Flashcards in Uworld Deck (1452):
What is Niacin (B3) a precursor for?
NAD and NADP.
What is NAD a cofactor for in the TCA?
Isocitrate DH, aKG DH, malate DH
What is the cofactor for succinate DH?
FAD made from Riboflavin (B6)
What produces myofiber disarray with interstitial fibrosis?
HCMP- mutation in beta-myosin heavy chain gene.
In LDH deficiency what other enzyme will become depleted?
NAD+ - it is the cofactor for LDH. Will lead to accumulation of glyceraldehyde 3-P bc it requires NAD+ for conversion to 1,3-BPG.
What is associated with a G:C --> T:A mutation in the p53 gene?
Aflatoxin, which greatly increases the risk of HCCa.
What disease has characteristic increase of osteoclasts that are abnormally lg. with an xs number of nuclei?
Paget’s – specifically the osteolytic phase. Will have increased ALP levels.
What is the most likely dx in a HIV pt. w/ multiple ring-enhancing lesions, and what’s the 1st line tx?
Toxoplasmosis- tx with pyrimethamine and sulfadiazine.
What is the 2nd most common cause of ring-enhancing lesions in a HIV pt?
primary CNS lymphoma caused by EBV.
Exposure to what is likely to cause hepatic angiosarcoma, and what tm. marker will these cells express?
Carcinogens like arsenic, thorotrast, and polyvinyl chloride. The tm cells express CD31 (aka PECAM1) an endothelial marker.
What vessel is likely associated with an ipsilateral nasal hemianopia?
The internal carotid a. An aneurysm or calcification in this vessel can impinge the optic chiasm and damage uncrossed optic fibers from the temporal portion of the retina.
What causes direct hernias to occur?
Weakness/breakdown in the transversalis fascia in the Hesselbach’s triangle.
What class of drugs does Pantoprazole belong in?
What is likely seen on histo of the esophageal mucosa in a patient with GERD?
Basal zone hyperplasia, elongation of lamina propria papillae, and scattered eosinophils.
In renal hypoperfusion, what cells are most likely to undergo hyperplasia and where are they located?
The JG cells (modified sm. mm. cells in the wall of the afferent arteriole) wil undergo hyperplasia in response to signals transmitted by the macula densa. They will increase the RAAS system.
A renal bx showing proximal tubular cell ballooning and vacuolar degeneration is likely caused by what?
Acute tubular necrosis. Will have normal glomeruli on histo.
What causes oxalate crystals in the tubular lumen?
Ethylene glycol poisoning.
What receptors are stimulated by NE?
a1 & 2, and B1. Has v little effect on B2.
Receptors containing zinc-finger (DNA) binding domains are stimulated by which substances?
Steroids (estrogen, progesterone, aldosterone, cortisol), thyroid hormones (not TSH), and fat-soluble vitamins. These are intracellular Rs.
What kind of receptors do ACTH and ADH bind?
GPCRs- Epi, NE, and glucagon also bind these.
What is the MoA of risedronate?
It is a BP and attached to the hydroxyapatite binding site on bones to inhibit bone resorption by mature osteoclasts.
What are the MAOIs and when should they be used?
Phenelzine, tranylcypromine, and selegiline. They are useful in atypical MDD (mood reactivity, leaden paralysis, rejection sensitivity, increased sleep and appetite), and tx-resistant MDD.
What is likely the result of a mutation in the factor V gene product?
Factor V Leiden, this is resistant to activated protein C and results in a hypercoagulable state DVT and PEs.
What are common mutations leading to Kallman syndrome?
KAL-1 gene, and FGFR-1.
Causes of coronary sinus dilation?
Most common- pHTN; others- anomalous venous drainage into the CS: persistent left SVC, and total anomalous pulmonary venous return.
What are common signs of atheroembolic disease?
Blue toes, livedo reticularis with normal peripheral pulses. Acute kidney injury (oliguria, azotemia) is most common sx.
How does Digoxin decrease HR?
By increasing PSNS tone, which leads to inhibition of AVN conduction.
What illnesses result in cold agglutinin formation?
M. pneumoniae, EBV, and heme malignancies.
What is the AA binding site on tRNA?
The CCA tail at the 3’ end
What is responsible for neutralizing ROS?
Antioxidant enzymes: superoxide dismutase, glutathione peroxidase, and catalase. ROS are extremely high in reperfusion injuries.
What will be the effects on LH, FSH, testosterone and sperm count in a pt. w/Klinefelter?
LH, and FSH both high bc no inhibin from sertoli cells and no testosterone from Leydigs. Low testosterone, and no sperm will be present.
What is responsible for a high Cl- content in venous RBCs in comparison to arterial?
The “chloride shift”: when CA forms HCO3- and H2O the HCO3- ions diffuse out into the plasma, and then the Cl- ions diffuse into the RBC to maintain electrical neutrality.
What is low in the CSF of pts w/ Narcolepsy?
What lies immediately posterior to the esophagus?
The descending aorta.
What labs and signs/sxs are seen in arginase deficiency?
The pt. will have hyperammonemia with significantly increased arginine levels. Results in progressive spastic diplegia, growth delay, and abnormal movements. Tx: arg-free, low-prot diet.
What does vWF bind?
Binds subendothelial collagen and then allows platelets to bind.
Of the antiarrhythmic Rxs that can cause QT prolongation and TdP which is associated with a lower risk than the others of TdP?
Which classes of antiarrhythmics prolong the cardiac AP/prolong the QT interval?
Class IA (Na+ channel blockers- Procainamide, Quinidine, Disopyramide) and Class III (K+ channel blockers- Amiodarone, Sotalol, Dofetilide, Dronedarone)
Which class of antiarrhythmics may decrease the QT interval?
Class IB Na+ channel blockers (Lidocaine, Mexilitine, Phenytoin), and Digoxin.
What causes edema in nephrotic syndrome?
Increased glomerular permeability --> loss of protein and DECREASED oncotic pressure --> hypovolemia, increased Aldo and ADH --> Na+ and H2O retention --> edema. The low oncotic P also leads to increased lipid synthesis.
Course of the great saphenous vein?
Originates on medial side of foot runs ant. to the medial malleolus, then up medial leg and thigh and drains into the femoral v. just inferolateral to the pubic tubercle.
What is the most likely cause of fever and fatigue with new-onset cardiac murmur?
Infective endocarditis. This may be complicated by proliferating glomerulonephritis d/t circulating immune complexes.
What will be seen on histo in an acute viral hepatitis infection?
“Spotty necrosis” with ballooning degeneration (hepato swelling w/wispy/clear cytoplasm), Councilman bodies (esosinphilic apoptotic hepatos), and mononuclear cell infiltrates.
What is opsoclonus-myoclonus a paraneoplastic syndrome of?
Neuroblastoma. Opsoclonus= uncontrolled eye movement (nystagmus). Neuroblastoma may present w/an abd mass, periorbital ecchymoses (d/t mets), and have increased catecholamine metabolites.
Where does neuroblastoma arise from, and what does it look like on Histo?
Neural crest cells of the adrenal medulla. Histo: small round blue cells, and Homer Wright rosettes.
What drug changes the composition of fungal cell membranes as well as inhibits P450s?
All the azoles (Ketoconazole, fluconazole, itraconazole, voriconazole). They inhibit ergosterol synthesis.
Characteristics of Dandy-Walker malformation:
Hypoplasia/absence of the cerebellar vermis, and cystic dilation of the 4th ventricle with posterior fossa enlargement. Often present w/ developmental delay, skull enlargement, cerebellar dysfxn, and non-comm hydrocephalus.
Endometrial adhesions in endometriosis may:
involve the uterosacral ligament --> fixed, retroverted uterus; infiltrate the posterior cul-de-sac and cause painful intercourse and tenderness to palpation of posterior fornix; cause dysmenorrhea if shed.
Where do the hip adductors originate and insert?
Originate on the ischium and insert onto the femur.
What is the function of ANP?
Inhibits renin release.
What drug is likely to improve lipid profiles but cause steatorrhea while treating obesity?
Orlistat- a lipase inhibitor.
What is the MoA of Bupivacaine?
Voltage-gated Na+ channel inhibitor- it decreases the permeability to Na+ and prevents depolarization.
What effect will shortening the C loop of tRNA have on mitochondrial function?
It will decrease protein synthesis.
What disease are you likely to see abnormal sarcomeres with paracrystalline inclusions in the mitochondria?
What are the observational studies?
Cross-sectional, case-control, cohort, twin concordance, and adoption studies.
Describe the characteristics of Normal Pressure Hydrocephalus:
Wet, wobbly, wacky. Urinary incontinence, ataxia, often wide-based shuffling gait, cognitive/memory dysfunction. Imaging will show marked enlargement of the ventricles.
Calculation for Loading Dose:
LD= (C*Vd)/F. Remember to adjust Vd if given in L/kg to the patients weight in Kg.
How can the longevity of herpes infection be explained?
It establishes latent infection in sensory nerve cells.
Common complication of cerebral vascular malformations?
Presence of more than one type of organellar genome (mitochondrial DNA or plastid DNA) within a cell or individual. Important in determining the severity of mitochondrial diseases.
What causes the hypercalcemia in multiple myeloma?
IL-1 and TNF-a effects.
What causes the cachexia of malignancy?
What organism is likely to cause sepsticemia in pregnant women and how will they present?
Listeria (G+, facultative intracellular): presents with fever, nausea, vomiting, and muscle aches. May also cause amnionitis and spontaneous abortions.
What are the characteristics of deficient Apo B?
Abetalipoproteinemia (deficient ApoB48 and 100), shows hypocholesterolemia, with steatorrhea, progressive vision loss, muscle weakness, ataxia, MR, retinitis pigmentosa, and acanthocytosis on peripheral blood smear.
Which component of the nephron is most likely to be damaged in ATN?
The PCT is v. susceptible in both nephrotoxic and ischemic ATN, the ThAL is also susceptible in ischemic.
How do macrolides affect bacterial protein synthesis?
The interfere with translocation.
What type of diet is most effective in decreasing the risk of developing DMII?
Low-calorie, bc this diet is most effective in lowering weight- a huge risk factor for DM.
What type of cells are downey cells in IM derived from?
CD8+ T cells. NOT B CELLS!
What stage of the ETC does CO inhibit?
Complex IV (CN also inhibits here). It decreases the proton gradient and blocks ATP synthesis
What type of cancer and tumor antigen will produce the highest antibody response?
Any cancer caused by a foreign antigen ex: HPV, EBV, HHV-8. Cancers caused by “self” proteins in the body (breast cancer, melanoma, etc.) will be poorly immunogenic.
How does power effect B/Type II error?
Increased power (1-B) decreases B. So a study with power 0.8 has a great chance of type II error than one with power 0.9.
What causes the myopathies and CNS disease in mitochondrial disorders?
Failure of oxidative phosphorylation.
What nerve is responsible for lateral forearm sensation and forearm flexion?
When is there going to be a higher amount of Ca2+ sequestered in the SR?
at more frequent, low frequency contractions as compared to one large contraction at a high frequency that releases all the stored Ca2+.
How does MPO help kill microorganisms?
By producing hydroxyl-halide radicals (hypochlorous acid).
How does chronic alcohol consumption contribute to acetaminophen toxicity?
Chronic alcoholism induces P450 which increases the rate glutathione depletion by acetaminophen hepatotoxicity.
Sampling through the census is what kind of technique?
What is the MoA of Praziquantel?
Increases cell membrane permeability to Ca2+ causes paralysis, dislodgement, and death of the parasite.
What is the cause of muscle atrophy during immobilization?
Increased protein degradation.
What is the MoA of Cisplatin?
It’s a platinum coordination complex, it binds DNA and forms cross-links which inhibits DNA synthesis and function. Binds at N7 position of guanine.
Monoclonal Abs inhibit ribosomal peptidyl transferase, what affect will this have?
It will disrupt the covalent bonding between AAs.
What are the signs/sxs of Amphetamine intoxication?
Pupillary dilation, diaphoresis, agitation, confused thought process, increased BP, HR, and RR.
What causes iron overload?
Increased intestinal iron absorption.
How does relative risk correlate with disease?
A RR < 1 means exposure decreases the risk of getting a disease. A RR >1 means exposure increases risk of getting a disease.
What are the most commonly reported sxs of Temporal Arteritis?
Craniofacial pain syndromes- jaw/tongue claudication, and facial pain. All common when chewing.
Polymyalgia rheumatica (occurs in >50%)- Neck, torso, shoulder and pelvic girdle pain and morning stiffness. May have fatigue, fever, and weight loss as well.
Sudden vision loss
Where is type I collagen present?
Osteoid (organic portion of bone matric), teeth, ligaments, skin and sclera.
What process is impaired in Osteogenesis Imperfecta?
Synthesis of type 1 collagen from Osteoblasts.
What disease is characterized by the impairment of hyaline cartilage deposition by chondrocytes?
Achondroplasia. Endochondral ossification involves deposition of hyaline cartilage by chondrocytes and is responsible for forming the long bones.
What disease is d/t defective mineralization of the bone matrix?
Vitamin D deficiency aka Rickets
Disease of Impaired bone remodeling?
Characteristics of Klebsiella pneumoniae:
Encapsulated, G- bacilli that grows pink, mucoid colonies on MacConkey (aka ferments lactose). Common cause of nosocomial pneumonia. Pseudomonas shares these characteristics except it does NOT ferment lactose, and is oxidase positive.
TPR for vessels arranged in parallel
1/TPR = 1/R1 + 1/R2 + … + 1/Rn
What cytokines circulate during sepsis?
TNF, Il-1, IL6 and IL-8. These activate pulmonary epithelium and contribute to ARDS during sepsis.
What is pulsus paradoxus?
Exaggerated drop in systolic blood pressure (>10mmHg) during inspiration. Classically seen in cardiac tamponade, but can also occur in asthma, COPD, Hypovolemic shock and constrictive pericarditis.
What is seen on EKG in cardiac tamponade?
There will be pericardial fluid accumulation with late diastolic collapse of the right atrium.
beat-to-beat variation in pulse amplitude due to change in SBP. Seen in severe LVF.
Common peroneal n. injury:
Injury is common at the lateral neck of the fibula from fracture or compression. Presents with weakness on dorsiflexion (foot drop), eversion, and toe extension. Sensory loss occurs over lateral leg and dorsolateral foot.
What is a complication of Nitroprusside infusion?
Cyanide toxicity. This Rx is metabolized into NO and CN- in the body, and the CN can accumulate and cause confusion and lethargy.
How do Sodium Nitrate, Sodium Thiosulfate, and Hydroxycobalamin manage CN toxicity?
Na+ Nitrite promotes metHb formation which then combines w/CN.
Na+ thiosulfate serves as a sulfur donor and promotes rhodanese-mediated conversion into thiocyanate.
Hydroxycobalamin binds CN and forms cyanocobalamin which can be excreted into the urine.
What vessel is located in the spermatic cord and where does it arise from?
The gonadal a. It arises from the abdominal aorta. Often injured in testicular torsion.
What would cause reduced salutatory conduction?
Demyelination- like in MS. In acute MS plaques the astrocytes are typically preserved, and only in chronic plaques do we see axonal degeneration.
What are the signs of hyperestrenism in a cirrhotic patient?
Spider angiomata, gynecomastia, testicular atrophy, decreased body hair.
Characteristics of Meniere disease:
Low-frequency tinnitus, vertigo, and sensorineural hearing loss. D/t increased volume and pressure of the endolymph.
What affects do B1-agonists have on myocardial oxygen consumption?
Agonists like Dobutamine increase both HR and contractility which increases oxygen consumption.
One of the most common causes of folate deficient anemia:
Alcoholism. PBS will show pancytopenia with hypersegmented (nuclei with >5 lobes) neutrophils.
What kind of Rx is Etanercept?
TNF-a inhibitor. Other TNF-a inhibitors are the monoclonal Abs Infliximab and adalimumab.
Which anticoagulant is most effective in inactivating thrombin?
Unfractionated heparin is superior to LMWH and Fonaparinux (Factor Xa inhibitor).
What are MMPs?
Zn-containing enzymes that degrade the ECM. Participate in tissue remodeling and tm. invasion through the basement membrane of connective tissue.
Deficiency in Pompe disease:
Acid a-glucosidase aka acid Maltase. Will lead to glycogen accumulation within lysosomal vacuoles on muscle biopsy.
Aka Type V. Muscle Glycogen phosphorylase deficiency weakness and fatigue with exercise, and no rise in blood lactate levels after exercise.
Characteristics of Dermatomyositis:
Cutaneous- Gottron papules over joints and bony prominences, esp. on the hands. Heliotrope rash- edematous eruption on upper eyelids and periorbital skin. Myopathy- Proximal m. weakness difficulty climbing stairs, combing hair etc.
Enzymes responsible for tissue damage and abscess formation?
Lysosomes released by neutrophils and macrophages.
What is IFN-y responsible for?
Phagolysosome formation, inducible nitric oxide synthase release, and development of granulomas and caseous necrosis.
What kind of hernia is commonly seen in Mallory-Weiss syndrome?
NOD2 gene mutations:
Crohn Disease. Mutations cause decrease in the NF-kB pathway and decreased cytokine production.
What is NF-kB?
A proinflammatory txn factor. It increases cytokine production.
Most common causes of SVC syndrome?
Lung cancer and then NH-Lymphoma. Aka MEDIASTINAL masses, NOT superior sulcus tumors.
What does an increase in the activity of enzymes responsible for DNA synthesis signify?
That the cell is in the S phase, and Rb is phosphorylated (aka it is inactive) allowing cells to progress.
What does Rb bind when it is active?
E2F txn factor. This stops cells from progressing from G1 S phase. Rb is hypophosphorylated when active.
What occurs after Ach binds Nicotinic receptors?
N receptors are the only ligand-gated ion channel Rs in the ANS. After binding Ach there is an immediate influx of Na+ and Ca2+ into the cell and an efflux of K+ from the cell. This generates the end-plate potential.
Common AEs of ACEIs:
Decreased GFR (increased creatinine), hyperkalemia, and cough. Angioedema is v. rare but most serious AE.
How do brown adipose tissue cells produce heat?
By uncoupling oxidative phosphorylation with the protein thermogenin.
Most common liver finding in Sarcoidosis:
Scattered granulomas- these affect the portal triads greater than the lobular parenchyma.
The portacaval anastomoses:
Esophageal varices: L. gastric v. (portal) w/ esophageal v. (systemic)
Anorectal varices: Superior rectal v. (portal) w/ Middle & Inferior rectals (systemic)
Caput medusae: Paraumbilical vv. (portal) w/ Superficial & Inferior epigastric vv. (systemic).
What disorders lead to persistent activation of STAT proteins?
Chronic Myeloproliferative Disorders with mutations in JAK2 (a non-receptor TK): Essential thrombocytosis, PCV, and primary myelofibrosis.
What translocation and protein are associated with Mantle Cell lymphoma?
t(11;14), leads to overexpression of Cyclin D.
What viruses replicate via the sequence: dsDNA --> dsDNA template --> dsDNA progeny?
Adenovirus, herpesvirus, and poxvirus.
Where does the intimal flap in Stanford type B aortic dissections (those involving the descending aorta) originate?
Near the origin of the left subclavian artery. Type A start in the sinotubular junction.
In Essential Fructosuria what compensatory enzyme metabolizes fructose?
Hexokinase. Fructokinase is deficient, so fructose can’t be metabolized into Fructose1P and is instead metabolized into Fructose6P by hexokinase.
What enzyme converts glucose to sorbitol?
What are the effects of osteoporosis on serum Ca2+, PTH, and PO4-?
They are all normal in primary osteoporosis, pts just have low bone mass.
In RHF with increased CVP, what compensatory mechanism prevents edema?
Lymphatic drainage increases as interstitial P increases which prevents edema.
What substances can phosphorylate serine and threonine residues of insulin receptors to cause insulin resistance?
TNF-a, catecholamines, glucocorticoids, and glucagon.
What Rx has an MoA of inhibiting fungal cell wall synthesis?
Echinocandins: capsofungin and micafungin. They block glucan synthesis an essential component of the fungal cell wall.
What are some of the AEs of isotretinoin therapy?
Fetal malformations and abortions, hyperlipidemia, chelitis/dry skin, myalgias, and pseudotumor cerebri.
Most common cause of spontaneous lobar hemorrhages?
Cerebral amyloid angiopathy. Common in the elderly and are often recurrent affecting the parietal and occipital lobes the most.
How do nitrates cause relaxation of vascular smooth muscle cells?
By increasing intracellular cGMP leading to myosin light-chain dephosphorylation.
What are craniopharyngiomas derived from and how do they present?
They’re derived from remnants of Rathke’s pouch (ectoderm) the same structure that gives rise to the AP. Grossly they show cystic spaces filled w/ thick, brown-yellow fluid rich in cholesterol. Dystrophic calcification is v. characteristic and may be seen on neuroimaging.
The partial or complete loss of epidermal melanocytes.
What disease has elevated levels of 14-3-3 protein in CSF?
What is the typical presentation of chronic mesenteric ischemia?
Postprandial epigastric pain (intestinal angina) with assoc. food aversion and weight loss. D/t atherosclerosis of the mesenteric aa. --> decreased intestinal blood flow after meals. Similar to angina pectoris.
In pts w/HF what causes the increased afterload, xs fluid retention, and cardiac remodeling?
Increased SNS activity and activation of the RAAS pathway.
Where do the autoAbs in myasthenia gravis originate?
The thymus. The Abs are directed against N-Ach receptors on postsynaptic membrane of the NMJ. Most MG pts also have thymic abnormalities (thymoma, thymic hyperplasia) presenting w/a mediastinal mass.
What affect does cancer have on coagulation?
It produces a hypercoagulable state.
What is atheroembolic dx, what organs does it effect, and what are the characteristic histologic findings?
It is a common cx of invasive vascular procedures, and most commonly involves the kidney. Other organs involves: GIT, CNS, and skin.
Histo shows obstruction of arterial lumen w/needle-shaped cholesterol clefts within the atheromatous thrombus.
Enlarged RBCs that appear blue on Giemsa stain:
These are reticulocytes, the reticular precipitates of residual ribosomal RNA give them the blue appearance on staining. Increased erythropoiesis d/t Fe therapy will increase the amount of reticulocytes in the blood stream.
What messenger system involves PLC?
Gq. PLC cleaves PIP2 into IP3 and DAG which leads to intracellular accumulation of Ca2+.
What is required to activate trypsin, and what would a deficiency in this cause?
Enteropeptidases in the brush border activate trypsin. Deficiency in these would cause diarrhea, failure to thrive and edema (d/t hypoproteinemia) bc trypsin activates the enzymes required for fat and protein absorption.
Conditions assoc. w/Primary Biliary Cirrhosis:
Sjogren’s, Raynaud’s, Scleroderma, AI thyroid disease, hypothyroidism, and celiac disease.
Penetrating neck trauma above the cricoid cartilage is likely to injure what?
The ansa cervicalis- from roots C1-C3. Lies superficial to the internal jugular in the carotid triangle.
Penetrating trauma just above the clavicle is likely to cause what?
Injury to the lung pleura leading to a pneumothorax, tension pneumothorax or hemothorax.
Gaucher disease- get glucocerebroside accumulation. Presents w/hepatosplenomegaly, bone pain, easy bleeding/bruising, pallor and fatigue d/t pancytopenia (invasion of BM w/gaucher cells).
What effects will lactose intolerance have on the stool, and the breath H+ content?
Undigested lactose will be fermented by bacteria leading to increased acid production and decreased pH in the stool. This process also produces hydrogen gas which will increase breath Hydrogen content. Undigested lactose will cause an increase in the stool osmolality.
What is characteristic of acute allergic contact dermatitis on histology?
Spongiosis: accumulation of edema fluid in the intercellular spaces of the epidermis.
Drug reaction with eosinophilia and systemic symptoms. Rare Rx rxn typically 2-8 wks after Rx exposure. Commonly assoc. w/ anticonvulsants, allopurinol, sulfas, and abxs (minocycline, vancomycin).
Presentation of DRESS syndrome:
Fever, generalized lymphadenopathy, facial edema, diffuse rash progressing to confluent erythema w/follicular accentuation. Can affect liver (jaundice), kidney (acute interstitial nephritis), and lung (cough, dyspnea).
Lab results in DRESS syndrome:
atypical lymphocytosis, elevated serum alanine transaminase, and eosinophilia.
Tx of Lyme Disease:
Tetracyclines (Doxycycline), and Penicillin-type abxs (Ceftriaxone)
What are xanthomas associated with?
Hyperlipidemia or lymphoproliferative malignancies.
What does treatment of Acute intermittent porphyria target?
Tx is with IV glucose (dextrose), or heme preparations which inhibit ALA synthase and reduce the accumulation of toxic intermediates of heme synthesis.
Common presentation of a pt. w/pancreatic adenocarcinoma:
Palpable but nontender GB (Courvoisier sign), weight loss, and obstructive jaundice (pruritis, dark urine, and pale stools). These sxs occur d/t pancreatic head tm. compressing the common bile duct.
Risk factors for pancreatic adenocarcinoma:
Age (65-75), smoking, DM, chronic pancreatitis, genetic predisposition.
Genetic disorders assoc. w/ pancreatic ca:
Hereditary pancreatitis, MEN, HNPCC & FAP
Activated Th1 CD4+ cells secrete IFN-y, which activates MPs. MPs then secrete TNF-a which results in further MP maturation and formation of the granuloma.
Histopath of Chronic lymphocytic (Hashimoto) thyroiditis:
Intense lymphocytic/mononuclear parenchymal infiltration with well-developed germinal centers. Residual follicles surrounded by Hurthle cells (large oxyphilic cells filled w/granular cytoplasm).
MoA of C. diff. toxins:
Toxin A (enterotoxin) and B (cytotoxin) both inactivate Rho-regulatory prots involved in signal transduction and actin cytoskeletal structure maintenance. These toxins disrupt intercell. tight jxns --> cell rounding/retraction and increased intestinal fluid secretion. Both toxins also have inflammatory effects and can induce apoptosis.
Characteristic histopath finding of chronic HBV infection:
HBsAg accumulation within the hepatocellular cytoplasm which appears as finely granular, pale eosinophilic, ground-glass appearing.
Hemoglobins Chesapeake and Kempsey:
Mutations that cause production of Hb with high O2 affinity. Reduces O2 unloading in tissues and can cause compensatory erythrocytosis.
Damage to which structure will cause hemiballism?
The Subthalamic nucleus. Lacunar strokes may cause damage to this and lead to contralateral hemiballism characterized by wild, involuntary, large-amplitude (contrasted w/sm amp in Hunt’s) movements of the limbs or body.
What are the steps in extracellular processing of collagen?
Terminal propeptides cleaved by N- & C- procollagen peptidases (often deficient in EDS), and covalent cross-linking by lysyl oxidase.
Blood gas in High-altitude sickness:
Hyperventilation stimulates changes, leads to increased pH from decreased PaCO2 (Respiratory Alkalosis). However, renal compensation should normalize the pH by 24-48hrs, but the PaCO2 and pO2 will both remain fairly low.
How does Epi contribute to increased glucose?
It increases gluconeogenesis in the liver and decreases glucose uptake by sk. Mm. It also increases alanine release from sk. mm. which serves as a source of gluconeo in the liver.
How does ACh produce dilation of epicardial coronary vessels?
Ach stimulates an increase in Ca2+ which activates eNOS to synthesize NO from Arginine, NADPH, and O2. NO then diffuses into the sm. mm. cells to increase cGMP and cause relaxation.
Areas affected in the 3 types of Lung transplant rejection:
Hyperacute rejection (w/in mins)- Graft blood vessel spasm and diffuse intravascular coagulation leads to ischemia.
Acute (1-2wks)- Causes vascular damage with perivascular and peribronchial lymphocytic infiltrates.
Chronic rejection- (mos-yrs) inflammation of the small bronchioles (bronchiolitis obliterans). Inflamm of bronchiolar walls --> narrowing/obstruction of the affected bronchiole.
affects lungs, brain and skin of IMCP’d. Results in cavitary pneumonia and brain abscesses. Tx w/cotrimoxazole
Branching/beaded G+ organism.
Cx of acute pancreatitis- collection of fluid rich in enzymes and inflammatory debris. The walls are lined with granulation tissue and fibrosis, in contrast to true cysts which are lined by epithelium.
How would a tm. in the temporal lobe affect the visual fields?
It would likely disrupt Meyer’s loop located in the temporal lobe and result in contralateral superior quadrantanopia.
What does the Romberg test, test for?
Proprioception (from Dorsal columns and DRG). It distinguishes sensory from cerebellar ataxia. Pts w/cerebellar ataxia will have a negative Romberg.
Inhaled anesthetic hepatotoxicity:
Often caused by Halothane, assoc. w/highly lethal fulminant hepatitis undistinguishable on histo from acute viral hepatitis. Pts. have significantly elevated aminotransferase levels from hepatocellular injury and prolonged PT time.
MoA of Thionamides (Methimazole & PPU):
decrease formation of hormones by inhibiting thyroid peroxidase, which is responsible for iodine organification and coupling of iodotyrosines. PPU also decreases peripheral T3-->T4 conversion.
Enterococcal aminoglycoside resistance:
Enterococci produce aminoglycoside-modifying enzymes that transfer different chem. groups to the aminoglycoside molecules, impairing the abx binding to ribosomal subunits.
What kind of Rx is acyclovir?
A nucleoside analog
What causes hypercalcemia in granulomatous disorders?
Activated MPs express 1-a-hydroxylase which causes PTH-independent production of 1,25-dihydroxyvitamin D.
Greatest prognostic predictors in cirrhosis pts?
Serum albumin levels, bilirubin levels, and PT time as these all are reflective of liver function.
What is the most common disorder of porphyrin synthesis?
Porphyria Cutanea Tarda.
Deficieny in uroporphyrinogen decarboxylase. Presents with photosensitivity that manifests as vesicle and blister formation on sun-exposed areas, as well as edema, pruritis, pain and erythema.
Susceptibility factors leading to acquired PCT:
Alcohol, smoking, halogenated hydrocarbons, HCV infection, and HIV.
Main Features of NF2:
Bilateral acoustic neuromas. NF2 gene mutation on Chrom. 22.
Renal Infarction (Cause and Presentation):
Most common cause is systemic thromboembolism from the LA or LV. Presents w/ flank pain, hematuria, elevated LDH (from cell necrosis), and a wedge-shaped renal lesion on CT.
Segment of intestines most affected by Celiac Disease:
Duodenum, then jejunum. Bx from these areas is required for diagnosis.
What is pathognomonic for Pyelonephritis in the setting of a UTI?
What is renal ammoniagenesis and what stimulates it?
Stimulated by acidosis, it’s the process by which the kidneys metabolize glutamine to glutamate which forms ammonium to be excreted in the urine and HCO3- to be absorbed in the blood. Responsible for the majority of acid excretion in chronic acidosis.
the compulsive consumption of a nonfood or non-staple food source for >/= 1 month. Common in pregnant women and schoolchildren. Often associated w/ nutritional deficiencies (Fe and Zn) and anemia of any sort.
Common in Neuroblastoma, and SCLC.
Preventable Adverse Event
A type of medical error- Injury to a patient d/t failure to follow evidence-based best practice guidelines (delayed diagnoses).
Near miss (medical error):
Error that is recognized before any harm is done to the patient.
Non-preventable adverse event:
Medical error that leads to a complication that cannot be prevented given the current state of medical knowledge. Ex: a Rx allergic rxn in a pt. w/o a hx of Rx allergies.
Net effects of Phenylephrine:
a selective a1-agonist- increases PVR and SBP which leads to a baroreceptor mediated decrease in HR --> decreased SV --> decreased PP.
Where is Histoplasma found, and what are the histologic features?
It is endemic to the MS and OH river basins, found in bird and bat droppings. Associated with cave exploring. It’s a dimorphic fungus located intracellular in MPs. Targets the lungs and RES system.
Spherules packed with endospores:
Coccidioides immitis. NOT associated w/caves. Endemic to southwestern US.
Budding yeast with a thick capsule:
Cryptococcus neoformans. Found in soil containing pigeon droppings.
What is the most likely complication of H.pylori antral gastritis?
Duodenal ulcers. The antrum is at the bottom of the stomach!!!!!!
In Primary Hyperaldosteronism why is serum Na+ concentration normal?
Aldosterone Escape. The increased intravascular volume increases RBF --> release of ANP which limits the net Na+ retention and prevents Vol. overload and significant hypernatremia.
Effects of Major Basic Protein:
kills helminths, and contributes to bronchial epithelial damage in asthmatic pts.
Cori Disease (Type III)
Deficient debranching enzyme. Leads to hepatomegaly, ketotic hypoglycemia, hypotonia, weakness, and abnorm. glycogen w/ v. short outer chains.
von Gierke Disease (Type I):
Glucose 6-phosphatase deficiency. Leads to hepatomeg., steatosis, fasting hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia.
Effects of Isoproterenol:
a non-selective B agonist, it increases myocardial contractility, and decreases SVR. Also causes bronchodilation and mild uterine relaxation.
an endothelin-receptor antagonist, inhibits endothelin-mediated vasoconstriction. It decreases pulm. a. pressure and lessens the progression of vascular hypertrophy and RVH in pts. w/pHTN.
How is Babesiosis transmitted and where is it endemic?
Via the Ixodes scapularis tick (same as Lyme and HGA) which is found in the NE US.
How do you diagnose Babesiosis?
Thin blood smear will show intraerythrocytic pleomorphic ring forms v. similar to malaria. May also see “Maltese crosses”
How does Babesiosis present?
Fever, fatigue, myalgias, HA (Flu-like sxs). If severe: ARDS, CHF, DIC and splenic rupture. Labs show anemia, thrombocytopenia and increased LFTs.
What tumor is characteristic of a central area of necrosis with surrounding pseudopalisading nuclei?
Glioblastoma multiforme- also has vascular proliferation.
What CNS tm. has a whorled pattern of growth w/psamomma bodies?
Tm. with reticulin deposits and chronic inflammatory infiltrates:
Pleomorphic xanthoastrocytoma (v. rarely can progress to GBM).
What disease will have IgA deposits in the mesangium?
IgA nephropathy, and Henoch-Schonlein pupura (NOT HUS!!!!!)
What are the histopath findings in HUS?
Platelet-rich thrombi in glomeruli and arterioles. Same for TTP. These are microangiopathic syndromes.
When do you see acalculous cholecystitis?
In critically ill-pts (sepsis, severe burns, IMCP’d, trauma). Acute inflam. of GB w/o stones. Assoc. w/high mortality.
What contributes to cavitary lesions in TB?
Aggregates of activated leukocytes (CD4+ cells) which activate MPs leading to caseous necrosis and formation of cavitary lung lesions.
What hematologic affects do androgens have?
Testosterone normally stimulates RBC production leading to a higher Hct in M than F. In androgen steroid abuse this is exaggerated and pts will have a largely increased hematocrit/erythrocytosis.
What affects do androgens have on lipid profiles?
They increase LDL and decrease HDL.
What are the common mutations in Medullary thyroid cancer, Follicular, and Anaplastic?
Medullary- RET (proto-oncogene)
Follicular- RAS (proto-oncogene)
Anaplastic- p53 (tm. suppressor).
What is Kussmaul sign and what is it associated with?
A paradoxical rise in JVP during inspiration. Often seen in constrictive pericarditis.
What are the hemodynamic signs found in constrictive pericarditis?
Increased JVP, Kussmaul sign, pulsus paradoxus, and pericardial knock (sharper, more accentuated sound heard earlier in diastole than S3).
What is a loud P2 associated with?
Mutations found in Hereditary Spherocytosis?
Ankyrin and Spectrin
Common cxs of Hereditary Spherocytosis:
Pigmented gallstones, and aplastic crises following parvoB19 infections.
What are the blood supplies to the Foregut, Midgut and Hindgut structures?
Foregut- Celiac trunk (from lower esophagus to 2nd part of duodenum).
Midgut- SMA (3rd part of duodenum to proximal 2/3rds of transverse colon).
Hindgut- IMA (distal 3rd of transverse colon to rectum).
What is Hyaline arteriolosclerosis?
Homogenous deposition of eosinophilic hyaline material in the intima and media of sm. aa. and arterioles. Most often in uncontrolled HTN or DM.
What is hyperplastic arteriolosclerosis?
Onion-skin, concentric thickening of arteriole walls d/t laminated layers of sm. mm. cells, and BM reduplication. Seen in malignant HTN.
How does MM cause nephropathy?
By xs excretion of Bence-Jones proteins that precipitate w/Tamm-Horsfall proteins to form tubular casts that obstruct the lumen. The casts look like amorphous hyaline material in the tubular lumen on histo.
Pathogenesis of McCune-Albright Syndrome:
Mutation in GNAS gene --> constant activation of Gs/cAMP/adenylate cyclase pathway --> hormone overproduction
Clinical features of McCune-Albright syndrome:
Precocious puberty (sex characteristics <8y/o in girls), Irregular café-au-lait macules (Norm. 1st sign; d/t GPCR activity in melanocytes), and Polyostotic fibrous dysplasia (d/t increased proliferation of fibroblast-like cells, increased IL-6, and increased activation of Osteoclasts).
Cxs of McCune-Albright syndrome
Thyrotoxicosis, Acromegaly, and Cushing’s.
What is Legg-Calve-Perthes Disease?
Disease of young kids, get isolated idiopathic osteonecrosis of the hip.
What cancers has EBV been associated with?
Burkitt lymphoma, and nasopharyngeal carcinoma (common in S. China and Africa).
Describe the physiologic changes in the lung caused by ARDS? What parameter will remain normal?
ARDS causes interstitial and alveolar edema --> increased capillary permeability. Leads to decreased lung compliance, increased work of breathing, and V/Q mismatching. The PCWP will remain normal bc this is a non-cardiogenic pulmonary edema.
What Rxs are used as N. meningitidis pphx in close contacts?
Rifampin, Ciprofloxacin (not in children), and Ceftriaxone. Pphx should be admin’d regardless of prior vaccination.
Most common CoD in pts. w/ DM?
Coronary Heart Disease.
Main cause of ESRD?
DM, and then HTN. But ESRD pts typically die of CVD or infections, not renal failure.
Optimal site for femoral n. block?
The inguinal crease at the lateral border of the femoral a. This will anesthetize the skin and mm. of the anterior thigh (quads), femur and knee.
In CF pts. what causes squamous metaplasia of the pancreatic ducts?
Vit. A deficiency. It is needed to maintain orderly differentiation of specialized epithelia.
What vitamin deficiency could cause infertility?
What enzyme is generated by G6PD and what is it used for?
NADPH is produced which goes on to participate in cholesterol & FA synth, and also glutathione antioxidant mechanism.
Which parts of the nephron are impermeable to H2O, regardless of ADH axn?
The thick and thin ascending limbs of LoH, and the early DCT.
What is dystrophic calcification?
Calcification occurring in damaged or necrotic tissue in the setting of normal Ca2+ levels. Responsible for aortic valve calcification w/aging.
What is metastatic calcification?
Calcification of normal tissue in the setting of hypercalcemia.
What is the MoA of Ribavirin?
Induces lethal hypermutation, inhibiting RNA polymerase and inosine monophosphate dehydrogenase (depletes GTP), causing defective 5’cap formation on viral mRNA transcripts. Aka interferes w/the duplication of viral genetic material. Txs HCV.
Abortion resulting in infected retained products of conception. Most common pathogens: S. aureus and E. coli.
What is the MoA of Milrinone?
It’s a selective PDE3 inhibitor which leads to an increase of cAMP in
- ca. mm. (+ inotropy/increased contractility)
- vascular sm. mm.--> systemic arterial and venous dilation.
Inamrinone is the other PDE3 inhibitor.
What is the intrapleural pressure at FRC?
The intrapleural pressure is -5 cm H2O at FRC.
At FRC the airway pressure equals zero, bc the intrapleural pressure and alveolar pressures cancel each other out.
What is the DoC for Restless Leg Syndrome?
Dopamine agonists- Pramipexole.
When are nitrates contraindicated?
HCMP- d/t increased outflow obstruction.
RV infarction- d/t reduced preload impairing CO.
Pts on PDE inhibitors- increases risk of severe HoTN.
Lead toxicity effects on heme synth:
Lead directly inhibits ferrochelatase and ALA dehydratase resulting in anemia, ALA accumulation and elevated Zn protoporphyrin levels. Neurotoxicity is a long-term cx. Can cause language regression in young children.
Children in impoverished areas are at the highest risk.
Most common causes of bacteremia in Sickle Cell pts?
#1: S. pneumoniae
#2: H. influenzae
Both are encapsulated organisms, difficult to eliminate in asplenic pts.
What enzyme has an associated risk with colon adenocarcinoma?
Increased activity of COX-2.
Regular aspirin has been shown to decrease risk of adenomatous polyp formation.
What are the likely causes of a bluish neoplasm underneath the nail bed?
Either a subungual melanoma, or a glomus tumor (originating from the modified sm. mm. cells that control thermoregulation).
Difficulties with key academic skills (reading, writing, or math). Children often have sxs of anxiety, inattention or hyperactivity when under stress to perform these activities.
What GI ulcer is least likely to be malignant?
Esophageal, gastric and colorectal ulcers all have risk of malignancy.
Which strain of E. coli does not ferment sorbitol?
STEC (aka EHEC). It also does not produce glucuronidase like the other strains.
What is the MoA of the shiga and shiga-like toxins?
They inactivate the 60S ribosomal subunit leading to inhibition of protein synthesis and cell death.
What is likely to present with painless waxing and waning lymphadenopathy?
Follicular Lymphoma- the most common indolent (non-painful) NH lymphoma.
What are the most common AEs of nondihydropyridine CCBs?
Aka Diltiazem and Verapamil.
They cause constipation, bradycardia, AV conduction block (d/t negative chronotropic effects), worsening of HF in pts w/ decreased LV fxn (d/t negative inotropy).
What happens to the serum ferritin and TIBC in Fe-deficient anemia?
Serum ferritin will decrease and TIBC & circulating transferrin will increase.
Where does amyloid deposit in Alzheimer disease?
In the brain parenchyma and walls of the cerebral vessels.
What drug can be given to increase the activity of Azathioprine?
Xanthine oxidase is one of the major enzymes that inactivates azathioprine, and allopurinol inhibits XO, leading to increased active metabolites (6-TG) of azathioprine.
What causes Diffuse Esophageal Spasm and how will it present on manometry?
It is d/t impaired inhibitory neurotransmission within the esophageal myenteric plexus. On manometry it is characterized by periodic, simultaneous, and non-peristaltic contractions.
Fracture of which ribs have the greatest risk of damaging the visceral pleura?
What structure is likely to be injured by a fracture of the L. 12th rib?
The left kidney.
Fracture of what rib will likely injure the spleen?
The L. 9th-11th ribs.
What is likely to cause perifollicular hemorrhages and coiled/corkscrew hairs?
Which cellular compartment has a high activity level of Vitamin C?
The RER, bc this is where the hydroxylation of proline and lysine during collagen synthesis occurs.
3 most common risk factors for hypoglycemia in DM1 pts?
xs insulin dose, inadequate food intake, physical activity/exercise.
What effect does sk. mm. contraction have on glucose uptake?
Contraction increases glucose uptake by mm. cells. This leads to decreased insulin release and increased endogenous glucose production to limit the glucose uptake by mm. cells and maintain serum glucose levels.
When is GLUT-4 translocated to the cell membrane?
In response to insulin and muscle contraction.
The primary action of PCP?
NMDA receptor antagonist.
Glutamate, aspartate and D-cycloserine
What causes Diabetic mononeuropathy and describe its effects of CN III?
Caused by ischemic nerve damage, in CN III it predominately involves the core and spares the periphery of the n. therefore sparing the PSNS. Presents as down-and-out w/ptosis. Pupillary size and reactivity will be normal.
Describe nonocclusive ischemic colitis and the areas most likely to be affected:
Low blood flow to the colon that often occurs in HoTve states esp in pts w/ vascular insufficiency. Affects watershed areas (splenic flexure and rectosigmoid jxn.). Presents as Abd pain and bloody diarrhea.
What is the cause of megaloblastosis and how is it assoc. w/alcoholism?
Megaloblastosis results from defective DNA (purine/pyrimidine) synthesis and can be seen in chronic alcoholics d/t poor nutrition --> folate or B12 deficiency. Alcohol-related macrocytosis may also occur independent of folate deficiency.
What catalyzes transaminase rxns and what will a deficiency lead to?
B6/Pyridoxine. Will lead to hypochromic, microcytic, sideroblastic anemia.
What would lead to impaired pyruvate decarboxylation?
Vitamin B1/Thiamine deficiency.
What are the most common manifestations of C. perfrigens infection?
Clostridial myonecrosis (gas gangrene), and late-onset, transient, watery diarrhea.
What toxin causes damage in myonecrosis?
Lecithinase, a phospholipase toxin (a-Toxin). It attacks cell membranes.
Explain the type of hypertrophy associated with mitral regurge:
Eccentric hypertrophy- see decreased LV wall thickness with an increase in chamber size from volume overload.
What kind of damage is caused by UV rays and how is it repaired?
Single strand breaks occur leading to pyrimidine dimers. These are then removed by nucleotide excision repair where endonuclease makes nicks on either side of the damaged DNA and removes it.
Disease of nucleotide excision repair?
What part of the spine is involved in RA?
The cervical spine- get subluxation and cord compression.
What causes Ebstein’s anomaly in infants?
Maternal lithium usage.
What provides sensation to the webspace b/w the 1st 2 toes?
The deep peroneal n.
What n. can be injured in anterior compartment syndrome?
The deep peroneal n. May lead to impaired dorsiflexion and sensory loss between the webspace.
DoC for oropharyngeal candidiasis, and its MoA?
Nystatin rinse. It binds ergosterol and forms pores in the cell membrane --> cell death.
What can cause a paraneoplastic hyperthyroidism?
High circulating levels of hCG from germ cell tumors in the testes and ovaries.
What is the source of Schistosomiasis?
What causes the clinical manifestations of Schistosomiasis?
Th2-mediated granulomatous response against the eggs. Will see infiltration of Th2 cells, eosinophils and M2 macrophages --> fibrosis, ulceration and scarring of the bowel or bladder/ureters.
What is periportal “pipestem” fibrosis pathognomonic for?
Hepatic schistosomiasis. D/t eggs settling into the presinusoidal radicals of the portal v.
What becomes compressed in a subfalcine herniation?
The anterior cerebral a.
Why are skeletal mm. resistant to CCBs?
Bc they have little dependence on extracellular Ca2+ influx. Ca2+ release by the SR is instead triggered by a mechanical interaction b/w L-type and RyR Ca2+ channels, unlike the Ca2+-dependent Ca2+ release seen in cardiac and smooth mm.
What would be seen on biopsy from a pt. w/ Primary Biliary Cirrhosis?
Lymphocytic infiltration and granulomatous destruction of interlobular bile ducts.
What are the associated neoplasms of VHL?
Hemangioblastomas, Clear cell renal carcinoma, and pheochromocytoma.
What electrolyte disturbances are assoc. w/Amphotericin B?
Hypokalemia and Hypomagnesemia.
What artery courses with the radial n. along the humerus?
The deep brachial a. It can also be injured in mid-shaft fractures affecting the radial n.
What artery may be injured in supracondylar fractures of the humerus?
The brachial a.
What is the MoA of opiates?
They bind Mu receptors on afferent neurons which blocks Ca2+ channels --> decreases release of excitatory neurotransmitters from the presynaptic terminal. Also bind Mu-Rs on the postsynaptic membrane which opens K+ channels to increase K+ efflux --> membrane hyperpolarization.
What reverses the effects of Warfarin in an overdose?
Fresh frozen plasma.
What is given to reverse heparin?
Protamine- it binds and chemically inactivates it.
Common cxs of varicose veins:
Skin ulcerations from venous stasis, stasis dermatitis, poor wound healing, superficial infections, painful thromboembolisms (less common).
What is the MoA of Diphtheria toxin?
It is an AB exotoxin, inhibits protein synthesis by ADP-ribosylation of EF-2 --> respiratory cell necrosis w/ fibrinous, coagulative exudates.
What bacterial exotoxin causes an increased sensitivity to histamine?
What is the associated mutation and characteristic features of spinal muscular atrophy?
Mutation in SMN1 gene which leads to impaired snRNPs in lower motor neurons. Infants present with flaccid paralysis d/t degeneration of anterior horn cells in the spinal cord.
What is Osgood-Schlatter Disease, and how will it present?
It is an overuse injury (from repetitive quadriceps contraction) of the secondary ossification center (apophysis) of the tibial tuberosity. Presents w/ pain and swelling at the tibial tubercle/the insertion point of the patellar ligament.
What vessels are likely to be injured in a anterolaterally displaced supracondylar humeral fracture v. an anteromedially displaced?
Anterolateral- Radial n.
Anteromedial- Median n. and Brachial a.
What AE of opioids is likely to cause RUQ abdominal pain?
Contraction of smooth muscles in the sphincter of Oddi --> spasm and an increase in common bile duct pressures.
What is the antidote for atropine poisoning?
Rxs for Focal seizures:
Carbamazepine, gabapentin, phenobarbital, phenytoin.
Rxs for generalized seizures:
Valproate, Lamotrigine, Topiramate, Levetiracetam.
What are some of the common AEs of TCAs?
Confusion, constipation, and urinary retention. TCAs are occasionally used to tx insomnia and pain syndromes.
During a water-deprivation test, what condition will not result in an increased urine osmolality after ADH admin?
Primary polydipsia and normal pts.
How many vertebral levels does a normal kidney usually span?
What is the first area damaged during global cerebral ischemia?
The Hippocampus (pyramidal cells)! The second area is the neocortex and purkinje cells of the cerebellum.
Damage to which structures will cause Decerebrate and Decorticate posturing?
Decerebrate- Damage at or below the Red nucleus: Midbrain tegmentum, or pons.
Decorticate- damage above the red nucleus: cerebral hemispheres or internal capsule.
What would cause resistance to anti-EGFR therapy?
An activating mutation in KRAS.
Characteristics of Myotonic Dystrophy?
AD disease of trinucleotide repeat expansion. Difficult loosening grip, cataracts, frontal balding, and gonadal atrophy. Type 1 fibers are most affected.
What is deficient in Type 1 hyperlipoproteinemia and what are the major manifestations?
LPL and ApoC-II are deficient.
Presents w/ recurrent acute pancreatitis, lipemia retinalis, and eruptive xanthomas mostly on extensor surfaces.
What enzyme is responsible for TXA2 production?
COX-1. Unaffected by tx w/celecoxib aka COX-2 selective.
Name the NSAIDs:
Ibuprofen, naproxen, ketorolac, diclofenac, meloxicam, piroxicam.
What are the splice donor and acceptor sites?
What is the equilibration of O2 and CO2 normally limited by?
Perfusion (not diffusion). Will show v. high pO2 concentrations and low pCO2 concentrations in the alveoli compared to normal.
What are normal values for alveolar pO2 and pCO2?
pO2= 104 mmHg
pCO2= 40 mmHg
What will CSF reveal in HSV encephalitis?
Hemorrhagic lymphocytic pleocytosis w/increased protein and normal glucose.
Common disease-causing intracellular fungi?
C. neoformans, H. capsulatum, P. jirovecii
What is the most common cause of viral meningitis?
Enteroviruses- Coxsackie, echo and polioviruses.
Describe Wallerian degeneration in the CNS following an infarct:
Axonal degeneration and breakdown of the myelin will occur distal to the injury site. Axonal regeneration will not occur in the CNS d/t the persistence of myelin debris, secretion of neuronal inhibitory factors and development of dense glial scarring. (regeneration will occur in the PNS).
Describe the gross liver pathology of Dubin-Johnson:
Liver will appear black d/t accumulation/impaired excretion of epinephrine metabolites (dense pigments w/in lysosomes).
What is the most common type of thyroid cancer and how will it appear histologically?
Papillary carcinoma. Appears as large cells w/overlapping nuclei containing finely dispersed chromatin w/ground glass appearance (Orphan annie eye); Psammoma bodies; Intranuclear inclusions and grooves.
What causes HoTN in opioid intoxication?
Release of Histamine
CLx = [(Urine Cx) x (Urine Flow Rate)] / (Plasma Cx)
What is the Filtration Fraction calculation and normal value in healthy pts?
FF = GFR/RPF. It is usually equal to 20%.
What substances are used to estimate GFR and RPF?
GFR is estimated by the clearance of Inulin or Creatinine. RPF is estimated by the clearance of PAH.
What is mesenteric adenitis?
Pseudoappendicitis caused by Yersinia enterolitica. Often in kids 5-14, presents w/fever, RLQ pain, and N/V.
What are the differences b/w gastric ulcers and erosions?
Ulcers extend through the mucosa, muscularis mucosa, and into the submucosa. Erosions extend through the mucosa and into the muscularis mucosa but do not extend all the way through into the submucosa.
What causes Cushing and Curling ulcers?
Cushing- head trauma/increased ICP. Thought to overstimulate Vagal n. --> xs gastrin release.
Curling- severe burns. Reduced plasma volume --> ischemia and necrosis of the gastric mucosa.
What chromosome is the Amyloid Precursor Protein (APP) on?
What Rx should be substituted to prevent a cardiovascular event in a pt. w/aspirin allergy?
Clopidogrel- it is as effective as aspirin in prevention. It irreversibly blocks the P2Y12 component of ADP-Rs on platelet surfaces and prevents their aggregation.
What is Stewart-Treves syndrome, its main risk factor and how will it appear histologically?
Cutaneous angiosarcoma. Chronic lymphedema is the main risk factor and on histo it will show infiltration of the dermis w/slit-like abnormal vascular spaces.
What effects does SIADH have on the volume compartments?
SIADH pts will have a clinically normal extracellular fluid volume and low plasma osmolality --> euvolemic hyponatremia.
What treatment can exacerbate thiamine deficiency and cause Wernicke encephalopathy?
Glucose infusion. Thiamine is a cofactor of enzymes responsible for glucose metabolism, so glucose w/out thiamine supplementation can exacerbate its deficiency.
What is the most common brain tumor of childhood and how is it differentiated on imaging?
Pilocytic astrocytomas- arise from the cerebellum. Differentiated from medulloblastoma by the presence of both cystic and solid components on imaging.
What do large eosinophilic casts in the tubular lumen suggest?
Multiple myeloma. The casts are composed of Bence-Jones proteins.
In DCMP what will be the cause of the pts sxs?
A decrease in ventricular contraction force --> systolic dysfxn. and progressive CHF. Ischemic heart disease will present similarly.
What are some of the less common causes of acute pancreatitis?
Rxs (AZT, sulfasalazine, furosemide, valproate)
Infections (mumps, coxsackie, M. pneumo.)
Surgery (esp. of the stomach/biliary tract, and cardiac surgery)
What effects will nitroprusside have on a P-V loop?
It is a venous and arterial vasodilator so it decreases both preload and afterload. This shifts the curve slightly left and shortens it, but the decreases are balanced, so the SV remains the same.
What are the features of Rx-induced Acute Interstitial Nephritis?
Fever, rash, and acute renal failure (elevated creatinine, oliguria) w/in 1-3 weeks of starting a Rx tx. Will have peripheral eosinophilia and eosinophiluria. Usually spares the glomeruli.
What is the MoA of Fibrates?
They activate peroxisome proliferator-activated receptor alpha (PPAR-a) which decreases hepatic VLDL production and increases LPL activity.
In pts. w/Duodenal ulcers where is the highest concentration of H. pylori found?
In the pre-pyloric/antrum area of the stomach.
How will malignant otitis externa present, and what is the most common cause?
Pseudomonas is most common cause. Presents w/exquisite ear pain and drainage, and granulation tissue within the ear canal.
Describe Adenocarcinoma in situ of the lung:
Considered a MALIGNANT neoplasm. A subtype of lung adenocarcinoma. Old name: bronchioloalveolar carcinoma. Histo: well-diff’d, dysplastic columnar cells lining the alveolar septa w/out vascular or stromal invasion. Undergoes aerogenous spread.
What are the Abs found in RA and which is the most specific?
RF- an anti-IgG Ab is v. sensitive but not at all specific. Also found in SLE and healthy pts.
Anti-CCP is very specific for RA.
What Rxs increase the risk of osteoporotic fractures d/t decreased Ca2+ absorption?
PPIs- they decrease the acidity of the stomach, which is required for proper Ca2+ absorption.
What would be seen in an optic tract lesion?
A contralateral homonymous hemianopia and a relative afferent pupillary defect in the contralateral pupil.
A lateral geniculate nucleus lesion would present w/ the same hemianopia but the pupils would react normally.
What Rx targets the CD20 surface immunoglobulin?
Rituximab- used in lymphoma tx. Can also be used to tx TTP.
What diseases is recombinant IL-2 used to tx?
RCCa and Melanoma.
What is the MoA of Ethosuximide?
Blocks thalamic T-type Ca2+ channels
What is the MoA of Levetiracetam?
Binds synaptic vesicle protein (SV2A) to modulate the release of GABA and glutamate.
How does Rheumatic fever cause mitral stenosis?
By diffuse fibrous thickening and distortion of the mitral leaflets w/ commissural fusion at the leaflet edges.
What causes a PDA?
Prostaglandin E2 production by the placenta
How does a PDA present in infancy?
A continuous murmur, with widened pulse pressures and signs of cardiovascular strain.
What are “Burr” and “Helmet” cells characteristic of?
Traumatic hemolysis d/t microangiopathic hemolytic anemia or mechanical damage (prosthetic valve).
What are Burr cells?
RBCs w/short, evenly-spaced projections. Seen in uremia, pyruvate kinase deficiency, microangiopathic hemolytic anemia, or mechanical damage.
What is Osler-Weber-Rendu syndrome?
Hereditary hemorrhagic telangiectasia. AD disorder w/telangiectasis in the skin, mucus membranes of the lips, oronasopharynx, resp. tract, GIT, and urinary tract. They can rupture --> epistaxis, GI bleeding, or hematuria.
What is affected in Tabes Dorsalis and how will it present?
Causes degeneration of the dorsal columns and roots of the spinal cord --> loss of proprioception and vibration, ataxia, and Argyll Robertson pupils.
What causes congenital torticollis and how will it present?
Results from Intrauterine malposition or birth trauma, and presents by 2-4weeks of age with the head tilted to one side. A soft-tissue mass may be palpable in the inferior 1/3 of the SCM.
What is the common histo finding of Kaposi sarcoma?
Spindle and endothelial cell proliferation, red blood cell extravasation, and inflammation. May spread to lungs and GIT.
What stains positive for terminal deoxynucleotidyl transferase (TdT)?
What stains positive for TRAP?
Hairy cell leukemia.
What does AML stain positive for?
What causes chronic non-atrophic gastritis affecting the antrum?
H. pylori infection
What risks does endotracheal intubation pose to a pt. w/ chronic RA?
Long-standing RA can affect the C-spine --> malalignment/subluxation most commonly involving the atlantoaxial joint. Intubation can worsen the subluxation and cause compression of the spinal cord --> flaccid paralysis w/hypo/areflexia at all levels below.
What is pulsatile GnRH commonly used to tx?
What is the best approach to addressing medication errors
A root cause analysis. This would include interviewing all people concerned in the error that was made.
How is tetanus diagnosed?
Clinically by a good hx and PE. There is no serum toxin assay or Ab test available and it is v hard to culture.
What is Erythema Multiforme?
A cell-mediated, systemic immune response to a LOCAL (not disseminated) infection. Often assoc. w/HSV and Mycoplasma.
How will disseminated HSV present?
Normally in IMCP’d with diffuse vesicles on an erythematous base.
How will a PCA lesion present?
As a contralateral homonymous hemianopia with macular sparing.
Anticonvulsants assoc. w/SJS:
Lamotrigine, Carbamazepine, Phenytoin, and Phenobarbital.
What is the MoA of resistance in Extended-spectrum B-lactamase producing organisms?
Plasmid-encoded gene resistance.
What affect does exercise have on SVR?
Exercise causes increased CO and splanchnic vasoconstriction which slightly increases BP, but there is vasodilation in the active skeletal muscles which significantly decreases the SVR.
What degrades bradykinin and substance P?
What is characterized by segmental vasculitis extending into contiguous veins and nerves?
What are hexagonal-shaped crystals on urinalysis pathognomic for?
Cystinuria. AR disorder. Causes recurrent nephrolithiasis. Get Aminoaciduria.
What features suggest malignancy in an enlarged lymph node?
Monoclonal lymphocyte proliferation of a single cell line with rearrangements.
What is Dermatomyositis a common paraneoplastic syndrome of?
Most commonly associated cancers are: ovarian, lung, colorectal, and NH lymphoma.
What cytokines are secreted by MPs?
IL-1, IL-6, IL-8, IL-12, and TNF-a
Who do we normally see isolated systolic HTN in, and what causes it?
It is common in pts. >60 yrs who have increased arterial stiffness d/t aging. This causes decreased compliance of the aorta (and major peripheral aa.) and an increase in pressures during systole.
How is Weber’s test interpreted?
It lateralizes to the unaffected ear in sensorineural hearing loss and to the affected ear in conductive hearing loss.
What is the pathogenesis of SSPE after Measles infection?
Accumulation of viral nucleocapsids w/in neurons & oligodendrocytes --> formation of intranuclear inclusions --> inflammation, demyelination, and gliosis in cerebral areas.
What is found in the CSF of a pt. w/SSPE?
Oligoclonal bands of measles virus Abs.
What are risk factors for primary psoas abscesses?
HIV, IVDA, DM
What kind of channel is the CFTR channel?
ATP-gated Cl- channel.
What nerves lie within the prostatic fascia and what will injury of them lead to?
The prostatic plexus (originating from the inf. Hypogastric plexus) lies in the fascia and is at risk of injury during prostatectomy. Injury can cause erectile dysfxn. bc the cavernous nn. that carry PSNS to the penis arise from this plexus.
What are the features of glucagonoma?
Necrolytic migratory erythema- painful and pruritic papules/plaques on face, perineum & extremeties; DM/hyperglycemia; GI sxs- D/AbdP/Anorexia. Dx w/elevated glucagon levels.
Why is a washout period necessary after discontinuing an MAOI before starting a SSRI?
Because MAOIs irreversibly bind MAO and deplete it. 2 weeks are needed for synthesis of new MAO to avoid causing serotonin syndrome.
What would be seen with tibial n. injury?
Weakened plantar flexion and inversion of the foot, and decreased sensation at the sole of the foot.
What food is strongly assoc. w/botulism contamination, and how will infant botulism present?
Presents w/constipation, mild weakness, lethargy, reduced feeding.
More severe: weakened suck, swallowing and crying. “floppy baby”
What affects do BBs have on an ECG?
They slow AVN conduction which leads to a prolonged PR interval. Does NOT affect QRS or QT intervals.
What are the characteristics of Gilbert Syndrome?
Mild unconjugated hyperbilirubinemia with no apparent liver disease. Triggered by fasting, exercise etc.
What is haptoglobin and why is it decreased in SCD?
Haptoglobin binds circulating Hb to reduce its renal excretion. There is increased Hb release in SCD so all of the haptoglobin is bound in these pts. leading to decreased levels in the serum.
What pathogens cause secondary bacterial pneumonia following influenza infection and who are at risk for this?
#1- S. pneumoniae
#2- S. aureus
#3- H. inflluenzae.
The elderly are at high risk for this complication.
What is the MoA of Latanoprost?
A topical prostaglandin used to tx Glaucoma. It increases the outflow of aqueous humour. May increase the pigmentation in eyelashes and iris.
What are the signs of irreversible neuronal damage, and what would occur in these areas?
Neuronal shrinkage and intense cytoplasmic eosinophilia. Astrocytes would proliferate in this area leading to gliosis/glial hyperplasia.
What is leukemoid rxn, and what will the lab values and PBS show?
Benign leukocytosis occurring in response to underlying conditions (infection, hemorrhage, malignancy or hemolysis).
Leukocyte alkaline phosphatase will be normal or increased.
PBS: increased bands, early mature NP precursors, and Dohle bodies in the NPs.
What states are S3 often heard in?
SHF, and those with high ventricular filling pressures and/or volume overload, particularly aortic or mitral regurgitation and DCMP.
What are the cutaneous manifestations of PAN?
Livedo reticularis and palpable purpura.
What cephalosporins have activity against pseudomonas?
Ceftazidime (3rd gen) and Cefepime (4th gen).
Where in the nephron are the lowest and highest tubular fluid osmolalities?
Lowest: In the DCT, it is ~100 mOsm/L.
Highest: The bottom of the LoH, it’s ~ 1200 mOsm/L
What is the MoA of Fidaxomicin and what is it used to treat?
It’s a macrocyclic antibiotic that inhibits the sigma subunit of RNA polymerase --> protein synth. impairment and cell death. Used to tx. C. diff infections, esp. in pts. w/recurrent cases.
What Rxs can be used to tx C. difficile?
Metronidazole, vancomycin or fidaxomicin.
What is claudication the result of?
Atherosclerosis of larger, named arteries.
Adding what to a Hemophiliacs blood will result in clotting?
It cannot be formed w/out factors VIII and IX, but fibrinogen is already there so adding thrombin will activate it to fibrin and result in clotting.
What is typically the first nutrient affected in malabsorption and how can it be tested for?
Fat is the earliest and most severely affected nutrient in generalized malabsorption. Can test by assay of stool with Sudan III stain. Fat should not be measurable in the stool.
Describe the murmur associated with VSDs and when are they first heard?
Harsh/blowing holosystolic murmur heard best at mid to lower left sternal border. Normally not heard at birth, audible by 4-10 days of life as PVR declines and allows L-->R shunting.
Large VSDs may not have a murmur.
Describe the clinical and lab findings of PSGN:
Gross hematuria, periorbital edema, and HTN. Urine will reveal RBCs, protein, and RBC casts. Serum shows increased creatinine and decreased C3.
What stimulates connective tissue synthesis and remodeling of the ECM?
What is responsible for fibrosis of the lung, liver, and kidney in chronic inflammation?
How do lung volumes affect PVR, and at which point is PVR the lowest?
PVR is lowest at FRC, bc both increased and decreased lung volumes increase PVR.
Increased lung volumes: increase PVR d/t stretching of the alveolar capillaries by the expanding alveoli.
Decreased lung volumes: Increase PVR d/t decreased radial traction from adjacent tissues on the large extra-alveolar vessels.
What organism is characterized as round/oval yeast w/broad-based budding?
Where is the CTZ located?
In the area postrema of the dorsal medulla near the 4th ventricle.
What are the inferior colliculi and medial geniculate bodies part of?
The auditory pathway.
What are the Cardiac effects of Carcinoid Syndrome?
Plaque-like deposits of fibrous tissue on the R-sided endocardium --> tricuspid regurg., pulmonary stenosis --> RHF.
D/t xs serotonin secretion --> stimulates fibroblast growth and fibrogenesis.
5-HIAA elevated in urine.
What diuretics should be given to pts. w/HF exacerbation & fluid overload?
Loop Diuretics. These are the most potent diuretics and provide the maximum amount of diuresis in the shortest period of time.
What are the Aldosterone antagonists?
Eplerenone and Spironolactone.
What Rxs likely cause Rx-Induced SLE?
Top 3: Hydralazine, Procainamide, Isoniazid.
Minocycline, TNF-a inhibitors (Etanercept), and Quinidine also can.
What is c-ANCA?
Cytoplasmic antineutrophil cytoplasmic Ab. It’s an Ab directed against lysosomal enzymes of neutrophils and monocytes. Would have positive indirect IF when added to neutrophils.
What is the MoA of Isoniazid and how does resistance to it develop?
INH inhibits mycolic acid synthesis. It requires mycobacterial catalase-peroxidase to be activated in the bacteria, so absence or mutations in this enzyme lead to resistance.
What is the cause of a cholesterol-mass obstructing the ileum?
Gallstone ileus- occurs when a large gallstone erodes into the intestinal lumen through a cholecystoenteric fistula. Will likely see air in the biliary tree, and small bowel obstruction w/air-fluid levels on imaging.
What is AI hemolytic anemia and what infections is it assoc. with?
AIHA is d/t production of Abs against RBCs. It often follows Mycoplasma and EBV infections.
What will Alport syndrome show on EM?
Lamellated appearance of GBM w/ irregular thinning and thickening (Basket-Weave appearance).
What are the Abs produced in Goodpasture syndrome, and the hallmarks of the disease?
Anti-GBM Abs are against the alpha 3 chain of Type IV collagen. They damage the glomerular and alveolar BMs --> RPGN and alveolar hemorrhage w/increased DLCO. Can be idiopathic or triggered by viral respiratory illness.
Myxomatous degeneration has a high risk of what complications?
Aortic aneurysms and dissection. Does not contribute to the pathogenesis of berry aneurysms.
What receptors are the primary site for sensing PaCO2 and PaO2?
Central chemoreceptors are primarily stimulated by PaCO2 and the decreased pH it causes in the CSF.
Peripheral chemoreceptors are the primary site for sensing arterial PaO2 and are stimulated by hypoxemia (v. important in COPD pts. who have a decreased sensitivity to PaCO2).
What type of tumors are S-100 positive?
Tumors of neural crest origin: Schwannomas, Melanomas.
Describe the pattern of a Schwannoma on histo:
They are biphasic with highly cellular areas intermixed w/myxoid regions of low cellularity. They are S-100 positive tms.
What is the effect of chronic hemolysis on the kidney?
Constant breakdown of RBCs may lead to Iron deposition in the kidney- hemosiderosis. This may interfere w/proximal tubule fxn --> interstitial scarring and cortical infarcts.
What does Thayer-Martin agar consist of?
Vancomycin- to inhibit G+.
Colistin/Polymyxin- inhibits G-s.
Nystatin- inhibits yeast.
Trimethoprim- inhibits proteus spp.
What would Abs to PLA2R be concerning of?
Idiopathic membranous nephropathy. PLA2R is a transmembrane receptor in high concentration in glomerular podocytes.
How will arsenic poisoning present and what is the DoC for tx?
It impairs cellular respiration --> Abd pain, V/D, HoTN, and garlic smelling breath. Can lead to TdP.
Commonly found in insecticides and contaminated water.
Dimercaprol is the DoC.
What are accessory nipples caused by?
Failure of involution of the mammary ridge.
What class of Rxs does Terbinafine belong to, and what is their MoA?
They inhibit squalene epoxidase and therefore inhibit ergosterol synthesis.
What is the DoC for Alcohol withdrawal?
Long-acting Benzos: Diazepam and Chlordiazepoxide.
Barbituates have a worse safety profile so they aren’t used.
What common laboratory abnormalities are assoc. w/Legionella?
Hyponatremia- possibly from xs ADH or impaired Na+ reabsorption; Elevated transaminases.
This is the only cause of pneumonia that hyponatremia is associated with.
Describe the characteristics of Hairy cell leukemia and what is seen on PBS:
Hairy cells aka LCs w/cytoplasmic projections are seen on PBS.
This cancer invades the BM and RES. In the BM it causes fibrosis -->pancytopenia and a “dry tap.” Will also infiltrate the splenic red pulp causing massive splenomegaly.
Common sxs: LUQ pain, fatigue, weakness, fever, recurrent infections. May not have lymphadenopathy.
What are ringed sideroblasts associated with?
What is defective in Glanzmann thombasthenia?
GP IIb/IIIa receptor
What causes the hemorrhagic cystitis assoc. w/Cyclophosphamide, and what is used to prevent it?
The toxic metabolite Acrolein causes it, and it can be prevented with Mesna.
What lab values should be measured before starting Metformin?
Serum creatinine to assess risk for lactic acidosis.
How does Shigella cause infection?
It is taken up by the M cells via endocytosis and then lyses them, multiplies and spreads laterally into other cells. Causes denuding/ulceration of the mucosa --> blood, mucus, and inflammatory cells into the intestinal lumen.
What part of the intestine does Shigella and Salmonella infect?
Shigella only infects the LI, Salmonella infects both the SI and LI.
What is the most common benign liver tumor and how will it appear on histo?
Cavernous hemangioma. They are well-circumscribed, spongy masses.
Histo: cavernous, blood-filled vascular spaces lined by a single epithelial layer. Biopsy may cause fatal hemorrhage.
Describe the MoA of Foscarnet and what it is used to tx:
Foscarnet is a pyrophosphate analog- doesn’t require intracellular activation. Directly inhibits DNA polymerase (txs Herpesviruses-including CMV), and RT (txs HIV).
What are the B-lactamase inhibitors and what is their purpose?
Tazobactam, Clavulanate, and Sulbactam. They are given w/B-lactam abx to prevent their inactivation and increase their spectrum of activity.
What are the biochemical abnormalities in Alzheimers?
Decreased acetylcholine levels in the hippocampus and nucleus basalis of Meynert.
This causes cortical and hippocampal atrophy and leads to cognitive and memory decline.
Why AchEIs are helpful in this disease.
What is transformation and what bacteria are able to undergo it?
The uptake of exogenous DNA from neighboring cells that have lysed. Strep., Bacillus, and Neisseria can all undergo transformation.
What is a common manifestation of ParvoB19 infection in adults?
Acute arthropathy- symmetric polyarthritis of the PIPs, wrists, knee and ankle joints. It is self-limited and d/t Immune complex formation.
What is 5th disease caused by and how does it present?
Aka Erythema Infectiosum- caused by parvoB19.
In children, presents w/ bright red rash on cheeks and circumoral pallor and fever. May also get reticular rash on arms, legs, and trunk.
What is the most common secondary tm. developed in pts. w/Familial Retinoblastoma?
What are the primary sources of ALP?
Bone and liver. If elevated, then GGT should be checked to determine if it is a bone or liver source of the elevation.
What enzyme converts pro-carcinogens into carcinogens?
The MICROSOMAL Cytochrome P450 monooxygenase system. If it is overactive it increases the risk of susceptibility to cancer.
What anesthetics are responsible for causing acute hepatitis and what will be seen on bx?
The halogenated inhaled anesthetics: Halothane, enflurane, isoflurane, sevoflurane, and desflurane. On bx it will look identical to viral hepatitis w/centrilobular hepatic necrosis.
In what setting will secretin increase gastrin release?
When a gastrin-secreting neoplasm is present, like in ZES or Gastrinoma. Will see ulcers distal to the duodenal bulb.
What will be the laboratory findings in a pt. w/Reye syndrome?
LFTS show elevated ALT, AST, Ammonia, BR, and prolonged PT and aPTT.
LM: microvesicular steatosis (small fat vacuoles in the cytoplasm of hepatos).
EM: Swelling, decreased mitochondria and glycogen depletion.
What causes encephalopathy in Reye syndrome?
Hepatic dysfxn --> hyperammonemia which is toxic to the CNS --> cerebral edema.
What type of arthritis is PCV associated with?
Gouty arthritis. Myeloproliferative disorders increase uric acid production.
What are acrochordons?
Skin tags- pedunculated outgrowths of skin.
What are cystic hygromas and what conditions are they associated with?
Lymphatic cysts lined by a thin endothelium. They’re benign and typically present at birth on the posterior neck or lateral chest wall. Assoc. w/ Turner’s and Downs.
What sensory losses are associated with ALS?
NONE! It only affects upper and lower MNs. Does not cause any sensory loss.
How can syringomyelia present with both UMN and LMN sxs?
It causes loss of pain and temperature initially with LMN signs typically of the upper limb, but the syrinx can expand over time to involve the lateral corticospinal tract causing UMN signs in the lower extremity w/loss of position and vibration. Scoliosis is also common d/t paresis of paravertebral mm.
What are the inflammatory mediators of anaphylaxis?
Histamine and Tryptase. Tryptase is specific to Mast Cells and elevated levels can be used to detect mast cell activation.
What will trigger degranulation after IgE receptor activation?
After an Ag binds IgE receptors on mast or basophils, the IgE Abs become cross-linked --> receptor aggregation, this activates non-R TKs, which triggers an intracellular cascade leading to cell degranulation.
What other AI disorders is DM-1 associated with?
Endocrinopathies: Hashimoto’s, Graves, and Addison’s
What should be suspected in a DM1 pt. w/hyperpigmentation, decreased insulin requirement and weight loss; What are the hallmarks of the disorder?
Adrenal Insufficiency/Addison’s- produces Abs to all 3 layers of the adrenal.
Decreased cortisol --> decreased insulin requirement.
No aldosterone --> hyponatremia, hyperkalemia, hyperchloridemia and non-anion gap metab. acidosis.
ACTH admin will not increase serum cortisol.
What would a Rx targeting HIV gp41 prevent?
These are fusion inhibitors (Enfuvirtide), and inhibit HIV fusion w/ the target cell membrane.
What are the key features of the Schizotypal personality disorder?
Eccentric, with odd thoughts, perceptions and behavior.
What structure becomes hypertrophied in spinal stenosis?
How is G6PD inherited?
X-linked recessive. Males are affected, Females are carriers.ritu
How is hereditary spherocytosis inherited?
Most structural abnormalities are AD, most enzyme deficiencies are AR (or XR).
What is permissiveness?
When one hormone without a particular action allows another to exert its maximal effect of that action (like cortisol increasing the vasoconstrictive effects of catecholamines).
What affect does citrate have on nephrolithiasis?
Hypocitraturia increases the risk of calcium oxalate precipitation and stone formation. Often seen in chronic metabolic acidosis (distal RTA, chronic diarrhea) d/t increased renal citrate reabsorption.
What are the features of anaplastic tms?
Multinucleated, giant cells
Loss of polarity w/disruption of normal tissue architecture
Cellular and nuclear pleomorphism
Increased nucleus:cytoplasm ratio
Numerous mitotic figures.
How will T-cell ALL likely present?
Often in a pediatric pt. as a mediastinal mass that can cause resp. sxs: dysphagia, or SVC syndrome. Numerous blast cells on PBS.
How will B-cell ALL present?
In a pediatric pt. w/fever, malaise, bleeding, bone pain and hepatosplenomegaly. NO mediastinal mass. Numerous blast cells on PBS.
Where does RCCa (clear cell) originate from?
The epithelium of proximal renal tubules.
What is axonal reaction?
What happens in a neuronal body after an axon has been severed. The cell body becomes swollen/rounded with peripheral displacement of the nuclei and dispersion of Nissl substance to the periphery of the cells. This is d/t increased prot. synth.
What Rxs are most effective in reducing cellular infiltration and inflammation of airways in asthmatics?
Glucocorticoids (Fluticasone); Leukotriene (montelukast) inhibitors are also useful but less effective.
What is the most common subtype of germ cell tm. in females and when do they present?
Teratomas. Typically present in females 10-30y/o. Will have cell lines of >1 germ layer.
Describe the difference b/w the murmurs in ASD and VSD:
Both are heard best in the Tricuspid auscultation area.
VSD= harsh, holosystolic “blowing” murmur.
ASD= Diastolic with fixed splitting of S2.
What is pneumoatosis intestinalis and how is it seen on XR?
It’s air in the bowel wall, seen as thin curvilinear areas of lucency that parallel the bowel wall lumen on XR. In infants this is diagnostic for necrotizing enterocolitis.
What is the most common complication of statin use?
Myopathy- presents w/myalgia and elevated creatinine kinase.
What is subacute cerebellar degeneration a paraneoplastic syndrome for?
SCLC, Breast, ovarian, and uterine cancers.
Occurs d/t anti-Yo, anti-P/Q, and anti-Hu Abs that cross-react with Purkinje neuron antigens.
Pts. exhibit progressive dizziness, limb and truncal ataxia, and visual disturbances (diplopia, oscillopsia).
Most common cause of Nodular glomerulosclerosis, and how it appears on LM:
DM 1 or 2.
See GBM thickening and increasing mesangial matrix deposition. Will see Kimmelstiel-Wilson nodules, which are diagnostic and indicate irreversible glomerular damage.
What area of the brain will have the greatest degree of atrophy in Alzheimer’s disease?
The hippocampus- atrophy on MRI is v. suggestive of alzheimers. It lives in the medial temporal lobe.
What are the key differences that colitis-assoc. carcinoma displays?
Affects younger patients
Progress from FLAT and non-polypoid dysplasia
Histo: mucinous and/or signet ring morphology
Early p53 mutations, late APC
Found in proximal colon
Multifocal in nature.
What is the cause of an increased ESR?
TNF-a, IL-1, and IL-6 all mediate systemic inflammatory response and stimulate secretion of acute phase reactants- Fibrinogen.
Fibrinogen causes RBCs to form rouleaux which sediment at a faster rate--> increased ESR.
What cytokines are secreted by MPs?
Il-1, IL-6, IL-8, IL-12, TNF-a
How does psoriatic arthritis present?
Can range from mild to severe. Often involves the DIPs, can be asymmetric or symmetric polyarthritis (resembles RA), spondylarthropathy, or the severe aggressive/destructive form is arthritis mutilans.
What is the DoC to tx Malignant hyperthermia and what’s its MoA?
It acts on the RyR and prevents further release of Ca2+ into the cytoplasm of muscle fibers. Also used to tx NMS.
What is the pathogenesis of HIV-assoc. dementia, and how will the pts present?
It's caused by inflammatory activation of microglial cells. HIV-activated MPs and microglial cells form microglial nodules (areas of necrosis) and may fuse to form multinucleated giant cells.
Pts. present w/ subcortical dementia- attn./working memory problems, executive dysfxn, slow processing.
Norm in pts w/ <200 CD4 cells.
What conditions are assoc. w/ Renal papillary necrosis?
Sickle cell disease OR trait, analgesics, DM, pyelonephritis and urinary tract obstruction.
What is fanconi syndrome characterized by?
Polyuria, acidosis, hypophosphatemia.
What can cause IgE-independent mast cell degranulation and how does it present?
Common with Rxs like opioids, radiocontrast agents, and some abx (vancomycin).
Common sxs: diffuse itching and pain, bronchospasm, and localized swelling/urticaria.
What cells synthesize collagen?
Fibroblasts, osteoblasts, and chondroblasts
What is the most common karyotype of a complete mole?
46, XX. D/t one sperm fertilizing an empty ovum and then duplicating. Much less common are 46, XY- an empty ovum fertilized by 2 different sperm.
What Rxs are used to treat rate v. rhythm?
Rate is controlled w. Rxs that block AVN conduction- BBs and CCBs. Rhythm is controlled w/ antiarrhythmics- Class I and III.
How do IFN-a and B participate in viral infections?
They are secreted by viral infected cells and bind to neighboring infected cells to increase txn of antiviral enzymes that halt viral protein synthesis.
Where is type I collagen located?
Dermis, bone, tendons, ligaments, dentin, cornea, BVs, and scar tissue.
Where is type II collagen located?
Cartilage, vitreous humor, and nucleus pulposus
Where is type III collagen found?
Skin, lungs, intestines, BVs, bone marrow, lymphatics, and granulation tissue.
Where is type IV collagen found?
What enzymes requires thiamine as a cofactor?
PDH, a-KG DH, BC a-ketoacid DH, and transketolase.
What are the characteristic lab abnormalities in HUS?
Decreased Hb and platelet count (may increase BT only), Increased LDH, Indirect BR, BUN and Cr.
What causes supine HoTN?
Compression of the IVC --> decreased VR and preload, which decreases the CO and causes HoTN. Common in pregnancy when uterus obstructs IVC.
What is the DoC in symptomatic management of PAD and what is it’s MoA?
Cilostazol- a platelet PDE inhibitor. It increases cAMP in platelets preventing their aggregation, and also is a direct arterial vasodilator which decreases sxs like claudication.
What does MELAS stand for?
Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes.
What are the PDE-3 inhibitors, and what are their CVS affects?
Milrinone and Inamrinone. They inhibit breakdown of intracellular cAMP, which promotes increased intracellular Ca2+ in myocytes and increased contractility. This causes vasodilation in vascular sm. mm.
What segment of the colon is always involved in Hirschprung and why?
The rectum, bc neural crest cells migrate caudally and reach here last, so if migration is disrupted at any point the rectum will always be affected.
What is given prophylactically to prevent damage from radioactive Iodine?
Potassium Iodide- it competitively inhibits uptake of radioactive Iodine.
When is S3 heard?
Systolic HF, Mitral Regurgitation, High-Output States. May also be heard in pregnancy and pts. <40y/o.
When is S4 heard?
Diastolic dysfxn (LVH), younger adults and children.
How do cholesterol, bile salts, and phosphatidylcholine contribute to gallstone formation?
Bile salts and PC both make cholesterol more soluble, so when these are decreased and cholesterol is increased it promotes the formation of gallstones.
What are the contact precautions for MDR organisms (MRSA, VRE), C. diff., and scabies?
Hand hygiene (soap and water- alcohol sanitizers don’t kill the spores), nonsterile gloves, and a gown. Private rooms are preferred.
What is deficient in pts. with Ehlers-Danlos?
Describe the presentation of Botulinum toxicity:
3 D’s: Diplopia, dysphagia, and dysphonia 12-36hrs after consumption. Ach release is inhibited which prevents muscular contraction seen as decreased CMAP, however rapid, repetitive stimulation will help increase CMAP.
What are the hallmarks of Rubella infection?
Rubella = Togavirus. It begins as a facial rash that rapidly (more rapid than Measles) spreads to the trunk and extremities. Postauricular and occipital lymphadenopathy are v. common in this disease.
What bacteria is most associated with ecthyma gangrenosum and how will it present?
Most commonly from P. aeruginosa bacteremia. Perivascular bacterial invasion w/exotoxin release causes necrosis and ulceration of skin patches not getting sufficient blood. Common in neutropenic patients susceptible to G- organisms.
What hematologic affect will COPD have?
Causes chronic hypoxia and increased EPO.
What are neurofibromas?
Benign nerve sheath neoplasms mostly made of Schwann cells- a neural crest derivative.
What is the most likely disease to display cystic degeneration of the putamen?
What affects do chronic NSAID use have on the kidney?
Chronic interstitial nephritis- patchy interstitial inflammation w/fibrosis, tubular atrophy, papillary necrosis and scarring, and distorted calyces. Calcium deposition may occur in the areas of chronic inflammation.
What are the AEs of Niacin?
Flushing, hyperglycemia, hepatotoxicity, and decreased urate excretion --> gouty arthritis.
What is it called when Aspergillus forms a fungus ball in a pre-existing lung cavity?
Colonizing. It colonizes a hole that has already been formed and forms an aspergilloma.
What are the precursors of NAD+?
Tryptophan, Niacin, and Nicotinamide
What is Arginine the precursor of?
Nitric oxide, Urea, Ornithine, and Agmantine. Also necessary to form creatinine.
Describe a crossover study:
2 groups are assigned to different treatments, then they undergo a washout period and undergo the opposite treatment of what they started with.
Describe Western blot:
Tests for proteins. Target proteins are separated via gel electrophoresis, then primed with an Ab for the protein, then treated with a second, marked Ab that binds to the primary Ab so that it can be detected.
What mutation and disorder are associated with deficient Fibrocystin?
PKHD1 mutation ARPCKD
What are the changes in pulmonary function that occur with aging?
Aging causes a decrease in chest wall compliance, but an increase in lung compliance d/t decreased elasticity. Overall this results in an increase in RV, a decrease in FVC, and TLC remains unchanged. FEV1 and DLCO will also decrease.
What is the single most preventable cause of death and disease in the US?
What are the most effective APC, why?
DCs, bc they constitutively express HMC-II and B7.
What should a pre-op verification process involve?
Independent identification of both the patient and surgical site by 2 different health care workers.
If the radius of a lumen is decreased by 50% what happens to flow?
It is reduced by a factor of 16 --> Flow/16 = r/2.
What the fuck bacteria is characterized as a spherule filled with endospores?????
COCCIDIOIDES YOU DUMBASS BITCH!!
What bacteria look like spores in a MACROPHAGE??
What bacteria is associated with pigeon droppings, and what is associated with birds/bats/caves?
Don’t you fucking dare mess this one up: C. neoformans is associated with pigeon droppings. Histoplasma is associated with Birds/bats/caving in MS/OH river basin.
What do Amatoxins inhibit?
RNA polymerase II --> inhibit mRNA synthesis.
What channels are responsible for Ca2+ release, and then uptake during excitation-contraction coupling?
L-type/Voltage-dependent Ca2+ channels, and RyR both release Ca2+ to allow for m. contraction.
Then, Na+/Ca2+ exchange pump (NCX) and the SERCA/Ca2+-ATPase pump are responsible for Ca2+ reuptake to allow for m. relaxation.
Organisms that require v. few cells to infect:
Shigella (10-500 cells depending on the spp.),
C. jejuni (~500cells),
Entamoeba (1-10 cells),
Giardia (1-10 cells).
What is Pentamidine used for?
PCP, African sleeping sickness, and leishmaniasis.
What Rx is used in status epilepticus to prevent recurrent seizures?
Phenytoin- Na+ channel blocker in cortical neurons.
What deficiency will mimic the neurologic symptoms of Freidrich Ataxia?
Vitamin E def. Both will have degeneration of spinocerebellar tracts (Ataxia), dorsal columns (loss of proprioception and vibration), and peripheral nerves (loss of DTRs). B12 def may present similar
What is the only Rx to show efficacy in tx-resistant Schizophrenia?
Where does the Trigeminal nerve exit the brainstem?
At the lateral aspect of the mid-pons at the level of the middle cerebellar peduncles.
What would fetal aromatase deficiency cause?
Ambiguous genitalia w/clitoromegaly d/t increased testosterone and androstenedione, as well as maternal virilization.
How are osteocytes connected to each other?
Via canaliculi and gap junctions.
How will a deficiency in galactokinase present?
This causes a buildup of galactitol bc Galactose can’t be converted to Galactose-1P so instead it is converted to galactitol by aldose reductase. This causes cataracts and the presence of reducing substances in the urine.
Supplementation of what cofactor may improve the condition of MSUD?
Thiamine. It is the cofactor required for Branched-chain a-ketoacid dehydrogenase.
What cofactors are required for BC a-ketoacid DH?
What is required for the transamination and decarboxylation of AAs?
Glutamate transferring N to OAA to form Aspartate and a-KG is an example of a transamination requiring B6.
What is BH4 the cofactor for?
The synthesis of Serotonin (via tryptophan hydroxylase), Tyrosine (via Phenylalanine hydroxylase) and DOPA (via Tyrosine hydroxylase).
What microorganisms does capsofungin have the best axn against?
Candida and Aspergillus.
What will be the results of a quadruple screen in a pt. w/a trisomy fetus?
Increased BhCG and Inhibin A. Decreased AFP and unconjugated estriol.
What is ANOVA used to determine?
If there are any significant differences between the means of 2+ independent groups.
What effects would a chronic arteriovenous shunt have, and how would it look on a crossplot?
The shunt will increase CO bc of increased SNS to the heart, decreased TPR and increased VR. The VR curve will shift to the right bc the circulating volume is increased. It presents the same as exercise on a crossplot.
What effect does sunlight have on Vitamin D metabolism?
It increases the conversion of 7-dehydrocholesterol (provitamin D3) to cholecalciferol (vitamin D3).
What Rxs bind a nuclear txn factor to tx Psoriasis?
Vitamin D analogs (Calcipotriene, calcitriol, and tacalcitol). They bind the Vit. D receptor which is a nuclear txn factor --> inhibits keratinocyte proliferation, stimulates keratinocyte differentiation.
How to calculate RPF from RBF:
RPF = RBF x (1-Hematocrit)
What 2 hormones have incretin effects?
GLP-1, and gastric inhibitory peptide.
What may be a complication of compression of the L. renal v. b/w the aorta and SMA?
Varicocele. Bc the L. spermatic/gonadal v. drains into the renal v. and may lead to buildup of fluid and varices in the testicular pampiniform plexus.
What nucleus mediates satiety?
Ventromedial of the hThal. Lesions will lead to hyperphagia.
Where is Wernicke area located?
At the posterior aspect of the superior temporal gyrus.
What should the first drug in organophosphate poisoning tx be?
Atropine, then pralidoxime.
What is the MoA of Bosentan?
A nonselective endothelin receptor blocker. Blocks initial transient depressor ETa and the prolonged pressor ETb responses to endothelin.
What are the excitatory neurotransmitters?
Glutamate and Aspartate
What are the inhibitory neurotransmitters?
GABA and Glycine
What is the MoA of Protease inhibitors?
They interfere with protein processing, by inhibiting HIV aspartyl protease which cleaves viral polyprotein into RT, protease, and integrase.
What is a likely cause of hypoxia in a patient post-MI?
LVF and pulmonary edema d/t increased pulmonary capillary pressure.
What Amino Acid is often the precursor of ammonia?
Glutamine. It is deaminated by Glutaminase in the kidney. Chronic acidosis will induce glutaminase as a defense mechanism to excrete excess ammonia.
Describe a paraesophageal hernia:
Protrusion of the fundus into the chest above the level of T10.
What type of vessels does Wegener’s affect, what will this cause in the kidney?
Small vessels. May lead to hematuria.
What kind of blood transfusion do we give SCID patients?
Irradiated packed RBCs.
What is slipped strand mispairing?
When a DNA strand “slips” while being transcribed and can lead to an insertion or deletion of nucleotides depending on where it begins transcribing from again.
What is the site of malformations in DiGeorge syndrome?
3rd and 4th POUCHES
What does the “empty can” test for?
Supraspinatous impingement, tear, etc. This is the most common rotator cuff injury.
What type of pulse abnormality will be seen in an aortic dissection?
Decreased femoral pulses.
What is increased in immature fetal lungs that decreases their ability for gas exchange?
Lung elastic recoil
What psychiatric illness are cancer patients at risk for?
How to calculate ejection fraction:
EF= SV/EDV = (EDV-ESV)/EDV
Where is B12 absorbed?
The ileum; Iron in duodenum, and Folate in jejunum.
Why can deoxygenated blood carry more CO2 than oxygenated?
DeoxyHb is a better buffer of H+ ions than oxyHb.
What are the types of Melanoma?
Superficial spreading, nodular, lentigo maligna, and acral lentiginous.
Describe lentigo malina?
Brown-black, mottled, scaly lesion w/irregular borders. On histo: atypical melanocytes spread along the basilar layer of the epidermis.
Describe the stage of embryo development at 20 days post conception:
Neural plate is present, but neural tube is not yet complete.
What are peroxisomes involved in?
Catabolism of VLCFAs (through B-ox), branched-chain FAs, AA, and ethanol.
What organelle is involved in degrading ubiquitin-tagged proteins?
What kind of acid-base disturbance may be seen in Loop Diuretics?
Volume contraction metabolic alkalosis.
What affect would insulin deficiency have on TGs?
TGs are degraded in adipose tissue into glycerol which is then used by glycerol kinase in the liver and kidney to synthesize glucose via gluconeogenesis.
What stages are oocytes arrested in?
Primary oocytes are arrested in Prophase of Meiosis I until puberty. Then every month a secondary oocyte is released at ovulation and arrested in Metaphase of meiosis II until fertilization.
Which type of cells require the action of lysosomes to process Ags?
APCs that express MHC-II. MHC-I Cells do not process Ags within acidified lysosomes.
What are P bodies?
They are cytoplasmic foci involved in mRNA regulation and turnover.
When is an S3 heard best?
At the end of expiration in the lateral decubitus position.
What would cause a decrease in PO2 from alveolar capillary blood to systemic arterial blood?
Mixture with deoxygenated blood. The LA and LV both have a small portion of deoxygenated blood in them.
What type of bleeding is described as non-pulsatile?
If the hepatoduodenal ligament is occluded and bleeding is still occurring what has likely been injured?
The IVC or hepatic veins.
What are the main features of Theophylline intoxication?
N/D/V, Abd P, arrhythmias (but not QT prolongation), and seizures.
In 21-Hydroxylase deficiency what hormone is directly suppressed during tx?
ACTH. This is overproduced d/t the lack of cortisol in these pts. which then leads to even more androgen production.
What auscultatory finding is the best indicator of the severity of MR?
Presence of an S3. This means that it has already lead to LV overload.
What is the cause of a Zenker diverticulum and how will it present?
It is d/t decreased relaxation of the cricopharyngeal mm. during swallowing. Presents in elderly pts w/oropharyngeal dysphagia, halitosis, regurgitation and recurrent aspiration.
What holosystolic mumur will increase with inspiration?
How does IL-2 reduce tumor burden?
By enhancing the activity of NK cells, and T cells.
What cytokine will increase MHC 1 & 2 expression?
What is G6PD the enzyme for?
Conversion of Glucose-6-P to 6-Phosphogluconate in the PPP. This reaction also produces NADPH.
What is the most important mediator of coronary vascular dilation?
What will PBC resemble on biopsy?
GVHD. Both will show lymphocytic infiltration/inflammation with destruction of intrahepatic bile ducts.
How are ARR, RRR, RR, and NNT all connected?
ARR= control rate- treatment rate
RRR= ARR/control rate
RR= treatment rate/control rate
What hematological/immune effects do corticosteroids have?
They cause neutrophil demargination which causes an increase in production leading to neutrophilia. Although the NPs are there, they are unable to respond to infection --> IMCP’d/increase risk of infection.
What n. is at risk of injury during a thyroidectomy and what would m. would be affected?
The external branch of the superior laryngeal n. is at risk. It innervates the cricothyroid m.
What cells are directly responsible for synthesizing the fibrous cap in atherosclerosis?
Smooth muscle cells.
Describe acute salicylate intoxication:
Presents w/N/V, confusion, tinnitus and tachypnea several hrs later. It beings w/ Respiratory alkalosis and then 12 HRS LATER anion gap metabolic acidosis beings to develop.
What is the MoA of the Shiga toxin?
Halts protein synthesis by disabling the 60S ribosomal subunit--> epithelial cell death and diarrhea
What toxins inhibit protein synth. By ADP ribosylation of EF-2?
Diphtheria toxin, and Pseudomonas Exotoxin A.
What toxins increase fluid secretion by increasing cAMP?
ETEC Heat labile toxin, and Cholera toxin both by overactivating adylate cyclase; Anthrax Edema toxin by mimicking adenylate cyclase.
What toxin inhibits phagocytic ability by increasing cAMP?
Pertussis toxin- it disables Gi which leads to overactivation of adenylate cyclase.
What toxins can lyse cell membranes?
C. perfringens a-toxin/lecithinase and S. pyogenes streptolysin O
What are the super-Ags that can cause shock?
S. aureus TSST-1 and S. pyogenes Endotoxin A
What muscle would be damaged by a chest tube inserted in the 5th ICS midaxillary?
What is linkage disequilibrium?
When a pair of alleles are inherited together in the same gamete more or less often than would be expected given their individual frequencies. Occurs more often when the genes are close together on the same chromosome.
What is adenomyosis and how will it present?
The presence of endometrial tissue in the myometrium. Often presents with menorrhagia and painful bleeding. The uterus will be uniformly enlarged and a biopsy will show normal endometrial tissue.
What is a direct indicator of alveolar ventilation status?
Arterial PaCO2. Hypocapnia implies alveolar hyperventilation (pneumonia, PE); Hypercapnia implies alveolar hypoventilation (Obstruction, decreased ventilatory drive, resp. m. fatigue, decreased chest wall compliance).
What does tetanus prevent the release of?
Glycine and GABA (both inhibitory NTs)
What are the most common organisms to infect a dog, cat, or human bite?
Dog: Pasteurella multocida, Streptococci, S. aureus;
Cat: P. multocida, B. henselae;
Human: Anaerobes, Strep., Eikenella corrodens.
What organisms will have a mouse-like odor when cultured?
Indole + species, P. multocida.
Where is airway resistance highest in the respiratory tract?
In the 2nd-5th gen. airways (the medium sized bronchi).
A pure hemisensory stroke is likely to have affected which structure?
The thalamus- particularly the ventral posterior thalamus where the VPL and VPM nuclei are.
What are lacunar infarcts the result of?
Small vessel occlusion d/t lipohyalinosis and microatheroma formation. This leads to liquefactive necrosis and cystic cavities
What is the DoC for Restless leg syndrome?
Dopamine agonists (Pramipexole, ropinirole)
What is the MoA of systemic progestins in combined OCs?
Reduce serum gonadotropins by suppressing GnRH and pituitary gonadotropin secretion --> inhibits ovulation.
What is hibernating myocardium?
LV systolic dysfxn d/t reduced coronary blood flow at rest. It prevents myocardial necrosis. Can be partially or completely reversed by coronary revascularization.
What are the hallmarks of Patau syndrome?
Midline defects: Cutis aplasia (part of skull missing), Microcephaly/holoprosencephaly, microphthalmia, cleft lip/palate, umbilical hernia/omphalocele. Also have polydactyly, cardiac defects, and renal defects w/rocker-bottom feet.
What are some factors that contribute to insulin resistance?
Elevated free FAs- they impair insulin-dependent glucose uptake and increase hepatic gluconeogenesis. Obesity, and sedentary lifestyle.
What is the MoA of Anastrozole, what are the other Rxs in this class?
Anastrozole, Letrozole, and exemestane are all aromatase inhibitors. They decrease estrogen levels and help tx ER+ tumors in POST-menopausal women (not as effective in pre-menos).
Stimulation of which n. is used to help tx OSA?
The hypoglossal n. It moves the tongue forward and opens the airway more.
What is the MoA of Diphenoxylate?
It and Loperamide are mu opiate R agonists and slow motility in the GIT. Helps tx diarrhea- not used in infections w/toxins or invasive organisms.
Mutations in what viral component are mostly responsible for changes in their host range?
The viral surface glycoprotein which mediates virion attachment to target host cell receptors.
What condition is characterized by black urine if left exposed to air?
Alkaptonuria- AR disorder lacking homogentisic acid dioxygenase. This blocks tyrosine metabolism, leads to accumulation of homogentisic acid and a lack of fumarate.
What is one of the most common AEs of Isoniazid therapy?
Hepatotoxicity. It typically subsides with continued treatment. Frank hepatitis (fever, anorexia, N, and rarely hepatic failure) occurs in a small percentage of patients.
What is the most serious complication of Kawasaki disease?
Coronary a. inflammation leading to aneurysm.
What n. and reflex may be impaired by a foreign body in the piriform recess?
The internal laryngeal n. may become damaged, impairing the cough reflex.
Which viruses acquire their envelope from the host cell nuclear membrane as opposed to the host plasma membrane?
Herpes family viruses are the only ones that do this.
What anti-lipids are contraindicated in pts. w/GB disease?
Fibrates- they reduce cholesterol solubility and promote gallstone formation.
What is the most common cause of bloody nipple discharge, how does it appear on histo?
Intraductal papilloma. Proliferation of papillary cells in a duct or cyst wall w/a fibrovascular core. May contain DCIS. Normally not a/w breast masses or skin changes.
What dx is a/w eczematous exudate over the nipple?
Paget disease. d/t malignant spread to the nipple surface.
How do you calculate the frequency of an allele in a population given the disease occurrence?
With Hardy-Weinberg: p^2 + 2pq + q^2 is the phenotypic frequency. So if a disease is AR and you know its frequency in the population is q, take the square root of q to find the allele frequency. Then divide that number by 2 to find the probability of someone being a carrier.
How to calculate Odds Ratio:
OR = (a x d) / (b x c)
What hemodynamic effects will Dopamine have?
DA has affinity for D1>B1>a1. It causes vasodilation w/decreased BP and icnreased RBF w/D1 agonsim.
With increasing doses it will activate B1 --> increased SBP, CO and HR w/out changing DBP. and then eventually decrease CO by a1R vasoconstriction.
What affect will Spironolcatone have on the CD?
It will increase Na+ secretion into the lumen, and will decrease the amount of both H+ and K+ secretion.
When is the membrane most permeable to K+?
During the repolarization phase, the downward slope, not the peak.
What will stain intensely pink with PAS and why?
Glycoprotein, bc it is diastase resistant. It is abundant in the cell walls of T. whippelii.
How are transpeptidases important in relation to abx?
Transpeptidases are a type of PBP that fxn to cross-link PDG in the bacterial cell wall. Penicillins and cephalosporins can irreversibly bind these to inhibit cell wall synthesis.
What abx can bind cell wall glycoproteins?
Vancomycin binds terminal D-ala residues of cell wall glycoprots to prevent transpeptidases forming cross-links.
What are the characteristics of Small Intestine bacterial overgrowth?
These enteric bacteria can lead to overproduction of Vitamin K and folate, but may lead to a deficiency in B12, Fe, Vits A, D, and E, and Zinc. Presents as N/AbdP, bloating, and malabsorption.
What is the cause of Scarlet fever and what are the complications?
GAS, can lead to acute rheumatic fever and glomerulonephritis just like normal Strep throat.
Describe the presentation of Idiopathic Intracranial HTN:
Aka pseudotumor cerebri. Often in young obese women w/daily HA, bilateral symmetric papilledema, and transient visual disturbances (d/t impaired cerebral venous outflow & increased ICP). Sxs worsen w/ Valsalva.
Why does increased ICP cause papilledema?
The pressure buildup compresses the optic nerves externally --> impairs axoplasmic flow w/in the optic nn. --> bilateral papilledema.
What dx is characterized by an acute increase in intraocular P, and how will it present?
Closed-angle glaucoma. Presents w/painful monocular vision loss, HA/V, conjunctival injection w/a poorly reactive mid-dilated pupil. Normally in older pts.
What affects do mu R Opioids have on ion channels?
Opioids that bind mu Rs, inhibit presynaptic Ca2+ channels to prevent NT release, and activate postsynaptic K+ channels to hyperpolarize the membrane.
What is the only cause of hypoxemia that has a normal A-a gradient?
Hypoventilation. Normal A-a gradient= 10-15
What is medial degeneration commonly associated with?
Aortic dissections. Not aneurysms.
How do aortic aneurysms a/w Syphilis start?
With vasa vasorum endarteritis and obliteration --> inflammation, ischemia, and weakening of the adventitia.
What is the primary function of the nucleolus?
The synthesis and assembly of immature 60S and 40S ribosomal subunits.
Is acute rejection humoral or cellular?
Can be either. Humoral is d/t C4d deposition, neutrophilic infiltrate and necrotizing vasculitis. Cellular is d/t lymphocytic interstitial infiltration and infiltration of the vessels (endotheliitis).
What is a common AE a/w 2nd gen anti-psychotics, and which carry the highest risk?
These have a risk of causing metabolic syndrome w/wt. gain, dyslipidemia, and hyperglycemia/new-onset DM. Clozapine and Olanzapine have highest risk. Should monitor BMI, fasting glucose & lipids, BP, and waist circumference while on these and at baseline.
Where is the transverse carpal ligament?
Aka the FLEXOR RETINACULUM. Stretches across the dorsal wrist. Cut in carpal tunnel surgery to take pressure off the median n.
What will be the effects of Multiple Myeloma on Ca2+ homeostasis?
The lytic bone lesions are what cause increased Ca2+ in serum, this causes decreased PTH to be released, leading to increased Ca2+ excretion in the urine. MM causes renal failure and will cause Vitamin D to be low.
What is Nifurtimox used to tx?
Its an antiparasitic, txs Chagas/American trypanosomiasis caused by T. cruzi.
What does pentamidine tx?
It is pphx and tx for PCP in HIV pts. May also tx African sleeping sickness and leishmaniasis.
What induces COX-2?
IL-1, TNF-a, inflammatory cytokines.
What are Cholesteatomas?
Collections of squamous cell debris, form pearly mass behind the tympanic membrane. D/t chronic negative pressure in the middle ear, can cause conductive hearing loss. If large enough can erode into CN VII or VIII and cause vertigo or facial palsies.
Which ligament attaches to the medial femoral condyle and which attaches to the lateral?
The PCL attaches to medial femoral condyle; ACL attaches to lateral femoral condyle.
What DNA exists as a small circular chromosome and resembles prokaryotic DNA?
What type of study uses populations, rather than individuals, as the unit of analysis?
Ecological. Cross-sectional studies use individuals.
What will be seen in the Resp. epithelium of CF pts in regards to ion transport?
There will be increased Na+ and H2O absorption, and decreased Cl- secretion. Opposite in sweat glands.
Where are collagen proline and lysine residues hydroxylated?
In the RER. Requires Vit. C
What will maintain CO in pts. w/severe AR?
The increased preload will lead to eccentric LVH, the increase in LV chamber size will eventually increase the SV to maintain CO.
What is the main MoA by which nitrates improve sxs of Stable angina?
The venodilate which reduces preload. They also modestly increase coronary blood flow and modestly reduce afterload by systemic arterial dilation, but the reduction in preload provides the most relief.
What Rx can treat MRSA, but has myopathy as an AE?
Daptomycin- it depolarizes cell membranes and creates transmembrane channels. May cause myopathy and CPK elevation (esp. if used w/statins). Not used to tx pneumonia, bc inactivated by surfactant.
What is the cause of lactic acidosis in septic shock?
Tissue hypoxia impairs oxidative phosphorylation which causes shunting of pyruvate to lactate.
In 3rd degree heart block, what paces the atria and ventricles?
The SAN causes atrial contraction, and the AVN causes ventricular contraction w/narrowed QRS complexes. The P waves and QRS complexes will be completely dissociated, but normal on their own.
Why do reticulocytes stain blue?
Bc of reticular precipitates of residual ribosomal RNA.
What enzyme converts T4-->T3?
What is the MoA of Terbinafine, what does it treat?
Terbinafine (an allylamine) inhibits squalene epoxidase and treats dermatophytosis.
What is Chlordiazepoxide?
A long-acting benzo
What does the third aortic arch form?
The common and proximal internal carotid arteries.
Describe the risk factors, causing organisms, and lab results in Parotitis:
Risks: Anything that decreases salivary output- Anticholinergics, obstruction, dehydration, postop/intubation
Bugs: S. aureus #1, anaerobes
Labs: increased amylase w/out pancreatitis
What is the MoA of Griseofulvin?
It interacts w/fungal cell microtubules, inhibiting mitosis. Used to tx dermatophyte infections.
Where is the AVN located?
In the interatrial septum near the opening of the coronary sinus.
In case-control studies how does matching subjects help?
It helps to control confounding.
What is Protein A from S. aureus?
It is the virulence factor that is part of the PDG wall, ie it is not secreted like most the other virulence factors. It binds to the Fc portion of IgG to prevent complement activation --> decreased C3 --> impaired opsonization and phagocytosis.
What anti-lipidemic can predispose to gouty arthritis?
Niacin. It decreases renal uric acid excretion.
What is Cheyne-Stokes breathing and what diseases is it seen in?
Cyclical breathing where apnea is followed by gradually increasing and then decreasing tidal volumes until the next apneic period.
Seen in pts. w/ CHF or neuro disease (Stroke, brain tm, traumatic brain injury, etc). Poor prognostic sign. (Looks like blender ball springs on graph).
What is Bortezomib?
A proteasome inhibitor. It’s a boronic-acid containing peptide and treats MM.
What vessel would be suspected if Leads I and aVL showed abnormalities?
LCX- these are lateral limb leads, and the LCX supplies the lateral left ventricle.
What are the complications of cavernous hemangiomas?
Intracerebral hemorrhage and seizures
If a fistula were to develop between the aortic root and RV what would be seen on Doppler?
A continuous blood flow from the aortic root to the RV (not just in systole) bc of the large pressure differences. May create a continuous murmur.
What are the cardinal findings of Wiskott-Aldrich?
Eczema, recurrent infections (d/t combined B and T cell deficiency), and thrombocytopenia.
What are the important clinical findings in Chediak-Higashi?
Oculocutaneous albinidm, peripheral neuropathy, and immunodeficiency d/t phagolysosome dysfxn.
How do spherocytes appear on PBS?
As small RBCs (about 2/3 normal size), densely hemoglobinized and lacking a zone of central pallor.
Why are Down syndrome pts. at increased risk for Alzheimer?
Because Amyloid Precursor Protein is on chromosome 21 and increases AB accumulation in the brain.
What effect will an AV shunt have on a P-V loop?
AV shunts allow arterial blood to directly enter the venous system. This will increase the blood returning to the heart/preload, and cause a decrease in the TPR --> decreased afterload.
What is derived from the dorsal pancreatic bud and the ventral pancreatic bud?
Dorsal: forms body, tail and most of the head (including superior aspect). Ventral: forms uncinate process, inf./post. head, and major pancreatic duct.
What is literally the only action of the supraspinatus muscle?
How to calculate the attributable risk in the exposed:
ARPexposed = 100 x [(RR – 1)/ RR]
What is the infectious and diagnostic form of Strongyloides stercoralis?
Infectious: Skin penetration by filariform larva.
Diagnostic: Rhabditiform larvae in the stool.
Where is PECAM-1 found and what role does it play in neutrophil function?
It is found at peripheral intercellular jxns of endothelial cells. NPs adhere to PECAM-1 to transmigrate out of the vasculature into inflammatory tissue.
What disease has a characteristic GI histology of normal mucosal architecture, with enterocytes containing clear/foamy cytoplasm?
What affect will activation of PPAR-y have on insulin?
It increases insulin sensitivity in muscle and liver --> decreased insulin resistance.
What should be suspected by fever and sore throat in a patient with Hyperthyroidism?
Thionamide-induced agranulocytosis. A CBC + differential should be obtained to rule this out before treating the condition.
What are the AEs of the tionamides?
Methimazole and PTU both can cause agranulocytosis, but PTU only has risk of severe hepatotoxicity.
What are the cxs of adult-type coarctation of the aorta?
These pts commonly die of HTN-assoc cxs: LVF, ruptured/dissecting aortic aneurysm, and intracranial hemorrhage.
There’s a large association bw CoA and congenital berry aneurysms which commonly rupture.
Blockage of what vein is basically going to cause a unilateral SVC syndrome?
If a subclavian were blocked it would just cause unilateral arm swelling.
What needs to be bound to RAS for it to be activated?
GTP – causes autophosphorylation.
What does MTX inhibit and what will accumulate because of this?
It inhibits DHF reductase causing accumulation of Folic acid and DHF polyglutamate.
What kind of vaccine is Rabies?
What are the toxoid vaccines?
ONLY tetanus and diphtheria
What are the main AEs of Statins?
Hepatotoxicity, and muscle toxicity. Should check LFTs prior to starting.
Why is albumin normal in acute liver injury?
Bc it has a long t1/2 (~20d) and will only decrease in chronic liver diseases.
What is a developmental field defect?
When multiple malformations occur secondary to one embryonic disturbance in an adjacent group of cells. Holoprosencephaly is an example.
What is the threat of using a combo of Rxs with negative chronotropic effects?
They may cause severe bradycardia and HoTN.
Negative chronotropes: BBs, ND-CCBs, Digoxin, Amiodarone, Stoalol, and cholinergic agonisits (pilocarpine, rivastigmine).
What makes up the lesser omentum?
The hepatogastric and hepatoduodenal ligaments. They extend from the liver to the lesser curvature of the stomach.
What is the DoC for PSVT and what are its AEs?
Adenosine- may cause flushing, chest burning (bronchospasm), HoTN, and high grade AV block.
What medical tx can be given to dissolve cholesterol gallstones?
Hydrophilic bile acid supplementation. These improve solubility by decreasing the amount of cholesterol secreted into the bile.
What is responsible for forming abscesses in the lung?
Lysosomal enzyme release from NPs and MPs.
What are features of HoThyroid myopathy?
Fatigability, weight gain, myoedema (focal mounding of m. following percussion), increased CK, myalgia, proximal m. weakness, and cramping.
This occurs secondary to slow reabsorption of Ca2+ by the SR. TSH levels should be checked in all pts. w/unexplained CK elevation.
What is the pathogenesis of B-thalassemia?
Defective txn, processing and translation of B-globin mRNA.
What kind of Acid-base disturbance will be seen in Pulmonary embolism?
Will cause hypoxemia --> hyperventilation --> hypocapnia --> respiratory alkalosis.
What is deficient in Xeroderma Pigmentosum?
U-V specific endonuclease.
What effect would a pituitary resection have on catecholamine synthesis?
It would decrease Epi synthesis in the adrenal medulla. ACTH is released from the AP, which stimulates cortisol synth. Cortisol increases the expression of PNMT to convert NE --> E. If cortisol were low then epi would be low as well.
How many calories are yielded per gram of: Fat, Protein, Carb, and EtOH?
Fat: 1g = 9cal
Protein & Carbs: 1g = 4cal
EtOH: 1g = 7cal.
Describe the bone structure in primary Hyperparathyroidism:
Osteitis fibrosa cystica- Subperiosteal resorption with cystic degeneration.
What vasculitide has granulomatous inflammation of the media?
Both Takayasu and GCA/Temporal.
What should be used as the initial empiric therapy for Coagulase negative Staph. Infections?
Vancomycin bc of common Methicillin resistance.
How is NSAID-assoc chronic renal injury characterized?
Chronic interstitial nephritis and papillary necrosis.
What would lead to a pure motor stroke?
Lesion in posterior limb of the IC or basal pons
What would cause an ataxia-hemiplegia syndrome?
Lesion in posterior limb of IC or basal pons
What would cause a dysarthria-clumsy hand syndrome?
Lesion in the genu of the IC or basal pons
PCO2 = 1.5 (HCO3-) + 8 +/- 2
What disease is Alpha-galactosidase A deficient in, how does it present?
Presents w/cataracts, neuropathic pain(numbness, tingling, burning in hands and feet), angiokeratomas (dark skin lesions/moles), telangiektasias, renal failure, CVA (recurrent TIAs), and Cardio disease (LVH).
How would chronic kidney disease affect thyroid hormones?
CKD leads to accumulation of uremic toxins (uremia), which can decrease the peripheral conversion of T4 to T3 --> functional HoThyroidism.
How do filtration and secretion of PAH change with its concentration?
PAH filtration cannot be saturated, but its secretion is carrier-mediated and has a maximum. So as PAH concentration increases so does filtration (to infinity) and secretion up to its saturation maximum (around 80).
What are the ionic effects of Addison’s?
Adrenal insufficiency leads to hypoaldosteronism --> hyponatremia, hyperkalemia, hyperchloremia, and non-anion gap MA. Decreased cortisol --> increased insulin sensitivity.
What causes Subacute granulomatous thyroiditis and how will it present?
Follows a viral illness, get painful thyroid enlargement, w/Hyperthyroid sxs. Histo shows inflammatory infiltrate with MPs and giant cells. Have increased ESR & CRP with decreased radio uptake.
How long do sxs have to be present to diagnose Schizophrenia?
At least 6 months!! Before that its Schizophreniform.
How long does it take for a lymphocytic response in TB?
2-4 weeks after the initial infection. Because it is intracellular the response takes longer to generate, and B-cells are ineffective bc they can’t gain access to the organism inside the cell.
How can neurocysticercosis be transmitted?
By eating eggs of infected pork, or by contact with feces of human carriers- the eggs are shed in the feces.
GI complications in Down Syndrome?
Most common: Duodenal atresia
Others: Imperforate anus, Hirschsprung, TEF, celiac.
What G+ organism commonly causes UTIs after GU procedures?
Enterococci- G+, catalase -, Gamma hemolytic. Grows in bile and 6.5% NaCl, PYR +. Can also cause IE after these procedures.
What vessels lie immediately beneath the Rectus abdominis and are at risk in C-sections?
Inferior epigastric vessels. The superior vessels also lie below the muscle but are further up.
How do you treat Hypoglycemia in an unconscious patient?
IV dextrose if available, IM glucagon if dextrose is unavailable.
What pathway would carnitine deficiency disrupt, what will be the results?
Carnitine is needed for B-oxidation of FAs, so Acetyl CoA would not be able to be synthesized, therefore leading to a deficiency of ketone bodies as well as an impaired TCA cycle.
What is the mechanism of liver injury by HBV?
CD8+ response to viral Ags on the cell surface --> hepatocyte damage.
P450 Inducers (12):
Phenytoin, Barbituates, Rifampin, Carbamazepine, Griseofulvin, Smoking, St. Jon's Wart, Ginseng, Sulfonylureas, Modafinil, Cyclophosphamide, and Chronic EtOH.
P450 Inhibitors (22):
Isoniazid, Cimetidine, Ciprofloxacin, Verapamil, Amiodarone, Fluoroquinolones, Macrolides, Azoles, grapefruit/cranberry juice, Vitamin E, GInko NSAIDs/Acetaminophen, Omperazole, Erythromycin, Ritonavir (PIs), acute EtOH, Allopurinol, Disulfiram, Sulfonamides, Thyroid hormone, SSRIs, Metronidazole.
What genitalia would develop in the presence of normal Leydig cells, and absence of Sertoli cells?
Sertoli cells produce AMH, if this is absent then female internal genitalia would be allowed to develop.
Leydig cells produce testosterone, which would form both internal and external male genitalia.
At what age should children be able to copy a circle and use utensils; Play cooperatively?
Age 3: copy circle, use utensils, imaginative play, walk up/down stairs w alternating feet.
Age 4: Copy cross, cooperative play, hop on 1 foot, identify colors.
What are the treatment options for Wilson disease?
Chelators: D-penicillamine (DoC), trientine; Zinc- interferes with copper absorption.
Where are uric acid crystals likely to precipitate and why?
In the distal tubule and collecting ducts d/t the low urine pH. Urate is soluble at physiological pH but can precipitate in acidic environments.
How can adjusting PaCO2 treat cerebral edema?
Hypercapnia causes vasodilation, and reversely hypocapnia will cause vasoconstriction. Decreasing PaCO2 in ventilated patients can cause vasoconstriction which will decrease ICP in cerebral edema.
What is Imatinib?
An inhibitor of the BCR-Abl protein tyrosine kinase. It inhibits cellular proliferation in cells expressing the mutant protein, without causing apoptosis. Txs CML.
How will MAC present and what can be given as pphx?
Disseminated infection in HIV pts w/ CD4 <50. Get Pallor, Hepatosplenomegaly, fever, wt. loss, diarrhea, elevated ALP and LDH. Azithromycin is used as prophylaxis in these patients.
What prevents lung infarctions from occurring as a cx of PE?
Dual circulation. The pulmonary and bronchial systems provide collateral circulation making infarction rare.
What is the pathophysiology of TTP?
Have decreased levels of ADAMTS13 --> uncleaved vWF multimers --> platelet trapping & activation. Results in hemolytic anemia w/schistocytes, thrombocytopenia, renal failure, neuro sxs, and fever.
What nerve is likely injured if a patient presents with both jaw pain and otologic sxs?
The Mandibular division of CN V. It supplies the mm. of mastication, and the middle ear. Can be damaged in TMD.
What affect does Valsalva have on venous return?
It decreases VR, just like standing. These maneuvers will decrease most heart sounds.
What is generated converting Pyruvate to Lactate via LDH?
How will a patient w/Mullerian aplasia/MRKH syndrome present?
They are 46XX females with variable uterine development and no upper vagina. They have primary amenorrhea, but normal ovaries --> regular secondary sexual development.
What other organ is commonly affected in pts w/Mullerian defects?
The kidney. Up to 50% have urologic anomalies like unilateral renal agenesis.
What is responsible for influenza viruses being able to gain infectivity of humans?
Genetic reassortment- it occurs between human and animal strains and leads to antigenic shift which is the cause of most pandemics and epidemics of influenza A.
What causes a drug to have a low Vd?
Large molecular weight, extensively bound by plasma proteins, or highly charged. All these things favor the drug staying in the plasma.
How do TGs affect the pancreas?
High TGs increase production of free FAs. If TGs are >1000mg/dL then the concentration of free FAs exceeds their albumin binding capacity and cause direct injury to the pancreatic acinar cells. So HyperTGemia can cause recurrent acute pancreatitis.
What happens to insulin and C-peptide once they are cleaved from proinsulin?
They are stored in secretory granules until they’re released via exocytosis.
What nucleic acid is most susceptible to folic acid deficiency?
Thymidine, bc it requires THF to be continuously regenerated from DHF. Supplementation with thymidine will allow synthesis and decrease apoptosis in the RBCs.
What condition is associated with bilateral renal angiolipomas?
Tuberous Sclerosis (AD)- cortical tubers, subependymal hamartomas in brain (lead to seizures and cognitive disability). Less common: ash-leaf skin patches, cardiac rhabdomyomas, facial angiofibromas.
What is heard on auscultation of a nonstenotic bicuspid aortic valve?
An aortic ejection sound heard in early systole- high frequency click heard over R 2nd ICS.
What are the main ways to prevent neonatal tetanus?
Immunization of MOTHERS/pregnant women/childbearing age Fs, and hygienic delivery and cord care.
When is the Tdap vaccine given?
Typically 1st dose at 2 months. Can be given 4-6weeks in endemic areas, but no earlier.
When are pressures highest in the LV?
During systole, they peak after the aortic valve opens, and start dropping right before it closes for diastole.
What is intraductal papilloma, how will it present on histo?
The most common cause of bloody nipple discharge, it is proliferation of papillary cells in a duct/cyst wall w/fibrovascular core. Typically does not present with a breast mass or skin changes.
What causes stromal proliferation compressing surrounding ducts to slits?
Fibroadenomas- small, firm and mobile breast masses.
What is the last structure the testes have to pass through to enter the scrotum?
The superficial inguinal ring- an opening in the external oblique muscle aponeurosis. This is above and medial to the pubic tubercle.
Before this they pass through the deep inguinal ring (opening of transversalis fascia) superior to the mid-inguinal point.
What is most useful to help distinguish the cause of a Metabolic Alkalosis?
The patient’s urine chloride and volume status.
What are the complications of Polymyositis?
Interstitial lung disease and myocarditis.
What is the inciting factor to cause hypoxemia at high altitudes?
The Partial P of inspired O2 (PiO2) falls at high altitudes --> hypoxemia and marked reduction in PaO2.
What is capacitance?
Capacitance = (change in volume)/(change in pressure). This will increase with decreased resistance/pressure, and decrease with decreased volumes or increased P.
What makes up the lentiform nucleus?
Putamen and globus pallidus. Wilson’s disease causes atrophy of these structures.
What makes up the striatum?
Putamen and caudate nucleus.
Which B receptor is found on JG cells and which in bronchial smooth muscle?
B1 is found in JG cells and cardiac myocytes. B2 is found on bronchial sm. mm. and vascular sm. mm.
How will Homocystinuria present?
(AR) Typically at age 3-10 with dislocated lens, and intellectual disability. Pts have Marfanoid habitus and high risk for thromboembolic occlusion of large and small vessels (brain, heart and kidney). Thromboembolic cxs are main CoD.
What is deficient in Homocystinuria?
Cystathionine B-synthase- requires B6 as a cofactor. About 50% of pts. respond to pyridoxine supplementation.
What cancers are a/w BRAF mutations?
Melanoma and Hairy cell leukemia
What mutations are a/w prostate cancer?
BRCA1 and BRCA2
What drugs will cause IgE-dependent vs. IgE-independent reactions?
IgE-dependent: B-lactams, and sulfas.
IgE-independent: Opioids, radiocontrast agents, some abx like vancomycin.
What are releasing factors?
They recognize stop codons and terminate protein synthesis --> release of the polypeptide from the ribosome, and dissolution of the ribo-mRNA complex.
What is the role of elongation factors?
They facilitate tRNA binding and the translocation steps of protein synthesis.
What is the DoC for Delirium?
Low-dose antipsychotics- esp. Haloperidol.
What axn do IFN-a and –B have?
They halt protein synthesis to suppress viral replication and promote apoptosis in infected cells.
What is the difference between repression and suppression?
Suppression is a mature defense and is a conscious effort to avoid unwanted thoughts/feelings.
Repression is an immature defense and blocks thoughts/feelings from entering conscious awareness.
What will a CXR in acute decompensated HF show?
Secondary pulmonary edema- cephalization of the pulmonary vessels, perihilar alveolar edema, and blunting of the costophrenic angles d/t pleural effusions.
Continuous/machinery-like w/inspiratory splitting of S2. Stop fucking it up!
What valvular pathology will increase LVDP?
Aortic dysfunction. In isolated mitral stenosis LVDP will be normal or decreased.
What gives elastin its stretch and recoil properties?
Extensive desmosine cross-linking between elastin monomers by lysyl oxidase (requires Cu as cofactor!).
What AEs are not decreased by adding Carbidopa?
The central AEs like anxiety and agitation. These may increase bc Carbidopa increases the amount of DA to the CNS.
It will reduce the AEs from peripheral DA: N/V, tachyarrhythmias, postural HoTN, hot flashes.
What are the endogenous opioids?
Enkephalins, endorphins, and dynorphins.
What is B-endorphin derived from?
Proopiomelanocortin (POMC), the same precursor of ACTH and MSH.
What are the Pressure ranges in the RA, RV, PCWP, and Pulmonary a.?
RA & SVC: 1-6 mmHg.
RV: 2-30 mmHg.
PA: 10-30 mmHg.
PCWP: 6-12 mmHg.
What is the function of Peroxisomes?
Oxidation of VLCFAs and Branched-chain FAs (phytanic acid). Also H2O2 degradation.
Defective peroxisomal biogenesis. Presents early infancy w/craniofacial abnormalities, hepatomegaly, and profound neuro defects (hypotonia, seizures).
Defective transport of VLCFAs into peroxisomes. Presents in child- or adulthood w/neruo deterioration and adrenal insufficiency.
What vessel should be ligated during post-partum hemorrhage to prevent a hysterectomy?
The internal iliac aa. This will stop hemorrhage, but the structures have enough collateral supply from other aa. (ovarian) to preserve their fxn/fertility.
What is lead time bias?
When a test detects or diagnoses a disease at an earlier stage than another test, without impacting the natural history of the disease.
What is latent period?
The time elapsed from initial exposure/pathogenic insult to clinical manifestation of a disease; The time between asbestos exposure and developing mesothelioma.
What type of BR will cause Kernicterus and Neuro impairment?
UC BR because it is water insoluble and gets deposited into the brain and other tissues.
AR. Deficient UGT enzyme needed to catalyze bile glucuronidation. UC Hyperbilirubinemia develops --> kernicterus, severe jaundice, muscle rigidity, lethargy, and neuro impairment (seizures) in infancy.
How to calculate renal excretion rate:
Excretion = Total filtration rate - Total tubular reabsorption.
Total filtration = GFR x Px
Porcelain gallbladder increases the risk of what?
Adenoca of the GB.
What is acute ascending cholangitis?
Normally from G- infection of the intrahepatic biliary tree. D/t biliary obstruction, presents w/fever, RUQ pain and jaundice.
What increases the risk of cholangiocarcinoma?
Fibrotic diseases of the bile ducts- PSC, congenital fibropolycystic disease, chronic infection w/Opisthorchis sinensis (liver fluke).
What quantifies pulsus paradoxus?
The difference b/w the SBP at which Korotkoff sounds become audible during expiration and the SBP at which they are heard throughout all of respiration. Anything >10mmHg qualifies as pulsus paradoxus.
What is the embryologic derivative of Rathke pouch?
What AAs will help generate energy in PDH deficiency without increasing lactate?
Ketogenic AAs- Lysine and Leucine.
A ketogenic diet forces the production of ketone bodies from fat to generate energy in the absence of glucose. This will decrease the amount of pyruvate and thus lactate generated which will improve sxs.
What are the manifestations of Mumps infection?
Parotitis, orchitis, and aseptic meningitis. Does not cause maculopapular rash.
What is the major virulence factor of S. pyogenes, what's its function?
Protein M. It inhibits phagocytosis and the activation of complement. Abs can be formed to this protein.
What vessel will have the lowest oxygen content in the body?
The coronary sinus- this is bc the coronaries extract the most O2 from the blood, compared to all other tissues in the body, so the blood returning from them to the coronary sinus will have less O2 than the blood returning from any of the other tissues.
What are some common extraintestinal manifestations of Crohn disease?
Ankylosing Spondylitis and peripheral arthritis.
What inhibits B-oxidation in the well-fed state?
Malonyl-CoA from FA synthesis increases and inhibits CAT to prevent B-ox from occurring at the same time.
What molecular technique uses a dsDNA probe?
SW-blot, detects DNA-binding proteins (txn factors, nucleases, and histones), like c-Jun and c-Fos (nuclear txn factors).
What does synaptophysin indicate?
A tumor of neuronal origin (neurons, neuroectodermal, neuroendocrine).
What is a complication of viral myocarditis; how will it present?
DCMP may occur after a recent viral illness and present w/ both L and R decompensated HF. Myocardial inflammation -> dilation/enlargement of the heart chambers (eccentric hypertrophy) and decreased contractility.
What is inhibited by integrase inhibitors (Raltegravir)?
Production of viral mRNA.
What would a lesion in the superior orbital fissure cause?
Dysfunction of CN III (difficulties adducting, etc.), and absence of the corneal reflex- the nasociliary n. (CN V) enters through here and carries afferent fibers for the corneal reflex.
What enters the orbit via the superior orbital fissure?
CN III, CN IV, CN VI, and nasociliary branch of CN V.
Is Adenoca. In situ of the lung benign or malignant?
What kind of Rx is Timolol, and how does it treat glaucoma?
It is a non-selective BB. Targets the ciliary epithelium to reduce secretion of aqueous humor.
What is the most common cause of viral gastroenteritis?
Sxs= N/V and watery diarrhea. Outbreaks common in schools, cruises, and nursing homes.
How long should it take for the umbilical cord to separate?
Less than 1 month.
What does a purulent and a clear/straw colored umbilical discharge signify?
Purulent is d/t urachal sinus (failure of the distal urachus to close) w/recurrent infections.
Clear discharge is a patent urachus from failure of obliteration of the urachus.
Treatment for Panic disorder:
Long-term: SSRI/SNRI or CBT
What would be the effect of an activating mutation of PRPP?
It would increase production of purines --> increased purine degradation, and gout.
What is the role of T-tubules in muscle cells?
They allow rapid propogation of depolarization so that Ca2+ is released in a uniform manner throughout the m. fiber, allowing for synchronized contraction of myofibrils in each muscle cell.
What is the effect of MG on post-synaptic muscle cells?
The Ach receptors are decreased which decreases the EPP following Ach release. The threshold won’t be reached bc of this and the cells won’t depolarize.
How does the PRP capsule protect Hib?
By binding factor H- a host serum protein that degrades C3b and inhibits phagocytosis and complement-mediated lysis.
What structures pass through the Jugular foramen?
CN IX, X, XI, and jugular vein.
What structures pass through the Foramen magnum?
Spinal roots of CN XI, brain stem, and vertebral aa.
What structures pass through the Foramen rotundum, oval and spinosum?
Foramen rotundum: CN V2 (Maxillary)
Foramen Ovale: CN V3 (Mandibular)
Foramen Spinosum: Middle meningeal a. and v.
What is the genome of HBV?
HBV is an enveloped, partially ds, circular DNA w/reverse transcriptase.
What are the light microscopy findings in Reye’s syndrome?
Microvesicular steatosis, and the presence of small fat vacuoles in the cytoplasm of hepatocytes. There will be no necrosis or inflammation in the liver.
How will a fat embolism present?
Triad of acute-onset neurologic abnormalities, hypoxemia and petechial rash. Fat microglobules will lodge in microvessels to cause the sxs.
What areas will show the greatest degree of atrophy in Alzheimer?
The temporoparietal lobes and the hippocampus.
What is seen on PBS of a leukemoid reaction?
Dohle bodies (basophilic oval inclusions/granules) inside mature neutrophils.
When is basophilic stippling seen?
Thalassemias, alcohol abuse, lead/heavy metal poisoning.
What would a Glutathione reductase deficiency present similar to?
Without glutathione reductase, NADPH can’t be used to reduce glutathione and may lead to hemolytic anemia d/t increased RBC susceptibility to oxidative damage.
Where is hepcidin released from, what conditions increase/decrease its release?
Hepcidin= the central regulator of iron homeostasis, released from liver.
High Fe levels and inflammation increases its synthesis. Hypoxia and increased erythropoiesis lower hepcidin levels.
What is the role of attached ribosomes to the RER?
They synthesize most secretory proteins and membrane proteins of the nucleus and cell membrane.
What is the role of free Ribosomes?
They translate proteins found w/in the cytosol, nucleosol, peroxisome matrix and nuclear-encoded mitochondrial proteins.
Tricuspid regurgitation murmur:
Holosystolic best heard at left sternal border. Increases with inspiration.
Note: MR does not change w/respiration.
What are the proteins associated with the different cell jxns?
Gap jxns- Connexins
Tight jxns- Claudins, Occludins
Adherens jxn- Cadherins
Desmosomes- Cadherins (desmogleins, desmoplakin)
What is the MoA of Rifaximin and what does it treat?
It is an abx that alters GI flora to decrease intestinal production/absorption of ammonia – this is useful in hepatic encephalopathy. May also tx traveler’s diarrhea by inhibiting RNA synth.
What would prevent recurrence rates of HSV infection?
Continuous daily acyclovir
What is a pulmonary complication of Systemic sclerosis?
pHTN- d/t damage of the pulmonary arterioles. Manifests w/accentuated S2 and signs of RHF from cor pulmonale.
What is the primary regulator of the zona glomerulosa?
What is the function of Thyroid peroxidase?
Oxidation of iodide to iodine.
Iodination of tyrosine residues.
Coupling to form T3 and T4.
How will a pineal gland mass present?
Obstructive hydrocephalus from aqueductal stenosis, and dorsal midbrain/Parinaud syndrome- limited upward gaze, bilateral eyelid retraction, and light-near dissociation- from pretectal midbrain compression.
Lamotrigine (MoA and Uses):
Blocks VG Na+ channels. Used for partial and generalized seizures, as well as bipolar. Has black box warning for SJS.
What is the main virulence mechanism allowing for Salmonella osteomyelitis?
Vi antigen in the capsule, this protects from opsonization and phagocytosis.
What is the MoA of Fibrates?
They activate PPAR-a --> decreased hepatic VLDL production and increased LPL activity.
What lipid lowering agent blocks intestinal cholesterol absorption?
What is the MoA of Zidovudine (AZT)?
An NRTI – competitively binds RT and incorporates into the viral genome. It lacks a 3’-OH group, inhibiting 3’-5’ phosphodiester bond formation causing chain termination.
What are some features of disseminated hisoplasmosis?
Hepatosplenomegaly (bc predilection for RES) and ulcerated tongue lesions.
What determines the statistical significance of a study?
If the CI crosses the null value. Most studies the null value will be 0 – representing that the null hypothesis is that there is no difference between the control group and experimental group.
What type of anticoagulant will increase both aPTT and PT but not affect Thrombin time?
Direct factor Xa inhibitors: Apixaban, rivaroxaban.
What is likely to create bilateral, wedge-shaped necrotic strips over the cerebral convexity?
Hypoxic-ischemic encephalopathy. The necrotic areas will represent the ACA-MCA and MCA-PCA watershed areas susceptible to infarction. Cardiogenic shock and profound systemic HoTN are common causes.
What is the difference between generalized and focal seizures?
Focal only involves 1 cerebral hemisphere at onset. Generalized will involve both hemispheres at onset.
What type of seizures may be associated with automatisms?
Absence and Complex Focal. Absence has no post-ictal state whereas complex focal will.
Broad spectrum anticonvulsants:
Lamotrigine, Levetiracetam, Topiramate, Valproate.
Narrow spectrum anticonvulsants:
Carbamazepine, Gabapentin, Phenobarbital, Phenytoin.
What is the main difference in immune response between IM inactivated and live oral vaccines?
The live oral vaccines are able to directly stimulate the gut mucosa to produce secretory IgA and therefore will have much higher levels of these Abs against the Ag.
What type of Rxs can redistribute blood flow away from ischemic myocardium, exacerbating ischemia?
Selective Coronary arteriolar dilators (Dipyridamole, and Adenosine). These cause coronary steal phenomenon.
What kind of receptor does ACTH bind?
What is the inheritance pattern of Hyper-IgM syndrome?
X-linked recessive. Deficient CD40L, so B cells can’t class switch.
Where is the majority of filtered H2O reabsorbed in the kidney?
In the PCT.
What are the features of Hartnup disease?
AR disorder with mutations affecting the neutral AA transporter.
Sxs: Pellagra-like skin eruptions, and cerebellar ataxia both as a result of niacin deficiency from impaired Tryptophan transport. Will have neutral AAs in the urine.
What would a Riboflavin (B2) deficiency present as?
This is the precursor for FMN and FAD synthesis and would cause sore throat, stomatitis, glossitis, normocytic anemia and seborrheic dermatitis.
What is the MoA of Canagliflozin?
It and Dapagliflozin are both SGLT2 inhibitors and decrease the reabsorption of glucose in the PCT. Bc of this, GFR, BUN and Creatinine should be checked before starting tx. AEs: UTI and genital mycotic infections d/t glucosuria.
What cells are responsible for clearing necrotic tissue after an ischemic stroke?
What are the possible paraneoplastic syndromes associated with RCCa?
Secretion of: EPO, renin, PTHrP, or ACTH. These tumors may be positive for epithelial membrane antigen
What are the common features of pericarditis and some associated conditions?
Sharp pain, aggravated by inspiration, relieved by sitting up and leaning forward. Friction rub throughout both systole and diastole.
Associated conditions: Viral, AI (SLE, RA), uremia, CVS (STEMI, Dressler), radiation tx.
What is the function of GTPase for Gs proteins?
It hydrolyzes GTP to GDP and inactivates the Gs. A lack of GTPase would lead to a constitutively active Gs --> increased adenylyl cyclase.
What microorganism may be seen as trophozoites displaying erythrophagocytosis; where is it endemic?
Entamoeba histolytica. Endemic in C. and S. America, Africa and India.
In a normal menstrual cycle with ovulation on day 14, when will estrogen be highest and progesterone lowest?
About Day 12.
What defines precocious puberty?
Development of secondary sexual characteristics less than 7 years of age.
What happens to the true vocal cords during irritation initiating a cough reflex?
Laryngeal irritation will immediately close the vocal cords, and then they will open again during coughing. These are also closed during normal swallowing.
What are the common cestodes and how are they treated?
Schistosomas, Clonorchis sinensis, Paragnimus westermani. All are treated with Praziquantel.
What is the difference between the precontemplation and contemplation stages?
Precontemplation the patient has not accepted there is a problem. Contemplation the patient knows they have a problem but aren’t ready to take action yet.
How do neutrophils perform intracellular killing?
Via the respiratory burst. They phagocytize the bacteria and then release NADPH oxidase which then produces superoxide dismutase and other ROS which kill the bacteria.
How will an aneurysm in the Posterior Communicating a. present?
With CN III abnormalities. The ipsilateral pupil will be dilated, and nonreactive to light. There will be impaired adduction of the same eye, possibly presenting as “down and out.”
What is the effect of DRESS syndrome on the kidney?
Causes interstitial nephritis.
Explain the late stages of a type I HS rxn:
Infiltration of mixed inflammatory cells leading to edema and tissue damage. MPs may influx releasing IL-1, IL-6, and TNF-a (causes edema). Bronchospasm may also occur in the late stage.
What protein is responsible for trafficking of vesicles into the golgi complex?
COPII does anterograde trafficking of vesicles from the RER into the golgi. Deficiency of this protein would lead to dilated RER on EM.
In patients with PCOS what will happen to the insulin level?
Most have insulin resistance, so the levels will INCREASE!
What mechanisms help to reduce the body temperature?
Evaporation of sweat and peripheral vasodilation.
What are the characteristics of Charcot-Marie tooth disease?
AD inheritance, mutation in myelin synthesis genes --> peripheral loss of myelin.
Presents with distal muscle pain/weakness, sensory loss, atrophy of the calf muscles (stork-leg deformity). Often have foot deformities (pes cavus, hammer toes) and kyphoscoliosis. Walk with high-stepping gait.
Calculation of Flow rate through a vessel:
Flow Rate = Area x Velocity
What would cause swelling of the PCT epithelial cells in HoTN?
HoTN and decreased blood flow --> ischemia and decreased ATP available --> decreased fxn of the Na+/K+ ATPase.
This means Na+ will accumulate in the cells and trap water in with it – swelling.
What is the axn of caspases?
In apoptosis they are responsible for nuclear fragmentation and cytoskeleton dispersion.
What is the role of Fas and FasL?
They initiate the extrinsic apoptosis pathway, and are responsible for T-cell negative selection in the thymus. Mutations in these can lead to increased self-reactive cells --> autoimmune disorders.
How will a deficiency in Factor XII present?
Factor XII = Hageman factor. A deficiency will be completely clinically silent and will not have increased bleeding like other clotting deficiencies, however it may increase the aPTT more than any other clotting disorder.
It will also have an abnormal Kallikrein formation.
Where is the lateral corticospinal tract located and what would a lesion cause?
It is the descending voluntary motor tract of the spinal cord and is found laterally between the dorsal and ventral horns. Damage would present as motor deficits in the ipsilateral limbs bc these fibers decussate in the medulla.
Describe Pseudofolliculitis barbae:
Inflammatory skin disorder- firm, hyperpigmented papules/pustules that are painful and pruritic. Norm on cheeks, jawline, and neck. Often occurs after shaving, and is more common in AfAm males.
What neurological conditions may be associated with hammer toes?
Friedrich ataxia, and Charcot marie tooth.
What are the requirements of viruses to replicate in the cytoplasm?
They must make their own 5’cap, or have an IRES element like the picornaviruses (polio, HAV).
What cells are responsible for the prevention of superficial vs. disseminated candidiasis?
T lymphocytes prevent superficial candida infections, so oropharyngeal, vaginal, etc are seen in HIV pts.
Neutrophils prevent hematogenous spread, so disseminated infections (candidemia, endocarditis) is seen in neutropenic/IMCP’d pts (chemo, etc) and those w/phagocyte impairments.
How can effect modification and confounding be differentiated?
In a stratified analysis effect modifcation will show that there is a statistical significance for one group, but not for the other. Confounding will show that there is an apparent, but false, significance for both groups.
What enzyme has fxn exclusively restricted to the nucleolus?
RNA polymerase I.
It transcribes rRNA, which only occurs in the nucleolus (dense, deeply basophilic region of the nucleus).
What is the mechanism of hepatocyte damage from HBV?
CD8+ Tcell response to Ags on the cell surface --> hepatocyte damage.
What effect would a febrile illness have on the P450s?
They inhibit them, increase drug levels.
What is the PDA a derivative of?
The Left 6th aortic arch.
How to tell the difference between hereditary fructosemia and galactosemia:
Galactosemia will present immediately with breast feeding, fructosemia will be silent during breastfeeding and present with the introduction of foods (esp. sugary foods).
What enzyme deficiency will cause both increased androgens in the fetus as well as the mother?
Deficiency will present similar to 21-a-hydroxylase deficiency in the fetus with clitoromegaly in females, and will lead to virilization of the mother.
21-a will not virilize the mother bc of intact placental aromatase that will convert the testosterone into estrogens.
What is the most likely disease to cause cystic degeneration of the putamen?
Continuous machinery like with inspiratory splitting of S2. Heard best in L infraclavicular region/L sternal border.
What visual disturbances are associated with RA?
Episcleritis or scleritis- present with ocular discomfort.
What causes a PV loop to expand L, R, or Up?
Expansion to the R: Increased Preload
Expansion to the L: Increased contractility
Upward Expansion: Increased Afterload
Both isolated increased preload or increased contractility will increase the SV.
What effect would decreased contractility have on LVESV?
Decreased contractility would cause excess blood to be left and increase the LV end-systolic volume.
What is responsible for most of the intrapleural P fall during inspiration, and what would cause a progressive decrease in amplitude?
The diaphragm contraction is responsible for the pressure drop, and rapid fatigue would cause decreasing amplitude.
Often d/t pathology of: the NMJ, the skeletal m., or lung tissue/chest wall.
What is the function of amino acyl tRNA synthetase?
It is the enzyme responsible for loading proper AAs onto the 3’ CCA tail of tRNA.
What is the MoA of Aminoglycosides?
They interfere w/the aminoacyl binding site on the 30S subunit --> misreading of mRNA and inhibition of protein synthesis.
What effect does estrogen have on thyroid hormones?
Estrogen increases the level of Thyroxine-binding globulin (TBG) which will increase the binding of free T3 and T4, causing an initial decrease in these levels.
However, feedback to the hThal will soon increase hormone production leading to a euthyroid state, with increased total T4 and T3 compared to normal.
What Rxs are given to pts w/TIA to prevent ischemic strokes?
Low-dose Aspirin and a statin.
How do the Influenza vaccines confer immunity?
They are inactivated vaccines which stimulate Ab response against HA-Ags, this prevents binding of HA to host cells and inhibits viral entry upon natural exposure to the virus.
Why aren’t mature RBCs able to synthesize heme?
Because mature RBCs lack mitochondria, which are responsible for the first, and last 3 steps of heme synthesis.
What pts should Succinylcholine be avoided in?
Those with severe burns, myopathies, crush injuries, and UMN injuries/denervation. May cause severe hyperkalemia in these pts --> vFib and cardiac arrest.
What causes splenomegaly in PK deficiency?
Red pulp hyperplasia occurs d/t increased work demand in removing the damaged RBCs that result from insufficient ATP production.
What part of the neuron cannot be seen with Nissl staining?
Axons. Nissl stains for RER and axons do not contain RER.
What is length time bias?
When subjects with a rapidly progressive form of disease are less likely to be detected by screening compared to those with slowly progressive disease.
What vessel is part of the spermatic cord, and where does it originate?
The gonadal artery is part of the spermatic cord and originates from the abdominal aorta. It can become twisted and ischemic in testicular torsion.
What protein is responsible for degrading foreign intracellular proteins for MHC I presentation?
Ubiquitiin ligase- part of the Ubiquitin proteasome pathway. It breaks down foreign particles, like viral proteins, to be coupled to MHC I and presented to CD8+ cells.
What is the course of the ACL and PCL?
ACL comes from anterior tibia to insert on the posterior femur. The PCL comes from the posterior tibia to insert on the anterior femur.
So on MRI if you see the tibia: ACL is anterior, PCL is posterior.
What kind of mutation is seen in Huntington:
CAG trinucleotide repeat --> gain of function. Causes deacetylation and repression of other txn factors.
What is ortner syndrome?
When Mitral stenosis dilates the LA enough to impinge the L recurrent laryngeal n.
What is tyrosine a precursor for?
Thyroxine, dopamine, Epi, Norepi, and Melanin.
What class of drug is Cyproheptadine?
It is a 1st gen anti-histamine w/anti-serotonergic properties. Used to tx serotonin syndrome.
What are the paraneoplastic syndromes associated with Lung Adenocarcinoma?
Hypertrophic osteoarthropathy, dermato/polyomyositis, and migratory thrombophlebitis.
What are the segmented viruses?
Reo (rotavirus), Orthomyxo (influenza), Arenaviruses (LCMV, Lassa), and Bunyaviruses (CEV, Hanta).
What muscles in the arm does the median n. run between?
It courses between the 2 heads of the pronator teres right below the articulation of the humerus and ulna, and then runs below the flexor digitorum superficialis on top of the flexor digitorum profundus into the hand.
What is the MoA of Cyanide toxicity?
CN is a mitochondrial toxin, binds Fe3+ in Cytochrome c oxidase (complex IV) to inhibit the ETC and aerobic respiration --> altered mental status, seizures, CVS collapse, lactic acidosis, and bright red venous blood.
What is the timeline of cellular response in an ischemic stroke in CNS?
48 hrs: Neurons display irreversible injury.
3-5 days: NPs and Microglia infiltrate. Microglia become filled w lipids from digestion of myelin debris.
2 weeks: Astrocytes migrate to area and form glial scar.
What feature of the respiratory epithelium is the last to disappear?
Cilia. They remain throughout the respiratory bronchioles, and only disappear in the alveoli.
Elevated levels of which AA are primarliy responsible for the neurotoxicity of MSUD?
What are some of the triggers for Variant Angina?
Dihydroergotamine (other ergot alkaloids), triptans, smoking, cocaine/amphetamines.
Vasodilators are used to treat (CCBs, nitrates).
What bacterial toxins increase cGMP?
ETEC (ST) and Yersinia enterocolitica.
They produce watery diarrhea and electrolyte loss.
What are some ototoxic Rxs?
Furosemide (loops), Aminoglycosides, salicylates, and cisplatin.
What kind of Drug is Indapamide?
What is responsible for Pill-induced esophagitis?
Tetracyclines, potassium chloride, and bisphosphonates.
What is the treatment of Diphtheria?
In order of importance: Diphtheria antitoxin (passive immunization), Penicillin or erythromycin, DPT vaccine.
By giving the antitoxin it will inactivate the already circulating toxin (except that already in the cardiac or neural cells).
What is Denosumab?
A monoclonal Ab- inhibits RANKL-RANK interaction to increase bone density and tx osteoporosis.
What mediates the flushing and warmth associated with Niacin treatment?
Prostaglandins (PGD2, PGE2), hence why aspirin is used as pre-tx to reduce these sxs.
What mediates the Vancomycin “Red Man Syndrome"?
Histamine release via IgE independent Mast cell degranulation.
What is the most common obstructive, and non-obstructive cause of fetal hydronephrosis?
Obstructive: Narrowing/kinking of the proximal ureter at the UPJ (unilateral hydronephrosis).
Non-Obstructive: Vesicoureteral reflux. Can be uni- or bilateral.
What kind of Rxs would Mycoplasma spp. be resistant to?
Any type of cell wall inhibitor- Penicillins, cephalosporins, carbapenems, vancomycin, etc. These spp. lack a cell wall.
What is the morphology of Candida as a yeast?
What is a trigger for HCC in HBV patients?
Integration of the viral DNA into cellular genome triggers neoplastic changes.
What are the Sulfonylureas and which have highest risk of hypoglycemia?
Glyburide and Glimepride are both long-acting and have highest incidence of hypoglycemia. Glipizide is a short-acting and has much less risk of hypoglycemia.
Budd Chiari v. Portal v. thrombosis:
Budd Chiari syndrome is thrombosis in the hepatic v., this will cause centrilobular congestion and fibrosis of the liver.
Portal v. thrombosis will not cause histologic change to the hepatic parenchyma, but will cause portal HTN, splenomegaly, and varices.
What is the pathogenesis leading to an AAA?
Chronic transmural inflammation and ECM degradation w/in the wall of the aorta --> weakening/expansion results in aneurysm.
What disease is associated with Cystic medial necrosis?
Marfan syndrome- often get cystic medial degeneration of aortic root --> ascending aortic aneurysm/dissection.
What ions will accumulate intracellularly in ischemia?
Na+ and Ca2+. K+ will accumulate outside of the cell d/t the failed Na+/K+ ATPase.
What are common features of Rxs eliminated via hepatic clearance?
High lipophilicity, and high volume of distribution. Highly lipohilic Rxs are poorly eliminated in the kidney bc they easily cross the tubular lumen and are reabsorbed back into the tissues.
What does RT-PCR detect?
It’s used to detect and quantify levels of mRNA. It creates cDNA to the mRNA sequence, which contains exons and the 3’/5’ UTR. No promoters/enhancers etc.
What is “clasp-knife” spasticity characteristic of?
UMN lesion. It is d/t lack of UMN inhibition on the spinal stretch reflex arc. Often occurs w/internal capsule strokes.
What is the MoA of Ciguatoxin, Saxitoxin, and Tetrodtoxin?
Saxitoxin and Tetrodotoxin: Inhibit Na+ channels
Ciguatoxin: Binds and keeps open Na+ channels.
What patients are especially susceptible to Listeria infections?
Those with impaired cell-mediated immunity (infants, chemo, HIV) bc it is an intracellular organism, and humoral immunity doesn’t play a role in defense against it.
What is the DoC for Listeria?
Ampicillin. It is resistant to cephalosporins d/t altered PBPs.
What is the difference b/w reassortment and recombination?
Recombination is the gene exchange through crossing over b/w 2 dsDNA molecules (viruses).
Reassortment is the mixing of genome segments in segmented viruses infecting the same host
What is the route of N. meningitidis to cause Meningitis?
It is transmitted via respiratory droplets, and colonizes the nasopharynx. It then gains access to the bloodstream, and will colonize the choroid plexus to then enter the meninges and cause Meningitis.
How does H. influenzae gain access to the meninges?
Colonization of the pharynx, then travels via lymphatics to the meninges to cause disease.
Histo of Epithelial ovarian cancer:
Anaplasia of epithelial cells w/ invasion into the stroma, multiple papillary formations w/cellular atypia and psamomma bodies.
What will constriction of the efferent arteriole cause?
It impedes blood flow through the kidney, therefore reducing RPF. It also will increase the GFR and FF.
Where is the red nucleus located?
What is the main mechanism of excess copper removal from the body?
Hepatic excretion into bile.
What is characteristic of the thoracic cord only?
The intermediolateral cell column w/preganaglionic SNS fibers. Sticks out on the side b/w dorsal and ventral horns.
What Abs will agglutinate at room temperature?
IgM- aka cold agglutinins.
What nerve roots is the femoral nerve derived from, and what does it innervate?
Femoral n= L2-L4, gives sensory to the anterior thigh and medial leg.
Motor to quads, iliopsoas, pectineus, Sartorius.
What do the labioscrotal swelling become in male and female?
Male: scrotum, Female: Labia majora.
What do the urogenital folds become?
Male- Penile shaft, Female- labia minora.
What effect will ANP have on ADH?
ANP opposes ADH, it promotes diuresis and therefore will result in a decreased ADH.
What is the treatment for Hereditary Spherocytosis?
Splenectomy. This will abolish the problem. Spherocytes do not pose a problem when the spleen is not there to destroy them.
What is the only type of shock that the CO is increased?
What will be the lab values in DIC?
Increased fibrin degradation products (D-dimers), decreased fibrinogen, and decreased factors V and VIII.
What is the difference in labs for Alcoholic hepatitis, and hepatic steatosis?
Alcoholic hepatitis is the only one with AST>ALT. Fatty liver changes may see a rise in these, but will still have ALT>AST like other liver disorders.
What is the mechanism of creating vaccines that are normally T-independent to T-dependent?
Conjugation with proteins makes vaccines like Hib, which are normally T-independent create a T-cell response as well as a B-cell to enhance protection.
What are the best lab tests to assess thyroid function?
Serum TSH should always be first, then serum free T4, and only occasionally serum total T3.
Measuring free hormone is always better than total, so that total active hormone levels can be assessed. Also, bc any changes in binding protein concentration will change total levels, but not free hormone levels.
What is the only lung pathology that has an increased tactile fremitus?
Consolidation: lobar pneumonia, and pulmonary edema.
What is going to be released in Rhabdomyolysis and how will it present?
Myoglobin is released which can cause renal failure, with markedly increased creatinine.
Presents w/muscle weakness, confusion, tenderness etc. Can be caused by strenuous exercise, infection, electrical injury, heat stroke, drugs etc.
What drugs bind the 30S subunit?
Aminoglycosides and Tetracyclines
Why does M. leprae affect the skin vs. the visceral organs?
Bc of its temperature sensitivity. Can only grow in cool temperatures- the skin and superficial nerves. Cannot be grown in vitro.
What is systemic mastocytosis and how will it present?
Clonal mast cell proliferation associated with KIT receptor TK mutations. Xs histamine release from these cells --> syncope, flushing, HoTN, pruritis and urticaria. Get gastric hypersecretion can –> ulceration.
What forms the IVC?
The union of the R and L common iliac veins at level L4-L5. IVC then drains into the RA.
What is pure red cell aplasia?
A form of BM failure with severe hypoplasia of the marrow erythroid elements, but normal granulopoiesis and thrombopoiesis. A/w thymoma, lymphocytic leukemias, and parvo B19.
Where do you see Rosenthal fibers?
Pilocytic astrocytoma. Also have Spindle cells w/hair-like glial processes.
What smear will show ringed sideroblasts?
They are only seen in the Bone Marrow, not seen on a PBS. Basophilic stippling is seen on PBS in most of the same disorders of sideroblasts.
How would a trisomy nondisjunction in meiosis I present on RFLP compared to meiosis II?
If a trisomy occurred d/t nondisjunction in meiosis I the child would have 3 separate bands on RFLP, 2 different ones from one parent, and a third from the second parent.
If it were in meiosis II, the child would have only 2 bands, one larger bc they gained 2 of the same from one parent and then on different from the second parent.
What is a common effect on the bladder d/t DM autonomic neuropathy?
Overflow incontinence d/t inability to sense a full bladder from impaired detrusor contractility. Often have increased PVR volume and incomplete emptying.
What are the nerve roots and areas supplied by the genitofemoral nerve?
L1-L2. Provides sensation to upper anterior thigh and motor to parts of genitalia (Cremasteric reflex in men, mons pubis in women).
What are the nerve roots and areas supplied by the Iliohypogatric n.?
L1 nerve root. Sensation to the suprapubic and gluteal regions. Motor to the anterolateral abdominal mm. Surgery/appendectomy can damage it --> decreased sensation and/or burning pain in suprapubic region.
When is work of breathing minimized for restrictive lung diseases?
When respiratory rate is high and tidal volume is low. So they take rapid shallow breaths. Opposite for obstructive diseases.
What is the DoC to treat ascites?
What is the “string of beads” sign in the renal a. associated with?
Fibromuscular dysplasia- get areas of stenosis and dilatation. One of the causes of secondary HTN.
Enzyme activity decreased by insulin:
Enzyme activity increased by insulin:
Acetyl CoA carboxylase
What’s the difference between BP I and BP II disorders?
BP I: Manic episodes lead to marked impairment in social/occupational functioning, or require hospitalization. MDD not required for dx.
BP II: Hypomanic- doesn’t cause marked dysfunction. Require 1+ MDD for diagnosis.
Most common AE of thrombolysis:
Hemorrhage- GI or intracerebral.
What medication will selectively decrease HR w/no effect on contractility or relaxation?
Ivabradine- a Funny Na+ channel blocker in phase 4. It prolongs phase 4- slowing depolarization and slows SAN firing. Does not affect contractility or relaxation. Used to tx HF w/reduced EF.
What tests are used to analyze qualitative variables, quantitative?
Qualitative/Categorical: Chi-squre, logistic regression.
Quantitative: t-test, ANOVA, linear regression.
What disease is characterized by Abs to presynaptic VG Ca2+ channels?
Lambert Eaton Myasthenic syndrome.
What kind of immune response is Erythema Multiforme?
Cell-mediated with an infiltration of mostly CD8+ cells.
What Rxs treat bacterial vaginosis?
Metronidazole (Inhibits NA synthesis), and Clindamycin (binds 50S and inhibits translation).
What would a chromosomal 3p deletion cause?
A mutation in the VHL gene which would then lead to renal cell carcinoma.
What cancers does Rb cause and what chromosome is it located on?
Chromosome 13. Mutations in Rb lead to retinoblastoma and osteosarcoma.
What is dysostosis multiplex?
Enlarged skull, abnormally shaped ribs and vertebrae. Seen in Hurler syndrome (a-L-iduronidase def.)- also causes corneal clouding and blindness.
What is the inferior alveolar n.?
Branch of V3- it supplies the lower teeth. Injured in mandibular trauma/fractures.
What are the effects of DKA on the respiratory system?
Normally it causes a compensatory respiratory alkalosis to offset the metabolic acidosis.
In severe DKA pts. can develop pulmonary edema, resp. fatigue, and decreased mental status --> HoVentilation, and hypercarbic respiratory failure.
What is operant conditioning?
Behavior becoming a/w an environmental consequence- Both +/- punishment and reinforcement.
In a pt. w/HoV shock what changes occur to TPR and contractility?
Both TPR and myocardial contraction are increased d/t SNS activation. Admin of fluids will decrease SNS and therefore decrease both of these.
Where do the ovarian vv. drain?
The L. ovarian v. drains into the L. renal v. The R. ovarian v. drains directly into the IVC.
What nerve provides sensation to the medial leg?
The saphenous n. (branch of femoral).
What are some features of signet-ring cell carcinoma?
Diffuse involvement of the stomach wall d/t loss of E-cadherin. Have plaquelike, ill-defined appearance, and infiltrate large areas of the stomach wall --> linitis plastica.
Injury to what nerve will cause Trendelenburg gait?
Superior gluteal nerve- innervates gluteus medius, gluteus minimus, and TFL.
Mutations associated with Pheochromocytoma:
NF-1, VHL, RET (MEN 2A/B), also associated with Sturge-Weber Syndrome
What affects will Thyroid function have on cholesterol?
Hypothyroidism causes a decrease in LDL receptor expression --> hypercholesterolemia and increased LDL serum levels.
Hyperthyroidism does the reverse (increased LDL receptors --> hypocholesterolemia).
How to calculate NNH:
NNH = 1/AR
AR = Adverse event rate in control group – AE in treatment group
What lab values will be seen in a pt. w/Methylmalonic academia?
Anion gap metabolic acidosis, hypoglycemia, ketosis, hyperammonemia, and increased urine methylmalonic and proprionic acids.
What are the retroperitoneal organs?
Suprarenal (adrenal) glands
Aorta & IVC
Duodenum (except 1st part)
Pancreas (head and body)
Ureters & Bladder
Colon (ascending and descending)
How to differentiate between Polycythemia vera and Secondary polycythemia:
PCV will increase all cell lines: RBCs, platelets, and WBCs. Often get splenomegaly and will have low EPO- its d/t increased BM sensitivity to growth factors.
Secondary polycythemia is only an increase in RBCs. Will have high EPO, normally no splenomegaly.
What are some common causes of Lithium toxicity?
Volume depletion (decr. GFR), Rx interactions with: Thiazides, NSAIDs (not aspirin), ACEIs, Tetracyclines, Metronidazole.
What is the most common presentation of C. neoformans infection?
What causes arcuate scotomas?
Damage to a particular region of the optic nerve head. The visual field defect will follow the arcuate shape of the nerve fiber pattern.
What is the MoA of gallstone formation in Crohn pts?
Increased bile acid wasting- decreased BA reabs in the inflamed ileum --> cholesterol supersaturation of bile --> gallstones.
Increased oxalate absorption is what forms KIDNEY stones in these pts.
What is the MoA of squatting to reduce cyanosis in ToF?
Squatting increases SVR and decreases R to L shunting, which increases pulmonary blood flow and improves oxygenation status.
What disease is d/t absence of CD18 antigens?
LAD- w/out CD18 Ags they can’t form integrins and can’t form tight adhesions to get to the infection.
What surface Ags do some tumor cells upregulate to inhibit cytotoxic T cells?
PD-L1. T-cells have PD-1 (programmed death receptor 1) on their surface and when bound to PD-L1 on the tumor cell the T cells are inhibited and the tm. cells survive. Mabs against PD-1 block the receptor on T cells so they are able to recognize the tm. cells and promote apoptosis.
Same with CTLA-4.
Antagonists at which receptors help tx Chemo-induced emesis?
DA antagonists (Prochlorperazine, Metoclopramide)
5-HT antagonists (Ondansetron, Granisetron)
Neurokinin 1 (NK1) antagonists (Aprepitant, Fosaprepitant)
Where are serotonergic neurons found?
What type of neurons are found in the nucleus basalis of Meynert?
In the HIV replication cycle, what is the only polyprotein that is glycosylated?
The env gene is glycosylated to become gp160. This is then cleaved to become gp41 & 120 which mediate viral attachment to target cells.
What are the common AEs of ganciclovir?
Neutropenia, anemia, thrombocytopenia, and impaired renal function.
What is beri-beri?
Deficiency of Thaimine (B1)
Dry: symmetrical peripheral neuropathy of distal extremities --> sensory & motor impairments.
Wet: Addition of cardiac involvement- CMP, High-output CHF, peripheral edema, tachycardia.
What is the MoA of Flutamide?
A competitive testosterone receptor inhibitor. Used in combo w/GnRH agonists to treat prostate cancer.
Presents w/ optic atrophy, developmental regression, and seizures.
Arylsulfatase A deficiency.
Progressive demyelination --> ataxia, peripheral neuropathy, seizures, and hypotonia.
What nerve could be injured at the supinator canal, and how would it present?
The radial nerve passes through this canal. Injury can present w/weakness during finger and thumb extension, without wrist drop or sensory deficits.
What cells make up the JG Apparatus, what will happen to these in hypoperfusion?
MD cells, JG cells, and extraglomerular mesangial cells make up the apparatus. In hypoperfusion/stenosis these cells will undergo hyperplasia.
Basement membrane splitting on LM:
Membranoproliferative glomerulonephritis. See granular deposits on IF.
Diffuse capillary wall thickening on LM:
Membranous glomerulopathy. Granular deposits on IF.
IgM and C3 deposits in sclerotic areas of the glomeruli:
What effect does acute MR have on preload and afterload?
It significantly increases the preload, and decreases the afterload. Together these cause an increase in EF.
ST elevation in leads I and aVL:
Left circumflex occlusion. May also affect V5-V6
When is BhCG detectable in the serum and urine?
Serum is 6-7 days post fertilization at the earliest. Urine is typically 14 days after fertilization.
Activity of which enzymes will increase in Lesch Nyhan?
Those in de novo purine synthesis: PRPP synthetase, PRPP amidotransferase.
Signs of acute Vitamin A toxicity:
N/V, vertigo and blurred vision.
Signs of Chronic Vit. A toxicity:
Alopecia, dry skin, hyperlipidemia, hepatotoxicity, hepatosplenomegaly, and visual difficulties.
Severe cxs: papilledema/cerebral edema from pseudotumor cerebri, and cirrhosis.
What should be given to prevent a newborn being infected with GBS?
What are fatty streaks?
Earliest form of atheroma. Consist of lipid-laden MPs in the intima.
Injectible hypoglycemic agents:
Insulin, Amylin analog (Pramlintide), GLP1 analog (Liraglutide)
What kind of viruses can be infectious on their own with their purified RNA molecules?
+ssRNA viruses. These are the only ones capable of replicating completely on their own by using the host cell machinery. Only exception is HIV- it is +ssRNA but requires reverse transcriptase.
What NT stimulates the eccrine sweat glands and adrenal glands?
Ach stimulates both. Adrenals have N receptors, and eccrine glands have M receptors, both activated by Ach.
What kind of vaccine is the HBV vax?
A recombinant surface protein vaccine.
How to calculate Minute and Alveolar ventilation:
Minute Ventilation = Vt x RR
Alveolar ventilation = (Vt – Vd) x RR
Diseases with target cells:
HALT said the hunter to his target-
What is the cause for decreased urinary pH in metabolic acidosis?
Increased excretion of free H+, NH4+ and H2PO4-.
What is the pathogenesis of alcohol-induced hepatic steatosis?
Primarily d/t decreased free FA oxidation secondary to excess NADH production by alcohol and aldehyde dehydrogenases. Impaired lipoprotein assembly/secretion may also contribute.
What is the MoA of Anastrozole?
It, Letrozole, and exemestane are all aromatase inhibitors, which are used to treat ER+ breast tumors by decreasing estrogen conversion.
What are the main AEs of MTX?
Ulcers of the oral and GI mucosa, stomatitis, alopecia, pancytopenia, hepatotoxicity (hepatitis, fibrosis, cirrhosis), and pulmonary fibrosis.
What components make up the crescents in RPGN?
Proliferation of glomerular parietal cells, monocytes, macrophages, and abundant fibrin.
Staining for fibrin will show positive crescents on IF. Crescents eventually become sclerotic and fibrotic --> irreversible injury.
In a pt. w/severe AS what would cause HoTN in the setting of aFib??
aFib would cause loss of atrial contraction and reduce the LV preload and CO to significantly drop --> HoTN.
Pts. w/severe AS rely on the atrial kick for ventricular filling. The loss of atrial contraction will also cause blood to backup and cause acute pulmonary edema.
What would cause gastric varices only in the fundus of the stomach?
Splenic vein thrombosis --> increased pressure in the short gastric vv. which only drain the fundus.
Buildup of pressure in the L. gastric vein would cause both gastric and esophageal varices.
What would cause a blood clot within the splenic vein?
Pancreatic inflammation- pancreatitis, cancer etc.
What are the major immune mechanisms against Giardia?
CD4+ cells and secretory IgA.
Clinical features of Niemann-Pick:
Heptaosplenomegaly, neuro/developmental regression, cherry-red macula, hypotonia and decreased DTRs.