test #7 3/16 Flashcards
initiation of translation in prokaryotes requires..
N-formylated methionine-tRNA. initiation codon AUG (methionine) is 6-10 bases downstream Shine-Dalgarno element.
Shine-dalgarno element (prokaryotic translation)
6-10 bases upstream intiation codon AUG. recognizes complementary sequences in 16S rRNA and 30S small ribosomal subunit.
how do aminoglycosides affected prokaryotic translation?
bind to 30S, inhibit formation of initiation complex and protein synthesis.
which antibiotic blocks peptidyltransferase activity of prokaryotic ribosome (1)
chloramphenicol
which antibiotics block the translocation of ribosome along mRNA (2)
clindamycin and erythromycin
difference in p-values between studies suggests..
difference in sample size (i.e. underpowered)
Berkson’s bias
selection bias created by selecting hospitalized patients as the control group
congenital torticollis
noted 2-4 wks of age, child prefers to hold head tilted to one side. usu result of malposition of head in utero (due to fetal macrosomia or oligohydramnios) or birth trauma (breech). sternocledomastoid injury and fibrosis. other musculoskeletal abnormalities: hip dysplasia, metatarsus adductus, talipes equinovarus (club foot)
resolve w/ conservative therapy / stretching
chin pointed away from contracted SCM. head tilted towards muscle.
maternal hypertension on intrauterine growth
intrauterine growth restriction w/ normal-almost normal headaize and reduced abdominal circumference
fragile X-syndrome characterestics
main: MR, facial dysmorphism, macroorchidsm. mild-severe mental retardation, long-thin face w/ prominent forehead and jaw, post-pubertal macroorchidism, large protruding ears, tooth crowding, arched palate
gene abnormality in fragile X syndrome
mutation in FMR1 gene, on long arm of chromosome X. normally has 5-55 CGG trinucleotide repeats. >200 repeats –> transcriptional instability. leads to hypermethylation –> gene inactivation.
chromosomal instability disorders (4)
related to mutations in DNA repair: xeroderma pigmentosum, ataxia-telangiectasia, fanconi’s anemia, bloom syndrome
defective mismatch repair genes result in..
Lynch syndrome (increased risk of heriditary non-polyposis colorectal cancer) and extraintestinal malignancy
tay sach’s deficiency & metabolite build-up
lysosomal storage disease. commonly seen in ashkenazi jews. deficiency in beta-hexosaminidase A. accumulation of cell membrane glycolipid GM2 ganglioside in lysosomes.
tay sach’s clinical presentation
2-6 months – progressive weakness, hypotonia, loss of motor skills, abnormal startle w/ acoustic stimuli, CHERRY-RED MACULA w/ NO hepatosplenomegaly. macrocephaly (accumulation of glycolipid in brain). eventually–> seizure, blindness, spasticity. life expectancy of 2-5 years.
histology of tay sach’s (EM)
neurons w/ cytoplasmic distension and lysosomes w/ onion skin lamellar lipid rings
tay sach’s vs. niemann-pick disease
both have cherry-red macular spot. niemann-pick has hepatosplenomegaly.
formula for NNH (number needed to harm)?
1/attributable risk.
attributable risk = adverse event rate in treatment group - adverse event rate in placebo group.
formula for NNT (number needed to treat)?
1/absolute risk reduction
combined OCP primary mode of action. secondary?
estrogen/progesterone suppress synthesis of FSH and LH (gonadotropins) in anterior pituitary (block LH spike needed for ovulation). also cause thickening of cervical mucus (prevent sperm from entering). also, prevents growth of endometrium, making it difficult for embryo implantation.
what is seen in periventricular plaques of MS? what is in CSF? on visual evoked potentials?
loss of myelin sheaths, depletion of oligodendrocytes, lipid-laden macrophages w/ myelin breakdown products. oligoclonal band on protein electrophoresis. slowed conduction velocity on visual evoked potentials.
PT and PTT and bleeding time in vWF deficiency?
both coagulopathy (factor VIII) and platelet deficiency. PTT and bleeding time elevated.
hemophilia C
very rare autosomal recessive, deficiency in factor XI
factor VIII deficiency
classic X-linked hemophilia. PTT prolonged.
which organ is least vulnerable to infarction? exception?
liver, has dual blood supply. portal vein and hepatic artery. also, retrograde arterial flow from accessory vessels (inferior phrenic, adrenal, intercostal). exception: transplanted liver –> hepatic artery thrombosis (collateral circulation severed during transplantation)
is the spleen vulnerable to infarction? why?
yes, bc perfusion via splenic artery = end-arterial. occurs in sickle-cell anemia, infective endocarditis, cardiac mural thrombosis
how long can the myocardium endure complete arterial ischemia
20-30min w/o severe consequence. briefer periods –> myocardial stunning.
organ susceptibility to infarction after occlusion of a feeding artery (greatest to least)
CNS, myocardium, kidney, spleen, liver.
what ions are responsible for -70mV resting potential?
high K+ conductance, low Na+ conductance (Cl- plays little if any role)
what role do the L-type Ca++ channels in myocyte T-tubules play in excitation-contraction.
NO significant flux of Ca++ from L-type Ca++ channels. Instead, they are triggered by depolarization and TETHERED to RyR1 channels in sarcoplasmic reticulum to release Ca++. skeletal muscles do NOT need extracellular Ca++ to contract!
why don’t calcium channel blockers (i.e. Verapamil, Diltiazem) affected skeletal muscles
these block extracellular Ca++ channels. skeletal muscles do NOT need extracellular Ca++ to contract. instead, L-type Ca++ are tethered to RyR1 on sarcoplasmic reticulum –> source of Ca++
describe cardiac muscle & smooth muscle excitation-contraction. how do they differ?
Ca++ through L-type channels stimulate sarcoplasmic RyR2 channels (calcium-induced calcium release). no mechanical coupling of L-type Ca++ channels and RyR. cardiac muscle = troponin. smooth muscle = calmodulin.
which muscle types have T-tubule system (plasma membrane near sarcoplasmic reticulum)?
cardiac and skeletal muscle (NOT smooth muscle)
describe biofilm formation (foreign body via staph epidermidis)
coated w/ fibrinogen & fibronectin –> serve as binding sites for S. epidermidis. bacteria induce ynthesis of extracellular polysaccharide matrix (encase bacteria). barrier to antibiotic penetration & interferes w/ host defenses (opsonization, neutrophil migration, T-lymphocyte activation). can later disperse pathogen seeds from biofilm.
HSV-1 presentation in children
gingivostomatitis, fever, and lymphadenopathy. intranuclear inclusions.
three endocrine effects of prolactinoma
- inappropriate milk production (galactorrhea) 2. suppression of gonadotrophin-releasing hormone (GnRH form hypothal) –> decreased libido, amenorrhea, infertility. 3. can compress normal pituitary cells (hypopitiutarism)
gonadotroph adenomas..
usu do not produce intact FSH or LH. instead, overproduce alpha subunit of glycoprotein hormones (mass effect & hypogonadism).
most non-secretory adenomas arise from…
gonadotrophs
normal distribution of cell types in anterior pituitary
50% somatotrophs, 20% lactotrophs, 15% corticotrophs, 10% gonadotrophs, 5% thyrotrophs
most common pituitary adenoma? most common cell type in normal pituary?
pituitary adenoma = prolactinoma. major pituitary cell type: somatotrophs.
what is contained in the posterior limb of the internal capsule? genu?
posterior limb: runs between globus pallidus/putamen and thalamus; corticospinal motor and somatic sensory fibers, as well as visual and auditory fibers. genu: corticobulbar fibers. anterior limb: separates caudate from globus pallidus, contains thalamocortical fibers.
insular cortex
limbic system, coordination of some autonomic fxn (cardicac)
25% of patients w/ subarachnoid hemorrhage following ruptured berry aneurysm experience… why? when? Rx?
vasospasm leading to clinical symptoms – altered mental status, focal neurological deficits. result of substances generated after degradation of aubarachnoid blood clots. NO EARLIER than 3 days. usu 7-8 days. rx: calcium channel blockers (decrease morbidity / mortality. nimodipine –> cerebral selective drug.
direct dilation of arteries and inhibition of platelet aggregation?
cilostazol (approved for treatment of intermittent claudication –> peripheral arterial disease. superior to aspirin)
cilostazol (2 effects)
(1) decrease platelet phosphodiesterase (high cAMP) –> inhibits platelet aggregation. (2) direct arterial vasodilator.
Rx: heparin-induced thrombocytopenia
argatroban (DTI)
what enzyme does warfarin block?
vitamin K epoxide reductase (decreases available vitamin K)
3 clinical indications for tPA (altepase)
MI, PE, acute ischemic stroke
Rx: peripheral arterial disease
cilastozol, better than aspirin.
stab above clavicle & lateral to manubrium will cause…
tension pneumothorax
symptoms of tension pneumothorax? tx?
decreased systemic venous return, reduced cardiac output –> tachycardia, hypotension, hypoxia, absence of breath sounds, hyperresonance to percussion on the affected side. tx: emergent needle thoracostomy
ansa cervicalis? how can it be injured?
arises from C1, C2, C3 nerve roots. innervates sternohyoid, sternothyroid, omohyoid muscles of anterior neck. injured if penetrating trauma to the neck superior to cricoid cartilage.
how can CN XI be injured?
surgery involving posterior triangle (sternocleidomastoid, clavicle, trapezius)
inferior thyroid artery course
thyrocervical trunk off subclavian artery. courses posterior to carotid artery and supplies inferior pole of thyroid gland.
anatomical landmark for carotid bifurcation?
just inferior to hyoid bone.
ubiquitination & ATP-dependent proteasome plays an important role in..
antigen processing, muscle wasting, cell cycle, DNA repair, disposal of misfolded proteins
how many ubiquitins needed for proteasomal degradation
at least 4 monomers
mutations in Parkin, PINK1, and DJ-1 related to? what system is messed up?
autosomal recessive forms of parkinson’s disease (early-onset <50y/o). code for protein complex that promotes degradation of misfolded proteins via ubiquitin-proteasome system
histone acetylation.. histone methylation
histone acetylation = euchromatin. histone methylation = heterochromatin
hepatic processing of bilirubin (3)
(1) carrier-mediated passive uptake of bilirubin at sinusoidal membrane (2) conjugation of bilurubin with glucuronic acid in endoplasmic reticulum (3) active biliary excretion of the water-soluble, nontoxic bilirubin-glucuronides.
Crigler-Najjar syndrome
lack enzyme needed to catalyze bilirubin glucoronidation.
beta-blockers affect which part of an EKG?
PR interval; no affect on QRS wave or QT interval
pO2 of inspired air, air in trachea, alveolar. normal pCO2 alveolar
pO2 of inspired air: 160mmHg. in trachea: 150mmHg (due to partial pressure of water vapor). in alveolar is 104mmHg (between trachea and venous blood of 40mmHg). normal alveolar PCO2 is 40mmHg (between 0 in trachea and 45mmHg in venous blood)
perfusion-limited (O2 and CO2)
complete equilibration of gas before venous blood exits pulmonary capillary. means perfusion determines speed at which alevolar air equilibrates w/ venous blood gas. PE could limit perfusion.
diffusion-limited states affect which gas more. why?
affect O2 concentrations more, since diffusion capacity of CO2 across respiratory membrane is 20x than of O2
when can O2 equilibration become diffusion-limited (as opposed to perfusion-limited)?
diseases states (emphysema & pulmonary fibrosis) or during exercise (high pulmonary blood flow)
jaw pain that starts in the middle of a meal (or tongue pain) characteristic for…
temporal arteritis; lumen of artery narrows and cannot respond to increase blood requirement
50% of patients w. temporal arteritis also present w/
muscle pain from polymyalgia rheumatica
diagnosis of temporal artertitis
- ESR should be elevated. 2. temporal artery biopsy for definitive diagnosis
parvovirus b19 receptor?
blood group p antigen, globoside, on erythrocytes and erythrocyte progenitors
hemoglobin A
predominant form in adults – 2 alpha, 2 beta. begins in final life of gestation, gradually replaces HbF
initial hemoglobin formed by fetus (few weeks into conception)
embryonic – gower – two zeta, two episilon, in embryonic yolk-sac
hemoglobin formed after gower by fetus
hemoglobin F (2 alpha, 2 gamma) major hemoglobin in gestation and few weeks of postnatal life
thalassemia
hereditary hemolytic anemia resulting from defective synthesis of globin chains. normally have 2 beta-globin genes (one from each parent). ppt of alpha chains, premature lysis of RBCs. won’t be symptomatic if gamma chains are available.
delta-globulin
minor globin gene expressed at very low levels in adults. hemoglobin A2 (combined w/ 2 alphas)
how do loop diuretics work?
decrease medullary concentration gradient, limiting maximum tonicity of urine
17a hydroxylase deficiency
female born w/ normal genitalia, male undervirilized. none undergo purberty bc lack sex steroids (androstenedione). have HTN and hypokalemia
21-hydroxylase deficiency
most common CAH. excess androgens. females have ambiguous genitalia, hypotension, and hyperkalemia
side chain cleavage (cholesterol desmolase)
cholesterol to pregnenolone.
5-alpha-reductase deficiency
ambiguous genitalia in males (defective conversion of testosterone to DHT). not CAH bc cortisol is not affected. females w/o 5-alpha-reductase do not have ambiguous genitalia.
GPCR-linked second messenger for D1 and D2
D1 –> Gs. D2 –> Gi
tamoxifen tissue targets & effects (4)
SERM. estrogen receptor antagonist in breast, but agonist in bone and endometrium. also, positive effects on serum lipid profile (normalize total cholesterol and LDL w/o significantly affected HDL)
side effects of tamoxifen (3)
endometrial polyps, endometrial hyperplasia, and endometrial cancer. (used as adjuvant therapy for breast cancer)
common peroneal nerve
originates from sciatic nerve. splits into deep peroneal (innervates extensor and great dorsiflexors) and superficial peroneal (peroneal muscles and skin of toes). traces the lateral neck of fibula.
femoral nerve (L2-L4)
largest nerve in lumbar plexus. innervates muscles of anterior and medial thigh. damage –> loose knee jerk
tibial nerve
off of sciatic. posterior compartment of thigh, flexors of foot. damage -> problems w/ plantar flexion
radial n injury
wrist drop, flexed forearm
pudendal n.
motor and sensory input to pelvic floor
lateral sural cutaneous
cutaneous branch of tibial, sensation to calf
side effects of low dose inhaled glucocorticoids (2)
(1) oropharyngeal candidiasis, most common (2) rare, dysphonia, due to myopathy of laryngeal muscles
systemic effects w/ higher dose glucocorticoids
increased intraocular pressure, cataracts, growth retardation in children, bone loss, suppression of HPA axis. rare: cushingoid symptoms
groin hernias (3)
(1) indirect inguinal - male infants (2) direct inguinal - older men (3) femoral - women
indirect inguinal hernia pathophysiology
enters internal inguinal ring lateral to inferior epigastric vessels. caused by persistent processus vaginalis & failure of internal inguinal ring to close. male infants. covered by all 3 spermatic fascial layers (vs. direct: only external spermatic fascia)
direct inguinal hernia pathophysiology
bulges through Hesselbach’s triangle, medial to inferior epigastric vessels to reach external inguinal ring. caused by weakness in transversalis fascia. older men. do not pass through deep inguinal ring; only through superficial inguinal ring. only covered by external spermatic fascia.
femoral hernia
protrudes through femoral ring, medial to femoral vessels & inferior to the inguinal ligament. femoral ring: medial to femoral sheath (femoral artery and vein) and lateral to the lacunar ligament.
Hesselbach’s triangle
inferior: inguinal ligament. lateral: inferior epigastric vessels. medial: rectus abdominus. direct hernia protrude through here. transversalis fascia forms the floor. results from: acquired CT abnormalities or chronic abdominal wall injury
spermatic fascia layers & origins
internal spermatic fascia (transversalis fascia), cremasteric muscle & fascia (internal oblique), external spermatic fascia (external oblique) – surrounds spermatic cord.
abdominal fascia / muscle layers near groin
parietal peritoneum, extraperitoneal fat (inferior epigastrics run through here), transversalis fascia (deep inguinal ring), transversus abdominus, internal oblique (spermatic cord runs through), inguinal ligament, superficial inguinal ring.
most common type of hernia in both genders?
indirect inguinal hernia (infants, children, young adults) failure of processes vaginalis to obliterate and internal inguinal ring to close
rheumatoid arthritis, serum antibodies with high specificity?
anti-citrullinated peptides (anti-CCP)
how does anti-CCP form in rheumatoid arthritis
tissue inflammation causes arginine residues in proteins (i.e. vimentin) to be enzymatically converted into citrulline (citrullination). alters the shape of proteins, serve as antigens and generate immune response. HIGH SPECIFICITY for RA. ELISA.
anti-centromere
CREST syndrome
anti dsDNA
specific for SLE
diagnostic utility of RF (IgM against Fc region of IgG)
occurs in 80% of patients w/ RA, but poor specificity (10% of healthy, 30% of SLE, all patients w/ mixed cryoglobulinemia)
anti ANA
nonspecific finding in many CT disorders
anti phospholipid antibodies
in SLE and antiphospholipid antibody syndrome (
antiphospholipid antibody syndrome (3)
anti-phospholipid Ab. (1) hypercoagulability, (2) paradoxical PTT prolongation, (3) recurrent miscarriages.
glomerulonephritis, photosensitive skin rash, arthralgia in young female
SLE, positive VDRL w/ negative treponemal Ab
why does SLE produce a positive VDRL?
circulating anti-phospholipid antibodies (reactive against epitopes of cardiolipin in which VDRL treponemal antigen is embedded)
antiphospholipid antibody syndrome may arise w/ SLE. what 3 things is it defined by [at least 1]
- venous thromboembolism 2. arterial thromboembolism 3. increased fetal loss
what % of individuals w/ lupus carry lupus anticoagulant?
10-30%, but not all symptomatic
repeated second / third trimester miscarriage
antiphospholipid antibody syndrome. perhaps due to APLA-mediated inhibition of t-PA activity necessary for trophoblastic invasion of the uterus.
sclerodactyly
CREST / scleroderma
most frequent cause of prolonged PTT and false positive VDRL w/o hematological abnormality?
lupus anticoagulant
treatment for nocardia? actinomyces?
SNAP. sulfonamides for nocardia. penicillin for actinomyces
treatment for cutaneous anthrax
ciprofloxacin
cut off for diagnosis of HTN and intiiation of treatment
systolic 140 and/or diastolic 90
what type of BP changes are expected after 50y/o? what is it caused by?
isolated systolic HTN. age-related decrease in compliance of aorta and its proximal major branches. many diff alterations in vessel strxr cause stiffening, inclu atherosclerotic. also have age-related increase in sympathetic cardiovascular tone, increases TPR in muscular arterioles (would lead to increased systolic and diastolic)
various formulas for MAP
MAP = CO x TPR. MAP = diastolic + 1/3 pulse pressure. MAP = 2/3 diastolic + 1/3 systolic.
prolonged systemic glucocorticoid use (even low dose) can develop.. explain 3 ways this can happen
osteoporotic bone changes. (1) decreased synthesis of bone matrix (2) inhibition of intestinal action of vitamin D- poor calcium absorption (3) increased PTH. pathologic vertebral fractures.
would rheumatoid arthritis affect vertebrae?
no, affects synovial joints (usu hands feet. also wrist and shoulders)
progesterone’s role in menstrual cycle
required for endometrial stromal cells to grow and differentiate into decidual cells. withdrawal causes APOPTOSIS of endometrial cells.
hibernating myocardium: cause & what it is. how is it reversed?
caused by repetitive ischemia or cardiac myocytes or persistent hypoperfusion of myocytes. energy metabolism is reduced, but there is sufficient ATP to prevent contracture. (1) increased gene expression of TNF-alpha and NOS –> inhibitors of contraction, (2) complex defects in calcium cycling, and (3) decreased B-adrenergic receptor density. rx: revascularization with CABG or ballon angioplasty.
ischemic preconditioning
development of resistance to infarction by cardiac myocytes exposed to prior repetitive non-lethal ischemia. protect against subsequence greater ischemic insults.
myocardial stunning
less severe form of ischemia-induced reversible loss of contractile function than hibernation. brief ischemic episodes ( stunning, full recovery over hours/days. chronic depression of myocardial contractility –> hibernation
histopathology of berger’s disease (IgA nephropathy)
light microscopy: no specific findings. IF: IgA in mesangium. EM: electron dense in mesangium.
IgA nephropathy vs. postinfectious glomerulonephritis
(1) timing of renal symptoms: IgA nephropathy - few days post-infection. PSGN - few weeks. (2) complement levels: IgA nephropathy - normal. PSGN - low C3. (3) mesangial deposition not seen in PSGN
IgA nephropathy (berger) presentation
painless hematuria 2-3 days after URI (when systemic IgA deposition –> HSP)
small cell carcinoma histology
neuroendocrine differentiation: neuron specfic enolase, chromogranin, synaptophysin, neurofilaments. most aggressive lung cancer. low 5-year survival. local invasion and distant mets
which cancers have EGF-R, mucin, and surfactant associated proteins
non-small cell lung cancers
vimentin is useful for..
diagnosing sarcomas. found within cells of mesenchymal origin.
which is the most aggressive lung neoplasm –
small cell lung cancer. local invasion and distant mets usu by presentation. chemo. low 5-yr survival.
small cell carcinoma histology
neuroendocrine differentiation: neuron specfic enolase, chromogranin, synaptophysin, neurofilaments. most aggressive lung cancer. low 5-year survival. local invasion and distant mets
which cancers have EGF-R, mucin, and surfactant associated proteins
non-small cell lung cancers
vimentin is useful for..
diagnosing sarcomas. found within cells of mesenchymal origin.
which is the most aggressive lung neoplasm –
small cell lung cancer. local invasion and distant mets usu by presentation. chemo. low 5-yr survival.
