why does C. perfringens make gas necrosis?
rapid metabolism of muscle tissue carbohydrate –> gas
fat = black
fat embolism syndrome
(1) respiratory distress
(2) nonfocal neurological disturbance
(3) chest lesions consistent w/ thrombocytopenia
describe path of fat emboli
dislodge from bone marrow, enter marrow vascular sinusoids,
- occlude pulmonary microvessels –> impair gas exchange
- occlude vasculature in CNS
describe promotion of parenchymal destruction w/ fat emboli (2)
- platelet & mediators coat & adhere to emboli –> thrombocytopenia
- systemic activation of LPL (lipoprotein lipase) releases oleic acid systemically –> toxic levels
often hemotological stain. purple platelets
iron stain // hemosiderin
brown on H&E
dark blue on prussian blue
second trimester quad screen for down’s syndrome:
increased: b-HCG, inhibin A.
decreased: AFP, estriol
first trimester findings in down’s syndrome:
increased nuchal translucency &
hypoplastic nasal bone.
edward’s syndrome (trisomy 18) screening findings
everything is down.
DOWN: PAPP-A and b-HCG
DOWN: AFP, b-HCG, estriol, inhibin-A (could be normal)
elevated b-HCG and inhibin in 2nd semester?
[low estriol and AFP]
low bHCG, inhibin, estriol, and ADP
patau syndrome screening findings
DOWN: bHCG, PAPP-A
increased nuchal translucency
low b-HCG and PAPP-A w/ nuchal translucency? without nuchal translucency
nuchal translucency: patau
w/o nuchal translucency: edwards
vast majority of trisomy 21 occur due to..
nondisjunction in meiosis I
failure of homologous chromosomes to separate
nondisjunction in meiosis I due to? nondisjunction in meiosis II due to?
meiosis I: failure of homologous chromosomes to separate
meiosis II: failure of sister chromatids to separate
lagging strand is CONSTRUCTED in which direction? SYNTHESIZED in which direction?
constructed in 3’->5’ direction.
synthesized in 5’->3’ direction
FIRST: try to speak to patient alone – to avoid intimidation.
1. do you feel safe at home
2. who prepares your meals
3. who handles your checkbook
REPORT only after information is collected
common in early menarche years.
longer menstrual cycles and irregular bleeding patterns due to presence of anovulatory cycles
no ovulation -> no corpus luteum -> no progesterone -> continuous estrogen
results in continued proliferation.
becomes disorganized, fragile, w/ unstable venous capillaries –> irregular periods of stromal breakdown w/ variable (spotting) & heavy bleeding.
three major causes of valvular aortic stenosis. most common world-wide? in USA?
(1) congenitally abnormal valve w/ calcification (i.e. biscuspid)
(2) calcified normal valve
(3) rheumatic heart disease
world-wide: rheumatic heart disease.
US: calcific aortic valve (either bicuspid/tricuspid)
right horn of sinus venosus
originally receives blood from IVC. l
becomes smooth part of right atrium.
(smooth part of left from primitive pulmonary vein)
forms beginning of ventricular outflow tract in embryonic heart. later –> smooth portion of left and right ventricles (adjacent to aorta and pulmonary artery, respectively)
receives blood from sinus venosus in embryonic heart, transmits to primitive ventricle.
primitive atrium –> rough portions of left and right atria
close PDA? keep it open?
keep open: PGE2
primitive pulmonary vein forms..
smooth part of left atrium
left horn of sinus venosus
right horn –> smooth part of right atrium
right common cardinal vein & right anterior cardinal vein
what is the first functional organ in human embryo? when does it function?
fetal heart. begins to pump 4 wks in.
first heart loop establishes
patent foramen ovalue
failure of septum primum and septum secundum to fuse. usu left untreated.
embryological origin of AV values (tricuspid and mitral)
from fused endocardial cushions of AV canal
embryological origin outflow valves (aortic/pulmonary)
endocardial cushion of outflow tract
PTH and Ca2+ abnormalities in osteoperosis? osteopetrosis?
osteopetrosis might have low Ca2+
PTH and Ca2+ in osteoperosis?
high PTH, low Ca2+
renal failure, vitamin D deficiency
causes of PTH-independent hypercalcemia?
humoral hypercalcemia of malignancy, vitamin D toxicity, excessive ingestion of Ca2+, thyrotoxicosis, immobilization
age of calcification w/ bicuspid aortic valve? tricuspid
bicuspid: premature: 60-70
tricuspid: senile: 80-90
damage to common peroneal n. sustained w/? physical finding?
lateral aspect of leg, fibular neck fracture.
foot dropPED & can’t feel foot dorsum
peroneal everts and dorsiflexes
damage to tibial n. sustained w/? physical finding
knee trauma, proximal: baker’s cyst. distal: tarsal tunnel.
can’t TIP toe & sense sole of foot
tibial inverts and plantar flexes
sensation to sole of foot? dorsum?
dorsum: superficial peroneal n.
sensation to medial leg? lateral leg?
medial: saphenous n. branch of femoral n.
lateral: superficial peroneal
superficial branch of common peroneal?
mostly lateral compartment: foot eversion & sensation of lateral leg & foot dorsum
deep branch of common peroneal?
anterior compartment: dorsiflexors of foot and toes. inversion of foot.
sensation to only region between 1st and 2nd digits.
where does the coronary sinus reside?
atrioventricular groove on posterior surface.
describe placement of biventricular pacemaker
2 leads -> right heart
via left subclavian -> SVC -> right atrium & ventricle
1 lead -> left ventricle
via right atrium -> coronary sinus (atrioventricular groove of posterior heart) -> lateral venous tribituaries
swan ganz catheter
insert catheter into pulmonary artery, diagnostic, test for heart failure
cataracts, frontal balding, gonadal atrophy, and muscle atrophy / myotonia
myotonic muscular dystrophy type 1. (autosomal dominant)
2nd most common muscular dystrophy (after duchenne’s)
typical symptom of myotonic muscular dystrophy type 1
difficulty loosening one’s grip after handshake. or inability to release doorknob.
pathogenesis of myotonic muscular dystrophy
CTG repeat expansion in gene for myotonia-protein kinase (DMPK gene)
4 diseases w/ trinucleotide expansion
fragile X: CGG
friederich ataxia: GAA
myotonic dystrophy: CTG
muscle histology in myotonic dystrophy
atrophy of type 1 muscle fibers (esp).
no necrosis or fibrofatty replacement (unlike duchenne’s)
2 inflammatory myopathy
dermatomyositis and polymyositis
ion channel myopathy
myotonia and episodes of hypotonic paralysis. often associated w/ exercise. no atrophy on light microscope.
PAS+ intracytoplasmic inclusions
side effect of corticosteroid treatment for atoptic dermatitis?
good: reduces inflammatory response
bad: decreases fibroblast production of ECM collagen and glycosaminoglycans
- -> atrophy of dermis w/ loss of collagen, drying, cracking, tightening in skin.
- -> also teleangiectasia, ecchymoses from mild trauma, atrophic striae
rx for conn syndrome
spironolactone / epeleperone
most common CNS tumor in immunosuppresed?
describe CNS lymphoma
micropscopically: dense cellular aggregates of uniform, atypical lymphoid cells. majority: B cells.
diffuse large B cell = most common type. (CD20, CD79a+)
associated w/ EBV
nonspecific clinical presentation
usu high grade, poor response to chemo
solitary mass in brain.
presentation of sporothrix schenckii. biopsy of innoculation site?
dimorphic fungi. via thorn pick. spread along lymphatics forming subcutaneous nodules & ulcers
biopsy of innoculation site: granuloma w/ histiocytes, multinucleated giant cells, neutrophils, surrounded by plasma cells.
fungus from animal contact?
dermatophytoses – microsporum species. i.e.
microsporum canis –> tinea capitis
exposure to animal products (hair, infected hides, hide-based clothing pdt, wool).
GOAT HAIR: most common implicated exposure
antiphagocytic D-glutamate capsule?
bacillus anthracis. required for pathogenicity.
describe pathogenesis of pulmonary anthrax:
ingested by pulmonary macrophages –> move to mediastinal lymph nodes –> cause hemorrhagic mediastinitis
when spores germinate into vegetative cells, begin to produce 3-part anthrax toxin. symptoms follow.
progression of symptoms of pulmonary anthrax
myalgia, fever, malaise.
rapidly progress to hemorrhagic mediastinitis (widened mediastinum on chest x-ray), bloody pleural effusions, septic shock, death
long chain “serpentine” or “medusa head” colonies. nonhemolyzing, standard culture medium?
protein A (bind Fc portion of IgG)
flagella distributed uniformly over entire surface of bacterial cell.
characteristic of highly motile organisms.
anterior hypothalamic nuclei? destruction?
cooling via parasympathetics. destruction = hyperthermia
posterior hypothalamic nuclei? destruction?
heating via sympathetics. destruction = hypothermia
ventromedial hypothalamic nuclei? destruction?
stimulated by leptin.
destruction = chubs.
lateral hypothalamic nuclei? destruction?
inhibited by leptin.
destruction = skinny.
arcuate nucleus of hypothalamus
- dopamine (inhibit prolactin)
paraventricular nucleus of hypothalamums
secrete oxytocin, ADH, TRH, CRH
supraoptic nucleus of hypothalamus
ADH and oxytoxin
input from retinohypothalamic tract (specialized photosensitive ganglion cells in retina)
secrete NE –> pineal gland –> melatonin
also regulates body temperature and production of cortisol.
regulate circadian rhythm.
dysynchrony between body’s circadian rhythm (sleep/wake cycle) and local environmental rhythm
diurnal variation: melatonin levels? cortisol levels
melatonin: high at night, low in day. secreted by pineal gland.
cortisol: high in day, low at night.
superficial candidiasis (thrush, esophagitis, cutaneous, vulvovaginitis) directly related to?
hematogenous candidiasis related to?
superficial: low T-LYMPHOCYTE
what type of candida infection are HIV pts susceptible?
what about neutropenic?
HIV: low T count: superficial (oral, cutaneous, etc)
neutropenic: disseminated (right sided endocarditis, liver & kidney abscesses, candidemia)
(note if HIV + neutropenic: susceptible to both)
C1 esterase deficifiency
ACE inhibitors contraindicated
(1) recurrent pyogenic sinus, respiratory tract infection.
(2) susceptible to type III HSR
both Neisseria (gonorrhea & meningitidis)
venodilator (large veins) reduce preload (decreased myocardial oxygen demand and treats angina pectoris)
note: reflex tachycardia and contractility, but overall low O2 demand in heart
modulated by nitroglycerin (venodilate)
small arteries & arterioles
primary site of hormonal regulation of systemic blood pressure & site of action of vasoactive antihypertensive drugs (nifedipine and prazosin)
large doses; nitrates affect arteries – flushing, headache
primary conduits for blood delivery to tissues. contain large amount of smooth muscle to regulate blood pressure and withstand high pressures
bands of smooth muscles at junction of capillary and arteriole. limit flow of blood. respond to NE & E (contract or relax)
also directly responsive to local environment (histamine, low O2, high CO2, decreased pH)
plantarflexed and inverted
damage to common peroneal n.
paralysis of peroneus longus and peroneus brevis muscle (eversion), tibialis anterior (dorsiflexion), and extrinsic extensors of toe.
what three rxns is pyrodoxine B6 important for
(1) transamination and (2) decarboxylation of amino acids. (3) gluconeogenesis.
between amino acid and alpha-keto acid
transamination w/ oxaloacetate (alpha-keto-acid) & glutamate (amino acid)
aspartate (amino acid) & alpha-ketoglutarate (keto-acid)
transaminases require what cofactor
hypertensive crisis defined as..
persistent diastolic pressure exceeding 130mmHg.
associated w/ acute vascular damage
hyperplastic arteriolosclerosis histology:
onion-like concentric thickening of walls:
due to (1) laminated smooth muscle cells & (2) reduplicated basement membranes
major toxicity of statins
hepatoxicity and myopathy (elevated creatinine kinase)
statins post MI?
decrease both incidence of 2nd MI and mortality. lower cholesterol & directly stabilize atheromatous plaques
statin myopathy amplified w/
concomittant use of fibrates & niacin
statins, fibrates, nitrates, hydroxychloroquine, glucocorticoids, colchicine, interferon alpha, penicillinaime.
reproductability (test, retest).
measured in terms of coefficient of variation (CV) = standard deviation of the set of repeated measurments divided by mean
ability to measure that which it is supposed to measure
test can be highly reliable but invalid
minute ventillation vs. alveolar ventilation
minute ventilation: total volume of air entering (or leaving) lungs per minute
Ve = Vt x RR
alveolar ventillation: air entering (or leaving) alveoli per minute
Va = (Vt - Vd) x RR
differ on dead space
formula for physiological dead space
Vd: Vt x ((PaCO2 x PeCO2)/PaCO2)
Taco, Paco, Peco, Paco
what part of bone is usu affected in hematogenous osteomyelitis in children? why?
metaphysis: has slow-flowing sinusoidal vasculature that is conducive to microbial passage.
progression of osteomyelitis
seeding event –> acute cellulitis of bone marrow. inflammation in confined boney space leads to increased intramedullarly pressure –> compromises blood flow and forces infectious exudate through vascular chanels into cortex & periosteal region (further compromises blood flow –> ischemia –> necrosis)
can progress to suppurative osteomyelitis (condition where necrotic bone [sequestrum] serves as reservoir for infection and becomes covered by poorly constructed shell of new bone [involcrum]
1+ sinus tracts develop to drain purlent material to soft tissue / out of skin surface
how does flat bone (skull, sternum, pelvis) osteomyelitis often occur?
contiguous spread of infection (mastoiditis or dental abscess)
most common site for hematogenous osteomyelitis in adults? children?
adult: vertebral body (location of pott’s disease, TB)
children: metaphysis of long bone.
(adults less likely to have osteomyelitis bc of changes due to epiphyseal closure)
which drugs are metabolized by liver (i.e. affected by inducers / inhibitors)
warfarin, cyclosporine, tacrolimus, phenytoin, isoniazid, rifampin, oral hypoglycemics
how do beta-blockers (i.e. timolol) help open-angle glaucoma?
reduce production of aqueous humor by ciliary epithelium
what does schlemm’s canal drain into
drains into episcleral and conjunctival veins
what drugs precipitate narrow angle glaucoma crisis?
anticholinergics (exacerbate small angle in posterior chamber) during mydriasis
what drugs reduce aqueous humor production in the eye?
(1) nonselective beta blockers (like timolol)
what drugs increase outflow of aqueous humor
(1) prostaglandin F2a (latanoprost, unoprostone, travoprost)
2) cholinomimetics (pilocarpine, carbachol
latanoprost, unoprostone, travoprost
prostaglandin F2a. increase drainage of aqueous humor: glaucoma
epinephrine & brimonidine for glaucoma
alpha-2 agonists: decreases aqueous humor secretion BUT causes mydriasis.
can use for open angle, but NOT closed angle glaucoma
exonuclease vs. endonuclease
exonuclease: remove nucleotide from the END of a DNA molecule
endonuclease: cut DNA at very specific DNA sequences within molecule (i.e. restriction endonucleases)
secondary structure (alpha helices & beta sheets) of amino acids dictated by..
- alpha, between every 4th AA
- beta, between all residues of antiparallel strands)
tertiary structures form what bonds
many; ionic, hydrophobic, hydrogen, disulfide
what is the first step in the pathogenesis of atherosclerosis?
from HTN, hyperlipidemia, smoking, diabetes, homocysteine, toxins (inclu alcohol), viruses, immune rxn
rare type of mechanical bowel obstruction, when a large gallstone (> 2.5cm) erodes into the intestinal lumen (via cholecystoenteric fistula)
eventually gets stuck in ileum: smallest lumen in intestinal tract
imaging: pneumobilia (air in billiary tree)
GI causes of left pleural effusion
pancreatitis, esophageal rupture
progression of irreversible neuronal injury? 12-48 hrs
“red neurons” – eosinophilic cytoplasm, pynkinotic nuclei, loss of nissl substance
progression of irreversible neuronal injury? 24-72 hrs
necrosis & neutrophil invasion
progression of irreversible neuronal injury? 3-5 days
macrophage infiltration and phagoytosis
progression of irreversible neuronal injury? 1-2wks
reactive gliosis & vascular proliferation around necrotic area
macroscopic: see liquefactive necrosis: well demarcated soft area (1wk-1month)
progression of irreversible neuronal injury > 2 wks
macroscopic: cystic area surrounded by gliosis (>1 month)
severe skin & subcutaneous fat necrosis soon after initiating warfarin?
related to early prothrombotic effects, as warfarin inhibits protein C early (shortest half-life), intitially pro-thrombotic
pronounced w/ high doses of warfarin & patients w/ preexisting protein C deficiency
definition of polycythemia in men? women
hematocrit > 52% in men
>48% in women.
differentiate between relative vs. absolute polycythemia?
measure RBC mass
secondary erythrocytosis can be driven by what level of hypoxia?
SaO2 < 92% (PaO2 < 65 mmHg)
‘classic’ phases of acid secretion within stomach
cephalic: ACh and vagal influence (thought sight, smell)
gastric: mediated by gastrin (which stimulates histamine, and therefore, acid secretion)
intestinal: when protein-containing food enters duodenum. THIS ACTUALLY DOWNREGULATES gastric acid secretion
role of the intestinal phase in gastric acid secretion
presence of protein in duodenum actually downregulates acid secretion.
ileum and colon release peptide YY, bind to receptors on ECL cells, inhibits gastrin-stimulated histamine release.
reflex that allows gastric fundus to dilate in anticipation of food passing through pharynx and esophagus.
prostprandial alkaline tide
increase in plasma HCO3- and decrease in plasma Cl- secondary to surge of acid within gastric lumen.
does not play a role in downregulating post-prandial gastric secretion
presence of a NON-BIZARRE delusion for at least one month.
unlikely, but possible, like being followed, cheated, or poisoned (as opposed to covert alien activity)
usu single overriding delusion w/ preserved occupational and social functioning. does not meet diagnostic criteria for SZ
paranoid personality vs. delusional disorder
paranoid personality disorder: pervasive pattern of suspiciousness vs. one fixed delusion (delusional disorder)
after ischemic injury in most tissue (except brain)
- architecture PRESERVED after death (due to denaturation of lytic enzymes & disrupted proteolysis)
- cell = ANUCLEATED w/ eosinophilic cytoplasm
- leukocytes eventually infiltrate & digest
- seen w/ focal BACTERIAL infection that stimulate MASSIVE leukocyte recruitment
- occurs in CNS infarcts due to LACK of substantive supporting STOMA.
- necrotic cells completely digested by hydrolytic enzymes, forming VISCOUS LIQUID MASS
- often creamy yellow due to dead leukocytes (PUS)
- associated w/ ABSCESS formation in peripheral tissue. brain = CSF-FILLED SPACES
- release of active pancreatic enzymes, included LIPASES, digest adipose cells & release free fatty acids
- SAPONIFICATION (CHALKY-WHITE DEPOSITS) form when fatty acids combine w/ calcium.
- most commonly withTB INFECTION
- also w/ FUNGAL (histo, cryptococcus, coccidioides)
- necrotic tissue = CHEESY TAN-WHITE gross appearance & consists of fragmented cells & acellular proteinaceous material.
- surrounded by macrophages & other inflammatory cells, forming GRANULOMA
TB in brain parenchyma
could cause CASEOUS NECROSIS (even though brain is often liquefactive necrosis)
histologic pattern of injury seen in walls of blood vessels affected by vasculitis syndromes (i.e. polyarteritis nodosa), malignant HTN, and diabetes mellitus
nonenzymatic fat necrosis
following trauma, female breast = common example. often mistaken for breast tumor.
gallbladder hypomotility? risk factors?
slow / incomplete gallbladder emptying in response to cholecystokinin stimulation
pregnancy, rapid weight loss, prolonged use of parenteral nutrition or ocreotide, high spinal cord injury.
describe biliary sludge
consequence of gallbladder hypomotility. results from bile ppt.
contains cholesterol monohydrate crystals, calcium billirubinate, & mucus.
known precursor to stone
acute cholecystitis can occur in 20% of patients w/ biliary sludge.
brown GB pigment stones
arise in cases of biliary tract infection
black GB pigment stones
arise in causes of intravascular hemolysis
cystinuria presents w/ defective transport of..
cysteine, ornithine, lysine, and arginine
when does scarlet fever begin post group A strep infection? symptoms?
- fever, malaise, abdominal pain, sore throat
- “strawberry tongue” - inflammed red papillae
- pharynx: erythematous, swollen, covered w/ gray-white exudate
after 1-2 days:
- rash on neck, armpit, groin.
- subsequently generalizes to rest of body
- ‘boiled lobster’ appearance - scarlet spots / blotches
- “sandpaper-like” - sunburn w/ goose pimples
cheeks: flushed, giving area around mouth circumoral pallow.
end of 1st wk:
- desquamation in armpits, groin, tips of fingers, toes
predispose to glomerulonephritis / rheumatic fever
differentiate kawasaki vs. scarlet fever
tonsilar exudate: scarlet fever
bilateral conjunctivitis: kawasaki
coronary aneursym: kawasaki
both have strawberry red tongue, desquamation
3 different neuro manifestations of measles
recovery: acute disseminated encephalomyelitis
years later: subacute sclerosing panencephalitis
factor V leiden
DVT, cerebral vein thrombosis, recurrent pregnancy loss.
most common inherited thrombophilia.
hets have 5-10x risk of thrombosis
homoz have 50-100x risk
- factor V has less susceptibility to protein C cleavage
- factor V cannot support activated protein C activity
(increased coag, decreased anticoag)
renal artery stenosis primary caused by (2)
where does malignant melanoma arise
can arise in: eye, esophagus, meninges, mucosal surfaces
risk factors: sun exposure, hereditary, history of pre-existent dysplastic nevus in same location.
describe appearance of melanoma gross?
either asymptomatic or pruitic. -
- usu > 1cm.
- demonstrated change in color, size, shape.
- variability in pigment: shades of black, brown, red, navy blue, gray
- borders irregular/notched
histology of melanoma?
congregate in poorly formed nests. large w/ irregular nuclei, clumped chromatin. prominent nucleoli.
risk of melanoma metastasis
based on growth phase.
radial growth: remain superficial and extend horizontal within epidermis / superficial dermis. no risk of metastasis
melanoma w/ vertical growth – atypical immature cells travel down into deep dermal layeres – increase risk of mets.
most important prognostic factor in malignant melanoma?
depth of invasion (breslow thickness)