where in the cell do they act?

Act in the cytosol as post-transcriptional regulation (only 1!) They are distinct parts of eukaryotic cells that play a role in translational repression until the cell is ready to translate and express the protein! Its basically mRNA storage until the right time

MOA of Baclofen?

Activates GABA-B receptors in spinal cord, inducing skeletal muscle relaxation. Does this via opening K+ channels causing hyperpolarization

How do TNF-alpha, catecholamines, glucocorticoids, and glucagon all induce insulin resistance?

Activates SERINE KINASES which phosphorylate serine residues on the beta subunits of the insulin receptor and IR substrates-1. This inhibits tyrosine phosphorylation of IRS-1 by the IR. *Phosphorylation of threonine residues has the same effect

Describe Sturge-Weber Syndrome

Activating mutation in GNAQ causes developmental anomaly of Neural crest derivatives. Mental retardation seen

When can IgM bind C1 to activate the Classical Complement pathway?

Activation of complement by IgM prior to antigen binding is prevented due to the fact that the C1 binding site on IgM is hidden while unbound IgM is circulating in its planar form. A conformational change occurs in the IgM molecule after antigen binds, resulting in exposure of the C1 binding site.

When is Rb active? Inactive?

Active when its HYPOphosphorylated-- grabs and holds onto E2F transcription factor, halting G to S phase Inactive via phosphorylation, it releases E2F

Morphine's Cardiovascular effects?

Acts a s vasodilator! Increases venous capacitance, reducing SVR, and potentially causing CNS sympatholytic effects on the cardiovascular system. It is used to treat ischemic chest pain, especially during acute MI

Why does erythromycin cause GI side effects?

Acts as an agonist at motion receptors in the stomach and duodenum, stimulating muscle contraction in the upper GI tract

What maintains cardiac output in acute aortic regurgitation? Chronic?

Acute = HR (LV doesn't have time yet to undergo eccentric hypertrophy) Chronic = Heart undergoes eccentric hypertrophy, allowing the SV to increase

MCC of acute endocarditis? Subacute?

Acute = S. aureus Subacute = Step viridians

What is Murphy's sign? What does it indicate?

Acute Cholecystitis Inspiratory pause during RUQ palpation

Granular muddy brown casts

Acute Tubular Necrosis

How does central retinal artery occlusion (CRAO) usually occur?

Acute and painless monocular vision loss usually due to athero- and thromboembolism (predisposing factors = a-fib and carotid artery stenosis, or vasculitides). Note- central retinal artery is a branch of ophthalmic artery, which arises from the internal; carotid artery! Fundoycopic exam: pale retina (due to ischemia and edema) and a cherry-red macula (fovea and foveola are thin and have a separate blood supply from the choroid artery)

Why do anti-cholinergic medications helps treat acute dystonic reactions from antipsychotic medications?

Acute dystonic reactions are the result from D2 receptor antagonism in the nigrostriatal pathway. In the striatum, the inhibitory effects of Dopaminergic neurons (D2) are normally balanced by the excitatory acton of muscarinic cholinergic neurons (M1). Strong dopaminergic blockage causes an excess cholinergic activity, resulting in extra-pyramidal side effects. Medications with M1 receptor antagonist properties, such as benztropine or the antihistamine diphenhydramine, help re-establism the dopaminergic-cholinergic balance and effectively treat acute dystonia and other extra-pyrmindal side effects (akathisia, parkinsonism).

Symptoms of Renal Papillary necrosis? What causes it?

Acute onset of gross hematuria and proteinuria "SAAD papa with papillary necrosis" -All due to lack of blood flow to small renal vessels, causing ischemia and renal papillary necrosis... Sickle Cell: sickled cells cause obstruction of small kidney vessels, predisposing to ischemia Analgesic Nephropathy (NSAIDS): inhibits renal blood flow leading to ischemia Acute Pyelonephritis/Urinary tract obstruction: Edematous interstitium compresses the medullary vasculature, leading to ischemia Diabetes mellitus: NEG of vasculature walls leads to renal vasculopathy and subsequent hypo perfusion

Describe the role of Hepcidin

Acute phase reactant from liver that acts as the central regulator of iron homeostasis. Hepcidin influences body iron storage through interaction with ferroportin, a transmembrane protein, found on intestinal cells and macrophages, responsible for transferring intracellular iron to the circulation! Upon binding hepcidin, ferroportin is internalized and degraded, decreasing intestinal iron absorption and inhibiting release of iron by macrophages.

What conditions have WBC casts? How do they form?

Acute pyelonephritis and Acute interstitial nephritis (no urinary symptoms) Formed in tubules, where WBCs precipitate with Tamm-Horsfall proteins secreted by tubular epithelial cells

Timeline cut-off between Acute stress disorder and PTSD?

Acute stress disorder = 3 days to 1 month PTSD = persistent symptoms for >1 month

Urine turns black on prolonged exposure to air. What is going on? Clinical symptom?

Alkaptonuria Deficiency of Homogentisate oxidase TYROSINE usually eventually broken down into FUMARATE so it can enter TCA cycle. This enzyme deficiency causes buildup of homogentistic acid. Homogentistic acid can build up in joints causing arthralgia. Will see bluish-black connective tissue and sclera (onchronosis)

Signs of Acute lithium toxicity? Chronic Lithium toxicity? What 3 drugs can cause lithium toxicity?

Acute: GI upset initially with later development of neurologic symptoms (eg, neuromuscular excitability, delirium) as the drug penetrates the CNS Chronic: Gradual onset of neurologic symptoms, such as worsening involuntary movements, ataxia, and tremor. *Since lithium behaves the same way as sodium, thiazide diuretics can lead to an increase lithium concentration over time. ACE inhibitors and NSAIDS also impair lithium clearance.

Vitamin A toxicity: Acute? Chronic? Teratogen?

Acute: Nausea, vomiting, vertigo, and blurred vision Chronic: alopecia, dry akin, hyperlipidemia, hepatotoxicity, hepatosplenomegaly, and visual difficulties *also increased ICP! Teratogen: microcephaly, cardiac anomalies, and fetal death (1st trimester)

How do the symptoms of alcohol withdrawal develop?

Acutely, ethanol potentiates GABA (primary inhibitory CNS NT) at GABA-A receptors, leading to sedation. Chronic ethanol use causes down regulation of GABA receptors. Ethanol also weakly inhibits excitatory NMDA receptors in brain, and chronic ethanol use causes up regulation of these receptors. The combo of increased NMDA receptors (excitatory) and decreased GABA-A receptors (inhibitory) leads to excitatory withdrawal symptoms, such as the tremulousness

Drug used for panic attacks? MOA?

Acutely: Benzodiazepines bind to its binding site on GABAa Receptor complex, allosterically modulating the binding of GABA, causing increased FREQUENCY of chloride channel opening! Long term: SSRI/SNRI/CBT (takes a couple weeks to start working)

Treatment for Herpes infections? MOA?

Acyclovir (Nucleoside analogue) Converted into acyclovir monophosphate (A-MP) via virus encoded thymidine kinase! Cellular enzymes then add 2 other phosphates to make Acyclovir triphosphate (A-TP), which can incorporate into replicating viral DNA and terminate viral DNA synthesis

DOC for paroxysmal supraventricular tachycardia (PSVT)? MOA? Side effects?

Adenosine Very rapid (10 secs)-- Slows conduction through AV node by hperpolarizing the nodal pacemaker and conducting cells. Causes flushing, chest burning (due to bronchospasm), hypotension, and high grade AV block

Drugs given during a cardiac stress test to induce coronary steal phenomenon?

Adenosine and dipyrimadole

What are the two types of vaccines for Strep pneumo? Who gets what? Why?

Adults = Pneumococcal *Polysaccharide* vaccine (PPSV23): Because the capsular polysaccharides alone cannot be presented to T-cells (no protein), the vaccine induces a relatively T-cell independent B-cell response (so its just IgM "Mezzanine in sketchy) that is much less effective in young children and elderly Children/elderly: Pneumococcal *Conjugate* vaccine (PCV13): consists of capsular polysaccharides that have been covalently conjugated to recombinant, inactivated diphtheria toxin. This protein conjugation induces active immunity via a T-cell dependent B-cell response (it can class switch to IgG "Ground in sketchy). This results in improved immunogenicity due to formation of higher affinity Abs and memory cells!

Explain the pupillary light reflex

Afferent = CN II Efferent = CN III

What is the afferent pathway for the corneal reflex? Efferent?

Afferent/sensory = nasociliary branch of CNV1 Efferent/motor = temporal branch of facial nerve (CNVII)

Corneal reflex: afferent? Efferent?

Afferent= Nasociliary branch of CN V1 Efferent= Temporal and zygomatic braches of CN VII

Body is going into a starvation state. Describe how it shifts its energy needs

After about 12-18 hours of fasting, the body's glycogens stores are depleted and gluconeogenesis is required to maintain blood glucose levels. However, as the fasting continues, the body limits its reliance on gluconeogenesis in order to conserve protein, and resorts instead to *ketone body synthesis*. Ketone bodies are generated in the liver from fatty acids and yield energy when converted to Acetyl CoA int he mitochondria of target cells!

Explain how a patent foramen ovale embryologically forms.

After delivery, umbilical cord clamping and the suddenly decreased pulmonary vascular resistance lower right atrial pressures and raise left atrial pressures. This change in pressure pushes the "flap" of *septum primum* against the *septum secundum*, closing the foramen ovale. Over time, fibrosis/tissue remodeling fuses the flap closed. *usually this is asymptomatic, but anything that increases right atrial pressure > left atrial pressure (ie. Valsalva) can cause a transient right-to-left shunt and cause a paradoxical embolization (DVT--> stroke)

Leading cause of blindness in industrialized countries? Progression of the disease? Treatment at each stage?

Age-related macular degeneration: degeneration of the macula (central area of retina), causes distortion of straight lines (metamorphopsia) and eventual loss of central vision (scotomas) Usually its DRY AMD (non exudative): due to chronic oxidative damage leading to deposition of yellowish extracullar material in and between Bruch's membrane (innermost layer of choroid) and retinal pigment epithelium ("drusen"), causing gradual decrease in vision. ***Tx = multivitamin/antioxidants to slow progression, smoking cessation Progresses to WET AMD (exudative): Progressive extracellular matrix accumulation leads to chronic retinal hypoxia, causing choroidal neovascularization via VEGF, causing leaky vessels and bleeding, leading to rapid loss of vision. ***Tx = anti-VEGF injections (RANIBIZUMAB, BEVACIZUMAB)

NMDA receptor agonists? antagonists?

Agonists = glutamate, asparatate, and D-cycloserine Antagonist = PCP

Findings in sensorineural hearing lost (involving the cochlea or auditory nerve)

Air conduction will be greater than bone conduction (normal Rinne test) Weber Test will lateralize to the unaffected ear!

Fructose Intolerance: enzyme deficiency? Whats the big deal?

Aldolase B deficiency causes decreased DHAP and G3P, and accumulation of Fructose-1-P This causes depletion of Phosphate, leading to inhibited glycolysis and gluconeogensis---> *life threatening HYPOGLYCEMIA* Tx = avoid dietary fructose and sucrose (glucose + fructose)

Enzyme responsible for conversion of glucose to sorbitol?

Aldolase Reductase

Describe the differences between Junctional nevi, compound nevi, and intradermal nevi

All are benign neoplasms composed of round, uniform melanocytes (nevus cells) that are mitotically quiescent

What are petechiae, purpura, and ecchymoses?

All are cutaneous or subQ collections of extravasated blood (smaller 2 are usually associated with platelet dysfunction or capillary fragility and occur in areas with increased venous pressure, such as lower extremities) Petechiae: <5 mm Purpura: 5mm--> 1 cm (if palpable = leukocytoclastic vasculitis) Ecchymoses: > 1cm

Describe the pathogenesis of congestive heart failure

All do to increased sympathetic output Note- Heart failure with symptoms of circulatory overload is called congestive heart failure

Which cells have MHC class I molecules? How do they present their antigen? Who do they stimulate?

All nucleated cells have MHC Class I proteins Virus/tumor cells (antigens processed endogenously in the cytoplasm) are bound by the MHC class I in the RER ***MHC Class I is made up of ONE HEAVY CHAIN and a BETA-2 MICROGLOBULIN They stimulate CD8+ cells (leads to apoptosis)

What muscle of the tongue doe the hypoglossal nerve not innervate?

All the muscles of the tongue except the palatoglossus! Palatoglossus = vagus nerve!

What is allelic heterogeneity? Genetic heterogeneity? Phenotypic heterogeneity?

Allelic heterogeneity: Different mutations at the same genetic locus cause similar phenotypes (all result in the same exact disease!) Genetic Heterogeneity: mutations of different genes cause similar phenotypes Phenotypic Heterogeneity: mutations in the same gene result in markedly different phenotypes

Valve most often affected in Rheumatic fever? What other valves can be affected?

Almost always affects the mitral valve, but it can also affect both the mitral valve and aortic valve! Can cause both aortic stenosis and aortic regurgitation, which combines to increase LV diastolic pressure. This can also predispose to infective endocarditis, which can throw off embolisms to the systemic circulation (ie. brain)

What are effective nasal decongestants used for rhinitis? What is an interesting side effect?

Alpha agonists (phenylephrine) are effective nasal decongestants due to their vasoconstrictive effects on the blood vessels of the nasal mucosa. Associated with *tachyphylaxis* (decreased effect after a few days due to negative feedback, or simply rapidly developing tolerance). Caused by decreased production of endogenous norepinephrine from the nerve terminals, resulting in relative vasodilation (removal of normal vasoconstrictive tone) and subsequent edema and congestion. Leads to exacerbation of symptoms known as *Rebound Rhinorrhea* (although no blood may be present). Occurs when nasal decongestants are used for >3 days.

Which is responsible for increasing diastolic pressure: alpha-1 or beta-2?

Alpha-1 - causes constriction and maintenance of pressure in arteries while heart isn't contracting The beta-2 receptors cause relaxation of the skeletal muscle arteries, causing a decrease in diastolic pressure!

Metabolic effects of thiazides?

Also hypomagnesemia

Signs of increased intracranial pressure in a baby?

Altered mental status, enlarging head circumference/fontanelle, and downward driven eyes

Which monosaccharide (galactose, mannose, glucose, or fructose) is metabolized by the liver the fastest? Why? How is this sugar metabolized?

Although all these monosaccharides enter glycolysis as intermediates at different points, only fructose can enter distally where it can bypass the rate limiting enzyme, Phosphofructokinase (PFK)! Fructose if first phosprylated by Fructokinase into F1P. Aldolase B then converts it into DHAP and glyceraldehyde. Glyceraldehyde can be phosphorylated by triokinase into glyceraldehyde-3-P, which enter glycolysis. DHAP can be converted by triose phosphate isomerase into Glyceraldehyde-3-P, which can also then continue down glycolysis!

If the flow velocity increases at points of narrowing in the Cardiovascular system, why is blood flows slower in the arterioles compared to the aorta?

Although individual capillaries have a small cross-sectional area, the flow velocity through these vessels is slow. This is because numerous capillaries arranged in parallel receive flow from a given feeder vessel; thus, the functional cross-sectional area of those capillaries combined is actually much larger than that of the feeder vessel from which they receive their flow! Total Flow = Flow Velocity x Cross Sectional area = Constant (ie. V1A1=V2A2)

Levels of melatonin have been shown to decrease with what disease?

Alzheimer's disease

How are tRNAs charged?

Amino Acids are incorporated into the 3' end of tRNAs via the enzymes aminoacyl-tRNA syntheses. *Each AA/tRNA pair has a specific AA-tRNA synthetase that links them together. *These AA-tRNA syntheses have proof-reading ability and hydrolyze incorrectly paired amino acids. This causes mistakes to very rarely occur!

Which antiarrhytmic that induces QT prolongation actually does NOT cause torsades de pointes?

Amiodarone Probably due to it having more of a homogenous effect on ventricular repolarization compared to other drugs (less QT dispersion)

Main side effect of Dihydropyridine calcium channel blockers? Why does this occur? How can you treat it? Why?

Amlodipine, Nifepidine PERIPHERAL EDEMA (in addition to dizziness/lightheadedness) This occurs bc they preferentially vasodilator the precappilary vessels (arteriolar dilation), which leads to increased hydrostatic pressure and fluid extravasation into the interstitium. Fix with ACEs/ARBs bc they preferentially dilate the post-capillary venules, normalizing the hydrostatic pressure and preventing edema from occurring!

Describe how Ammonia is recycled and broken down by the liver

Ammonia is normally produced by the GI tract as a result of enterocyte catabolism of glutamine and colonic bacterial catabolism of dietary protein. Gi bleeding causes increased nitrogen delivery to the gut in the form of hemoglobin, which is then converted into ammonia and absorbed into the blood stream. The ammonia then enters the liver through the portal vein and is detoxified into urea. Portal shunting in chronic liver leads to accumulation of ammonia in circulation. Results in increased inhibitory neurotransmission (GABA) and impaired excitatory neurotransmitter release (glutamate, catecholamines)

Which bugs can infect a human with only a small inoculum (only a few organisms are needed)?

Shigella (acid stabile) Campylobacter jejuni Entamoeba Histolytica Giardia lamblia

What is hematocolpos?

An imperforate hymen is an obstruction caused by incomplete degeneration of the central portion of the fibrous tissue band connecting the walls of the vagina. At birth, vaginal secretions stimulated by the mother's estrogen can cause mucocolpos (accumulation of mucous in the vaginal canal), which may manifest as a building introitus. If the condition remains asymptomatic until menarche. The patient may then present with primary amennorhea and normal secondary sexual characteristics with cyclic abdominal or pelvic pain due to accumulation of menstrual blood in the uterus and vagina (hematocolpos). May see a vaginal budge or mass on palpation anterior to the rectum

What does foul-smelling sputum usually indicate?

Anaerobic bacteria!

How exactly does cellular swelling occur in ischemic cells?

Anaerobic metabolism causes decreased ATP levels. Without ATP, the membrane Na/K ATPasse and SR Ca-ATPases fail, leading to increased intracellular Na and Ca and increased Mitochondrial Ca concentrations. These increased concentrations attract free water, causing cellular and mitochondrial swelling! *Failure of the SR to resequester Ca leads to cessation of contraction within ischemic zones of myocardium!

Effect of anaphylaxis on C.O. / Venous Return curve

Anaphylaxis causes widespread venous and arteriolar dilation with increased capillary permeability and third spacing of fluids! Results in a serious drop in venous return (shifted down and leftward). Cardiac contractility also increases as the body attempts to maintain BP against decreased after load.

Function of hemidesmosomes?

Anchor cell to basement membrane via integrins

What is an angioma? Difference between capillary hemangioma and cavernous hemangioma?

Angiomas are chronic vascular malformations that most commonly appear as soft, well-demarcated, red or blue nodules. Capillary hemangiomas are usually small and superficial (picture) whereas cavernous hemangiomas are usually larger and more likely to involve deeper structures!

Low back pain and morning stiffness in a young man?

Ankylosing Spondylitis! Will improve with exercise but not with rest. Pain at night

Describe the embryology between the anterior and posterior pituitaries

Ant Pituitary (Adenohypophysis): Rathkes pouch, which is an evagination of surface ectoderm that lines the fetal oral cavity/roof of the mouth Post Pituitary (Neurohypophysis): out pouching of the diencephalon (infundibulum), which is derived from neuroectoderm

There is a MRSA outbreak at your hospital. Where do epidemiologists sample in order to find out if you are a carrier?

Anterior Nares--- asymptomatic colonization of the nasopharynx is the most common site

Sensory deficits in femoral nerve lesion?

Anterior and medial thigh, and medial leg

What makes up the scalene triangle? What runs through here?

Anterior and middle scalene muscles and the 1st rib Brachial plexus trunks In Thoracic outlet syndrome (TOS), the lower trunk is most likely to get compressed. If subclavian artery compressed, it may cause extertional arm pain

Most common site for Acute Compartment Syndrome (ACS)? Whats in there?

Anterior compartment of the leg. Includes the foot extensor muscles, anterior tibial artery, and the deep peroneal (fibular) nerve. Injury to the deep peroneal nerve can cause decreased sensation between the 1st and 2nd toes!

What are anterior NT defects? Posterior? What is seen in the amniotic fluid?

Anterior: anterior neuropores fail to close-- Encephalocele (herniation of brain tissue through a cranial defect) and anencephaly (total absence of brain and calvarium) Posterior: Posterior neurpores fail to close-- spina bifida occulta, meningocele, and meningomyelocele ***AFP and AChE leaks out of fetal cerebrospinal fluid into amniotic fluid! (AFP also crosses placenta, can be seen in Mom's serum.

Which HBV marker will be present in the goddam window period?

Anti-HBc IgG

What Ab is present during the window period of HBV infection?

Anti-HBc IgM Window period = when both HbsAg and anti-has are absent

Antibody for drug induced lupus? Which drugs can cause this? Why?

Anti-Histone Abs Procainamide, Hydralazine, and INH (among others) These drugs are metabolized via phase II acetylation in the liver (conjugation). Hepatic expression of N-acetyltransferase is genetically determined, and slow acetylators are at great risk of developing Drug-induced lupus (lacks malaria rash)

What is given to moms in order to prevent hemolytic disease of the newborn in subsequent pregnancies? When is it given?

Anti-Rh(D) IgG at 28 week gestation and in the immediate post part period. The IgG abs do not cause significant transplacental fetal hemolysis because the quantity of anti-Rh(D) administered is very small compared to that produced in a typical immunological rxn

What antibody is highly specific for RA? How does this form exactly?

Anti-cyclic citrullinated peptide (anti-CCP) Abs Tissue inflammation causes arginine residues in proteins such as vimentin to be enzymatically converted to citrulline via citrullination. This significantly alters the proteins, now making them antigens for the immune system to mount a response against! *Measured by ELISA

Specific Antibodies for Lupus? Which is diagnostic?

Anti-dsDNA = prognostic for renal disease (poor prognosis) Anti-smith = anti-snRNPS

Ab specific for primary biliary cirrhosis?

Anti-mitochondrial Abs

Serum findings of PSGN

Anti-streptolysin O, anti-DNAase B, anti-Cationic proteinase LOW C3 CONCENTRATION (suggests activation of ALTERNATIVE complement pathway) *in some pts, C4 is also low, suggesting involvement of the classical pathway as well. Its usually normal though!!!

How exactly does auto-Abs caused by strep pyogenes lead to acute rheumatic fever?

Antibodies directed against GAS antigens (*M-protein* and *N-acetyl-ß-glucosamine*) attack myosin (a cardiac protein) and lysoganglioside (neuronal cell surface protein)

What causes antigenic drift? Shift?

Antigenic drift = point mutations Antigenic Shift = Reassortment!

Why can't we make a vaccine against Hep C?

Antigenic variability of envelope

What is Antiphospholipid syndrome (APS)? What is seen on labs?

Antiphospholipid Abs in the setting of venous/arterial thromboembolism (hypercoaguable state) and/or recurrent pregnancy loss! Antiphospholipid Abs cause aPTT prolongation in vitro, they act in vivo to produce a *hypercoaguable state* due to the activation of phospholipid-dependent coagulation pathways. These Abs can also cause *false positive results* on nontreponemal serologic syphillis tests (RPR and VDRL) by reacting with cardiolipin

Specific Abs for systemic sclerosis?

Antitopoisomerase I (Scl-70) Anti-Centromere (CREST syndrome) Anti-RNA Polymerase III

If a patient has severe portal hypertension, what can the spleen look like?

Any condition with portal hypertension will likely result in congestive hypersplenism. This congestion of blood will result in an apparent *expansion of the red pulp of the spleen*, which is composed of blood-filled sinuses and cords lined by reticuloendothelial-type cells.

What is seen on an echocardiograph of transposition of the great vessels?

Aorta lying anterior and to the right of the pulmonary artery

Difference between aplastic crisis and aplastic anemia?

Aplastic Crisis = only deficiency in RBCS (seen with parvovirus B19 in sickle cell pts) Aplastic Anemia = damage to hematopoietic stem cells leads to pancytopenia!

Describe the pathway from aqueous humor production to drainage. What are some symptoms of open-angle glaucoma?

Aqueous humor is produced by the EPITHELIAL CELLS of the CILIARY BODY. It is secreted into the posterior chamber and transferred through the pupil into the anterior eye chamber. The inter chamber angle (iridocorneal angle) contains a trabeculae meshwork through which the aqueous humor diffuses into the canal of Schlemm (sclerous venous sinus) and subsequently into the episcleral and conjunctival veins Symptoms include: Chronic, progressive loss of *peripheral vision* due to an optic neuropathy characterized by atrophy of the optic nerve head.

Importance of the arcuate line in reference to the rectus abdominus? Blood supply to rectus abdominus? When can that supply be damaged?

Arcuate line is a horizontal line located below the umbilicus that de,arcades the lower limit of the posterior rectus sheath. Above the arcuate line = rectus abdominus is surrounded by an anterior AND posterior sheath. Below = covered by only anterior sheath Rectus abdominus is supplied by superior and inferior epigastric arteries, respectively. Below arcuate line though, the inferior epigastric artery ascends posteriorly, so if it gets damaged, there is no posterior sheath to help cover and stop the bleed, leading to sever hemorrhage. Can be easily damaged during an extra horizontal incision to make room in a C-section. Must ligate the inferior epigastric arteries during this procedure.

What are pigmented gallbladder stones? What can cause brown pigmented stones? Black?

Arises from conditions that increase the amount of unconjugated bilirubin in bile Brown: Biliary tract infections (microbes producing ß-glucouronidases) black: chronic hemolytic anemia (eg, sickle cell disease) and increased enterohepatic cycling of bilirubin (eg. Crohn Disease)

Describe arsenic poisoning. How does this occur? Present? Treatment? Why does this treatment work? Side effects of treatment?

Arsenic binds to sulfhydryl groups, impairing cellular respiration via inhibition of* pyruvate dehydrogenase* and disruption of gluconeogenesis and glutathione metabolism Presents with GI issues, including *severe watery diarrhea*, hypotension, QT prolongation (torsades de pointes), and *GARLIC ODOR* breath or stool Tx with chelating agent *Dimercaprol*, which increases urinary excretion of heavy metals by forming stable, nontoxic soluble chelates. The sulfhydryl of dimercaprol combines with arsenic and displaces arsenic from the sulfhydryl groups of enzymes. Adverse effects = nephrotoxicity, HTN, and fever

Treatment for Plasmodium falciparum?

Artemisins or atovoquone-progaunil. Can also use IV: artesunate or quinidine

How does a tension pneumothorax lead to hypotension?

As an increasing volume of air accumulates within the pleural space, the lungs and mediastinum deviate to the opposite side of the chest. Increased pressure within the chest cavity causes decreased systemic venous return to the heart, leading to decreased cardiac output, decreasing BP! Signs and symptoms of a tension pneumo include tachycardia, hypotension, tachypnea, hypoxemia, and absence of breath sounds and hyperresonance to percussion on the affected side. Treat with emergent needle thoracostomy or chest tube

What is Charcot's Triad? What is it seen in?

Ascending Cholangitis 1. Fever 2. RUQ pain 3. Jaundice

Describe Ascorbic Acid and its deficiency

Ascorbic Acid = Vit C

What type of pneumonia is most likely found in an elderly patient with dementia or hemiparesis, and dysphagia? Which part of the lung is probably affected? Which type of bug?

Aspiration pneumonia in the superior regions of the lower lobes (or posterior regions of upper lobes) by anaerobic bacteria!

What forms the "glial scar" in CNS healing?

Astrocytes migrate to area of necrosis w/in 2 weeks of injury. As necrotic tissue is resorbed, a cystic space forms that is then surrounded my astrocytes and newly formed capillaries. This enlargement and proliferation of astrocytes peripherally around the area of necrosis is called gloss (aka glial scar)

Where does Cryptocossus Neoformans usually infect first before the CSF? Why does it like to infect the CSF?

Asymptomatic lung infection first Likes to infect the CSF because the CSF does not contain the complement components of the alternative pathway!

What stage of breathing is Pulmonary Vascular Resistance (PVR) the lowest? Why?

At FRC Increased lung volumes increase PVR due to longitudinal stretching of alveolar capillaries by the expanding alveoli. Decreased lung volumes ALSO increase PVR due to decreased radial traction from adjacent tissues on the large extra alveolar vessels. So the lowest PVR would be in-between! (at FRC)--- this is also when the collapsing pressure of the lung is in perfect balance with the expanding pressure of the chest wall, meaning the its the resting state where the airway pressure equals zero and there is no airflow in or out-- yields an intrapleural pressure of -5!

Injury to popliteal nerve at popliteal fossa? At tarsal tunnel?

At popliteal fossa = problems in leg and foot, will keep foot in a dorsiflexed everted fashion At tarsal tunnel = Only foot deficits. Plantar flexion and inversion remain intact

Examples of Protease Inhibitors for HIV? MOA?

Atazanavir Darunavir Indinavir Ritonavir "NAVIR (never) tease a Protease!" Inhibits HIV polyprotein cleavage

What is allergic dermatitis? How does it present? What causes it? What else is it associated with?

Atopic dermatitis is a chronic inflammatory skin disorder triggered by environmental factors, such as ingestion of certain foods or exposure to certain environmental irritants. In patients less than 5, it presents in extensor surfaces (not diaper). In older kids, it presents in flexural surfaces. Remission and relapses occur, and there must always be *intense pruritus*. Caused by mutations affecting proteins such as filaggrin or other components of the epidermis, resulting in impairment of the skin's barrier function. This increases immunologic exposure to environmental allergens and microbial antigens, leading to immune hypersensitivity. Affected patients have high serum levels of IgE, peripheral eosinophilia, and high levels of cAMP phosphodiesterase in their leukocytes. Children with AD often have a family history of allergic disorders and are at risk of developing other atopic diseases, such as allergic rhinitis and asthma (*allergic triad*)

What does the EKG look like in 3rd degree (complete) AV block?

Atria depolarize via SA node, while the ventricles depolarize via the AV node (AV disassociation). QRS complexes are narrow since ventricular depolarization process normally, but the HR will be slower due to the AV node's 45-55 bpm *Prolonged, abnormally shaped QRS complexes are indicative of electrical impulses generated below the AV node/bundle of His

Fixed, wide splitting of S2?

Atrial septal defects Allows equalization of left and right atrial pressures, thus minimizing the respiratory variation in left and right ventricular blood flow Causes increased blood flow through the pulmonary arteries, which can eventually lead to medial hypertrophy, increasing pulmonary arterial pressure! Once pulmonary vascular resistance > SVR = Eisenmenger syndrome (reversal of shunt!)

What is the round ligament of the liver? Whats in it?

Attaches the liver to the anterior abdominal wall. Its is a derivative of the embryologic ventral mesentery and contains the round ligament( aka Ligamentum Teres), the remnant of the fetal umbilical vein

MOA of risperidone? Adverse effect?

Atypical antipsychotic that primarily inhibits D1 and D2 receptors (also inhibits serotonergic and alpha-adrenergic pathways) Stimulation of D2 by dopamine normally inhibits prolactin release, do blockage of D2 leads to hyperprolactinemia! Presents as amenorrhea, galactorrhea, and breast soreness in a female

Patient has increase HbA2, microcytic anemia, with poikilocytes. Diagnosis? Due to?

Beta thalassemia minor Due to mutations that affect the transcription, processing and/or translation of the beta-globing mRNA (usually splicing or premature chain termination)

Rxns that occur in the mitochondria

Beta-oxidation, Ketogenesis, TCA cycle, ETC, initial and final steps of urea cycle, and decarboxylation rxns

How exactly does Myasthenia Gravis affect the NMJ?

Auto-Abs against post-synaptic Nicotinic ACh receptors bind, resulting in blockade of the receptor's active site, receptor internalization and degradation, and damage to the motor end plate due to complement fixation. Overall, this leads to decreased number of functional ACh receptors at the NMJ. The decrease in the number of available cation channels reduces the end-plate potential following ACh release. Because the threshold potential is not reached, the muscle cells do not depolarize!

How exactly does SLE lead to multi system vasculitis?

Autoantibodies bind autoantigens and form immune completes that deposit on vessel walls Immune complex deposition (TYPE 3) leads to complement activation -- inflammation/injury Acute phase = fibrinoid necrosis Chronic phase = fibrosis/narrowing of vessel lumen

What is primary biliary cirrhosis?

Autoimmune Rxn--- lymphocytic infiltrate + granulomas that cause destruction of INTRALOBULAR bile ducts Anti-mitochondrial ab positive

Describe Dermatomyositis

Autoimmune disorder characterized by inflammatory myopathy (proximal muscle WEAKNESS with elevated muscle enzymes, ie. creatine kinase/aldolase) with cutaneous involvement (Gottron papules on hands which are papules or heliotrope rash). Increased ANA although *Anti-Jo-1* is most specific. Muscle biopsy shows perimysial inflammation and perifasicular atrophy/fibrosis. If develops in patient older than 50, its most likely a paraneoplastic disorder from an underlying malignancy (most likely gastric adenocarcinoma)

What is chronic atrophic gastritis? What does a secretin stimulation test show?

Autoimmune gastritis: CD4 destruction of parietal cells in body/fundus of stomach, leading to no acid and no IF, causing achlorydia and pernicious anemia. Low levels of acid stimulated gastrin release, but these gastrin levels can be suppressed with an exogenous secretin test (NOT SUPPRESSED IN ZE SYNDROME)

Anti-smooth muscle antibodies?

Autoimmune hepatitis type I

How does dermatomyositis present?

Autoimmune, presents with proximal muscle weakness and skin involvement including a violaceous discoloration of upper eye lids (heliotrope rash) and scaling eruption of the knuckles (Gorton's sign).

What is an average volume of distribution for a drug that is: -Large, hydrophilic? -Small hydrophilic? -small hydrophobic?

Average total body water is 41 L, ECF is 14 L (1/3 of it). Within the ECF, the plasma volume is about 3 L and interstitial fluid makes up the rest. Large hydrophilic- bound extensively by plasma proteins since its large, and charged, it remains in plasma compartment (about 3-5 L) Small hydrophilic- Since its not large enough to be bound to plasma proteins, can distribute to both the plasma compartment and interstitial fluid (so all of the ECF), so about 14-16 L Small hydrophobic- can cross membranes and reach the ICF within cells. So it can go to all the water compartments of the body, so roughly 41 L. The Vd is usually much higher than 41 L because the drug accumulates in cells/tissues, thereby maintaining low plasma concentrations!

Cholinergic drug used to treat what kind of urinary problems?

Bethanochol can treat an atonic bladder (non-obstructive urinary retention)

How can you get Kluver-Bucy Syndrome?

Bilateral Amygdala lesion or Temporal lobe lesion

Signs of self-induced vomitiing?

Bilateral parotid-gland enlargement Erosion of dental enamel Electrolyte abnormalities (hypokalemia, hypochloremia, metabolic alkalosis) Increased salivary amylase Calluses on dorm of hand (Russel Sign)

What is biliary atresia?

Biliary tree is normal at birth, then undergoes *Extrahepatic bile duct destruction* due to immune related or viral induced.

How does Staphylococcal Protein A work?

Binds Fc portion of IgG, preventing complement fixation!

MOA of sirolimus (Rapamycin)?

Binds with FK-binding protein (FKBP) forming a complex to inhibit mTOR, which is the signal transducer from IL-2 binding to a T cell! PREVENTS RESPONSE TO IL-2! Used in Kidney transplants! (the kidney "sir"vives)

Are psychotic features seen in Bipolar I or II?

Bipolar I; This has Manic episode(s)

What kind of renal cast can be seen in multiple myeloma?

Bene Jones proteins (IgG light chains) get filtered and reabsorbed in the kidney. When the levels exceed the reabsorptive capacity of the tubules, the IgG light chains will precipitate with Tamm horsfall proteins forming intensely eosinophilic casts that can cause signs of obstruction!

Benign causes of Aconthosis nigricans? malignant causes?

Benign = Insulin resistance. Increased levels of insulin and insulin-like growth factors stimulates epidermal and dermal proliferation Malignant = Usually in elderly, signifies underlying GI or Genitourinary carcinoma, usually a Gastric Adenocarcinoma.

Describe the S4 heart sound

Benign in elderly (unless its super loud) and always pathologic in younger patients (opposite of S3) atrial contraction causing blood to hit a STIFF LEFT VENTRICLE!!! (decreased compliance) -seen in restrictive cardiomyopathy or left ventricular hypertrophy (most likely due to prolonged HTN)

What are endometrial polyps? How do they present?

Benign projections from the uterine lining resulting from hyper plastic growth of both glands AND stroma. Causes AUB, but not uterine enlargement

What is 1st line therapy for psychomotor agitation from Alcohol withdrawal?

Benzodiazepines (mimic alcohol's GABA-A effects) Especially the long-acting ones, such as diazepam and chlordiazepoxide Benzos also help prevent the progression to seizures/delirium

Is IgA a good or bad method of killing N. meningitidis?

BAD! Too much IgA binds to the bacterial surface, and it BLOCKS the binding of IgM and IgG. This is not good because only IgM and IgG activate compliment, NOT IgA! "GM makes Classic cars"

BMI of anorexia nervosa? 2 subtypes? Some complications?

BMI <18.5 Restrictive and binging/purging subtypes Osteoporosis, amenorrhea, hair loss, hypotension, bradycardia, arrhythmias, cardiomyopathy, cardiac atrophy

MC mutation in melanoma? Why does it cause cancer? Treatment?

BRAF mutation V600E (valine --> glutamic acid) leads to over activation of BRAF, causing increased signaling for survival/growth Vemurafenib targets mutated BRAF and shuts it down!

Symptoms of Neonatal Abstinence Syndrome (NAS)? Tx?

Baby having withdrawal from mom who used opioids in utero Classically crying, tremors, tachypnea, sneezing, irritability, and diarrhea Tx = methadone or morphine, then gradually wean them off

How to diagnose intussusception? Tx?

Barium enema is diagnostic and maybe even therapeutic! If it isn't, then surgery ***Currant jelly stools indicate blood and mucous!

Function of the nucleolus?

Basophilic, synthesizes rRNA via RNAPI Makes the 45S pre-rRNA which can they be processed into mature 18S, 5.8S, and 28S rRNAs. Also involved in the maturation and assembly of Ribosomal subunits. Ribosomal protein components are synthesized in the cytoplasm and then transported into the nucleolus where they combine with the rRNA to form 40S and 60S ribosomes. These ribosomes are then transported out of the nucleus into the cytoplasm!

What diseases are caused by these reservoirs? Bats? Dogs? Pork? Fish?

Bats = Rabies virus Dogs = Echinococcus granulosus (int. host = sheep) Pork = Taenia solium (neurocystercosis) Fish = Diphyllobothrium latum (Vit B12 deficiency leads to megaloblastic anemia)

Adverse effects of high dose levodopa/carbidopa?

Behavioral changes (all in CNS): anxiety, insomnia, agitation, confusion, delusions, and hallucinations If you can't lower the dose, switch to atypical antipsychotic such as clozapine

What is a congenital predisposition to testicular torsion?

Bell-clapper deformity Horizontal positioning of the testes due to messed up tunica vaginalis

Findings in conductive hearing loss

Bone conduction will be greater than air conduction (abnormal Rinne test) Weber test will lateralize to affected ear (conduction deficit masks the ambient noise in the room, allowing vibration to be better heard)

What can stimulate glycogen break down in skeletal muscle? Which is stronger? Why is this good?

Both Calcium and epinephrine can activate Phosphrylase Kinase, which activates glycogen phosphorylase by phosphorylating it. Calcium is better at doing this. This is good because when the skeletal muscle is activated, it triggers an increase in intracellular Ca via the SR. This both causes muscle contraction and breakdown of glycogen for energy, thereby coupling the two events!!!

GGT and ALP increased? GGT normal and ALP increased?

Both GGT and ALP increased = LIVER (not bone) pathology. ***GGT is found in organs like liver, NOT BONE ALP increased but not GGT = pathology of bone

What is the difference between adherens junctions and desmosomes?

Both are composed of cadherins (require calcium) Adherens junctions = anchor to actin filaments Desmosomes = anchor to intermediate filaments

In stress-related mucosal disease, what is the pathogenesis of the 2 types of ulcers that can occur?

Both are due to local ischemia caused by systemic hypotension and splanchnic vasoconstriction. 1. Curling's Ulcers: ulcers in the proximal duodenum in *BURN* patients. 2. Cushing's Ulcer: ulcers in the esophagus, stomach, or duodenum in patients with Intracranial injury which causes *direct vagus nerve stimulation*, resulting in ACh release and hyper secretion of gastric acid!

Difference between phentolamine and phenoxybenzamine?

Both are nonselective alpha-adrenergic receptor blockers Phentolamine = Competitive (reversible) Phenoxybenzamine = Noncompetitive (irreversible)- used for pheochromocytoma

What causes the increased collagen deposition seen in scleroderma?

Both diffuse and systemic scleroderma are due to increased deposition of collagen in tissues. Collagen deposition is due to increased proliferation and accumulation of monoclonal T cells in affected tissues that secret a variety of cytokines (especially TGF-ß), which increases production of collagen and ECM proteins by fibroblasts.

Inheritance pattern of androgenetic alopecia (male pattern baldness)?

Both hormonal (circulating androgens) and genetic factors--- POLYGENIC INHERITANCE with VARIABLE EXPRESSIVITY! Some of the genetic influences have been see on short arm of chromosome 20, X and Y. Therefore some can be XR, others can be AD

Difference between vasogenic and cytotoxic edema in ischemic neuronal cell injury?

Both occur in acute setting after ischemic neuronal injury! Vasogenic edema: Extracellular edema caused by increased vascular permeability due to the effects of pro-inflammatory cytokines Cytotoxic Edema: Intracellular edema caused by impaired function of ATP-dependent sodium/potassium pumps on neuronal cell membranes!

What is the main difference between NMS and serotonin syndrome?

Both present very similarly, but the key differences are: NMS = Rigidity, bradyreflxia Serotonin syndrome: Neuromuscular hyperactivity

Difference between Hb Barts and HbH?

Both seen in degrees of alpha thalassemia: 3 allele deletion = HbH (ß4) 4 allele deletion = Hb Barts (4-gamma chains together --- hydrops fettles) *Think of The Simpsons opening scene with Bart grabbing the GAMMA radiation, he will die (incompatible with life)

Alcohol and tobacco: Which is a risk for Breast CA? Cervical CA?

Breast CA = Alcohol Cervical CA = Tobacco

Psychotic disorder timeline

Brief Psychotic Disorder (<1 month) Schizophreniform D/o (1-6 months) Schizophrenia (>6 months)

What is ischemic preconditioning of the heart?

Brief episodes of myocardial ischemia, followed by reperfusion, protect the myocardium from subsequent prolonged episodes of ischemia (ie. MI).

Patient has epilepsy involving both arms with flailing movements. Tx?

Broad spectrum anticonvulsant, like Valproic Acid!

Describe the respiratory tract epithelial lining as it goes down:

Bronchi-- pseudostratified columnar ciliated epithelium with goblet cells and submucosal mucoserous glands and cartilage Bronchioles, terminal bronchioles, and respiratory bronchioles LACK goblet cells, glands, and cartilages. By the level of the terminal bronchiole, the epithelium is ciliated simple cuboidal until the respiratory bronchiole! ***Cartilage is only in bronchi ***smooth muscle persists all the way down to respiratory bronchiole

What type of gallstones are associated with infections of the biliary tree (i.e. liver fluke infection)

Brown PIGMENTED stones

What are the key differences between brown and white adipose tissue?

Brown adipose tissue is found in newborns and hibernating mammals. They contain several intracytoplasmic fat droplets (white = single) and many more mitochondria than white adipose cells. ***They function to produce heat by uncoupling oxidative phoshoryaltion with the protein thermogenic (allows H+ to flow back into mitochondria bypassing ATP synthase)

How exactly do brown pigment gallstones form? Black?

Brown pigment stones typically arise secondary to bacterial (E coli) or helminthic (Ascaris lumbricoides, Clonorchis sinensis) *infection of the biliary tract*, which results in the release of *ß-glucuronidase* by injured hepatocytes and bacteria. This enzyme hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin. The liver fluke C. sinensis is a common cause of pigmented stones. It has a high prevalence in East Asia countries and can have a prolonged quiescent phase before inducing symptoms. Pigmented stones are common in Asian populations, with incidences increased in women and older people. Pigmented stones can also be seen in chronic hemolytic anemia (black stones). These patients excrete large amount of conjugated bilirubin into the bile, which is then deconjugated by ß-glucuronidase in the biliary tract!

How do you culture legionella? Common lab findings?

Buffered charcoal yeast extract (BCYE) agar supplemented with L-cysteine and iron Hyponatremia (due to inappropriate ADH secretion and/or renal tubulointerstitial disease impairing sodium reabsorption)

What causes the cataracts seen in Galactokinase deficiency?

Build up of Galactitol due to Aldolase Reductase!

How does Vitamin B12 deficiency lead to neurologic problems?

Buildup of methylmalonic acid causes demyelination of nerves, leading to damage to the dorsal columns, lateral corticospinal tract, and spinocerebellar tract ***Only water soluble vitamin with large stores (hepatic)

Describe each: Bulbus Cordis Primitive Atrium Sinus Venosus

Bulbus Cordis = forms the beginning of the ventricular outflow tract in the embryonic heart. Forms the smooth portions of the left and right ventricles adjacent to the aorta and pulmonary artery Primitive Atrium = Receives blood from the sinus venosus in embryonic heart and transmits it to the primitive ventricle. Forms the rough portions of the left and right atria Sinus Venosus = receives blood from the venae cavae. Forms the smooth portion of the right atrium, known as the sinus venarum.

How exactly does buprenoprhine cause opioid withdrawal?

Buprenorphine is a partial opioid agonist that has low efficacy for opioid mu receptors. However, it binds with high affinity (potency) and can prevent binding of other opioid medications! This is why buprenorphine acts as an opioid receptor antagonist int he presence of full opioid agonists and can precipitate withdrawal!

Which is better at activating the classical complement pathway, IgM or IgG? Why?

C1 must bind the Fc portions of two different Abs at specific C1 binding sites in the Fc portion near the hinge region. Because IgM circulates in a pentameric form (5 IgM Abs joined together at their Fc regions by a J-chain), it is much more effective at activating complement than IgG which circulates in a monomeric form!

Muscles innervated by the ansa cervicalis?

C1-C3 Innervates Sternohyoid, sternothyroid, and omohyoid muscles

Hereditary angioedema seen in what disease? Why? Tx?

C1 Esterase Inhibitor Deficiency C1INH usually blocks kallikrein, which blocks conversion of kininogen into bradykinin, a potent vasodilator that increases vascular permeability Excess Bradykinin = edema everywhere Tx = C1INH concentrate or a kallikrein inhibitor

Pt has excessive active levels of complement protein C1, and is excessively cleaving C2 and C4. Why??

C1 Esterase Inhibitor Deficiency. C1INH: - prevents C1-mediated cleavage of C2 and C4, thereby limiting compliment cascade - blocks kallikrein, which converts kininogen to bradykinin

What causes the gas in gas gangrene caused by Clostridium perferinges?

C. perferinges uses carbohydrates for energy. Its rapid metabolism of muscle tissue carbohydrates produces significant amounts of gas, which can be demonstrated radiographically by plain film/x-ray or CT scan

What are the 2 main opsonins?

C3b and IgG! Phagocytes have Fc IgG receptors and C3b receptors! *IgM a potent stimulator of C3b opsonization via activation of the complement cascade, but IgM itself does NOT act as an opsonin because phagocytes do not have receptors for the Fc portion of IgM!

What is CA-125? What expresses it?

CA-125 is a protein expressed by epithelial cells lining Mullerian organs (ovary, fallopian tubes) and the peritoneum. Epithelial ovarian cancers secrete this, so its marker. However, numerous other benign conditions that disrupt epithelial cell membranes (i.e. endometriosis) can also increase CA-125 in the blood stream!

2 portions of DNA that function as promoters? How do they work?

CAAT and TATA boxes Bind Tsc factors and RNAP II

What increases the secretion of pancreatic enzymes like trypsinogen?

CCK and Cholinergic stimulation

NK Cells: CD markers? Mature in thymus? What do they recognize? What activates them?

CD 16 or CD 56 Do not require thymus for maturation. Can mature in athymic patients Recognize cells with decreased/absent MHC Class I proteins (virally infected or tumor cells) Activated by interferon-gamma and IL-12

Target of Rituximab? Indication?

CD20 (that TUX was only $20!?!) Used for B-cell NHL, CLL, RA, and ITP

5 common causes of myopathy? What are the 3 different isoforms of CK enzymes?

CK-MB = Cardiac Muscle CK-BB = Nervous System CK-MM = Skeletal muscle!

Most common cause of retinitis in HIV patients? CD 4 count? Most common complication? Treatment?

CMV, CD 4 counts <50 MC complication is retinal detachment due to tearing of thin, atrophic scar tissue that forms in areas of prior inflammation Treat with ganciclovir, a guanosine nucleoside analogue structural similar to acyclovir but with greater activity against CMV DNAP

Which Cranial Nerve can never become a Scwannoma? What do Schwannaomas stain positive for?

CN II (its an extension of the brain, so it had oligodendrocytes)-- forms optic glioma instead (NF-1) S-100 + (its neural crest origin)

What travels through the superior orbital fissure?

CN III CN IV (trochlear) CN VI Nasociliary nerve of CN V1 Superior ophthalmic vein

What travels through the inferior orbital fissure?

CN V2 Infraorbital vessels Branches of the sphenopalatine ganglion

What does the neruoectoderm give rise to?

CNS, preganglionic autonomic neurons, retina, and posterior pituitary

Role of serotonin in the CNS? Platelets? Gut?

CNS: regulates mood Platelets: vasodilators and increases vascular permeability Gut: released from enterochromaffin (Klutchitsky) cells where it plays a role in peristalsis and nausea

Formula that uses Fick's principle to calculate CO?

CO = rate of oxygen consumption/(arterial O2 content - venous O2 content)

Explain the blood findings seen in Carbon monoxide poisoning:

CO binds to oxygen with 250x affinity, blocking O2 from binding the Hb Carboxyhemoglobin increases Decreased Oxygen carrying capacity Decreased oxygen content NORMAL PaO2 (amount of of oxygen dissolved in the plasma) *also causes a left shift in the Hb-Oxygen dissociation curve!

Differences between COX-1 and COX-2? Why does COX-2 cause CV problems?

COX-1 is in a number of normal physiologic tissues (ie. platelets, GI tract), COX-2 is generally only at sites of inflammation (no anti-platelet activity) Both COX-1 and COX-2 are expressed in renal tissue, so blockage of either can can fluid retention and aggravation of HTN COX-2 is also expressed in vascular endothelial and smooth muscle cells, and helps produce PGI2, an anticoagulator and vasodilator. ***Blockage of only COX-2 leads to less PGI2, which is why it has been shown to increase cardiovascular events!!!

Which is inducible: COX -1 or 2?

COX-2 -- inducible at sites of inflammation

Why does COX-2 inhibitors cause CV problems?

COX-2 only expressed at sites of inflammation COX-1 constitutively expressed in platelets and GI tract If you are only blocking COX-2, then platelets can still aggregate like usual. This leads to increased thrombotic events!

Ab of patients with limited scleroderma?

CREST Syndrome Anti-centromere Ab

Negative affects inhaled anesthetics have on different organ systems?

CV: Myocardial depression --> Decreased CO--> Increased atrial and ventricular pressures--> hypotension Respiratory: respiratory depressants (except nitrous oxide)--> hypercapnia. Also causes suppression of mucociliary clearance--> post op atelectasis. Halothane/Sevoflurane have bronchodilators effects (go for pts with asthma) Brain: increased cerebral blood flow --> increased ICP Kidneys: Decrease GFR, increase renal vascular resistance, and decrease renal plasma flow Liver: decreased hepatic blood flow

What is a CaSR? what disease is it associated with?

Ca sensing receptor: its a transmembrane G-protein-couples receptor AD Familial Hypocalciuric hypercalcemia has a mutation in these CaSRs causing them to have a HIGHER serum Ca level in order to inhibit them (binding of Ca to CaSR causes inhibition of PTH release)

Histo/gross finding of silicosis?

Calcification of the rim of *hilar lymph nodes* (*eggshell calcifications*) and birefringent silica particles surrounded by fibrous tissues

Which immunosuppressive agents are nephrotoxic? Why?

Calcineurin Inhibitors (Cyclosporine and Tacrolimus) --- cause afferent and efferent arteriolar vasoconstriction

How do you treat Central DI? Nephrogenic DI?

Central DI = Desmopressin (synthetic ADH) Nephrogenic DI = THIAZIDE diuretics (induces mild hypovolemia, increasing proximal tubule Na and water reabsorption) or INDOMETHACIN (decreases synthesis of PGs, which inhibit ADH)

Why can hypercalcemia lead to constipation and decreased gut motility? Why do calcium channel blockers also cause this then?

Calcium can block sodium channels, hence why hypercalcemia can lead to weakness, hypotonia, and hyporeflexia. Its also a CNS depressant of ratios reason. Hypercalcemia would also have this effect on the enteric neurons, inhibiting their function: GI motility. Thus, reduced GI motility and constipation. Hypercalcemia also induces polyuria, which leads to dehydration, which would also worsen the constipation. Ca channels blocks also lead to GI constipation, both by blocking enteric NT release and by limiting calcium influx and release in GI smooth muscle

What types of stones does citrate treat? How does it work?

Calcium stones! It binds free (ionized) calcium, preventing precipitation and facilitating its excretion

What is Russel's sign?

Calluses on dorm of hand -Indicative of purging subtype of anorexia nervosa

What is Neuroepileptic Malignant Syndrome? What can cause it? How does it present? Lab findings? Treatment/

Can be caused by antipsychotic medications. Presents with diffuse muscle rigidity, high fever, autonomic instability (HTN, tachycardia), and altered sensorium. Lab findings = increased creatine kinase (CK) due to rhabdomyolysis (can progress to myoglobinuria and acute renal failure Treatment = Stop the antipsychotic and give DANTROLENE. Can also maybe give Bromocriptine (a DA agonist), but be careful bc it may induce more psychotic symptoms in these patients

What can germinal matrix fragility cause? What patient population? Why?

Can cause intraventricular hemorrhage in premature infants. The germinal matrix starts involuting around 28 weeks gestation and disappears by the time an infant is full term. Premi's lack the ability to auto regulate their blood flow. This leads to increase in cerebral arterial BP and subsequent rupture/hemorrhage

What can a hot shower lead to in patients with polycythemia?

Can cause pruritus when exposed to hot shower because of the release of histamine from BASOPHILS! It can also cause a stroke due to vasooclusion.

Which cells have telomerase? How does it work?

Cancer cells and stem cells Its an *RNA-Dependent DNA Polymerase*. 2 main subunits: -Telomerase RNA component (TERC): built in RNA template that is repetitively read by TERT -Telomerase Reverse Transcriptase (TERT): repeatedly reads the RNA template and adds TTAGGG DNA

What drugs classically cause microangiopathic hemolytic anemia?

Cancer drugs such as cisplatin and cyclophosphamide

Explain exactly how prostate cancer can metastasize to bone?

Cancers of the pelvis, including prostate, spread to the lumbosacral spine via the *Vertebral Venous Plexus* (VVP). The VVP communicates with a number of venous networks, including the *Prostatic Venous Plexus*, which receives the venous supply from the prostate, penis, and bladder. It runs up the entire spinal column and connects with the venous supply of the brain via a valveless system, which allows for bidirectional flow and regulation of ICP. This venous connection to the cerebral circulation may help explain the propensity of tumors to metastasize to the brain! *Note- Most skeletal system metastasizes are due to *hematogenous* spread! *Note- The VVP also communicates with the azygous vein in the chest, explaining why breast and lung cancers frequently metastasize to the thoracic spine!

What are the 3 causes of infectious esophagitis? What will you see for each?

Candida = white pseudomembranes, pseudohyphae HSV-1 = punched out ulcers with nuclear inclusions CMV = linear ulcers with nuclear/cytoplasmic inclusions

What is it called when HMOs make an arrangement in which a payor pays a fixed, predetermined fee to cover all medical services?

Capitation

Drug that treats Trigeminal Neuralgia? MOA? S/E's?

Carbamazepine Inhibits neuronal high-frequency firing by reducing the ability of sodium channels to recover from inactivation (just like phenytoin) Can cause aplastic anemia (monitor CBC). Also is a *P450 Inducer*

How many calories are made from 1 gram of protein? Carbs? Fat? Alcohol?

Carbs/protein = 4 Fat = 9 Ethanol = 7

What is Beck's triad? What does it suggest?

Cardiac Tamponade! 1. Hypotension 2. Distended neck veins 3. Distant muffled heart sounds on auscultation

What muscle cells contain T-tubules?

Cardiac and Skeletal NOT SMOOTH MUSCLE!

What is the main negative side effect seen with TCA overdose? How do you treat it? Why does it work?

Cardiotoxicity (arrhythmias due to Na channel inhibition) *Sodium bicarbonate* increases serum pH, which favors the neutral form of the drug, preventing it from binding to sodium channels! Also, NaHCO3 increases extracellular sodium concentration, which helps overcome the competitive rapid sodium channel blockade induced by TCAs!

How does a carotid sinus massage help treat paroxysmal supraventricular tachycardia?

Carotid sinuses are bulges in the internal carotid artery just distal to the bifurcation point. Afferent limb travels to the vagal nucleus and medullary centers via CN IX. The efferent fibers carries parasympathetic impulses to the SA node and AV node via the Vagus nerve (CN X). Carotid sinus massage leads to increased afferent firing from the carotid sinus, which causes increased vagal parasympathetic tone. The *slows the conduction through the AV node and prolongs the AV node refractory period*, helping to terminate the reentrant tachycardia!

Absent Red reflexes on eye exam. Differential?

Cataract or tumor (Retinoblastoma)

Definitive host of Toxoplasma gondii?

Cats

What causes the clinical manifestations of reactive arthritis?

Caused by *immune complexes* involving bacterial antigens. However, it does not represent disseminated infection, and joint aspirates are sterile (ie. it is a "reactive", not an infectious arthritis!)

What type of ophthalmoplegia is seen in Diabetics when they have decreased perfusion of CNIII?

Central infarction of CN III can lead to down and out pupils (dysfunction of somatic/motor portion)!

What is the pathophysiology of psoriasis? How does it present?

Caused by CD4 T cells that activate CD8 t cells in the epidermis after interacting with dendritic APC cells int he skin. This interaction leads to the production of cytokines (TNF, IL-12, INF-gamma) and keratinocyte growth factors. In response, keratinocyte proliferation, inflammation, and angiogenesis occurs Will see hyperparakeratosis (nuclei still in stratum corneum), acanthosis (thickening of the skin), elongation of the pete ridges, mitotic activity above the epidermal basal layer, and reduced/absent stratum granulosum. Will see Auspitz sign (bleeding on scratching due to superficial angiogenesis). May see Munro micro abscesses (neutrophils form spongiotic clusters in the superficial dermis and the paraketotic stratum corneum)

What is myelodysplastic syndrome?

Caused by a defect in the stem cell maturation leading to ineffective differentiation of cell lines, and therefore, pancytopenia. Bone marrow biopsy will be hyper cellular with abnormally differentiated cells (misshapen nuclei). Usually occurs in older patents (>65)

Describe the pathogenesis of ARDS:

Caused by injury and inflammation of the alveolar pneumocytes and pulmonary endothelium. This initial inflammation is a result of recruitment of neutrophils to the lungs. Once in the pulmonary tissues, neutrophils release inflammatory mediators (eg., proteases and free radicals) that cause further inflammation and tissue damage, resulting in a self perpetuating cycle of worsening alveolar and endothelial injury. This process leads to increased pulmonary capillary permeability (allows fluid to enter the alveoli), diminished surfactant production (causes alveolar collapse), and thick protein rich fluid/necrotic debris (*HYALINE MEMBRANE FORMATION*). The net effect is impaired alveolar gas exchange with resulting respiratory failure!

What causes binasal hemianopsia?

Caused by pressure on the lateral areas of the optic chiasm, usually due to calcified carotid arteries

How does parvovirus affect the blood? What is this known as?

Causes *Aplastic Crisis* due to the virus destroying ONLY erythroid precursor cells, diminishing the # of reticulocytes available on demand. Contrast this with *Aplastic Anemia*, which paradoxically affects pancytopenia (not just anemia)

How does Anorexia nervosa lead to secondary amenorrhea?

Causes *Functional Hypothalamic Amenorrhea* Due to reduced circulating levels of leptin as a result of diminished adipose in tissue stores. The decreased leptin inhibits pulsatile GnRH release from the hypothalamus, causing decreased pituitary LF and FSH secretion, and low circulating estrogen levels, and amenorrhea!

What happens with Klebsiella granulomatis? Presentation? Diagnosis? Complication?

Causes Granuloma Inguinale (donovanosis). Presents as a PAINLESS genital papule that eventually ulcerates. *However, Lymphadenopathy is uncommon. **Intracytoplasmic Donovan Bodies are diagnostic. *If donovanosis is left untreated, scarring and strictures can lead to severe lymphatic obstruction and lymphedema (elephantiasis)

What is breast milk jaundice? What causes it?

Causes an indirect hyperbilirubinemia that peaks at age of 2 weeks. Due to ß-glucuronidase in breast milk which deconjugates bilirubin in the baby's GI tract. This causes increased resorption of bilirubin and increased enterohepatic circulation of bilirubin. Urine and stool color are unaffected

What happens with Haemophilus ducreyi?

Causes chancroid, an ulcerative STI characterized by PAINFUL red papule on the genitals that eventually erode to become tender ulcer. Regional lymph nodes may swell and become chronic ulcers. You "DO CRY" with H. ducreyi!

MC benign liver tumor? Describe ti

Cavernous Hemangioma Pts btw 30-50, dont biospy (fatal hemorahge, love to bleed). Can also be in brain above the cerebellum (can lead to seizures). Enlarge via ectasia (hollow spaces), and lined by a single layer of epithelial cells

Classic presentation of an aspiration pneumonia?

Cavitary lesion with air-fluid levels are signs of a *lung abscess*, which usually occurs as a complication of aspiration pneumonia with lung parenchyma necrosis and cavity formation. Clinically, causes fever, malaise, weight loss, clubbing, and leukocytosis, with a cough that has copious production of green, foul smelling sputum Usually caused by anaerobic oropharyngeal bacteria (fusobacterium, peptostreptococcus, bacterioides) Associated with: -*Altered consciousness* (alcoholics, seizures, coma, dementia, neurologic disease) -Immunosuppression -Impaired swallowing (NG tube, mechanical ventilation) -Poor oral hygiene, dental infections, and gingival disease

Anti-fungals that work on the cell membrane? Cell wall?

Cell Wall = Echinocandins (capsofungin) -- inhibits the synthesis of gluten, a component of the fungal cell wall Cell membrane: 1. Polyenes= Amphotericin b and Nystatin bind ergosterol 2. Azoles inhibit synthesis of ergosterol

Holocrine gland mechanism? Examples?

Cell lysis releases entire contents of the cytoplasm and cell membrane Ex: Sebaceous glands and Meibomian glands (eyelid)

Anti fungal that targets the fungal cell wall? Cell membrane?

Cell wall = Capsofungin (echinocandins)- inhibits synthesis of 1,3-beta-D-glucan Cell membrane: -amphotericin B and nystatin bind ergosterol -Azoles inhibit synthesis of ergosterol

What does the endoderm give rise to?

Cells derived from inner lining of primitive gut tube: -thyroid follicular cells -epithelial surface of trachea, bronchi, and lungs -liver and biliary tree - pancreas -GI and bladder epithelium

Apocrine gland mechanism? examples?

Cells secrete via budding of membrane bound vesicles ex: Mammary Glands

Merocrine gland mechanism? examples?

Cells secrete via watery secretory product via exocytosis with NO LOSS of plasma membrane ex: Salivary glands, eccrine sweat glands, apocrine sweat glands (formerly thought to be apocrine)

What 3 general cells have a particularly active PPP pathway?

Cells that require NADPH! 1. Cells experiencing *high oxidative stress* (eg, RBCs), where NADPH is used to regenerate reduced glutathione 2. Organs (eg, liver and adrenals) involved in *reductive biosynthesis* (eg, fatty acids, cholesterol, and steroids) and Cyt P450 metabolism! 3. Phagocytic cells generating a respiratory bursty (NADPH oxidase)

What are 2 important steps to working up a metabolic alkalosis?

Checking the patient's* volume status* and *urine chloride*. MCC of metabolic alkalosis is: 1. Vomtiing or NG tube suctioning: loss oh H+ and Cl- ions (hydrochloric acid) in gastric secretions causes a net gain of alkali in the body, leading to a metabolic alkalosis. Loss of Cl- (hypochloremia) also impairs HCO3- excretion by the kidney, worsening the metabolic alkalosis. These patients present with hypotension (due to volume loss) and low urine Cl_ (<10). This can be corrected by volume and Cl- repletion with isotonic saline (its *saline responsive*) 2. Thiazide or loop diuretic use: Thiazides and loop diuretics block absorption of Na+ and Cl- ions at the DCT and loop go henle. As a result, distal delivery of NaCl increases while ensuing volume depletion stimulates aldosterone secretion. These mechanisms increase Na reabsorption int he collecting tubule at the expense of increasing H+ and K+ urinary loss, leading to a metabolic alkalosis. Patients present with high urine Cl- (>20) when diuretic use is ongoing, and low urine (<10) after it is stopped. The alkalosis can be corrected by volume and NaCl repletion with isotonic saline (*saline responsive*) 3. Mineralocorticoid excess state: The increased mineralocorticoid activity seen in primary hyperaldosteronism (Conn syndrome) or primary hypercortisolism (Cushing syndrome) is also associated with metabolic alkalosis. Same mechanism as above, leads to relative increase in serum HCO3-. These patients present with HTN and high urine Cl- (>20) due to expanded extracellular fluid volume causing pressure natriuresis. The alkalosis cannot be corrected with isotonic saline due to persistent mineralocorticoid activity (*saline unresponsive*)

Immunodeficiency with albinism and neurologic defects in childhood?

Chediak-Higashi Syndrome

Drugs that cause bone marrow suppression?

Chemotherapeutic agents Chloramphenicol Zidovudine Gold-containing meds

How does the spleen look in children with Sickle Cell anemia? Adults?

Children = Congested due to splenic sequestration crisis, which develops due to vasooclusion and splenic pooling of erythrocytes. Manifests as marked Hb decrease, rapidly enlarging spleen, and hypovolemic shock Adult = repeated infarction leads to functional asplenia (appears atrophied and fibrosed--autosplenectomy).

MCC of death due to Sickle Cell anemia in children? Adults?

Children = infection with encapsulated organisms (autosplenectomy can't remove them). Strep pneumo is most common, followed by Haemophilus. If osteomyelitis, then salmonella! Adults = Acute Chest syndrome after pneumonia

Examples of 1st generation antihistamines? What are they used for?

Chlorpheniramine, Diphenhydramine, promethazine, hydroxyzine Used for allergic reactions (prevent/tx) and motion sickness as antiemetics

Patient with conductive hearing loss and otorrhea. What are you thinking?

Cholesteatoma -- overgrowth of desquamated keratin debris in middle ear space-- may erode ossicles and mastoid air cells

1st generation Antihistamine side effects? What are some examples of 2nd gen antihistamines?

Cholinergic/Muscarinic- blurry vision, exacerbation of glaucoma, urine retention, delirium, constipation Alpha-adrenergic- postural dizziness, falls) Serotonergic- appetite stimulation, weight gain Lipophilic- easily crosses the blood/brain barrier, leading to sedation/cognitive dysfunction 2nd gen ("-adine") = Loratidine, Cetirizine, fexofenadine, and desloratidine *These cause less side effects of all of the above!

What is organophosphate poisoning? How do you treat it? What is not fixed by one of the medications?

Cholinesterase Inhibitor Poisoning causes massive increase in ACh, leading to DUMBBELSS symptoms. Treat with atropine (muscarinic antagonist) and pralidoxime (restores AChE from its bond with the poison if given early) ***Atropine does NOT fix the effects of ACh at Nicotinic Receptors (skeletal muscle and CNS)

MOA of Donepezil?

Cholinesterase inhibitor, used in AD

Describe the histology of Moles versus Gestational choriocarcinoma

Choriocarcinoma has NO VILLY PRESENT!!! Its only proliferation of cytotrophoblasts and syncytiotrophoblasts

CMV-related complications observed in infants exposed to the virus in utero?

Choriretinitis (MC eye problem) Sensorineural deafness Seizures Jaundice Hepatosplenomegaly Microcephaly

Pathogenesis of Systemic Sclerosis?

Chronic autoimmune inflammation, vascular endothelial injury resulting in chronic ischemic tissue damage (eg. fingertip ulcers) and excessive activation of fibroblasts leading to progressive tissue fibrosis

What is primary biliary cirrhosis? Histology? Gross? Clinical symptoms?

Chronic autoimmune liver disease characterized by dense portal tract infiltrate of lymphocytes, that results in the GRANULOMATOUS destruction of INTRAHEPATIC, INTERLOBULAR BILE DUCTS Middle aged women, presents with fatigue, pruritus. As it progresses, hepatosplenomegaly and cholestasis. Also may have reduced biliary cholesterol excretion leading to hypercholesterolemia and xanthelasma formation. Late manifestations = cirrhosis and portal HTN

Pigmented gallstones usually due to what?

Chronic hemolytic anemia develops pigmented gallstones due to increased secretion of conjugated bilirubin into bile.

What is bronchiolitis obliterans?

Chronic transplant rejection of the lungs Affect the small bronchioli producing an obstructive airway disease. Lymphocytic inflammation and destruction of the epithelium of the small airways is seen (both Type II and Type IV hypersensitivity). Subsequently, fibrinopurulent exudate and granulation tissue are found in the lumen of the bronchioli, which ultimately leads to fibrosis, scarring, and the progressive obliteration of small airways!

How is Citrate formed? What does it regulate?

Citrate is formed from the condensation of Acetyl CoA with oxaloacetate in the 1st step of the TCA cycle Citrate is a powerful inhibitor of Phosphofructokinase-1 (PFK-1)- its like yo bro, were good down here in the TCA cycle, stop breaking down glucose via glycolysis homie

Why do Class IC antiarhythmics display use dependence? What Class displays reverse use-dependence?

Class IC drugs are the slowest of the class I agents to dissociate from the sodium channel. This results in a phenomena known as *use-dependence*, in which their sodium channel blocking effects intensify as the heart rate increases due to less time between action potentials for the medication to dissociate from the receptor. Class III demonstrate reverse use-dependence (the slower the rate, the more the QT interval is blocked!)

How do cleft lips form?

Cleft lip = maxillary prominence fails to fuse with the inter maxillary segment during 4-6th week of development Cleft palate = palatine shelves fail to fuse with one another or with the primary plate

How do cleft palates form?

Cleft palate = palatine shelves fail to fuse with one another or with the primary plate

Drug that helps women get pregnant? MOA?

Clomiphene citrate SERM that stimulates FSH and LH production, stimulating follicular development in the ovaries.

What is systemic mastocytosis? What causes it? Clinical presentation?

Clonal mast cell proliferation in bone marrow, skin, and other organs. These cells have prominent expression of mast cell tryptase. Due to mutations in the KIT receptor tyrosine kinase. Excessive histamine release from degranulation of mast cells mediates syncope, flushing, hypotension, pruritus, urticaria, gastric acid secretion (ulcers & inactivation of pancreatic enzymes causing diarrhea!)

What is seen in VACTERL association?

Co-occurence of birth defects/anomalies: -Vertebral -anal atresia -cardiac -tracheoesophageal fistula -Renal ( ***urogenital tract MC***) -limb

How do you measure reliability?

Coefficient of variation: -Standard deviation/mean

Function of the epididymis? What bugs can infect it?

Coiled tube posterior to the testicle responsible for storage, maturation, and transportation of sperm. Epididymitis is associated with Gonorrhea and Chlamydia infection

Compare colitis (eg. UC) associated carcinoma and sporadic colorectal carcinoma:

Colitis associated carcinoma: -Younger patients -Progress from flat and non-polyploid dysplasia -Histologically are mucinous/signet ring -Early p53 mutations and late APC gene mutations (opposite of sporadic- AK-53) -Located in proximal colon (especially with Crohns disease of concurrent primary sclerosing cholangitis) -Be MULTIFOCAL in nature *Usually develops after 10 years of colitis.

Tracheal deviation towards problem side of thorax-- what is going on?

Collapsed lung due to bronchial obstruction

What cancer does 5-FU treat?

Colorectal cancer--- often given with Leucovorin to potentiate its effects

What is the most optimal way to treat Parkinsonism?

Combinations of selegiline (MAO-B inhibitor), anticholinergics, and amantadine until hey no longer provide control of symptoms. Only then is levodopa/carbidopa introduced

Why should you never use beta-blockers with non-dihydropyridine calcium channel blockers (i.e., Verapamil and dilitazem)

Combined additive negative chronotropic effects yield severe bradycardia and hypotension

MOA of flutamide?

Competitive non steroidal testosterone receptor inhibitor. Blocks the stimulatory effect of androgens on primary tumor of prostate cancer and the metastases too.

Pathophys of Toxic Megacolon? How do you Dx?

Complication of Ulcerative colitis (C. diff as well) Severe, occasionally transmural inflammation causes release of inflammatory mediators, bacterial products, and induction of NOS leading to increased NO, which contributes to colonic smooth muscle paralysis. Rapid colonic distension ensues, thinning the intestinal wall and making it prone to perforation. Dx via X-Ray. Do NOT do barium enema or colonoscopy as they may precipitate perforation

What kind of ocular findings are seen with an uncal herniation?

Compressed ipsilateral CN III as it exits the midbrain --- leads to palsy and fixed dilated pupils (due to preganglionic parasympathetic nerve fiber damage). Can progress to bilateral fixed pupils if herniation involves midbrain

What is Tarsal Tunnel Syndrome?

Compression of the tibial nerve where it runs under the flexor retinaculum posterior to the medial malleolus Note-- compression of the saphenous nerve can cause numbness/paresthesias anterior to the medial malleolus

Function of aromatase? How would aromatase in an embryo present?

Concerts androstenedione to estrone, and testosterone to estradiol Presents the same as 21-hydroxylase deficiency, but with maternal visualization (placental aromatase not there to convert the excess androgens into estrogen!)

Symptoms of serotonin syndrome? How does this occur?

Confusion, agitation, tremor, tachycardia, hypertension, clonus, hyperreflexia, hypethermia and diaphoresis High doses of SSRIs or combining SSRIs with MAO inhibitors

What is Sturge-Weber Syndrome (encephalotrigeminal angiomatosis)

Congenital non inherited neurocutaneous disorder with cutaneous facial angiomas (port wine stain on face) and leptomeningeal angiomas. Skull radiographs may show tram-track calcifications

Disorders of bile conjugation? Disorders of hepatic excretion of bilirubin glucuronides?

Conjugation (Defective UDP-Glucouronyltransferase): -Gilbert Syndrome (mild) -Crigler-Najjar Syndrome (severe-absent)- type II is worse Excretion (mutation in canalicular membrane transport protein): -Dubin-Johnson (black liver) -Rotor Syndrome (milder)

Name for primary hyperaldosteronism?

Conn Syndrome Due to bilateral adrenal hyperplasia or an aldosterone-producing adenoma

What are the function of intrafuscal fibers?

Connected in parallel with extrafuscal fibers. They are innervated by group Ia and II sensory axons and are sensitive to changes in muscle length. Muscle spindles mediate the stretch reflex (myostatic reflex), which is tested via DTRs! When muscle is stretched, there is a monosynaptic reflex activation of the alpha motor neuron (of the same muscle), causing contraction that resists the stretch!

What does the omphalomesenteric (vitelline) duct connect? What can occur if it doesn't obliterate completely or is an abnormal obliteration?

Connects the midgut lumen with the yolk sac cavity (normally obliterates during 7th week of development) 1. Persistent Vitelline duct: (fistula)- meconium comes out of umbilicus 2. Meckel Diverticulum: MC, partial closure, patent portion at ileum 3. Vitelline sinus : partial closure, patent portion at umbilicus 4. Vitelline duct cyst: (enterocyst): central cyst forms between the 2, connected via fibrous bands

Most common side effect of opioids? How do you try to prevent this?

Constipation (stimulates mu receptors in GI tract, decreases secretions and gastric motility) Pts should receive a prophylactic bowel regimen (increased fluid intake, dietary fiber, and laxatives) to minimize constipation

Describe the Neisseria meningitidis vaccine

Contains capsular polysaccharides from serotypes A, C, and D. NOT B!!!

What is in Cryoprecipitate? What is it used for?

Contains factor VIII, Factor XIII, vWF, and fibrinogen. Used for coagulation factor deficiencies involving fibrinogen and Factor VIII

Bilateral ACA occlusion. Symptoms?

Contralateral leg and foot motor/sensory deficits BEHAVIORAL SYMPTOMS (diminished motivation) URINARY INCONTINENCE (if the frontal micturition center) is affected

Injury/stroke to the base of the pons?

Contralateral weakness and ataxia due to involvement of descending motor tracts (corticospinal and corticobulbar) and pontocerebellar fibers

How do steroids (ie. methyltestosterone) contribute to acne?

Converted to DHT, which then promote both follicular epidermal hyper proliferation and excessive sebum production. All that is left for acne to develop is inflammation and colonization via P. acnes!

Function of kallikrein? What inhibits it? Deficiency of inhibitor leads to what?

Converts kininogen into bradykinin Inhibited by C1 Esterase Inhibitor (if deficiency = hereditary angioedema)

What does a copper reduction test look for? What about glucose oxidase on a urine dipstick?

Copper reduction test: -Detects the presence of reducing sugars (fructose, glucose, and galactose) Glucose oxidase dipstick test: -only tests for urinary glucose

Describe Glycogen Storage Disease type III

Cori Disease -- deficient Debranching enzyme (alpha-1,6-glucosidase) Milder form of Von Gierke with *normal blood lactate*. Accumulation of limit dextrin in cytosol. Gluconeogenesis is intact (Glucose-6-P can leave the liver!)

Explain what is associated with each: -Cortical Bridging veins -Middle meningeal Artery -Dural Venous Sinuses -Saccular (Berry) Aneurysm -Germinal Matrix

Cortical bridging veins = subdural hematoma MMA = Epidural hematoma Dural venous sinuses = Thrombosis from malignancy, hyper coagulable states, trauma Saccular (Berry) aneurysm = Subarachnoid hemorrhage (Ehlers-Danlos and ADPKD) Germinal Matrix = Intraventricular hemorrhage in a premature infant

Since Oxygen equilibration in the lungs is normally perfusion limited, when can it become diffusion limited?

Disease states = emphysema and pulmonary fibrosis Physiological = Very high pulmonary blood flow, such as intense exercise

What would the clinical symptoms be of an infarct of the anterior pons?

Corticospinal tract = contralateral hemiparesis and babinkski sign Corticobulbar tract = contralateral lower facial palsy, dysarthria Corticopontine fibers (convey motor information from the context to the ipsilateral pontine grey) = contralateral dysmetria and dysdiadokinesia (ataxic hemiparesis). The cerebellar deficits are contralateral bc the pontocerebellar fibers (relay info from pontine grey to cerebellum) decussate and enter the cerebellum through the contralateral middle cerebellar peduncle.

What upregulates expression of PNMT? Why?

Cortisol increases expression of PNMT, which converts NE to epinephrine in the adrenal medulla. This occurs bc the venous drainage of the adrenal gland goes from the cortex to the medulla!

Why does adrenal insufficiency cause a hypotensive crisis?

Cortisol up regulates alpha-1 adrenergic receptors on vascular smooth muscle. Low glucocorticoid (cortisol) levels help contribute to hypotensive crisis by decreasing vascular responsiveness to Angiotensin II and Norepinephrine (concept of *permissiveness*) This is why we give corticosteroids STAT to a patient in adrenal crisis (hypotensive, tachycardia, and hypoglycemic!). Cortisol "permits" the vasopressors of the body to start working!

4 "C's" of Measles prodrome? Which one is pathognomonic for Measles? What do these symptoms precede?

Cough Conjunctiva Coryza (rhinitis) ***Koplik Spots- small white blue or grey specks on erythematous base on buccal mucousa (pathognomonic) Then comes maculopapular exanthem (rash) that starts on the face and spreads down trunk/extremities and becomes confluent

What does UV radiation do to DNA? How is it repaired? What is the disease when this repair pathway is defective?

Creates PYRIMIDINE DIMERS Repaired via NNUCLEOTIDE EXCISION REPAIR (NER) Mutations in NER = XERODERMA PIGMENTOSUM

Spongiform transformation of the cerebral cortex of elderly patient with rapidly progressing dementia?

Creutzfeldt-Jakob Disease (sporadic form) If pt was younger and ate so bad meat, it would be the acquired or variant form

Pain with swallowing and choking/"food-sticking" sensation?

Cricopharyngeus Muscle failing to relax

What intrinsic muscle of the larynx is NOT innervated by the recurrent laryngeal nerve? What is it innervated by?

Cricothyroid muscle (C**T muscle!) Its innervated by the External laryngeal nerve

Where do you make an incision when you need to establish an airway through the throat?

Cricothyrotomy through the cricothyroid membrane Incision through the following structures: 1. Skin 2. Superficial cervical fascia (including subQ fat and platysma muscle) 3. Investing and pre tracheal layers of the deep cervical fascia 4. Cricothyroid membrane

Function of Homeodomain (homeobox) genes during development?

Critical for the sequential development or organs and tissues along the body axis

Why do Crohn's disease patients have an increased risk of gallstones?

Crohn's loves the terminal ileum, where bile acids are reabsorbed. This leads to decreased bile acid reabsorption. This leads to less bile acid in bile, and the ratio of Cholesterol:bile acids INCREASES. Cholesterol precipitates in the bile and forms gallstones

Location of stem cells in the intestines?

Crypts of Lieberkuhn in the mucosa

Describe the saphenous nerve

Cutaneous branches of saphenous nerve innervate the skin of the medial leg. ("Saddle side") The saphenous nerve is a branch of the femoral nerve and courses to the medial leg together with the great saphenous vein!

What is an ecchymosis?

Cutaneous or subQ collection of extravasated blood measuring atlas 1 cm in diameter. Can be superficial without trauma, but frequently indicate deep hemorrhage (hematoma) due to a bony fracture, ligamentous rupture, or muscular injury. (i.e. "bruise") ***These lesions do NOT blanch under pressure bc the RBCs are not contained within the vasculature!!!

How does cyanide affect PaO2, SaO2, and CaO2? Tx?

Cyanide inhibits cellular oxidative phosphorylation by inhibiting Fe3+ in cytochrome c oxidase, lowering peripheral tissue oxygen consumption. Arterial PaO2 , SaO2, and CaO2 remain unchanged, but the venous oxygen content rises and the arterial-venous oxygen gradient falls. Cyanide may also bind to the ferrous (Fe2+) iron of Hb to form cyanoHb, but only in small amounts Tx = hydroxycobalamin (vit B12 precursor) binds to intracellular cyanide forming cyanocablamin, which can be readily excreted in the urine!

What does the word "caspase" stand for?

Cysteine-aspartic acid-protease

Classic examples of Autosomal Recessive inheritance?

Cystic Fibrosis Hemochromatosis Sickle Cell Anemia

What is Amifostine used for?

Cytoprotective free-radical scavenger used to decrease nephrotoxicity associated with platinum containing and alkylating chemo agents and to Decrease xerostomia (dry mouth)

Components of the DPT vaccine? What are the Abs that are made?

Diphtheria-Pertussis-Tetanus It contains dptheria toxoid, which causes the host to initiate a IgG response to the B subunit (binding) of the exotoxin (protein), thereby neutralizing any future exotoxin release!

Function of surfactant? Where is it produced? Where is it stored?

Decreases the surface tension within alveoli, helping to prevent collapse. (in NRDS, decreased surfactant = increased alveolar surface tension = collapse/atelectasis) Produced via Type II pneumocytes (cuboidal), stored and transported to cell surface by LAMELLAR BODIES (organelles containing parallel stacks of membrane lamellae)

Inguinal Canal. What makes up the deep ring? Superficial Ring?

Deep Ring = Transversalis Fascia (internal spermatic fascia) Superficial Ring = External oblique muscle (external spermatic fascia)

What is androgen insensitivity syndrome? How does it typically present?

Defect in Testosterone Receptors Usually a 46 X,Y child who appears phenotypically female but has primary amenorrhea due to absence of internal female reproductive tract and presence of cryptorchid testes

Describe the clinical presentation of Maple Syrup Urine Disease:

Defect in branched-chain-alpha-ketoacid dehydrogenase Neurotoxicity: Buildup of leucine in serum/tissues Sweet Urine Odor (burnt sugar): metabolite of isoleucine

Refuse disease pathogenesis and Tx

Defect in peroxisomal alpha oxidation causes accumulation of phytanic acid, leading to neuronal defects Tx = NO dietary Chlorophyll

If a neonate gets HBV, will their liver enzymes be up or down? Why?

DOWN! This is because neonate's immune system is immature, so no inflammation will occur!

In the presence of ADH, which segments of the nephron contain the most dilute urine? Most concentrated?

Dilute =TAL and Distal convoluted tubule Concentrated = Cortical Collecting Ducts

What are calcifications of an aortic valve due to in old age?

DYSTROPHIC Calcifications due to damaged/necrotic tissue from chronic hemodynamic stress. (normal calcium values) Once cells die, they release cellular degradation products into the valvular interstitial, promoting calcification and thickening of valve leaflets/annulus Goes from aortic sclerosis (benign) to calcified aortic stenosis (outflow obstruction)

Presenting Sign of Sickle Cell anemia?

Dactylitis

What is diffuse esophageal spasm?

DES is due to *impaired inhibitory neurotransmission within the esophageal myenteric plexus*. In DES, several segments of the esophagus contract inappropriately at the same time, which appears as disorganized *non-peristaltic contractions* on esophageal manometry and "corkscrew" esophagus on barium esophagram. Pts present with solid/liquid dysphagia

What causes male-pattern hair loss? Treatment?

DHT *Finasteride* --- inhibits 5-alpha reductase (converts testosterone to DHT)

What are 3 causes of Microangiopathic hemolytic anemia (MAHA)?

DIC, TTP, and HUS

How does drug induced lupus usually present? Ab? What drugs are metabolized via acetylation?

DILE typically lacks the cutaneous manifestations (i.e.. no malaria rash) and is rarely associated with neurologic or renal complications. Anti-Histone Ab Procainamide, Hydralazine, and isoniazid are metabolized via phase II acetylation in the liver. Hepatic expression of N-acetyltransferase is genetically determined, and patients with a slow acetylator phenotype are at greater risk for DILE. Also, slow acetylators are predisposed to INH induced peripheral neuropathy due to increased drug concentrations!

Anti fungal that targets fungal DNA and RNA synthesis? Mitosis?

DNA and RNA synthesis = flucocytosine (typically used in conjunction with amphotericin B for C. neoformans Mitosis: Griseofulvin (binds microtubules- useful for dermatophytes since it accumulates in keratin containing tissues)

Where are DNA glycosylases used?

DNA base excision repair

DNAP I and III. What do they do? Exonuclease activity?

DNAP III: primary enzyme responsible for synthesis of daughter strands. Only has 3'-->5' exonuclease activity (proofreading function) DNAP I: Replaces RNA primers with DNA. Has both 3'-->5' exonuclease activity and 5'-->3' exonuclease activity (allows DNA to remove the RNA primers!)

Are cerebral aneurysms seen in in autosomal dominant or recessive polycystic kidney disease?

DOMINANT

For Traumatic brain injury, Describe damage to the brainstem at/below the level of the red nucleus? Above?

Damage to brainstem at/below level of red nucleus (midbrain, tegmentum, pons) often causes decerebrate (extensor) posturing due to loss of descending excitation to the upper limb flexors (via the rubrospinal tract) and extensor predominate (due to unopposed vestibulospinal tract output). Damage above the red nucleus (cerebral hemispheres) typically results in decorticate (flexor) posturing due to loss of descending inhibition of the red nucleus and subsequent hyperactivity of upper extremity flexor muscles. (Note-- the vestibulospinal tract originates from the vestibular nuclei at the pontomedullary junction and does not receive descending cortical inhibition)

Features of ALS

Damage to the motor neurons of the anterior horn (LMN lesion) and demyelination of the corticospinal tracts (UMN lesion). The result is denervation atrophy of the muscles (amyotrophy). Usually die from respiratory complications (i.e. respiratory pneumonia)

What can excessive consumption of nitrites cause? How does our body fix it exactly?

Deamination of: Cytosine ---> Uracil Adenine ---> Hypoxanthine Guanine ---> Xanthine Fixed by Base Excision Repair: -Glycosylases recognize the abnormal bases, cleave out the base -Endonuclease then comes in and cleaves the 5' site -Lyase (phosphodiesterase enzyme) cleaves the 3' site, removing the entire sugar-phosphate group -DNA polymerase fills the gap -Ligase seals the nick

During exercise, venous content of O2, CO2, pH?

Dec O2 Inc CO2 and pH

Common side effects of ACE-Inhibiotrs?

Decrease GFR, hyperkalemia, and cough, are rarely angioedema

How do you treat glaucoma?

Decrease IOP either by decreasing production or increasing excretion *Timolol and Acetozolamide-- decrease aqueous humor secretin by ciliary epithelium *Prostaglandin F2alpha and cholinomimetics-- Increase outflow of aqueous humor

What changes are seen in compression atrophy?

Decrease in size AND number of neurons!

Do statins cause increased or decreased gallstones?

Decreased Inhibits HMG--CoA Reductase, the rate limiting step of cholesterol synthesis. This reduces the cholesterol:bile acid ratio

You hike up to the top of Mount Everest. Whats going on with your breathing?

Decreased FiO2, triggers hyperventilation to get more oxygen in. This also makes you exhale a ton of CO2, leading to respiratory alkalosis. 24-48 hours later the kidney is like shit, lets stop making bicarb, and bicarb drops

2 Causes of PKU? Which is worse? Why?

Decreased Phenylalanine Hydroxylase Deficiency of Dihydrobiopterin Reductase (Reduces BH2 back to BH4)-- known as malignant PKU Deficiency of Dihydrobiopterin Reductase is worse because BOTH Phenylalanine hydroxylase and Tyrosine hydroxylase use BH4 as a cofactor, so you knock BOTH of these out! Administration of Tyrosine will NOT help with the synthesis of downstream products!

Would an AV fistula cause increased or decreased TPR? Venous return? CO?

Decreased TPR Increased VR Increased CO Think about just taking blood from the arterial system and just throwing it back into the venous system so it gets back into the heart earlier!

Describe the progression of the 3 phases of Acute Tubular Necrosis

Decreased blood flow to the kidneys triggers a pathophysiological change in the nephron that causes tubular epithelial necrosis and acute renal failure. Initiating stage = usually unnoticed by clinicians due to it being overshadowed by the main disorder (hemorrhage, MI, sepsis, etc.). If significant damage occurs, then... Maintenance phase (oliguric stage) = follows in 24-36 hours. Urine output decreases. Other changes include: 1. Increased extracellular fluid volume can cause weight gain, edema, and pulmonary vasculature congestion 2. Hyperkalemia is usually asymptomatic if <6. Above 6 causes peaked T waves on EKG and risk of fatal ventricular arrhythmias 3. Retention of both H+ and anions (sulfate, phosphate, urate) leads to high anion gap metabolic acidosis. 4. Decreased sodium and calcium concentration, and increased level of phosphate and magnesium 5. Urinalysis reveals muddy brown casts, low urinary osmolarity (<350), high urinary sodium (>30), and high urinary fractional sodium excretion (FeNa>1) Tx = conservative management and dialysis. If patient survives, then... Recovery Phase = Follows in 1-2 weeks. Vigorous diuresis but because the renal tubules can't function fully yet, electrolyte balance is still altered. A high volume, hypotonic urine leads to decreased serum concentrations of K, Mg, phosphate and calcium. May lead to *HYPOKALEMIA*. Hypocalcemia occurs due to decreased levels of 1,25-dihydroxyvitamin D

How exactly do anorexic/female athletes get amenorrhea? Why do they also get osteoporosis?

Decreased fat leads to decreased circulating LEPTIN levels, leading to inhibition of pulsatile GnRH release! Loss of estrogen = early onset osteoporosis!

Patient is in Diabetic Ketoacidosis. What is going on in his adipocytes? Why is Glycerol Kinase activity unregulated?

Decreased insulin causes increased activity of Hormone Sensitive Lipase (HSL), which breaks down TGs stored in adipocytes into FFAs and Glycerol. Adipocytes can't metabolize the glycerol further, so it ships it out to the liver, where it can be phosphorylated by *Glycerol Kinase* into glycerol-3-P, which can then be converted into DHAP by glycerol-3-P Dehydrogenase. DHAP can then be used to produce ATP through glycolysis or glucose through gluconeogenesis.

What are some signs of intracerebral hemorrhage?

Decreased levels of consciousness Asymmetric pupils Irregular breathing pattern

What exactly is the problem in osteomalacia? What causes it?

Decreased mineralization of osteoid, which can be due to inadequate levels of calcium and phosphorus, intrinsic osteoid matrix defects, or other factors that impair mineralization (acidosis, aluminum, fluoride) MC due to Vitamin D deficiency. Low vit D causes reduced calcium absorption, leading to secondary hyperparathyroidism and renal phosphate wasting. The resulting hypophosphatemia impairs the mineralization of newly deposited osteoid matrix on Haversian canal and trabecular surfaces!

What is Kallmann Syndrome?

Decreased synthesis of GnRH in Hypothalamus (hypogonadotropic hypogonadism) Presents with an olfactory sensory defect (Anosmia)

MOA of finasteride? used for?

Decreases peripheral conversion of Testosterone to DHT by inhibiting 5-alpha reductase Used for BPH and male-pattern baldness

What is Familial Hypocalciuric Hypercalcemia? What will we see?

Defective Ca-sensing receptor (CaSR) in multiple tissues (parathyroids, kidneys). HIGHER than normal calcium levels are needed to activate these CaSRs which suppress PTH secretion. (normal binding of Ca to CaSR causes inhibition of PTH release) Will see mild hypercalcemia and hypocaliuria with normal/slightly increased PTH, causing excessive renal Ca reuptake!

Pathogenesis of Lesch-Nyhan Syndrome?

Defective HGPRT, main enzyme of purine salvage pathway. Since we can't resalvage, there is increased degradation of guanine and hypoxanthine into uric acid, which increase the demand to produce MORE PURINES to make up for this loss! The first step then in the synthesis of purines is the formation of PRPP from PRPP synthetase, which then gets deaminated by PRPP Deaminase and then goes on to from more purines!

PKU defect? Clinical fts?

Deficiency of phenylalanine hydroxylase, causing impaired conversion of Phenylalanine to tyrosine (tyrosine becomes ESSENTIAL AA) Leads to CNS abnormalities (developmental delay/mental retardation) Albinism and musty body odor

What is Dengue Fever? Is primary of secondary infection more severe?

Dengue hemorrhagic fever causes fever, headache, retro-orbital pain, bleeding, diffuse macular rash, muscle/joint pain ("break-bone fever"), leukopenia, thrombocytopenia, and elevated LFTs. Primary disease can be asymptomatic or self-limiting. Secondary disease is usually due to a DIFFERENT VIRAL SEROTYPE and causes much more severe diease

Blood side effect of INH?

Depletes Vit B6, leads to Sideroblastic anemia (microcytic, ALA synthase can't perform rate limiting step of heme synthesis in the mitochondria)

What are xanthelasmas made of?

Dermal accumulations of benign-appearing macrophages with abundant, finely vacuolated (foamy) cytoplasm containing cholesterol (free and esterified), phospholipids, and TGs. Due in part to insulin resistance promoting increased VLDL production, diabetics may develop secondary Type IV or V hyperlipidemia (increased VLDL, chylomicrons) and/or diabetic dyslipidemia with elevated LDL cholesterol and low HDL cholesterol.

Biotin deficiency --- symptoms?

Dermatitis, alopecia, enteritis due to Abxs or raw egg whites containing avidin

What are the features of a glucagonoma? Treatment?

Dermatitis: *necrolytic migratory erythema*, which is an elevated painful/pruritic rash typically of face, groin, and extememties. It can coalesce to form large lesions with central clearing of bronze-colored induration. Can affect mucous membranes, leading to glossitis, chelitis, and blepharitis. Rash is due to low amino acid levels in serum. Diabetes (hyperglycemia) DVTs Declining weight Depression nonspecific GI pain *Treat with Ocreotide/surgery

What does the mesoderm give rise to?

Dermis as well as most bones, muscles, blood vessels, and visceral tissue

Describe the course of the Tibial nerve

Descends though the popliteal fossa with popliteal A/V. It then traverses the posterior compartment of the leg deep to the soleus muscle. After providing innervation to the posterior compartment muscles, the nerve enters the plantar aspect of the foot through the tarsal tunnel (btw the flexor retinaculum and medial surfaces of the talus and calcaneus). Here, it divides into the medial and lateral plantar nerves.

What are the 2 longest acting insulins? Why are they so long lasting?

Detemir = Fatty acid bound to one of the lysine on insulin. Allows it to bind to albumin and slowly dissociate. Glargine (large = long) = pH of 4 forms a microprecipitate in the subQ tissue after injection, causing a very slow release

Etiology of urge incontinence

Detrusor overactivity

Pathophysiology of Heparin induced thrombocytopenia (HIT)?

Development of auto-Abs against heparin bound platelet factor 4 (PF4). These activate the platelets, causing paradoxical thrombosis and thrombocytopenia!

Drug given to blunt adverse effects of Doxorubicin?

Dexrazoxane is an iron-chelating agent that helps prevent the generation of oxygen free radicals, prevent the dilated cardiomyopathy caused by doxorubicin

Immunodefiencies with absent thyme shadow on CXR? What is going on with their hearts?

DiGeorge Syndrome and SCID Cotruncal (outflow tract) defects, such as persistent truncus arteriosus, tetralogy of Fallot, and interrupted aortic arch

Pathogenesis behind diabetes and HTN leading to chronic kidney disease? How do you treat?

Diabetes -- causes loss of autoregulation of glomerular blood flow, leading to significantly elevated intraglomerular pressures and chronic glomerular injury. HTN -- elevated levels of Angiotensin II causes preferential efferent arteriole constriction, elevating intraglomerular pressure Treat with ACE inhibitors or ARBs so stop the dilation of efferent arteriole!

Causes of gastroparesis (gastric hypomobility)?

Diabetes Mellitus, uremia, hypothyroidism, and other metabolic disorders Presents as constipation, early satiety, and food stasis with vomiting

What is fibrocystic change of the breast? Is there an increased risk for cancer?

Diffuse small cysts with or without metaplasia and frequently causes cyclic breast pain without nipple discharge. Occurs premenopausal women >35 No increased risk for cancer!

Adverse effect of Doxorubicin? How does this happen? Microscopy? Clinical presentation?

Dilated cardiomyopathy (cardiotoxicity) due to generation of free radicals Early stage = Swelling of SR Later stage = loss of cardiomyocytes (myofibrillar dropout) Presents as biventricular CHF (orthopnea, peripheral edema)

What is Meniere Disease? What is the classic triad of symptoms?

Disorder of the inner ear that has increased volume/pressure of endolymph (endolymphatic hydrops) that is thought to be due to defective resorption of endolymph. The resultant dissension of the endolymphatic system causes damage to the vestibular and cochlear components of the inner ear. 1. Low frequency tinnitus with a feeling of fullness 2. Vertigo (N/V, lightheadedness) 3. Sensorineural hearing loss (worsens over time)

Describe lepromatous leprosy

Disseminated infection of the leprosy spectrum. Th2 response (humoral- IL4,5 and 10) since its now out of the macrophages. Typically systemic leprosy presentation. NEGATIVE lepromin skin test

Why does normal pressure hydrocephalus lead to "Wet, Wacky, and Wobbly"?

Distended ventriculi history the surrounding white matter that carries cortical afferent and efferent fibers (corona radiata). Ataxic gait and urinary incontinence occur due to traction on the sacral motor fibers that innervate the legs and bladder. Distention of the periventricular limbic system leads to the progressive dementia the occurs (reversible!)

Examples of proteins that can be detected via Southwestern blot?

Dna-Binding proteins that bind dsDNA Example = c-JUN and c-FOS, both of which are nuclear transcription factors that bind to DNA via a leucine zipper motif. They are both photo-oncogenes

Examples of Integrase Inhibitors for HIV? MOA?

DolutTEGRAVIR RaltTEGRAVIR "TEGRASE" Inhibits HIV DNA integration into host genome

Damage to inferior parietal lobe/cortex on dominant side? Non-dominant side?

Dominant side = Gerstmann Syndrome---right/left confusion, dysgraphia (can't write appropriately), dyscalculia (can't do math), and finger agnosia (can't recognize fingers). Non dominant = Contralateral heme-neglect syndrome with apraxia (disorder of motor planning)

Where are Dopamine, NE, and epinephrine each produced?

Dopamine and NE are produced by in CNS and PNS Epinephrine is only produced in the adrenal medulla

Low serum AFP and low unconjugated estriol in a quad screen. Also increased ß-hCG and increased inhibit A. What are you thinking?

Down syndrome

Which patients have an increased risk for ALL?

Down's syndrome, ataxia-telangiectasia, and NF-1

What can cause an abducens palsy due to increased ICP?

Downward displacement of brainstem (central herniation) due to nerve traction along the clivus

How is AC joint subluxated?

Downward force on tip of shoulder Clavicle gets displaced upward, no nerve deficits

Examples of X-linked Recessive diseases?

Duchenne and Becker Muscle Dystrophy Hemophilia G6PD Defiency

Briefly describe bilirubin metabolism. What gives bruises that nasty green color after a couple days?

Due to Heme oxygenate breaking down heme into biliverdin (green)

Why are pregnant women at an increased thrombotic risk? What is an ovarian vein thrombosis?

Due to Virchow's triad: 1. Stasis from pregnancy-related venous dilation and compression of IVC/iliac veins by gravid uterus 2. Hypercoaguable due to physiologic increase in factors 7, 8, 10 and vWF and fibrinogen (to protect from hemorrhage during miscarriage or birth) 3. Endothelial damage due to uterine infection or intrapartum vascular trauma Ovarian vein thrombosis is an example of septic pelvic thrombophlebitis, a complication that can occur via vaginal or cesarean silvery. Patients present with fever and localized abdominal pain one week after delivery and are usually hospitalized with a presumed uterine infection. When fever persists despite Abxs, a CT/MRI can confirm the presence of a thrombus in the ovarian vein

How does chronic alcoholism lead to chronic alcoholic pancreatitis?

Due to alcohol-induced secretion of protein rich-fluid in the pancreatic duct. These preinacious secretions can precipitate within the pancreatic ducts, forming *ductal plugs* that may *calcify*, causing obstruction which can cause exocrine insufficiency due to atrophy of the pancreatic acing cells and pancreatic fibrosis.

What is the difference between black and brown gall stones? How are they formed?

Due to conditions that increase the amount of unconjugated bilirubin in bile, which promotes calcium bilirubinate precipitation. Brown pigmented stones: Biliary tract infections (microbes producing *ß-glucuronidase* (deconjugates bile)). These are radiolucent Black stones: chronic hemolysis (sickle cell anemia, ß-thalassemia, hereditary spherocytosis) and increased enterohepatic cycling of bilirubin (ileal disease). These are radiopaque (appear on x-ray due to high amounts of calcium carbonates and phosphates)

Why do patients with multiple sclerosis feel even more fatigued with more neurological deficits after a hot shower?

Due to decreased axonal transmission associated with increased heat (heat sensitivity). May cause optic neuritis

Why does cirrhosis induce hyperestronism? Describe spider angiomata

Due to increased adrenal production of androstenedione with aromatization to estrone and eventual conversion to estradiol. Estradiol induces SHBG (primarily in liver, but also in uterus and testes), which results in increased testosterone binding and a decreased free testosterone/estrogen ratio. Spider angiomata are subQ vascular lesions consisting of a central arteriole surrounding by many smaller vessels that blanch on compression.

What is responsible for the green color of pus/sputum?

Due to neutrophilic MYELOPEROXIDASE in common bacterial infections. It is a blue-green-gene based pigment contained w/in the azurophilic granules of neutrophils and catalyzes the production of hypochlorous acid (aka bleach) from chloride and hydrogen peroxide during phagocytic respiratory burst

What is the ectropion?

Due to ongoing metaplasia, the locations of the Squamocolumnar junction (SCJ) and Transformation zone (TZ) differ at various stages of life. In adolescents, the TZ is on the exocervix and is called an Ectropion. The cervix shrinks with age due to decreasing estrogen and the TZ recess into the cervical canal.

Constrictive Pericarditis: Symptoms? What is see on jugular venous pressure tracing? What causes it?

Due to radiation therapy to the chest, cardiac surgery, and TB Presents as slowly progressive dyspnea, chronic edema, and ascites Will see a rapid y-descent that becomes both deeper and steeper during inspiration (its the rapid RA emptying when the tricuspid valve opens)

What GI malformation is associated with Downs Syndrome? What is seen clinically?

Duodenal atresia Bilious vomiting without abdominal dissension usually noted on the 1st day of life. Peristaltic waves may be visualized in the abdomen, also may have polyhydramnios

What activates trypsinogen?

Duodenal enterokinase in the duodenal lumen. Trypsin itself can also activate more trypsinogen

What is seen in the heart with Carcinoid syndrome?

Endocardial thickening and fibrosis of tricuspid and pulmonary valves since serotonin stimulates fibroblasts! Pulmonary vascular endothelial cells secrete MAO which inactivates serotonin. Can also see tricuspid regurg, right sided heart failure (ascites, peripheral edema) as well

How does vitamin K get into the body? Who is at risk of a vitamin K deficiency? How do you treat?

Endogenous colonic bacterial flora generate Vitamin K2 (menaquinones). Leafy green veggies are rich in Vitamin K1 (phylloquinone or phytonadione) Neonates have low Vitamin K stores due to poor tranplancental transfer, low content in breast milk, and lack of endogenous colonic bacterial flora. *Treat with IM Vitamin K at BIRTH! *******Children born at home is a BIG CLUE!!!

What cells release EPO?

Endothelial cells of the peritubular capillaries in the Renal cortex

How does thyroid uptake iodide? What drugs stop this?

Energy dependent (against concentration gradient) via sodium-iodide transporter at basolateral membrane Competitively Inhibited by the anions Perchlorate and Pertechnetate

MCC of UTI?

E. coli

What causes extramedullary hematopoiesis? Clinical fts of extramedullary hematopoiesis?

EPO stimulated, hyperpplastic marrow cell invasion of extramedullary organs (liver and spleen). Most frequently causes by severe chronic hemolytic anemias, such as ß-thalassemia. Extramedullary hematopoiesis causes a range of skeletal abnormalities. The expanding mass of progenitor cells in the bone marrow thins the boney cortex and impairs bone growth. Pathological fractures are common. Maxillary overgrowth and frontal bossing are associated with the classic "chipmunk facies" observed in the pediatric population.

Does P. aeruginosa cause otitis media or externa?

EXTERNA!

3 types of diabetic neuropathy?

Each caused by NEG (increased thickness, hyalinization, and narrowing of the walls of arteries) and sorbitol accumulation in nerves leading to osmotic stress

Heme synthesis pathway: Enzyme deficiencies in: Clinical fts in Early Steps? Clinical fts in Late Steps?

Early = Neuropsychiatric manifestations and abdominal pain; port-wine urine Late = PHOTOSENSITIVITY (due to accumulation of porphyrinogens that react with oxygen when excited by UV light), tea-colored urine

How would the internal/external genitals of a 46 XY patient with no functional Sertoli cells, but functional leydig cells, present

Early in gestation, the embryo his primitive/indifferent gonads. The presence of a Y chromosome induces the development of male gonads (testis). The SRY gene on the Y chromosome codes for Testis-determining factor (TDF) which causes this. The testis contain sertoli and leydig cells. Sertoli cells secrete mullerian-imhibiting factor (MIF), which causes the Mullerian (paramesonephric) ducts to involute. No sertoli cells = no MIF = persistence of the Mullerian duct. Leydig cells secrete testosterone which stimulates the mesonephric (Wolfian) duct to develop male internal genitalia. Testosterone is also converted to DHT, which induces male external genitalia! Thus, this fetus will have both female and male internal genitalia, but only male external genitalia!

What mutations are associated with an early onset Familial Alzheimer disease (onset <60)? Late onset familial Alzheimer?

Early onset: -APP (chromosome 21) -Presenillin 1 (Chromsome 14) -Presenillin 2 (chromosome 1) Late Onset: -ApoE4 *ApoE2 is protective! (increases ACh)

Examples of NNRTIs? MOA?

EfaVIrenz and NeVIRapine Allosteric Reverse Transcriptase inhibitor

Acute bacterial parotitis commonly occurs in who? What bug? how to diagnose?

Elderly post-op patients who are intubated or dehydrated Usually due to Staph aureus Diagnose with imaging and elevated serum amylase level (with a normal serum lipase level and no evidence of pancreatitis)

What does a loud/accentuated 2nd heart soul indicate?

Elevated Pulmonary Artery pressure (PAH).

What causes glaucoma? How is it diagnosed?

Elevated inctraocular pressure (IOP) due to increased production or decreased outlaw of aqueous humor Diagnostics: -Increased IOP -Abnormal visual field testing with decreased peripheral vision -Fundoscopic exam shows increased cup-to-disk ratio due to loss of ganglion cell axons

What does a deficiency of C1 complement leave a patient susceptible to?

Encapsulated bacteria SLE

What are the homeobox genes? What do they control? What is a disease that occurs if its mutated?

Encodes tsc factors known as homeodomain proteins, which modulate expression of other genes in the cell and guide the growth pattern of the embryo along the rostro-caudal, limb, and genital axes. HOXA13 is a homeobox gene mutated in hand-foot-genital syndrome, a rare AD condition characterized by malformations of the distal limbs, such as hypo plastic 1st digits, and mullerian fusion abnormalities (ie. uterus didelphys)

Why does expiration help hear left sided heart sounds like S3?

End of expiration make the sound more audible by decreasing lung volume and bringing the heart closer to the chest wall!

Waxy casts

End stage renal disease, chronic renal failure

Where is the endemic form of Burkit's lymphoma usually occurring? Non-endemic?

Endemic = African form: -Jaw or other facial bones Non-endemic = American form: -Pelvis or abdomen, specially near the ileo-cecal region

How is iodide taken up by the thyroid follicular cells? What stimulates this uptake? What inhibits it?

Energy dependent process carried out by a sodium-iodide symporter Stimulated by TSH Competitively inhibited by Perchlorate and Pertechnetate

How exactly does a strain of bacteria power efflux pumps that pump out the antibiotic in question?

Energy is derived from a proton gradient, pumping out hydrogen ions down its concentration gradient while simultaneously pumping out the antibiotic. Can also be due to sodium gradients or direct ATP expenditure in some cases.

Examples of fusion inhibitors for HIV? MOA?

Enfuvirtide- Inhibits HIV fusion with target cell membrane by binding to HIV gp41

How does tolcapone and entacapone treat parkinson disease?

Entacapone inhibits peripheral COMT, which is another enzyme that breaks down Levodopa. Tolcapone inhibits both peripheral and central COMT, but is associated with hepatotoxicity.

Eosinophilia, MPO-ANCA, wrist drop. Diagnosis?

Eosinophilic granulomatosis with polyangitis (Churg-Strauss)--- small-medium vessel vasculitis characterized by late-onset asthma, rhinosinusitis, and eosinophilia. Mononeuritis multiplex due to involvement of the epieneural vessels of peripheral nerves is common (ie. wrist drop due to radial nerve involvement)

Sputum findings in allergic asthma?

Eosinophils and Charcot-Leyden Crystals (contain eosinophil membrane protein). Eosinophils are recruited and activated by IL-5 secreted by Th2 type helper T-cells

Difference between Ephelides and solar lentigines?

Epheledines (freckles) = increased melanin production Solar lentigines = increased proliferation of melanocytes

What does the surface ectoderm give rise to?

Epidermis and its appendages, mammary glands (modified sweat glands- apocrine), lens of the eye, and adenohypophysis (ant. pituitary)

Faulty positioning of genital tubercle in a male in week 5 of development?

Epispadias

Too much acid produced by colonic bacteria causes bicarb to be released from where?

Epithelial cells of ILEUM (villi) and COLON (crypts)

What composes granulomas? How do they form?

Epithelioid cells (activated macrophages) and multinucleate giant cells. Macrophages present antigen to T cells and secrete IL-12, causing T cells to differentiate into Th1 type. Mature Th1 T cells secrete interferon-gamma to stimulate macros to try and kill the infection. Macrophages also release TNF-alpha, which helps recruit additional monocytes and macrophages

Newer aldosterone antagonist that produces fewer endocrine side effects, such as gynecomastia?

Eplerenone

Dopamine agonists used to treat Parkinson Disease. Ergot? Nonergot?

Ergot compounds (derived from ergot fungi) = Bromocriptine Nonergot compounds = Pramipexole and Ropinirole

Difference between erosions and ulcers?

Erosions = confined to the mucosa. can involve the muscularis mucosa, but it can not go through it! Ulcers = ca extend into the submucosa and muscularis propria (inner circumferential and out longitudinal smooth muscle layers)

Which 2 cells are the primary sites for heme synthesis?

Erythrocyte precursor cells in bone marrow (while they still have their mitochondria) Hepatocytes (heme is used in the microsomal cytochrome P450 system)

Estrogen (either via pregnancy or OCPs) effects on thyroid hormone regulation?

Estrogen increases the synthesis and sialyation of Thyroxine-Binding Globulin (TBG), leading to elevated TBG levels. A transient increase in TSH will lead to increased TH production, saturation of the increased TBG binding sites, and restoration of homeostasis. Therefore, an increase in TBG levels leads to an increase in total T4 (bound T4 plus free T4) as well as total T3. However the level of free TH remains normal, patients remain euthyroid, and TSH levels once again normalize!

Predominant circulating estrogen in menopause?

Estrone, produced outside of the ovaries (ovaries are not making estradiol anymore!)

How exactly does ethanol cause acute pancreatitis?

Ethanol induces pancreatic secretions with a high protein concentration and low fluid content. These secretions are prone to precipitate and form plugs that can obstruct the lumen of the pancreatic duct. Ethanol also causes spasms of the sphincter of Oddi and has direct toxic effect on the acinar cells.

Damage to the pudendal nerve. Common findings?

Fecal incontinence (loss of anal sphincter control) Decreased penile sensation (provides sensation to external genitalia) External urethral sphincter paralysis

Describe what happens when someone ingests anti-freeze. Note that this commonly occurs as suicide or alcoholics looking to get a fix

Ethylene glycol (antifreeze) is rapidly absorbed from the GI tract and metabolized to glycolic acid (toxic to Renal tubules) and oxalic acid, which precipitates as *calcium oxalate crystals* (most common come of renal stone). Pts initially present with signs of ethanol intoxication; signs of acute renal failure (oliguria, anorexia, flank pain) develop about 24-72 hours after ingestion. A high anion gap metabolic acidosis and osmolar gap are seen. Urinalysis will show tubular casts and oxalate crystals. Will see PCT necrosis (due to Acute tubular necrosis--- PCT ballooning and vacuolar degeneratoin)

Clinical presentation of somatostatinoma? Tx?

Excess somatostatin from pancreatic delta cell tumor causes abdominal pain, gallstones, constipation, hyperglycemia, and steatorrhea. This is all due to somatostatin-induced inhibition go insulin, glucagon, gastrin, secretin, and CCK, and inhibition of GI motility Tx= surgery with subsequent somatostatin analogues for symptom control

Insulin resistance is associated with what, which can be measured with a tape-measure

Excess visceral fat! Can be indirectly measured via waist circumference or wast-to-hip ratio >40inches in men and >35 inches in women gives higher risk for insulin resistance

What happens in osteoporosis?

Excessive bone resorption out of proportion to new bone formation with otherwise normal mineralization. It may affect both compact (dense, hard outer bone shell) and trabecular/cancellous (inner cancelous/spongy bone separated by interconnecting marrow spaces) bone.

What can lead to biotin deficiency? Type of enzyme that gets messed up?

Excessive raw egg white consumption (due to high levels of biotin-binding AVIDIN in egg whites, prevents absorption of biotin) Biotin = Vit B7--> Used by Carboxylase enzymes which transfer CO2 groups! (biotin is the carrier for CO2)

Explain the toxin in Staphylococcal Scalded Skin Syndrome (SSSS). What is basically a localized version of SSSS?

Exfoliative exotoxin is a protease that cleaves desmoglein in desmosomes, causing damage to the epidermis that has a positive Nikolsky's sign (skip slipping with gentle pressure). Bullous impetigo's a more localized form of SSSS with the bulla formation being another effect of the exfoliative toxin!

Femoral nerve roots? Optimal location of a femoral nerve block? Why?

Femoral Nerve = L2-L4 Inguinal crease at lateral border of femoral artery, before it passes under inguinal ligament and into femoral ring. Once it passes under inguinal ligament, it BRANCHES into anterior and posterior division!

Parts of the quad screen that correspond to the fetal levels (meaning if low, it can be due to suboptimal fetal tissue function)? Which are secreted by the placenta?

Fetus = AFP and unconjugated estriol Placenta = ß-hCG and Inhibin A

What gives elastin its elastic properties?

Extensive desmosine cross-linking between elastin monomers via lysyl oxidase (requires copper) gives it its rubber-like properties

What does the external jugular vein drain? Internal jugular vein?

External = scalp and portions of the lateral face Internal = brain and superficial face/neck

What does the external iliac artery supply? Internal Iliac artery?

External Iliac = Becomes femoral artery, supplies leg Internal Iliac = supplies pelvic organs

What types of cells are seen in Left sided heart failure?

Extravasation of RBCs into the alveoli causes alveolar hemorrhage. The RBCs are eventually phagocytksed by macrophages and the iron from Hb is converted into hemosiderin. These *Hemosiderin-Laden Macrophages* (aka Heart failure cells or siderophages) will stain positive for *Prussian Blue Stain!

Hereditary fructose intolerance versus Classic galactosemia?

FAB - GUT Fructose-1-P, Aldolase B Galactose-1-P, Uridyl Transferase

How do you calculate the FF?

FF = GFR/RPF ***RPF = Renal PLASMA Flow, NOT renal BLOOD Flow In order to get RPF from RBF, must multiply: RPF = RBF * (1-Hematocrit)

What does filtration fraction equal? What is it in a normal healthy individual?

FF = GFR/RPF Its the portion of Renal plasma flow that is filtered from the glomerular capillaries into Bowman's space! *normally 20%

X-linked Recessive Lysosomal Storage Diseases

Fabry's and Hunters

Factors needed for H. influenza to be plated? What is the "satellite" phenomenon that can also be used?

Factor V= NAD+ Factor X = Hematin (hema"ten") Can grow Staph aureus on Sheep blood agar, and the H. influenza will grow around the ß-hemolytic S. aureus because it secretes NAD+ into the medium and the hemolysis facilitates the release of hematin!

What is Kallman's Syndrome? How does it occur? Clinical features?

Failure of GnRH-secreting neurons to migrate from their origin in the olfactory placed (outside the CNS) to their normal location in the hypothalamus. Usually do to a mutation in the KAL-1 gene or FGF Receptor-1 gene, which code for proteins required for this migration. Pts present with central hypogonadism (delayed puberty) and ANOSMIA. Pts can also have other midline defects, such as cleft lip/palate

How does an imperforate anus present? What most commonly accompanies an imperforate anus?

Failure to pass the meconium, or passage of meconium through urethra or vagina if fistulas are present Usually associated with Genitourinary tract anomalies, such as renal agenesis, hypospadias, epispadius, and bladder extrosohphy. *VACTERL syndrome also less commonly occurs

Most common site for ectopic pregnancy? Presentation?

Fallopian tube (extrauterine blastocyst implantation) Will have amenorrhea, positive beta-HCG, and +/- lower abdominal pain

Why can't woman with previous PID get pregnant?

Fallopian tube scarring/occlusion, loss of ciliary action, and subsequent infertility

Malingering: key fts?

Falsification or exaggeration of symptoms to obtain external incentives (like get out of work) *CONSCIOUSLY creates symptoms for secondary (external) gain

Function of integrins?

Family of transmembrane protein receptors that interact with the ECM by binding to specific proteins (collagen, fibronectin, and laminin). Plays a role in cellular adhesion. Can be disrupted by cancer cells to promote metastasis

How would you stain a fat emboli in the pulmonary vasculature? What would it look like?

Fat emboli stain black with osmium tetroxide

MCC of death in a lightning strike?

Fatal arrhythmias and respiratory failure

Clinical fts of cholestasis? Causes?

Fatigue, pruritus, hepatomegaly, and elevated Alkaline phosphatase. Chronic can lead to fat malabsorption (including vitamins ADEK)

Rate limiting enzyme in Fatty Acid Synthesis? Degradation?

Fatty Acid Synthesis = Acetyl CoA Carboxylase Degradation/ß-Oxidation (breaking FFAs down so you can make ketone bodies or throw them right into the TCA cycle) = *Acetyl CoA Dehydrogenase*

Illness anxiety Disorder: key fts?

Fear of having a serious illness despite few or no symptoms and consistently negative evaluations *Illness production and motivation are of UNCONSCIOUS drives

Classic triad of bacterial meningitis? What leads to it?

Fever, stiff neck, and altered mentation Inflammatory cytokines (IL-1,6) increase, leading to fever, inflammation, and injury to the BBB. Continued injury can cause vasogenic brain edema, decreased cerebrovascular autoregulaiton, and increased ICP. Patients can eventually develop severe and generalized headache, stiff neck, photophobia, and altered mentation!

Why is myopathy increased when statins are combined with fibrates (gemfibrozil)?

Fibrates impair the hepatic clearance of statins and lead to excessive blood levels of statins ---> myopathy increased

Function of Fibrillin-1? Disease where its dysfunctional?

Fibrillin-1 is a major component of microfibrils that forma sheath around elastin fibers. Microfibrils are abundant in blood vessels (aortic media), periosteum, and the suspensory ligaments of the lens. Fibrillar in the extracellular space acts as a scaffold for deposition of elastin extruded from connective tissue cells. Defects in fibrillar-1 cause technical weakening in the connective tissues and abnormal activation of TGF-ß. Marfan syndrome is an AD defect in fibrillin-1 gene. Cause of death is usually CV related (aortic root dilation, dissection, and rupture)

Presentation of fibromyalgia? Dermatomyositis? Polymyalgia Rheumatica?

Fibromyalgia = MSK pain and fatigue Dermatomyositis = B/L proximal muscle weakness Polymyalgia rheumatica = Pain and stiffness in shoulders/hips

In postmenopausal osteoporosis, which type of bone if affected first?

First cancellous/trabecular (compression factors) Then with advancing age = cortical bone (hip fracture)

Treatment for P. vivax and ovale?

First, treat with chloroquine if its not resistant to it yet (most are). If resistant, use mefloquine. Can also use atovoquone-progaunil. Since these 2 species ha shypnozoites dormant in liver, must also use primaquine to penetrate this and kill those suckers.

What causes pulsus parvus et tardus

Fixed LV outflow tract obstruction (eg, valvular aortic stenosis) Palpable as a slow-rising, low amplitude pulse due to diminished SV (pulsus parvus) and prolonged LV ejection time (pulsus tardus)

Contents of carpel tunnel? What do you cut to fix carpel tunnel syndrome?

Flexor digitorum profundus tendons (4) Flexor digitorum superficialis (4) Flexor Policus Longus (1) Median Nerve (1) Longitudinal incision is made through the transverse carpal ligament (flexor retinaculum) to relieve the pressure

Treatment given with amphotericin B for cryptococcal infections? How does it work?

Flucocytosine is a fluorinated analogue of cytosine. It is converted by a fungus-specific cytosine deaminase to 5-fluorouracil (5-FU). 5-FU causes RNA miscoding and inhibition of DNA synthesis

Describe endometrium in secretory phase

Fluffy Glands increase in size and become more coiled, and the cells lining the glands acquire large cytoplasmic vacuoles. Glycogen rich mucin is released into glandular lumens. The stroma becomes increasingly EDEMATOUS, and the prominent tortuous spiral arteries extend to the ENDOMETRIAL SURFACE! (from the deeper layer all the way to the uterine lumen)

How does heart failure lead to orthopnea?

Fluid backs up into lungs, and hydrostatic pressure causes transudation of fluid from the pulmonary capillaries into the lung *interstitium*. Fluid in interstitial causes swelling of the affected tissue, increasing resistance to movement (DECREASING lung compliance). Results in poor gas exchange and shortness of breath

What is a bursa? How are they injured? How does injury present?

Fluid filled sac that serves to alleviate pressure from bony prominences and reduce friction between muscles and tendons. Acute trauma or chronic repetitive use can cause injury, leading to localized pain and tenderness on activate motion testing, NOT PASSIVE MOTION TESTING

Describe Pancreatic bicarb secretion after prolonged stimulation with secretin

Fluid of pancreas is alkalinized via the action of a Chloride/bicarb ion exchange protein. So as more bicarb is secreted in, more chloride is reabsorbed

Tx for Tourettes?

Fluphenazine (dopamine antagonist) its a high potency antipsychotic

Components of Prenatal vitamins (PNVs)? What purpose do they serve?

Folic acid = NT defects Iron = Hb synthesis Calcium = Bone growth Iodine = thyroid function

MOA of methotrexate? How do you reverse it? Why does this work?

Folinic analogue that inhibits Hihydrofolate Reductase (DHFR). Used as chemo by inhibition of DNA synthesis and anti-psoriasis agent through immunomodulatory effects on activated T cells. Reversed via Reduced form of Folinic Acid (LEUCOVORIN) if given early. Rescues the negative side effects of GI, mucous and bone marrow suppression *Leucovorin also potentiates the effects of 5-FU by binding thymidylate synthetase

Most common indolent NHL? Who does it mainly infect?

Follicular Lymphoma Adults

What causes atheroembolic disease? What can it lead to?

Following a invasive vascular procedure, cholesterol containing debris gets dislodged from the larger arteries and lodges in smaller vessels, leading to signs of embolism (blue toe, livedo reticularis). Results in ischemia of corresponding organs/tissues w/in a few days to weeks. Acute Kidney Injury is most common injury, most commonly seen in patients with preexisting renal atherosclerosis. However, since the emboli are so small, they wedge deep into the smaller arcuate or intralobular lobular arteries (no flank pain or hematuria noted). Note- cholesterol is dissolved during tissue preparation for microscopic evaluation, leaving needle-shaped clefts in its wake

Describe the wacky life cycle of HBV

Following virion entry and nuclear import, the (repaired) ds-circular DNA serves as a template for transcription into an intermediate +single-stranded RNA. This RNA strand in turn serves as a template for both translation of viral proteins (including a polymerase/reverse transcriptase) and reverse transcription into a ssDNA intermediate, converted back into partially dsDNA.

Why can blood type O mothers cause hemolytic disease of the newborn if the child is A, B, or AB?

For some reason, in a type O mom, she makes anti-A and anti-B *IgG* Abs that can cross the placenta! Can occur in 1st pregnancy (in contrast with Rh disease) (usually people make ant-A or Anti-B IgM Abs that normally can't cross the placenta)

What is the levator ani? What muscles make it up? What can happen if injury occurs to levator ani?

Forms the pelvic floor/diaphragm (with the coccygeus), which is a U-shaped sling around the pelvic viscera, helping to hold the bladder and urethra in appropriate anatomical position. Made of iliococcygeus, pubococcygeus, and puborectalis Injury results in urethral hyper mobility and/or pelvic organ prolapse (ie. cystocele) --- Treat with Kegel exercises to strengthen levator ani muscles!!!

Where is alkaline phosphatase found? Conditions its elevated in? How do you differentiate between the different main forms?

Found in bone, liver, bile ducts, and placenta Elevated in biliary conditions, bone disease (osteomalacia), and leukemia/lymphoma Bone and liver ALP can be differentiated via electrophoresis, monoclonal Abs, and heat denaturation (bone = boil, breaks down in heat)

What does myeloperoxidase do? What will NBT test or DHR test show in myeloperoxidase deficiency?

Found in neutrophilic azurophilic granules that catalyzes the production of bleach (hypochlorite) from hydrogen peroxide and chloride DHR and NBT tests will be normal since NADPH oxidase in fine!

Male with long narrow face, prominent forehead and chain, large testes, hyper laxity of joints?

Fragile X Syndrome

Describe what happens to B cell on exposure to antigens

Frist exposed to antigen in lymphoid organs and peripheral tissues.On first exposure, a clone of B cells become activated. Some activated B-cells become activated into short lived plasma B cells and begin spitting out IgM (independent of T cells). However, most activated B cells migrate to lymphoid follicles located in the lymph node *CORTEX* where they form *Germinal centers* that are the site of B cell proliferation during the immune response. A portion of these activated B cells form dormant long lived memory B cells, but most become Ab-secreting plasma cells.

What is Pick's Disease?

Frontotemporal dementia Characterized by degeneration of the frontal lobes that eventually progresses to include the temporal lobes. Symptoms include *EARLY personality and behavioral changes* (ie. disinhibition, apathy, social inappropriateness, compulsive disorders) and altered speech patterns. Neurocognitive deficits occur LATER in the course (opposite of Alzheimers)

Essential Fructosuria: enzyme?

Fructokinase

What is AV nicking a sign of?

Fundoscopic finding of chronic HTN. Its an early manifestation of retinopathy in patients with years of HTN due to exudative vascular changes, a consequence of endothelial necrosis.

Explain how G cells cause gastric acid release

G cells release gastrin, which stimulate Enterochromaffin-like cells (ECLs) to release histamine, which bind to H2 receptors (Gq), increasing cAMP, stimulating the H+/K+ ATPase

Does TSH, LH, and FSH bind to cytoplasmic or PM protein receptors? Describe the receptor it binds to:

G-proten couples receptors in PM Contains alpha helices with hydrophobic AA's that anchor within the PM.

Why do patients with G6PD deficiency get hemolysis?

G6PD is an enzyme of the pentose phosphate pathway that in RBCs is essential for maintaining adequate levels of NADPH. Insufficient NADPH results in the inability to maintain glutathione in a reduced state, leaving the RBCs susceptible to oxidative stress which manifests with hemolysis

Mutations induced by aflatoxin? What can it cause?

G:C to T:A transversion in codon 249 of the p53 gene *Leads to Hepatocellular Carcinoma!

How does baclofen treat muscle spasticity?

GABA-B agonsit

How does GH work?

GH is secreted by the anterior pituitary and directly acts on tissues to increase insulin resistance, fat utilization, and protein synthesis *** GH's growth-promoting effects are due to IGF-1, which is released from the LIVER following stimulation of hepatic GH receptors via the JAK-STAT pathway

Side effects of metronidazole?

GI disturbances Neurologic Disulfiram-like Rxn when combined with EtOH

Function of Glucose-like-peptide-1 (GLP-1)? Drug that is exogenous version of this?

GLP-1 is secreted by intestinal L cells in response to food intake and regulates glucose by decreasing gastric emptying and increasing insulin release Exentanide is an example of a long acting GLP-1 agonist

Describe GLUT 1-5

GLUT 1: basal glucose transport in RBCs and BBB GLUT 2: hepatocytes, pancreatic ß cells and basolateral membrane of renal tubules and small intestinal mucosa. Plays a role in absorption of dietary glucose, reabsorption of glucose from renal tubules, hepatic glucose regulation, and sensitivity of ß cells to circulating glucose GLUT 3: placental and neuronal glucose transport GLUT 4: Skeletal muscle and adipose *insulin sensitive* GLUT 5: fructose transporter found in spermatocytes and GI tract

Histology/Symptoms of Giant cell Arteritis

GRANULOMATOUS inflammation centerred on the media with intimal thickening, elastic lamina fragmentation and giant cell formation fever, fatigue, malaise, wt loss Headache JAW CLAUDICATION visual disturbances (ischemic optic neuropathy) Polymyalgia Rheumatica

Why does Tb affect the lower lobes in a primary infection?

GRVAITY! The larger droplets get trapped in the larger upper airways (trachea and bronchi) and are expelled via the mucociliary elevator. The smaller droplets get all the way down to the alveoli in the lower loves due to gravity. They are then phagocytksed by alveolar macrophages and subsequently replicate inside them!

Splenic vein thrombosis can lead to what?

Gastric varices in fundus of stomach

What is Zollinger-Ellison Syndrome (ZES)

Gastrin-secreting tumors (gastrinomas) that are often malignant and in the small intestine or pancreas. Gastrin causes parietal cell hyperplasia and stimulates gastric acid secretion, resulting in peptic ulcers and heart burn/

What negative outcome can a gastric bypass result in?

Gastro-jejunal anastomosis Can lead to SIBO- small intestinal bacterial overgrowth (in gastric-duodenal sectional this is bypassed). ***SIBO can result in overproduction of FOLATE and VITAMIN K since normal enteric bacteria usually produce this! ***Can also result in cobalamin deficiency due to decreased absorption of both free and IF-bound Vitamin B12. (the bacteria itself can also overutilize the Vitamin B12) ***other stuff as well (other card)

What causes the initial insult in Paget's Disease of the bone?

Gene mutations cause excessive RANK signaling and NF-kß activation--? increased osteoclast activation

Thiopental MOA? Uses?

General IV anesthetic that is a short-acting barbiturate that increases GABA inhibitory potential. Used for induction of asthenia, which is then maintained with an inhaled anesthetic

Galactokinase Deficiency symptoms

Generally benign, but with infantile cataracts

What is Williams Syndrome?

Genetic disorder characterized with "elfin" facies, supravalvular aortic stenosis, and an extroverted personality

What is Treacher-Collins Syndrome (TCS)? Pathophysiology? Clinical presentation?

Genetic disorder resulting in abnormal development of 1st and 2nd pharyngeal arches 1st pharyngeal arch= Trigeminal nerve (CN V)--- *M* -Bones: maxilla, zygoma, mandible, incus and malleus -Muscles: Muscles of mastication 2nd Pharyngeal arch= Facial nerve (CN VII)--- *S* -Bones: styloid process of temporal bone, lesser horn of hyoid, and Stapes -Muscles: Facial expression Present with airway compromise, feeding difficulties, and profound conductive hearing loss (no ossicles)

Most important factor in differing bone mass between 2 women of the same age?

Genetics (Africans have higher bone mass, less likely to fracture)

Nerve involved in cremasteric reflex? What can cause loss of this reflex?

Genitofemoral nerve (L1-L2) Loss of reflex = testicular torsion

Describe the diagnostic requirements for preeclampsia. Pathophysiology?

Gestational HTN (>140/90 after 20 weeks) with either Proteinuria or signs of end organ damage Due to abnormal placentation. Abnormal placental vasculature leads to placental hypoxia and ischemia, which in turn results in the release of antiangiogenic factors into maternal circulation. The release of these inflammatory factors from the hypoxic placenta causes endothelial injury. Damage to the endothelium increases its permeability, resulting in proteinuria. In addition, dysregulation of vascular tone results in elevated BP, which in turn can cause end organ damage (headaches, visual changes, abdominal pain due to liver, etc.)

Most common enteric parasite in US/Canada?

Giardia

How do you diagnose plasmodium infections?

Giemsa stain

Most commonly dislocated joint in body? Why? How does it dislocate? What nerve is damaged?

Glenohumeral joint, due to shallow articulation between humeral head ad glenoid fossa of scapula Usually dislocated Anteriorly damaging the Axillary nerve

What is the MC brain tumor in adults? Describe it

Glioblastoma Multiforme (Grade 4 Astrocytoma)

Which sulfonyurea carries the least risk of hypoglycemia?

Glipizide! (think of the short-zig-zagging swan in the sketchy). All other 2nd generation sulfonylureas (ie. glyburide) have a long duration of action and carry an increased risk for hypoglycemia!

Earliest morphological change of Diabetic Nephropathy?

Glomerular Basement Membrane Thickening with resultant mesangial matrix expansion!

Disease that presents with IgG4 Auto-Abs to PLA2R (Phospholipase A2 receptor)?

Glomerulonephritis, especially Membranous Nephropathy

Acetal-CoA is an allosteric activator of which metabolic process?

Gluconeogenesis (activates Pyruvate carboxylase)

Describe the mutation seen in HbC disease

Glutamic Acid (negative) --> lysine (basic = positive--- moves less) on beta chain

How is glycogen broken down? What regulates this enzyme?

Glycogen Phosphorylase Activated by Phosphorylase Kinase

Describe how the H. influenza type B vaccine and the Pertussis vaccine are both modified in order to stimulate T-cell dependent immunity?

H. influenze type B = polysaccharide conjugated with diphtheria toxoid Pertussis: purified components of Bordatella pertussis and detoxified pertussis toxin (toxoid)

Explain how glycogenolysis occurs. Names/ inheritance patterns of the diseases?

Glycogen phosphorylase (myophoshphorylase in muscle) shortens the glycogen chains by cleaving alpha-1,4-glycosidic linkages between glucose residues, liberating glucose-1-P in the process. This occurs until *4* residues remain before a branch point (the "limit" dextrin). At this point, the deb ranching enzyme preforms 2 enzymatic functions: 1. Glucosyltransferase cleaves the 3 outer glucose resides f the 4 that are left by glycogen phosphorylase and transfers them to a nearby branch 2. The enzyme alpha-1,6-glucosidase removes the single remaining branch reside, producing free glucose and a linear glycogen chain that can be further shortened by glycogen phosphorylase! *"Very Poor Carbohydrate Metabolism" Von Gierkes = Type I Pompe = Type II Cori = Type III McArdle = Type V **All are AR

How is glycogen broken down? How does this enzyme become active?

Glycogen phosphorylase breaks it down. This enzyme needs to be phosphorylates to be active, and epinephrine does this by increasing cAMP (and PKA). Non-phosphorylation dependent activation of glycogen phosphorylase occurs in extreme situations via Calcium or AMP

Explain how Pompe disease can cause problems

Glycogen storage disease type II---deficiency in acid alpha-glucosidase (acid maltase)-- breaks down glycogen w/in acidic environment of lysosome Although most glycogen is degraded in the cytoplasm, some is inadvertently engulfed by lysosomes, especially in cells with high amounts of glycogen (hepatocytes and myocytes). As such, deficiency in acid maltase results in pathologic accumulation of glycogen w/in liver and muscle lysosomes. Cardiac and skeletal muscle are particularly susceptible, as the ballooning lysosomes interferer with contractile function!!!

What si Periodic Acid-Schiff (PAS) used to detect? How does it work?

Glycoprotein in the cell walls of Tropheryma Whipplei magenta! Note- These glycoproteins are diastase resistance, which helps determine the bacteria from normal glycogen in the body that stain positive for PAS, such as skin, liver, skeletal muscle, etc.

Does prolactin inhibit GnRH or both LH and FSH?

GnRH! (duh! makes more sense to inhibit 1 rather than 2!)

What are the 3 disaccharides? What are they broken down into?

Go Grand Ma! Go Father Son! Go Good Luck!

Describe the course of the ureters in regards to the arterial vessels that are around that area

Gonadal artery/vein cross anterior to the ureters (water under the bridge). The ureters then gain excess to the pelvis by crossing over the anterior surface of the common iliac artery near its bifurcation. At this point, the ureter lies medial to the ovarian vessels and anterior to the internal iliac artery!

Gain of function mutation in PRPP synthetase. What are you concerned about?

Gout! PRPP synthetase increases production of purines, which will also increase the degradation of purines, leading to hyperuricemia!

Normal flora of vagina? pH? What can disrupt this? What does it lead to?

Gram positive lactobacilli with a pH of 3.8-4.5 Can be disrupted by Abxs, High estrogen levels (pregnancy), Steroids, DM, and immunosuppression Can lead to Candida vaginitis if disrupted ***pH is not disrupted though!

What is CD15 a marker for

Granulocytes and Reed Sternberg Cells (Hodgkin Lymphoma)

What is the body's reaction to a foreign body, such as retained sutures?

Granulomatous response, seen clinically as a tender, erythematous brown or purple papule, nodule or plaque.

What is endometrial hyperplasia? How does it present?

Greater increase in endometrial glands compared to stroma (usually due to excessive estrogen stimulation) Presents with irregular but NON-painful menstrual bleeding

Patient presents with Meconium Ileus. What is it? What disease is it associated with?

Green inspissated (thickened via dehydration) mass (dehydrated meconium) in the distal ileum in a neonate. Associated with Cystic Fibrosis. Abnormalities in chloride, sodium, and water transport by the ductal epithelium of intestinal mucous glands cause isotonic dehydration of the lumen contents, causing the secretion of abnormally viscous mucus into the bowel!

Beta hemolytic organisms?

Group B step (step agalactiae) and Listeria monocytogenes

What are Chiari malformations? Describe I versus II

Group of congenital disorders caused by underdevelopment of the posterior fossa. Small size of the fossa causes parts of the cerebellum and medulla to herniate through the foramen magnum. Chiari I: MC and more benign; low-lying cerebellar tonsils that extend below foramen magnum and into vertebral canal. Pts will have paroxysmal occipital headaches (meningeal herniation) and cerebellar dysfunctions (dizziness, ataxia) due to compression of cerebellar tonsils. Can be associated with syringomelia. Chiari II: more severe, seen in neonates. Downward displacement of cerebellum (vermis, tonsils) and medulla through foramen magnum. *Non-communicating hydrocephalus* almost always occurs due to aqueductal stenosis . Compression of medulla can cause dysphagia, stridor, and apnea. Patients may have associated lumbosacral myelomeningocele (leading to lower limb paralysis).

How exactly does H. pylori lead to duodenal ulcers?

H pylori gets in antrum of stomach, is acid labile but can't be killed because of mucus layer and urease production. H pylori injures the gastric epithelial cells, causing local inflammation, causing astral gastritis. This chronic inflammation leads to a decrease in the number or *somatostatin-producing cells (delta cells)*. Somatostatin normally inhibits gastrin release High gastrin both directly (via cholecystokinin B receptors) and indirectly (histamine release from entrerochromaffin-like cells) increases hydrogen ion secretion from parietal cells Extremely acidic gastric fluid can't be neutralized by duodenal bicarb production, leading to duodenal ulceration and duodenal gastric metaplasia!

How does chlorthalidone lead to hypokalemia and metabolic alkalosis?

Its a thiazide! Decreased intravascular volume stimulates aldosterone release, which causes potassium and hydrogen ion excretion

How does a H. pylori infection lead to ulcers?

H. pylori is associated with chronic astral-predominant gastritis, which may lead to a reduction in the somatostatin-[producing delta cells! Lack of inhibition by somatostatin leads to uncontrolled hypergastrin secretion and proximal duodenal ulcer formation.

What tumors have increase serum alpha-fetoprotein (AFP)

HCC Ovarian germ cell tumors (eg. endodermal sinus tumor/yolk sac tumor, which have Schiller-Duval bodies which resemble primitive glomeruli!)

Describe HDV. Is it worse with confection or superinfection?

HDV = negative sense RNA virus Often referred to as the delta agent, hepatitis D virus is a double shelled particle that resembles the Dane particle of HBV. The internal polypeptide assembly of HDV is designated hepatitis D antigen. Associated with this antigen is a very short, circular molecule of single-stranded RNA. HDAg is considered replication defective as it *must be coated by the external coat HBsAg of HBV in order to penetrate the hepatocyte.* Basically, HDV requires the presence of replicating Hepatitis B virus to supply HbsAg, the envelope protein for HDV! Superinfection of a chronic HBV carrier is WORSE!

What is HER2? What cancer is it found in? Tx against it?

HER2 (aka ERBB2) is a transmembrane glycoprotein with tyrosine kinase activity Over expressed in 20% of breast cancers and in adenocarcinomas of the ovary, stomach, lung and salivary glands. Trastuzumab is directed against it

Where does metastatic calcification like to occur?

HIGH BLOOD CALCIUM LEVELS, normal tissues Occurs more often in alkaline tissues involved in acid secretion, such as the kidneys, lungs, systemic arteries, and gastric mucousa

Do high or low doss of Nitrates cause a decrease in after load?

HIGH! Low dose only preferentially dilates veins > arteries

How exactly does HIV gain entry into cells? What renders some people resistant to HIV infection?

HIV virus uses CD4 Receptor as primary receptor, and CCR5 as the co-receptor. Both are bound by HIV's outer envelope protein gp120, which then promotes viral fusion. Pts with homozygous deletion for CCR5 are resistant to HIV infection because it can't get into T cells!

What components of each virus bind to what components of host cells? -HIV -EBV -Parvovirus B19

HIV: gp120, gp41 bind CD4 on T cells EBV: gp350 binds CD21 Parvovirus B19: binds erythrocyte P antigen (all erythroid cells express this, especially immature cells)

Pathophysiology of an aortic dissection. Difference between Stanford Type A and B?

HTN is the PRIMARY risk factory. In pts with longstanding HTN, there is medial hypertrophy of the aortic vasa vasorum, and consequently, reduced blood flow to the tunica media or the aorta. This can cause medial degeneration with a loss of smooth muscle cells, leading to an aortic enlargement and increased wall stiffness. Both of these changes exacerbate aortic wall stress, which is already increased due to the HTN itself. This synergistic increase in aortic wall stress greatly increases the risk of intimal tearing. A = Involving the Ascending Aorta B = Confined to descending aorta and/or aortic arch, but NOT THE ASCENDING AORTA

What is aldosterone escape in the context of Conn syndrome?

HTN leads to pressure natriuresis, increased ANP, and sodium lost, "escaping" the effects of aldosterone!

Only 2 STIs that are painful?

Haemophilus ducreyi and HSV 1 and 2

Most common pathogen to cause acute epiglottis? How is it normally prevented?

Haemophilus influenza -- cherry red epiglottis that can present with drooling Vaccine against H. influenza type B (HiB) capsule (PRP) is given to children between 2-18 months. It is a polysaccharide conjugated to the diphtheria toxoid.

MOA of PCP? Clinical symptoms?

Hallucinogen that works primarily as a NMDA receptor ANTAGONIST. Also inhibits the reuptake of norepinephrine, dopamine, and serotonin, maybe even some acton at sigma opioid receptors. Causes dissociative symtoms, maybe anger and stuff. Will see VERTICAL and horizontal nystagmus

Most common benign lung tumor? Describe it

Hamartoma (disorganized growth of normal tissue in native location). Asymptomatic, peripherally located "coin lesions/popcorn calcifications" in pts 50-60 yrs old. Composed of disorganized Hyaline cartilage, fibrous, and adipose tissue

Hamartoma versus choristoma

Hamartoma = disorganized growth of normal tissues in their native locations Choristoma = normal tissue in a foreign location (ie. Meckel's diverticulum)

Describe Vitamin K

Hard to get severe vitamin K deficiency since bacteria in large intestine normally produce functional forms of Vitamin K!

What do you find on clinical exam of hypertrophic cardiomyopathy?

Harsh crescendo-decrescendo systolic murmur at the apex and left lower sternal border. Note-- Systolic anterior motion of the mitral valve toward the inter ventricular septum can cause eccentric mitral regurg and exacerbate LVOT obstruction

What is the Hawthorne effect? Pygmalion effect?

Hawthorne = subjects change their behavior when they know they are being studied Pygmalion = a researcher's beliefs in the efficacy of treatment can potentially affect the outcome (ie. students with randomly assigned high IQ scores did better bc teachers gave them unconscious special treatment)

What does Hb electrophoresis show in Sickle cell disease?

HbS moves slower/not as much due to replacement of glutamic acid with valine

Mutation in Sickle Cell Disease?

HbS point mutation in BETA chain causes AA replacement from Glutamic Acid (negative) to Valine (neutral). ***Hydrophilic to hydrophobic molecule causes aggregation of Hb molecules (in anoxic conditions) and subsequent RBC sickling (distortion and inflexibility)!!!

What causes a heat stroke? How do you treat?

Heat stroke is a condition in which the hypothalamic thermoregulatory set point is normal but heat production exceeds heat dissipation, is generally caused by environmental exposure (children in hot cars). Above 42.2 C (108 F) causes oxidative phosphorylation to cease and ATP becomes rapidly depleted, leading to end organ damage. Patient should be rehydrated and rapidly cooled

What is seen in the blood of patients with G6PD?

Heinz bodies form in RBCs -- dark irregular purple granules -*They are insoluble denatured Hb Leads to BITE CELLS when splenic macrophage/monocyte system tries to eat this Heinz Bodies

Describe the vaccine against Haemophilus influenza

Helps protect against epiglottis and meningitis Vaccine is against type B capsule (opposite of N. meningitidis). The type B capsule is immunogenic and composed off a linear polymer composed of ribose, ribitol, and phosphate referee to as PRP. Abs against PRP facilitate complement-dependent phagocytosis and killing through opsonization. Its also usually conjugate to Diphtheria toxoid First dose is given o infants at 2 months, second usually at 18 months.

How do interferons alpha and ß (Type I) help the host stop the viral infection?

Helps synthesize enzymes tat halt protein synthesis. These enzyme become active only in the presence of dsRNA, which forms in infected cells as a result of viral replication (gives selectivity!) Also increases MHC Class I expression on all cells, increases activity of NK cells and cytotoxic T cells.

Patient has erythrocytosis/polycythemia. What is erythrocytosis defined as? How do you distinguish between absolute virus regular erythrocytosis?

Hematocrit level >52% in men, >48% in women. Absolute = true increase in RBC mass Relative = Decrease in the plasma volume 1. Absolute versus relative erythrocytosis: -Measure RBC mass (normal in relative) 2. Primary verus secondary Erythrocytosis: -Use EPO levels to differentiate -Low EPO = Primary (myeloproliferate disorder such as polycythemia vera causes expansion of all 3 cell lines) -High EPO = Secondary due to chronic hypoxia or EPO secreting tumors/kidney 3. Hypoxic versus other causes of secondary erythrocytosis: -Measure of arterial O2 saturation (SaO2)-- helps exclude hypoxia -SaO2 <92% (PaO2<65 mmHg) = hypoxic!

Where does osteomyelitis normally occur in children? How does this occur?

Hematogenous osteomyelitis normally affects boys, and it infects the metaphysis of long bones, as this region contains slow-flowing, sinusoidal vasculature that is conductive to microbial passage. Adults are less likely to get hematogenous osteomyelitis in long bones due to changes associated with epiphyseal closure. They usually get hematogenous osteomyelitis of the vertebral body! Hematogenous osteomyelitis begins with a seeding event that causes an acute cellulitis of the bone marrow. The resulting inflammation within the confined boney space leads to increased intrameddulary pressure, which compromises blood flow and forces infectious exudate through vascular channels into the cortex and periosteal region. Disruption of the periosteal blood supply further contributes to bone ischemia, leading to necrosis. W/o tx, the infection can progress to chronic supportive osteomyelitis, where necrotic bone (sequestrum) serves as a reservoir for infection and becomes covered by a poorly constructed shell of new bone called an involcrum. One or more sinus tracts develop to drain the purulent material into soft tissue or out to skin surface. Tx includes Abxs and debridement of necrotic bone!

What causes the hematologic abnormalities in patients with lupus? What about the renal abnormalities?

Hematologic = Type II hypersensitivity. Anemia is caused by autoimmune hemolysis, which develops due to the formation of warm IgG Abs against RBCs (spherocytes, Positive Coombs, extravascular hemolysis). SLE-thrombocytopenia can occur, which is essentially the same as idiopathic thrombocytopenia purpura (Abs formed against platelets causing their destruction). Same can happen of neutrophils Renal = Type III Hypersensitivity. Immune complex deposition in the mesangium, sub endothelial, and/or sup epithelial space causes lupus nephritis (usually diffuse proliferative glomerulonephritis)

What is the Battle Sign?

Hematomas over the mastoid process (battle sign), along with periorbital ecchymosis and clear otorrhea are signs of basilar skull fractures *CSF fluid is leaking out and causing the otorrhea!

Aplastic Anemia: Pathogenesis? Cause? Clinical findings?

Hematopoietic Stem cell deficiency (CD34+) Due to autoimmune, infections (parvovirus B19, EBV), and drugs (carbemazapine, chloramphenicol, sulfonamides, radiation) Will see pancytopenia

Clinical manifestation of hereditary spherocytosis?

Hemolytic anemia Jaundice (inc RBC destruction = greater bilirubin production) Splenomegaly (sperocytes have rough time passing through the cords of Billroth and accumulate in the spleen) *Infections can trigger hemolysis episode!

Whom does intracellular hemosiderin accumulation normally affect?

Hemolytic anemia or frequent blood transfusions

What are the histological findings of hepatitis B in the liver? Hepatitis C?

Hep B = Hepatocyte cytoplasm fills with HBV Surface antigen inclusions, which have a finely granular, dull eosinophilic "ground glass" appearance Hep C = lymphoid aggregates w/in portal tracts and focal areas of macro vesicular steatosis

How do you prevent mother-to-child perinatal transmission of Hep B? Hep C?

Hep B = infants should receive the Hep B vaccine and Ig's within hours of birth to prevent perinatal transmission Hep C = No effective prevention

Why is it hard to make a vaccine against HCV?

Hep C is genetically unstable due to it lacking a proofreading 3'--5' exonuclease activity in its RNA polymerase. Also, its envelope glycoprotein sequences also contain a hyper variable region prone to frequent mutations!

Treatment for Heparin overdose? Warfarin?

Heparin = Protamine sulfate. Directly binds to heparin. In LMWH, it is still used but does not completely reverse the antiXa-activity of LMWH Warfarin: Acute = FFP (contains clotting factors). Subacute = Vitamin K

Difference between unfractionated heparin and LMWH?

Heparin is a naturally found negatively charged chemical in mast cells! Unfractionated heparin- Potentiates ATIII to block both factor Xa and thrombin. Short half life, given IV LMWH- Mainly act on Factor Xa, longer half live, subQ (enoxaparin, dalteparin, etc.)

In Reyes syndrome, how exactly does aspirin cause hepatic dysfunction? Encephalopathy?

Hepatic dysfunction: manifests with vomiting and hepatomegaly, but jaundice is rare. Light microscopy shows *microvesicular steatosis*, the presence of small fatty vacuoles in the cytoplasm of hepatocytes. No necrosis or inflammation is present in the liver! Electron microscopy shows swelling, a decreased number of mitochondria and glycogen depletion! It basically causes mitochondria dysfunction that causes impaired metabolism/ß-oxidation of fatty acids, leading to the micro vesicular steatosis! Encephalopathy: Hepatic dysfunction causes toxic levels of ammonia to accumulate causing hyperammonemia of the CNS leading to cerebral edema

What are some causes of increased ammonia? 2 treatments?

Hepatic encephalopathy, GI bleeding (bacteria in gut break down Hb into nitrogen products), excess dietary protein intake, infection, sedatives, metabolic derangements (eg. hypokalemia) Rifaximin = nonabsorbable Abx that alters GI flora, to decrease intraluminal ammonia production Lactulose = Catabolized by gut flora into short chain fatty acids, lowering the colonic pH and protonating the ammonia into ammonium (NH4+), trapping it in the GI tract!

Diseases of RBC cytoskeletal abnormalities?

Hereditary spherocytosis Hereditary eliptocytosis Hereditary stomatocytosis

How would the onset of action for an inhaled anesthetic be influenced by an INCREASED arteriovenous concentration gradient?

High Arteriovenous concentration gradient means more drug is being taken up by the tissues, meaning it needs to be replaced! So more drug is needed, so its going to have a slower onset of action since we need more of it in the blood to make up for the tissue extraction!

Dyslipidemia seen in insulin resistance?

High TGs and low HDL *LDL levels do not increase!

How does hypertriglyceridemia cause acute pancreatitis?

High levels of circulating TGs leads to increased production of FFAs within the pancreatic capillaries by pancreatic lipase. Normally, fatty acids exist in serum bound to albumin. However, if serum TGs rise to >1000 mg/dL, the concentration of FFAs exceeds the binding capacity of albumin and leads to direct injury to the pancreatic acing cells. Thus, hypertriglyceridemia causes acute pancreatitis via direct tissue injury

Where does Thiopental go after injection?

High lipid soluble Goes to brain rapidly (why we use it for induction of anesthesia) Short acting effects because after equilibrating with brain, it redistributes quickly into Skeletal Muscle and Fat

What can cause the deconjugation of bile acids in the bowel? What does this cause?

High numbers of Anaerobes and S. aureus can result in deconjugation (via removal of glycine and taurine) of bile acids, rendering them less soluble and therefore less able to form micelles! Will cause less reabsorption of bile acids into portal circulation at the terminal ileum, resulting in lipid malabsorption!

21-alpha-hydroxylase deficiency screening measurement?

High serum 17-hydroxyprogesterone

How does age-related aortic stiffening present on the bp cuff?

High systolic pressure with normal-to-low diastolic pressure Decreases in compliance of the aorta and proximal major branches.

Giant Cell Arteritis Tx

High-dose Glucocorticoids (EMERGENCY) Tocilizumab (Monoclonal Ab against IL-6) is a new Tx

Common side effect of halogenated inhaled anesthetics, especially halothane?

Highly lethal fulminant hepatitis that cannot be distinguished histologically from acute viral hepatitis. Patients have significantly elevated AST (due to massive hepatocellular injury) and prolonged PTT (since Factor VII has the shortest half life) due to failure of hepatic synthetic function!

Describe the histopathology and clinical presentation of Hepatitis A infection

Histo: "spotty necrosis" with ballooning degeneration (hepatocyte swelling with wispy/clear cytoplasm), Councilman bodies (eosinophilic apoptosis hepatocytes), and mononuclear cell infiltrates Pts present acutely with a prodrome of fever, malaise, anorexia, N/V, and URQ abdominal pain. After 1 week, prodromal symptoms lessen as patients develop signs of cholestasis, such as jaundice, pruritus, dark-colors during (due to increase conjugated bilirubin levels), and acholic stool (lacks bilirubin pigment).

Celiac sprue: Histology? Pathophysiology? Clinical presentation? Diagnosis?

Histo: Blunted intestinal villi, crept hyperplasia, and increased intraepithelial lymphocytes Pathophys: hypersensitivity to gluten, causing *villous atrophy* and chronic inflammation of the lamina propria, impairing aborsortion in the *duodenum and jejunum* where the conc. of gluten is the highest! Presents with *malabsorption*, delayed puberty/growth failure in children, difficulty gaining weight/anemia in adults Diagnosis: Test for *IgA anti-endomysial* and *anti-tissue transglutaminase Abs* before endoscopy

New drug class under investigation for treatment of up regulating survival genes in Huntington Disease? Why does this work?

Histone Deacetylase Inhibitors The AD disease increases CAG repeats, expanding the huntingtin protein's polyglutamine region causing a gain of function mutation. This abnormal huntingtin protein now causes INCREASED HISTONE DEACETYLATION, silencing the genes necessary for neuronal survival! (the hypoacetylated histones bind tightly to DNA, surpassing transcription)

What are the homeobox (Hox) genes? What do they regulate?

Homeobox genes encode DNA-bidning transcription factors that play an important role in the segmental organization of the embryo along the crania-caudal axis. If interrupted = skeletal malformations such as improperly positioned limbs and appendages (syndactyly and polydactyly)

What is the MCC of homocystinuria? Levels of what AA become high? What AA becomes essential? Clinical presentation?

Homocystinuria is MCC by a defect in cystathione synthase, resulting in an inability to form cysteine from homocysteine. Cysteine becomes an essential AA, and homocysteine buildup leads to elevated methionine Homocysteine is prothrombotic, resulting in premature thromboembolic events (atherosclerosis, acute coronary syndrome)

What 2 things can cause marfanoid habitus? How do you differentiate?

Homocystinuria will cause intellectual deficits, thrombotic events (ie. MI), and downward dislocation of lense among other things

Describe Secretin

Hormone produced by duodenal S-cells and released in response to increased duodenal H+ conc. Stimulates release of pancreatic bicarb in order to neutralize this!

Classic examples of AD inheritance?

Huntington Disease Marfan Syndrome MEN NF-1 and NF-2

Lesion to caudate nucleus? Lesion to subthalamic nucleus? Lesion to the nucleus ambiguous?

Huntington's = Caudate nucleus "Hunting 4 CAG's" -*C*audate loses *A*ch and *G*ABA Hemiballismus = subthalamic nucleus (usually due to a lacunar infarct) Myoclonus = nucleus ambiguous

Classic triad of congenital toxoplasmosis? How is it transmitted to the fetus?

Hydrocephalus (seizures) Chorioretinitis Intracranial calcifications (maybe deafness too) TORCH infection = transmitted through placenta intra-utero

What in brain can cause impaired upward gaze?

Hydrocephalus due to dilation of 3rd ventricle with compression of dorsal midbrain (pretectal area)

In stomach, rugal hypertrophy with acid hypersecretion? rugal hypertrophy with acid hyposecretion?

Hyper secretion = ZE syndrome Hypo secretion = Menetrier Disease (due to parietal cell atrophy)

Describe exactly how hyperammonemia results in hepatic encephalopathy

Hyperammonemia in hepatic encephalopathy results in depletion of alpha-ketoglutarate, causing inhibition of the Krebs cycle. Excess ammonia also depletes glutamate, an excitatory NT, and causes accumulation of glutamine, resulting in astrocyte swelling and dysfunction. Within the brain, astrocytes and neurons interact to regulate the metabolism of glutamate, glutamine, and ammonia in a process known as the glutamate-glutamine cycle. Glutamate released by neurons during neurotransmission is taken up by astrocytes and converted to glutamine, a non-neuroactive compound. Glutamine is then released by astrocytes and taken up by neurons, where it is either converted back to glutamate as a neurotransmitter, or transaminated into alpha-ketoglutarate for use in the Krebs cycle. Ammonia toxicity results in part from depletion of glutamate and alpha ketoglutarate in the brain during the process of ammonia detoxification. Hyperammonemia increases the conversion of glutamate into glutamine by glutamine synthetase w/in astrocytes. The resulting increase in glutamine leads to hyperosmolarity and mitochondrial dysfunction, causing astrocytic swelling and impairment. Increased glutamine formation also decreases total brain glutamate stores, impairing excitatory neurotransmission (mediated by NMDA, AMPA, and kainate receptors) and neuronal energy production. In addition, ammonia can be detoxified to glutamate via glutamate dehydrogenase, depleting alpha-ketoglutarate and further impairing energy metabolism in the brain!

How can Hypercalcemia lead to nephrogenic DI?

Hypercalcemia (ie squamous cell lung cancer) causes dehydration by down-regulation of aquaporin in the collecting tubule, leading the tubules to be resistant to the effects of vasopressin!

What electrolyte abnormality is seen in sarcoidosis? Why?

Hypercalcemia! Its seen in any kind of granulomatous disease (sarcoidosis, Tuberculosis, etc.) The activated macrophages in granulomatous diseases have increased expression of 1-alpha-hydroxylase (independent of PTH), leading to increased activation of Vitamin D, stimulating calcium reabsorption from the gut, causing HYPERcalcemia and HYPERcalciuria *This is also seen in Hodgkin's and NHL

Does primary hyperparathyroidism cause hyper or hypocalciruria? What are the effects on bone?

Hypercalciuria! (although it causes increased Ca reabsorption at the DCT, the hypercalcemia spills over into urine and forms stones--- "Stones, bones, abdominal groans and psychic moans") Increased osteoclast reabsorption of bones causes subperiosteal thinning of the cortical (compact) bone, mostly in the appendicular skeleton, especially the hands. Will see a granular "salt-and-pepper" skull, and osteolytic lesions in the long bones (osteitis fibrosa cystica)

Cardiac findings in Obstructive sleep apnea?

Hypercapnia and hypoxemia leads to systemic/pulmonary vasoconstriction, as well as sympathetic cardiac stimulation! Prolonged OSA can lead to pulmonary HTN and right heart failure. Also systemic HTN, a-fib, arrhythmias, coronary artery disease, and increased risk of sudden cardiac death

Jejunal ulcer?

Hypergastrinemia (ZE-Syndrome)

What are xanthomas usually associated with? What do they look like histologically?

Hyperlipidemia or lumphoproliferative malignancies. They are yellow nodules composed of lipid-laden histiocytes (macros) in the dermis They are benign macrophages composed of finely vacuolated "foamy" cytoplasm. These are frequently enclosed by inflammatory cells and fibrotic stroma.

What drugs typically cause ANCA-associated vasculitis?

Hyperthyroidism drugs (propylthiouracil and methimazole) and hydralazine

MCC of sudden cardiac death in a young, previously healthy individual?

Hypertrophic Cardiomyopathy

Bifid carotid pulse with brusk upstroke ("spike and dome")?

Hypertrophic obstructive cardiomyopathy--- subset of hypertrophic cardiomyopathy. asymmetrical septal hypertrophy and systolic anterior motion of the mitral valve causes an outflow obstruction, leading to dyspnea and possible syncope!

Symptoms of Hereditary Fructose Intolerance

Hypoglycemia, vomiting, jaundice, cirrhosis

Bipolar II disorder definition

Hypomanic episode and a depressive episode

What are some key distinguishing factors they patients with Lambert-Eaton Syndrome have that patients with Myasthenia Gravis do not?

Hyporeflexia/areflexia Autonomic symptoms (dry mouth, impotence) Incremental response to repetitive stimulation *Seen with small cell lung cancer!

How do patients with a Right Ventricular MI present?

Hypotension Distended Jugular veins *CLEAR LUNGS*

How do Right Ventricular MI's present? What is it due to?

Hypotension, inc JVP, and clear lungs Usually occurs via acute inferior wall MI due to occlusion of the proximal right coronary artery before the origin of the RV branches. Will see reduced PCWP and C.O.

What is volume of distribution? How do you calculate it?

Hypothetical volume of fluid into which the administered amount of drug would need to be uniformly distributed to produce the observed plasma concentration. The volume of distribution is determined by administering a drug IV and then measuring the initial plasma concentration of the drug Vd = amount of drug given / plasma concentration of drug

Does amiodarone cause hyper or hypothyroidism? How? How do you treat?

Hypothyroidism in patients living in iodine sufficient areas. Thyroxicosis due to excessive production of TH in iodine-deficient areas! It is 40% iodide by weight, so the excessive iodine shuts down the thyroid. Treat with levothyroxine while continuing amiodarone

What are the 3 main openings in the diaphragm, and what passes through each?

I 8 10 Eggs At 12 T8 = Inferior Vena Cava T10 = Esophagus, Vagus nerve, and esophageal artery branch off the left gastric comes on up through it T12 = Aorta, thoracic duct, and azygous vein

Compare and contrast MHC Class I vs II -Structure? -Who has each? -Function? -Type of Antigen? -What is stimulated?

I = Beta-2 microglobulin II = invariant chain

Transbronchial biopsy showing non-caseating granulomas and chest x-rays are essential for diagnosis of sarcoidosis. What will you see in CXR of stage I? II? III? IV?

I = Bilateral hilar lymphadenopathy II = Bilateral hilar lymphadenopathy + pulmonary infiltrates usually in upper lobes III = No more hilar lymphadenopathy, but will see lung infiltrates IV = Lung Fibrosis

What makes up the spermatic cord? What are the derivates of each?!?

ICE-TIE Internal spermatic fascia = transversalis fascia Cremesteric muscle/fascia = internal oblique External spermatic fascia = external oblique

What advantage does the Interferon-gamma release assays (IGRAs) have over the PPD skin test?

IGRAs measure if a T-lymphocyte produces INF-gamma in response to mycobacterium. BOTH the PPD and IGRA test for latent TB infection. IGRAs are better because they do NOT react with the BCG vaccine, so an unnecessary followup is not required! However, neither PPD or IGRAs distinguish an active TB infection from a latent TB infection!

What is somatomedin C?

ILGF-1

Explain how collagen in synthesized

IN ROUGH ER: 1. PRE-PRO-COLLAGEN alpha chain translated that is *Gly-X-Y* (where x and y are proline and lysine) 2. Hydroxylation of proline and lysine, requires VITAMIN C 3. Glycosylation (adds sugar) and then 3 of these alpha collagens bind together via hydrogen/disulfide bonds to form PRO-COLLAGEN (triple helix of 3 collagen alpha chains). Problem forming pro-collagen = osteogenesis imperfecta! 4. Secreted out of RER, out through golgi into extra cellar space 5. Cleavage of disulfide rich C and N terminals to form insoluble TROPOCOLLAGEN 6. Many staggered tropocollagens are cross-linked together by covalent lysine-hydrolysine cross-linkage via the enzyme lysol oxidase, which requires COPPER! -Problems with cross-linking = Ehlers-Dalos syndrome or Menkes Disease

What is a D-xylose test used to differentiate between?

Its absorbed at the proximal small bowel via passive diffusion. Used to differentiate pancreatic from intestinal malabsorption!

Describe the insulin receptor and how it signals

IR is a tetrameric structure. 2 extracellular alpha subunits where insulin binds. 2 intracellular beta subunits that contain tyrosine kinase that autophosphorylate the IR. This allows then for phosphorylation of tyrosine on the Insulin receptor substrates 1 and 2 (IRS-1/2), ultimately leading to translocation of GLUT-4 to PM

Concentration of Pancreatic juice compared to plasma?

ISOTONIC Contains same amount of Na and K Contains MORE BICARB Contains less Cl

DOC for acute status epilepticus?

IV Benzodiazepines (eg. lorazepam)

Function of the Golgi tendon organ?

Ib sensory axons from the GTO contact inhibitory interneurons in the spinal cord, which in turn synapse with the alpha motor neurons that innervate the same muscle. Thus, the golgi tendon circuit is a negative feedback system that regulates and maintains muscle tension. When a muscle exerts too much force, the GTOs inhibit contraction of the muscle, causing sudden muscle relaxation, helping to prevent the muscles from ripping off the bone! *They are in series with extrafuscal muscle fibers

What lung disease is associated with honeycombing? Why does this occur?

Idiopathic Pulmonary Fibrosis (IPF) *Progressive exertional dyspnea and dry cough on a restrictive profile of pulmonary function testing = classic presentation "Usual Interstitial Pneumonia" shows a patchy involvement with dense fibrosis and fibroplastic fox. Alveolar wall collapse leads to formation of cystic spaces (*honey combing!*) lined by hperplastic type II pneumocytes or bronchiolar epithelium. Occurs more often in the sub pleural and paraseptal spaces.

When would you give Vampiric acid instead of Ethosuximide to a kid?

If he has BOTH absence seizures and tonic-clonic seizures

Describe the Pringle Maneuver

If hepatic bleeding persists, the IVC or hepatic vein are most likely injured

How can an appendix be identified during an appendectomy?

If not by palpation, then you can follow the taenia coli to its origin at the cecal base where the appendix lives

What triggers mast cell degranulation in anaphylaxis?

IgE receptor aggregation

How do certain drugs lead to mast cell degranulation?

IgE-INDEPENDENT Some meds (opioids, radio contrast agents, vancomycin) can induce mast cell degranulation by activation of PKA and PI3 Kinase. Results in release of several mediators such as histamine, bradykinin, heparin, and chemotactic factors. Common symptoms include diffuse itching and pain, bronchopsasm, and localized swelling (urticaria)

Most abundant Ig? Does it cross placenta?

IgG (monomer) crosses the placenta and enters fetal blood stream to provide passive immunity

Type of antibody made against Diphtheria vaccine (DPT)? How about against actual Cornybacterium diptheriae infection?

IgG made against exotoxin IgA can be made against adhesion proteins of C. diphtheria, but not a capsule IgA bc it has NO CAPSULE!

Which Antibody(s) has a J-chain? Purpose of J chain?

IgM - circulates an pentamer IgA - circulates as a dimer Binds the Fc portion of heavy chain in order to form pentamer/dimer

What is Rheumatoid Factor? What does it mean?

IgM Ab against Fc portion of IgG Pretty much tells you nothing

Narrowest portion of the small intestine where a gallstone illeus can become lodged?

Ileum

What results in thalassemia? What is seen on blood smear?

Imbalance between alpha global and beta global chain production Will see target cells and hypo chromic microcytes

Immediate treatment for panic disorder? Long term treatment?

Immediate = Benzodiazepines Long term = SSRI's, SNRI's, and/or CBT

Pathogenesis of ITP? Tx?

Immune Thrombocytopenia Purpura Anti-GpIIb/IIIa Abs (IgG from spleen) complex with platelets, and then are removed via splenic macros Treat with steroids, IVIG, or last resort splenectomy

What would be seen with a lesion to Broca's area?

Impairment in motor planning -- difficulty writing, signing, and speaking (Broken speech) Its the caudal part of the inferior frontal gyrus of dominant (usually left) hemisphere (Brodmann area 44/45) May have right sided hemiparesis as well

MOA of amantadine for Influenza A

Impairs uncaring of the influenza A visions after host cell endocytosis

What is Retinopathy of prematurity? What causes it?

In Neonatal RDS, some infants will be given hyperbaric O2. Temporal hyperoxia in the retina is thought to induce changes that cause up-regulation of proangiogenic factors such as VEGF upon returning to normal room air ventilation. Retinal vessel proliferation (neovascularization) and possible retinal detachment can occur.

Describe the pathogenesis of pulmonary artery hypertension. What gene is mutated in familial PAH?

In familial PAH, its usually due to an inactivating mutation of the pro-apoptotic gene BMPR2--- leads to increased in endothelial and smooth muscle cell proliferation! Will hear accentuation of the pulmonary component of the second heart sound (P2)

What is the point of converting cholesterol into bile acids when we want to remove cholesterol from the body?

In liver, free cholesterol is converted into cholic and chenodeoxycholic bile acids via cholesterol-7å-hydroxylase. These bile acids are then conjugated to either glycine or taurine (improving their solubility/emulsifying ability) to create bile salts that are secreted into bile canaliculi. We do this because when water insoluble cholesterol is also secreted into the bile canaliculi, the bile salts can emulsify them, making the cholesterol soluble, so no cholesterol can precipitate! But if we have decreased bile salts or phosphatidylcholine, or increased cholesterol, the cholesterol doesn't get emulsified and can precipitate!

Type of kidney stones seen in Crohn's disease/small bowel resection? Why?

In normal pts, dietary calcium binds to dietary oxalate, producing insoluble calcium oxalate salts that promote oxalate excretion. In Crohn Disease, the terminal ileum is often involved, leading to impaired reabsorption of bile acids, causing fat malabsorption. These excess lipids in the bowel lumen *bind to calcium* ions, and these soap complexes are then excreted with the feces. This leaves free oxalate in the bowel, and oxalate absorption increases, promoting the formation of oxalate kidney stones! (enteric oxaluria)

What initiates DIC in pregnancy?

In pregnancy, DIC is mediated by *tissue factor (thromboplastin)*, which is found in high amounts in the placental trophoblast. Tissue factor is released from sites of placental injury, initiating the coagulation cascade etc. Risk factors for DIC include placental injury (ex: placental abruption), sepsis, postpartum hemorrhage, acute fatty liver pregnancy (can't make clotting factors), and amniotic fluid embolism (fetal antigens from amniotic fluid can activate the clotting cascade)

How does L-asparaginase treat leukemia?

In rapidly dividing leukemia cells, the synthesis of asparagine is impaired, so these cancerous cells survive by collecting asparagine from the circulating plasma. L-asparaginase works by lowering circulating asparagine levels so the cancer can't scoop it up!

What is wrong in lactase deficiency? Symptoms? What is seen on biopsy of primary lactase deficiency? Secondary?

Incomplete hydrolysis of the disaccharide lactose into glucose and galactose. Undigested lactose attracts water into gut lumen causing osmotic diarrhea. Stool pH will be *ACIDIC* since bacteria ferments lactose into short-chain fatty acids! Mucousa will look NORMAL in primary Secondary lactase deficiency is usually secondary to some sort of injury to GI mucousa, such as celiacs or virus

MOA of thiazolidinediones? Adverse effect?

Increase insulin sensitivity in peripheral tissues; binds to PPAR-gamma in the nucleus Side effects: -also increases levels of adiponectin (weight gain) -Edema --> Heart failure -Hepatotoxicity --> Must check LFTs Long term use can lead to urinary bladder cancer

What are the compensatory physiologic changes due to chronic long-term high altitude acclimation?

Increased 2,3-BPG Increased Hb production (via EPO) Increased pulmonary diffusing capacity VEGF-induced angiogenesis Increase in cellular mitochondria Hemoconcentration (due to bicarb diuresis, decreasing bicarb, and fluid shift)

What is associated with increased AFP levels in a triple screen? Decreased AFP levels?

Increased AFP: -Most commonly is dating error (underestimation of gestational age- confirm with fetal ultrasound) -*Neural tube defects*, anterior abdominal wall defects (omphalocele, gastrochisis), and multiple gestation Decreased AFP: -Down's Syndrome

What is pseudotumor cerebri? What physical exam finding will you see?

Increased ICP without a tumor! AKA benign intracranial HTN Will see papilledema

How do combined oral contraceptives help treat excess hirsutism in PCOS?

Increased LH secretion causes increased androgen production. OCPs work by suppressing LH secretion from the pituitary, thereby decreasing ovarian androgen production. They also increase SHBG synthesis by the liver, decreasing free testosterone levels. *Note- Spironolactone can function as a testosterone receptor antagonist which suppresses androgen-dependent hair growth, but it is highly teratogenic!

What would you see on a WBC count of someone on corticosteroids?

Increased Neutrophil count (demmargination of neutrophils previously attached to the vessel wall) Decreased lymphocyte, monocyte, basophil, and eosinophil counts

What is primary hypertryglyceridemia? Tx?

Increased VLDL Fibrates and Niacin, both decrease hepatic VLDL production

S3 gallop signifies what? Heard in what heart defect?

Increased left ventricular fill rate Seen in Mitral Regurg

Infections of vagina with increased pH? Normal pH?

Increased pH = Trichomonas and Gardnerella Normal pH = Candida

What causes a functional Mitral Regurg? How do you treat it?

Increased preload can dilate left ventricle, spreading valve leaflets leading to functional mitral regurg Can be eliminated by preload reduction (diuretics) and reduced by lowering afterload

What is responsible for the 4-8 week delay in effects from SSRIs?

Increased serotonin levels causes down-regulation of the post-synaptic serotonin receptors, decreasing their density within the synaptic cleft!

What is the Wolff-Chaikoff effect seen in the thyroid?

Increased serum iodide levels leads to inhibition of iodide organification!

What is hypergranulosis? Example of a skin condition that has it?

Increased thickness of the stratum granulosum Seen in lichen planus

MOA or meglitinides and sulfonylureas?

Increases insulin secretion by inhibiting ß-cell K+ATP channels, thereby causing insulin secretion

What can using nicotine during pregnancy cause?

Increases risk of prematurity and low birth weight Also placenta prevue and abruption

What 2 things increase the myometrial excitability prior to delivery?

Increasing Estrogen levels cause: 1. Upregulation of gap junction (composed of connexin) between myometrial smooth muscle cells 2. Increased expression of uterotonic (ie. oxytocin) receptors, which mediate calcium transport through ligand-activated calcium channels

Moving rostrally in the spinal cord, what changes do you see?

Increasing amounts of white matter, decreasing amounts of grey matter, and more oval shaped (like a football)

What do high levels of acetyl-CoA indicate? What enzyme does it activate?

Indicates energy excess, activates pyruvate carboxylase (uses biotin as cofactor) which forms oxaloacetate, which then can be converted by PEP carboxykinase into PEP and go through gluconeogenesis!

Describe Spinal muscular Atrophy

Infant with delayed motor development and flaccid paralysis (eg, hypotonia, decreased DTRs). Caused by mutations in the survival motor neuron (*SMN1*) gene, which encodes a protein involved in assembly of snRNPs in lower motor neurons. Defective snRNP assembly results in impaired spliceosome function and degeneration of anterior horn cells of the spinal cord!

Difference in infection between adult and infant botulism?

Infants = infected with spores Adults = infected with pre-formed toxins

Patient with ST elevation in the inferior leads is treated and develops glaucoma. What the hell happened?

Inferior MI is due to blockage of right coronary artery, which knocks out the SA and AV node. This will cause bradycardia In order to treat the bradycardia, you can give atropine, which blocks vagal influence on SA and AV node, thereby increasing HR. This muscarinic blockage can also lead to mydriasis, narrowing the anterior angle chamber, leading to obstruction of aqueous humor outflow, leading to acute closed-angle glaucoma (increased intraocular pressure)!

2 branches of the external iliac artery?

Inferior epigastric artery and deep circumflex iliac artery

Diaphragmatic surface of the heart is what? Supplied by what artery?

Inferior wall of left ventricle supplied by posterior descending artery (usually right coronary artery)

What exactly causes the opthalmopathy in Grave's disease?

Infiltration of Th1 lymphocytes into extra ocular muscles--- secretes cytokines--- stimulates retro-orbital fibroblasts--- produce excess GAGs---bulges eyes out High-dose Glucocorticoids (prednisone) help decrease the severity of inflammation and decrease extra ocular volume.

Breast cancer with Peau' de orange caused by neoplastic cells blocking lymphatic drainage?

Inflammatory Breast CA

What is Lichen Sclerosis? Dangerous sequelae? Tx?

Inflammatory autoimmune disease with auto-Abs against the ECM1 protein. Typically affects females in the genital and perineal region. Lesions begin as white, atrophic macule that can coalesce into plaques as the condition progresses. Can develop genital SCC and genital disfigurement. Tract with high potency topical corticosteroids.

What is seborrheic dermatitis? If severe enough, what diseases is it associated with?

Inflammatory condition characterized by accumulation of scaly, greasy skin on scalp, face, ears, eyelids, and eye brows. Severe seborrheic dermatitis is seen with HIV or Parkinsons

Disease caused by ingestion of Taenia solium larval cysts from infected uncooked pork? Ingestion of eggs from stool of tapeworm?

Larval Cysts = Taeniasis Eggs from stool = Neurocystercosis

What 2 drugs can inhibit TNF-alpha? How?

Infliximab-- Monoclonal Ab against TNF-alpha Etanercept -- recombinant receptor fusion protein (aka decoy receptor) Since TNF-alpha is a key mediator of the inflammatory process, it is used to treat autoimmune inflammatory conditions such as RA, Crohns, Ankylosing spondylitis, and Psoriasis

Where do AAA typically occur? Why?

Infrarenal because there is no longer a vaso vasorum

Describe Fanconi Anemia

Inherited cause of aplastic anemia that presents with short stature and absent thumbs, and is associated with an increased risk of malignancy (Myelodysplastic syndrome, AML)

How does antagonism of muscarinic receptors cause facial flushing?

Inhibition of eccrine sweat gland secretions can result in fever and compensatory vasodilation (to get rid of the heat!)

Why is Paclitaxel coated onto coronary artery stents?

Inhibition of intimal hyperplasia! (Sirolimus does this too) Complications following placement of a metal stent include acute stent thrombosis and restenosis due to intimal hyperplasia! Paclitaxel is an antineoplastic agent that functions by finding ß-tubulin and preventing microtubule breakdown thus causing arrest of the cell cycle in the M phase.

MOA of Mycophenylate?

Inhibits IMP dehydrogenase, a critical step in de novo purine synthesis--- required for proliferation of active lymphocytes. Its an immunosuppressant

Cyclosporine MOA

Inhibits NFAT from entering nucleus thereby decreasing tsc of IL-2, causing decreased activation of resting T-lymphocytes via IL-2

alpha-Amantin (death cap mushroom, Amanita phalloides) toxin MOA

Inhibits RNAP II in Liver Cells --> Decreases mRNA *Rampant, massive, tiny

MOA of theophylline? What can precipitate its toxicity? Symptoms of toxicity?

Inhibits phosphodiesterase (PDE), leading to an increase in cAMP causing bronchodilation. Its metabolized by Cyt P450, so inhibitors can cause increased levels of theophylline! Theophylline toxicity: CNS stimulation (tremor, insomnia, seizures), GI probs, CV abnormalities (hypotension, tachycardia, arrhythmias)

MOA of terbinafine?

Inhibits the fungal enzyme squalene epoxidase, which ultimately results in decreased ergosterol synthesis. Accumulates in skin and nails, treats dermatophytosis

Fibrates MOA? Adverse effect?

Inhibits the rate limiting step of bile acid synthesis (cholesterol-7-alpha-hydroxylase). Also activates PPAR-alpha, which leads to decreased hepatic VLDL production and increased LPL. LPL hydrolyzes TGs in chylomicrons and VLDL to release free fatty acids! Can develop gallstones since this superstores the bile with cholesterol (increases the Cholesterol:bile acid ratio)

MOA of statins? What are they good for?

Inhibits the rate limiting step of cholesterol synthesis (HMG-CoA-Reductase), leading to an increase in liver LDL Receptors. Also reduces the risk of acute coronary events. -Anti-inflammatory properties -improves endothelial dysfunction ("slicks the vessels") -stabilizes atherosclerotic plaques

Describe tuberculoid leprosy

Initial infection of the leprosy spectrum. Th1 response (cell mediated- IL2 and INF-gamma), contained within macrophages. Localized inflammation damages skin and cutaneous nerves, leading to small number of hypo pigmented, well demarcated plaques with decreased sensation. POSITIVE lepromin skin test

Explain the pathophysiology of Infective Endocarditis

Initial process is a *disruption of normal endocardial surface*. This occurs most often at areas of maximal turbulence to blood flow in preexisting valvular lesions, typically in the atrial surface of incompetent AV valves or ventricular surface of incompetent semilunar valves! This is followed by focal adherence of *fibrin and platelets*, forming a *sterile fibrin-platelet nidus*! During bacteremia, microorganisms colonize this sterile nidus, causing further activation of the coagulation system. ***Streptococcus infect valves with preexisting endothelial lesions, while Staph aureus can adhere to damaged or normal endothelial cells!

Pt has an uncle herniation that compresses the cerebral peduncles, resulting in corticospinal tract injury with hemiplegia. What will reflexes be initially? week later?

Initially pt will have flaccid paralysis with hyporeflexia (ie. spina shock) Develops spasticity/hyperreflexia days to weeks following acute UMN damage

Brief explanation of apoptosis

Initiator caspases = 8 and 10 Executioner Caspases= 3 and 6 Terminal processes of apoptosis = cleavage of DNA, fragmentation of the nucleus, organelle autodigetsion, and plasma membrane blebbing

What are the 2 forms of the influenza vaccine? How do they prevent infection?

Injection = Inactivated (killed) -Induces neutralizing Abs (humoral immunity) against hemagglutinin antigen in the selected strains. Upon subsequent exposure to the virus, these Abs inhibit the binding of hemagglutinin to sialylated receptors on host cell membrane. This prevents the virus from entering the host cells via endocytosis! Nasal Spray = live attenuated -Infects host cells, entering the MHC Class I antigen processing pathway, generating a significant CD8+ cell mediated immune response that kills infected cells in addition to providing Humoral immunity!

What central brain lesions can cause complete ptosis?

Injury to the oculomotor nerve fibers within the upper midbrain and is typically associated with contralateral hemiparesis due to adjacent corticospinal tract involvement (Weber Syndrome)

Difference between schizoaffective D/O and Major depressive disorder with psychotic features?

Inn MDD with psychotic features, the psychotic features ONLY occur with the major depressive episodes. In Schizoaffective D/O, the psychotic features persist for >2 weeks in the absence of the more depressive episode!

How do insulin and glucagon directly influence each other?

Insulin inhibits suppresses glucagon secretion Glucagon stimulates insulin secretion by acting on pancreatic ß-cells (allowing glucose to be taken up by insulin-sensitive tissues) ß-cells are on the inside of an islet of langerhans! (Insulin is INSide)

Does ADPKD present in childhood or adulthood?

Later in Life! **Note- Most AD diseases present later in life!

Why do people with Type II DM have increased FFAs in their serum?

Insulin resistance in adipose cells hinders the antilipolytic effects of insulin, leading to lipolysis and release of FFAs. In turn, chronically elevated FFA levels contribute to insulin resistance by impairing insulin-dependent glucose uptake in liver and muscle, and increasing hepatic gluconeogeneisis. will see acanthosis nigricans in insulin resistance

Describe the histology of Hashimoto's Thyroiditis

Intense mononuclear infiltrate (attracted via cytokines released from T helper cells, Type IV hypersensitivity) consisting of lymphocytes and plasma cells, often with *germinal centers* (Type II hypersensitivity). Residual follicles are surrounded by Hurthle Cells (large oxyphilic cells filled with granular cytoplasm)

Factitious Disorder: key fts?

Intention falsification or inducement of symptoms with goal to assume SICK ROLE *Patient CONSCIOUSLY creates symptoms in order to get primary (internal) gain

Adenosine: -MOA? -Indication? -What else behaves almost the exact same way?

Interacts with A1 receptors on the surface of cardiac pacemaker cells thereby prolonging phase 4 (funny currents of Na+) via: 1. Increasing K+ channel conductance (hyper polarization) 2. Inhibits L-type Ca channels (prolongs depolarization-) *These actions result in a transient slowing of sinus rate and an increase in AV nodal conduction delay. Adenosine is used in the termination of paroxysmal supraventricular tachycardia. Acetylcholine behaves almost the same exact way, except also decreasing inward Na+ current in Phase 4

Treatment for chronic HCV?

Interferon alpha and Ribavirin

Control of internal urethral sphincter? External?

Internal = Sympathetic Nervous system (its smooth muscle at junction of bladder and urethra) External = Pudendal Nerve (voluntary- its skeletal muscle)

Trace the drainage of internal versus external hemorrhoids. Which ones are painful?

Internal Hemorrhoids (above dentate line): -Superior Rectal veins drain to Inferior Mesenteric Vein -Middle Rectal vein drains to Internal Iliac vein External Hemorrhoids (below dentate line, painful): -Inferior Rectal vein to the internal pudendal vein, then to internal iliac vein

Where does the internal pudendal artery come from? Where does it supply?

Internal pudendal artery branches off the anterior trunk of the internal iliac artery and runs through the sciatic foramina to supply the perineum.

Where do you do a nerve block if you want to knock out the brachial plexus? Common complication?

Interscalene nerve block is done in the Scalene Triangle (between the middle and anterior scalene muscles) where the 3 trunks of the brachial plexus emerge You also knock out the phrenic nerve (C3-C5) causing ipsilateral diaphragmatic paralysis, so don't do this in patients with Chronic lung disease of contralateral phrenic nerve dysfunction!

Most common form of pulmonary complication in RA?

Interstitial Lung disease *The use of Methotrexate to treat RA can also lead to interstitial fibrosis!

Explain a myocardial biopsy of Acute Rheumatic fever

Interstitial fibrosis with central lymphocytes and macrophages as well as scattered multinucleated giant cells. This *INTERSTITIAL MYOCARDIAL GRANULOMA* (aka ASCHOFF BODY) is pathognomonic for ARF. Plump macros with abundant cytoplasm and central. slender chromatin ribbons called Anitschkow (or caterpillar cells) are also often present. Over the years, Aschoff bodies are replaces by *fibrous scar tissue*, leading to chronic *mitral valve stenosis and regurgitation*!

What type of microbial infection do eosinophils combat?

Intestinal helminthic infections **NOT Giardia!

Cystinuria symptoms

Intestinal symptoms = none really, the COLA amino acids can be absorbed as oligopeptides Kidney symptoms = high urinary cysteine causes cysteine kidney stones (other AA's are soluble). Forms hexagonal crystals in a low urine pH

Describe the 2 morphological variants of gastric adenocarcinoma

Intestinal type = solid mass that projects into the stomach lumen, composed of glandular-forming cuboidal/columnar cells Diffuse Carcinoma (linitis plastica) = diffusely infiltrates stomach wall (due to loss of E-cadherin) and displays signet-ring cells on light microscopy

What does a Prussian Blue Stain detect?

Intracellular Iron. Colorless potassium ferrocyanide is converted by iron to blue-black ferric ferrocyanide! ***Golden cytoplasmic granules in macrophages that turn blue with Prussian Blue Staining are consistent with *hemosiderin laden macrophages* (aka Heart Failure Cells or siderophages)

Abusive head trauma (AHT) aka Shaken baby syndrome. How does this occur? Clinical symptoms?

Intracranial injury due to blunt force trauma or vigorous shaking in a to-and-fro fashion. 1. Since infants have larger heads, enlarged subarachnoid spaces, higher brain water content, and decreased cervical muscle tone, the brain can move much more in relation to the skull. This causes *tearing of the bridging veins* and *subdural hemorrhages*. Can have an acute on chronic hemorrhage 2. *Retinal hemorrhages* due to rupture of congested retinal veins. ***Big clue 3. Posterior Rib fractures (perpetrators grasp on infant's torso)

MCC of blood nipple discharge? What exactly causes the bleeding? Is there an increased risk for cancer?

Intraductal papilloma Small papillary tumor with a fibrovascular core and intact myoepithelial layer within the lactiferous duct, right under the areola. Bloody discharge is from twisting of the vascular stalk of the papilloma in the duct There is a slight increase risk for breast cancer (1.5-2X risk)

Do serum levels of haptoglobin decrease with intra or extravascular hemolysis? Why?

Intravascular Hemolysis! Intravascular hemolysis causes free Hb i serum (hemoglobinemia) and urine (hemoglobinuria) as well as increased serum LDH. Haptoglobin is a serum protein that binds free Hb and promotes its uptake by the RES system. Haptoglobin levels decrease when significant quantities of Hb are released intro the circulation!

Where do spliceosomes remove introns?

Introns with GU at 5' splice site and AG at 3' Slice site

What is a T-tubule in a skeletal muscle fiber? What triad does it form? What purpose dose it serve?

Invagination of sarcolemma (muscle cell PM). Triad = 1 T-tubule contacts 2 terminal cisterns (part of the Sarcoplasmic Reticulum) Functions to trans,mit a depolarization in a rapid and UNIFORM manner, allowing coordinated contraction of the myofibrils! (causes all the calcium to be released at once!)

Breast cancer with orderly row of cells ("Indian file")? What is this due to?

Invasive lobular CA *Due to decreased E-cadherin expression

What lesion(s) in the brainstem cam cause oropharyngeal dysphagia?

Involvement of CN's IX, X and XII and/or their nuclei. Cerebral cortical and subcortical lesions affecting the descending corticobulbar tracts may also lead to oropharyngeal dysphagia

What type of anemia is dysphagia and disfigured finger nails (spoon nails or koilonychia) specific for? How do you tx it?

Iron deficiency anemia Tx with oral iron. Vitamin C can be added to improve oral iron absorption

Histological finding of iron overload? Age/wear and tear?

Iron overload = hemosiderin Age/ wear and tear = lipofuscin

MOA of Capsaicin?

Irritant found in the chili pepper family Causes excessive activation of TRPV1 (a transmembrane cation channel), causing a buildup of intracellular Calcium that results in long lasting dysfunction of nociceptive nerve fibers (defunctionalization) Also causes release and depletion of Substance P--- initial application causing burning/erythema, but overtime pain goes away

How does HBV lead to HCC?

It INTEGRATES into the host cell genome bc it has a REVERSE TRANSCRIPTASE! Allows continued transcription of oncogenic viral proteins, such as HBx, which activates photo-oncognes and inhibits p53!

Function of surfactant on small alveoli? Large alveoli?

It all comes back to LaPlace's law of distending pressure = 2T/r Surfactant decreases surface tension (T) as alveoli decrease in size. As the alveoli radius decreases, the surfactant becomes more concentrated and thus is able to relieve surface tension to a greater extent. Conversely, as alveoli get bigger, the surfactant molecules become spread out and and do not reduce surface tension as much. Thus, surfactant reduces the variation in distending pressure amongst alveoli of various sizes, preventing the collapse of smaller ones and the unchecked expansion of larger ones! Functionally, surfactant helps to prevent small alveoli from collapsing during expiration and assists in regulating alveolar expansion during inspiration to ensure that all alveoli expand at similar rates. Its mostly compromised of dipalmitoylphosphatidylcholine (DPPC), other lipids, and surfactant protein!

Why is Daptomycin ineffective against pneumonia infections?

It binds to and is inactivated by pulmonary surfactant

Why is toxicity of vitamin E bad?

It can inhibit Vitamin K, acting as an anticoagulant. This can lead to an increased risk of Hemorrhagic stroke in adults and higher rates of necrotizing enterocolitis in infants

Exercise physiology: Does the total systemic vascular resistance increase or decrease? Why?

It decreases! Sympathetics discharge causes contraction of arterioles in all tissues except the actively working muscles, effectively shunting blood towards the exercising muscle. This results in only a modest increase in systolic BP, which helps improve perfusion of actively contracting skeletal muscle. The rise in the mean arterial pressure is not that high due to an overall decrease in systemic vascular resistance. This occurs due to the substantial arteriolar vasodilation in active skeletal muscles, which is mediated by local release of adenosine, K+, ATP, CO2, and lactate.

How does MDR1 gene give cancer cells resistance to chemotherapy?

It expresses P-glycoprotein, a transmembrane ATP-dependent efflux pump that pumps out hydrophobic agents like anthracyclines Normally found in renal tubular cells, intestinal epithelium, and BBB cells to keep toxic stuff out of body/brain

How exactly does folate deficiency lead to megaloblastic anemia?

It inhibits the formation of dTMP, which limits DNA synthesis and promotes megaloblastosis and erythroid precursor cell apoptosis. Thymidine supplementation can moderately increase dTMP levels, leading to reduced erythroid precursor cell apoptosis

Is Meckels's Diverticulum a true or false diverticulum? What type of tissue is found there?

It is a TRUE diverticulum-- has all 3 parts of the intestinal wall, including mucosa, submucosa, and muscularis (false diverticulum will only have mucosa and submucosa!) Can have ectopic gastric and pancreatic tissue. Ectopic gastric tissue secretes gastric acid that can cause ulceration of adjacent mucosa and lower GI bleed (melena/hematochezia)

Bortezomib MOA? What does it treat?

It is a boronic acid-containing dipeptide that functions as a PROTEASE INHIBITOR Treats multiple myeloma *Inhibiting the proteasome causes accumulation of toxic intracellular and proapoptotic proteins, which BOTH increase apoptosis!

What is erythema multiforme (EM)? What infections is it seen in?

It is a cell-mediated immune process, with in inflammatory infiltrate predominated by cytotoxic CD8+ lymphocytes. EM is most frequently associated with infections (especially herpes simplex virus and mycoplasma) and may be due to an immune response against antigens deposited in the skin! EM can also be seen in association with certain medications (sulfonamides), malignancy, and collagen vascular diseases. NOTE---- EM does NOT appear in disseminated herpes simplex infections( i.e. patients who are immunocompromised), but is a systemic immune RESPONSE to a LOCALIZED infection!

What does it mean if a virion contains a phospholipid membrane very similar to that of the host cell nuclear membrane?

It means its probably a Herpesvirus! Most ENVELOPED nucleocapsid viruses acquire lipid bilayer envelopes by budding through the plasma membrane of the host cell. However, the herpesvirus family bud through and acquire the lipid bilayer envelope from the host cell NUCLEAR membrane!

Explain what happens to lesions of each of the nuclei of the hypothalamus: -lateral -Ventromedial -Anterior Hypothalamus -Posterior hypothalamus -Suprachiasmatic nucleus

Lateral = shrink laterally (lose hunger drive) Ventromedial = grow ventrally and medially (lose satiety control) Anterior = hot (lose your cooling unit "A/C") Posterior = cold (lose heating unit) Suprachiasmatic = lose circadian rhythm (need sleep to be charismatic!)

What is the Metyrapone stimulation test? How does it work? Explain the results

It measures the integrity of the HPA axis for cortisol. Metyrapone blocks 11-ß-hydroxylase, which converts 11-deoxycortisol to cortisol in the zone fasiculata. Because 11-deoxycortisol lacks glucocorticoid activity, it does not negatively feedback to inhibit ACTH release. Therefore ACTH levels surge. This leads to even more production of 11-deoxycortisol, which gets into the serum and then gets metabolized by the liver into 17-hydroxycorticosteroids, which can be measured in the urine! Serum 11-deoxycortisol and urinary 17-hydroxycorticosteroids will normally rise in response to metyrapone, indicating HPA integrity! If not, then we have either primary of secondary adrenal insufficiency (based off plasma ACTH levels!)

What exactly causes fatty change in the liver?

Its TGs accumulating within the hepatocyte cytoplasm. Mainly due to a *decrease in free fatty acid oxidation secondary to excess NADH production* by the 2 major alcohol metabolism enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Can also result from impaired lipoprotein assembly and secretion, as well as increased peripheral fat catabolism In the hepatocyte, decreased production of lipid acceptor proteins prevents the normal incorporation of TGs into lipoproteins. Since TGs cannot be rapidly exported from the cell in the form of lipoproteins, they accumulate intracellularly-- Voila, Fatty Change

What is a leukemoid reaction? What is seen on peripheral smear?

Its a benign leukocytosis (>50,000) that occurs in response to an underlying condition (basically normal inflammation). There will be an increase in bands (left shift) and early mature neutrophils (increased or normal LAP). Peripheral smear: -Dohle Bodies: light blue (basophilic) granules (RER remnants) in neutrophils -Increased bands (left shift) -Toxic granulation -Cytoplasmic granules

MOA of Cinacalcet? Indication?

Its a calcimimetic that shuts down the CaSR's in the Parathyroid gland to decrease PTH secretion! Used in primary or secondary hyperparathyroidism

Explain the pathogenesis of poison ivy

Its a contact dermatitis to urushiol, which causes an immune response when attached to proteins (ie. a hapten)/ This is a type IV hypersensitivity rxn that takes place in 2 phases: 1. Sensitization phase: Cutaneous dendritic cells take up hapten, express it on MHC class I and II, and run to the draining lymph nodes to interact with CD4 and CD8 cells, causing activation and clonal expansion 2. Elicitation Phase: Occurs w/in 2-3 days of reexposure to same antigen. Hapten is taken up by skin cells and causes activation of hapten sensitized T cells (usually CD8) in the dermis/epidermis. Inflammation then occurs = rash!

Describe the toxins of Pertussis

Its a gram negative coccobacillus Pertactin = adherence to upper respiratory epithelium (basis of acellular vaccine) Tracheal toxin = local tissue destruction, responsible for whooping cough Adenylate cyclase toxin (like anthrax EF) and pertussis toxin (ribosylates Gi, theres increasing cAMP) = prevent phagocytosis, persistence of organism in alveolar macros and ciliated epithelial cells (prolonged disease course) Note-- lymphocytosis is induced by Pertussis toxin

MOA of oseltamivir?

Its a neuraminidase inhibitor used for Influenza! (aka Tamiflu) Prevention of vision release from infected cells

Describe Postpartum endometritis. what bugs can cause this? Risk factors?

Its a polymicrobial uterine infection (Gardnerella, Peptococcus, bacteroides, Staph epidermidis, Group B Strep) that is especially common following a C-section (allows foreign bodies into normally sterile uterus). Presents as fever, lower abdominal pain, malodorous discharge after delivery. Physical findings include uterine funal tenderness and leukocytosis. Peritonitis and sepsis can occur with hematogenous spread of pathogens.

Clinical manifestations of West nile virus?

Its a positive sense RNA virus Fever Rash Neuro manifestations (encephalitis, flaccid paralysis, meningitis, seizures, coma)

Why might arginine help treat stable angina?

Its a precursor for Nitric oxide, which will lead to relaxation/vasodilation of smooth muscle cells!

Foscarnet MOA? Used for? Does it need to be Phosphorylated?

Its a pyrophosphate analogue that does NOT require intracellular activation. In treating Herpes Virus, it inhibits DNAP In treating HIV, it inhibits reverse transcriptase Used for Ganciclovir resistant CMV or Acyclovir resistant Herpes Virus infections

What is Cushing's triad? What is it for?

Its a response to increased ICP 1. Increased BP 2. Irregular breathing (ie. bradypnea) 3. Bradycardia

What does the methacholine challenge test evaluate? How does it work?

Its a sensitive test for asthma Measures Bronchial hyperactivity (BHR). Its quantified as the concentration of inhaled aerosolized bronchoconstrictive substance required to produce a 20% decline in FEV1.

What does polycistronic mean? Is it typically in pro or eukaryotes?

Its a single mRNA molecule which codes for more than 1 protein. More commonly found in prokaryotes

MOA of Canagliflozin? Side effects? What must you check before starting a patient on this?

Its a sodium-glucose cotransporter 2 (SGLT2) inhibitor that functions in the PCT to block reabsorption go filtered glucose. Causes glucosuria, which leads to UTIs, Yeast infections, and maybe symptomatic hypotension (due to loss of osmotic substance). *Must check pts renal function first to make sure the drug can reach the kidney and so it doesn't build up in serum leading to side effects!

How exactly does ocreotide treat esophageal varices?

Its a somatostatin analogue. It is able to reduce splanchnic blood flow and divert blood flow from the portal system to the systemic circulation by indirectly inducing splanchnic vascular constriction. This process is accomplished by the inhibition of the release of hormones that produce splanchnic vasodilation, such as glucagon and VIP. Also, it does NOT cause systemic vasoconstriction, which is good!

What is isotretinoin? What is it used to treat? How does it work?

Its a synthetic 13-cis-isomer of naturally occurring all-trans-retinoic acid (tretinoin), a derivative of Vitamin A. It can be used orally to treat severe acne associated with scarring. Its also indicated in pts who fail therapy with topical tretinoin/benzoyl peroxide and antibiotics. Retinoids inhibit follicular epidermal keratinization, thereby loosening the keratin plugs of comedones and facilitating their expulsion. They also reduce the size of sebaceous glands and inhibit sebum production!

What are the causes of clubbing? What is the actual pathophysiology of clubbing?

Its all due to HYPOXIA: 1. Lung Diseases: Lung cancer (especially Large cell CA), tuberculosis, cystic fibrosis, bronchiectasis, pulmonary HTN, empyema, and many other chronic lung disease associated with hypoxia 2. Herat diseases: Cyanotic congenital heart diseases (5 T's, especially tetralogy of fallot) and bacterial endocarditis 3. Other: IBD, hyperthyroidism, and malabsorption Not really sure what causes it, but in diseases with R-to-L shunting, it is though to be caused by a failure of platelet precursors to fragment completely into platelets within the pulmonary circulation. The result is an increase in peripheral circulation of megakaryotcytes and platelet clumps. These impact in the fingers and toes, and release PDGF and VEGF (promotors of vascularity). This results in increased fibrovascular proliferation, leading to clubbing of the fingers and toes. Elevated levels of PGE2 (which activates platelets via the EP3 receptor) have also been implicated in the pathogenesis of clubbing.

Describe the function of the CFTR that gets mutated in cystic fibrosis:

Its an ATP-binding cassette transmembrane ion transporter that pumps Chloride ions out of epithelial cells against a concentration gradient using ATP hydrolysis for energy. By pumping chloride out of the cell, the CFTR also establishes a membrane potential that draws sodium and water out of the cell as well! Also directly inhibits apical ENaC) channels that reabsorb Na+. By pumping NaCl and water across epithelial membranes, the CFTR hydrates mucous surfaces like airways, bowel, and exocrine pancreas! ***CFTR also plays a role in the production of hypotonic sweat. In the eccrine gland, sweat is initially isotonic with plasma. During transport through the eccrine duct, Cl- is normally reabsorbed from the duct lumen via CFTR, and it also stimulates ENaC to increase luminal Na+ reabsorption. Patients with CF however have an elevated sweat chloride level due to a CFTR defect (hypertonic sweat)! (screening test)

Describe the actions of Hormone Sensitive Lipase during times of starvation

Its an enzyme found in adipose tissue that catalyzes the mobilization of stored Triglycerides into *Free Fatty Acids and Glycerol*. HSL is activated in response to stress hormones and inhibited by insulin. When stress hormones stimulate Gs protein coupled receptors on adipocytes, it causes increased cAMP production and activation of PKA, which phosphorylates/activates HSL, stimulating lipolysis. FFAs and glycerol released into circulation can be taken up by the liver, where the glycerol can be used as a primary carbon source for gluconeogenesis (maintaining blood glucose levels). The liver oxidizes the FFAs to Acetyl-CoA, which can then be further metabolized to *ketone bodies* or shunted into the TCA cycle to generate energy for gluconeogenesis. During starvation, most tissues utilize a combo of FFAs and ketones for their energy needs. Important exceptions are the brain (FFAs do not cross the BBB, so only ketone bodies/glucose can be used) and RBCs (can only use glucose due to lack of a mitochondria)

How does coagulase add to Staph aureus's virulence?

Its an enzyme that activates prothrombin, causing conversion of fibrinogen to fibrin. This process leads to fibrin-coating of Staph aureus and resistance to phagocytosis!!!

What is pseudobulbar palsy? What causes it?

Its caused by neurological conditions such as multiple sclerosis and is characterized by dysarthria, dysphagia, dysphonia, and impaired movement of the tongue/facial muscles

What is the septum transversum? What does it give rise to? What is its remnant?

Its composed of mesoderm ally-derived tissue that extends ventral to the the gut tube from the umbilicus to the pericardium. Gives rise to the myoblasts that form the diaphragm Exists as a vestige as the central tendon of the diaphragm

What is intestinal atresia of the midgut? How does it present?

Its the result of *vascular occlusion* in utero. Diminished intestinal perfusion leads to ischemia if a segment of bowel. The result is a proximal segment that ends in a blind pouch, followed by an area of absent small bowel and associated dorsal mesentery. Finally, a distal segment of ileum that assumes a *spiral configuration* around an ileocolic vessel. This specific pattern is known as an *apple-peel or Christmas tree* deformity

Treatment for onchocerciasis?

Ivermectin

Where are most dietary fats absorbed in the GI tract?

Jejunum Once absorbed, the fatty acids, monoglycerides, and cholesterol and reconstructed into TGs, phospholipids, and cholesterol esters with apolipoproteins to form chylomicrons, which are released into the intestinal lymphatics

What are 2 congenital long QT syndromes, and what is the main difference between each?

Jervell and Lange-Nielsen syndrome: AR, *sensorineural deafness* ("small jerk that can't hear") Romano-Ward Syndrome: AD, pure cardiac phenotype (NO DEAFNESS) ("Mr. Romano thought he was an alpha male") Both are usually due to a POTASSIUM channel defect

Vasculitis associated with MI?

Kawasaki disease common in children, coronary aneurysms and subsequent thrombosis Tx with ASPIRIN (screw Reyes syndrome)

Difference between keloid and hypertrophic scar?

Keloid extends BEYOND the borers of the original wound and do not regress spontaneously!

What nerve can be injured during hyper flexion of the thighs in the lithotomy position for pelvic/vaginal surgery?

Lateral femoral cutaneous nerve Courses deep to inguinal ligament to innervate the anterolateral thigh and skin. If injured, numbers ensues = *meralgia paresthetica*

What type of breathing is associated with a metabolic acidosis (especially DKA)?

Kussmaul breathing- deep and labored

For coronary bypassing graft after an MI, what does the surgeon use if its a blockage of the LAD? What if its multiple vessels?

LAD alone = left internal mammary (thoracic) artery-- superior patency rates Multiple coronary arteries = Great saphenous vein (medial aspect of leg-- "Saddle side")

Describe LAD type 1? type 2? type 3?

LAD-1: Absence of CD18 (can't synthesize ß2 integrin needed to attach to ICAM-1 during tight adhesion). Will get recurrent infections WITHOUT PUS and DELAYED DETACHMENT OF THE UMBILICAL CORD LAD-2: impaired fucosylation of Sialyl Lewis bodies prevents them from binding to selectin, so no rolling occurs. Milder condiiton LAD-3: impaired cytokine signaling prevents intern activation. Almost exact same clinical manifestation at type 1 "2,3,1"

PSGN findings on: LM? IF? EM?

LM = hypercellular glomeruli (all lobules of all glomeruli due to leukocyte infiltration and mesangial/endothelial proliferation) IF = Coarse GRANULAR deposits of IgM, IgG, and C3 with "STARRY SKY" appearance (lumpy bumpy) EM = immune complexes (type III HS) deposit on epithelial side of BM (sub epithelial) --> humps

What causes the sickling in Sickle cell anemia?

LOW OXYGEN levels, increase acidity, increased 2,3-BPG, or low blood volume. Also occurs due to organs with high metabolic demands (brain, muscles, placenta) due to increased oxygen extraction from blood (oxygen unloading).

Function of LPL? What must you give in order to measure it in the laboratory?

LPL is bound to heparin sulfate moieties on the vascular endothelium, allowing it to interact with chylomicrons and VLDL in the circulation and release free fatty acids into adjacent tissues. Heparin administration released these endothelium-bound ligases, allowing LPL activity to be measured in the laboratory.

What is seen in the CSF of patients with narcolepsy?

Lack of hypocretin-1 (orexin-A) and hypocretin-2 (orexin-B) These are produced only in neurons located in the lateral hypothalamus. These neuropeptides function to promote wakefulness and inhibit REM sleep-related phenomena. Hypocretin levels are only measurable in the CSF, not the blood!

What are lacunar infarctions? Risk factors?

Lacunar infarctions are the result of small vessel occlusions (due to lipohyalinosis and microatheroma formation) in the penetrating vessels supplying the deep brain structures (the lenticulostriate arteries). *Risk factors include uncontrolled HTN and Diabetes Mellitus.

What poses a physical barrier against the sprouting of new blood vessels?

Laminin in the BM

Function of the splenic red pulp? Why are spleens so good at removing encapsulated bacteria?

Large numbers of macrophages line the red pulp cords and sinusoids and ingest any particulate matter that becomes trapped. The red pulp is important for: 1. Destroying aged/abnormal RBCs and serving as an emergency store of RBCs and platelets that can be released when needed 2. Clearance of circulating bacteria that become lodged in cords. Macrophages then present captured antigens to the B and T cells residing int he splenic white pulp to generate an activate immune response ***Splenic opsonizing antibody that is secreted by splenic B lymphocytes is very important in the clearance of encapsulated species, as the capsule allows them to resist innate phagocytosis!!!

What lesions in the brain cause bilateral pinpoint pupils?

Large, bilateral pontine lesions caused by damage to the descending sympathetic tracts

Where are ringed sideroblasts seen? What about basophilic stippling?

Lead poisoning can cause basophilic stippling, which can be seen in peripheral blood smear. Its due to abnormal degradation of rRNA since lead inhibits a nucleotidase) Ringed sideroblasts are typically seen in sideoblastic anemia, and are found in the bone marrow!

How can a Ras mutation lead to cancer?

Leads to an inability to split GTP (via a GAP protein), resulting in a permanently activated Ras bound to GTP that stimulates proliferation via the MAP-kinase pathway, leading to cancer!

In the event of a nuclear reactor accident, what should patients take to minimize thyroid effects?

Leakage of Iodine-131 is radioactive Pts should take potassium iodide Energy dependent transport of inorganic iodide into the thyroid follicular cell (iodide trapping) is accomplished by the sodium-iodide symporter located on the basolateral membrane. Because this symporter takes up all iodide (as well as other ions such as pertechnetate and perchlorate), high serum levels of nonradioactive iodide can *competitively inhibit* radioactive I-131 from entering the thyroid follicular cells. Large increase in serum Iodide levels can also inhibit iodide organification (Wolff-Chaikoff Effect) and reduce thyroid hormone release!

Main toxin of C. perferinges? How does it add to its virulence?

Lecithinase (alpha toxin) is an enzyme with phospholipase C activity, increasing platelet aggregation and adherence molecule expression on leukocytes and endothelial cells! This results in vasooclusion and ischemic necrosis of affected tissues!!!

Where does the AV node usually get its blood supple from?

Left Coronary Artery

Front lobe infarcts can cause "Frontal Lobe Syndromes." What is seen with a Left-sided frontal lobe lesion? Right sided?

Left Sided Frontal Lobe lesion: -*APATHY* and depression. "Lose your Love with Left" Right Sided Frontal Lobe lesion: -*Disinhibited Behavior* "Right makes you raunchy!"

Where are clots most likely to form in a patient with a-fib?

Left atrial appendage

Where does blood supply come from for left gastro-eiploic vein? Right?

Left gastroepiploic = Splenic Vein Right gastroepiploic = Superior Mesenteric Vein

Fractured distal left 12th rib. What organ can be punctured?

Left kidney! (can be right kidney too if on right side)

What are fibroids? How does the uterus look?

Leiomyomas -- proliferation of myometrial smooth muscle. Can cause heavy menstrual bleeding, but the uterus is IRREGULARLY enlarged

How does myelin affect the length constant? Time constant?

Length constant = measure of how far along an axon an impulse can propagate. More myelin = Higher length constant. Time constant = measure of how long it takes for a change in membrane potential (want it to be low) More myelin = lower time constant

How is the degree of severity of Mitral stenosis determined?

Length of time between S2 (specifically A2) and the opening snap! Decreased time between A2 and OS = increased severity! As MS worsens, left atrial pressures increase due to impaired movement of blood into the left ventricle. High pressures actually cause the valve to open early and more forcefully; as a result, the A2-OS interval becomes shorter as the left atrial pressure increases!!! This is usually measured via 2-D Doppler Echocardiography

What is jugular foramen (Vernet) syndrome? Clinical symptoms?

Lesion in the jugular foramen where CN's 9, 10, and 11 pass through Dysphagia, hoarseness, loss of gag reflex on ipsilateral side, and deviation of uvula toward normal side

Lesions to which part of the cerebellum can cause limb dysmetria (overshoot/undershoot during targeted movement)?

Lesions affecting the cerebellar hemispheres due to involvement of the lateral descending motor system (eg., lateral corticospinal tract, rubrospinal tract). Hemispheric cerebellar lesions may also cause tremors during goal-directed activity (intention tremor)

What lesions cause nystagmus usually?

Lesions to the pons, medulla, or cerebellum due to disruption of vestibular pathways

Where do most gastric ulcers occur? Why?

Lesser curvature of the stomach in the transitional zone between the acid secreting epithelium of the gastric corpus/body and the gastrin secreting G cells in the epithelia of the antrum. May be due to best micro environment of pH for H pylori to survive

Which Amino Acids are exclusively ketogenic? Which are both gluconeogenic and ketogenic?

Leucine and Lysine = Ketogenic (produces acetoacetate or its precursors)----*** Treatment for patients with PDH deficiency Phenylalanine, Isoleucine, and Tryptophan = Both gluconeogenic (produces intermediates of the TCA cycle or pyruvate)and ketogenic

Delayed separation of the umbilical cord. Which disease?

Leukocyte Adhesion Deficiency (LAD) type I AR defect in LFA-1 Integrin (CD18) protein on phagocytes, causing impaired migration/chemotaxis. Integrins bind to ICAM/VCAM to mediate tight binding! Presents with recurrent bacterial skin and mucousal infections, *absent pus formation*, impaired wound healing, and *delayed separation of the umbilical cord*! (>30 days) Will see neutrophilia in blood (can't get out of vessels) and absent neutrophils at sites of infection!

What muscle do Kegel exercises strengthen?

Levator Ani (part of the anal triangle and pelvic floor)

What foramen does the piriformis overly? What runs above the muscle? Below it?

Lies over the greater sciatic foramen Above = superior gluteal nerve/vessels Below = Inferior gluteal vessels, internal pudendal vessels, and SCIATIC NERVE (+others)

Limiting factor of glycolysis in strenuous exercise?

Limited regeneration of NAD+ from NADH

How does Linezoid cause serotonin syndrome?

Linezolid has MAO-inhbiitor activity and therefore can contribute to serotonin syndrome when concomitantly used with an SSRI, SNRI, or TCA!

Difference between LPL and HSL?

Lipoprotein Lipase (LPL) = enzyme found on endothelial cells that functions to degrade TGs found in Chylomicrons and VLDL. It works in the bloodstream to form FFAs that are then transported into adipocytes storage or used by tissues for energy production HSL = activated by stress hormones during starvation. Stimulates the hydrolysis of TGs into FFAs and glycerol. Glycerol is used as carbon backbone for gluconeogenesis, FFAs are converted to Acetyl CoA by liver for use in ketone synthesis or shunted into TCA cycle.

How does Listeria escape the phagosome into cytosol?

Listeria Lyses the vacuolar membrane with Listeriolysin O, a pore forming toxin that is selectively activated within acidified phagosomes!

Name some of the specialize monocytes in our body

Liver = Kupffer cells Bone = osteoclasts CNS = microglial cells Kidney = mesangial cells Lung = alveolar macrophages Inflammation = multinucleated giant cells Granulomatous inflammation = epithelioid cells

Cut P450 is found in what 2 locations?

Liver and small intestine wall

Blood tests to determine: -Liver functionality? -Structural integrity/intactness of liver? -Structural integrity/intactness of the biliary tree?

Liver functionality = PT, PTT, Albumin, and cholesterol Liver structure = Transaminases Biliary Tract Structure = ALP, GGT

Are drugs with a high volume of distribution usually cleared by the liver or kidneys? Why?

Liver! These drugs are lipophilic and readily enter hepatocytes as well as many other tissues. They do not like being in the blood stream and filtered by the kidneys. Even if the drug is somehow filtered by the glomerulus, it will be rapidly reabsorbed by crossing the tubular cell membranes to reenter the tissues.

Peaked T-waves on an ECG?

Localized HYPERKALEMIA (1st sign of MI on an EKG, followed by Q-waves)

Common cervical findings seen in RA? If you intubate the patient, what is a possible complication?

Long-standing RA can affect the cervical spine, causing vertebral malalignment (subluxation) that can affect the AA joint! Extension of the neck during intubation can worsen the subluxation, leading to acute compression of the spinal cord and/or vertebral arteries!

What are anal fissures? Why do they occur? Where do they most often occur?

Longitudinal tears in the mucousa. Usually due to passage of hard stool in patients with chronic constipation. Most occur at the posterior midline distal to the dentate line, likely due to decreased blood flow in this area

Why does NSAID use with loop diuretics lead to a blunted response?

Loop diuretics also stimulate PG release, causing afferent arteriole dilation, increasing RBF leading to an increased GFR and enhanced drug delivery! *Loop diuretics also stimulate renin release!

What are the 2 opioid anti-diarrheal agents? How are they ensured not to be abused?

Loperamide and Diphenoxylate They are combined with atropine, which produces adverse effects (nausea, blurred vision, dry mouth) if taken at high doses These drugs should not be used for diarrhea due to toxin producing or invasive organisms

Electrolyte disturbance in diarrhea?

Lose water, K+ and HCO3- (leads to metabolic acidosis)

Explain the dexamethasone suppression test

Low dose (0.5 mg) and it suppresses--- they are "sad, fat, or normal" High dose (1mg) and it suppresses --- Pt has a pituitary adenoma If it does NOT suppress, they have an adrenal adenoma or ectopic secreting ACTH tumor (small cell lung cancer)

Actions of Dobutamine is dose increases?

Low dose = Stimulates D1 receptors in renal vasculature, dilating them (increases RBF and GFR), also mesenteric vasodilation Medium dose = ß1-adrenergic activation High Dose = alpha-1 receptor activation "DBA"

Treatment for 21-hydroxylase deficiency?

Low dose corticosteroids to suppress the secretion of ACTH (brain senses low cortisol so it pumps that shit out) Less ACTH will lead to less androgen production by the adrenal zone reticularis

Where is the optimal site for obtaining vascular access in the lower extremity during cardiac catheterization? Why?

Lower extremity through the Common femoral artery (CFA) BELOW the inguinal ligament If you puncture the artery above the inguinal ligament, you can get retroperitoneal bleeding, which can not be easily stopped!

Most common metastatic tumors to the brain?

Lung cancer, Renal cancer, and malignant melanoma

What is LGV? What disease causes this? Explain the course.

Lymphpgranuloma venereum - Chladmydia trachomatis serotypes L1-L3 Starts as PAINLESS, small, shallow genital ulcer containing infected cells. Weeks later they get swollen, PAINFUL coalescing INGUINAL LYMPH NODES ("BUBOES"). Can lead to fibrosis, lymphatic obstruction, and anogenital strictures/fistulas

What disease/syndrome is characterized by defective DNA Mismatch Repair? How does MMR work?

Lynch Syndrome (HNPCC) Mismatch repair begins with MutS homolog detecting a mismatch on the newly created daughter strand, which is distinguished from the parental strand by occasional nicks in the phosphodiester bonds. MutL homolog is then recruited, and the resulting complex slides along DNA molecule until 1 of the daughter strand nicks is encountered. At this point, exonuclease-1 is loaded onto and activated by the repair complex. The daughter strand is then degraded backward past the initial mismatch point, leaving a variable gap of ss-DNA that is stabilized by ssDNA-binding proteins. The complex then dissociated while DNAP delta loads at the 3' end of the discontinuity and begins synthesizing a new daughter strand segment. Finally, DNA ligase I seals the remaining nick to complete repair process. *Note- AD mutation in either MutS or MutL is responsible for Lynch Syndrome!

How does activation of M3 receptors lead to vasodilation?

M3 receptors are present on the endothelial surface, causing the synthesis of NO! NO then diffuses into vascular smooth muscle cells, increasing cGMP and activating myosin light chain phosphatase! (just like nitrates)

Type of Urinary Incontinence in Multiple Sclerosis

MC is Urge incontinence due to loss of CNS inhibition of Detrusor contraction in the bladder (UMN lesion can cause hyperreflexia) As disease progresses, bladder can become atonic and dilated, leading to overflow incontinence

Protein spike in Multiple myeloma? MGUS? Waldenstrom Macroglobulinemia?

MM = IgG MGUS = IgG, asymptomatic Waldenstrom Macroglobulinemia = IgM, hyperviscosity syndrome

Structures arising from neural crest?

MOTEL PASS Melanocytes Odontoblasts Tracheal cartilage Enterochromaffin cells Laryngeal cartilage Parafollicular Cells of thyroid (C cells) Adrenal medulla Schwann Cells Spiral membrane

What are the 2 most important factors for osteoclastic differentiation? Where does osteoprotegrin come into play?

Macrophage-colony stimulating factor (M-CSF) and NFkß (RANK-L), both made by osteoblasts and bone marrow stromal cells OsteoPROTEGrin (OPG) PROTECts the bone from osteoclasts! It is a decoy receptor that binds to RANK-L so RANK-L cant bind RANK (the receptor). This decreases the differentiation and survival of osteoclasts! This is exactly how Denosumab works! -Loss of function of Osteoprotegrin is seen in juvenile Paget's disease of the bone!

What is the major humoral protection from re-infection with the same strain of influenza A? What is another weaker one?

Main protection is from Abs against hemagglutinin, which neutralize the virus and prevent entry into most cells. (its on the exterior of the virus!) Abs to neuraminidase have some protection too, but not as much (decreases extent of viral invasion and shedding)

What inhibits Carnitine acyltransferase in order to prevent breakdown of newly synthesized Fatty acids?

Malonyl-CoA

Gamma glutamyl Transpeptidase: where is it found?

Many organs, including liver

Example of CCR5 Antagonist in HIV therapy? MOA?

Maraviroc- Inhibits HIV entry by allosteric blocking of HIV p120 interaction with CCR5 on target host cell

What is Pure Red Cell Aplasia (PRCA)? What can cause it?

Marrow failure characterized by severe hypoplasia of marrow erythroid elements in the setting of normal granulopoiesis and thombopoeisis. Its due to inhibition of erythroid precursors by IgG auto-Abs or cytotoxic T-lymphocytes Associated with thymomas, lymphocytic leukemias, and parvovirus B19 infection.

Technique employed to limit confounding?

Matching

Structure of the brain frequent to undergo necrosis in the setting of thiamine deficiency in an alcoholic? What are other lesions of the brain that can cause this?

Maxillary body It is part of the Papez circuit, which is a neural pathway of the limbic system that is involved in the cortical control of emotion and memory Can be caused by other structures of the Papez circuit: Fornix- bundle of axons from hippocampal subiculum that project to maxillary body Anterior nucleus of the thalamus

Describe Glycogen Storage Disease type V

McArdle Disease --- deficient Skeletal muscle glycogen phosphorylase (Myophosphorylase) Increased glycogen in muscle, but muscle can't break it down! Causes painful muscle cramps, Myoglobinuria (red urine) with strenuous exercise and arrhythmias from electrolyte abnormalities. Second-wind phenomenon noted during exercise due to increased muscular blood flow. (*lots of "M's") Blood glucose levels are typically unaffected (muscles are greedy)

Where is the optic canal in relation to the superior orbital fissure? What runs through it?

Medial to the superior orbital fissure Optic nerve (CN II) and ophthalmic artery

MC Thalassemia is pts of: -Mediterranean descent? -Southeast Asian descent?

Mediterranean = Beta thalassemia Southeast Asia = Alpha thalassemia

Breast tumor with a lymphocytic infiltrate?

Medullary Carcinoma *seen a lot with BRCA1 mutations

Which skin cancer is the most likely to metastasize? Where does it like to go?

Melanoma Brain, GI tract, bone, liver, and lungs

Trisomies that are associated with myelomeningocoele? omphaloceoele?

Meniingocoele = Edwards Syndrome (Trisomy 18) Omphalocoele = Edwards and Patau (Trisomy 18 and 13) *Will see elevated AFP levels in each! (leaks right out of defects in maternal serum!)

Brain tumor with psammoma bodies? Describe it

Meningioma

How is cryptococcus neoformans diagnosed if: meningoencephalitis? Pneumonia?

Meningoencephalitis = India Ink stain of CSF (stains the background really dark--negative staining technique) Pneumonia = mucicarmine staining of lung tissue and bronchoalveolar (BAL) washings

Woman can't get pregnant. Decides to try Menotropin therapy followed by some other drug. What the hell is the theory behind all of this?

Menotropins = human menopausal gonadotropin These mimic FSH and trigger the formation of a dominant follicle. When the follicle appears mature, you give hCG, which stimulates the LH SURGE (rupture of the dominant follicle, releasing the ovum). The alpha subunit of hCG is structurally similar to LH!

3 types of exocrine glands?

Merocrine Apocrine Holocrine

Antipsychotics block dopamine in which pathway? (aka which dopaminergic pathway is hyperactive in schizophrenia?)

Mesolimbic-Mesocortical pathway, which is responsible for regulating behavior (also known as frontal cortex pathway)

What metabolizes marijuanna? Where is it stored?

Metabolized by the liver, stored in the fat for up to 30 days

Describe how the fetal kidney develops

Metanephric blastema = functional renal parenchyma by 10 weeks and the ureteric bud (a dorsal outgrowth from the mesonephric duct)= renal pelvis/ureter (due to canalization)

MOA of Rituximab? Indication?

Monoclonal Ab against CD20, used to treat B cell NHL, CLL, Rheumatoid Arthritis, and ITP

MOA of PCSK9 inhibitors?

Monoclonal Abs that reduce LDL receptor degradation in the liver, leading to increased LDL reuptake!

MOA of biguanide use? Side effects?

Metformin! Inhibits mitochondrial glycerophosphate dehydrogenase and complex I (first ETC enzyme). The resulting decrease in energy stores causes AMPK activation, leading to decreased hepatic gluconeogenesis. Also increases peripheral glucose utilization. GI upset and LACTIC ACIDOSIS. -Lactate is normally produced in the intestine, and converted to glucose via gluconeogenesis in the liver. Inhibition of mitochondrial enzymes by metformin increases intestinal production of lactate (due to increased aerobic glycolysis) and reduces hepatic metabolism of lactic acid (due to decreased gluconeogenesis). This increase the risk of lactic acidosis, particularly in older pts with significant renal or hepatic disfunction. Must measure renal function via serum creatinine measurements!

Treatment for methemoglobinemia

Methylene blue Acts as an artificial electron transporter for reduction of methemoglobin through the NADPH pathway!

Tx for C. diff?

Metronidazole or oral vancomycin Maybe fidaxomicin for recurrent infections

Defect in Chediak-higashi syndrome? What bugs are they susceptible to? What are other sequela due to this dysfunction?

Microtubule dysfunction in phagolysosome fusion due to mutation in Lysosomal Trafficking regulatory gene (LYST). Susceptible to pyogenic infections (Staph and Strep) Albinism bc melanocytes can't "hand off" melanin to nearby keratinocytes due to microtubule problems Same reason for peripheral neuropathy ***Horizontal nystagmus seen

Describe the murmur heard in MVP. Why does squatting cause the murmur to disappear?

Mid systolic click followed by a mid to late systolic murmur at the cardiac apex Squatting increases venous return into the LV, helping to bring the valves into a more anatomic alignment.

Where is clavicle most often fractured?

Middle 1/3

What is the artery injured in an epidural hematoma? Where does it branch off of? Symptoms of an epidural hematoma?

Middle Meningeal Artery (foramen spinosum) Branches off the maxillary artery, which is a branch of the external carotid artery Requires prompt treatment since its under arterial pressure and can expand rapidly causing increased ICP (Cushing Reflex), brain herniation (uncal herniation with oculomotor nerve palsy), and death!

When does foregut become midgut?

Midway between 2nd part of duodenum! Proximal half of 2nd part of duo = foregut Distal half of 2nd part of duo = midgut

What 3 medications can induce an abortion? How do they work?

Mifepristone: Progesterone antagonist. In the first 7 weeks of pregnancy, progesterone is secreted by the corpus luteum; thereafter, its secreted by the placenta. Progesterone receptor blockade via mifepristone causes apoptosis and necrosis of the uterine decidua and prevents further development of a 1st trimester pregnancy! Misoprostol: Prostaglandin E1 analogue that causes vertical softening and uterine contractions leading to expulsion of the pregnancy Methotrexate: Folic Acid antagonist that inhibits trophoblast division, therefore decreasing trophoblast survival, hindering implantation, and encouraging expulsion. *Normally Mifepristone is used in conjunction with misoprostol. If mifepristone is not available, can use methotrexate *Methotrexate is used for ectopic pregnancy

What is Trousseau's syndrome? What is it seen in? What causes it?

Migratory superficial thrombophlebitis due to an adenocarcinoma (usually pancreatic, but also colon and lung) that secretes Mucin/thromboplastin-like molecules that cause intravascular coagulation, leading to a hypercoaguable state!

What is Trousseau Syndrome? What is it associated with? What causes it?

Migratory thrombophlebitis classical associated with pancreatic cancer or other disseminated cancers. It occurs due to the PROCOAGULANT effects of MUCIN in the blood stream. That is why it is most often seen with mucinous adenocarcinoma of the pancreas or lungs!

How do mitochondrial defects usually manifest?

Mitochondria are responsible for ATP production via oxidative phosphorylation, so defective mitochondria manifest as lactic acidosis and primarily affects tissues with the highest metabolic rates (neural and muscular tissue)

Why do mitochondrial diseases display 100% frequency but with varying degrees of severity? What are 3 examples of this?

Mitochondrial DNA (inherited from mother) can under go mutations during mitosis, just like any other DNA from the nucleus The variability occurs because some cells receive normal mitochondrial genomes, while other cells receive damaged Mitochondrial DNA! This mixture of the two types of DNA is called HETEROPLASMY Seen with Leber hereditary optic neuropathy, Myoclonic epilepsy with ragged-red fibers, and Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS)

MC underlying valvular disease predisposing to the development of IE? Why?

Mitral Valve Prolapse Microscopic deposits of platelet and fibrin occur due to endocardial injury from turbulent blood flow. These deposits easily get colonized by microorganisms during episodes of bacteremia (ie. dental procedures)

Function of MAO?

Monoamine Oxidase--- responsible for the breakdown of monoamine neurotransmitters (serotonin, dopamine, and Norepinephrine). Half life = 2 weeks (must wait 2 weeks after stopping MAO-ihibitor therapy before switching to SSRIs) MAO-inhibitors work by irreversibly blocking these enzymes, increasing the levels of these NTs in the synaptic cleft.

Characteristics of atypical depression? Treatment?

Mood reactivity, leaden paralysis, rejection sensitivity, and reversed vegetative symptoms (increased sleep and appetite) Tx: CBT and SSRI, but can use MAO-I if they don't work (3rd line due to increased risk of side effects)

Restless Leg SyndromeL: Who usually gets it? Pathophysiology/Tx?

More common in older pts, especially those with chronic kidney disease and diabetes (especially with neuropathy). Mostly involves the dopaminergic pathways and responds to dopamine agonists (ropinirole, pramipexole). Functional iron deficiency in the CNS is linked to dysfunction of dopaminergic pathways (iron-dopamine model). Iron deficiency is common in RLS, and low iron concentrations have been found in the substantia nigra of patients with RLS, even in the absence of systemic iron deficiency Think about Rob Dow, and how he was a little crazy. Probably was treating with Dopamine agonists

What is McCune-Albright Syndrome? Type of inheritance? Triad?

Mosaicism somatic mutation in the GNAS gene, which encodes the stimulatory alpha submit of G-protein, causing constitutive activation of adenylate cyclase in certain cells. 1. Fibrous Dysplasia (increased fibroblast and osteoclast function) 2. Endocrine abnormalities (precocious puberty) 3. Unilateral Cafe-au-lait spots (persistent activation of melanocytes)

What causes most duodenal ulcers? What if the ulcer is in the distal duodenum, past the duodenal bulb?

Most are due to H. pylori and NSAIDS Ulcers beyond the duodenal bulb = Zollinger-Ellison Syndrome (gastrinoma) *these also have multiple ulcers, ulcers refractive to therapy, and diarrhea due to inactive pancreatic digestive enzymes due to low pH

What mutations are seen in Congenital Long QT syndrome? What does this predispose patients to?

Most are due to mutations in the K+ channel protein that contributes to the outward-rectifying potassium current. A decrease in the outward K+ current leads to propagation of action potential duration and QT interval. This prolongation predisposes to the development of life-threatening ventricular arrhythmias (torsades de pointes) that can cause palpations, syncope, seizures, or sudden cardiac death

Describe how K+ is handled in the kidney

Most of the K+ filtered by the glomeruli is reabsorbed by the PCT and Loop of Henle. Normal conditions/Increased K+ load: Principal cells secrete K+ Hypokalemia: Stimulates alpha intercalated cells to reabsorb extra K+

Describe the structure of a secretory IgA molecule? How does it become that?

Most of the components are synthesized by plasma cells. Plasma cell makes 2 complete IgA molecules (4 heavy chains and 4 light chains) bound together by a J-CHAIN. The SECRETORY COMPONENT is made by epithelial cells in mucousa epithelium, and allows the IgA dimer to be secreted in mucus, tears, saliva, and colostrum.

Describe airway resistance in the lower respiratory tract:

Most of the resistance occurs within the 1st 10 generations of bronchi due to turbulent airflow. Resistance is maximal in the 2nd-5th generation always, including the segmental bronchi Resistance than drops suddenly due to the decreased radius of the airways, forcing smooth laminar flow

What types of drug overdose is very similar to that seen in rodenticides? tx?

Most rodenticides contain brodafacoum (*"superwarfarin"*) Tx overdose with FFP

How do you differentiate between Mullerian Agenesis (Mayer-Rokitansky Kuster-Hauser Syndrome) and Androgen Insensitivity?

Mullerian Agenesis will have pubic and axillary hair!

What do the sertoli cells of the testis secrete to cause degeneration of the Mullerian duct?

Mullerian Inhibitory Factor is secreted by the Sertoli Cell--- Causes ACTIVE Mullerian duct regression

What is the etiology of Osteoarthritis? Most significant risk factor?

Multifactorial, with excessive biomechanics stress and increased intraarticular metalloprotease activity as the major contributors to cartilage destruction Old age is the most significant risk factor, as well as obesity and underlying joint deformities

What are Multiple Myeloma cells particularly susceptible to? Why? How does this treat it?

Multiple Myeloma plasma cells are particularly susceptible to proteasome inhibition due to the large amount of proteins they manufacture. Inhibiting the proteasome causes accumulation of toxic intracellular and proapoptotic proteins, which BOTH increase apoptosis!

Describe how the skin ages. What happens to collagen?

Multiple environmental factors, especially UV light, contribute to again of the skin UVB wavelength are predominantly absorbed in the upper dermis and contribute too sunburn and increased risk of malignancy. UVA penetrate deeper into the skin and cause photoaging. UVA produces ROS which activate multiple inflammatory cell-surface receptors and nuclear transcription factors. This leads to *decreased collagen fibril production*, along with up regulation of metric metalloproteinases (including collagenases) that subsequently degrade type I and III collagen and elastin! Photo aging can be visible by age 30. Gradual thinning of the epidermis is seen, with reduction in subQ fat, blood vessels, hair follicles, sweat ducts, and sebaceous glands. Rate ridges at the dermoepidermal junction become flattened. This loss of subQ tissue causes the skin to be atrophic and more vulnerable to damage! Also there is increased cross-linking of collagen with deposition of collagen breakdown products. Th atrophic dermis and increased collagen cross linking, along with desiccation of the stratum corner, produces the characteristic wrinkling of photo aged skin!

What is associated with increased hCG in a triple screen?

Multiple gestation, hydatidiform mole, and choriocarcinoma

Why do Type-I diabetics have an increased likelihood to become hypoglycemic during exercise?

Muscle contractions cause non-insulin mediated GLUT-4 translocation *Exogenous insulin will continue to be released from the injection site despite falling glucose levels. Also, exercise can increase blood flow to the injection site, causing increased insulin absorption!

What is piriformis syndrome?

Muscle injury or hypertrophy to the piriformis can injure the sciatic nerve (runs below the muscle) This compression of the sciatic nerve can cause sciatic-like symptoms (pain, tingling, and numbness in the buttocks and along the nerve distribution)

When is dantrolene used? MOA?

Muscle relaxant effective in malignant hyperthermia. Binds ryanodine receptors on the SR and prevents Calcium release into cytoplasm of muscle fibers

What is the problem in Bruton X-lined agammaglobulinemia?

Mutation in Bruton Tyrosine Kinase (BTK) gene causes failure of bone marrow pre-B cells (CD 19,20+) to develop into mature circulating B lymphocytes (CD 19, 20, and 21+) They don't mature, so they don't become 21+!

What causes autosomal recessive polycystic kidney disease (ARPKD)? What is normally seen?

Mutation in PKHD1, the gene for fibrocystin. Fibrocystin is found in epithelial cells of both the renal tubule and bile ducts. Deficiency in fibrocystin leads to polycystic dilation of both structures

Why is the liver black in Dubin-Johnson Syndrome?

Mutation in the canalicular membrane transport protein leads to decreased excretion of bilirubin glucuronide Liver is black due to impaired excretion of epinephrine metabolites, which histologically appear as dense pigments within lysosomes

What bug knocks off HIV patients with CD4 counts <50?

Mycobacterium avium complex (MAC) = M. avium + M. intracelulare MAC presents with nonspecific symptoms of fever, weight loss, and diarrhea in an HIV+ patient. Different from Tb by: marked anemia, hepatosplenomegaly, elevated alkaline phosphatase and LDH, and *grows well at high temperatures and will exhibit optimum growth at 41 C* Tx = Azithryomycin/Clarithromycin with Rifampin or Ethambutol. May start prophylaxis with weekly Azithromycin is at risk pts.

Diseases that present with cold hemagluttinins?

Mycoplasma pneumonia EBV Hematologic malignancies

What kind of anemia does Mycoplasma cause?

Mycoplasma pneumonia can lead to a complement-mediated intravascular hemolytic anemia, due to the similarity between antigens in the cell membrane of Mycoplasma and the cell membrane of RBCs (I-antigen). Elevated levels of the cross-reacting IgM Abs ("cold agglutinins") can help diagnose this infection. Evidence of hemolytic anemia is seen (positive Coombs test, elevated reticulocyte count, elevated Lactate Dehydrogenase)

What are the direct negative effects of aldosterone on the heart?

Myocardial fibrosis and ventricular remodeling leading to ventricular hypertrophy! *This is why we give spironolactone to pts with CHF or decreased ejection fraction

Examples of Mitochondrial inheritance?

Myoclonic Epilepsy Leber Hereditary optic neuropathy

What is responsible for phase 0 of cardiac myocyte? Pace-Making cell?

Myocyte = Na+ influx Pace-Maker = Ca+ influx

Why can't oxytocin be used to terminate a 1st term pregnancy?

Myometrial oxytocin receptor concentration increases at term. Therefore, oxytocin has limited use on the uterus in early gestation

What is myxomatous change? Which disease involves myxomatous change?

Myxomatous changes (pathological weakening of connective tissue) in the media of large arteries are found in *cystic medial degeneration*. Medial degeneration is characterize by the fragmentation of elastic tissue ("basket weave appearance") and separation of the elastic and fibromuscular components of the tunica media by small, cleft like spaces that become filled with amorphous extracellular matrix. Marfan syndorme is a frequent cause of cystic medial degeneration in younger patients. It is characterized by an AD defect in the extracellular glycoprotein fibrillin-1. Fibrillar-1 is a major component of extracellular matrix microfibrils, which form the scaffolding for elastic fibers. Mutation of the fibrillin-1 gene predisposes to aortic aneurysms and dissections!

Which bacteria utilize IgA Proteases?

N. meningitidis N. gonorrhea Step Pneumo H. Influenza

2 ways to diagnose Chronic granulomatous disease?

NADPH Oxidase Defiency: 1. Nitroblue Tetrazolium Testing (NBT): -Add NBT (yellow) to patient's neutrophils. Properly functioning neutrophils produce ROS that reduce the NBT to DARK BLUE formazan. Will NOT TURN BLUE IN CGD 2. Dihydrorhodamine (DHR) flow cytometry: assess the production of superoxide radicals by measuring the conversion of DHR to rhodamine (fluorescent green). Cells deficient NADPH oxidase activity will exhibit decreased fluorescence

Defect in CGD?

NAPDH Oxidase deficiency, susceptible to catalase positive organisms

What is responsible for the acute inflammatory response in acute gouty arthritis? Treatment?

NEUTROPHILS! They phagocytize uric acid crystals, and then release inflammatory mediators 1st line Tx = NSAIDS If pt can't take NSIADS, then COLCHICINE! impairs neutrophil migration/phagocytosis by interfering with microtubule formation. Also decreases tyrosine phosphorylation (decreases neutrophil activation)

Describe how ammonia is transported from peripheral tissues to the liver so it can undergo the urea cycle

NH3 added to alpha-ketoglutarate to form glutamate, which hands it off to alanine, which takes it to the liver. This is called transamination and requires Vitamin B6

Is the femoral nerve in the femoral ring/sheath?

NO Contains Femoral artery, vein and canal (deep inguinal lymph nodes)

Is there proof reading action during translation?

NO! The proof-reading occurs during tRNA "charging" with amino acids vida Aminoacyl tRNA synthetases!

What is Kussmaul sign? What is it seen in?

Normally, the JVP will decrease in inspiration. Kussmaul's sign is a paradoxical RISE in JVP on inspiration. It indicates the right ventricle can't accommodate the increase in preload. Seen in constrictive pericarditis, because the thick fibrous tissue in the pericardial space restricts ventricular filling!

Would giving a drug that dilates coronary arteries in someone with chronic stable angina help?

NO! (ie. Adenosine or dipyrimadole) Coronary arteries in this case are in an area of flow-limited stenosis and are typically maximally dilated to maintain resting blood flow. Meds that cause dilation of coronary arteries (dihydropyridine Ca channel blockers) can divert blood AWAY from the ischemic area, bypassing any collateral circulation that has developed! (coronary steal phenomenon seen in cardiac stress testing!)

Does ASD lead to increased risk of infective endocarditis?

NO! The low pressure differential between the atria and absence of high velocity intra-cardiac flow jets do not damage any valves! *Bicuspid aortic valve, VSD, PDA, and unprepared tetralogy of fallot all predispose to IE!

Does a mid-shaft humeral fracture cause weakness in the triceps?

NO! The triceps are already innervated before the radial nerve travels through the radial groove.

How can a NOD2 mutation lead to Crohn's Disease?

NOD2 mutation--> Dec NF-kß secretion --> Dec pro inflammatory cytokines --> Dec innate immunity of gut--> Inc bacterial invasion into submucosa --> Chronic inflammation

Which beta blockers can cause Hyperkalemia?

NON-selective Beta blockers -Hyperkalemia occurs via beta-2 blockade. Interferes with beta-2 mediated intracellular K+ uptake

Treatment for anorexia nervosa?

NOT PHARMACOTHERAPY! Use CBT

Zolpidem structure, MOA, properties

NOT structurally related to benzo's Short acting, Binds to same portion of GABAa receptor as benzo's and enhances the inhibitory effect on CNS No real tolerance/addiction, no anti-convulsant properties, no muscle relaxing effects

How does chronic NSAIDS use lead to Chronic Interstitial nephritis?

NSAIDS concentrate int he renal medulla along the medullary osmotic gradient, with higher levels in the papillae. These drugs uncouple oxidative phosphorylation and are thought to cause glutathione depletion with subsequent lipid peroxidation, resulting in damage to tubular and vascular endothelial cells. Prolonged use results in chronic interstitial nephritis, seen as patchy interstitial inflammation with subsequent fibrosis, tubular atrophy, papillary necrosis and scarring, and caliceal architecture distortion. Calcium may deposit in areas of chronic inflammation and this calcification is visible on renal imagining. NSAIDS also decrease PG synthesis, causing constriction of medullary vasa recta and ischemic papillary necrosis!

Tell me about Listeria monocytogenes?

Narrow zone of Beta hemolysis Immotile at 37 C, but has tumbling motility at 22 C Can multiply at temps as low as 4 C

How does N. meningitidis go from infecting you to meningitis?

Nasopharyngeal colonization Proliferates, gets into blood Colonizes choroid plexus Enters meninges

Function of Nef and Tat HIV genes?

Nef = decreases expression of MHC class I on surface of virally infected cells Tat = plays a role in viral replication

RBC casts

Nephritic Syndrome, Malignant HTN

Fatty casts

Nephrotic syndrome (Maltese cross sign)

Most dangerous side effect of Amphotericin B? What can it lead to?

Nephrotoxicity-- decrease in GFR and direct toxic effects on the tubular epithelium Can lead to Hypokalemia and hypomagnesemia due to increase in membrane permeability of distal tubule Hypokalemia can lead to weakness and arrhythmias. Seen as T-wave flattering, ST-segment depression, prominent U waves, and premature atrial and ventricular contractions!

What endogenous enzyme degrades BNP? In what disease can inhibiting this enzyme be useful for

Neprilysin is a metalloprotease that degrades BNP. Medications that inhibit Neprilysin are being used for CHF!

What type of cell is melanoma derived from? Clinical features?

Neural crest cells

What tumor has a neuritic process called neuropil? What are some other characteristics about this tumor?

Neuroblastoma, the most common extra cranial solid tumor in children. Neuropil (neuritic process) are pathognomonic NSE, chromogranin, synaptophysin, and S-100 are all positive stains. Increased urinary levels of HVA and/or VMA. Most important biblical maker is N-MYC on chromosome 2!

Where are Merkel cells found? Function?

Neuroendocrine cells of the basal layer of epidermis that play a role in the perception of touch! Usually found in association with nerve projections. *Rarely can transform into malignant skin cancer known as Merkel cell carcinoma

What causes Neuroleptic malignant syndrome (NMS)?

Neuroleptic = antipsychotic medication Antagonism of central dopaminergic systems involved in thermoregulation and regulation of muscle tone and movement. The 4 primary clinical features: 1. Hyperthermia 2. Severe, generalized, "lead-pipe" rigidity 3. Autonomic instability 4. Altered mental status *Differs from serotonin syndrome in that serotonin syndrome has neuromuscular hyperactivity (shivering, clonus, and hyperreflexia)!

Conversion disorder: key fts?

Neurologic symptom incompatible with any neurologic disease; often acute onset associated with stress *Illness production and motivation are of UNCONSCIOUS drives

Tryptophan is the precursor molecule for what 3 things?

Niacin (requires Vit B6) Melatonin Serotonin (think carcinoid)

How many ATP's does Niacin make?

Niacin = Vit B3 Niacin makes NAD = 3 ATP

How does Nifedipine and indomethacin cause tocolysis of pre-term labor?

Nifedipine (calcium channel blocker) decreases intracellular calcium, which blocks myosin knives phosphorylation, causing myometrial relaxation! Indomethacin stops prostaglandin synthesis, which decreases uterine contractility!

What is the actual problem in Parkinson's Disease in regards to the Basal Ganglia? What 2 structures can you "zap" to help medically intractable symptoms?

Nigrostriatal degeneration in Parkinson Disease results in excessive inhibition of the thalamus. Reduced activity of the thalamus and its projections to the cortex consequently result in rigidity and bradykinesia. High-frequency deep brain stimulation (misnomer, actually knocks out the structure in "stimulates") can knock out the globus pallidus internus or subthalamic nucleus, resulting in thalamo-cortical disinhibition with improved mobility!

Effects of Verapamil on Skeletal muscle? Why?

No effect Skeletal muscle does NOT require an influx of Xtracellular calcium for contraction, whereas cardiac and smooth muscle do! (they need the calcium induced calcium release) Skeletal muscle relies on a physical interaction from the L-type Calcium channel to open the SR Ryanodine calcium channel!

What can cause gallbladder hypomobility? What can this cause?

No response to CCK. Can be caused by pregnancy, rapid weight loss, TPN, ocreotide, and high spinal cord injuries. Gallbladder functions to reabsorb water from bile, thereby concreting the bile. Biliary stasis causes over concentration which can lead to *biliary sludge*. Sludge formation is a precursor to stone formation (especially cholesterol).

Alcoholic walks in a stupor. Do you give dextrose right away? Why not? What do you give first? Why?

No! You must give thiamine first. If you give dextrose before thiamine, it can precipitate a Wernicke encephalopathy. Thiamine is a key coenzyme for pyruvate dehydrogenase, used in glucose metabolism. Thiamine deficiency results in the brain's inability to properly metabolize glucose and turn it into energy.

Is the liver prone to infarction? Why? Exception?

No! it has a dual blood supply (hepatic artery and portal vein) Exception is when a transplanted liver undergoes hepatic artery thrombosis. Liver can develop biliary tree infarction and organ failure due to collateral blood supply being severed during transplantation!

Explain how prolonged exposure to loud noises can cause hearing loss

Noise-induce hearing loss results from trauma to the stereo ciliated hair cells of the organ of Corti. The acoustic reflex normally dampens the effects of loud noises by causing the stapedius and tensor tympani muscles to contract, which lessens the responsiveness of the ossicles to sound. However, prolonged noise exposure can cause distortion or fracture of the stereocilia due to shearing forces against the tectorial membrane. High frequency hearing is lost first, regardless of the frequency of sound causing the damage!

Isoproterenol MOA

Non-selective Beta adrenergic agonist

Function of Club (Clara) cells?

Nonciliated secretory constituents of the terminal respiratory epithelium that secrete protein and surfactant compounds. They also help detoxify inhaled substances (ie. tobacco smoke) by a Cty P450)

Phentolamine MOA

Nonselective alpha blocker

What is sciatica? Nerve roots of sciatic nerve?

Nonspecific term for low back pain that radiates down the leg due to compression of the lumbosacral nerve roots (disk herniation or foraminal stenosis) Sciatic nerve roots = L4-S3

Alveolar gas equation? Normal values at sea level? Normal A-a gradient?

Normal A-a gradient = 10-15 mmHg

Where is Moraxlla catarrhalis normally found? What diseases does it cause?

Normal flora of Upper respiratory tract Causes otitis media and sinusitis, can exacerbate COPD

How does the initiation of Gout actually occur?

Normally the rate crystals have a protective coating of Apolipoprotein E or B. When uric acid levels fluctuate or micro trauma occurs, bare rate crystals are shed and exposed to IgG Abs. The subsequent Ab binding leads to neutrophil phagocytosis and release of inflammatory cytokines (primarily IL-1). This leads to infiltration by neutrophils and macrophages and subsequent inflammatory changes!

Umbilical hernia: -How does this occur? -Associated conditions? -Clinical features?

Normally the umbilical ring (aka the congenital fascial opening for the umbilical cord) closes and forms the linea alba, a midline band of fibrous tissue. Umbilical hernias are caused by an *incomplete closure of the umbilical ring (defective linea alba)*, thereby allowing protrusion of the bowel through the abdominal musculature! Occurs with Down Syndrome, HYPOTHYROIDISM (aka cretinism), and Beckwith-Wiedemann Syndrome These are reproducible, asymptomatic, and resolve spontaneously in first few years of life

Describe the tonicity/composition of salivary glands at low/high rates

Normally, Na and Cl are reabsorbed while K and bicarb are secreted When salivary glands are maximally secreted, the concentrations of the secretions reach that of plasma because there is not enough time to modify the secretions!

Patient with myopia has better vision as she reaches her 50's. What the hell is going on?

Normally, in accommodation, when focusing on near objects (like reading), ciliary muscle contraction relaxes the zonula fibers, allowing the lens to become more convex so the image focuses on the retina. Starting around age, 40-50, almost all individuals develop an inability to focus on near objects. In this condition, called *presbyopia* (far sightedness due to old age, most likely due to impaired lens elasticity from protein denaturation, less lens curvature changes, and diminished ciliary muscle strength), the image focuses *behind the retina*. Therefore, presbyopia can compensate for myopia (nearsightedness caused by image being focuses in front of the retina) by displacing the image backward, so it focuses on the retina. Patients with mild myopia often note improvement with age as presbyopia develops.

How does Diabetes cause albuminuria? (aka diabetic nephropathy, DN)

Normally, the GBM has negatively charged heparin sulfate moieties that form a *CHARGE* barrier preventing the leakage of negatively charged proteins, like albumin, into Bowman's Capsule. In diabetes, there is progressive loss of this negative charge due to up regulation of heparanase expression by renal epithelial cells, which results in leakage of *albumin* and other plasma proteins. In the initial stages of DN, only small amounts of albumin are lost (<300 mg/day). Detect with albumin-specific urine dip-stick test.

Cause of anteriomedial knee pain in runners?

Pes Anserinus bursitis *sartorius is longest muscle in body

What is superior mesenteric artery syndrome? What causes it?

Normally, the SMA (at level of L1) comes off aorta at 45 degree angle. If angle is less than 20 degrees, the *transverse portion of the duodenum* can get entrapped between the SMA and aorta, leading to symptoms of partial small bowel obstruction. Narrowing of the aortomesenteric angle can occur with any condition that causes *diminished mesenteric fat*, including low body weight, recent wt loss, severe burns, etc. Can ALSO occur with pronounced lordosis or after surgical correction of scoliosis, as this procedure lengthens the spine resulting in decreased mobility of the SMA!

Describe Hairy Cell Leukemia

Note- Cladribine and Pentostatin are adenosine analogues that inhibit Adenosine Deaminase!

How can a portal vein thrombosis lead to esophageal varices?

Note-- Ascites is uncommon since sinusoidal HTN does NOT develop with portal vein thrombosis

What are some risk factors for nephrolithiasis

Note-- Increased acid load in the renal tubules increases citrate reabsorption in the PCT, causing hypocitraturia! Note-- Calcium follows sodium/water reabsorption. Increased dietary sodium = less sodium reabsorbed = less calcium reabsorbed = stone Note- Pyridoxine (B6) decreases endogenous oxalate production and therefore decreases the rate of stone formation if patient is suffering from hyperoxaluria causing calcium oxalate stones!

What pathogens cause watery diarrhea? Dysenterry or inflammatory diarrhea? Enteric Fever?

Note-- V. cholera toxin also induces mucin ejection by goblet cells in the intestine, causing there to be flecks of mucus and sloughed epithelial cells, which is why its described as "Rice Watery Stools"!

Describe the normal migration of the thyroid, and where ectopic thyroid tissue can be found?

Note-- lingual thyroid contains no C cells since the parafollicular C cells are derived from a different embryological origin!

Where is rRNA synthesized?

Nucleolus

What is Lambert-Eaton syndrome MC associate with?

Oat cell carcinoma of the lung

What is Wallenberg syndrome?

Occlusion of the PICA leads to lateral medullary (Wallenberg) syndrome 1. Contralateral loss of pain/temp 2. Ipsilateral deficits in CN's 5,8,9,10,11 3. Horner syndrome

What is pleiotropy?

Occurrence of multiple phenotypic manifestations on different organs from one single gene defect

How does a nursemaid's elbow occur? How do you fix it?

Occurs in children 1-4. Radial head subluxation due to annular ligament tear from its periosteal attachment to the radial neck. It then slips over the head of the radius and slips into the radiohumeral joint, where it becomes trapped. Child presents with arm held close to body in extension and pronated. Fix by adding traction, supinating, and flexing it up all the way. Can also do the "hyperpronation" method.

Describe what is seen histologically in ischemic acute tubular necrosis (ATN). What parts of the nephron does this usually occur in?

Occurs in patients with prolonged hypotension, dehydration, or shock in post surgical patients. The classic pathologically features include *detachment of tubular cells from the BM* and occlusion of tubular lumens (mostly DCT and collecting ducts) with casts composed of intact or degenerating epithelial cells. The *outer medullary regions* are most predisposed to cellular necrosis due to relatively *low blood flow and high metabolic activity* of the tubular segments in this region (straight portion of the PCT and TAL)

Where does class switching of Abs take place? How does this occur?

Occurs in the germinal centers in the late primary immune response. First requires interaction of the CD40 receptor on activated B cells with CD40L expressed on activated T cells. Afterwards, isotope switching can occur through genetic rearrangement of the heavy chain constant regions, which is mediated via cytokines. After the primary immune response, subsequent encounter with the same antigen generate a predominantly IgG response (or IgA in the case of a mucousal response)

What is an anovulatory cycle? What do their periods look like? Why?

Occurs in younger girls. The ovarian follicle never degenerates, so no corpus luteum develops, so no progesterone levels. So the endometrium stays in the proliferative phase the whole time, leading to spotting. When ovulation does finally occur, there will be heavy bleeding

How does subacute sclerosing pan encephalitis (SSPE) form? How is it diagnosed?

Occurs several years after infection with Measles virus. It is formed by a virus with a mutated/ABSENT MATRIX PROTEIN that prevents mature (enveloped) vision particles from forming. However, the virus continues to replicate intracellularly, leading to persistent infection. ACCUMULATION OF VIRAL NUCLEOCAPSIDS within neurons and oligodendrocytes results in the formation of intranuclear inclusions and inflammation, demyelination, and gliosis in cerebral areas. *Pts will have high titers of measles antibodies in the serum and CSF (detectable as oligoclonal bands)

When does axonal reaction occur? What happens?

Occurs when axon is severed. Cell body swells, nucleus moves eccentrically to periphery, nucleolus enlarges, Nissl substance dispersion (RER)

What is affected from compression versus ischemia of the 3rd cranial nerve?

Oculomotor nerve is a pure motor nerve with both General visceral efferents (surface of nerve) and General somatic efferents (interior of nerve) Compression (aneurysm, tumor) will knock out GVE Injury due to ischemia (small-vessel disease due to DM) will knock out the GSE

How does S. epidermidis form biofilms?

Once introduced into the body, foreign bodies quickly become coated with a layer of host proteins, including fibrinogen and fibronectin. These proteins then serve as binding sites for S. epidermidis. After attachment occurs, the bacteria multiply and communicate with one another to induce synthesis of an extracellular polysaccharide matrix that encases the bacteria. The resulting biofilm functions as a barrier to antibiotic penetration and interferes with host defenses including opsonization, neutrophil migration , and even T lymphocyte activation. Once mature, these biofilms can disperse individual pathogen "seeds" (planktonic cells) into the blood stream and surrounding areas, further disseminating the infection. Definitive treatment of infection caused by biofilm producing organisms often requires surgical removal of the foreign body

What is a big clinical difference seen between PKU and maple syrup urine disease?

Only PKU has HYPOPIGMENTATION!

How are humans infected with toxoplasma gondii?

Oocysts = food or water contaminated with cat feces Pseudocysts = undercooked meat

Wernicke Encephalopathy triad?

Ophthalmoplegia Ataxia Confusion

What is the most common drug overdose?

Opioids (heroin)

Non-rhythmic conjugate eye movement associated myoclonus? What else will be found on physical examination?

Opsoclonus-myoclonus syndrome--- Its a paraneoplastic syndrome due to Neuroblastoma! Associated with Neuroblastoma: -Due to increased copies of N-myc Gene! -MC extra cranial mass in children -Derived from neuroblasts located in adrenal medulla -(fts in chart)

Treatment for C. diff?

Oral metronidazole (mild to moderate), oral vancomycin (severe), or fidaxomicin (prevents recurrence, doesn't mess up normal flora)

Course of the Round ligament of the uterus? What vessel is in there?

Originates at the uterine fundus, anterioinferior to the fallopian tubes, coursing through the inguinal canal out to the labia majora Contains the artery of Sampson

What enzyme deficiency leads to hyperammoniaemia and retardation?

Ornithine transcarbamoylase (#20)

MC complication of inhaled glucocorticoid therapy? treatment?

Oropharyngeal candidiasis Spacer and mother rinsing

Which 2 disorders present with increased urinary orotic acid? How do you differentiate between the 2?

Orotoic Aciduira (deficiency in UMP synthase)-- megaloblastic anemia, NO hyperammonemia Ornithine Transcarbamylase Deficiency --- HYPERammonemia, no megaloblastic anemia! (excess Carbamoyl phosphate gets shunted into orotic acid production in the de novo pyrimidine synthesis pathway!)

Patient presents with skin and mucousal telangiectasis as well as recurrent severe nosebleed. Diagnosis?

Osler-Weber-Rendu Syndrome (Hereditary Hemorrhagic Telangiectasia), a condition characterized by the AD inheritance of congenital telangiectasis to the skin and mucous membranes. Rupture of these telangiectasis can lead to severe epistaxis, GI bleeding, and hematuria

MOA of mannitol? S/E's?

Osmotic diuretic that functions in the proximal tubule and descending loop of henle to reduce Na and water reabsorption Can cause hypernatremia and pulmonary edema

Increased Alkaline phosphatase in an elderly patient? Ddx?

Osteoblastic metastasis Paget's Disease of the Bone

Describe how the structure and how osteocytes function within a boney structure

Osteocytes live within lamellae Delicate canaliculi radiate from each lacuna to create a reticular network with adjacent lacunae, and the cytoplasmic processes if the osteocytes lie within these canaliculi! These cytoplasmic processes send signals to and exchange nutrients and waste products within the osteocytes within neighboring lamellae via *gap junctions* Osteocytes maintain the structure of the mineralized matrix and control the short-term release and deposition of calcium (calcium homeostasis). The plasma calcium level directly dictates the metabolic activity of osteocytes, while PTH and calcitonin indirectly influence their metabolic activity. Osteocytes can also sense *mechanical stress* and send signals to modulate the activity of surface osteoblasts, thereby helping to regulate boney remodeling

Lumbosacral radiculopathy: At the L5-S1 vertebral level. Osteophyte injures what nerve? Vertebral disk herniation?

Osteophyte = L5 (spinal foramina stenosis) Disk herniation = S1 (lower nerve segment)

What drug classes should be avoided in patients taking benzodiazepines?

Other CNS DEPRESSANTS! Alcohol, barbiturates, neuroepileptics, and 1st gen antihistamines

What is Osgood-Schlatter disease (OSD)? Who does it occur in? How does it occur?

Overuse injury of the secondary ossification center (apophysis) of the tibial tubercle Common cause of knee pain in young adolescent athletes after recent growth spurt and repeated quads use (rectus femoris, vastus lateralis, vastus medialis, and vastus intermedius)

What are the 2 phases of the HMP shunt? Which is reversible? Which cells have each?

Oxidative (reversible) = G6PD helps make cytosolic NADPH, not all cells have this Nonoxidative (Reversible) = Transketolase (uses Vit B1) and transaldolase help make ribose-5-P for nucleotide synthesis, ALL cells can do this!

Purpose of MacConkey Agar?

Restricts growth of gram positive organisms using crystal violet and bile salts. You can then differentiate these gram negs based on lactose fermentation. If they ferment lactose, they will be pink on this agar

What will the PaO2, SaO2, and Oxygen content be in someone with anemia?

Oxygen is carried in the blood both as a dissolved gas and in combination with hemoglobin. The total oxygen content of the blood is determined by the amount of Hb in the blood and its percent saturation (SaO2). Dissolved oxygen is not bound to Hb and accounts for a very small proportion of the total oxygen content of the blood due to low solubility in plasma. Changes in arterial oxygen tension (PaO2) affect both the SaO2 and the amount of oxygen dissolved in the plasma; however the change in SaO2 is far more influential on the total oxygen content of the blood! This patient will have normal PaO2 and SaO2, but decreased total blood oxygen content (CaO2). If the PaO2 and SaO2 are both normal, the lower total blood oxygen content is most likely secondary to a lower Hb concentration!

How does Pseudomonas aeruginosa cause ecthyma gangrenosum

P aerginosa can lead to bacteremia/sepsis in immunocompromised patients. Perivascular bacterial invasion of arteries and veins in the dermis and subQ tissue, with subsequent release of exotoxins destructive to human tissue, leads to characteristic skin patches exhibiting ulceration and necrosis as a result of insufficient blood flow. Virulence factors that may contribute to this include exotoxin A (protein synthesis inhibition via ribosylation of elongation factor 2), elastase (degrades elastin-- important for BV destruction), Phospholipase C (degrades cellular membranes), and pyocyanin (generates ROS)

Which is secreted more by the renal tubules: PAH or creatinine?

PAH! completely secreted, thats why it is a good measurement of RPF Creatinine is only secreted a little bit, which is why it slightly overestimates GFR

How do you diagnose C. diff?

PCR detection of Toxin A and B genes in stool

What 5 cofactors do all Dehydrogenase enzymes of metabolism require?

PDH and branched-chain-alpha-ketoacid dehydrogenase "TLC For Nancy" 1. Thiamine (Vit B1) 2. Lipoic Acid 3. CoA (Vit B5) 4. FAD (Vit B2) 5. NAD (Vit B3) *Vit B 1, 2, 3, and 5! (there is no Vit B4)

What does pre-test probability (ie. prevalence) affect: PPV/NPV or Sensitivity/Specificity?

PPV/NPV!

How exactly does PTH cause bone resorption?

PTH acts on OSTEOBLASTS to increase the production of RANK-L and Monocyte colony stimulating factor (M-CSF): These 2 factors helps stimulate osteoclastic precursors to differentiate into mature osteoclasts Also, PTH decreases the release of osteoprotegerin (OPG), which is a decoy receptor for RANK-L. Less OPG means more RANK-L can bind to RANK, stimulating osteoclast differentiation!

Side effects of PTU? Methimazole? Both?

PTU = hepatotoxic Methimazole = Teratogenic Both can cause agranulocytosis (look for sign of infection, bleeding, anemia, etc.)

What is the major stimulator of respiration in healthy people? People with COPD?

PaCO2 is the major stimulator of respiration in healthy people. Even a slight increase in PaCO2 results in an increased pulmonary ventilation. In COPD, response to PaCO2 is blunted/desensitized, and hypoxemia becomes an important contributor to the respiratory drive. Peripheral chemoreceptors are primarily responsible for sensing arterial PaO2 and can be suppressed with Oxygen administration!

Function of Pacinian corpuscles? Ruffini end organs?

Pacinian Corpuscles: *rapidly* adapting mechanoreceptors located in subQ tissues of the skin as well as the mesentery, peritoneum, and joint capsules. Ruffini end organs: *slowly* adapting mechanoreceptors that exist in the skin, subQ tissue, and joint capsule. ***Both help to mediate touch, proprioception, and vibratory sensation and are innervated by myelinated A-beta fibers!

What is linkage disequilibrium?

Pair of alleles are inherited together in the same gamete (haplotype) more or less often than would be expected given random chance ***This can occur even if the genes are on DIFFERENT chromosomes (due to mutations, genetic drift, etc.)

What are baby boys with Bruton X-lined agammaglobulinemia at increased risk for? Why?

Pan-hypogammaglobulinemia (due to decreased B-cells, CD 19,20,21) Increased risk of infection of: -pyogenic (encapsulated) bacteria -enteroviruses -Giardia Lamblia *Due to the absence of neutralizing Abs!

What is the difference in presentation between a Pancoast tumor and a mediastinal tumor if they were to cause Superior Vena Cava syndrome?

Pancoast tumor would also present with shoulder pain, brachial plexus involvement, and Horner Syndrome!

What is aplastic anemia? What causes it?

Pancytopenia with bone marrow hypocellularity Most cases are acquired from a direct toxic insult or T-cell response to apoptosis of pluripotent stem cells. The etiology is unknown in most children, but may be due to drug exposures (chemo, benzene found in gasoline or tobacco), carbamazepine, and viral infection (hepatitis or Epstein Barr) *Note- Parvovirus B19 presents with Aplastic CRISIS, which is just a RBC aplasia. Can have pancytopenia in immunocompromised pts

What is used to estimate RPF? How? Why?

Paraaminohippuric Acid (PAH) *Freely Filtered and Secreted Calculate the clearance of PAH to estimate Renal *PLASMA* flow Clearance = UV/P ***If you want renal BLOOD flow, they you must divide the clearance of PAH by (1-Hematocrit)

Signs of purging subtype of anorexia nervosa?

Parotid gland hypertrophy (chipmunk facies) dental carries, halitosis calluses on dorsum of hand (Russel's sign)

What types of cells does Parvovirus B19 infect? Potential sequelae?

Parvovirus B19 replicates in erythrocyte precursors in the bone marrow. Those cells express blood group P antigen (also known as globoside) which is the cellular receptor for Parvovirus B19. Viral replication in the nucleus leads to cell lysis. Acute and chronic sequelae of parvovirus B19 infection can occur in specific populations (chronic anemia in immunosuppressed patients, aplastic crisis in those with sickle cell anemia.

Describe pathway of radial nerve in forearm

Passes anterior to later condyle to enter forearm. Splits into superficial (cutaneous) and deep radial nerve. Deep radial nerve pierces supinator, continues to wrist to become posterior interosseous nerve. *Triceps brachia and extensor carpi radialis longs already innervated by radial nerve BEFORE it pierces the supinator!

Describe the course of the ulnar nerve. Where can it get injured in the wrist?

Passes behind the medial epicondyle of the humerus. Within the forearm, it innervates the flexor carpi ulnaris and the medial portion of flexor digitorum profundus. The nerve then enters the wrist between the *hook of hamate* and the pisiform bone in the fibroosseous tunnel known as *Guyon's canal*. Here it divides into a superficial branch that provides sensation over the medial 1 and a half digits and hypothenar eminence, and a deep motor branch that supplies the intrinsic muscles of the hand. *Can get injured at the elbow or as it runs through Guyon's Canal

Describe trisomy 13:

Patau Syndrome

Which type of diuretic is most likely to cause hyponatremia. Loops or thiazides?

Patients on thiazides have a normal corticomedullary concentration gradient (compared to loops) and are better able to retain free water in response to increased vasopressin levels. Thus, patients taking thiazide diuretics are more likely to retain free water and develop hyponatremia!

Clinical symptoms of urethral injury? How to diagnose?

Pelvic fracture, inability to void, blood at urethral meatus, high-riding boggy prostate (from hematoma formation below the gland). Diagnose with retrograde urethrogram (NOT A FOLEY!)

Which involves the oral mucousa: Pemphigus Vulgaris or Bullous Pemphigoid?

Pemphigus Vulgaris! (think "vulgar")

Difference in MOA between Penicillins and vancomycin?

Penicillins: binds covalently to PBPs / Transpeptidases, which catalyze the final cross linking step in peptidoglycan cell wall synthesis Vancomycin: Directly binds to the D-ALA-D-ALA resides, preventing the incorporation of new subunits into the cell wall!

2 Treatments for motion sickness?

Perception of motion and orientation is determined by input from vestibular, visual, and somatosensory systems. These 3 systems are usually congruent, but conflicting input can lead to motion sickness, which is characterized by nausea, dizziness, and autonomic symptoms (ie. diaphoresis). Integration of these sensory pathways occur in the vestibular nuclei via muscarinin M1 and histaminic H1 neurotransmission. As such, *antimuscarinics* (scopolamine) and 1st gen *antihistamines* (meclizine, dimenhydrinate) are most effective for management of motion sickness!

When is a triple test performed? What are the next steps if abnormal?

Performed between weeks 16-18 -Start with triple test. If abnormal, go to: -Fetal Ultrasonography (USG): if nothing explains the abnormal triple test, perform: -Amniocentesis

Describe the typical presentation of Pericarditis

Pericarditis presents with severe and constant middle or left chest pain that may radiate to the neck and shoulders (trapezius ridge). The pain increases on inspiration (pleuritic) and is relieved but sitting up and leaning forward (postural). Auscultation of the chest revels a scratchy sound called a pericardial friction rub that is best heard when the patient is eating forward or lying prone.

How do glucocorticoids lead to hyperglycemia?

Peripheral antagonism of insulin effects in muscle and fat (causes catabolism). Also causes gluconeogenesis and glycogensis in liver, leading to increased glucose levels!

Describe the Train-of-Four stimulation used during anesthesia to assess the degree of paralysis induced by NMJ-blocking agents (2 types)

Peripheral nerve is stimulated 4 times in quick succession and the muscular response is recorded. Height of each bar represents the strength of each twitch; higher bars indicate the activation of increasing numbers of individual muscle fibers. Non depolarizing have gradual decline due to less ACh being released with each impulse! (Functionally similar to Phase II of depolarizing)

Where are VLCFA and fatty acids with branched points at odd numbered carbons (phytanic acid) broken down?

Peroxisome They can't undergo normal mitochondrial beta oxidation

What is PPAR-gamma? What does it do? What drugs target it?

Peroxisome-proliferator activated Receptor-gamma (PPAR-gamma), is a transcriptional regulator of genes involved in glucose and lipid metabolism. Causes increased expression of GLUT-4 and Adiponectin (cytokine secreted by fat tissue that increases the number of insulin-responsive adipocytes and stimulates fatty acid oxidation Fibrates (lowers TG's) and thiazolidinediones both target PPAR-gamma

What are clinical features of borderline personality disorder? Key defense mechanism employed?

Persistent pattern of unstable relationships, mood lability, and impulsivity, and suicidal ideation. SPLITTING

Describe Wallerian Degeneration of the CNS:

Phagocytic macrophages/microglia are recruited much more slowly compared to the PNS because of the BBB. Myelin-producing oligodendrocytes also become inactive or undergo apoptosis and do not assist with phagocytosis. This slows removal of myelin debris, which can persist for YEARS in the degenerating tracts and suppress axonal growth via myelin-associated inhibitory factors. Astrocytes also release inhibitory molecules and proliferate in the weeks to months following injury, formatting a GLIAL SCAR that acts as a BARRIER to axon regeneration!

How does H. influenza go from infecting you to meningitis?

Pharynx --> lymphatics --> meninges

Describe the two phases of Succinylcholine

Phase I block: Stimulates nicotinic ACh Receptors, but does not get degraded. Causes repeated depolarizations (can see fasciculation's initially). Sodium channels become inactivated and can't open until repolarization occurs, resulting in flaccid paralysis Phase II block: With continued succinylcholine, the continuous depolarizations gives rise to gradual repolarization as the receptors become desensitized to ACh. *This phase is similar to a non-depolarizing blockade

What is PCP? MOA? Clinical features?

Phencyclidine (PCP) is a hallucinogen that works as a NMDA receptor antagonist, leading to the excess release of excitatory NTs. It can also inhibit the reuptake or NE, dopamine, and serotonin. Moderate amounts = Dissociative symptoms (sometimes used as anesthetic) including detachment and withdrawn. Higher doses = agitation, hallucinations, and *violent behavior*. Ataxia, *nystagmus* (both HORIZONTAL AND VERTICAL), and memory loss

How can you treat Crigler-Najjar Syndrome?

Phenobarbital -- increases liver enzyme synthesis (its an inducer!!!)

What enzyme converts NE to Epinephrine? Where does this occur?

Phenylethanolamine-N-Methyltransferase (PNMT) Occurs in the adrenal medulla

Ratio of what 2 molecules determines the degree of fetal lung maturity?

Phosphatidylcholine/Lecithin:Sphingomyelin Phosphatidylcholine/Lecithin are components of pulmonary surfactant Sphingomyelin is a component of membrane phospholipid ***Want is to be >2!

How is pyruvate formed? Is there normally a lot or little in the cell?

Phosphoenolpyruvate is converted to pyruvate via pyruvate kinase *** Pyruvate is normally present in large quantities in the cell

Which cholinergics treat glaucoma? How does it work?

Pilocarpine and Carbachol lower intra-oscular pressure Cholinergic associated miosis causes the IRIS to move FURTHER FROM THE CORNEA. This WIDENS the Anterior chamber angle, allowing better outflow of the aqueous humor!

How does placenta accreta occur?

Placenta attaches directly to myometrium. Scar tissue from prior surgery (eg, C-section) might result in a malformed or absent decimal layer between the placenta and myometrium, which allows for myometrial invasion by the villous tissue. Its usually diagnosed prenatally and treated with a C-section followed by hysterectomy

Wat determines the likelihood of a plaque rupture?

Plaque stability (not size!) Plaque stability depends on the mechanical strength of the fibrous cap. Inflammatory macrophages in the intimate may reduce plaque stability by secreting metalloproteinases, which degrade collagen!

What do patients with sickle cell trait have protection against? Why?

Plasmodium falciparum. Possibly due to increased sickling of parasitized sickle cell trait RBCs and accelerated removal of these cells by the splenic monocyte-macrophage system!

Function of Kozak Sequence?

Plays a major role in the initiation of the eukaryotic translation process

What is pentamidine used to treat?

Pneumocystis pneumonia

Complications of Measles AFTER prodrome?

Pneumonia Secondary bacterial infx (pneumonia and otitis media) Neurologic problems: -Encephalitis (within days) -Acute disseminated encephalomyelitis (within weeks) -Subacute sclerosing pan encephalitis (SSPE) (within years)

Giant (temporal) cell arteritis occurs commonly with what MSK disease?

Polymyalgia Rheumatica

Describe Glycogen Storage Disease Type II

Pompey Disease -- deficient lysosomal alpha-1,4-glucosidase with alpha-1,6-glucosidase activity (acid maltase) Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, early death Pompe trashes the Pump! (heart, liver, and muscle)

What causes primary MVP? Secondary?

Primary MVP is due to myxomatous degeneration (pathologic deterioration of the connective tissue) affecting the mitral valve leaflets and chordae tendieae. Secondary MVP is due to inherited connective tissues disorders, such as ED and Marfans, or Osteogenesis imperfecta. Myxomatous lesions are characterized by proliferation of spongiosa of the valve leaflets, fragmentation of elastin fibers with increase in mucopolysaccharide, and type III collagen deposits!

Describe the leprosy spectrum. Which will have a positive lepromin skin test?

Positive in tuberculoid leprosy bc it requires a strong Th1 response!

Which purified RNA is more infectious? positive sense RNA or negative sense?

Positive sense RNA because it can be directly translated into viral proteins by the HOST CELL PROTEINS! Negative sense RNA requires RNA-Dependent RNA polymerase provided by the virus itself in order to replicate in a host cell! dsRNA viruses also require additional enzymes

Hypercellular glomeruli on light microscopy, hematuria, proteinuria, RBC casts?

Post Strep Glomerulonephritis (PSGN)

Describe the male urethral anatomy

Posterior = Prostatic then membranous Anterior = Bulbous then penile segment

An aneurysm of which vessels can cause a third nerve palsy?

Posterior Cerebral artery and the Superior cerebellar artery! *3rd nerve runs between the two arteries as it leaves the midbrain. It is very susceptible to injury from expanding aneurysms from these vessels on the ipsilateral side!

How/Where are posterior urethral injuries? Anterior urethral?

Posterior= Usually due to pelvic fractures. Occurs most often at bualbomembranous junction Anterior = Straddle injuries. The bulbous urethral segment is commonly injured

Functions of PGE1

Potent vasodilator that maintains potency of the ductus arteriosus and causes afferent arteriolar vasodilation of kidneys

Patient is kneeling in garden all day, complains of knee pain when walking. Diagnosis?

Pre patellar bursitis (bursa between patella and skin)

Is reliability the same as precision or accuracy?

Precision

Describe what is seen in Vitamin E deficiency

Predispose cell membranes to oxidative injury. Most susceptible cells are those neurons with long axons (due to large surface area) and RBCs (high oxygen exposure). Neuromuscular disease seen (same as vitamin B12 deficiency!) and hemolytic anemia

Where are glucocorticoids catabolic? Anabolic?

Predominantly catabolic everywhere peripherally. Causes muscle weakness, skin thinning, impaired wound healing, osteoporosis, and immunosuppression. However, they INCREASE liver protein synthesis, specifically the enzymes involves in gluconeogenesis (PEP carboxykinase and Glucose-6-phosphatase) and glycogenesis.

What are some causes of Carpel Tunnel Syndrome?

Pregnancy (fluid accumulation) Hypothyroidism (glycosaminoglycan buildup) DM (connective tissue thickening) RA (tendon inflammation) Dialysis (deposition of ß2-microglobulin, aka dialysis-associated amyloidosis, in the carpel tunnel)

How to diagnose Down's syndrome in utero? Gi abnormalities in Downs?

Prenatal screening: decreased maternal serum AFP Ultrasonography: increased nuchal translucency Confirmed with chorionic villous sampling or amniocentesis Duodenal Atresia Imperforate anus Hirschsprung Disease TE fistula Celiac Disease

What is Heteroplasmy?

Presence of different mitochondrial genomes within a single organism Severity of disease related to proportion of normal to abnormal mitochondria within a patient's cells

What is adenomyosis? Clinical presentation?

Presence of endometrial glandular tissue within the myometrium. Caused by hyperplasia of the basal layer of the endometrium. Middle aged multiparous women. Symptoms include heavy menstrual bleeding (increased endometrial surface), dysmenorrhea, and a UNIFORMLY enlarged uterus (due to hormonal stimulation of endometrial glands in the myometrium). Tx = GnRH agonists or hysterectomy

What is Fanconi Syndrome?

Pretty much no absorption occurs at the PCT of the kidney, so you get no absorption of any amino acids or anything else really

Describe the insulin signaling pathway

Primarily dephosphorylates enzymes

Stabilizing force for primary structure or proteins? Secondary? Tertiary?

Primary = peptide bonds Secondary = Hydrogen Bonds (alpha helices and beta pleated sheets) Tertiary = many, including ionic, hydrophobic, hydrogen bonds and disulfide bonds

Difference between healing by primary versus secondary intention?

Primary = surgical closure of well approximated wound edges--- decreases likelihood of scarring Secondary = spontaneous healing, more likely to scar due to pr longed remodeling

What is tachyphylaxis? Which two drugs demonstrate this?

Rapidly declining effect of a drug after a few days of use. It occurs because of decreased production (negative feedback) of the desired effect. Phenylephrine (alpha-agonist used to treat rhintis) and Nitroglycerine (maintain drug free intervals from 8-10 hours)

What are the 3 biliary tract diseases? Briefly describe each

Primary Sclerosing Cholangitis (PSC): -onion-skinning of intra and extra hepatic ducts -Associated with *UC*, p-ANCA, IgM Primary Biliary Cirrhosis: -Autoimmine, granulomas, intra-hepatic duct destruction -AMA positive, IgM, other autoimmune conditions Secondary Billiary Cirrhosis: -secondary cause of extra hepatic obstruction leading to back pressure in liver

What is Conn syndrome? What electrolyte abnormalities occur? Clinical presentation? Does aldosterone escape occur?

Primary hyperaldosteronism due to an aldosterone producing adenoma Will lead to hypernatremia, hypokalemia, and metabolic alkalosis (paresthesias and muscle weakness). Aldosterone escape DOES OCCUR! This prevents significant ECF volume expansion. Causes pressure natriuresis and increased ANP secretion, causing sodium levels to be normal, but potassium and proton levels will still be low!

Difference between all the different Ghon stuff in Tb

Primary infection = Ghon focus (in mid to lower lobes) Bacteria spread to hilar lymph nodes = Ghon Complex Lesion heals in lungs = Ranke complex Reactivation in upper lobes = Cavitation!

How can several units of infusions lead to hypocalcemia? What about potassium?

Prior to storage, whole blood (for transfusions) is generally mixed with solutions containing *citrate anticoagulant*. Packed cells derived from these whole blood collections also contain citrate. Infused citrate can chelate serum calcium, causing hypocalcemia. (this is only seen with massive transfusions involving 5 or 6 liters of blood over 24 hours!) Stored RBCs gradually lose intracellular potassium to surrounding solution, and can cause hyperkalemia!

Best treatment for lung abscesses in an alcoholic?

Probably an aspiration pneumonia with mixed polymicrobial infection involving anaerobes (air fluid levels) and aerobes Preferred Tx = Clindamycin Metronidazole not preferred because it doesn't cover tx for aerobic streptococci!

During pregnancy, what hormone inhibits lactation?

Progesterone (from corpus luteum and then placenta) inhibits prolactin release from anterior pituitary

21-alpha hydroxylase rxn

Progesterone --> 11-deoxycorticosterone

What is the main component of all hormonal contraception?

Progestin (synthetic progesterone) More potent = systemic effects -- suppresses GnRH in the hypothalamus-- decrease FSH and LH -- no LH surge == NO OVULATION Less potent = local cervical mucus thickening impairing sperm penetration. Also thins the uterine lining, disrupting implantation

Which is polycistronic: prokaryotes or eukaryotes?

Prokaryotes (bacteria)! Contains multiple open reading frames that are translated into several proteins

Dopamine decreases release of what hormone?

Prolactin Suprasellar and infundibular lesions can suppress dopamine secretion, leading to a prolactinoma

What happens in the proliferative phase of an HBV infection? Integrative?

Proliferative Phase: Infected hepatocytes display HBsAg and HBcAg on their MHC class I molecules, causing CD8+ T cells to come and destroy the infected cells! Integrative phase: HBV DNA is incorporated into the hepatocyte genome. Increased risk of HCC since every time the cell divides, the HBV DNA is integrated in there to mess it up and induce mutation! Note-- Host HBsAb only neutralizes extracellular HbsAg on the HBV virus that has not yet infected a hepatocyte. This neutralization occurs before the virus enters the hepatocyte, so no there would be no hepatocellular damage!

Location of most RCC? Risk factors? MC subtype?

Proximal Renal tubules Smoking and obesity = risk factors Clear cell CA

Describe lymphatic drainage above and below dentate line

Proximal: -Inferior mesenteric and internal iliac lymph nodes Distal: -Inguinal lymph nodes, although some can reach the inferior mesenteric and internal iliac nodes

Describe the difference between pseudohypoparathyroidism and psuedopseudohypoparathyroidism

Pseudohypoparathyroidsim (aka Albright hereditary osteodystrophy): Unresponsiveness of kidney to PTH--> hypocalcemia despite high PTH levels. Will have shortened 4th/5th digits and stature. Due to autosomal dominant defect in GNAS1, the gene that encodes for the Gs alpha subunit in the signaling pathway of PTH due to MATERNAL IMPRINTING Pseudopseudohypoparathyroidism: Same physical exam features as Albright hereditary osteodystrophy but without the end organ resistance to PTH! Due to a defective protein from the FATHER!

Innervation of Psoas? Iliacus?

Psoas = lumbar plexus L1-L3 Iliacus = Femoral Nerve

Describe a Psoas Abscess

Psoas attaches from TPs of T12-L5 Infection spreads to psoas, forms an abscess. Symptoms include fever, back/flank pain, inguinal mass, difficulty moving. Pain is worse by things that cause hip extension (Psoas Sign). Patients prefer hip flexion and lumbar lordosis to alleviate pain

Explain the urease breath test

Pt consumes 13-C labeled urea. When present, urease will degrade urea into CO2 and ammonia. The radio labeled 13-CO2 is absorbed into blood stream, and then exhaled in patient's breath!

Schizoaffective disorder: what is it?

Pt must meet criteria for a major depressive episode or manic episode concurrent with the active-phase symptoms of schizophrenia. Delusions or hallucinations must occur in the absence of mood symptoms for >2 weeks at some point in the illness *Pyscho only for 2 weeks, then MDD or mania with psycho symptoms

Lesions associated with Horner syndrome?

Ptosis, myoissi, and anhydrous (also enopthalmos) Due to lesion affecting the lateral hypothalamus or sympathetic tracts in the brainstem (eg. lateral medulla)

What heart problems can amyloidosis lead to?

Restrictive cardiomyopathy and heart failure

Explain Vasooclusive symptoms in Sickle Cell Disease

Pts get pain from hypoxic tissue injury and infarctions due to obstruction of small vessels by sickled cells. Usually involves bone marrow, periosteum, and deep muscles. Causes dactylitis in children. In older children/adults, vasooclusion leads to pain crises, acute chest syndrome, leg ulceration, priapism (boners), autosplenectomy, and stroke.

Japanese delicacy that can cause problems? How? Treatment?

Pufferfish contains Tetrodotoxin (neurotoxin) Blocks Na channels -- No depolarization -- weakness, paresthesias, etc. Tx = supportive care and decontamination with gut lavage and charcoal

Common extra dermal manifestation of scleroderma?

Pulmonary Hypertension

What causes the tissue damage and reluctant abscess formation seen in some pulmonary pneumonias?

Pulmonary abscesses are local supportive collections within lung parenchyma that result in necrosis of the surrounding lung tissue. If the abscess cavity communicates with an air passage, the semiliquid exudate within will partially drain, creating an air-containing cavity that can be identified on chest radiograph Histologically, supportive destruction of lung parenchyma within the abscess cavity is seen! This destruction occurs to a large extent secondary to the release of *lysosomal enemies by neutrophils and macrophages*!

Cause of pulmonary HTN in someone with CHF?

Pulmonary venous congestion causes high pressures, resulting in endothelial damage and capillary leakage of proteins into the interstitium. This leads to decreased production of NO (vasodilator) and increased production of *endothelim* (vasoconstrictor) but he dysfunctional endothelium, resulting in increased vascular tone. Over time, remodeling of the pulmonary vasculature occurs with increased smooth muscle hypertrophy (medial hypertrophy) and collagen/elastase deposition (intimal thickening/fibrosis). This process is reversible!

Where must a lacunar infarct occur for these symptoms to be seen? -Pure motor hemiparesis -Pure sensory stroke -Ataxia-hemiplegia syndrome -Dysarthria-clumsy hand syndrome

Pure motor hemiparesis: posterior limb of the internal capsular basal pons Pure sensory stroke: ventroposterolateral or ventroposteriomedial thalamus Ataxia-hemiplegia syndrome: posterior limb of the internal capsule or basal pons Dysarthria-clumsy hand syndrome: genu of the internal capsule or basal pons

1st line medication for nausea and vomiting in pregnancy?

Pyridoxine (Vitamin B6)

Enzyme in gluconeogenesis that utilizes Vit B7? Deficiency of Vit B7 can cause what in this step?

Pyruvate Carboxylase uses Biotin (vit B7) to convert pyruvate into oxaloacetate Biotin-deficient individuals will have increased pyruvate levels which get shunted into lactic acid instead, resulting in a metabolic acidosis!

What is primary polydipsia?

Pyshcogenic increased intake of free water causing hyponatremia and production of large dilute urine

What causes hereditary Spherocytosis? Lab findings? Symptoms?

RBC membrane defect due to a mutation in spectrin or ankyrin, the plasma-membrane scaffolding proteins. Results in small, round RBCs with less surface area and no central pallor (increased MCHC, mean corpuscular hb concentration), causing premature removal by the spleen Labs: *Increased MCHC, spherocytes,* negative coombs test, and increased osmotic fragility on *acidified glycerol lysis test* Will see hemolytic anemia (pigmented gallstones made of calcium bilirubinate), jaundice, and splenomegaly, and possible aplastic crises if infected with parvovirus B19!

What tissues can use ketone bodies? Which can't? Why?

RBCs can NOT use ketone bodies because it lacks a mitochondria Liver can NOT utilize ketone bodies because it lacks the enzyme succinyl-CoA-acetoacetate CoA transferase (thiophorase), which is required to convert acetoacetate to Acetyl CoA! In the initial fasting stages, the heart and skeletal muscles consume primarily ketones while the glucose that is left is reserved to the brain. But in prolonged starvation, even the brain will utilize ketones for energy for the majority of its energy needs. Renal cortex can utilize ketone bodies as well

How do RBCs produce 2,3-BPG that helps deliver oxygen in peripheral tissues?

RBCs sacrifice the ATP they would normally generate from converting 1,3-BPG into 3-Phosphoglycerate via phosphoglycerate kinase. Instead, RBCs convert 1,3-BPG to 2,3-BPG via *Biphosphoglycerate Mutase*.

What is IL-2 (Aldesleukin) used to treat?

RCC and melanoma! (increased activity of T cels and NK cells provide anti-tumor effects)

What disease is characterized by the presence of crescents in the glomerulus? What are the crescents composed of?

RPGN *Fibrin*, Monocytes/macrophages, and glomerular parietal cells

Spiral fracture of humerus typically damages what nerve?

Radial nerve

Drug of choice for insomnia in elderly patients?

Ramelteon (melatonin agonist in suprachiasmatic nucleus). Few side effects DONT use benzo's, antihistamines, or sedating antidepressants due to adverse effects

RNAP I, II, III

Rampant, Massive, Tiny

Adverse effects of Vancomycin?

Rapid administration = Redman Syndrome due to histamine release causing flushing Nephrotoxicity Ototoxicity

Clinical presentation of cyanide poisoning? What is the Tx, and why does this work?

Rapidly developing cutaneous flushing, tachypnea, headache, and tachycardia with N/V, confusion and weakness. Severe lactic acidosis and a lessened difference between arterial and venous oxygen content, meaning the venous blood is still oxygenated (this occurs bc cyanide bind cytochrome a-a3 complex in mitochondria of cells, inhibiting oxidative phosphorylation in the electron transport chain) Tx = Nitrites oxidize hemoglobin to form methemoglobin (Fe3+). Methemoglobin can't carry oxygen, but it has a high affinity for cyanide, so it can bind any cyanide in the blood and sequester it from entering cells and messing up oxidative phosphorylation! -Sodium thiosulfate is also useful because it combined with cyanide to form the less-toxic thiocyanate, which is excreted in the urine!

What is DRESS syndrome? What can cause it? How does it occur?

Rare life threatening dug reaction occurring 2-8 weeks after drug exposure (fever, rash, lymphedema, EOSINOPHILIA) Due to drugs: -Anticonvulsants (ex: phenytoin, carbamazepine) -Allopurinol -sulfonamides -Abxs (ex: minocycline, vancomycin) Drug induced herpesvirus reactivation followed by clonal expansion of T cells that cross react with the drug!

Quickly describe pathogenesis of hemochromatosis?

Recessive mutation in HFE, the receptor on hepatocytes that senses transferin levels and helps endocytose transferring with bound iron. If can't endocytose, hepatocyte thinks their is low iron. So it up regulates DMT1 expression on apical enterocytes to absorb more iron, and it decreases hepcidin synthesis, which normally shits down feorrportin. So therefore there is more ferroportin activity on the basolateral surface of enterocytes, causing more iron to be pushed into the blood stream!

Difference between recombination and reassortment in viruses?

Recombination = gene exchange that occurs through the crossing over of 2 dsDNA molecules Reassortment = mixing of genomes in segmented viruses that infect the same host cell

Explain the type of arrhythmia that can develop in WPW

Recurrent temporary tachyarrhythmias due to an AV re-entry circuit involving the AV node and accessory pathway (Bundle of Kent). Will see a NARROW QRS complex ("supraventricular ") tachcardyia

Which has a fast onset of action: Regular insulin or NPH?

Regular Insulin! Although neither has any amino acid modifications, NPH is composed of a crystalline suspension of insulin with protamine and zinc, which delays absorption

What is responsible for the delayed onset in action of regular insulin when diabetics inject it? What are some short acting insulins?

Regular insane is in a dimer and hexameter formation, which takes time to dissociated after injection, causing some absorption delay. Short acting = Glulisine, Aspart, and Lispro *"Girls And Lads, Rest Now, Don't Go!!!"

Why does fat embolism cause petechiae?

Release of mediators from platelets which adhere to and coat the fat emboli --- results in thrombocytopenia = petechiae Petechiae and neurologic impairment can also occur due to fat "escaping" the pulmonary vasculature due to high pulmonary blood pressures leading to the formations of arteriovenous shunts, allowing some small emboli to leak out into systemic circulation!

Function of Secretin?

Released from duodenum in response to acid and fat in small intestine. Secretin increases pancreatic bicarb secretion and inhibits gastrin release from normal gastric G cells

MOA of contraception of Copper IUD?

Releases copper ions that elicit an inflammatory rxn in uterus that is toxic to sperm and prevents fertilization

Side effects of the non-depolarizing agent atracurium?

Releases histamine, resulting in bronchoconstriction, hypotension, and flushing. Its metabolized to laudanosine, which can provoke seizures

A patient walks in with nephrotic syndrome and subsequently develops flank pain, hematuria, elevated LDH, and right sided varicocele. Diagnosis?

Renal Vein Thrombosis! In nephrotic syndrome, many important substances are lost in the urine, one of which is ATIII, which leads to a now hypercoaguable state, of which RVT can be a manifestation. Right sided varicocele is rare, and may indicate that the clot may have expanded into the IVC, disrupting venous return from the right gonadal vein!

How does the kidney generate NH3 so it can be secreted into the lumen to bind H+ in an acidosis?

Renal epithelial cells metabolize glutamine to glutamine, generating NH3 and bicarb! Bicarb gets reabsorbed to buffer the blood, NH3 gets excreted so it can bind NH4+ and sequester it in the lumen, dooming it to excretion!

Explain Cell Disease induced hemolysis

Repeated sickling of RBCs leads to permanent deformation and premature RBC destruction by macros and mechanical stress. Causes intra and extravascular hemolysis causing inc indirect bilirubin, inc lactate dehydrogenase, and DECREASED HAPTOGLOBIN Haptoglobin binds circulating Hb and reduces renal exertion of free Hb, preventing tubular injury!

What is tardive dyskinesia? What causes it?

Repetitive, rhythmic, involuntary movements of the tongue, lips, face and trunk and extremities. Usually its orofacial (Lip-smacking, puckering, facial grimacing, and tongue movements) Due to older age and chronic use of 1st generation antipsychotics. Must switch pt to 2nd generation antipsychotic (Clozapine). *This can occur with any long term treatment with dopamine antagonistic medications. May be due to development of supersensitivity of post-synaptic D2 receptors following prolonged D2 blockade

What is a PYR test? What does it indicate?

Replaced the bacitracin test If positive, its a Step Pyogenes (PYR is much more specific for S. pyogenes)

What is vaginal adenosis? What is it associated with? What can it lead to?

Replacement of vaginal Squamous epithelium with glandular columnar epithelia, Occurs in the female children go women exposed to *DES* during pregnancy. Its a precursor of clear cell adenocarcinoma of the vagina.

What is postherpetic neuralgia? How do you treat it?

Residual neuropathic pain in the affected dermatome after the rash from herpes zoster has subsided Treatment: Systemic: TCAs, Anticonvulsants (i.e.. gabapentin, pregabalin), Opioids -Nonsystemic: Lidocaine patches or topical capsaicin

How do people with Restrictive lung diseases breath? Obstructive?

Restrictive (increased elastic resistance) = Rapid shallow breaths Obstructive (increased airflow resistance)= slow deep breaths

Clinical manifestations of Schistosomiasis?

Results from TH2-mediated granulomatous response directed against the eggs that is composed of infiltrating TH2 cells, eosinophils, and M2 macrophages. Leads to marked fibrosis and ulceration/scarring of the bowel or bladder/ureters (depending on species).

What causes the bleeding seen in fibroids?

Results from impaired contractility, increased uterine surface area, and ulceration of endometrium over a submucosal fibroid. In addition, biochemical vasoactive growth factors expressed by the fibroids cause venous ectasia (dilation). During menstrual bleeding, the large caliber venules overwhelm normal hemostatic mechanisms that control menstrual blood loss.

Describe how appendicitis may lead to peritonitis

Retained mucus causes the appendicular wall to distend, which impairs venous outflow. The resulting hypoxia causes ischemia and associated bacterial invasion. Inflammation and edema of the appendicular wall occurs, causing further distention. Necrosis of the wall with rupture follows. Inflammatory fluid and bacterial contents spill into the peritoneal cavity causing peritonitis

Explain the anatomy of the retinal artery

Retinal artery is one of the first braces off the ophthalmic artery, which receives its supply from the internal carotid artery. *It travels within the retinal nerve to supply the inner retina and the surface of the optic nerve!

Retinal Detachment? Lens Displacement?

Retinal detachment = Ehlers Danlos Lens Displacement = Marfan Syndrome

Which parts of the pancreas are retroperitoneal? Which are intraperitoneal?

Retroperitoneal = Head, neck and Body Intra = Tail (w/in splenorenal ligament)

Toxin that inhibits protein synthesis by cleaving the rRNA component of the eukaryotic 60S subunibit

Ricin (from the castor oil plant Ricinus communis)

Where does the SA node usually get its blood supply from?

Right Coronary Artery (infarct of RCA can lead to bradycardia and hypotension)

What does the right brachiocephalic (innominate) vein drain?

Right Internal jugular and right subclavian vein Right external jugular vein drains directly into subclavian first. Also drains the right lymphatic duct

What are the epicardial vessels?

Right coronary artery,Left main coronary artery, LAD, and Circumflex artery

How does the Risocetin aggregation test occur? What will it show in von Willebrand Disease? What else can it be used to differentiate between?

Ristopetin its just activates GP1b receptors in platelets' surface, making them available for vWF to bind in vitro. Aggregation = vWF is there and able to bind to the activated GP1b receptors, causing aggregation in vitro Poor platelet aggregation = there is no vWF in the patient's serum to bind to the activated GP1b receptors, so no aggregation will occur! Indicates von Willebrand Disease! Can also help distinguish between Bernard Soldier and Glanzmann Thrombocytopenia. -Glanzman = dysfunctional GP2b/3a. Ristopetin would normally activate the GP1b, causing normal aggregation when vWF binds to them! -Bernard soldier = Deficiency in GP1b to begin with, so giving ristocetin would activate anything. vWF bind to anything, so no aggregation would occur! Even if given normal plasma with vWF, aggregation still would NOT occur (differentiates it from vpn Willebrand disease)

Describe leukocyte extradition? Molecules involved in: -Rolling -Tight Adhesion -Transmigration

Rolling = Sialyl-Lewis Bodies or PSGL-1 to L-SELECTIN or E/P-SELECTIN Tight Adhesion = CD18 ß2-integrins (LFA-1) to ICAM-1 Transmigration = PECAM-1

What is the major cause of primary spontaneous pneumothorax?

Rupture of apical sub pleural blebs! This occurs when a large change in alveolar or intrapleural pressure results in breaks in the visceral pleura and subsequent air trapping between the parietal and visceral spaces. The superficial alveoli in the apices experience greater pressure from changes (due to the weight of the lungs pulling down on the apical tissue), predisposing them to the formation of sub pleural blebs. The blebs can spontaneously rupture through the visceral pleura, frequently while the pt is at rest. Tall, thin males around the age of 20 who smoke commonly get this.

What does S-100 stain? What is it?

S-100 proteins are homodimeric calcium-binding proteins, similar to calmodulin and are important in intracellular functions such as protein phosphorylation and cell growth an differentiation. S-100 is a marker for cells of neural crest derivation (melanocytes and shwann cells) as well as langerhans cells and other dendritic cells!

Difference in food poisoning from Staph aureus/B. cereus versus C. perferinges?

S. aureus/B. cereus cause early onset food poisoning due to ingestion of pre-formed toxins C. perferinges causes delayed onset food poisoning (watery diarrhea) because the pt must ingest the spores first, which then go on to make the toxins!

MCC of community acquired lobar pneumonia?

S. pneumo

MCC of meningitis in adults?

S. pneumo

What allows a virus to undergo genetic shift? Why? Which viruses can do this?

SEGMENTED genomes allows REASSORTMENT involving exchange of entire genomic segments, leading to a dramatic change in surface proteins or other virulence factors. "BOAR" -Bunyavirus -Orthomyxovirus -Arenavirus -Rotovirus (Reovirus)

Clomiphene MOA? Used for?

SERM Used for ovulation induction

Difference btw SJS and TEN?

SJS = <10% body surface area involved TEN = >30% body surface involved

What are some serosal manifestations of SLE? Cardiac?

SLE causes serosal inflammation, and commonly manifests as pleuritis and pericarditis. Other cardiac manifestations of SLE include pericardial effusion, verrucous (Libman-Sacks) endocarditis, and increased risk of coronary artery disease.

Treatment for bullemia nervosa?

SSRI (Fluoxetine) Nutritional rehabilitation CBT

How is generalized anxiety disorder treated?

SSRI's/SNRI's and/or CBT

First line treatment for generalized anxiety disorder? What can you give in the meantime?

SSRIs and SNRIs. These may take up to 6 weeks though to kick in, and their initial activating effects can lead to an increase in anxiety. So in the meantime, you prescribe a short-acting benzodiazepine: Lorazepam Oxazepam Temazapam Alprazolam Clonazapam Triazolam ***First 3 are useful in patients with impaired hepatic metabolism

Describe how salmonella typhi infects us and its clinical symptoms

Salmonella penetrates the gut mucosa via phagocytosis by M cells and bacteria mediated endocytosis by enterocytes. It then survives/prolferates within macrophages in Peyer's Patches (submucosa of Ileum usually), causing severe inflammation and ensuing bacteremia. Fever with relative bradycardia followed by watery (pea-soup) diarrhea OR constipation, abdominal pain, and salmon colored rose spots on the chest/abdomen. Widespread dissemination across the RES can lead to hepatosplenomegaly. Ulceration in peyers patches can cause GI bleeding. Severe cases can cause bowel perforation, leading to polymicrobial peritonitis, sepsis, and death Patients with cholelithiasis or other biliary tract abnormalities are at risk at allowing S. typhi to persist in bile, making them chronic carriers!

Action of leptin? How does it do this?

Satiety 1. Leptic decreases the production of Neuropeptide Y (a potent appetite stimulant) in the arcuate nucleus of the hypothalamus. 2. Leptin stimulates the production of POMC in the arcuate nucleus. Alpha-MSH is produced by the cleavage of POMC and inhibits food intake! *Note-- fat people can become "leptin resistant", just like what is seen with insulin in diabetes. Therefore, these obese people will keep on eating!

Which carpel bone is at risk for avascular necrosis and nonunion?

Scaphoid (MC fractured bone in risk)

What types of injuries are seen in a FOOSH injury? (Fall on outstretched hand)

Scaphoid Fracture, Lunate Dislocation, and Distal radius fracture Note- Articulation of carpal bones with radius = Scaphoid + Lunate Articulation with ulna = Triquetrum

What type of cell gives rise to the cuteness neurofibromas seen in NF-1?

Schwann cells (Neural crest derived)

Describe Wallerian Degeneration in the PNS. Also, what is axonal retraction?

Schwann cells sense the axonal degeneration and begin to degrade their myelin and secrete cytokines and chemokine that recruit macrophages. This allows for effective clearance of myelin debris which, along with trophic factors secreted by Schwann cells, stimulates formation of a growth cone from the stump of the proximal axon and facilitates nerve regeneration! Proximal segment of axon degenerates to the closest node of Ranvier. The changes seen in the neuronal body after the axon is severed are called *axonal retraction*. The cell body shows signs of cellular edema. It becomes swollen and rounded, with the nucleus displaced to the periphery. Nil substance becomes fine, granular and dispersed throughout the cytoplasm (central chromatolysis). Usually takes about 12 days for complete recovery, which is seen as increased synthesis of protein by the cells in order to regenerate the severed axon!

Explain how a secretin stimulation test works in ZE syndrome

Secretin should normally inhibit gastrin release from G cells In ZE syndrome, exogenous secretin actually stimulates gastrin release from gastrinomas! Helps differentiate ZE syndrome from other causes of hypergastrinemia, such as atrophic gastritis.

Describe how IgA is activated in order to produce long lasting immunity

Secretory IgA is the major Ab associated with mucosal immunity. Upon initial exposure to a novel antigen, B cells found in Peyer's patches and mesenteric lymph nodes become activated and preferentially migrate to the lamina propria underlying intestinal mucosa. There, they become FULLY DIFFERENTIATED plasma cells that begin to synthesize IgA dimers (linked by *J chain*). These IgA dimers then bind to the polymeric immunoglobulin receptor (pIgR) found on the basolateral surface of intestinal epithelial cells and undergo transcytosis. As the linked IgA dimer is released into the intestinal lumen, a portion of the pIgR remains attached to the Ab (*secretory component*), forming the complete secretory IgA molecule. This is the response seen with liver attenuated oral (sabin) poliovirus vaccine!

MOA of Trazodone? Adverse effect?

Sedating Antidepressant most often used as a hypnotic to treat insomnia associated with depression or antidepressant treatment MOA: Serotonin modulator (antagonizes postsynaptic serotonin receptors and inhibits serotonin reuptake). Also blocks alpha-1 (priapism) and histamine H1 (why its sedating) Can cause priapism. Careful in prescribing to patients with sickle cell disease or multiple myeloma (predisposes pts to priaprism)

Describe Supine Hypotension Syndrome

Seen in Pregnant women >20 weeks gestation (big uterus) In supine or right lateral decubitus position, the bug uterus compresses the IVC, leading to dec venous return, reduced preload, reduced CO = hypotension Have pregnant moms lay on their LEFT SIDE!

Where is McBurneys Point? What is it seen in? Why does this occur?

Seen in appendicitis after the appendix gets so inflamed that it irritates the PARIETAL PERITONEUM. *2/3 the distance from the umbilicus to the ASIS

How does liquefactive necrosis occur?

Seen in bacterial abscesses and brain infarcts (due to increased fat content and lysosomal enzymes in neurons) Neutrophils or the ischemic neurons release LYSOSOMAL ENZYMES that digest the tissue; enzymatic degradation first, then proteins denature. Early: cellular debris and macrophages Late: cystic spaces and cavitation (brain)

What is Cheynes-Stokes Breathing? How does it happen?

Seen in patients with advances CHF and neurologic diseases (poor prognosis). Cyclic breathing pattern where apnea is followed by gradually increasing then decreasing tidal volumes, and then another apnea period. -CHF pts have chronic hyperventilation, leads to hypocapnia and apnea during sleep once the PCO2 drops below a certain threshold -Apnea causes an excessive buildup of CO2 -Stimulates a ventilatory response that overshoots (hyperpnea) causing the PCO2 to again fall below a certain threshold

What cancer is subacute cerebellar degeneration associated with? What causes it?

Seen in small cell lung cancer It is a paraneoplastic cerebellar degeneration due to an immune response against tumor cells that *cross react with Purkinje neuron antigens*, leading to acute-onset rapid degeneration of the cerebellum Anti-Yo, anti-P/Qm and anti-Hu are commonly seen in the serum

Fibrinoid Necrosis causes? histological appearance?

Seen in walls of BVs affected by vasculitis syndromes (PAN), malignant HTN, DI. Results from immune complexes and/or plasma proteins (i.e.. fibrin) leaking through the damaged intimate and being deposited in vessel was. Appears as circumferential ring of pink, amorphous material surrounding the vascular lumen

Picture of the layers of the suprapubic abdominal wall

Seen with a suprapubic cystotomy

Major side effects of theophylline? Tx for overdose?

Seizures (neurotoxicity) and Tachyarrhythmias (cardiotoxicity) Overdose: -Activated Charcoal to reduce GI absorption -ß-blockers = tx for tachyarrthymias -Benzos/Barbs = seizures

Examples of: Selective media? Differential media? Enrichment media?

Selective media = Thayer-Martin VCN media Differential media = MacConkey and Eosin methylene blue (EMB) for lactose fermenters Enrichment media = X (hematin) and V (NAD+) factors for Haemophilus influenza

Which Beta blockers can you give to a diabetic patient? Why these ones?

Selective ß1 blockers and ß-blockers with intrinsic sympathomimetic activity (pindolol, acebutolol) should be used since these have minimal effect on glucose metabolism and adrenergic symptoms! Nonselective ß-blockers would mask the adrenergic symptoms mediated by Norepi/epi in hypoglycemia as well as exacerbate hypoglycemia by not allowing ß2 receptors to stimulate gluconeogenesis/lipolysis

How can an UTI end up causing Acute respiratory Distress syndrome?

Sepsis causes massive cytokine release into circulation (TNF-alpha, IL-1, 6 and 8). These activate the pulmonary epithelium. This results in increased recruitment and extravasation of neutrophils into the lung tissues, provoking an inflammatory response that leads to capillary damage and leakage of protein and fluid into the alveolar space. As more alveolar space becomes fluid filled, patients develop worsening hypoxia and respiratory failure. Results in formation of hyaline membranes

Precursors for each of these molecules: -Serotonin -Histamine -Cysteine/carnitine/taurine/lecithin -Thyroxine

Serotonin is made from Tryptophan Histamine -- histidine Cysteine, carnitine, taurine, and lecithin -- methionine Thyroxine -- tyrosine

Difference between Neuroepileptic Malignant Syndrome (NMS) and Serotonin syndrome? How do you treat each?

Serotonin syndrome does NOT cause diffuse muscle rigidity! -Treat with Cyproheptadine (serotonin receptor antagonist) NMS does cause muscle rigidity -Treat with Dantrolene or bromocriptine

What 3 things is tetrahjydrobiopterin (BH4) a cofactor for?

Serotonin, Tyrosine, and DOPA

Patient has empyema and you need to place a chest tube to drain the pleural cavity. You decide to make an incision in-between the 4th or 5th intercostal space in the anterior axillary or mid axillary line. What are you cutting through?

Serrates anterior, intercostal (external, internal, innermost) muscles, and parietal pleura to reach the pleural cavity

How does IgA circulate in the serum? Secretory form?

Serum = monomer Secretary form = dimer

Which conditions usually cause renal papillary necrosis?

Severe acute pyelonephritis, sickle cell disease, DM, or analgesic nephropathy

How to diagnose WPW on an EKG when its not causing any paroxysmal supra ventricular tachycardia

Shortened PR interval Widened QRS Delta Wave ***If a re-entrant circuit back to the atria develops causing a paroxysmal supra ventricular tachyarrhythmia, we would see NARROW QRS complexes!

How does irreversible neuronal injury manifest?

Shrinkage of the neuronal body, deep eosinophilia of the cytoplasm, pyknosis of the nucleus (condensation), and loss of nissl substance (RER)

What are pyramidal signs?

Signs of *Upper motor neuron lesion* -Spasticity -muscle paralysis or weakness -hyperreflexia -Positive babinksi (dorsiflexion/toe spreading response; can be positive in newborns up to 12 months of age due to incomplete myelination of the corticospinal tracts

How does silicosis lead to increased suscpeitbiulity to TB infection?

Silicosis impairs macrophage functioning. Macrophage phagolysosomes are disrupted by internalized silica particle, causing release of the particles and viable mycobacteria, which inhibits the immune system's ab slitty to control the infection. This extracellular release of lysosomal enzymes is thought to contribute to alveolar and interstitial lung injury in silicosis. Prolonged exposure of macrophages also appears to increase macrophage apoptosis! Note- macrohages respond to silica by releasing fibrogenic factors that cause fibrosis, but this does not increase susceptibility to Tb

What is secreted at each layer on the stomach body/fundus: Simple columnar epithelial cells: Upper glandular layer of parietal cell: Deeper aspect of gastric glands:

Simple columnar epithelial = Mucus (protects from acid) Upper glandular of parietal cell = IF Deeper aspect of gastric gland = chief cells that secrete pepsin

What is the general makeup of the lac operon? 2 ways its regulated?

Single promoter, operator, and a set of regulatory elements Regulated Negatively = Binding of repressor protein to OPERATOR (lactose inhibits the binding of repressor to operator) Regulated Positively = cAMP-CAP binding upstream from promotor! (High glucose will decrease adenyl cyclase activity, thereby decreasing cAMP)

What do all veins of the developing embryo drain into?

Sinus Venosus Left sinus venosus = Coronary Sinus Right sinus venosus = Right atrium

What is "sis"? What cancers is it over expressed in?

Sis is a proto-oncogene that encodes PDGF Over expression of Sis is seen in astrocytomas and osteosarcomas

Describe the skeletal symptoms related to ankylosing spondylitis. Extra skeletal symptoms?

Skeletal: *Sacroiliac joint* and apophyseal joints of the spine are most commonly affected, leading to restricted spinal mobility. Can also develop peripheral arthritis and *enthesitis* (inflammation at the sites of tendon insertion onto bone) Extraskeletal: -Respiratory: involvement of the thoracic spine and enthesopathies of the costovertebral and costosternal junctions can limit chest wall expansion, leading to hypoventilation. Should monitor *chest expansion*! -CV: *Ascending aortitis*, can lead to dilation of the aortic ring and aortic insufficiency Eye: *Anterior Uveitis* can present with pain, blurred vision, photophobia, and conjunctival erythema.

Why does skin dimpling occur sometimes in invasive breast carcinomas?

Skin dimpling signals the involvement of suspensory ligaments (Cooper Ligament). Malignant infiltration of these ligaments causes fibrosis and shortening, leading to traction on the skin with distortion in breast contour

What happens to the skin as patients age?

Skin rhytides (wrinkles) are directly caused by chronological aging (with a contribution from UV light). With aging, skin becomes atrophic and fragile, with reduced elasticity and subdermal fat. There is dermal and epidermal thinning, flattening of the dermoepidermal junction, a *decreased number of fibroblasts*, and reduced synthesis and increased breakdown of collagen and elastin.

What are acrochordas?

Skin tags that are benign and pedunculated and normally form in areas exposed to chronic friction, such as beneath breast or in axilla

Describe normal Vitamin D metabolism

Skin--> liver --> kidney

Describe the MOA of Ivabradine? Use?

Slows the SA node firing rate by selective inhibition of *funny sodium channels* Indicated in certain patients with HF with reduced Ejection fraction and persistent symptoms despite appropriate medical therapy. *Its the only drug that slows the heart rate with no effect on cardiac contractility and/or relaxation

What can SIBO cause?

Small intestine bowel overgrowth seen in gastric bypass surgery -*Overproduction of Vitamin K and folate* -Vitamin B12 deficiency -Iron Deficiency (decreased absorption due to mucous injury from bacterial toxins, etc.) -Malabsorption of fat-soluble vitamins EXCEPT Vitamin K (overproduces it) -Zinc deficiency (small intestine malabsorption) ***Increased Folate and Vitamin K, decreased everything else!

What does it mean when we see palpable purpura?

Small vessel vasculitis (immune complex Type III, causes activation of complement, C5a recruits neutrophils to do its damage!)

What are fibroadenomas? Who do they occur in? Cancerous risk?

Small, firm and mobile breast masses that occur due to proliferation of breast stroma and ducts (estrogen sensitive), with stroma proliferation compressing the ducts to slits an histo. Usually in women <35, no cancer risk.

What increases the cardiovascular risks in patients taking OCPs?

Smoking and age >35

Clinical features of Fetal alcohol syndrome

Smooth philtrum, thin vermillion border, and small palpebral fissures

Symptoms of CN III palsy? Most dreaded cause of isolated acute CN III palsy?

Somatic = the R3 in SO4L6R3 and Levator palpebrae muscles (causes ptosis) Parasympathetic = Iris sphincter and ciliary muscle. If knocked out, can cause a fixed, dilated pupil and loss of accommodation Actively enlarging intracranial aneurysm (risk of imminent rupture) is of great concern!

Patient with CHF has hypokalemia from loop diuretic use. What do you want to put them on?

Spironolactone or eplerenone > amilioride or triamterene Spironolactone and eplerenone (more specific with fewer s/e's) are preferred in heart failure as they also prevent the deleterious effects of aldosterone-inducing cardiac remodeling

Is spleen from foregut or mesoderm? Where does it get its blood supply from?

Spleen is from MESODERMAL origin (dorsal mesentery) But it gets its blood supply from the FOREGUT!

What types of cancers are the majority of cancers in the head and neck?

Squamous cell carcinomas, usually in the oral cavity. Most are due to either tobacco or alcohol

What should children with Tetralogy of Fallot do to relieve a Tet spell? Why does this work? What causes TOF?

Squat! (or bring knees to chest) -Increases SVR without changed pulmonary vascular resistance (PVR), increasing the SVR:PVR ratio, forcing more blood into the pulmonary circulation to get oxygenated instead of the normal R-->L shunt! Due to Abnormal neural crest cell migration that leads to *anterosuperior deviation of the infundibular septum* during embryologic development, resulting in a malaligned VSD and overriding aorta!

A stable atheromatous lesion without overlying thrombus, but obstruction greater than 75% of coronary artery lumen?

Stable angina (need at least 75% obstruction for symptoms)

What are Auer rods? What are they made of? What are they seen in?

Stain for Myeloperoxidase (MPO), indicator of myeloid differentiation Seen in AML, specifically the M3 subtype of AML = Acute promyelocytic myelogenous leukemia (APL)

Describe the 2 muscles of the middle ear? What innervates them? What do they function to do? Which would be knocked out with Bell's Palsy?

Stapedius = wall of tympanic membrane to neck of stapes; innervated by stapedius nerve (branch of facial CNVII). If knocked out = hyperacusis *Knocked out in Bell's Palsy (ipsilateral hyperacusis) Tensor tympani muscle = sphenoid to malleus; innervated by CN V3. Dampens sound transmission. If knocked out, can also cause hyperacusis

Describe the progression of pain from appendicitis:

Starts as visceral pain (dull, periumbilcal) due to T10 autonomics. As appendix becomes more inflamed, it irritates the PARIETAL PERITONEUM and causes severe somatic pain that localizes to McBurneys Point (2/3 the distance from umbilicus to ASIS).

What is myocardial hibernation? What does it lead to? How can it be reversed?

State of chronic myocardial ischemia in which both the metabolism and function are reduced to match a contaminant reduction in coronary blood flow, preventing any necrosis from occurring. Leads to decreased contractility and LV systolic dysfunction. Can be mostly reversible by coronary revascularization

Describe what happens with glucagon binds to its receptor on a hepatocyte

Stimulated *G-protein coupled receptors* on hepatocyte, increasing intracellular cAMP and activating PKA. PKA activates the key glycogenolysis enzyme, glycogen phosphorylase! It also stimulates gluconeogenesis by activating rate-limiting gluconeogenetic enzymes (pyruvate carboxylase, PEPCK) and decreasing intracellular fructose-2,6-bisphopshate levels (inhibits glycolysis)

What does FSH stimulation of a Sertoli Cell lead to?

Stimulates Sertoli cell to produce *inhibin B* and *androgen-binding protein locally* w/in seminiferous tubules. This androgen-binding protein is responsible for the high local testosterone concentration and is different from Sex-hormone binding globulin (found in blood). High local levels of testosterone and FSH are necessary for spermatogenesis!

Examples of vaccines to capsular polysaccharides?

Strep Pneumo N. meningitidis H. influenzae These are all protein independent, so most are conjugated to diphtheria toxin to induce a T-cell dependent B-cell response in order to get class switching to IgG!

Which bug typically causes exudation and alveolar hepatinization of the lung?

Strep pneumo! Red hepatinization develops when extravasated neutrophils and RBCs accumulate w/in alveolar spaces and the lung assumes a liverlike appearance. Subsequently, gray hepatinization occurs due to disintegration of red cells and formation of fibropurulent exudates!

How exactly does PSGN form? What is seen on labs?

Strep progenies causes either strep throat (pharyngitis) or impetigo (skin infection). Abs against streptococcal Ag form, bind the Ag in the blood, and the immune complexes land in the glomeruli where they subsequently fix complement causing inflammation and kidney problems. This is why there is a latent period! Elevated titers of Antispreptolysin O and anti-DNase B, with LOW serum complement levels

What do you see with a subfalcine herniation? Tonsilar herniation? Transtenrorial/Uncal herniation?

Subfalcine -- Compresses ACA Tonsilar -- cerebellar tonsils herniate down and compress the medulla Transtentorial/Uncal herniation: usually due to ipsilateral mass lesion (brain tumor, subdural or epidural hematoma, and inctracerebral hemorrhage). Causes compression of: 1. Ipsilateral CN III -- fixed and dilated pupil on ipsalteral side. Later paralysis of the occulomtor muscles, leading to ptosis and down and out position of ipsilateral eye 2. Ipsilateral PCA-- contralateral homonymous hemianopsia with macular sparing 3. Contralateral cerebellar peduncle against the tentorium. Damage to the contralateral corticospinal tract = ipsalteral hemiparesis. Compression of the ipsalteral cerebral peduncle can also cause contralateral hemiparesis! 4. Brainstem hemorrhages (ie. Duret hemorrhages) may occur in the pons and midbrain due to stretching and rupture of the Basilar artery. This is usually fatal!

What is a crossover study? Pros? Cons?

Subjects are randomly allocated to a sequence of 2 or more treatments given consecutively. Good bc patients serve as their own controls. A washout (no treatment) period is often added between treatment intervals to limit the confounding effects of prior treatment.

What causes vasospasm following a sub-arachnoid hemorrhage? How does it present? What drug can prevent this?

Substances generated by the degradation of subarachnoid blood clots are the cause of vasospasm Presents 3-8 days after the SAH. Causes altered mental status as well as focal neurological deficits Tx = *Nimodipine* (Dihydropyridine-- Calcium channel blocker) -Has been shown to decrease morbidity and mortality due to cereprospasm when used as a preventative agent following SAH!

What is comedocarcinoma of the breast? How does it look histologically?

Subtype of DCIS Appears as a ductal, central necrosis, can lead to calcification of that necrosis

Best screening test for malabsorption?

Sudan III stain Dyes any fats/lipids, allowing you to quantify any steatorrhea that may be present. Should normally be zero

How do ACL tears normally occur? Which artery supplies blood supple to it?

Sudden deceleration and direction change that involves valgus stress on the knee Middle geniculate artery provides primary blood supple to ACL, and injuries are characterized by rapid onset hemarthrosis and knee swelling

What is associated with decreased estriol levels in a triple screen?

Suggests placental insufficiency and intrauterine growth restriction (estriol levels reflect both placental and fetal function)

Where is IF secreted from? Describe these cells

Superficial region of parietal cells of the gastric glands Parietal cells are oxyntic (pale pink), round, plate-like cells found predominantly in the upper glandular layer that secrete gastric acid and IF in the body and funds of the stomach

What are 2 areas to give intragluteal injections?

Superiolateral quadrant or anterolateral gluteal area (von Hochstetter triangle)

Where do the superior and inferior gluteal nerves exit the pelvis in relation to the piriformis?

Superior gluteal nerve exits the greater sciatic foramen above the piriformis Inferior gluteal nerve exits the greater sciatic foramen below the piriformis

Describe a Trendelenberg Gait. What causes it?

Superior gluteal nerve injury causes dysfunction in gluteus medius, gluteus minimus, and tensor fascia latae.

What do each of the 3 meatuses of the nasal canal drain?

Superior meatus: drains sphenoidal and posterior ethmoidal sinuses Middle Meatus: drains the Frontal, Maxillary, and anterior ethmoidal sinuses ***MC place for Nasal Polyps Inferior Meatus: drains the Nasolacrimal duct

Why is the ligamentum artery off the obturator artery important in children?

Supplies a minor portion of the femoral head, which supplies the region proximal to the epiphyseal growth plate

Where does the bronchial circuit drain?

Supplies oxygen and nutrients to the pulmonary parenchyma from systemic circulation, but drains mostly to the left atrium as opposed to the right atrium (which creates a right to left shunt that acts as a partially independent circuit). However, this typically accounts for <5% of the CO!

Tx for PSGN?

Supportive Most children recover with no long term complications

What does the empty can test evaluate?

Supraspinatus -abduction of humerus in parallel to the axis of the scapula (30 degrees toward flexion) while in full internal rotation (thumb pointed to floor)

What is the most commonly torn rotator cuff muscle? Why?

Supraspinatus due to chronic repeated drama from impingement between the head of the humerus and the acromion during abduction

Where is Rathke's pouch derived from?

Surface ectoderm

What causes the hypertension in preeclampsia?

Swollen fenestrae in renal glomerular capillary endothelial cells *new onset HTN and proteinuria or end organ dysfunction at >20 weeks gestation

Main enzyme in synthesizing fatty acids? What about breaking down fatty acids into ketone bodies?

Synthesis = Acetyl CoA Carboxylase Degradation = Acyl-CoA Dehydrogenase

What stimulates the release of Atrial natriuretic peptide (ANP)? What are its actions?

Systemic volume expansion causes atrial stretch, which then releases ANP from atrial cardiomyocytes, which then lowers BP through peripheral vasodilation, natriuresis, and diuresis. ANP binds to its receptor on cell membranes, activated guanylate cyclase and forming cGMP. This occurs in: 1. Kidney: ANP dilates afferent arterioles, increasing GFR and urinary excretion of sodium and water. Also inhibits sodium reabsorption (PCT and inner medullary collecting duct) and inhibits renin release. 2. Adrenal gland ANP restricts aldosterone secretion, causing increased sodium and water excretion in kidneys 3. Blood vessels: ANP relaxes vascular smooth muscle in arterioles/venules, causing vasodilation. Also increases capillary permeability, leading to fluid extravasation into the interstitial and a decreased in circulating blood volume!

What is seen on an EKG in hypokalemia?

T wave flattening ST-segment depression Prominent U-waves Premature atrial and ventricular contractions

Parasite that causes achalasia? What else can it cause?

T. cruzi (knocks out myenteric plexus- inbtw inner circular and outer longitudinal muscle layers of muscularis) Can also cause megacolon and megaureter

What molecule causes cachexia? What happens in cachexia?

TNF-alpha Its produced by the macrophages in response to infection as well as by some neoplastic cells (paraneoplastic-- can also secrete IL-1ß and IL-6). Its role in cachexia is explained by its influence on the hypothalamus, causing appetite suppression. It also increases BMR.

Mom has Condyloma Accuminata. She gives birth to neonate. Where is he infected? Why?

TRUE VOCAL CORDS--- HPV infects *stratified squamous epithelium* cells (anal canal, vagina, cervix) True vocal cords are stratified squamous epithelium since they undergo near-consent friction/abrasion to produce speech!!!

What should you monitor while taking lithium?

TSH and BUN/creatinine (renal function)

How does Graves Disease lead to pretrial myxedema/exopthalmos?

TSH receptors are distributed moreso on adipocytes and fibroblasts, especially in the orbit and tibia. Lymphocytic infiltration of the orbital and pretrial connective tissue due to increased TSH receptors in these regions. Cytokines released by activated T cells increase fibroblast proliferation and secretion of glycosaminoglycans, resulting in mucinous edema and tissue expansion

Cherry Red Macula Diseases

Tay Sachs or Neimann-Pick Disease

What is Biceps Tendonitis? origin/attachment of long head of bicep?

Tenderness at the bicipital groove (separates lesser and greater tubercles of humerus). Long head of biceps originates on supraglenoid tubercle of scapula and inserts onto radius

Does collagen provide compression or tension strength?

Tensile strength

How do you diagnose Mycoplasma infection? How does this work?

Test for cold agglutinins Take patient's blood, add to a tube pretreated with anticoagulant (eg. EDTA) and place tube in cup of ice. The RBCs agglutinate at low temperatures and return into suspension when warmed

What does the deep inguinal lymph node drain?

Testes, Glans penis, Posterior calf, and the superficial inguinal lymph node

Stroke with 1-sided pure hemisensory loss of face and body?

Thalamic Stroke *Thalamic Ventral posterior LATERAL nucleus (receives input from the spinothalamic tract and dorsal columns- body has the legs) *Thalamic Ventral posterior MEDIAL nucleus (receives input from trigeminal pathway- face is the muncher) Both of these nuclei send somatosensory projections to the cortex via the thalamocortical fibers. Therefore if we damage both of these nuclei with one big thalamic stroke, we can get complete contralateral sensory loss!!!

Describe accommodation of the eye. How do antimuscarinics effect this?

The *ciliary muscle* attaches to the lens via the zonular fibers. Contraction of the muscle reduces tension on the fibers, allowing the lens to become more spherical and increase its refractive power. The ciliary muscle is under parasympathetic control from the *Edinger-Westphal nucleus/ciliary ganglion*. Inhibiton of this pathway via antimuscarinics will limit accommodation, causing blurring of the vision for close objects. *The pupillary sphincter also receivers parasympathetics input from the EW nucleus, and patients on antimuscarinics may have mydriasis as well!

Explain the Bohr-Haldane effect in the lung:

The O2 kicks off the H+ and bicarb

MOA of Gardos channel blockers in Sickle cell anemia?

The calcium-dependent (Gardos) potassium change; regulates the transport of K+ and water through the RBC membrane. When blocked, the K+ and water efflux is reduced, preventing dehydration of the RBCs and reducing the polymerization of HbS!

Describe the clinical presentation of an acute lesion to the cerebellar vermis

The cerebellar vermis modulates axial/truncal posture and coordination via connections with the MEDIAL descending motor systems (eg, anterior corticospinal tract, reticulospinal, etc.). Consequently, acute lesions to this region (usually due to hemorrhage) typically result in *truncal ataxia*, characterized by a wide-based, unsteady gait. Pts may also develop *vertigo and nystagmus* due to involvement of the inferior vermis and flocculonodular lobe (vestibulocerebellum), which modulates balance and ocular movements via connections with the vestibular nuclei and MLF!

How can endometriosis lead to a retro-verted uterus?

The ectopic endometrial glands undergo bleeding with the menstrual cycle. The blood undergoes hemolysis and induces inflammation. Chronic inflammation can lead to adhesion formation. If the adhesions involve the uterosacral ligament, it can result in a fixed. retroverted uterus! This infiltration of the posterior cul-de-sac can present with painful intercourse and tenderness with palpation in the posterior vaginal fornix.

How does Clostridium perferinges lead to watery diarrhea?

The endotoxin binds to claudin, and interferes with the tight junctions in the intestinal barrier, leading to water loss from the tissue into the intestinal lumen!

Long term glucocorticoid therapy suppresses what parts of the HPA axis?

The entire HPA axis is shut down!

What is Globus sensation?

The feeling of a "lump in the throat" without any accompanying physical, endoscopic, or radiologic findings of esophageal obstruction. No other symptoms really seen, its a functional disorder

What is an ecological study?

The frequency of a given characteristic (Vitamin D intake) and a given outcome (multiple sclerosis) are studied using *POPULATION DATA*. Ecological studies are useful to generate hypotheses but should not be used to make conclusions regarding individuals within these populations, which would be known as *ecological fallacy*

Why are pregnant women at increased risk of UTIs? Why do pregnant women also get stress incontinence?

The gravid uterus causes ureteral compression that may result in physiologic hydronephrosis. Urinary stasis becomes a breeding ground for bacteria! Pregnancy hormones decrease decrease urethral tone and relax the pelvic floor muscles (*levator ani and coccygeus*), which function with the urethral valve to maintain continence

Describe the appearance of osteoporotic bone

Trabecular (spongy) and cortical (compact) bone loss/thinning with fewer interconnections. The trabecular architecture remains relatively conserved though!

Which part of the venous system contains the most deoxygenated blood? Why?

The heart! Myocardial oxygen extraction so very high. The heart has a capillary density for exceeding that of skeletal muscle. Oxygen extraction from arterial blood is very effective within the heart as the resting myocardium extracts 60%-75% of oxygen from blood. This amount is higher than that extracted by any other tissue or organ in the body! Moreover, myocardial oxygen demand and coronary blood flow are tightly coupled. During exercise when the heart needs more oxygen, increased oxygen delivery to the heart can only be achieved through increased coronary blood flow. Adenosine and nitrous oxide are the most important vasodilators responsible for increasing coronary blood flow.

MOA of nitrates?

The increase in cGMP leads to decreased intracellular Calcium, causing decreased activity of Myosin light chain kinase and increased activation of *Myosin light chain phosphatase*, leading myosin light chain dephospho rylation and vascular smooth muscle relaxation!

What is the postprandial alkaline tide?

The increase in plasma Bicarb and a decrease in plasma Cl- secondary to the surge of acid within the gastric lumen. This causes an increase in blood pH. Seen after meals or vomiting

If a Hb-Oxygen binding curve is shifted to the left, what can be seen on peripheral smear?

The increased affinity of Hb to Oxygen will cause less Oxygen unloading at tissues, causing hypoxia. This will stimulate the kidneys to release EPO, leading to an *erythrocytosis/Polycythemia*

What does the gubernaculum become in the female?

The inferior portion of the gubernaculum becomes the round ligament of the uterus, which passes through the inguinal canal and attaches to the labia majora. The superior portion persists as the proper ovarian ligament, which connects the uterus to the ovary!

What nerve mediates the afferent limb of the cough reflex above the vocal chords? Efferent limb? Where can foreign bodies lodge to damage this reflex?

The internal laryngeal nerve (branch of superior laryngeal nerve, CN X) is responsible for the afferent limb. *Both the afferent and efferent limb are from CN X! Foreign bodies can become lodged in the piriform recess and damage the internal laryngeal nerve, impairing the cough reflex

Describe the lymphatic system of the lower leg. Where does each side drain?

The lymphatic system of the lower extremity is divided into the superficial vessels (follows the venous system-- receives lymph from skin and subQ) and the deep lymphatic vessels (follows the arterial system-- receives lymph from both the deep muscles and superficial vessels!) In the lower extremity, the superficial lymphatic system is divided into medial and lateral tracts. -Medial tract: runs along the LONG SAPHENOUS VEIN to the superficial inguinal lymph node, bypassing the popliteal lymph node. Lesion on the medial foot can cause inguinal lymphadenopathy, but not the popliteal lymph node! -Lateral tract: drains the lateral leg and drains into the popliteal lymph node. lesions here can cause lymphadenopathy in both the popliteal and inguinal areas!

What is the normal pO2 of the trachea? Alveoli?

Trachea = 150 mmHg (atmosphere is 160, drops little due to pp of water vapor) Alveoli = 104 mmHg

Why does the midgut herniate through the umbilicus during development?

The midgut herniates through the umbilicus at the 6th week of development to allow the rapid growth of the intestines/liver despite the slower growth of the abdominal cavity! The midgut returns to the abdominal cavity at the 10th week of fetal life, simultaneously completing a 270 degree turn counterclockwise around the SMA. This rotation allows for the proper placement and fixation of the intestine in the abdominal cavity! If process is abnormal, intestinal malrotation occurs. In this condition, the cecum is found in the RUQ, fixed with fibrous bands (Ladd's bands) to the 2nd portion of the duodenum. The entire mid gut is fixed to the SMA. Intestinal obstruction usually occurs due to adhesive bands compressing the duodenum. Obstruction manifests with bilious vomiting during the first few days of life. Twisting of the intestine around the SMA can cause impaired perfusion and midgut volvulus with intestinal gangrene and perforation!

Why is succinylcholine a terrible drug to give to patients with burns, myopathies, crush injuries, or denervating injuries/diseases?

The nicotinic ACh receptor is a nonselective cation channel, so succinylcholine can bind to K+ channels and cause release of K+ into the extracellular fluid. These pathologic states in the question cause an up-regulation of muscle nAChR's and/or rhabdomyolysis, which can result in the release of large amounts of K+ when succinylcholine is administered. Can lead to hyperkalemia and life-threatening arrhythmias Treat with non-depolarizing agents (vecuronium or rocuronium)

How does the mini-mental state examination (MMSE) help diagnose dementia?

The patient must demonstrate impairment across several cognitive domains during testing as well as functional impairment in activities of daily living!

What is the internal capsule of the brain? What lies in the posterior branch? Genu? Anterior branch?

The poster dumb of the internal capsule separates the globes pallid us and putamen from the thalamus and carries corticospinal motor and somatic sensory fibers as well as visual/auditory fibers. the function of this limb is extremely important!!! The gene/"knee" of the internal capsule lies between the anterior and posterior branches and carries corticoBULBAR fibers. The anterior limb of the internal capsule separates the caudate nucleus from the globus pallidus and putamen and carries a portion of the thalamocortical fibers

Why is the FEV1/FVC increased in interstitial lung diseases?

The progressive pulmonary fibrosis with thickening/stiffening of the pulmonary interstitial causes increased lung elastic recoil as well as airway remodeling due to increased outward pulling (radial traction) by the surrounding fibrotic tissue, causing large dilated bronchioles that can exhale air faster/more. This causes both the FEV1 and FVC to decrease. But the FEV1 decreases less, due to airway widening relative to the low lung volumes. So the FEV1/FVC increases!

What complication can occur during a prostatectomy that can cause erectile dysfunction?

The prostatic plexus, which arises from the inferior hypogastric plexus and carries post-ganglionic parasympathetic fibers, lies within the fascia of the prostate. The prostatic plexus gives off the cavernous nerves, which facilitate erections

MCC of unilateral fetal hydronephrosis? Bilateral?

Unilateral = Obstruction at Ureteropelvic Junction (due to inadequate canalization) Bilateral = Posterior urethral valves (picture)

What causes gram negative sepsis?

The release of LPS from bacterial cells during division or by bacteriolysis LPS IS NOT ACTIVELY SECRETED BY BACTERIA Lipid A is the toxic component of LPS -it causes activation of macros leading to the widespread release of IL-1 and TNF-alpha, leading to septic shock (fever, hypotension, DIC, etc.)

What causes the motor fluctuations seen in Parkinsons disease patients who are taking Levodopa/Carbidopa?

The therapeutic window for levodopa narrows due to natural or levodopa-induced nigrostriatal degeneration!

In a patient with normal pressure hydrocephalus, what causes the "wet" part (incontinence) ?

The ventricular enlargement place traction on the cortical efferent and afferent fibers (corona radiata). This traction disrupts the periventricular pathways that transmit impulses from the cortex to the sacral micturition center (normally the cerebral cortex will inhibit the sacral micturition center, so you don't pee your pants!) Later in the disease process, lack of inhibition from the cerebral cortex leads to frequent and uncontrolled micturition, or urge incontinence. The bladder fills with urine and empties reflexively when full. The patient has no sensation of bladder fullness and no control over bladder function (bc the sacral micturition center is not inhibited by the cerebral cortex!). Note-- voluntary relaxation of the external urethral sphincter remains intact

Why are elderly patients susceptible to a bacterial pneumonia after a viral pneumonia? Which bacteria normally cause this?

The viral pneumonia damages the mucociliary clearance mechanism of the respiratory epithelium In order: Strep pneumo, Staph aureus, and Haemophilus

What is a vasectomy? How soon can patients begin ejaculating? Is pregnancy prevented right away?

Transection of the vas deferens, which functions as a transport duct between the epididymis and ejaculatory duct, and also serves to store/protect sperm Intercourse can be resumed in a week, but viable storm in the distal vas can be present for 3 months and atlas 20 ejaculations!

Woven versus lamellar bone?

These are the 2 main microscopic forms of bone. Woven bone= immature and is 1st to be laid down during fetal osteogenesis and following a fracture Lamellar bone= woven bone is later remodeled into lamellar bone, which is stronger and contains regular, parallel collage fibers in sheets!

Lipohylanosis and microatheromas. What are they seen in? What are they?

These are the primary cause of lacunar infarcts since they are what is responsible for the small vessel occlusion. Lipohyalinosis = leakage of plasma proteins through damaged endothelium causes hyaline thickening of vascular wall, collagen sclerosis, and accumulation of mural foamy macrophages Microatheromas = atherosclerotic accumulation of lipid laden macrophages in the tunica intima of a penetrating artery near the origin off it's parent vessel!

Why must you be careful when giving blood to someone who has Selective IgA deficiency?

These patients often form IgG antibodies directed against IgA (anti-IgA antibodies). When transfused with blood or blood products containing small amounts of IgA, these patients develop potentially fatal anaphylactic reactions. Gamma-globulin preparations should not be used for the treatment of these patients as it may increase the synthesis of IgA antibodies!

What makes up the "envelope" of enveloped viruses? Are they susceptible to organic solvents (i.e. ether)?

These viruses have an outer lipid bilayer coat acquired from the host cell plasma or nuclear membranes Ether will dissolve the lipid bilayer leading to decreased infectivity!

Function of A-delta fibers?

They are thin, myelinated nerve fibers whose free nerve endings detect temperature and nociceptive stimuli. They are associated with acute, sharp pain and constitute the afferent portion of the reflex arc that mediates withdrawal from noxious stimuli (ex: retracting hand away from stove).

What happens to strawberry hemangiomas of children as they age?

They grow in proportion with the growth of the child, and then regress spontaneously usually by 5-8 years old!

Why do almost all diuretics cause potassium loss?

They increase the volume delivered to the collecting duct, where aldosterone then attempts to reclaim all that additional volume at the expense of potassium!!!

MCC of death in TCA (amitriptyline) overdose?

They inhibit fast sodium channel conduction, slowing down myocardial depolarization and leading to *cardiac arrhythmias* Will cause *QT Prolongation*!!!

What types of GI issues are patents who have had a cholecystectomy susceptible to?

They now have constant release of bile into the duodenum. This continuous drainage can overwhelm the absorptive capacity of bile salts in the ileum and may lead to chronic secretory diarrhea in some patients.

What are the effects of nitrites and benzocaine on hemoglobin?

They oxidize Fe2+ to Fe3+! The partial pressure of oxygen in blood (the amount of oxygen dissolved in plasma) is unchanged though!

What do Beta blockers effect on an ECG?

They slow the AV nodal conduction, which PROLONGS the PR INTERVAL No effect on QT interval (except sotalol, which has class III properties)

Deficiency of what vitamin can lead to cardiac dilation?

Thiamine (Vit B1) -- alcoholics

Tell me about Vitamin B1. Who gets deficient in this?

Thiamine --- deficiency seen in Alcoholics (cant absorb it). Leads to decrease ATP (glycolysis shut down) and increase in lactic acid. Shuts down brain and heart (highly aerobic tissue), leading to Wernicke-Korsakoff

How do thiazides cause an increase in sodium reabsorption?

Thiazides limit sodium reabsorption in the distal tubule, causing mild volume depletion (and potential hyponatremia) which stimulates the proximal tubular sodium reabsorption, which can lead to hypernatremia! *Note: lithium behaves the same way as sodium, so thiazides can cause increased blood lithium levels leading to toxic effects!

Explain the Bohr-Haldane effect in tissues:

This effect is due to the histidine side chains on the alpha and beta hemoglobin subunits. The bicarb gets shifted out of the RBC in exchange for Cl-, and the H+ stays in the cell and is buffered by the histidine side chains. The H+ with the histidine side chains helps stabilize the deoxygenated form of Hb and decrease its affinity for oxygen while being transported to the lung! *The CO2 entering kicks off the oxygen

Pt was abonded by father, so now he thinks you will abandon him too since you cancelled on one of his appointments

Transference ***Counttransference is when Pt does it back to the patient!

Ulcerated atherosclerotic plaque with partially obstructive thrombus in coronary artery?

Unstable angina, subendocardial MI, or sudden cardiac death

What are febrile seizures? How do you treat? What are they at risk for?

This is the most common neurological disorder affecting children. Risk factors include high temperatures and family history of it. Basically its just a super high temperature due to cytokines that increased the hypothalamus set point that causes seizures. Usually occurs after an infection. Must rule out any infectious causes first though Treat with antipyretics (acetaminophen or ibuprofen) to decrease PGE2 levels which will decrease the thermoregulatory set point in the hypothalamus, lowering body temperature. Children who experience a febrile seizure are at risk for recurrence but have low risk of developing epilepsy!

Pt excessively using screw driver. What motor deficits will he have? Cutaneous innervation deficits?

This will cause injury to radial nerve as it pierces the supinator. -Motor deficits = Triceps and extensor carpi radialis longus will be fine, everything below it knocked out. Presents as finger drop -Cutanous Deficits = none, superficial radial nerve branches off before it pierces the supinator

Side effects of using EPO in chronic kidney disease?

Thromboembolic events due to increased blood viscosity HTN due to activation of EPO-receptors on vascular endothelial and smooth muscle cells

What happens in a V/Q mismatch from a PE?

Thrombotic occlusion of a pulmonary artery leads to increased pulmonary resistance, increasing RV afterload (and may cause Right sided heart failure). These alveoli are being ventilated but with no blood flow. Blood is shunted to other areas of the lung. Hypoxemia due to increased perfusion of poorly ventilated regions of the lung

Common side effects of amiodarone?

Thyroid dysfunction Corneal micro-deposits Blue-grey skin Drug-related hepatitis Pulmonary fibrosis

Tolerance with opioids develops to what? What does NOT develop tolerance?

Tolerance develops to analgesia and most side effects NO TOLERANCE TO CONSTIPATION or myosis (pin-point pupils)

Topical Tx for psoriasis

Topical Vitamin D analogs (calcipotriene, calcitriol, and tacalcitol) These bind to Vitamin D receptors (nuclear transcript factor) which inhibits Keratinocyte proliferation and stimulates Keratinocyte differentiation (since its parakerotosis, hyperkeratosis with retention of nuclei)

MOA of capsaicin?

Topical capsaicin causes release of substance P, resulting in burning pain in the area of application. Prolonged use causes depletion of substance P, and the pain diminishes with time!

Difference between Topoisomerase I and II? Drugs that inhibit each?

Topoisomerase I: -Single-stranded nicks to release negative super coiling -Irinotecan and Topotecan inhibit this Topoisomerase II: -Transient breaks in both DNA strands to relieve both positive and negative supercoiling -Etoposide (testicular and small cell lung cancer) and Podophyllin (topically to treat genital warts) inhibit this

What causes transient Diabetes Insipidus? Permanent DI?

Transient DI = Injury to posterior pituitary or infundibulum. Since hypothalamus nuclei are intact, axonal regeneration and hypertrophy will allow adequate ADH release into circulation. Central DI = Loss of the paraventricular and/or supraoptic nuclei of the hypothalamus leads to permanent DI!

How do AAA develop?

Transmural inflammation of the aortic wall. Chronic inflammation leads to degradation of elastin and collagen by proteases, leading to loss of elastin and smooth muscle cells, and abnormal collagen remodeling and cross-linking. Leads to weakening and expansion of aortic wall, leading to an aneurysm *not due to atherosclerosis! (limited to tunica intimate/media)

How do you treat an acute delirium attack? What if the delirium was due to alcohol or benzodiazepine withdrawal?

Treat the underlying cause, can give *Haloperidol* to alleviate the behavioral/psychotic manifestations. When used in low doses, haloperidol has minimal sedative, anticholinergic, hypotensive, and extrapyramidal side effects ***If due to alcohol/benzos withdrawal, then give benzodiazepines

Is Oseltamivir (Tamiflu) used to prevent or treat influenza? How does it work?

Treat, especially if given w/in 48 hours of symptoms onset. It inhibits Neuraminidase, not allowing the release of attached virions from the respiratory tract lining (they are bound via hemagglutinin). Neuraminidase usually cleaves the terminal silica acid residues, allowing for the release of attached virions from infected cells and subsequent viral spread!

Briefly describe the 3 types of headaches

Treatment: Clusters and migraines = Triptans Tension = NSAIDS

Tell em about Vitamin A. What is it also used to treat?

Treats AML subtype M3 (APML) and Measles *Stored mainly in liver in the perisinusoidal stellate (Ito) cells. Toxicity more likely to occur if ingested in its "re-made" form (retinol). Teratogenic, especially in 1st trimester due to spontaneous abortion and fetal defects (microcephaly, cardiac anomalies, early epiphyseal closure, cleft palate, and growth retardation) Deficiency of Vitamin A causes specialized endothelium to resort to keratinized squamous epithelium

Function of Desmopressin?

Treats Central Diabetes Insipidus and nocturnal enuresis, also Hemophilia A ***Also increases circulating levels of vWF and promotes the coagulant activity of Factor VIII. Factor VIII is produced in the liver sinusoidal epithelial cells, and DDAVP significantly increases circulating Factor VIII levels. DDAVP also stimulates von Willebrand Factor (vWF) secretion from endothelial cells!

What is the only cranial nerve that exits the brainstem at the lateral aspect of the mid pons at the levels of the middle cerebellar peduncles (key neuro-anaotmic land mark for locating the nerve!)

Trigeminal nerve! (CN V)

Describe Patau Syndrome

Trisomy 13

Describe Edwards syndrome

Trisomy 18

What are rocker bottom feet associated with?

Trisomy 18 (Edwards Syndrome) and Trisomy 13 (Patau Syndrome)

Describe Edwards Syndrome. What causes it?

Trisomy 18 due to meiotic nondisjunction

What is the only CN that decussates before innervating its target? What cranial nerve is the only one to exit the brainstem posteriorly?

Trochlear nerve (innervates superior oblique muscle) Also the only CN that exits the brainstem posteriorly!

Describe the histology seen for: -Partial mole -Complete mole -Invasive Mole: -Gestational choriocarcinoma What is secreted by a trophoblastic tumor?

Trophoblastic tumor can secrete human placental lactogen

Describe how Calcium induces skeletal muscle contraction

Tropomyosin normally lying over top actin, shielding the myosin head binding sites on actin. Calcium binds to troponin C on tropomyosin, causing tropomyosin to shift, exposing the myosin binding sites on actin!

Difference between a true cyst and a pseudocyst?

True cyst = line day epithelial cells Pseudocyst = consists of granulation tissue and is not lined by epithelial cells. Fibrosis and thickening of the walls occur over time! Usually occurs in the lesser peritoneal sac

Serum levels of what substance are used to detect anaphylaxis?

Tryptase! Anaphylaxis results from widespread mast cell and basophil degranulation and resultant histamine and tryptase release. Trypatase is an enzyme relatively specific to mast cells, and elevated serum levels of tryptase help diagnose anaphylaxis after the patient has been stabilized!

Name of the pathway that connects to hypothalamus and the pituitary gland? What is made here?

Tuberoinfundibular dopaminergic pathway Dopamine is made here, where it inhibits the release of prolactin from the anterior pituitary!

WBC Casts

Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection

Characteristics of a testicular torsion?

Twisting of the spermatic cord causes compression of pampiniform plexus of testicualr vein and impeding venous outflow. Arterial blood flow is initially persevered, leading to engorgement and eventual hemorrhagic infarction. Characterized by acute, severe pain with N/V, an asymmetrically *high-riding testis*, and absent cremasteric reflex

Which type of muscle fibers have a lot of myoglobin and mitochondria? Why?

Type 1 (1 slow red ox) The myoglobin functions as oxygen storage and the mitochondria perform aerobic respiration. Needed for constantly firing muscles like paraspinal muscles.

What are the 2 types of 5-alpha reductases? Where are each found and when are they expressed? A deficiency in which one can cause male pseudohermaphroditism at birth?

Type 1 = present in POSTpubescent skin Type 2 = predominantly in genitals *Defiency in Type 2 will cause male pseudohermaphroditism until puberty, when Type I kicks in and starts masculinizing the boy

What type of collagen is the nucleus pulposus?

Type II (along with cartilage and vitreous humor)

What type of hypersensitivity Rxn is a hyperacute transplant rejection?

Type II Hypersensitivity Preformed IgG Abs attack either ABO group or MHC.

Brief description of what happens in an acute hemolytic transfusion reaction

Type II Hypersensitivity Rxn. Anti-ABO Abs (IgM) in the recipient bind the corresponding antigen on transfused donor erythrocytes, leading to complement activation. Anaphylotoxins (C3a and C5a) cause vasodilation and symptoms of shock, while the formation of the membrane attack complex (C5b-C9) leads to *complement mediated cell lysis*. Same thing occurs in Rh- incompatibility!

What is serum sickness? What can cause it? What are the histologic/lab findings? Clinical findings?

Type III hypersensitivity (immune complex mediated, IgG/IgM) reaction to nonhuman proteins (chimeric monoclonal Abs), nonhuman Ig's, and nonprotein drugs such as penicillin and TMP-SMX) Causes vasculitis with fibrinoid necrosis and intense neutrophil deposition! The immune complexes also activate complement, leading to hypocomplimentemia (dec C3 & C4 levels) Arthralgias, urticaria, fever, proteinuria, and lymphadenopathy 5-10 days after exposure to drug (antigen)

Difference between Type IIa and Type IIb muscle fibers?

Type IIb fibers derive ATP energy though anaerobic glycogenolysis and subsequent glycolysis. Type IIa fibers (fast twitch) are intermediate between Type I and Type IIb. They generate ATP via aerobic metabolism.

Describe acute allergic contact dermatitis. What is it? Gross findings? Histological findings?

Type IV hypersensitivity rxn to an antigen on the skin surface. Gross findings include erythematous, papulovesicular. weeping lesions. Histology is characterized by SPONGIOSIS (an accumulation of edema fluid in the intercellular spaces of the epidermis) With chronic exposure, lesions become less edematous, with thickening of the stratum spinosum (acanthosis) and stratum corneum (hyperkeratosis)

Symptoms of Sickle Cell Trait?

Typically asymptomatic with normal Hb level, retic count, etc. May develop hematuria, priapism, and increased incidence of UTIs. Splenic infarctions at high altitudes are possible.

Albinism is due to a deficiency in what enzyme? What is the rxn of this enzyme?

Tyrosinase deficiency Causes decreased conversion of tyrosine to melanin

In which IBD is the rectum always involved?

UC

Difference between UV and ionizing radiation?

UV radiation (non-ionizing= less energy): forms thymine dimers. Repaired by NER Ionizing radiation (gamma rays, x-rays= higher energy, can remove an electron): DNA Double strand breakage, free radical formation. Fixed via Non-homologous end-joining

What is Tommy John surgery? What does it fix? how does this happen?

Ulnar collateral ligament strengthens the ulnoumeral joint!! Ulnar collateral ligament injuries occur most often in throwers (baseball pitchers) due to intense valgus stress at the elbow. Tommy John Surgery is reconstruction of the ulnar collateral ligament

Describe Fetal circulation. Adult remnant of the umbilical vein? Ductus venosus?

Umbilical vein = Ligamentum Teres Ductus venosus = Ligamentum venosum

What kind of bilirubin can cause kernicterus?

Unconjugated bilirubin!

Which is toxic: Unconjugated or conjugated bilirubin?

Unconjugated! Conjugated bilirubin is water soluble. loosely bound to albumin, and excreted in urine when present in excess. Unconjugated bilirubin binds tightly to albumin and is highly insoluble in water. When bound, uncinjugated bilirubin cannot be filtered by the glomerulus and is therefore not excreted in the urine. Instead, the unconjugated bilirubin is gradually deposited in various tissues, including the brain. These can cause kernicterus (bilirubin encephalopathy)

What does the Quellung reaction do?

Under the microscope, the capsule of Strep. pneumo swells and appears as a halo around the blue-stained bacteria cells when specific anti-capsular Abs and methylene blue dye are added! In vivo, these Abs help prevent against reinfection! Hard to make vaccine though due to so many different capsule variants due to polysaccharide variations!

Are hepatic abscesses more common in developed or underdeveloped countries? What is usually the cause of each?

Underdeveloped = More common, PARASITIC (ie. entamoeba histolitica, echinococcal) Developed = Rare, usually bacterial

What is Potter Sequence?

Urinary Tract Anomaly (usually renal, bilateral renal genesis, ARPKD, etc.) causes baby to not pee, causes OLIGOHYDRAMNIOS (not enough amniotic fluid to protect baby) This causes external compression of face (low set ears, flattened nose, retrognathia/overbite) and lower extremities (clubbed feet) Umbilical cord is compressed and fetal HR anomalies seen during delivery ***Pulmonary Hypoplasia results due to the lack of normal alveolar distension by aspirated amniotic fluid. Leads to respiratory failure, the most common cause death

Best serum/urine markers to measure osteoclast activity?

Urinary deoxypyridinoline (*best one*) Urinary hydroxyproline (breakdown protein of collagen) Tartrate-resistant acid phosphatase

Neonate: Urine discharge from umbilicus? Meconium?

Urine = Patent Urachus (allantois remnant) Meconium = Vitelline fistula (omphalomesenteric duct)

Enzyme deficiency in Porphyria cutanea tarda?

Uroporphyrinogen Decarboxylase (causes photosensitivity)

Orlistat. MOA? Indication?

Used for weight loss Intestinal laps inhibitor that reduces absorption of dietary fat. Side effect = steatorrhea

MOA of fidamicin? indication?

Used to treat C diff Its a macrocyclic abx (related to macrolides) that inhibits RNAP. Its an oral drug with bactericidal activity. It has less effect on normal colon flora than metronidazole or vancomycin Used to treat recurrent C diff infections. Helps prevent recurrent infections!

Pathogenesis of HIV-associated Dementia?

Usually affects the subcortical/deep grey matter structures (attention/working memory problems, executive dysfunction, slow information processing) Caused by inflammatory activation of microglial cells. HIV-infected monocytes initially cross the BBB to become perivascular macrophages. Activated macrophages and microglial cells (resident macrophages of the CNS) form groups (*microglial nodules*) around small areas of necrosis and may fuse to form multinucleated giant cells. Neuronal damage os believed to occur from inflammatory cytokines released by macrophages/microglial cells and the direct toxic effects of HIV-derived proteins!

When is gestational diabetes usually diagnosed? What is it due to?

Usually diagnosed around weeks 24-28 Its a state of insulin resistance causing fasting hyperglycemia due to increased levels of human placental lactogen

Most common cause of orchitis? What about in young children/adolescents? Adults?

Usually do to Mumps Young children/adolescents = C. trachomatis or N. gonorrhoeae Adults = E. Coli

MCC of traumatic aortic rupture? Where alone the aorta is injury most likely to occur?

Usually due to rapid deceleration that occurs in Motor vehicle accidents. Most commonly injured at aortic isthmus (where it is tethered by the ligamentum arteriosum-- high torsional forces).

MCC of cretinism? Clinical features?

Usually due to thyroid dysgenesis (agenesis, hypoplasia, or ectopy) and iodine deficiency is a common cause in endemic areas (europe) Initially, asymptomatic at birth due to maternal T4 crossing the placenta. Once maternal T4 wanes, constipation, lethargy, hypotonia, MACROGLOSSIA, UMBILICAL HERNIA, and a large anterior fontanelle, and irreversible CNS issues

What causes autoimmune hemolytic anemias?

Usually from extrinsic antibody-mediated hemolysis and associated with a positive Coombs test. These anemias are usually accompanied by SLE or other autoimmune diseases, lymphomas, Mycoplasma infections (cold agglutinins), and mono

Characteristic Histological findings of GERD in esophagus?

Usually its Stratified squamous epithelium! -Basal Zone hyperplasia -Elongation of lamina propia papillae (tips of papilla) -Scattered eosinophils and neutrophils *Eosinophilic esophagitis will cause numerous eosinophils that are superficially located

How does Graft versus Host Disease (GVHD) occur? Clinically how does this present?

Usually occurs after allogenic bone marrow transplant, or organs rich in lymphocytes (ie. liver) Recipient is usually immunocompetent due to primary disease itself or immunosuppressive meds. This allows for DONOR T CELLS from the graft to survive and migrate into host tissues, where they recognize HOST MHC ANTIGENS as foreign and become sensitized. On activation, DONOR CD4 and CD8 T CELLS (not B cells) participate in host cell destruction Any organ can be affected, but most commonly involves the skin, liver, and GI tract. Early signs include a diffuse *Maculopapular rash that likes the palms and soles* and may *desquamate in severe cases*. GI tract involvement causes N/V/D, intestinal bleeding, and abdominal pain. Liver damage causes elevated LFTs

Describe what happens in Acute interstitial nephritis. What will you see on labs?

Usually to hypersensitivity reaction to a medication IgE or cell mediated hypersensitivity (type IV), depending on the drug. Primarily involves the renal interstitium, causing interstitial edema and infiltration with mononuclear cells (lymphocytes, macros, and eosinophils). Inflammatory cells commonly infiltrate the tubular epithelium (tubulitis) and granuloma formation may occur. Will see eosinophilia or eosinophiluria (detected by Hansel or Wright stain)

Explain the metabolic fate of glucose in anaerobic metabolism

Usually, pyruvate gets converted to Acetyl-CoA by PDH. But under hypoxic conditions, intracellular accumulations of NADH *inhibits PDH*, causing pyruvate to get converted into lactate instead via lactate dehydrogenase which will regenerate NAD+ from NADH in the process!

What key growth factors promote angiogenesis in neoplastic and granulation tissue?

VEGF and Fibroblast Growth Factor-2 (FGF-2)

What changes more during exercise: Arterial or Venous values of O2 and CO2?

VENOUS Muscles extract more O2 and produce more CO2, but arterial PaO2 and PaCO2 stay close to resting values

Is Chloride higher in the venous RBC or arterial RBC?

VENOUS! Chloride shift kicks out bicarb for Cl at tissues when its getting ready to go back to the lung. ***Only a small amount of chloride is transported this way

Hydrophobic amino acids?

VIP-GAL Valine Isoleucine Proline Glycine Alanine Leucine Phenyalanine Tryptophan Methionine

low pitched, holosystolic murmur at left sternal border. Accentuate with handgrip.

VSD

Where are ADH and Oxytocin secreted from?

VSOP

Describe Mullerian Agenesis (Mayer-Rokitansky Kuster-Hauser Syndrome)

Variable uterine development and NO UPPER VAGINA (short vagina). They are 46, XX with normal ovaries and secondary sex characteristics (bc ovaries are making enough estrogen). Will have normal pubic and axillary hair (opposite of Androgen insensitivity) Primary Amenorrhea is usually the presentation Usually co-occurs with a urologic anomaly, such as renal agenesis or Horseshoe kidney!

Why are nitrates given for chronic stable angina?

Vascular smooth muscle relaxation (veins>arteries) ***Decreases myocardial oxygen demand due to decreased preload (dec LVEDV and pressure) Little reduction in after load Mild coronary artery dilation and reduction of coronary vasospasm

What is Kawasaki Disease? How do you diagnose it? Complication?

Vasculitis of medium sized arteries in Asian children <5. Diagnosis based on fever for >5 days plus 4 of the following: 1. B/L non-exudative conjunctival erythema 2. Cervical Lymphadenopathy 3. Mucositis (strawberry tongue) 4. Extremity changes: erythema/edema of palms/soles 5. Rash: erythematous rash that spreads centripetally to trunk Can cause coronary artery inflammation leading to development of coronary artery aneurysms -- MI in young child!!!

Is CO2 a cerebral vasodilator or vasoconstrictor?

Vasodilator! This is why patients with cerebral edema are hyperventilated in order to decrease ICP

Vasopressin's effects on urea?

Vasopressin 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 increased the medullary osmotic gradient, allowing the production of maximally concentrated urine!

Pathogenesis of varicose veins

Venous blood normally flows from superficial veins to perforating veins to deep veins, then back to the IVC. Valves located in each of these prevent back flow from deep to superficial. Chronically elevated intraluminal pressure can lead to dilation of the veins (varicose veins) and incompetence of the valves. This allows retrograde blood flow, further increasing the increase in venous pressure. The resulting tissue ischemia can cause venous stasis dermatitis and is associated with poor wound healing. Extravasation of RBCs into the tissues leads to iron deposition and the characteristic brawny discoloration!

Describe the lung "slinky effect"

Ventilation increases from apex to base because gravity acts to stretch the lungs downward for the apex, which is effectively fixed to the pleural cavity by the low intrapleural pressure. As a result, at end-expiration, alveoli at the apex are expanded more than those at the base. During inspiration, a smaller amount of air is directed to the lung apex since the alveoli there are more distended and less compliant!

What does the ventral pancreatic bud give rise to? Dorsal pancreatic bud?

Ventral = Uncinate process portion of the head and main pancreatic duct Dorsal = pancreatic tail, body, and remainder of head ***Both from foregut

Explain how annular pancreas form.

Ventral bud rotates behind duodenum, where it fuses with dorsal pancreatic bud.

What areas within the spinal cord are most oftenly damaged in syringomelia?

Ventral white commissure! Will cause bilateral loss of pain and temp due to destruction of the lateral spinothalamic tract, which decussates in the ventral white commissure. Deficits will be seen starting 1 to 2 levels below the lesions due to the transient ascent in the zone of Lissaurer before snypasing!

What do non-didropyridines work on? Dihydropyridines?

Verapamil and Dilitazem block Ca channels in the myocardium and vascular smooth muscle, resulting in vasodilation and decreased myocardial oxygen demand. Amlodipine works on arteries, including coronary arteries! (can lead to coronary steal syndrome)

Which blood vessels are the most susceptible to atherosclerosis?

Vessels with bends or branch points, which cause turbulence and local blood flow disruption that leads to endothelial dysfunction and prolonged contact with cholesterol particles. *Lower abdominal aorta and Coronary Arteries*!!! (can be present in patients as young as 10-20!)

How does CCl4 cause hepatocyte necrosis?

Via free radical injury! CCl4 gets oxidized by lover P450 oxidase system, generating CCl3, which reacts with lipids on cell membranes to generate hydrogen peroxide formation (H2O2). This is known as *lipid peroxidation*! The peroxides go on to form new free radicals, leading to a vicious cycle of lipid degradation. This injury develops rapidly and leads to swelling of the ER, destruction of mitochondria, and increased cell membrane permeability, all causing hepatocyte necrosis!

Describe subacute granulomatous thyroiditis (de Quervain thyroiditis)

Viral illness-- Hyperthyroid -- Hypothyroid Early neutrophilic infiltrate followed by lymphocytes with macrophages and multinucleated giant cells

How does HBV infection lead to the development of HCC?

Viral integration into the host genome in hepatocytes triggers neoplastic changes. -Hbx gene activates IGF-1 -Suppresses p53 -Chronic inflammation

What cells have decreased or absent MHC Class I proteins? What cells kill them? How?

Virally-infected cells and tumor cells Killed by Natural killer cells (NK cells), via perforin and granzymes that induce apoptosis

Describe visceral abdominal pain versus somatic pain seen in appendicitis:

Visceral pain = dull, non localized pain due to luminal dissension and stretching of smooth muscle. Carried by general visceral afferent fibers of autonomic nervous system (T10). Pts can get N/V and sweating due to autonomic stimulation Somatic Pain: severe, well localized. Due to the irritation of the PARIETAL PERITONEUM

Describe how pleuritic pain occurs

Visceral pleura has no innervation Parietal pleura is well innervated, and is divided into 4 parts: -Mediastinal and Diaphragmatic pleura has the phrenic nerve carry afferent pain signals to C3-C5, which then refers to the shoulder area -Costal and cervical pleura are innervated by intercostal nerves where the pain is felt near the sourer of the pain

What are scotomas? What causes a central scotoma?

Visual field defect that occurs due to pathological process that involves part of the retina or optic nerve resulting in a discrete area of altered vision surrounded by zones of normal vision Lesions of the macula cause central scotomas

What causes elevated homocysteine levels? Why is this bad?

Vit B 9/12 deficiency Homocysteine damages the endothelium, leading to CV events (venous thromboses, coronary artery disease, and ischemic stroke) *supplementation with Vit B9/12 has NOT been shown to help decrease CV events

Tell me about Vitamin B6

Vit B6= pyridoxine Needed for synthesis of Niacin (and tryptophan) and for heme synthesis (1st step ALA synthase requires Vit B6 as cofactor, if not = siderblastic anemia)

Vitamins/minerals deficient in vegans?

Vitamin B12 Calcium Vitamin D

Tell me about Vitamin B5

Vitamin B5 = Pantothenic Acid Essential component of CoA

Describe tocopherol/tocotrienol? Deficiency?

Vitamin E --- inhibits Vitamin K leading to anticoagulant effects

What vitamins does breast milk lack?

Vitamin K --- IM injection given at birth to prevent hemorrhagic disease of the newborn Vitamin D --- usually from sunlight, but don't want baby to get sunburn. Black babies severely lack vitamin D due to increased melanin blocking the UV rays from stimulating Vit D synthesis. Must supplement in all breast feeding children. Formula is fortified with Vitamin D Note-- there is sufficient iron in breast milk until about 4 months, at which point they probably should start supplementing it

How does Vitamin K promote clotting?

Vitamin K is an essential cofactor for gamma-glutamyl carboxylase, the enzyme responsible for conversion of glutamyl residues to gamma-carboxyglutamates. This carboxylation is essential for factors 2, 7, 9 and 10 because it creates *Ca-binding sites*. These Ca-binidng sites attract the clotting factors to negatively charged phospholipids on platelets and endothelial cells, encouraging clotting coagulation and thrombin formation.

Describe Glycogen Storage disease type I

Von Gierke Disease-- Defiance Glucose-6-phosphatase Severe fasting hypoglycemia. Huge increase of glycogen in liver. Increased blood *lactate*. Increased TGs, uric acid (gout), hepatomegaly Tx: frequent oral glucose/corn starch; avoidance of fructose and galactose

Presentation of VIPoma

WDHA syndrome Watery Diarrhea Hypokalemia Achlorhydria May also have hypotension due to dehydration and vasodilatory effect of VIP

What is the preferred drug for long term anticoagulation of mechanical prosthetic valves?

Warfarin

What 2 areas does ischemic colitis usually affect?

Watershed areas 1. Splenic flexure (SMA and IMA) 2. Rectosigmoid Junction (Sigmoid Artery and Superior Rectal Artery Note-- Rectum is less prone to ischemia due to collateral supply from the rectal arteries

Ophthalmoplegia, Ataxia, and Confusion?

Wernicke Encephalopathy

Describe how the ESR works

When an injury occurs, local neutrophils/macrophages release TNF-alpha, IL-1, and IL-6 into circulation. These stimulate APP's (fibrinogen, ferritin, C-reactive protein, serum amyloid A, serum amyloid P, complement factors). Fibrinogen causes RBCs to form stacks (rouleaux) that sediment at a faster rate than do individual erythrocytes. This aggregation rate is termed ESR, and is a marker of inflammation!

When is celecoxib generally prescribed?

When you want anti-inflammatory effects with less risk of bleeding and GI ulceration (someone with a history of peptic ulcer disease)

Pt has involuntary head bobbing. Why?

Widened pulse pressure due to Aortic Regurg

What is fibromyalgia? How can we treat it?

Widespread MSK pain and fatigue due to abnormal central processing of painful stimuli Can treat with incremental aerobic exercise, TCAs, and SNRIs

What causes DIC? What is seen on labs?

Widespread activation of clotting factors---> deficiency in clotting factors---> bleeding state Will have thrombocytopenia with prolonged PT and aPTT, schistiocytes

What will one see on a Water Deprivation Test of Primary polydipsia? How do you treat it?

Will see increase in urine osmolarity as time progresses, Then when given vasopressin (ADH analogue), there is NO further increase in urine osmolarity because the patient already has maximal endogenous ADH effect. Tx with restriction of water intake

Sideroblastic Anemia: inheritance? Stain? MCV? Causes?

X-Linked, microcytic anemia Bone Marrow Biopsy with Prussian Blue stain shows ringed sideroblasts (iron-laden macrophages) Can be due to X-linked mutation causing ALA Synthase mutation (in MITOCHONDRIA, rate limiting step of heme synthesis), myelodysplastic syndrome, alcohol abuse, copper deficiency, and medications that deplete Vit B6 (INH, chloramphenicol, linezolid) ALA Synthase uses Vit B6 as a cofactor!

Pathogenesis of Fragile X syndrome?

X-linked Loss of function mutation of the fragile X mental retardation 1 (FMR1) gene on the *long arm of chromosome X*. FMR1 normally has 5 to 55 CGG repeated and can potentially expand during *meiosis in oocytes*. "Full mutation" is characterized by >200 CGG trinucleotide repeats, which causes *FMR1 HYPERMETHYLATION*. DNA methylation inactivates FMR1, preventing production the protein, thereby impairing neural development!

Tell me about Lesch-Neyhan syndrome

X-linked Recessive, defect in purine salvage pathway

Problem in Wiskott-Aldrich syndrome? Features?

X-linked mutation in WAS gene causes B and T cell deficiency since they can't reorganize actin cytoskeleton to respond to signals from environment. (actin involved in cell signal transmission) WATER: Wiskott Aldrich Thrombocytopenia Eczema Recurrent Infections

What is Klinefelter Syndrome? What is going on with the gonads?

XXY male with eunuchoid body shape Destruction and hyalinization of the seminiferous tubules causes the testis to be small and firm. Serum inhibin levels are decreased a s a result of the Seertoli cell damage. Leydig cells are dysfunctional too, causing reduced testosterone levels. FSH and LH will both be high! The high gonadotropin levels also up regulate aromatase activity, leading to hyperestrogenism-- causing gynecomastia!!!

What is xerosis? How do you treat it?

Xeroxes ('winter's itch") is an itchy rash with dry cracked skin seen in the winter due to indoor heaters lowering the relative humidity of ambient air. Extracellular ceramides, fatty acids, and sterols in the stratum corneum normally provide a permeable barrier that prevents excessive transepidermal water loss and hinders skin penetration by chemicals and other irritants. Patients with xerosis have a defect int he stratum corneum permeability barrier. Tx = retaining normal skin barrier and replenishing it from water loss. Bath with lukewarm water with immediate moisturizing afterwards!

Does jaundice lead to pruritus?

YES

Does the prevalence of a disease affect the NPV?

YES! A high pre-test probability will lead to a low NPV (meaning that might have been a false negative bro, you should get checked again)

Typical presentation of sarcoidosis?

Young black woman with fever, malaise, and weight loss. Lung involvement is usually present (cough, dyspnea, and chest pain). Skin involvement is varied from macules to plaques to erythema nodosum

What is Legg-Calve-Perthes Disease?

Young children with isolated idiopathic osteonecrosis of the hip

Features of constrictive pericarditis?

note-- may hear a "pericardial knock", which is similar to an S3, but sharper and more accentuated sound heard earlier in diastole (its because the reduced ventricular compliance is via an OUTSIDE force!)

What is another name for p-ANCA? c-ANCA?

p-ANCA = Myeloperoxidase ANCA c-ANCA = PR-3-ANCA *There are Abs against enzymes found in neutrophils!

What are telangiectasias?

abnormal dilations of capillary vessels ***Will blanch under pressure since the blood/RBCs are still inside the vasculature!

What are the afferent/efferent fibers of the corneal reflex?

afferent = CN V1 Efferent = CN VII

Symptoms of someone who took too much Jimson weed?

aka ANTICHOLINERGIC Poisoning via Atropine! Hot as a Hare Dry as a bone Red as a Beet Blind as a Bat*** Mad as a hatter!

Describe Von Recklinghausen's disease

aka NF-1 its an INHERITED PERIPHERAL NERVOUS SYSTEM TUMOR SYNDROME

What 2 things is leucovorin used for?

aka Reduced Folinic Acid 1. Reverse negative side effects of methotrexate (GI and bone marrow suppression) 2. Potentiates the effects of 5-FU by binding to thymidylate synthetase

Describe Buerger's Disease

aka Thromboangitis obliterans Heavily associated with smoking or an immune sensitivity to tobacco/smoke. Vasculitis of medium/small arteries (tibial and radial arteries usually). Histologically, there is acute and chronic inflammation of arterial walls, often with thrombosis of the lumen, which can undergo organization and recanalization. This SEGMENTAL thrombosing vasculitis often extends into continuous veins and nerves (rare for other vasculitides). The inflammatory process may eventually encase all 3 structures (arteries, veins, and nerves) in fibrous tissue.

Causes of orthostatic hypotension?

alpha-1 blockers (terazosin, doxazosin) volume depletion autonomic dysfunction (Parkinson's, Diabetes)

What receptor causes dependence on nicotine? What drug targets this to help smoking cessation? How does this work?

alpha4-beta2-nicotinic ACh receptors present in the CNS Varenicline is a partial agonist at this receptor that competes with nicotine (full agonist) and prevents it from binding! It helps prevent the withdrawal symptoms by mildly stimulating the receptor. Also, this partial stimulation only causes limited downstream release of dopamine, resulting in less stimulation of the reward pathway as compared to nicotine!

Does the endometrium undergo atrophy or apoptosis right before menstruation?

apoptosis

Bipolar I disorder definition

at least 1 Manic episode with or without a hypomanic episode or depressive episode

Malunion of the labioscrotal folds in male?

bifid scrotum (2 separate sacs)

Intracellular bacteria that survive by: -blocking phagolysosome fusion? -inhibiting phagolysosome acidification? -escaping phagosome inro cytosol?

blocking phagolysosome fusion: -Salmonella and TB inhibiting phagolysosome acidification: -TB escaping phagosome inro cytosol: -Listeria and Shigella (both MOTILE!)

Disease caused by Isospora belli

chronic watery diarrhea in AIDS pts

Magnesium Ammonium Phosphate crystal shape

coffin lids (staghorn calculi)

Describe the murmur of PDA? Who is at risk of developing a PDA?

continuous murmur heard best at LEFT INFRACLAVICULAR region with maximal intensity at S2 patients born prematurely or those with cyanotic congenital heart disease

Histology seen in: -de Quervain Thyroiditis? - Riedel Thyroiditis? -Hashimoto's thyroiditis?

de Quervain (subacute granulomatous) thyroiditis-- first neutrophils, then lymphocytes with macrophages that form multinucleated giant cells (granuloma) Riedel thyroiditis: young female; extensive fibrosis that extends into surrounding tissues (thyroid is hard and nontender---- mimics anaplastic carcinoma which occurs in the elderly) Hashimoto's thyroiditis: diffuse, painless enlargement; diffuse lymphocytic infiltration with formation of germinal centers (Hurtle cells)

Post-op urinary retention: cause? Tx?

decreased micturition reflex activity, decreased contractility of detrusor, and/or increased vesicular sphincter tone Tx = Bethanochol or alpha-1 receptor antagonists

What vein is messed up in a varicocele?

dilation/varices of the left pampiniform plexus

What is pulsus paradoxus? What causes it? What can it maybe suggest?

drop in systolic BP of >10 mmHg on inspiration. During inspiration, the decreased pressure in pleural space/lung interstitial increases pulmonary vascular capacitance, causing a fall in venous inflow to the left heart, resulting in a decreased LV stroke volume and a drop in systolic BP. The inspiratory drop in systolic BP is exacerbated in cardiac tamponade due to extrinsic compression on the ventricles. *Under normal conditions, the increased venous return to the right heart during inspiration causes the RV to expand into the pericardial space with little impact on the left side of the heart. HOWEVER, in conditions that impair expansion into the pericardial space (ie. acute cardiac tamponade), the increased RV volume occurring with inspiration leads to *bowing of the inter ventricular septum* toward the LV. This further reduces the LVEDV and LV stroke volume, leading to a drop in BP > 10 mmHg during inspiration! Suggests Cardiac tamponade when coupled with acute onset hypotension, tachycardia, and JVD. Can also suggest constrictive pericarditis, *COPD, asthma*, and pulmonary embolism.

Why is intussusception bad? Where is the most common location? Why?

leads to impairment of venous return of invaginated segment of bowel, causing ischemia and subsequent necrosis of the intestinal wall Most commonly occurs at ileocecal junction due to SIZE difference between ileum and cecum!

Describe paget disease of the nipple. How does it occur?

eczematous exudate over the nipple/areola and is due to ductal spread of malignant cells to nipple surface. Can have bloody discharge Will see Paget cells!

What infections are SCD pts at increased risk for?

encapsulated organisms bc repeated splenic infarcts causes functional aplsenia

Key features of somatic symptom disorder?

excessive anxiety and preoccupation with 1 or more unexplained symptoms *Illness production and motivation are of UNCONSCIOUS drives

Describe a cardiac Pacemaker action potential

exhibit automaticity due to slow, inward sodium current during phase 4 ("funny current")

Describe the metabolism of galactose:

fyi Lactase is a type of ß-galactosidase

What step of glycolysis requires NAD+? How does it get regenerated in aerobic conditions? Anaerobic?

glyceraldehyde-3-phopshate (G3P) is converted into 1,3-bisphosphoglycerate (1,3-BPG) by glyceraldehyde-3-phosphate dehydrogenase, requiring NAD+ Aerobic = Electron transport chain Anaerobic = When pyruvate is converted into lactate by lactate dehydrogenase

Explain the murmur of hypertrophic cardiomyopathy. What would increase it or decrease it?

harsh crescendo-decrescendo Systolic ejection murmur best heard along lower left sternal border and apex Decreases with maneuvers that increase either afterload or preload, as increases in these parameters attenuate the left ventricular outflow tract obstruction (and associated mitral valve regurg due to impaired mitral valve closure) by increasing LV volume. Murmur would be accentuated by anything that decreases preload (valsalva straining phase/phase II) or afterload, which would reduce the LV chamber size, which decreases the separation between the mitral valve and inter ventricular septum, increasing obstruction.

Causes of Restrictive Cardiomyopathy?

hemochromatosis, sarcoidosis, amyloidosis, and radiation therapy

Cysteine crystal shape

hexagonal

Etiology of overflow incontinence

impaired detrusor contractility or bladder outlet obstruction (big dilated bladder) Causes dribbling of urine, incomplete emptying

Giant Cell Arteritis--- serious complications?

ischemic optic neuropathy (ophthalmic artery occlusion) Cerebral infarction leading to central field visual defects

Sensory innervation of the Deep peroneal nerve?

its so deep it only gets the little "web"

For patients with a metabolic acidosis, how can the kidney increase acidic buffer excretion?

pH changes rapidly with relatively small changes in H+ concentration, limiting the amount of acid that can be secreted as free H+ in the urine. Therefore, the kidney utilizes acid buffers to trap H+ and allow the excretion of much larger amounts of acid without markedly lowering urinary pH. 2 ways it does this: -HPO4^2- is a titratable acid that combines with H+ to form H2PO4-. -NH3 is generated by the PCT cells via metabolism of glutamine and combines with H+ to form NH4+. This is the MOST IMPORTANT of the 2 compounds, as kidneys can greatly increase NH3 production in chronic acidosis!

How do bacteria gain resistance to vancomycin?

plasmids/transposons give the bacteria ligases that alter the D-alanyl-D-alanine cell wall precursors (target of vancomycin) to D-alanine-D-lactate (now vancomycin can't bind!)

What represents the bluish color seen on Wright-Giemsa Stain of reticulocytes?

rRNA

Describe riboflavin

riboFlavin = Vitamin B2 Makes FAD and FMN = 2 ATP Used in succinate dehydrogenase which is the in TCA cycle, and its Complex II in the Electron transport chain!

Phenylephrine MOA

selective alpha-1 agonists

Short term treatment for RA? Long term?

short term = anti-inflammatories, such as NSAIDS or glucocorticoids (systemic or intra-articular) long term = DMARDS (ie. Methotrexate, sulfasalazine, hydrochloroquine, minocycline, and TNF-alpha inhibitors)

Why do patients with small cell lung cancer cause SIADH? Why does this result in a euvolemic hyponatremia instead of hypervolemic hypernatremia?

small cell lung cancer is a neoplasm of *neuroendocrine cells (Kulchitsky cells that stain positive for Chromogranin A and neuron specific enolase) Increased ADH causes a subclinical hypervolemia initially. This mild increase in extracellular fluid volume suppresses the RAAS and stimulates the production of natriuretic peptides (ie. ANP, BNP), leading to the excretion of sodium in urine (natriuresis), making the hypinatremia even worse! As a result, patients with SIADH have a clinically normal body fluid volume and low plasma osmolality, aka *euvolemic hyponatremia!*. Pt will NOT have clinical symptoms of volume overload (no peripheral edema, JVD, pulmonary crackles)

Calcium Oxalate crystal shape

square with X in center

What is NBTE? What is the pathogenesis of Nonbacterial thrombotic endocarditis (NBTE)??

sterile, Vegetations consisting of bland thrombus without accompanying inflammation or valvular damage. They are the result of a hypercoaguable state, usually due to a MUCINOUS secreting cancer, such as mucinous adenocarcinoma of the pancreas or lung. Mucin is a PROCOAGULANT! ***This is the same reason why you see Trousseau syndrome (migratory thrombophlebitis) in adenocarcinoma of the pancreas, due to the mucin getting in the blood stream!!! ***NBTE can also be called marantic endocarditis when it is due to the circulating products of cancers (marasmus = cancer-related wasting of body tissues)

Deposits in glomerulus seen in MPGN type 1?

sub endothelial C1q deposits

What secretes ß-hCG?

syncytiotrophoblast during first trimester, rising to highest level in 9th week. Maintains corpus luteum unit placenta takes over for estrogen and progesterone synthesis. Levels of ß-hCG drop mid-pregnancy when corpus luteum degenerates

What can cause anterior mediastinal masses?

the 4 "Terrible" T's! 1. Thymoma 2. Teratoma 3. Thyroid Cancer 4. Terrible Lymphoma

What are the three types of brain herniation?

transtentorial = aka uncle herniation

Describe the endometrium in proliferative phase

uniform development, with a gland:storm ratio of <1. The glands are straight and narrow, and contain small lumens

Which part of the lungs do PEs most often affect? Why do they cause *hemorrhagic" infarcts?

w32PE's are usually multiple and occur most often in the lower lobes Because the lung has a dual blood supply from both the pulmonary and bronchial arteries, bronchial blood usually hemorrhages into the ischemic area, causing a hemorrhagic infarct.

What composes the pseudomembranes of pseudomembranous colitis?

white/yellow plaques with fibrin

Different between mast cell degranulation by ß-lactam abxs/sulfonamide abxs and vancomycin?

ß-lactams and Sulfonamide abxs = Ige-DEPENDENT mast cell degranulation Vancomycin = IgE-INDPENDENT mast cell degranulation