5.13.2015 UWorld Notes Flashcards
Bitemporal hemianopsia; not menstruated in 4 months, which of the following embryologic layers does this woman’s lesion most likely originate?
Surface ectoderm (anterior pituitary)
Intense generalized pruritus, found to have high alkaline phos, high titers of antimitochondrial Ab. Liver biopsy performed. What will be shown on liver biopsy?
Graft vs host disease
Primary biliary cirrhosis: Chronic liver disease characterized by autoimmune destruction of intrahepatic bile ducts and cholestasis.
Disease is focal and variable with wide range in severity evident in different portions of liver. In precirrhotic stage, interlobular bile ducts are destroyed by granulomatous inflammation and heavy portal tract infiltrate of macrophages, lymphocyte PREDOMINANT, plasma cells, and eosinophils.
It looks most similar to immunologic injury that also happens in graft vs host disease.
End-stage liver findings in PBC look like secondary biliary cirrhosis or chronic hepatitis.
Other liver diseases and findings:
Alcoholic hepatitis: Hepatocellular swelling and necrosis, Mallory bodies, neutrophilic infiltration, fibrosis.
Acetaminophen overdose: Liver failure and centrilobular necrosis that can extend to include entire lobule.
Reye’s syndrome: Microvesicular steatosis.
Hemochromatosis: Deposition of hemosiderin in liver. Cirrhosis may eventually happen.
Budd Chiari syn: INCREASED INTRAHEPATIC BLOOD PRESSURE. Hepatomegaly, abdominal pain, ascites secondary to thrombosis of hepatic vein. Liver=swollen, red, purple, tense capsule, centrilobular congestion and necrosis.
Lead tie bias, allocation bias, detection bias
Lead time bias: Screening test diagnoses a disease earlier than it would have appeared by natural history so time from diagnosis until death is prolonged.
Allocation bias: Subjects assigned to study groups in non-random fashion.
Detection bias: A risk factor may lead to extensive diagnostic investigation and increase probability that disease is identified. Patients who smoke may undergo increased imaging surveillance due to smoking status.
Likelihood ratios
Likelihood ratios>1 indicate respective test result is associated with presence of disease; likelihood ratios
Lyonization
Uneven inactivation of maternal/paternal X chromosome due to chance alone.
May result in females developing X-linked recessive condition.
Inactive X chromosome condensed heterochromatin which can be identified as compact body at periphrey of nucleus (Barr body).
Heterochromatin is heavily methylated DNA and deacetylated histones. Low level of transcriptional activity.
A small proportion of genes remain transcriptionally active on inactivated X chromosome. This leads to clinical sx of Turner and Klinefelter syndromes (gene-dosage effect).
Other random info:
During DNA replication, supercoiling occurs in region ahead of replication fork and most be removed by topoisomerases.
Double strand DNA breakage can occur after ionizing radiation. These are more prone to faulty repair.
Impaired mismatch repair is associated with hereditary nonpolyposis colorectal cancer.
Which of the treatment options would increase patient’s (with T2DM) serum C-peptide level?
Glyburide
Insulin synthesized in pancreatic B cells as prepronsulin which is guided by signal peptide into rough ER. Signal peptide is removed and preproinsulin converted to proinsulin. Protein folding and disulfide bond formation take place as proinsulin traverses RER. Proinsulin is then transported to Golgi where it is packaged with proteolytic enzymes into insulin secretory granules. In these granules, proinsulin is cleaved into mature insulin and C peptide. C peptide stays in circulation and is marker of insulin!
T2DM: Insulin resistance and relative insulin deficiency.
Sulfonylureas (glyburide) increase insulin secretion rate of residual pancreatic islet B cells and reduce blood glucose levels in patients with Type 2 diabetes mellitus. Circulating C peptide levels rise with sulfonylurea use.
Other medications:
Acarbose inhibits alpha glucosidase in intestinal brush border impairing hydrolysis of carbs and leading to decreased glucose absorption. May indirectly decrease endogenous insulin by reducing postprandial hyperglycemia.
ACE inhibitors: Renoprotective agents that decrease progression of diabetic nephropathy. They do not affect insulin secretion.
Metformin and rosiglitazone do not have direct effect on insulin secretion. They reduce hepatic glucose production and increase insulin sensitivity.
Precocious puberty and height
Precocious puberty in Caucasian females is development of secondary sex characteristics at age less than 7 years.
Sex steroids initially increase linear growth but they encourage closure of epiphyseal growth plates. Growth spurt then irreversible closure of epiphyseal plate.
Gigantism is caused by excessive pituitary production of GH. These patients acheive enormous heights because excessive IGF1 does not lead ot premature closure of epiphysis. Somatomedin C=IGF1
Long hx of diarrhea, crampy abdominal pain. Ulcerative cholitis. Patient’s condition improves w/o treatment. Increase in which of the following cytokines would contribute to this?
IL10: Inhibits IL2 and IFN gamma production by TH1 cells. Enhances IL4 and IL5 production by TH2 cells. Inhibits TNF-alpha and IL12 production by monocytes and decreases NK cell IFN gamma production.
TGFB is another inhibitory cytokine.
Other cytokines:
TNFalpha: Proinflammatory synthesized by T cells and monocytes. Induces nuclear factor KB to produce inflammatory mediators: IL1, IL4, IL5, IL12. IL promotes fever and other systemic responses.
7 yo male colicky abdominal pain and arthralgias. Stool is positive for occult blood and u/a shows mile proteinuria. Palpable lesions over LE which are caused by
Circulating immune complexes
Palpable skin lesions in associated with abdominal pain, arthralgias, renal involvement: Henoch-Schonlein pupura. This disease affects kids aged 3-10. Antigen exposure from bacterial/viral infection in susceptible individuals leads to IgA production and immune complex formation. Deposition of these IgA immune complexes on blood vessel walls and in renal mesangium activates complement and leads to inflammation. HSP manifests cutaneously as form of leukocytoclastic vasculitis. Pts have elevated serum IgA and circulating IgA containing immune complexes.
Other disorders:
Meningococcemia: Petechiae on trunk/legs and spreads over entire body. Fever, hypotension, tachycardia (severe sepsis).
IgE dependent basophil degranulation occurs in atopic and anaphylatic reactions (Type I hypersensitivity). Ag binds to ag-specific IgE on surface mast cells and basophils and triggers degranulation with release of histamine, serotonin, other vasoactive substances.
Ab-dependent cellular cytoxicity: Part of body’s defense against viral and parasitic infections. Fc receptor on NK cells, macrophages, and eosinophils binds to Ag-Ab complexes and signals death of infected cells.
Delayed hypersensitivity reactions with intracellular organisms such as M TB and fungi. Delayed hypersensitivity is mediated by activated macrophages that form granulomata.
Gene coding enzyme that synthesizes fungal cell wall polysaccharide is mutated. Fungal pathogen might develop resistance to which of the following agents?
Caspofungin=Cell wall (most active gainst candida species and aspergillus; not active against cryptococcus neoformans and has limited activity against Mucor and Rhizopus species).
DNA/RNA synthesis=Flucytosine
Cell membrane=Amphotericin B and Nystatin bind ergosterol
Azoles inhibit synthesis of ergosterol
Terbinafine used in skin and nails to treat dermatophytosis. Inhibits fungal enzyme which ultimately results in decreased synthersis of ergosterol.
Griseofulvin enters fungal cells, binds to mts and inhibits mitosis. Antifungal drug is effective only againster dermatophyte fungi. Accumulates in keratin containing tissues.
Flucytosine plus amphotericin B used in cryptococcal meningitis.
Amyl nitrite from lab safety kit administered which affects affinity of Hb for what?
Cyanide
Cyandie binds to iron containing enzymes like cytochrome a-a3 complex which is needed for electron transport during oxidative phosphorylation. Inhibits aerobic metabolism and rapidly results in death.
Amyl nitrite causes formation of methemoglobin which cannot carry O2 but has high affinity for cyanide. Sequesters it in the blood and keeps poison away from mitochondrial and other enzymes.
Sodium thiosulfate also used for cyanide poisoning: Combines with cyanide to form less toxic thiocyanate which is excreted in urine.
Lead poisoning=defective heme synthesis. Chelation therapy with dimercaprol or CaNaEDTA should be started.
GFR, RPF, FF
GFR=Volume of fluid filtered from renal glomerular capillaries into Bowman’s capsule per unit time.
RPF is volume of plasma delivered to kidney per unit time. Depends on circulating blood volume and resistance of afferent and efferent arterioles. RPF is maintained at constant level by local changes in vascular resistance (between 100-200 mm Hg).
Filtration fraction is ratio of glomerular filtration rate to renal plasma flow: FF=GFR/RPF.
Pt is severely hypovolemic (profuse diarrhea and vomiting). This leads to decrease in RPF which is intensified by baroreceptor mediated increase in renal symp. vasoconstriction. Hypovolemia also stimulates renin–>angiotensin II which constricts EFFERENT glomerular arteriole which increases hydostatic pressure in glomerular capillaries to maintain GFR.
Decrease in GFR in hypovolemia is less pronounced than decrease in RPF resulting in increased filtration fraction because FF=Low GFR/lower RPF.
Coffee ground appearing emesis: BP of 70/40 mm Hg, heart rate 130/min, extremities cool to touch. Infusion of 2L normal saline will…
Increase end-diastolic sarcomere length
Brisk upper GI bleed. Coffee ground color=blood oxidized/exposed to gastric acid. Hypovolemia=symph. n.s. which constricts arteirolar and venous beds and stimulates heart. Constriction increases total peripheral resistance to maintain end organ pressure. Shunt blood away from extremities and skin and toward vital organs. Constriction of venous circulation increases blood return to heart maintaining PL. Stimulation of heart results in increased CTY and HR.
PL increase from fluids extends end diastolic sarcomere length in ventricular myocardium increasing SV and CO.
Diastolic ventricular compliance is affected by pathologic processes acting on heart: Amyloid cardiomyopathy and hypertrophic cardiomyopathy (two processes that decrease compliance). Dilated cardiomyopathies increase ventriuclar compliance.
56 homeless man with increased fatigability and exertional dyspnea. PE shows significant LE edema and decreased sensation over ankles and feet. Cardiac dilation and increased cardiac output. Nutrient deficiency?
Vitamin B1 (Thiamine)
Thiamine deficiency associated with berberi and Wernicke Korsakoff syndrome. Infantile berberi=cardiac syn with cardiomegaly, tachycardia, cyanosis, dyspnea, vomiting.
Adult beriberi=Dry or wet
Dry=Symmetrical peripheral neuropathy with sensory and motor impairments especially of distal extremities.
Wet beriberi=Neuropathy plus cardiac (cardiomegaly, cardiomyopathy, CHF, peripheral edema, tachycardia)
Vitamin A deficiency=Night blindness, xerophthamlia, vulnerable to infection (esp measles)
Vitamin B2 (riboflavin) deficiency: Cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization, and ariboflavinosis.
Pyridoxine (Vitamin B6) deficiency is characterized by cheilosis, glossitis, dermatitis, peripheral neuropathy.
Niacin deficiency: Pellagra (dementia, dermatitis, diarrhea)
Ascrobic acid (vitamin C deficiency is scurvy (hemorrhages, bleeding into joint spaces, gingivial swelling, impaired wound healing, weakened immune response to local infections.
Vitamin B12 (cobalamin) deficiency is associated with pernicious anemia. Older mentally slow woman of northern European descent with is lemon colored (anemia and icteric) and has smooth shiny tongue indicative of atrophic glossitis and has shuffling broad based gait.
Burn patient infection
Pseudomonas aeruginosa is major pathogen in burn patients.
Only a few specific penicillins (ticarcillin, piperacillin) and cephalosporins (ceftazidime, cefepime) have activity against it.
Aminoglycosides, fluoroquinolones=ciprofloxacin, levofloxacin, carbapenems=meropenem, imipenem are also effective.
