test #9 3.23 Flashcards
which antidepressant is good for (1) depression w/ psychomotor retardation or hypersomnia (2) depression w/ smoking cessation desire (3) w/o sexual dysfxn
buproprion (NDRI and nAch-agonist). has stimulatory effects.
which antidepressant is good for patients w/ insomnia. side effect?
trazodone (highly sedating antidepressant, but can cause priapism & other sexual side effects. SARI – 5-HT antagonist and reuptake inhibitor.
SSRI-induced sexual dysfxn in what %age? what 3 types?
50%. decreased libido, anorgasmia, and increased latency to ejaculation.
electrolyte abnormalities w/ hyperaldosteronism
hypokalemia, metabolic alkalosis. normal Na+ bc of aldosterone escape
describe aldosterone escape
hypernatremia is not seen w/ hyperaldosteronism. increased Na+ reabsorption –> intravascular hypervolemia –> promote ANP release –> diuresis –> compensatory Na+ loss.
presentation of primary mineralcorticoid excess
HTN, hypokalemia, suppressed renin, non-suppressible aldosterone
normal serum Na+, hypokalemia, metabolic acidosis suggests..
renal tubular acidosis
renal tubular acidosis types (1, 2, and 4)
1: distal: failure of H+ secretion by alpha-intercalated cells (hypokalemia) 2: proximal: failed HCO3- reabsorption in PCT 4: adrenal: aldosterone deficiency or resistance
renal tubular acidosis explanation
inability to acidify urine
how do CAG repeats in huntingtin gene lead to disease
code for abnormal huntingtin protein that decreases expression of OTHER genes by inhibiting transcription (hypermethylation of histone fragments). SILENCE of other neurotrophic genes
mutation of homeodomain gene would lead to..
alteration in body structure // spontaneous abortion
is macrocephaly a typical feature of common chromosomal syndromes
no
cleft palate, polydactylyl, rocker-bottom feet associated w/
trisomy 13 (patau syndrome)
down’s syndrome have increased risk of..
AML-M7 and ALL in childhood. Alzheimer’s in adulthood
common presentation of trisomy 21 (5)
mental retardation, facial dysmorphism, single palmar crease, endocardial cushion defects, duodenal atresia
case-control
select those w/ disease & w/o disease. then look back to look at exposure. calculate odds ratio
controls in a case-control experiment
individuals w/o disease (w/ and w/o exposure). goal: exposure frequency among non-disease general population
carcinoid heart disease (associated w/ carcinoid syndrome)
fibrous intimal thickening w/ endocardial plaques limited to the RIGHT heart (bc both 5-HT and bradykinin in blood are inactivated distally by pulmonary vascular endothelial monoamine oxidase). can result in pulmonic stenosis and restrictive cardiomyopathy.
carcinoid syndrome symptoms. results from?
skin flushing, abdominal cramping, nausea, vomiting, diarrhea. results from production of serotonin, kallikrein, bradykinin, histamine, prostaglandins and/or tachykinins produced by carcinoid tumor.
degree of endocardial fibrosis seen in carcinoid heart disease correlates w/..
plasma levels of serotonin and urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid)
elevated plasma levels of homocysteine associated w/..
arterial and venous thrombosis. also atheroscerlosis
common way to injur PCL
MVA
lateral vs. medial meniscus
lateral – rounder and covers a larger portion of the articular surface
lateral vs. medial articular surface of knee size
medial articular surface is larger, as it bears more body weight
conversion disorder
characterized by neurological symptoms (nonepileptic seizures, blindness, loss of sensation, weakness, paralysis) that are anatomically or physiologically inconsistent w/ neurologic disease but are NOT FEIGNED.
2 most important mechanisms involved in the development of complications w/ diabetes
(1) advanced glycosylation end products (2) polyol pathway impairment
describe how advanced glycosylation end products –> diabetic complications (microangiopathy, neuropathy, atheroscerlosis)
attach glucose to amino acids (reversible –> irreversible), accumulate & cross-link w/ collagen in blood vessel walls & interstitial tissue (MICROANGIOPATHY and NEUROPATHY). cross-linking also facilitates inflammatory cell invasion & deposition of LDL in vascular walls –> ATHEROSCLEROSIS
describe how polyol pathway impairment –> diabetic complications (cataracts & peripheral neuropathy)
in tissues that do not depend on insulin for glucose transport (lens, peripheral nerves, blood vessels, kidney). glucose –> sorbitol (via aldose reductase). sorbitol –> fructose. both sorbitol & fructose increase osmotic pressure in tissue –> osmotic cellular injury. increased water in lens fiber cells –> rupture of cells –> opacification of lens and CATARACT formation. osmotic injury of Schwann cells –> PERIPHERAL NEUROPATHY
which main tissues do not rely on insulin for glucose transport
lens, peripheral nerves, blood vessels, and kidney
why do patients w/ galactosemia get cataracts?
galactose –> galactitol (via aldose reductase) –> osmotic damage of lens cells
silent mutation
code for same amino acid
missense
conservative: diff amino acid, but similar. nonconversative: diff amino acid entirely
nonsense
premature stop codon
short-acting benzodiazepine (2)
triazolam, alprazolam (<6 hours)
intermediate acting benzodiazepine (1)
lorazepam (6-24 hours)
long-acting benzodiazepine (3)
diazepam, flurazepam, chlordiazepoxide ( > 24 hours)
if patient has increasing anxiety before SSRI effects kick-in (as it takes 4 wks).. you can..
give a benzodiazepine (choose short, intermediate, long)
benzodiazepine of choice for person in mission-critical position?
triazolam, short short-acting
triad of congenital toxo
hydrocephalus, intracranial calcifications, and chorioretinitis (inflamm of choroids and retina that can leave cotton-like white/yellow scars on retina)
when can toxoplasma be transmitted in utero
only if mother infected during first 6 months of pregnancy.
common complication of prematurity is?
intraventricular hemmorhage (can lead to long-term neurodevelopmental impairment) almost always occurs in infants born before 32 wks and/or birthweight <1500g. within first 5 postnatal days
presentation of intraventricular hemorrhage in infant (3 levels of severity)
either (1) silent (2) altered consciousness, hypotonia, decreased spontaneous movt (3) bulging anterior fontanelle, hypotension, decebrate posteruring, tonic-clonic sz, irregular respiration, coma
where does intraventricular hemorrhage in infant originate?
germinal matrix: highly cellular and vascularized layer in subventricular zone (from which neurons and glial cells migrate out during brain development). less prominent in 24-32 wks.
describe the germinal matrix
in ventricles, contains numerous thin-walled vessels lacking glial fibers that support other blood vessels throughout the brain (contribute to intraventricular hemorrhage) becomes less prominent in 24-32 wks of gestation (reducing risk of IVH)
shaking baby syndrome causes
tear of cortical bridging vein. subdural hematoma
epidural hematoma
head trauma, tear middle meningeal artery. usu associated w/ temporal bone fracture
PE results in…
acute pulmonary V/Q imbalance –> hypoxemia –> hyperventilation –> respiratory alkalosis
LPS structure (3 regions)
very long, heat-stable molecule. 3 regions: O antigen, core polysaccharide, lipid A. lipid A –> toxic properties.
how is LPS released into circulation
released during division or bacteriolysis. NOT ACTIVELY SECRETED>
septic shock associated w/ systemic release of which signals
IL-1 and TNF-alpha (fever, hypotension, diarrhea, oligouria, vascular compromise, and DIC)
what innervates the posterior wall of the external auditory canal? remainder external portion? internal portion?
posterior wall external auditory canal – Vagus (small auricular branch)
remainder of external auditory canal including the external portion of the tympanic membrane – Trigeminal (mandibular division) via auriculotemporal branch.
inner surface of TM –> glossopharyngeal nerve (tympanic branch)
cutaneous sensation from vagus nerve?
to posterior external auditory canal via small auricular branch. (rest of canal is CN V3)
vasovagal syncopal episode during otoscope exam?
touch posterior wall of external auditory meatus, decrease BP and HR
chorda tympani carries (2)
(1) afferent taste fibers from anterior 2/3 of tongue (2) efferent parasympathetic preganglionic fibers to submandibular and sublingual glands
anatomical landmark of left ventricle
fifth left intercostal space at left midclavicular line. covered by LUNGS. to penetrate left ventricle, would need to be DEEP. all other heart structures lie left to midclavicular line
anatomical landmark of right ventricle
forms anterior (sternal) surface of heart, and majority of inferior border. lies left of midclavicular line
t/f: lung overlies much of the anterior surface of heart
TRUE
first line treatment for atrial fibrillation w/ rapid ventricular response (AF w/ RVR)? second line?
first line: diltiazem, verapamil and B-blockers. second line: digoxin, bc it slows conduction through AV node (via vagal stimulation)
delayed afterdepolarizations. what drug can trigger this?
can occur after complete repolarization of the cardiac myocytes in states of hyperexcitability (i.e. very high intracellular Ca++ or high catecholamine stimulation states). digoxin toxicity can lead to this (as it increases intracellular Ca++)
what does decreased AP duration lead to?
decreased refractory period –> allow cardiac pacemaker cells to fire / conduct AP w/ greater frequency.
the shorter the refractory period of atria..
the more frequently the cells can depolarize (predispose to atrial fibrillation)
what are the blood pressure limits in diabetics?
normal blood pressure limits LOWER.
normal loss of albumin in urine? microalbuminuria?
normal loss: 20mg/day or less. microalbuminuria: loss of 30-300mg/day. indicates diabetic nephropathy.
what level of protein concentration can be detected by urinalysis
MACROalbuminuria: greater than 300
note: microalbuminuria 30-300mg/day
name 3 alpha-1-blockers (HTN and BPH)
doxazosin, prazosin, terazosin
drug of choice for HTN in patients w/ coronary artery disease & CHF?
cardioselective beta-blockers like metoprolol and atenolol
drug of choice for essential HTN in general population, osteoperosis, and isolated systolic HTN?
hydrochlorothiazide
isosorbide dinitrate
rx: stable angina pectoris. decrease CO by venodilitation –> decrease preload.
almost half of all UTIs in sexually active young women caused by
staphylococcus saphrophyticus (resistant to novobiocin & coag neg)
which bacterial species produces DNAse?
group A strep. degrades DNA in pus to facilitate spread of organism. (can use antiDNAse test in pts w/ strep infxn and glomerulonephritis)
cushing disease (excess ACTH) results in hyperplasia of..
adrenocortical zona fasiculata and reticularis
(1) acute-onset CVP >15 cm H20 (central venous pressure, as demonstrated by increased JVD) and (2) hypotension w/ tachycardia indicates (3) pulsus paradoxus
cardiac tamponade or tension pneumothorax
cause of cardiac tamponade
serous viral pericarditis and significant acute pericardiac effusion
beck’s triad of cardiac tamponade
(1) hypotension (2) distended neck veins (3) distant/muffled heart sounds on auscultation, as well as tachycardia. also, pulsus paradoxus
acute fibrinous pericarditis follows? causes?
follow an URI. causes pleuritic chest pain and pericardial friction rub
constrictive pericarditis
chronic process that requires months-> years to produce constriction sufficient to cause tamponade. not acute!
maple syrup urine disease
defective breakdown of branched chain amino acids (leucine, isoleucine, and valine). defective branched chain alpha-keto acid dehydrogenase. build up of alpha-keto acid in tissue and serum –> neurotoxicity
when does maple syrup urine disease manifest? rx?
usu first few days of life. urine –> burned caramel. can be life threatening. rx: dietary restriction of branched-chain amino acids
hypermethioninemia
benign disorder, defective metabolism of methionine by enzyme methionine adenosyltransferase.
where is PAH secreted into nephron lumen?
proximal tubule. lowest conc of PAH in luminal fluid is bowman’s space
most common congenital anomalies seen in women and men are..
accessory nipples (polythelia). usu asymptomatic, but can swell or become tender along w/ other breast tissue. and become symptomatic in pregnancy.
how does polythelial occur? where do they occur?
accessory nipples. failure of appropriate involution of mammary ridge. can occur anywhere along embryonic milk line at lower chest and abdomen, and are bilateral in 50% of patients.
what are ephelides
freckles. hyperpigmented, usu not raised. small and found on sun-exposed areas. don’t change w/ hormone
keloid
raised and can be pigmented. occur as a result of scarring from some type of trauma to skin. not influenced by menstrual cycle
lipomas
benign fatty tumors felt under skin. no hyperpigmentation. not influenced by mentstrual cycle hormone changes
cutaneous neurofibromas are? what do they contain?
benign, soft, flesh-coloured, or lightly pigmented skin nodules. consisting of schwann cells and neural fibroblasts.
button-hole sign of neurofibroma
applying pressure to neurofibroma can cause them to retract into subcutaneous tissue.
the most common skin lesion
nevi, often confused w/ accessory nipple. can be raised and hyperpigmented. not influenced by hormonal changes.
jaw claudication // chewing difficulty
most specific symptom of giant cell (temporal) arteritis. granulomatous inflammation of the media. tend to be > 50y/o
medial granulomas are seen in which vasculitides?
(1) giant cell / temporal arteritis (2) takayasu arteritis
takayasu arteritis
usu affects aortic arch (w/ remainder of aorta and its branches in 1/3 of pts) medial granuloma. usu females < 40.
distinction between dian cell lesions of aorta is often made on..
patient’s age. > 50 = giant cell (temporal) arteritis. < 40 y/o female = takayasu arteritis.
leukocytoclastic vasculitis = microscopic polyangiitis, microscopic polyarteritis, hypersensitivity vasculitis
segmental fibrinoid necrosis of small vessels. histologically similar to polyarteritis nodosa
polyarteritis nodosa
segmental transmural necrotizing inflammation of medium to small-sized arteries.
thromboangiitis obliterans (buerger’s disease)
thrombosing vasculitis of medium and small sized vasculature (principally tibial and radial artery). most commonly seen in heavy smokers w/ onset prior to 35 y/o
rheumatoid arteritis
hypersensitivty vasculitis affecting arterioles and arteries of any size. visceral infarctions after long-standing rheumatoid arthritis. pathology = similar to polyarteritis. diff from giant cell.
immunity to reinfection w/ influenza type A (and likely B and C) mediated by..
predominately by specific anti-hemagglutinin IgA and IgG antibodies
rx: for acute decompensated congestive heart hailure?
aim to reduce volume overload. LOOP DIURETICS. maximum diuresis in shortest test.
3 common uses for furosemide, toresmide, bumetanide, ethacrynic acid
(1) pulmonary edema (2) venous and pulmonary congestion secondary to CHF (3) peripheral edema
common and less common side effects of loop diueretics
common: hypokalemia, hypomagnesemia, hypocalcemia. less common: volume depletion, hponatremia, decreased GFR, hypotension, OTOtoxicity
who secretes von willebrand factor? what is it attached to?
endothelial cells; circualtes in multimers that are noncovalently attached to factor VIII (increases its stability)
DDAVP causes..
increases vWF secretion from endothelial cells (increase in 30-60min). useful in mild vWD. is similar to vasopressin but not identical
how is DDAVP unlike vassopressin.
DDAVP has only minimal effect on V1 vasopressin receptor (therefore, little vasoconstriction)
DDAVP in hemophilia A?
increases vWF, increases stability of factor VIII
where are most clotting factors formed. what is the exception
most clotting factors = liver. vWF = endothelial cells.
treatment of enuresis
DDAVP tablets
definition of orthostatic hypotension
fall of >20mm in systolic or >10mm in diastolic BP when upright. standing causes pooling of significant amount of blood in veins (500-1000ml)
list 4 ways standing alters hemodynamics
(1) decreased venous return to heart (2) decreased ventricular filling and subsequent drop in CO and BP (3) drop in BP stimulates compensatory baroreceptor reflex (4) increased sympathetic tone raises peripheral vascular resistance through alpta-1-adrenoreceptors –> increased venous return and cardiac output
what does active antithrombin III do?
binds factor Xa and prevents it from converting prothrombin –> thrombin
partial pressure of oxygen at which 50% of hemoglobin are saturated (P50)? myoglobin
hemoglobin P50: 26mmHg. myoglobin p50: 1mmHg; has only 1 heme group.
individual subunits of hemoglobin
structurally analogous to myoblohin
hemodynamic actions of epinephrine on 1. HR 2. systolic BP 3. diastolic BP & associated receptors
(1) HR increases, B1 (2) systolic BP increases, B1 and A1 (3) diastolic BP decreases at LOW dose (B2 > A1); increases at HIGH dose (A1 > B2)
effect on diastolic BP depends on dose! low –> B2. high –> A1
phenlyephrine
selective alpha-adrenergic agonist. elevated systolic and diastolic BP, may cause reflex bradycardia.
phentolamine
nonspecific alpha1 and alpha 2 blocker (no beta effect). causes fall in diastolic BP and reflex tachycardia.
isoproterenol
nonspecific beta agonist. vasodilation (B2) and increased HR and contractility (B1)
paroxysmal supraventricular tachycardia caused by…? Rx?
typically results from re-entrant impulse traveling through slowly and rapidly conducting segments of AV node. rx: increase cardiac parasympathetic tone –> carotid sinus massage and valsalva. or adenosine in hospital
how does parasympathetic nervous system slow heart rate?
primarily by slowing conduction through AV node
autosomal dominant polycystic kidney disease pathologic features
mutations in PKD-1 or PKD-2 –> tubular cell proliferation & secretion. any point in nephron, but <5% nephrons affected. microscopic cysts at birth, enlarge over decades. compress renal parenchyma – atrophy & fibrosis
autosomal dominant polycystic kidney disease clinical features
freq clinically SILENT, 50% undiagnosed. flank pain, hematuria, HTN. renal failure slowly over 10-20 yrs. ESRD by 70. extrarenal manifestations (liver cysts, cerebral aneursyms)
multicystic kidney dysplasia
characterized by multiple cysts of varying size in kidney and ABSENCE OF NORMAL PELVOCALICEAL system. condition associated w/ ureteral or ureteropelvic atresia. affected kidney –> nonfxnl. abdominal ultrasound of fetus -> diagnostic.
Auer rods are highly suggestive of..
AML, esp M1 M2 M3, but can be any type.
AML diagnostic criteria
> 20% myeloblasts in peripheral blood or marrow. usu adults, median age 65
presentation of hairy cell leukemia
splenomegaly, cytopenia, circulating hairy cells (small-medium lymphoid cells w/ hairy projections)
why do infants maintain babinski up to 12 months?
incomplete myelination of corticospinal tracts
positive straight leg test
pain elicited in supine patient when leg held straight while raised off examining table – sign of sciatic nerve root (L4-S3) irritation. sensitive for intervertebral disc hernation –> sciatica
how commonly is medullary thyroid cancer familial
20% (part of MEN type 2A&B) or familiary medullary thyroid cancer syndrome
familial medullary thyroid cancer often have
germ-line mutations in RET proto-oncogene.
medullary thyroid cancer arises from..
parafollicular calcitonin-secreting C-cells. uniform polygonal or spindle-shaped cells w/ extracellular amyloid deposits. amyloid stains w/ congo Red
papillary thyroid cancer
papillary structure w/ calcifications (psammoma bodies) and large, ground glass, grooved nuclei.
PSAMMOMA mnemonic
papillary carcinoma of thyroid, serous cystadenocarcinoma, meningioma, and mesothelioma.
large pleomorphic cells in thyroid..
anaplastic thyroid carcinoma, poor prognosis.
collagen subtype 1 & associated disease
bone, ligament, skin (dermis), dentin, cornea, blood vessels, SCAR tissue. associated disease: osteogenesis imperfecta
collagen subtype 2
cartilage, vitreous humor & nucleus pulposus
collagen subtype 3 & associated disease
reticular fibers: skin, lungs, intestines, blood vessels, bone marrow, lymphatics & granulation tissue. associated w/ ehlers-danlos syndrome (type 3 & 4)
collagen subtype 4 & associated disease
basement membrane; associated w/ alport syndrome
evolution of myocardial infarction: (a) 0-4hr (b) 4-12hr (c) 12-24hr (d) 1-5d (e) 5-10d (f) 10-14d (g) 2wk-2mo
(a) 0-4hr: minimal change.
(b) 4-12hr: early coagulation necrosis, edema, hemorrhage, wavy fibers
(c) 12-24hr: coagulation necrosis & marginal contraction band necrosis
(d) 1-5day: coagulation necrosis & neutrophilic infiltrate
(e) 5-10day: macrophage phagocytosis of dead cells
(f) 10-14day: granulation tissue & neovascularization
(g) 2wk-2mo: collagen deposition & scar formation
p27
cell cycle inhibitor. acts during G1 by inhibiting CDKs. normal tissue have high levels of p27. malignant tissues have low p27
retinoblastoma regulation of G1-S transition
active (hypophosphorylated) and inactive (hyperphosphorylated). resting cells (G0) have active Rb. when growth factor stimulation, activation of cyclin D, cyclin E, and *CDK 4 (upreg in response to signal) and 6 occurs, and Rb is hyperphosphorylated (inactivates)–> releases E2F transcription factor. allows progress through G1->S
Ras
part of MAP-kinase cascade. not associated w/ G1-S transition
important CYP inducers
carbamazepine, phenobarb, pheytoin, rifampin, griseofulvin
important CYP inhibitors
cimetidine, ciprofloxacin, erythromycin, azole antifungals, gradefruit juice, isoniazid, ritonavir (protease inhibitors)
general note re: oral antibiotics and drug interaction w/ warfarin
oral antibiotics reduce intestinal bacteria load, reduces vitamin K synthesis, could potentiate warfarin’s anticoagulant effects
structure of collagen molecule
3 polypeptide alpha chains held together by H-bonds (rope-like triple helix)
Ehlers-Danlos clinical manifestation & pathophys
group of rare heriditary disorders involving defect in synthesis of collagen found in skin, tendons, ligaments, and muscles. manifests as over-flexible joints, over-elastic skin, and fragile tissue susceptible to bruising, wounding, and hemarthrosis.
common mutations leading to ehlers-danlos (2)
either deficiencies of (1) lysyl-hydroxylase or (2) pro-collagen peptidase enzymes responsible for collagen synthesis
fibrillin-1 is present in? defects related to
major component of microfibrils that form sheath around elastin. abundant in blood vessels and suspensory ligaments of lens. defects in fibrillin-1 –> autosomal dominant marfans
laminins
heterotrimeric glycoproteins that bind to type IV collagen underlying epithelial cells (organization and fxn of basement membrane)
fibronectin
binds to integrins on cell surface and components of ECM (i.e. collagen and fibrin). fxns as adhesive protein; involved in cellular differentiation, phagocytosis, platelet adhesion, thrombus formation
keratin
major component of hair and skin (in epidermal cells, makes outmost layer of skin waterproof). defects in keratin 5 and 14 –> epidermolysis bullosa simplex
elastin
fibrous protein in CT, can be stretched but will recoil. synthesized from polypeptide precusor tropoelastin. in skin, blood vessels, and lung alveoli
atrophy
loss in cell substance that results in reduced cell size or death. physiologic –> early in develop: regress
physiologic atrophy
regression of notochord & thyroglossal duct in fetus. reduction in maternal uterine size after childbirth.
pathologic atrophy
usu in response to something: decreased physical workload, loss of innervation, decreased blood supply, inadequate nutrition, absent endocrine stimulation, aging, pressure
