Uworld 5/10/18 - 5/16/18
What histopath abnormalities do you expect w/ aortic dissection? Classic sx for aortic dissection
Intimal tear and medial degeneration (elastic tissue fragmentation and separation of elastic fibromuscular components of tunica media by small, cleft-like spaces) (Dissection = severe pain radiating to back!)
Where are leads placed in a biventricular pacemaker?
2 or 3 leads 3 leads used: first two in RA and RV; third in LV Difficult to place LV lead (vs right leads, which can just go thru Subclavian and SVC). Preferred approach for LV lead is to pass lead from RA into coronary sinus (which is in AV groove on posterior aspect of heart) --> then advanced into lateral venous tributary to optimize left ventricular pacing
What is definition of osteoporosis?
2.5 or more SDs below mean (T score < or = 2.5)
What drains into superficial inguinal lymph nodes? What are exceptions to the genera l rule?
Cutaneous lymph from umbilicus down External genitalia and anus (below dentate line) Exceptions: glans penis and posterior calf (popliteal lymph nodes) --> bypass superficial nodes to drain into deep inguinal nodes
What are symptoms of Down syndrome?
Dysmorphic features (flat face, protruding tongue, small ears, upslanting palpebral fissures) Cardiac defects (endocardium cushion defect like AV septal defect)
What motor protein carries vesicles/organelles away from cell body toward nerve terminal?
Kinesin
Which one is anterograde vs retrograde motor protein? Kinesin Dynein
Kinesin - anterograde to mictrotubule (- --> +); + end usually distant from nucleus Dynein - retrograde to microtubule (+ --> -) Both are ATP motor powered
What is most commonly associated w/ necrotizing pneumonia in elderly or immunocompromised patients?
Klebsiella
What are radiologic findings and sx that make you think of lung absces
Fever, cough, copious sputum (foul smelling) CXR - cavitation w/ air fluid level
What drug when combined with statins increases risk of severe myopathy? How does it to this?
Fibrates (especially gemfibrozil) Impair hepatic clearance of statins --> lead to excessive blood levels of statins --> myopathy more severe
What are primary side effects of niacin?
Flushing (can reduce by taking NSAIDs) Hyperglycemia Hyperuricemia Hepatotoxicity
What does lipase due in acute pancreatitis?
Forms calcium soap bubble deposits (fat necrosis)
Which diseases have trinucleotide repeats?
Fragile X Huntington Myotonic dystrophy
What type of signaling system/receptor does glucagon use?
G protein coupled receptor Cyclic AMP Protein kinase A
Lymph from prostate drains into...
Internal iliac nodes
What initial lesions would you expect in someone he who has aortic aneurysm due to atherosclerosis? What part of aorta do they most commonly occur
Intimal streak lesion --> severe complicated intimal at hero as destroy, weaken underlying media --> aortic aneurysms Abdominal aorta (below renal arteries)
E. coli - what are general micro characteristics? (Motility, gram stain, shape, aerobe vs anaerobes, fermenting, agar growing patterns)
Motile, gram negative, bacilli Facultative anaerobic Ferments lactose and glucose Grows on blood (beta hemolysis), MacConkey, and EMB agar (on EMB - green metallic sheen) O antigen - on extra cellular polysaccharide outer membrane, for classifying gram neg bacteria
From mesoderm
Muscles (skeletal, cardiac, smooth) Connective tissue, bone and cartilage Aerosol linings (peritoneum) Cardiovascular and lymphatic system Spleen and hematopoietic cells Kidneys and ureters, internal genitalia Adrenal cortex
What are sx of schizophrenia?
Must be >or= 2 of the following, one of which must be "active" sx: Delusions Hallucinations Disorganized speech Grossly disorganized behavior -- Negative sx: Flat affect Abolition Alogia (poverty of speech) Anhedonia Asociality Functional decline
SIADH lab values (plasma osmolality, sodium osmolality, urine osmolality)
Na osmolality - hyponatremic Decreased serum osmolality Elevated urine osmolality (normally should be <100 mOsm/kg given hyponatremia) Urine osmolality > serum osmolality
Prader Willi: which gene is silent, which gene is deleted/mutated? Angelman: which gene is silent, which gene is deleted/mutated?
Prader Willi - maternal imprinting = silent; paternal deleted/mutated Angelman - paternal imprinting = silent, maternal deleted/mutated
Which leads have ST elevations if LAD is occluded? What region of heart is affected? Remember differences between proximal vs distal LAD
Proximal V1-V4 (septal leads and anterior leads) Anterior aspect of LV and interventricular septum Distal V3, V4 (just anterior leads) Anterior aspect of LV
What organism causes rapidly progressive, necrotic cutaneous lesions in immunocompromised patients?
Pseudomonas Lesions are called ecthyma gangrenosum - have necrosis and ulceration as a result of insufficient blood flow
Horner syndrome
Ptosis, meiosis, and anhidrosis Damage to lateral hypothalamus, hypothalamospinal tract, paravertebral/Stella the ganglion (pancoast tumor) or ICA (carotid dissection)
Nissl substance in neurons corresponds to what organelle?
Rough ER
How do you differentiate SIADH from primary polydipsia
SIADH have inappropriately concentrated urine (>100 mOsm/Kg) for hyponatremia If urine osmolality <100 (maximally dilute), then there is appropriate suppression of ADH --> primary polydipsia
How do you treat PTSD?
SSRIs, venlafaxine (SNRI) Trauma- focused CBT ^^ first line Prazosin for nightmares
What is difference between schizoaffective disorder vs major depressive disorder/bipolar w/ psychotic features?
Schizoaffective - >2 weeks of hallucinations or delusions w/o major mood episode Bipolar/MDD with psychotic features - psychotic sx occur ONLY during depressive or manic episode
What is timeline for different schizophrenia disorders (schizophrenia, brief psychotic, schizophrenia or, and schizoaffective)?
Schizophrenia: require "active" sx for >1 month during a period of >6 months with prodromal or residual sx occurring the rest of the time Brief psychotic: >1 day but <1 month Schizophreniform: 1-6 months Schizoaffective: Schizophrenia + Major mood disorder (MDD or BP); >2 weeks of hallucinations/delusions without major mood episode (vs MDD w/ psychotic features)
What does TGF-beta do?
Secreted by inflammatory cell Helps w/ recruitment of fibroblasts and depositition of connective tissue Contributes to scar formation post injury; fibrosis w/ chronic inflammation
How does cinacalcet work??
Sensitizes CaSR in parathyroid gland to circulating Ca --> leads to decreased PTH Use in hyperparathyroidism
What happens when you combine B blocker and non-dihydropyridines CCB?
Significant sinus bradycardia Hypotension (Even sinus arrest w/ AV junction also or idioventricular rhythm) **need monitoring!
Which cancer most associated with SIADH?
Small cell lung carcinoma
Actions of glucagon
This activates: 1) glycogen phosphorylase (important for glycogenolysis) 2) gluconeogenesis ==> activates rate-limiting gluconeogenetic enzymes, e.g. Pyruvate carboxylase, and phosphoenolpyruvate carboxykinase 3) decrease intracellular fructose 2,6, BP levels (inhibits glycolysis, favors gluconeogenesis) 4) stimulates insulin secretion from pancreas Actions are on skeletal muscle, adipose tissue, and renal cortex
Pathogenesis of acute pancreatitis
Toxic/ischemic injury to acinar cells leads to premature activation of trypsin inside pancreatic acini Trypsin activates proteolytic enzymes --> self sustaining cycle of inflammation/autodigestion Ischemic injury can be due to Ducati obstruction (e.g. Gallstones/tumors in ampulla or ducal concretions from alcoholism --> impair blood flow --> ischemia --> acinar cell dysfunction)
What kind of receptor is a calcium-sensing receptor (CaSR)?
Transmembrane GPCR (metabotropic)
What is triad of hemolytic uremic syndrome?
Anemia, thrombocytopenia, acute renal failure (Shiga like toxin - EHEC)
Structures that derive from surface ectoderm?
Anterior pituitary (rathke pouch) Lens and cornea Inner ear sensory organs, olfactory epithelium Nasal and oral epithelial linings, salivary glands Epidermis, sweat, and mammary glands
What is major adaptive immune mechanism that prevents re-infection with influenza virus?
Anti-hemagluttinin Ab (Ab to neurominidase are not main source of protection, but they offer some protection, decreased viral invasion and shedding)
What drugs for RA provide the most rapid relief?
Anti-inflammatory therapies like glucocorticoids and NSAIDs Glucocorticoids inhibits PLA2, decrease PG and LK synthesis. Also depress immune response by inhibiting txn of multiple cytokines and adhesion proteins, reducing leukocyte recruitment and activation. (DMARDS like MTX, sulfasalazine, hydroxychloroquine, and leflunomide, take weeks to get response)
What lowers bone mass?
Asian/white ethnicity Chronic inflammatory disease Exposure to glucocorticoids Sedentary lifestyle Low BMI (<22) Smoking Too much caloric deficit (from excessive exercise) --> functional hypothalamic amenorrhea, suppress estrogen --> bone loss
Where does coronary sinus reside?
Atrioventricular groove on posterior aspect of heart
What is inheritance pattern for VWD?
Autosomal dominant Most common inherited bleeding disorder Variable penetrance PTT and Bleeding time prolonged!
What are drugs that have negative chronotropic effects? (I.e. Slow HR, AV node conduction, myocardial contractility)?
B blockers Non-dihydropyridines CCBs (verapamil, diltiazem) Cardiac glycosides (digoxin) Amiodarone and sotalol (class III antiarrhythmics) Cholinergic agonist (pilocarpine, rivastigmine)
Robertsonian translocation
Chromosomal translocation involves pairs 13, 14, 15, 21, 22 Occurs when long arms of 2 Afrocentric chromosomes (chromosomes with centromeres near ends) fuse at centromere and 2 short arms are lost Balanced - no abnormal phenotype Unbalanced - miscarriage, stillbirth, chromosomal imbalance (Down, Patau e.g.)
What abnormalities are associated with chromosomal deletions?
Cri-du-chat (5p deletion) DiGeorge (22q11 microdeletion) Velocardiofacial (22q11 microdeletion) Prader-Willi (15q deletion) Williams (7p deletion)
What is inheritance pattern for Hemophilias?
A: X linked B: X linked C: AR
What is inheritance pattern and defect in familial hypocalciuric hypercalcemia (FHH)?
AD Benign Defective CaSR in parathyroid gland and kidneys This means that in CaSR needs higher serum calcium levels to inhibit PTH. --> raises set point of calcium --> mild asymptomatic hypercalcemia, reduced urinary excretionof calcium, and high normal or mildly elevated PTH
What filament does microvilli contain?
Actin
How are PMNs activated?
After being recruited by chemokines, they are activated by microbial molecules (LPS, peptidoglycan, bacterial DNA) and opsonizing factors (IgG and complement) to phagocytize and destroy pathogenic bacteria
What are symptoms of parotid gland tumor?
B/c it can compress and disrupts ipsilateral facial nerve and branches, causes facial droop (Loss of forehead and brow movements, inability to close eyes and drooping eyelids, loss of nasolabial folds and drooping of lower lip)
Which other cholesterol drug when combined w/ station can reduce GI aborprtion of statin?
Bile acid resins like cholestyramine
What do CaSR (calcium-sensing receptors) do?
Binding of calcium (calcium rich enviro) to CaSR inhibits PTH release Lack of calcium binding (hypocalcemia) to CaSR leads to increased PTH release
What symptom do you get when you have tumor compress optic chaise?
Bitemporal hemianopsia (Usually due to craniopharyngeoma or pituitary adenoma)
From neural tube?
Brain and spinal cord Posterior pituitary, pineal gland Retina
Course of recurrent laryngeal nerve?
Branch of vagus - loops below aortic arch on left, and below subclavian artery on right -> provides motor innervation to laryngeal muscles (If damaged often during thyroid surgery b/c --> unilateral damage - hoarseness; bilateral damage - inspiration strider and resp distress b/c of complete vocal cord paralysis)
CNV - function and course?
CNV (trigeminal) Provides sensation to face and motor innervation to muscles of mastication CNV follows a deep course
Describe path of CNVII from skull to innervation site.
CNVII (Facial nerve) exits skull thru stylomastoid foramen --> goes thru parotid gland --> within gland divides into 5 branches (Temporal, Zygomatic, Buccaneers, Mandibular, and Cervical).
What is the polymerase and exonuclease activity of DNA polymerase III and I? (Prokaryotes)
DNA Pol III - has polymerase activity in 5' --> 3'. Has exonuclease activity in 3' --> 5'. DNA Pol I - has exonuclease activity in 5'-->3'. Allows to excise RNA primers.
How do glucocorticoids lead to osteoporosis?
Decrease GI absorption of calcium Inhibit collagen synthesis of osteoblasts Decrease GnRH (hypogonadism --> less estrogen) Increase urinary calcium loss
How do compensatory mechanisms of CHF lead to further cardiac deterioration?
Decreased CO leads to: 1) increased sympathetic nervous system activation --> increased hr and contractility, and VASOCONSTRICTION 2) increased RAAS --> vasoconstriction and increase extracellular volume 3) increased ADH --> increased extracellular volume While 1-3 help maintain BP, but also increased preload and afterload of heart --> increased hemodynamics stress and exposure to neurohormones long term (e.g. RAAS, symp, ADH)...eventually leads to deleterious cardiac remodeling
What is the difference between a dihydropyridiines and non-dihydropyridine CCB?
Dihydropyridines (amplodipine, clevidipine, nicardipine, nifedipine, nimodipine) act on vasc smooth muscle. Has minimal effects on SA node and cardiac conduction! Non-dihydropyridines (diltiazem, verapamil) act on heart
Down, edwards, Patau - number of chromosomes for each, and rank based on prevalence from highest to lowest?
Down (21) > Edwards (18) > Patau (13)
Renal gluconeogenesis
Epinephrine > glucagon in stimulating gluconeogenesis
What is the volume status of someone with SIADH? Why?
Euvolemic Increased ADH --> excessive water absorption by kidneys --> transient subclinical hypervolemia Mild increase in EC fluid volume suppresses RAAS --> stimulates natriuretic peptide production --> excrete Na in urine (natriuresis) --> clinically normal EC fluid volume THEREFORE, no volume overload sx
What are the virulence factors for pseudomonas?
Exotoxins A (protein synthesis inhibition, inactives EF-2) Elastase (degrades elastin, important for blood vessel destruction) Phospholipase C (degrades cellular membranes) Pyocyanin (generates reactive oxygen species) Endotoxins (Fever, shock)
What hormones work by TM receptors that recruit Janus kinase from cytoplasm? (JAK-STAT txn factors)
GH, prolactin, EPO
From endoderm
GI tract, liver, pancrea Lungs Thymus, parathyroid, thyroid follicular cells Middle ear epithelium Bladder and urethra Thyroid follicular cells
What are you more susceptible to in neutropenia (ANC<500)?
Gram neg infections
What is necrotizing pancreatitis
Gross areas of parenchymal necrosis w/ high propensity for secondary bacterial infection
What hormones work by stimulating TM receptors with intrinsic tyrosine kinase activity in intracellular domain, initiating downstream phosphorylation cascade?
Insulin, IGF
What is the role of the following enzymes in DNA replication? (Prokaryotes) Helicase DNA gyrase (topoisomerase II) Primase (DNA-dependent RNA polymerase) Ligase DNA polymerase I DNA polymerase III
Helicase - binds double stranded DNA at origin or replication with DnaA protein. Acts at replication fork to unwind and separate DNA (Single stranded DNA binding protein then attaches to separate strands to prevent reannealing) DNA gyrase (topoisomerase II) - relieves the tension created during unwinding by, introduce negative supercoils into DNA (positive supercoils created from unwinding and separation produce positive supercoils that lead to DNA fracture if not relieved) Primase - synthesizes RNA primer (short RNA sequences) base paired to parent DNA DNA polymerase III - elongates leading strand by adding DNA to 3' end. Elongates lagging strand until it reaches primer of preceding fragment. 3' --> 5' exonuclease activity proofreads each added nucleotide. Ligase - binds okazaki fragments in lagging strand together (after RNA primers have been removed and replaced w/ DNA) DNA polymerase I - only DNA polymerase with 5' to 3' exonuclease activity! This allows it to remove RNA primers.
What are main side effects of statins?
Hepatotoxicity (increased LFTs) Myopathy (esp w/ fibrates, somewhat w/ niacin, even less so w/ ezetimibe) Severe myopathy - increased CK and rhabdo possible
Which leads have ST elevations if left circumflex is occluded? What region of heart is affected?
I, aVL (lateral limb leads) Possibly V5-6 Lateral infarcation of LV
Which leads have ST elevations if right main coronary is occluded? What region of heart is affected?
II, III, aVF (inferios) RV and inferior aspect of LV (inferior)
Name 3 skin infections caused by strep pyrogeness?
Impetigo, erysipelas, necrotizing fasciitis, cellulitis
What happens to NPV with increase in prevalence? What happens to NPV with decrease in prevalence?
Increase prevalence - less true neg, more false neg, so lower npv Decrease prevalence - more true neg, less false neg, so higher npv
What happens to PPV with increase in prevalence? What happens to PPV with decrease in prevalence?
Increase prevalence - more true pos, less false pos, so higher PPV Decreased prevalence - less true pos, more false pos, so lower PPV
Actions of epinephrine to increase glucose levels
Increased glycogenolysis Increased gluconeogenesis in liver Decreased glucose uptake by skeletal muscle Increased alanine release from skeletal muscle (source of gluconeogenesis) Increases breakdown of triglycerides - increases circulating FFA and glycerol (used as gluconeogenesis substrates)
What are risk factors for meiotic nondisjunction?
Increased maternal age probably b/c Cumulative oxidative stress, depletion of available mature oocytes, and shortening of oocyte telomeres.
What are borders of femoral triangle?
Inguinal ligament, sartorius, adductor longus
Positive likelihood ratio - definition and equation? Negative likelihood ratio - definition and equation?
LR+ = sensitivity/(1-specificity) Ratio representing the likelihood of having the disease given a positive result LR- = (1-sensitivity)/specificity Ratio representing the likelihood of having the disease given a negative result Neither affected by prevalence LR > 1 --> test result is associated w/ presence of disease LR < 1--> test result associated w/ absence of disease
Medial inflammation of artery is associated with?
Large vessel arteritis
What are DMARDs? Name examples, how they work
MTX (first line) Sulfasalazine Hydroxychloroquine Minocycline TNF-alpha inhibitors (etanercept, infliximab, adalimumab, certolizumab, golimumab) Alleviate pain, inflammation, reduce long-term joint destruction and disability
What do you get when nondisjunction happens in meiosis I? What about meiosis II?
Meiosis I --> 2 trisomy gametes and 2 monosomy gametes Meiosis II --> 2 normal gametes, 1 monosomy, 1 trisomy
What is embryologic origin of spleen?
Mesoderm! From condensed mysechymal tissue in dorsal mesentery during embryonic development (arises in mesentery of stomach) Mesenchyme tissue = loosely associated cells surrounded by EC matrix Unique from other gut tissue (which is endoderm)
From notochord
Mesodermal derived structure Nucleus pulposus of intervertebral disc
From neural crest
Neural ganglia, adrenal medulla Schwann cells; pia and arachnoid Aorticopulmonary septum and endocardium cushions Bronchial arches (bones and cartilage) Skull bones Melanocytes
What hormones bind to transmembrane ligand-gated ion channels (ionotropic receptors)?
Neurotransmitters that workivia ion channel-linked receptors Acetylcholine, serotonin, N-methyl-D-aspartate, GABA
What immunologic response is most important in abscess formation (type of cell and its action)?
Neutrophils Lead to release of cytotoxic granules (lysosomes) containing myeloperoxidase and other digestive enzymes that kill extracellular bacteria and cause liquefying necrosis of surrounding tissue (and potentially abscess)
What do PT, PTT, and bleeding time test?
PT: extrinsic and common pathway, I, II, V, VII, and X PTT: intrinsic and common pathway, all except VII and XIII Bleeding time - platelet function, prolonged by quantitative and qualitative platelet defects.
Describe normal pancreatic enzyme cascade
Pancreatic acinar cells synthesize zymogens Zymogens are secreted from apical surface of acinar cells into lumen Traverse pancreatic duct and drain thru ampulla of Vader into duodenum Enterokinase (secreted from intestinal mucosa) cleave trypsinogen into trypsin Trypsin activates chymotrypsin, elastase, phospholipase a2 (damage cell membranes), and carboxypeptidase. LIPASE DOES NOT REQUIRE TRYPSIN ACTIVATION. Trypsin cleaves trypsinogen --> trypsin --> accelerates pancreatic enzyme activation in duodenum
What determines bone mass in adulthood?
Peak bone minus subsequent bone loss Peak bone mass - genetics, environmental factors (nutrition, physical activity). Usually achieved by early adulthood. Declines w/ age
What is ecthyma gangrenosum?
Perivasc invasion and release of tissue-destructive exotoxins --> vascular destruction and insufficient blood flow to patches of skin --> edema, necrosis Pseudomonas Neutropenia, hospitalized, burns, in dwelling catheters (pseudomonas)
What hormones behind to intracellular receptors with DNA-binding domain?
Steroid, thyroid, vitamin D
Where does lymph for superior bladder drain? What about inferior bladder
Superior - external iliac Inferior - internal iliac
TB --> granuloma --> what is the pathophysiology?
TB is ingested by macrophages TB survives and reproduces within phagolysosomes Infected macrophages --> pulm lymph nodes, present mycobacterium antigens to naive cd4 helper t cells; also secrete il-12 which induces activated t helper cells to differentiate into T helper subtype (th1) cells Proliferating Th1 cells --> migrate to infection site --> release IFN-gamma --> activates macrophages Macrophages are amped up and have better ability to kill ingested mycobacterium and produce TNF-alpha (recruits additional monocytes and macrophages). They form mature phagolysosomes that destroy phagocytosis mycobacterium and differentiate into epitheliod and Langerhans giant cells to wall of extracellular mycobacterium within caseating granulomas
Which leads have ST elevations if left main coronary is occluded? What region of heart is affected?
V1-V4 (anterior) and lateral (V5-V6, I, aVL) Anterolateral (because left main = LAD and circumflex)
What are the cardiac findings you see in tertiary syphilis?
Vasa vasorum endarteris and obliteration --> inflammation, ischemia, weakening adventitious --> aneurysmal dilation of thoracic aorta --> extends to involve aortic valve ring --> aortic regurgitation murmur and mediastinal widening Luetic aneurysm
what are the e coli virulence factors, mechanisms of action, and what presentations/symptoms do each lead to?
format = virulence factor, mechanism, presentation lipopolysaccharide (lipid A component specifically) - macrophage activation causes widespread release of il-1, il-6, and TNF-a --> BACTEREMIA AND SEPTIC SHOCK K1 capsular polysaccharide - prevents phagocytosis and complement-mediated lysis --> NEONATAL MENINGITIS Verotoxin (shiga-like toxin) - inactivated the 60S ribosomal component, halting protein synthesis, and causing cell death --> GASTROENTERITIS (bloody) Heat-stable/heat-labile enterotoxins - promotes fluid and electrolyte secretion from intestinal epithelium --> GASTROENTERITIS (watery) P fimbrae - allows adhesion to uroepithelium --> urinary tract infections (UTIs) Type 1 fimbrae - epithelial cell adhesion S fimbrae - Enterocyte adhesion