Uworld 8 Flashcards
What is seen on duodenal biopsy for celiac disease?
crypt hyperplasia, villous atrophy, and intraepithelial lymphocyte infiltration.
What is amyloid precursor protein? (APP) What happens with abnormal APP processing?
APP gene is located on c.21 and encodes a cell-surface protein that can be degraded into beta amylid.
Abnormal APP processing, impaired beta-amyloid clearance, and production of higher levels of APP are associated with the increased formation of the neurotoxin plaques that characterize ALzheimer dementia.
MOA of selective serotonin reuptake inhibitors
Inhibition of serotonin reuptake by blocking the serotonin transporter
What is the main adverse effects seen with nitrate therapy?
Headache and cutaneous flushing along with lightheadedness and hypotension due to systemic vasodilation
The great saphenous vein drains into?
Th femoral vein within the region of the femoral triangle, a few centimeters inferolateral to the pubic tubercle.
The great saphenous vein is a superficial vein of the leg that originates on the medial side of the foot, courses anterior to the medial malleolus, and then travels up the medial aspect of the leg and thigh.
Oncogenesis in pancreatic ductal adenocarcinoma is almost always due to?
An early activating mutation in the KRAS oncogene, which produces a constitutively active protein that allows for uncontrolled proliferation of tumor cells.
What is obstructive sleep apnea due to?
Due to relaxation of oropharyngeal muscle tone with occlusion of the upper airway.
Sx: daytime sleepiness, headaches, and depression.
Complications: systemic and pulmonary HTN, right heart failure, and an increased risk for cardiac events
CMV can cause what in AIDS patients?
CMV is a common cause of colitis in patients with advanced AIDS.
It is the second most common CMV reactivation disease in this population (CMV retinitis is the most common).
Patients with CMV colitis often have abdominal pain, fever, diarrhea, and weight loss.
Colonoscopy usually shows erythema, erosions, and ulcerations; colonic biopsy typically reveals large cells with prominent basophilic intranuclear inclusions.
Protease inhibitors block?
viral protease from cleaving gag-pol polyproteins, which results in the formation of immature virions that are noninfectious.
Decompensated heart failure is a common cause of which murmur?
Common cause of secondary (functional) mitral valve regurgitation.
Increased left ventricular end-diastolic volume causes dilation of the mitral vale annulus and restricted movement of the chordae tendineae with subsequent regurgitation.
Txt: diuretics and vasodilators can improve heart failure induced MR.
What is a common side effect of atropine?
increased intraocular pressure.
It may precipitate acute closed-angle glaucoma in susceptible individuals.
Atropine is indicated for the txt of?
Bradycardia as it decreases vagal influence on the SA and AV nodes
Hepatic encephalopathy is caused by?
Increased levels of ammonia and other neurotoxins in the circulation that lead to increased inhibitory neurotransmission and impaired excitatory neurotransmitter release.
Frequently precipitated by a stressor (eg, GI bleeding, infx) that increases blood ammonia levels.
What response does inactivated (killed or component) viral vaccines primarily generate?
Primarily generate a humoral immune response against extracellular viral antigens, preventing viral entry into the cell.
Live attenuated viral vaccines can generate what kind of response?
A strong cell mediated immune response that can kill virally-infected cells, in addition to providing humoral immunity.
Pain due to diabetic neuropathy may be difficult to control and require multiple medications. To reduce the risk of adverse effects and improve pain control, medications should work through different mechanisms. One such combination may include?
a tricyclic antidepressant (eg nortriptyline) and an anticonvulsant (eg, gabapentin)
Mutations in factor V Leiden predisposes to?
Heterozygote carriers of a mutation in factor V Leiden, which is modified to resist activated protein C, have a hypercoagulable state that predisposes to deep vein thromboses (the source of most pulmonary emboli)
Malignant pleural effusions are usually exudative by Light criteria and can occur via several mechanisms, including?
An inflammation-induced increase in vascular permeability (leading to increased inflow) and blockage of pleural fluid reabsorption by parietal pleura lymphatics (leading to decreased outflow)
S3, a third heart sound occurs due to?
Sudden limitation of ventricular movement during passive ventricular filling in diastole.
An S3 in patients age>40 suggest?
abnormal ventricular cavity enlargemnt such as occurs in chronic severe mitral regurg, chronic aortic regurg, or dilated cardiomyopathy
Transudative effusions are characterized by?
Low protein and lactate dehydrogenase content compared to serum values.
Heart failure can cause what type of pleural effusion?
Transudative pleural effusion due to an increase in pulmonary capillary hydrostatic pressure
Burkitt lymphoma is associated with which translocation?
Translocations of the MYC gene on chromosome 8 to the immuniglobin heavy chain region of c.14 (t8;14), resulting in MYC over expression.
Presents with rapidly growing mass (eg, jaw) and histo: starry sky appearance, with numerous mitotic figures and apoptotic bodies
Pregnant women with severe preelampsia can develop?
HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome.
Nausea/vomitting and RUQ pain occur due to liver ischemia and/or hemorrhage (eg subcapsular hematoma).
Also at risk for seizure, renal insufficiency, and disseminated intravascular coagulation due to widespread endothelial dysfunction
What is the MOA of class IC antiarrhythmics such as flecainide?
Potent sodium channel blockers that have increased effect at faster heart rates (use-dependence).
This makes them more effective at treating tachyarrhythmias, but can also cause prolonged QRS duration (a proarrhythmic effect) at higher heart rates
What is asthma characterized by?
Chronic airway inflammation, which leads to airway remodeling, airway hyperresponsiveness, and bronchoconstriction.
Treatment for asthma
Corticosterioids reduce airway inflammation and are used for both chronic asthma management (inhaled adminstration) and acute exacerbations (systemic adminstration).
What are the most prominent organisms in intraabdominal infections?
Bacteroides fragilis and E. coli
Cardiac auscultation in patients with mitral stenosis reveals?
A loud first heart sound, an early diastolic opening snap after the second heart sound, and a low-pitched diastolic rumble best heard at the cardiac apex
The opening snap is caused by the sudden opening of the mitral valve leaflets when the left ventricular pressure falls below the left atrial pressure at the beginning of diastole.
ACTH regulates which zones in the adrenal?
ACTH is the major trophic hormone of the zona fasciculata and reticularis
Zona glomerulosa is regulated by?
angiotensin II
Excess production of ACTH causes?
increased cortisol synthesis within the zona fasciculata (Cushing’s manifestations) and increased androgen production within the zona reticularis (irregular menstruation, hirsutism in women)
A deformation anomaly is caused by?
Abnormal extrinsic forces on a developing fetus.
Talipes equinovarus (clubfoot) is an anomaly in which the foot is plantarflexed and pointed inward due to restricted in utero movement.
Transudative pleural effusions result from?
Increased intracapillary pressure (eg, heart failure)
Exudative effusions develop from?
Inflammatory disruption of the vascular membrane
What are the labs for transudative pleural effusions?
Transudative pleural effusions have low fluid/serum ratios of total protein and lactate dehydrogenase and low absolute levels of lactate dehydrogenase compared to exudative effusions
Methanol and ethylene glycol have relatively little direct toxicity (similar to ethanol) but are metabolized into highly toxic compounds by alcohol and aldehyde dehydrogenase. Treatment involves?
Adminstration of fomepizole, a competitive inhibitor of alcohol dehydrogenase (increases Km without reducing Vmax)
Parkinson disease is caused by?
bradykinesia, resting tremor, and rigidity are features of Parkinson disease, which is caused by dopaminergic neurodegeneration.
Traumatic brain injuries can accelerate neurodegeneration, leading to a higher incidence and earlier onset of Parkinson disease
Acute cardiac transplant rejection usually occurs weeks to months following transplantation and is primarily a cell-mediated process. In acute cellular rejection, endomyocardial biopsy shows?
An interstitial lymphocytic infiltrate with myocyte damage.
What is renal ammoniagenesis?
Acidosis stimulates renal ammoniagenesis, a process by which renal tubular epithelial cells metabolize glutamine to glutamate, generating ammonium that is excreted in the urine and bicarbonate that is absorbed into the blood.
This process is responsible for the vast majority of renal acid excretion in chronic acidotic states.
Septic arthritis in a young, sexually active adult should raise suspicion for?
Disseminated Neisseria gonorrhoeae infection.
Patients may also have the triad of polyarthritis, a vesiculopustular skin rask, and tenosynovitis.
N gonorrhoeae is G- diplococci that is usually identified by microscopy, culture, or nucleic acid amplification.
Norepinephrine-releasing agents (eg, phentermine) are sympathomimetic weight loss drugs indicated for short term treatment of obesity. MOA?
They stimulate the release and inhibit the reuptake of norepinephrine.
Subjective effects: increased sensation of satiety, leading to reduced caloric intake.
Weight regain after cessation is common with these drugs.
What is responsible for converting nonpathogenic Corynebacterium into toxigenic Corynebacterium?
Lysogenic bacterophages are responsible.
Toxigenic strains elaborate the diphtheria exotoxin, which causes pseudomembreanous pharyngitis and potentially life threatening systemic effects (eg, myocarditis, neuritis)
How does erythrocytes bypass the ATP generating step of glycolysis?
2,3-BPG decreases hemoglobin’s affinity for oxygen. Therefore, in the presence of lower blood oxygen concentrations, higher 2,3-BPG levels within erythrocytes enable increased oxygen delivery in the peripheral tissues.
2,3-BPG is produced from 1,3-BPG by the enzyme bisphosphoglycerate mutase. This reaction bypasses an ATP-generating step of glycolysis, causing no net gain in ATP.
What are signs of cocaine intoxication?
Cocaine intoxication can produce psychotic symptoms (eg, paranoid delusions), euphoria, and agitation.
Physical signs indicating sympathetic stimulations (eg, tachycardia, diaphoresis, mydriasis) can assist in differentiating cocaine intoxication from primary psychiatric disorders
Why is the pO2 in the left atrium and ventricle lower than in the pulmonary capillaries?
Due to mixing of oxygenated blood from the pulmonary veins with deoxygenated blood from the bronchial circulation and thebesian veins
What is the mechanism of diphtheria toxin?
Irreverisibly inhibits host protein synthesis due to ADP-ribosylation of elongation factor-2.
Local effects include pseudomembranous pharyngitis; systemic effects include potentially life threatening myocarditis and neuritis
Immunization with diphteria toxoid generates protective circulating IgG against the exotoxin B subunit
ACE inhibitors (eg, lisinopril) MOA
ACE inhibitors block the conversion of angiotensin I to angiotensin II, thereby reducing vasoconstriction and aldosterone secretion.
Decreased aldosterone leads to potassium retention, which can cause hyperkalemia, especially in patients with renal insufficiency and those taking other medications that raise potassium levels (eg, angiotensin II receptor blockers, mineralocorticoid receptor blockers)
MOA of flutamide
Flutamide is a nonsteroid anti-androgen that acts as a competitive inhibitor of testosterone receptors
It is used in combo with long acting gonadotropin-releasing hormone agonists for the treatment of prostate cancer
What is multiple myeloma associated with?
Elevated circulating paraproteins (monoclonal immunoglobins), which causes erthrocytes to stack like coins (rouleaux formation).
Patients classically have normocytic anemia, hypercalcemia, bone pain, and renal insufficiency
Function of kinesin
Kinesin is a microtubule-associated motor protein that functions in the anterograde transport of materials and organelles within cells
Reactivation of latent herpes simplex virus requires anterograde transport of viral particles from neuronal cell bodies in the sensory ganglia to the skin and oral mucosa
Immunization against hepatitis B virus uses what antibodies?
Uses recombinant HBsAg to generate anti-HBs antibodies. These antibodies prevent infection by binding to the envelope of circulating virus and inhibiting viral entry.
What is hypersensitivity pneumonitis?
Hypersensitivity pneumonitis involves an exaggerated immunologic response to an inhaled antigen and can have an acute or chronic presentation.
Chronic disease presents with gradually progressive cough, dyspnea, fatigue, and weight loss, and lung biopsy reveals lymphocytic infiltrate, poorly formed noncaseating granulomas, and septal fibrosis
What can suggest chronic pancreatitis?
Diarrhea, weight loss, and epigastric calcifications in a patient with chronic alcohol use suggest chronic pancreatitis with resulting pancreatic exocrine insufficiency and malabsorption
TSH from the anterior pituitary stimulates the thyriod to produce?
thyroxine (T4) and a small amount of triiodothyronine (T3).
T4 is converted in peripheral tissues to T3 (active form) and reverse T3 (inactive form). TSH secretion is under negative feedback by thyroid hormone on the hypothalamus and pituitary
What is a frameshift mutation?
A frameshift mutation occurs with the deletion/addition of a number of bases not divisible by 3 in the coding region of a gene.
Frameshift mutations alter the reading frame of the genetic code, dramatically changing the protein structure and often resulting in the formation of a premature stop codon.
Rapid correction of chronic hyponatremia may lead to?
Osmotic demyelination syndrome (also known as central pontine myelinolysis).
It typically manifests 2-6 days after the osmotic insult with spastic quadriplegia, pseudobulbar palsy, and locked in syndrome
Left sided heart failure leads to chronically elevated pulmonary venous and capillary pressures, with resulting?
Pulmonary edema and extravasation of red blood cells into the alveolar parenchyma.
The iron from red blood cells is taken up by alveolar macrophages and stored as hemosiderin, appearing as brown pigment on microscopy.
Where do most gastric ulcers arise?
Most gastric ulcers arise along the lesser curvature of the stomach, usually at the transitional zone between the gastric corpus (body) and the antrum.
What arteries run along the lesser curvature of the stomach?
The left and right gastric arteries run along the lesser curvature and are likely to be penetrated by ulcers, causing gastric bleeding
How does staph aureus cause hepatic abscesses?
Staph aureus can cause hepatic abscesses via hematogenous seeding of the liver
How does enteric bacteria (e. coli, klebsiella, and enterococci) cause hepatic abscesses?
By ascending the biliary tract (ie, ascending cholangitis), portal vein pyemia, or direct invasion from an adjacent area (eg, cholecystitis)
Penicillins and cephalosporins are common triggers for drug-induced hemolytic anemia because?
They can bind to the erythrocyte surface and act as haptens for IgG attachment.
Subsequent clearance of IgG-coated erythrocytes by splenic macrophages leads to hemolytic anemia.
Withdrawal of the offending drug usually leads to complete resolution of symptoms.
Subclavian steal syndrome occurs due to?
Severe stenosis of the proximal subclavian artery, which leads to reversal in blood flow from the contralateral vertebral artery to the ipsilateral vertebral artery.
Patients may have symptoms related to arm ischemia in the affected extremity (eg, exercise-induced fatigue, pain, paresthesias) or vertebrobasilar insufficiency (eg, dizziness, vertigo)
What is the relation of plasma cells and multiple myeloma?
Multiple myeloma is associated with the clonal proliferation of plasma cells in the bone marrow.
This prevents normal B cell lymphogenesis and increases the risk of bacterial infection due to decreased production of normal immunoglobulins
What is seen in patients with mullerian agenesis (ie, Mayer-rokitansky-kuster-hauser syndrome)?
Patients have variable uterine development and no upper vagina (eg, shortened vagina). These patients are 46,XX females with normal ovaries and secondary sex characteristics.
Upper motor neuron lesions (ie, internal capsule stroke) cause what?
Contralateral weakness with clasp-knife spastic rigidity, hyperreflexia, and a positive Babinski sign.
These lesions damage the pyramidal motor system (eg, corticospinal tracts), which runs from the precentral gyrus (primary motor cortex) through the internal capsule to the brainstem and spinal cord
What is nonexertional heat stroke? What meds can cause it?
Nonexertional heat stroke is a life threatening disorder characterized by hyperthermia (typically >104F) associated with CNS dysfunction (eg, encephalopathy, syncope).
Anticholinergic meds (amitrptyline, scopolamine) promote heat stroke by impairing diaphoresis. Other meds: sympathomimetics, dopamine antagonists, diuretics, and beta blockers
What is hereditary hemochromatosis?
Characterized by increased intestinal iron absorption with deposition of excess iron in parenchymal tissues.
Men typically develop manifesations in their 30s/40s. However, premenopausal women have ongoing blood and iron losses due to menstruation, which partially offsets the excess iron absorption and delays the onset of symptoms
What meds should not be used in patients with hereditary angioedema?
ACE inhibitors (-prils)
What is Duchenne muscular dystrophy caused by?
Caused by frameshift mutations (most common) or nonsense mutations in the dystrophin gene that lead to the formation of a truncated, defective protein.
Duchenne musclar dystrophy presents with progressive proximal muscle weakness in young boys due to increased muscle fiber degeneration.
Nonsense mutations introduce premature stop codons (UAA, UAG, UGA) in the coding sequence of mRNA.
What is seen in 17-alpha hydroxylase def?
A rare form of congenital adrenal hyperplasia characterized by impaired synthesis of androgens, estrogens, and cortisol with excess production of mineralocorticoids,
Genetic males with this may have phenotypically female external genitalia and present with hypertension and hypokalemia around the expected time of puberty.
What is seen in Niemann-Pick disease?
AR disorder; Ashkenazi Jews
It is characterized by sphingomyelinase def and sphingomyelin (phospholipid) accumulation, which cause neurologic regression, hepatosplenomegaly, and retinal opacification (ie, cherry red macula)
What is first seen microscopically for an ischemic stroke?
12-24 hours after irreversible ischemic injury = intense eosinophilic staining of the neuronal cytoplasm (red neurons) and nuclear fragmentation.
Neuronal damage after hypoxic-ischemic injury is often related to the formation of?
Reactive oxygen species, which mediate widespread cellular damage.
Therapeutic hypothermia decreases the formation of reactive oxygen species by decreasing cellular metabolism and slowing reperfusion.
Adverse effects of amphotericin B
nephrotoxicity, hypokalemia, and hypomagnesemia
MOA of amphotericin B
binds the ergosterol of fungal cell membranes to exert its antifungal effects. However, it also binds cholesterol to some degree, causing toxicity to human tissues.
What is Wilson disease?
AR; excessive copper deposition into tissues (liver, basal ganglia, cornea).
Presents in young adults with liver disease, neuropsychiatric symptoms (eg, gait disturbance, dysarthria, depression, personality changes) and Kayser-Fleischer rings on slit lamp exam.
What is pernicious anemia>
Autoimmune disorder caused by the cell-mediated destruction of parietal cells in the superficial upper glandular layer of the gastric body and fundus.
Parietal cells are responsible for the secretion of hydrochloric acid and intrinsic factor, a glycoprotein involved in the absorption of B12. Def leads to megaloblastic anemia and neurologic dysfunction.
What is horseshoe kidney?
A congential anomaly in which fusion of the metanephros (specifically, metanephric blastema) results in fused renal parenchyma along the inferior poles.
Most patients are asymptomatic, but some may develop recurrent urinary tract infections or nephrolithiasis due to abnormal urine flow through the malpositioned kidney and ureters.
Mutations affecting the Kozak consensus will effect?
The Kozak consensus sequence occurs on eukaryotic mRNA and helps initiate protein translation by identifying the proper methionine start codon AUG
B thalassemia results in what type of anemia?
Hypochromic, microcytic anemia due to decreased B globin chain synthesis.
Unpaired alpha chains precipitate within red cells and cause membrane damage, leading to ineffective erythropoiesis and hemolysis
Hypertrophic cardiomyopathy is a common cause of sudden cardiac death in young adults. Histologic features include?
Cardiomyocyte hypertrophy and myofiber disarray with increased interstitial fibrosis. The structural disarray creates a substrate for ventricular arrhythmia (eg, ventricular tachycardia, ventricular fibrillation) that can lead to SCD.
Gout occurs with increased frequency in patients with what mutations?
Activating mutations involving phosphoribosyl pyrophosphate synthetase due to increased production and degradation of purines
What is first line therapy for acute gouty arthritis?
NSAIDS. They inhibit cyclooxygenase and exert a broad anti-inflammatory effect that includes inhibition of neutrophils.
When NSAIDS are contraindicated (eg, peptic ulcer disease, renal impairment), colchicine is useful in the acute management of gout as it inhibits neutrophil chemotaxis and phagocytosis by preventing microtubule formation
How does potassium pass through the nephron?
K+ is freely filtered by the glomeruli and is mostly reabsorbed in the proximal tubule and loop of henle.
As such, the late distal and cortical collecting tubules are the primary sites for regulation of K+ excretion in the urine.
K+ depletion stimulates alpha-intercalated cells to reabsorb extra K; principal cells secrete K under conditions of increased K+ load.
A stroke impacting the thalamus can lead to?
Sensory loss affecting all tactile modalities (eg, touch, pain/temp, vibration/proprioception) in the contralateral face, arm and leg
Lacunar infarctions are the result of?
Small vessel occlusion (due to lipohyalinosis and microatheroma formation) in the penetrating vessels supplying the deep brain structures.
uncontrolled hypertension and diabetes are major risk factors.
Where does clear cell carcinoma (renal cell subtype) like to metastasis?
Clear cell carcinoma is the most common subtype of renal cell carcinoma and is composed of large,rounded, or polygonal cells with clear cytoplasm.
These tumors are often detected incidentally at an advanced stage; the lung is the most common site for metastasis, followed by osteolytic bone and liver
What is postpartum thyroiditis?
Postpartum thyroiditis occurs within 12 months of pregnancy and is characterized by autoimmune destruction of thyroid follicles.
It typically begins with a hyperthyroid phase due to the release of preformed thyroid hormone, following by a hypothyroid phase due to depletion of thyroid hormone and an eventual return to a euthyroid state.
What is seen on histo for postpartum thyroiditis?
lymphocytic infiltration with the formation of germinal centers, which is similar to chronic lymphocytic (Hashimoto) thyroiditis
What is monoamine oxidase?
Monoamine oxidase is a mitochondrial enzyme that breaks down monoamine neurotransmitters (eg, dopamine, norepi, serotonin).
Tyramine-induced hypertensive crisis can occur in patient taking MAO inhibitors who consume foods containing high amounts of tyramine (eg aged cheeses, cured meats, draft beers)
In silicosis, internalized silica particles impair?
Impair macrophage function by disrupting phagocytosis and promoting apoptosis. This increases the risk of mycobacteria infection (particulary M tuberculosis)
What is cholangiocarcinoma? Imaging shows?
A malignancy of the bile duct epithelium that eventually obstructs biliary drainage, resulting in cholestasis (elevated alkaline phosphatase, hyperbilirubinemia) with jaundice, weight loss, pain the RUQ, and hepatomegaly.
Imaging: dilated bile ducts in the absence of an obstructive gallstone, and biopsy reveals adenocarcinoma with columnar cells, mucin production, and a significant desmoplastic reaction.
What can be injured during pelvic surgery>
The ureter can be injured during pelvic surgery due to its proximity to major pelvic ligaments and vessels such as the uterine artery within the cardinal ligament.
Unintentional suturing of the ureter can present postoperatively with unilateral back pain (ie hydronephrosis) due to ureteral obstruction
Cleavage of proinsulin in pancreatic beta cell secretory granules yields?
insulin and C-peptide, which are stored in the granules until they are secreted in equimolar amounts
How does T1DM typically present?
Typically presents sub acutely with polyuria and polydipsia accompanied by fatigue and weight loss.
Dx can be confirmed with a fasting blood glucose or hemoglobin A1c measurement.
What is efficacy?
A measure of the maximum pharmacodynamic effect achievable with a drug
What is potency?
Refers to the dose of drug that is required to produce a given effect
Drugs that bind their receptors with a higher affinity or are better able to gain access to their target tissues will have greater potency (lower ED50).
What is referred otalgia?
Referred otalgia is common in head and neck pathology because many cranial nerves innervate the ear (eg, CN V, VII, IX, X).
In particular, tumors in the hypopharynx, larynx, or base of tongue cause referred otalgia due to sensory contributions from the glossopharyngeal and vagus nerves.
