Flashcards in test #22 4.12 Deck (133):
signs of hypothyroidism
fatigue, weight gain, constipation, SLOWED RELAXATION of deep tendon reflexes, dry coarse skin
most sensitive marker for diagnosis of hypothyroidism
(though, will not be elevated in patients w/ hypothyroidism due to TSH deficiency [central hypothyroidism]
neural tube defects (1-3% risk)
valproate inhibits intestinal folic acid absorption
signs of duodenal atresia?
clinical hallmark: bilious vomiting w/o abdominal distension. usually noted on 1st day of life.
peristaltic waves may be visualized in abdomen & history of polyhydramnios due to failure of amniotic fluid reabsorption in distal instestine
often seen in down syndrome
death resulting from bilateral renal agenesis
death from pulmonary hypoplasia shortly after birth
ebstein's anomaly? cause?
atrialized right ventricle (downward displacement of tricuspid valve).
occurs when mom takes lithium early in pregnancy.
anaphylactic reaction to type O blood products in person w/ recurrent sinopulmonary and GI tract infections?
selective IgA deficiency.
anaphylaxis to IgA! make IgG against it. IgA = foreign
C1 esterase inhibitor deficiency
hereditary angioedema. rare. AUTOSOMAL DOMINANT. ace inhibitors are contraindicated.
C1 esterase inhibits nonspecific C1 fixation
delirium: 'waxing & waning' fluctuations in consciousness. acute, global memory impairment, visual hallucinations. 'altered sensorIUM'
reversible & commonly occurs in hospital setting
alcohol, electrolyte imbalace, iatrogenic (i.e. meds), oxygen hypoxia, uremia. trauma, infxn, posion, seizure (post-ictal)
delirium vs. dementia
onset, consciousness, course, prognosis, memory
acute, impaired consciousness, fluctuating symptoms, reversible, GLOBAL memory loss.
gradual, intact consciousness, progressive decline, usu irreversible, remote memory SPARED.
(reversible, at least partially, with: NPH, vitamin b12 deficiency, hypothyroidism, neurosyphilis, HIV)
Reye's syndrome description and pathogenesis
hepatic failure and acute encephalopathy. associated w/ use of aspirin in patients 5-14 y/o.
pathogenesis: unknown; affected children have metabolic error sensitizing to toxic effect of salicylates. especially in virally-infected cells. causes mitochondrial dysfunction.
mechanism: aspirin metabolites decrease beta-oxidation by reversible inhibition of mitochondrial enzymes.
describe lab findings & histology in reye's
vomiting, hepatomegaly. jaundice = rare.
increased ALT, AST, ammonia, bilirubin, prolonged PT and PTT.
light microscope: microvesicular steatosis. NO necrosis or inflammation.
EM: swelling, decreased mitochondria, glycogen depletion.
do not give aspirin (salicylates) to kids under..
16 y/o (except if Kawasaki)
histology of viral hepatitis
apoptosis of hepatocytes, acinar necrosis, periportal mononuclear inflammatory infiltration
liver findings in patients w/ right-sided heart failure
histology of primary biliary cirrhosis
bile duct destruction, periductal granulomatous inflammation, bile duct proliferation
respiratory epithelium with stratified squamous epithlium
response to chronic irritation: METAPLASIA.
adaptive: resistant to irritation than columnar cells.
HOWEVER: no cilia/goblet cells: no mucociliary clearance. can lead to dysplasia (low-grade atypical cells). risk factor for carcinoma (high-grade atypia).
REVERSIBLE, can resolve upon discontinuation of smoking.
renal response to markedly narrowed renal artery (i.e. stenosis)
compensatory RENIN secretion (juxtaglomerular apparatus)
eventually: juxtaglomerular apparatus undergoes hypertrophy & hyperplasia (to make more renin).
juxtaglomerular apparatus: JG cells and macula densa
juxtaglomerular cells: modified SMOOTH MUSCLE CELLS located in alls of afferent and efferent arterioles.
macula densa: tall, narrow cells in distal tubules. monitor osmolarity and volume of urine that passes into distal tubules. pass info to JG.
juxtaglomerular apparatus (2)
juxtaglomerular cells: modified smooth muscle cells in afferent & efferent arteriole. secrete RENIN.
macula densa: tall narrow cells in distal tubules, sense osmolarity & volume in tubules
noise-induced hearing loss?
trauma to sterociliated hair cells of organ of orti. >85dB. distortion / fracture of stereocilia due to shearing forces against tectorial membrane.
loose high frequency first (4000Hz)
frequency of speech
dampens effects of prolonged loud noise by contracting stapedius & tensor tympani.
tensor tympani & stapedius
note. paralysis of mandibular CNV3 results in hypoacussis -- complete loss of tensor tympani tone = hard to hear (even though it normal fxn dampens sounds at other extreme).
loss of stapedius (CNVII) = hyPERacussis
lies at apex of cochlea. has cells that sense rotation.
enhance LVOT in HCM by.. (3)
decreases venous return (valsalva, standing suddenly).
/ admission rate bias. when cases & controls differ due to admission / referral processes.
i.e. enroll patients from all over nation, but use hospitalized control subjects form local institution
a risk factor itself may lead to extensive diagnostic investigation & increase probability that disease is identified.
i.e. detecting more cancer in smokers, but smokers have more imaging surveillance due to smoking status!
non-random sampling of population. lead to study population having characteristics different from target population.
severely ill patients are more likely to enroll in cancer trials -- so results may not be applicable to patients w/ less advanced cancer.
lightning-related complications (5 systems)
(1) cardiac: arrest, arrhythmia
(2) neurologic: perihperal n. damage, seizure, confusion, respiratory arrest, autonomic dysfxn.
(3) dermatologic: lichtenberg figures (pathognomonic of lighting strike)
(4) MSK: rhabdomyolysis, bone fracture, compartment syndrome
(5) cataractsery (late sequelae), ruptured tympanic membrane, curling ulcers.
erythematous cutaneous marks in a fern-leaf pattern & second degree burns..
lichtenberg figures -- LIGHTNING INJURY
why are deep tissue burns relatively rare post-lightning strike?
short duration of electrical contact & flashover effect: tendency of lightning to travel over skin surface and discharge on ground --> lichtenberg figures
how does lightining cause skeletal fracturs?
rapid heating of surrounding air, generating shock waves, can travel through body & cause mechanical trauma.
rules re: cardiac pressure
1. left > right
2. atria ~ 10mmHg max.
3. max pressure in right ventricle & pulmonary artery ~ 25mmHg.
4. max pressure in aorta & LV ~ systolic BP
normal pulmonary pressure at rest? pulmonary HTN at?
at rest: 10-14mmHg.
pumonary HTN > or equal to 25mmHg.
protein A. protein cell wall component (a single polypeptide chain)
1. staph aureus
2. binds to Fc region of IgG, causing epitope binding sites to face AWAY from bacteria. prevents complement fixation and phagocytosis
sounds from opening snap in mitral stenosis
abrupt halting of leaflet motion during mitral valve opening (due to fusion of mitral valve leaflets).
most common cause of mitral stenosis
prior rheumatic carditis
secretin S cells located...
duodenum. increase bicarb secretion from exocrine pancreas. stimulated by HCl in duodenum.
role of thyroglobulin peroxidase (3)
(1) oxidation of inorganic iodine
(2) formation of mono- and diiodotyrosine
(3) coupling that forms T3 and T4.
high molecular weight, glycosylated protein that is present within the thyroid follicle. TSH increases its gene transcription.
role of thyroglobulin
iodine is added to tyrosine residues on thyroglobulin & stored there until thyoid follicular cells engulf, cleave for use.
how does N. meningitidis get into the meningies
pharynx --> bloodstream --> choroid plexus ---> meninges
remember hematogenous bc of systemic signs (i.e. sepsis & characterestic petechial signs, waterhouse-friderichsen, etc)
how does haemophilus influenza get into the meninges?
pharynx --> lymphatics --> meninges
how can S. pneumonia get to meninges post0otitis media?
middle ear --> contiguous tissues --> meninges
how does s. pneumonia and TB from lungs get into meninges?
primary lung focus --> blood --> meninges
describe TB meningitis
chronic, characterized by monoctes & lymphocytes in CSF, primarily affecting BASAL meninges.
typical adenovirus presentation
acute, self-limited, febrile pharyngitis cough, nasal congestion, conjunctivitis, enlarged cervical nodes.
accounts for only 2-4% of acute viral illnesses in general population, but common in crowded quarters (barracks, camp)
Norwalk virus -- epidemic outbreaks of viral gastroenteritis
bronchiolitis in infants caused by
lymphocytic choriomeningitis virus (LCV). febrile aseptic meningoencephalitis or milk systemic influenza-like illness in humans exposed to infected HAMSTERS or MICE. (not person-to-person)
transport of unconjugated bilirubin into hepatocytes?
transported of conjugated bilirubin out of hepatocytes?
indirect unconjugated bilirubin. PASSIVE. via organic anion transporting polypeptide (OATP).
secreted ACTIVE via an ATP-binding cassette protein MRP2.
(if impair MRP2, conjugated bilirubin can passively diffuse via basolateral OATP --> conjugated hyperbillirubinemia.
describe conjugated bilirubin.
water soluble, non-toxic, loosely bound to albumin. can be excreted in urine.
unconjugated bilirubin: insoluble in water at physiological pH, tightly complexed to albumin. cannot be excreted in urine.
which type of bilirubin can lead to jaundice?
BOTH unconjugated & conjugated (bilirubin glucuronides) can accumulate systemically and deposit in tissues --> jaundice.
what 5 things can cause jaundice. which type of bilirubin is at play?
1. excessive production of bilirubin
2. reduced hepatocyte uptake
3. impaired conjugation
4. decreased hepatocellular excretion
5. impaired bile flow (intrahepatic or extrahepatic)
first 3 --> unjconjugated.
last 2 ---> mostly conjugated
mild; low activity in UDP glucoronyl transferase (like in babies).
mild increase in unconjugated bilirubin
see jaundice with stress & fasting. otherwise, clinically silent.
ABSENT UDP-glucoronyl transferase. increased unconjugated bilirubin. die within a few years
rx: plasmaphoresis and phototherapy
defective secretion of conjugated bilirubin. black liver. conjugated hyperbillirubinemia.
benign, autosomal recessive.
mild defect in excretion of conjugated bilirubin. no black liver. conjugated hyperbillirubinemia.
produced by liver. released via exocytosis. decreases in hemolysis bc bound by free hemoglobin & removed by RES (liver and spleen).
conjugated bilirubin in gut
converted into urobillinogen by gut bacteria. 80% further broken into sterobilin and pooped out.
20% reabsorbed. 80% of this back into hepatocytes. 20% urobilin in urine.
indirect billirubin =
direct billirubin =
heme metabolism in RES (reticuloendothelial system)
heme ---> biliveridin (via heme oxygenase).
biliveridin ---> bilirubin
small nuclear ribonucleoproteins. bind pre-mRNA to form splicesosome.
DNA-binding protein. probe w/ double stranded protein.
detects transcription factors, nucleases, etc
c-Jun & c-Fos
nuclear transcription factors that bind to DNA via leucine zipper motif.
proto-oncogene that codes for membrane-bound G protein. activates leads to MAP kinase pathway.
homodimeric calcium-binding protein (similar in structure to calmodulin). important for protein phosphorylation & cell growth & differentiation.
marker for cells of neural crest derivation (melanocytes & schwann cells) & langerhan cells & dendritic cells.
SERM: binds to estrogen receptors. exhibits tissue specific behavior that can mimic or antagonize natural estrogen.
AGONIST on bone, cardiovascular system, blood lipoproteins.
ANTAGONIST: on breast and uterus
helps reduce breast & endometrial cancer and osteoperosis.
oral medroxyprogesterone acetate
synthetic progesterone. reduces incidence of endometrial hyperplasia.
associated w/ decreased bone density
bisphosphonate analogue of pyrophosphate. binds hydroxyapatite. stops osteoclasts.
AGONIST: uterus & bone
good for rx: breast cancer incidence and osteoporosis.
BUT, associated w/ endometrial cancer.
antagonist to ER in hypothalamus, blocks negative feedback to increase GnRH secretion (rx: infertility)
who determines pairing of tRNA and amino acid
each AA tRNA combo has own AA-tRNA synthetase to link them. some can proofread their tRNA.
error rate = VERY LOW.
sequence of amino acids in growing polypeptide chain determined by..
interaction between mRNA codon and tRNA codon. if wrong AA on tRNA, wrong AA will be in peptide (no amino acid proofreading during translation).
causes of sensorineural hearing loss
meniere's disease, acoustic neuroma, presbycusis, ototoxic drugs
involving inner ear, cochlea, or auditory nerve.
causes of conductive hearing loss
cerumen impaction, cholesteatoma, otosclerosis, external/middle ear tumor, tympanic membrane rupture, severe otitis media
obstruction of external sound vibrations to inner ear
what metabolism processes occur in mitochondria?
pyruvate carboxylation, TCA, beta-oxidation, ketogenesis.
part of heme metabolism, urea cycle, gluconeogenesis.
enzyme in pentose phosphate pathway (HMP shunt).
uses B1 as cofactor
test for B1 (thiamine deficiency)
converts ornithine + carbamoyl phosphate --> citrulline
succinate --> fumarate. inner mitochondrial membrane protein & fxn in electron transport chain too.
HMG CoA lysase. mitochondrial enzyme, responsible for ketogenesis.
HMG CoA results from degradation of leucine & synthesis by HMG CoA synthase. also intermediate in formation of cholesterol.
name a thiazolidinedione. mechanism?
reducing insulin resistance by binding to PPAR-gamma (peroxisome proliferator activated receptor gamma).
PPAR-gamma: transcriptional regulator of genes involved in glucose & lipid metabolism.
most important gene regulated by PPAR-gamma: adiponectin (cytokine secreted by fat tissue.
adiponectin levels low in type 2 diabetes. TZD increase adiponectin levels, which decrease insulin resistance.
levels low in type2 DM, leading to insulin resistance.
rx with thiazolidinediones increases adiponectin expression.
1st generation sulfonylureas? 2nd generation?
1st: tolbutamide, chlorpropamide
2nd: glyburide, glimepiride, glipizide
amylin analogs, decrease gastric emptying, decrease glucagon
exenatide & liraglutide
GLP-1 analogs; increase insulin and decrease glucagon
DPP-4 inhibitors: linagliptin, saxagliptin, sitagliptin
increase insulin, decrease glucagon release
glutamate is a precursor for.. (2)
GABA and glutathione
pheylalanine is a precursor for
tyrosine is a precursor for
thyroxine (T4), DOPA (-->melanin), dopamine, NE, E
cofactors in DOPA to NE synthesis
DOPA -> dopamine (B6).
dopamine -> NE (vit C).
NE -> E (SAM)
B6 is generally required for what reactions
(3) glycogen phosphorylase
histidine is a precursor for
glycine is a precursor for..
porphyrin --> heme
tryptophan is a precursor for (2)
2. 5-HT & melatonin
arginine is a precursor for.. (3)
creatinine, urea, and nitric oxide
rx for serotonin syndrome
cyproheptadine. first generation histamine antagonist w/ nonspecific 5-HT1 and 5-HT2 receptor antagonist properties.
antidote for benzo overdose
antidote for narcotic overdose
mycobacteria cell wall
incorporate mycolic acid into the outer portion of peptidoglycan.
what anti-microbial agent is chemically similar to pyridoxine B6
first line against legionella
etiology of Hirschsprung's disease
failure of neural crests to migrate to the intestinal wall. rectum is always involved (travel caudally).
both submucosal (Meissner's) and myenteric (Auerbach)
appears NARROWED. proximal dilation bc of fecal retention
nitrate agent with highest bioavailabilty (~100%) if given orally?
isosorbide mononitrate (active metabolite of isosorbide dinitrate)
only IV. used in hypertensive emergency. notable cyanide toxicity.
SUBLINGUAL. straight into systemic circulation (no first pass metabolism in liver)
examples of lower motor neuron diseases (2)
poliomyelitis and werdnig-hoffman (autosomal recessive)
rx for paroxysmal supraventricular tachycardia?
try valsalva & carotid massage to increase vagal tone to AV. if doesn't work, give adenosine.
increase K+ efflux, hyperpolarize and decrease Ca++ current
multiple rounded & polygonal cells w/ abundant clear cytoplasm
clear cell carcinoma (most common subtype of renal cell carcinoma)
presentation of renal cell carcinoma
triad of (1) hematuria (2) flank pain (3) palpable abdominal mass.
often have paraneoplastic (EPO, ACTH, PTHrP)
hematuria, flank pain, palpable abdominal mass & elevated hemtocrit
EPO producing RCC
metastatic brain cancer
metastasize within CNS, but rarely metastasize outside of CNS
smoking and cervical cancer?
smoking is an independent risk factor!
along w/ HPV, immunosuppresion, low socioeconomic status, sexual activity
not: diet, alcohol, family history
2 binding sites for ACh. Na+ and Ca++ influx, K+ efflux
what happens to nonfunctional monoiodotyrosine and diiodotyrosine in thyroid
deiodination and iodine recycling
ADH signalling cascade
activates V2 receptors (GPCR). transposition of aquaporin 2 to luminal cell membrane.
water deprivation & vasopressin challenge.
1. deprive water. if urine does not concentrate in one hour ( 10% = central DI.
complete central DI = >50% change.
moderate change = partial central DI = some vasopressin present, but not enough to make kidney function
primative neuroectoderm tumor
medulloblastoma. 2nd most common posterior fossa tumor. DROP METS
3 prominent features of glioblastoma multiforme
1. white matter, cross midline
2. florid vascular prolif
3. pseudopalisading necrosis
roof of 4th ventrical. pseudorossettes with GFAP+ processes tapering towards blood vessels.
most common extracranial solid tumor in children
neuroblastoma. undifferentiated are small, blue, round cells. pathognomonic feature: neuritic process: neuropil. NSE, chromogranin, synaptophysin, S-100+. most important biological marker N-myc of chromosome 2
c-myc normal function
nuclear phosphoprotein that functions as TRANSCRIPTION ACTIVATOR controlling cell proliferation, differentiation, and apoptosis.
overexpressed in Burkitt's Lymphoma t(8,14)
mutation in DNA repair leading to anemia?
5 year survival for small cell carcinoma (even w/ treatment)
< 1 year. usu have distant mets by diagnosis.
pure red cell aplasia
rare form of marrow failure characterized by severe hypoplasia of marrow erythroid elements, in the setting of normal granulopoesis (WBC) and thrombopoiesis (platelets)
pathogenesis: inhibition of erythropoietic precursors & progenitors by IgG autoantibodies or cytotoxic T lymphocytes.
associated w/ thymoma or lymphocytic leukemia.
can also occur w/ parvovirus B19 infection (preferentially kills proerythroblasts).
all patients with pure red cell aplasia should undergo..
chest CT, to see if thymoma present. resection can cure disease.
MAJOR virulence factor of s. pneumonia
CAPSULE. without it, would not cause disease. has 82 diff capsules
Ab against capsule causes capsular swelling in vitro
pneumolysin secreted by.. what does it do
s. pneumoniae. suppresses oxidative burst by phagocytes.