test #30 4.20 Flashcards
opsoclonus-myoclonus syndrome
non-rhythmic conjugate eye movement w/ myoclonus
non-rhythmic conjugate eye movement w/ myoclonus?
opsoclonus-myoclonus
most common extracranial childhood tumor
neuroblastoma, usu from adrenal medulla
Wilm’s tumor vs. neuroblastoma
neuroblastoma: firm, irregular mass. cross midline.
wilm’s tumor: smooth and unilateral
presentation of neuroblastoma?
child ~2y/o. retroperitoneal mass, HTN.
neuroblastoma mets
invasion of epidural space: “dumbbell tumor” spinal cord compression
bone: pancytopenia
liver: hepatomegaly
skin: palpable nodules
periorbital: proptosis, periorbital ecchymoses
paraneoplasic: opsoclonus, myoclonus, truncal ataxia
urine w/ neuroblastoma
increased HVA in urine
genetics of neuroblastoma
n-myc amplification
prognosis
better if <1 y/o
worse with higher n-myc amplification
formation of annular pancreas
ventral pancreatic bud cleaves into two parts, fuse w/ dorsal bud on either side – can compress duodenal lumen
heteroplasmy
mixture of two types of genetic material (i.e. inherit some normal & mutated mitochondria)
mitochondria inheritance
ovum has many mtDNA. few copies in sperm are lost during fertilization.
variability bc during mitosis, mitochondria are RANDOMLY distributed between daughter cells
characterestics of mitochondrial diseases
- affect both male & female w/ equal frequency
2. variable degrees of severity: due to heteroplasmy
three mitochondrial diseases
- leber hereditary optic neuropathy
- myoclonic epilepsy w/ ragged red fibers MERRF
- mitochondrial encephalomyopathy w/ lactic acidosis and stroke-like episodes MELAS
myoclonic seizures and myopathy associated w/ exercise. skeletal biopsy w/ irregularly shapped muscle fibers (ragged red)
myoclonic epilepsy w/ ragged red fibers.
mitochondrial disease
leber hereditary optic neuropathy
mitochondrial disease.
bilateral vision loss
seizure disorder, several stroke-like episodes, increase lactic acidosis.
affected siblings w/ variable degrees of severity
MELAS
mitochondrial encephalopmyopathy w/ lactic acidosis & stroke-like episodes (MELAS)
variable expressivity vs. variable degrees of severity
variable expressivity: differences in severity of autosomal dominant disorders. i.e. Marfan w/ only tall stature, others w/ also root dilation.
NOT a feature of mitochondrial diseases (variable degree of SEVERITY)
gram negative lactose non-fermenters?
oxidase positive: p. aeruginoas
oxidase negative: shigella, salmonella, proteus
differentiate shigella vs. salmonella & proteus in culture
all non-lactose fermenters, oxidase negative.
salmonella & proteus: (1) H2S production (black on TSI agar) (2) mobile
shigella: (1) NO H2S production, not black (2) NOT mobile
essential pathogenic mechanism for shigella
musocal invasion!
via M cells in peyer’s patches
induces apoptosis of host cell and spreads to adjacent ones via protrustions (via host cell-actin polymerization)
less important in pathogenesis: also releases shiga toxin. A subunit inactives 60s ribosome (halts protein synthesis).
does NOT colonize in intestine. only there during active infection.
does NOT cause bacteremia. survives within mucosal layer of intestine
which enteric bacteria penetrate mucosa & proliferate in mesenteric nodes?
salmonella typhi and yersenia enterocolitica.
which bacteria causes pseudoappendicitis?
yersenia enterocolitica. mesenteric lymph node infection, RLQ pain.
work of breathing is a balance between..
against elastic resistance of lung and against airflow resistance
when is work done against elastic resistance HIGH?
high tidal volumes
when is work done against airway resistance HIGH
respiratory frequency
relationship of elastic resistance and air flow on work of breathing.
inverse relationship.
elastic recoil favors low tidal volume (high respiratory rate)
airflow resistance favors high tidal volume (low respiratory rate)
COPD / asthma (high airway resistance) minimize work of breathing by..
have increased airway resistance, so increase TV, minimize RR
pulmonary fibrosis / edema (stiff lungs: high elastic resistance) minmize work of breathing by
rapid shallow breaths (low TV, high RR)
fate of mRNA once it leaves cytoplasm (2)
(1) associate w/ ribosomes = translation
(2) associate w/ P body proteins: distinct foci in eukaryotic cytoplasm, involved w/ mRNA regulation & turnover. role in translation repression and mRNA decay, contains numerous proteins and RNA exonucleases, mRNA decapping enzymes, constituents involved in mRNA quality control and microRNA-induced mRNA silencing. also: mRNA storage (for later use)
polyadenylation sequence
3’ end of RNA
no need for templatte. recognition sequence AAUAAA
5’ cap on mRNA?
7-methylguanosine. unique 5’ to 5’ linkage.
cytoplasmic P bodies
impt role in mRNA translation regulation, degradation and storage
likelihood ratio positive
sensitivty / 1-specificity
test w/ LR+ greater than 10 significantly increases likelihood that patient will have disease for which they are being tested
right brachiocephali is forned by union off..
right subclavian and right internal jugular.
right external jugular drains into right subclavian
brachiocephalic obstruction vs. SVC obstruction?
right side only vs. both sides of face & arms
guyon’s canal
between hook of hamate and pisiform bone. cause ulnar n. (dysesthesia on ulnar side of hand and weakness of intrinsic muscles of hand)
axillary n. innervates
deltoid and teres minor.
affected w/ fracture of surgical neck of humerus
brown pigment stones in gallbladder
(asian) usu arise secondary to infection of biliary tract, which results in release of B-GLUCORONIDASE by injured hepatocytes & bacteria. –> h
ydrolysis of bilirubin glucoronides and increased amount of UNCONJUGATED BILIRUBIN in bile.
recall unconjugated bilirubin = not water soluble!
7-alpha-hydroxlase
converts cholesterol into bile acids.
vassopressin. ADH receptor actions (2)
primary inhibitor of free water excretion
V1: vasoconstriction & prostaglandin release
V2: increase H20 permeability urea
how does vasopressin maximally concentrate urine
(1) express aquaporin receptors in collecting duct.
(2) increases number of passive urea transporters in inner medullary collecting duct (allows substantial number of highly concentrated urea to enter medullary interstitium)
when ADH = high, urea resorption contributes 50% of total osmolarity of medulla
which infections increase risk of brown pigment stones?
bacteria w/ beta-glucoronidase to unconjugate bilirubin in gallbladder OR damage heptocytes to release beta-glucoronidase.
biliary infection w/ (1) e. coli (2) ascaris lumbricoides (3) liver fluke Opisthorchis sinensis
how is copper normally excreted?
into BILE
via hepatocyte copper transporting ATPase (ATP7B gene
wilson’s disease: 2 pathogenesis
autosomal recessive, chr. 13.
(1) defect in Cu2+ excretion into bile (ATPase transporter in hepatocytes)
(2) failure of copper to enter circulation as ceruloplasmin
all leads to copper accumulation in liver, brain, cornea, kidney, and joints
manifestations of wilson’s disease
Copper is Hella BAD
C: decreased ceruloplasmin cirrhosis corneal deposits (kayser-flesicher rings) copper accumulation carcinoma (hepatocellular)
H:
hemolytic anemia
B:
basal ganglia degeneration (parkinsonian symptoms
A:
asterixis
D:
dementia, dyskinesia, dysarthria
kernicterus
billirubin-induced brain damage. often in (1) basal ganglia (2) auditory nucleus (3) oculomotor nucleus
where can urea be reabsorbed (3)
(1) PCT – (reabsorbs about half of filtered load)
(2) thin ascending loop of henle
(3) medullary collecting duct – ADH sensitive
differentiate atypical CD8+ lymphocytes in infectious mononucleosis vs. immature blasts?
atypical CD8+ lymphocytes: abundant blue cytoplasm, basophilic rim <3 RBCs.
immature blasts: less cytoplasm, no bizzarre nuclear changes
EBV increases risk of what 3 things
(1) Hodgkin’s lymphoma
(2) non-hodgkin’s – Burtkitt
(3) nasopharyngeal carcinoma
which macrolide does not inhibit CP450?
azithromycin
which statin is not metabolized by p450 (so less at risk for drug intxn)
pravastatin
hepatitis B viral replication process
DNA hepadnavirus
partially DS
polymerase has DNA polymerase & RNA-reverse transcriptase dependent properties
- partially DS DNA enters nucleus
- viral polymerase finishes –> DS DNA (dna-dep-dna pol)
- host RNA pol makes viral transcripts
- viral polymerase reverse transcribes viral transcripts – DNA (dna-dep rna pol)
viral class for hep A?
RNA picornavirus (naked icosahedral)
viral class for hep E?
RNA hepevirus (naked icosahedral)
viral class for hep C?
RNA flavivirus (enveloped icosahedral)
viral class for hep D?
delta virus
- SS circular
- uncertain capsid
- requires hep B coinfection
viral class for hep B?
DNA hepadnavirus
- enveloped icosahedral
- circular partial DS DNA
replicative sequence for retroviruses (HIV, HTLV)
one stranded + RNA –>
template DS DNA –>
progeny one stranded +RNA
replicative sequence for hepatitis B?
(partial) DS DNA –>
template +RNA –>
progeny DS DNA
has RNA intermediate!
replicative sequence for papovavirus, adenovirus, herpesvirus, poxvirus?
DS DNA –>
template DS DNA –>
progency DS DNA
affect of EBV infection on B cells
enter cell cycle & proliferate continuously (transformation / immortalization)
EBV encoded oncogenes activate & proliferate anti-apoptotic signaling pathways. can propagate indefinitely in vitro.
Tzanck test identifies
HSV or VZV
epithelial cells from ulcer, Wright-Giemsa stain. look for..
(1) multinucleated giant cells and
(2) intranuclear Cowdry bodies
cryoglobulinemia associated w/
associated w/ hep C infection.
cold-precipitable serum proteins that contain immunogloblins.
heterophile Ab test for EBV during latent infection
will NOT be positive.
latent infection: perisstence of full viral genome in B cells, but..
NO full virion replication
NO lytic release
SPARSE expression of viral proteins
hemadsorption of virally infected cells onto RBCs suggests
hemaggltins or glycoprotein expression on host cell. associated w/ influenza and parainfluenza viruses.
carbamazepine is first line for… (3) function?
increase Na+ channel inactivation..
partial simple
partial complex
tonic clonic
feared complications of carbamazepine
agranulocytosis or aplastic anemia
side effects of ethosuximide?
block thalamic T-type Ca2+ channels
EFGHIJ ethosuximide fatigue GI upset headache itching steven-johnson
characterize absence seizures
generalized, nonconvulsive. episodic loss of awareness (<10sec).
associated with 3 Hz generalized spike & slow wave EEG.
rx: ethosuximide & valproic acid
methyphenidate used for (2)
narcolepsy and ADHD
HIV gp120 important for? gp41?
gp 120: docking glycoprotein: viral adherance
gp 40: transmembrane: fusion & entry
HIV early coreceptor? late?
early coreceptor: CCR5
late: CXCR5
both on T cells (CD4+).
CCR5 on macrophages
enfurvirtide binds to..
gp41, prevent fusion
methionine processing (4 major products in cycle)
(1) methionine
(2) s-adenosyl methionine
(3) s-adenosylhomocysteine
(4) homocysteine
fates of homocysteine (2)
(1) converted to methionine (gains methyl group_
- requires B12 (methylcobalamin -> cobalamin) and methyl-THF -> THF
- via homocysteine methytransferase// methionine synthase
(2) converted to cystathionine.
- requires B6 and serine
via cystathionine synthetase
cystathione -> cysteine
via cystathionase
requires B6
three ways to get homocysteinuria (3)
- cystathionine synthase deficiency
(rx: reduce methionine. supplement B12, folate, and cysteine) - decreased affinity for cystathionine synthase for pyridoxal phosphate B6
(rx: more B6 and cysteine) - homocysteine methyltransferase / methionine synthase deficieny
(rx: supplement methionine)
presentation of homocysteinuria
intellectual disability, osteoperosis, tall stature, kyphosis, lens subluxation (down and in)
** arterial and venous thrombosis –> stroke and MI
note: marfanoid! like marfans (genetic heterogenity)
B12 specifically (i.e. no folate) needed for what pathway
methylmalonyl-CoA –> succinyl-CoA (methylmalonyl CoA isomerase)
succinyl-CoA –> myelin, TCA, and heme
methylmalonyl-CoA comes from odd chain fatty acid oxidation & branched-chain amino acid oxidation
kussmaul’s sign
paradoxical increase in JVP with inspiration
found in patients w/ CHRONIC constrictive pericarditis – takes months/years to develop
S3 suggests (2)
(1) rapid rate of diastolic ventricular filling w/ large volume of blood and/or
(2) reduced ventricular complicance
pulsus paradoxus
drop in systolic BP of 10mmHg or more in inspiration.
exaggeration of a normal physiological response
seen in cor pulmonale, chronic constrictive pericardial disease, and tamponade
pericardial knock
in chronic constrictive pericarditis.
brief, high frequency precordial sound heart in early diastole (shortly after S2). early than an S3 even. can be confused w/ opening snap.
acute pericarditis form. sign?
usu fibrinous or serofibrinous. pericardial friction rub: high pitched, leathery, scratchy
tracheal deviation towards opacified lung? away from opacified lung?
tracheal deviation away from lucent lung?
towards opaque: atelactasis (lung volume loss, i.e. bronchogenic carcinoma occluded airway –> atelactasis)
away opaque: pleural effusion
away lucent: pneumothorax
radiographic signs of PE
westermark sign – lucent region due to oligemia distal to PE
hampton’s hump – opacity at phrenic angle
nephrogenic diabetes insipidus caused by lithium?
due to antagonism of vasopressin. resolves w/ discontinuation usu, though permanent is possible.
side effect of metformin
lactic acidosis
collagen synthesis main steps
ER:
(1) SYNTHESIS in ER: Gly-X-Y (proline & lysine usu)
(2) HYDROXYLATION of proline & lysine in ER ( vit C dep hydroxlyation)
(3) GLYCOSYLATION of lysine in ER
(4) FORMATION of procollagen in ER (hydrogen and disulfide bonds between alpha-fibrils)
(5) EXOCYTOSIS
(6) CLEAVAGE of N & C terminal disulfide linkages (procollagen to insoluble tropocollagen)
(7) COLLAGEN formation– linking lysine to hydroxylysine residues (lysyl-oxidase Cu2+ dependent)
uric acid ppts at what pH
acidic pH (prone to ppt at acidic DCT and collecting ducts)
which kidney stones ppt at acidic pH? basic?
acidic pH: calcium oxalate, uric acid, and cystine
basic pH: calcium phosphate, and AMP (phosphates)
shape of.. calcium stones AMP stones uric acid stones cysteine stones
calcium: envelope or dumbell
AMP: coffinlid
uric acid: rhomboid or rossettes
cysteine: hexagonal
AMP stone producing bacteria
proteus mirabilis or vulgaris
staph
klebsiella
(hydrolyze urea to ammonia)
what drug signicantly decreases heart failure progression & all-cause mortality in patients w/ CHF?
beta-blockers (carvedilol – block alpha & betas)
decrease cardiac rate (slow rate & decrease afterload)
diabetic mother –> (2)
caudal regression & transposition
drag queens & trans
drugs for congestive heart failure (esp those that decrease mortality)
ace inhibitors, ang II blockers, digoxin
MORTALITY HELPERS:
(1) beta blockers (carvedilol), (2) spironolactone (block aldosterone mediated remodeling
thiazide/loop diuretics for symptoms
hydralazine WITH nitrates reduce symptoms and mortality in selet group (not nitrates alone)
milrinone
phosphodiesterase inhibitor, increases contractility and reduces both prelaod and afterload.
short-term therapy
cystinuria
autosomal recessive.
common 1:7000
hereditary defect in amino acid transporter for cysteine, ornithine, lysine, and arginine.
COLA – dibasic amino acids
in PCT and intestine
rx: alkalinization (via potassium citrate, acetazolamide) and chelating agents that increase solubility, good hydration.
diagnostic: urinary cyanide-nitroprusside test
sodium cyanide + sodium nitroprusside in urine –> red purple?
cystinuria
defects sulhydryl groups
hexagonal stones pathognomonic for..
cysteinuria!
peaked T waves
hyperkalemia
chemo for high grade lymphoma, leukemia, or any other cancer w/ rapid cell tunover, substantial tumor burden, or sensitivity to chemo can result …
TUMOR LYSIS –> hyperuricemia –> renal impairment
reducing risk for tumor lysis?
aggressive fluid hydration
allopurinol or rasburicase (reduce uric acid levels)
rasburicase
recombinant version of URATE OXIDASE (in nonhuman mammals)
convert uric acid –> allantoin. 5-10x more soluble that uric acid
effective in preventing and treating hyperuricemia & renal issues with tumor lysis
denosumab
Ab against RANK-L
prevent osteoclast activation
N-acetylcysteine (4)
(1) enhances glutathione production
(2) conjugates toxic NAPQI metabolites
(3) mucolytic
(4) prevents radiocontrast-induced nephropathy in patients w/ renal insufficiency
probenicid
uricosuric agent: increases excretion of uric acid in urine.
rx: for gout and hyperuricemia. but only effective if have good renal function. NOT used for patients at risk for nephrolithiasis or uric acid nephropathy
NEW findings in patient w/ acute left ventricular failure?
CHRONIC/later findings?
new: pulomary edema: interstitial & alveolar edema
prior episodes: hemosiderin-containing macrophages in alveoli (siderophages or heart failure cells
hemosidering-containing macrophages in alvoli suggest
prior / chronic episodes of pulmonary congestion and edema that arose due to CHRONIC left heart failure.
erythrocytes extravasate into alveoli (increased intravascular pressure in pulmonary capillaries). macrophage eat and accumulate hemosiderin
side effect of ethambutol
optic neuritis – decreased visual acuity, color blindness, central scotoma
side effects with isoniazid
peripheral neuropathy and hepatoxicity
INH
gatifloxacin toxicity
hypoGlycemia
cipro toxicity
tendon rupture
B cell precursors proliferate and mature in..
BONE MARROW (undergo VDJ recombtination etc)
B cell meet antigen & undergo somatic hypermutation & isotype switching in..
germinal centers of lymph node
what happens in lymph node germinal center
(1) isotype class switching
(2) affinity maturation (somatic hypermutation)
(3) antibody production
where does VDJ and VJ recombination occur?
bone marrow! gives B cell initial specificity
– more specific in germinal centers w/ somatic hypermutation & isotype switching
VDJ - heavy chain
VJ - light chain
worst prognostic factor in alcohol-associated hepatic injury?
- prolonged PT (reduced synthesis of factors)
- less albumin
reduced SYNTHETIC fxn
progression of alcohol-related hepatic injury
alcoholic stetosis (reversible) alcoholic hepatitis (reversible) alcoholic cirrhosis (irreversible)
hepatic injury signs?
increased transaminases & bilirubin
ALP elevated: biliary or bone?
check serum GGT (gamma glutamyl transferase)
elevated in biliary injury
thrombocytopenia in alcoholics due to..
direct toxic effects of alcohol on bone marrow & hypersplenism // splenic sequestration
immediate risk of warfarin
procoagulant – esp in protein C deficiency –> hypercoagulable state w/ thrombotic occlusion of microvasculature and skin necrosis
rx: FFP
impaired absorption of B12 on schilling test that is not corrected w/ instrinsic factor?
malabsorption syndrome (like celiac or diphyllobothrium latum infxn)
reactive arthritis joint aspirate
STERILE. ‘reactive’ not ‘infectious’
though it results from nongonococcal urethritis (chlamydia, or GI: camplyobacter, shigella, salmonella, yersinia, bartontella
can’t see, can’t pee, can’t climb a tree
conjunctivitis, urethritis, arthritis
ecthyma grangrenosum
skin finding associated w/ pseudomonas aeruginosa
vascular destruction and cutaneous necrosis
perivascular bacterial invasion of arteries and veins in dermis and subcutaneous tissue. subsequent release of exotoxins that are destructive to human tissue.
release:
- exotoxin A (protein synth inhib)
- elastase (damages vasculature)
- phospholipase C (degrades cellular membrane)
- pyocyanin (generates reactive oxygen species)
persistant colonization w/ pseudomonas aeruginosa due to..
biofilm production (esp in chronic pneumonia in CF patients)
erysipelas
unique form of skin infection
causes lesions involving superficial layers of skin. results in painful erythematous plaques w/ raised and well-demarcated borders
strep pyogenes
liver mass w/ increasesd aFP
hepatocellular carcinoma
how does hepatitis B increase development of hepatocellular carcinoma
integration of viral DNA into genome
viral HBx triggers
(1) IGF II
(2) IGF-1 receptors
(3) inhibit p53
(4) general state of inflammation
rx for new onset diabetes type 1 (DKA)
regular insulin!
1 bolus, then continuous intravenous regular insulin
monomeric insulin. rapid acting
lispro, aspart, glulisine
do not polymerize – rapidly absorbed after subcut injection
start 15min –> peak 45-74min.
rx postmeal hyperglycemis
rapid acting insulin (lispro, aspart, glulisine)
NPH
crystalline suspension of insulin w/ protamin and zinc, prolongs its actions
starts ~2hrs, peaks 4-12 hrs, last 18
determir
long acting insulin. fatty acid bound to one of the lysine on amino acid. allows albumin binding & slow dissociation.
starts working in 2 hrs, peaks 3-9, lasts 24
glargine
long duration action insulin. pH of 4. forms microprecipitate in subcutaneous tissue after injection. very slow release. 24 hrs
cachexia
syndrome of anorexia, malaise, anemia, weight loss, generalized wasting due to underlying disease
what cytokine produces cachexia
TNF-alpha
aka cachectin
made by macrophages in response to infxn as well as neoplastic cells
IL-1 and TNF-alpha in bacterial infection?
symptoms of septic shock. hepatic release of acute phase reactants: C-reactive protein, fibrinogen.
TNF-alpha cachexin effects
- hypothalamus -> appetite supprssion
- inhibit lipoprotein lipase
- increase insulin resistance of peripheral tissue
mallory bodies
intracytoplasmic eosinophilic inclusions – alcoholic hepatitis
presentation of acute hepatitis B infection
incubation 30-180 days
sexual, parental, vertical tranmission
insidious onset:
“serum-sickness” like. malaise, fever, skin rash, pruritis, lymphadenopathy, join pain.
eventually SIGNIFICANT elevation in ALT > AST, rise in bilirubin, and ALP
presentation w/ acute hepatitis C
mild. patients usu asymptomatic. some have malaise, nausea, right upper quadrant pain.
hepatic steatosis affects which part of liver..
alcohol, reversible.
usu centrilobular.
macrovesicular steatosis
liver enzymes in hemachromatosis
MILDLY elevated
moldy grains..
aspergillus flavus & aspergillus parasiticus, grow on corn, soybeans, peanuts.
AFLATOXIN! (b1 most common & toxic)
increase risk of hepatocellular carcrinoma
aflatoxin-induced p53 mutations. classic G:C –> T:A in codon 249
