genetic pulmonary hypertension? demographic?
inactivating mutation in BMPR2. normally inhibits smooth muscle proliferation.
uterine leoimyomas presentation? demographic?
some asymptomatic. others: pelvic pressure, pain, menorrhagia, reproductive difficulties.
more common in women in thirties and forties. black women esp.
mucosal hemorrhage, patchy areas of necrosis.
eventually becomes edematous and bowel wall thickens. then transmural infarction –> bowel perforation.
crampy abdominal pain, tenderness to palpation, bloody stool.
caused by (1) hypoperfusion 2nd to diministed cardiac output (2) occulusion of bowel vascular supply (atheroma, thrombosis, embolism)
common cause of GI hemorrhage in elderly.
presentation of whipple’s disease
PAS+ foamy macrophages in lamina propria
CANN: cardiac symptoms (valves), arthalgia (synovial), mesenteric Nodes, and Neurologic symptoms (CNS).
–> fat malabsorption // steatorrhea bc of occlusion of lymphatics
nfxn w/ tropheryma whipplei (gram positive)
type 1 collagen important in
bone, fibrous tissue, tendon, ligament, skin, sclerae.
body is 30% collagen by weight
mutations in osteogenesis imperfecta
COL1A1 and COL1A2. both combine to form type 1 collagen –> results in qualitative and quantitative type I collagen defects
brittle bone, short stature, scoliosis, blue sclerae (translucent CT over choroidal veins), hearing loss (abnormal ossicles), skin and ligament laxity, easy bruising.
blue sclerae seen in..
osteogenesis imperfecta, progeria, menkes syndrome, cutis laxa
general beta oxidation & ketone production
sequential removal of two-carbon units (acetyl-CoA) from fatty acids
first step. Acyl CoA dehydrogenase. when a lot of acetyl-CoA is made via beta oxidation, shunt to ketone body production (acetoacetate, 3-hydroxybutyate, acetone)
3 forms of acyl CoA dehydrogenase
short, medium, long-chain
most common genetic defect in beta oxidation
medium chain acyl CoA dehydrogenase deficiency. symptoms first few years of life w/ prolonged fasting.
see increased dicarboxylic acids [from omega oxidation]. low glucose & ketones. acetyl-CoA low, cannot stimulate pyruvate carboxylase in gluconeogenesis. low acetyl-CoA, low glucose.
[energy from beta oxidation needed for gluconeogenesis!]
cleave alpha-1,4-glycosidic link between glycogen, liberates glucose-1-phosphate.
results in McArdles, when missing from muscle.
results in Hers disease, when missing from liver.
oncoprotein component of MAP-kinase. inactive-GDP bound. active-GTP bound.
brings signal from receptor of cell surface into nucleus – promote mitogenesis.
nuclear phosphoprotein. fxns as a transcription activator controlling cell proliferation, differentiation, and apoptosis.
nuclear phosphoprotein, regulates G1-S checkpoint.
velocity of a chemical reaction depends on.. (3)
concentration of enzyme, substrate, and product
increasing enzyme concentration
lower Y intercept on lineweaver-burke plot
increased Km on lineweaver burke plot
right on x-intercept (-1/Km)
what do chlamydia have INSTEAD of cell wall
cysteine-rick out membrane w/ S-S bridges
multicellular branching filaments
four rRNA in eukaryotic cells
28S, 18S, 5.8S, 5S.
first: 45S transcript made by rRNA (pre-RNA) and cleaved in nucleolus by ribonucleases to make 28S, 18S, 5.8S rRNA molecules.
(ensures equal amounts are made)
5S rRNA made separately by RNA pol III
note additive, based on molecule size and how they move during centrifugation in a viscous medium.
how do thiazolidinediones increase insulin sensitivity
increase GLUT4 expression, increases number of insulin-responsible adipocytes.
second generation sulfonyurea. closes K+ channel of pancreatic B cell, induces depolarization and L-type Ca2+ opening; stimulating insulin release.
meglitinide dervative: short-acting insulinotropic agent. adjunct to diet & exercise in DM-2. mechanism similar to sulfonyureas.
unlike sulfonyureas, repaglinide does NOT stimulate insulin release when extracellular glucose levels are lw
first generation sulfonyureas
second generation sulfonyureas
glyburide, glimepiride, glipizide
pramlintide; reduce gastrin emptying, reduce glucagon
increase insulin release, reduce glucagon release
like DDP-4 inhibitors
(side effect: pancreatitis
linagliptin, saxagliptin, sitagliptin
increase insulin, reduce glucagon (like GLP-1 analogs).
side effect: urinary or upper respiratory infection
can be used in absence of B cell function. decrease gluconeogenesis and increases glycolysis in cells
Crohn’s disease extrainstestinal signs
perineal abscess, kidney stones, sacroilitis, strictures/fistula
(ankylosing spondylitis, uveitis, apthous ulcers, pyoderma gangrenosum, erythema nodosum)
Ulcerative colitis extraintestinal signs
primary sclerosing cholangitis
pyoderma gangrenosum, erythema nodosum, ankylosing spondylitis, apthous ulcers uveitis
crohn’s disease vs ulcerative colitis on barium swallow
crohn’s = string sign (bowel wall thickening)
ulcerative colitis = loss of haustra (lead pipe sign)
common area involved in crohn’s disease? second?
1st: terminal ileum
common area involved in ulcerative colitis
always rectal involvement. only colon (no small bowel)
normal half life of warfarin
40 hours (steady state 4 hours later – 6.7 days)
therefore, P450 inducers/inhibitors take a few days to alter levels
warfarin in pregnancy
crosses placenta! teratogenic
why does warfarin cause skin / tissue necrosis
early –> prothrombotic bc kills off protein C before factors 2, 7, 9, 10 (due to protein C half life)
rx for hepatic encephalopathy
remove ammonia, acidify intestinal contents (i.e. lactulose –> lactic acid), to increase NH4+
lactulose rx for hepatic encephalopathy
nonabsorbable dissacharide, degraded by colonic bacteria –> lactic & acetic acid. acidify GI content – convert NH3 -> NH4+ –> osmotic effect, results in luminal distention, promote peristalsis –> levels of ammonia in circulation gradually declines
how does B2 agonist cause bronchodilation
increase cAMP INHIBITS myosin light chain kinase
after trauma: firm but flexible hyaline cartilage, gradually strengthened by Ca2+ deposition and a surrounding meshwork of woven bone.
physical signs of peripheral artery disease (i.e. DM)
thinning of skin, calf claudication (w/ rest pain), prolonged venous filling time, shiny coloured skin, hair loss, nail changes.
signs & symptoms of DVT
leg pain, tenderness, edema, fever, Homan’s sign, venous distension
diabetic patient w/ foot infxn
think peripheral artery disease
RET in MEN2
single allele ACTIVATING mutation, predisposes to malignancy
DDx for hoarseness
laryngitis (most common), vocal cord paralysis, vocal cord nodules, laryngeal cancer, GERD, thyroid masses, overuse
path of right and left recurrent laryngeal n
RIGHT: loops below right SUBCLAVIAN (junction between brachiocephalic artery)
LEFT: loops below AORTIC ARCH
fxn of recurrent laryngeal
intrinsic muscles of larynx except CRICOTHYROID (external laryngeal)
most DNA virus replicate where? except one DNA to replicate in cytosol completely? partially?
most in nucleus
completely cytosol: pox virus (largest DNA virus, carries own DNA-dependent RNA polymerase)
membrane of Herpesvirus?
from nuclear membrane
circular DNA viruses (3)
polyoma, papilloma, hepadna
RNA viruses mostly replicate in? except?
except: retrovirus and influenza virus
naked DNA viruses
parvovirus, adenovirus, polyoma virus, papilloma virus
naked RNA virus
calicivirus, picornavirus, reovirus, hepevirus
capsid of all DNA viruses
icosahedral (except pox, complex)
all arboviruses cause.. name classes (3)
encephalitis & fever.
flaviviridae, togaviridae, bunyviridae
papillomavirus and polyomavirus
infection w/ coccidiodes immitis
spherules w/ endospores that propogate. usually mild pneumonia w/ pleural effusion, can have thin-walled cavities (fever, hemoptysis)
currant jelly hemopytsis
klebsiella! lobar, alcoholic
less than 200ml. weakness and dyspnea, ground glass on x-ray
walking pneumonia. fever, malaise, nonproductive cough
which cells are affected in hashimoto thyroiditis?
auto-immune mediated apoptosis of epithelial cells in thyroid gland.
see intense, diffuse (B & T) cell lymphocytic infiltration, germinal center formation.
high levels of serum thyroid autoantibodies (anti-TG & TPO)
histology of graves disease
thyroid gland follicular epithelium TALL & crowded, forming pseudopapillae into follicular lumen
diffuse, nontoxic goiter. can occur sporadically. flattening of crowded columnar epithlium in follicles. gland becomes enlarged and colloid rich.
follicular adenoma presentation
presents as unilateral neck mass. intact capsule separate normal thyroid tissue from numerous large, well-differentiated, colloid-containing follicles
single nodule in older woman. relatively uniform cells forming small follicles, nests, or sheets. colloid may be in follicles. capsular invasion with areas of hemorrhage or vascular invasion are common,
holosystolic murmur over left sternal border
PDA on oxygenation of blood
allows oxygenated blood to flow from AORTA to pulmonary artery (spike in PO2)
by when does Duchenne’s present?
age 3-5 progressive weakness, gower’s.
by age 12: loose ability to walk
supression vs. repression
suppression: mature, conscious, TEMPORARY withhold unpleasant information from one’s awareness to postpone dealing with it.
repression: immature, unpleasant feelings pushed away, not to be dealt with.
two key features of achalasia
hypertensive LES. absence of esophageal peristalsis in distal esophagus
due to less inhibitory ganglion cells in esophageal wall (imbalance favoring activity of excitatory ganglion cells)
reduced GpIIb/IIIa. labs: no platelet clumping on smear (less platelet-platelet interaction)
like ITP / abciximab
Bernard Soulier syndrome
reduced GpIb (less platelet-vWF interaction)
what motor abnormality often accompanies broca’s aphasia?
located inferior frontal gyrus.
head and upper limb (near primary motor cortex
damage to frontal eye field (frontal lobe)
IPSILATERAL eye deviation
normally points eye in opposite direction
inability to identify objects based on touch
inability to identify characters drawn on skin by touch alone
loss of sensation on one side of body
on axial MRI, prostate is located
posterior to the pubic symphysis
can be related to MAP and total vascular resistance in afferent and efferent arterioles
RPF = MAP / TVR
TVR = resistant in afferent + efferent
postganglionic autonomic nervous system axons are..
important unmyelinated axons
(1) postganglionic autonomic axons
(2) afferent neurons that conduct heat sensation & from slow-onset dull, burning or visceral pain.
(3) first order bipolar sensory neurons of OLFACTION
unmyelinated referred to: group C fibers
preganglionic autonomic nervous system fibers are..
both sympathetic and parasympathetic.
grey vs. white rami communicans
white: preganglionic (myelinated) fibers from spinal cord to sympathetic chain.
grey: post-ganglonic (unmyelinated) fibers from sympathetic chain to spinal nerve.
shared psychotic disorder
development of delusion in a person who is in a close relationship w/ a delusional person
(when not better explained by another psychotic disorder, medication, drug of abuse)
magical thinking in schizotypial
odd beliefs (telepathy, superstitions, bizarre fantasies, preoccupations)
eccentric behavior, odd thinking, & ideas of reference
often lack close relationship
non-bizarre delusions present for at least one month.
non-bizzare: situations that, while unlikely, are possible. being followed, cheated, poisoned.
also: preserved occupational/social functioning, failure to meet diagnostic criteria for schizophrenia.
formula for standard error
standard deviation / square root of n (same size)
SE decreases when sample size is increased
larger sample size, smaller standard error
aseptic meningitis often caused by
(usu enteroviruses: poliovirus, coxsackie A & B, echorvirus)
enterovirus that doesn’t cause asceptic meningitis: hepatitis A)
picornavirus that is not an enterovirus: rhinovirus
two important arenaviruses
- LCV (lymphocytic choriomeningitis virus): aseptic meningitis
- lassa virus: hemorrhagic fever virus, passed to humans when dirt / dust contaminated by rodent urine inhaled.
- ss RNA
always bring polymerase or fail replication
must bring own RNA-dependent RNA polymerase
arenavirus, bunyviridae, paramyxovirus, orthomyxovirus, filovirus, rhabdovirus
note: FILO (not flavi) and RHABDO (not reo or retro)
filo - ebola, marbug, crazy.
rhabdo - rabies, crazy
what’s included in paramyxoviridae
mumps, measles, RSV, parainfuenza
mumps & measles can cause encephalitis
most common cause of infant pneumonia? croup?
infant pneumonia & bronchiolitis: RSV
MHC II coded by
HLA-DR, DP, DQ
MHC I coded by..
HLA-A, B, C
composition of MHC class I? class II
MHC I: alpha chain & b2 macroglobulin
(proteosomal fragments load peptides (via TAPs) into ER, assemble w/ b2 macroglobulin and alpha chain)
TAP = transporter associated w/ antigen processing
MHCII: alpha & beta chain
(invariant chain in ER) – invariant chain degraded in endosome
possible presentation of iron deficiency anemia
(typical anemia: weakness, fatigue, headache, irritability)
& glossal pain, dry mouth, atrophy of tongue papillae, alopecia, pagophagia (eating ice)
craving for ice, specific for iron deficiency
presentation of folate deficiency
megaloblastic anemia w/..
sore tongue, pain on swallowing, angular stomatitis, GI upset, hyperpigmentation
inheritance of sideroblastic anemia
associated w/ MDS
x-linked recessive defect in d-ala synthase
(can’t turn glycine + succinyl CoA —> d-ALA)
acquired sideroblastic anemia causes
most common: alcohol. also, lead, B6 deficiency, Cu deficiency, isoniazid
histology of sideroblastic anemia
ringed sideroblasts w/ iron-laden mitochondria.
presentation of pernicious anemia
usu older women of northern european descent.
- lemon-yellow colouring
- smooth shiny tongue (atrophic glossitis)
- shuffling broad-based gait
high baseline plasma insulin w/ normoglycemia?
EARLY insulin resistance
(even when glucose levels are normal, and respond to oral glucose just fine)
eventually, amyloid deposition in pancreas w all this glucose secretion will make it fail
early insulin resistance vs. insulinoma
both have chronically elevated insulin levels.
normal serum glucose w/ EARLY insulin resistance.
insulinoma: fasting HYPOGLYCEMIA (i.e. after exercising)
marfan syndrome (fibrillin gene mutation) and homocystinuria (cystathione beta-synthase deficiency) both result in..
genetic heterogeneity. mutations of diff genes –> same phenotype.
marfanoid body habitus, tall, thin stature, elongated extremities, arachnodacty, ectopia lentis.
how many ATP made in glycoylsis? anerobic. (aka RBC; no mitochondria, no oxidative phosphorylation)
2 ATP per glucose (+ 2 NADH, which are used to convert pyruvate to lactate)
how many ATP made with aerobic metabolism of 1 glucose
38 per glucose
1 cycle of TCA (w/ 1 acetyl-CoA) makes
consume acetyl-CoA –> 3 NADH, 1 FADH2, 1 GTP
how many ATP per NADH? FADH? GTP
NADH = 3 ATP
FADH2 = 2 ATP
1 GTP = 1 ATP
net aerobic metabolism of glucose via malate/aspartate shuttle (heart and liver)? via glycerol-3-phosphate shuttle (muscle)
net glucose via malate/aspartate: 32
net glucose via glycerol-3-phosphate: 30
enzyme inhibited by -azoles
prevent ergosterol synthesis.
build up lanosterol
antifungal, disrupts nucleic acid synthesis, inhibits thymidylate synthetase
V max depends on…
concentration of enzyme.
Km depends on..
affinity of drug for enzyme, inverse
enzyme inhibited by -binafine’s
prevent formation of lanosterol.
block squalene epoxide
build up squalene
lichen sclerosus et atrophocis
inflammatory condition. thought to have underlying autoimmune pathophysiology. autoantibodies against ECM1 protein.
both genders, any part of body. females –> genital and perineal region usu.
pruitis, dysuria, pain w/ defecation and dyspareunia.
lesions: white, atrophic macules w/ a “cigarette paper” quality. coalesce into plaques as condition progresses.
long term sequelae: squamous cell carcinoma, genital disfigurement.
rx: ultra high potency topical corticosteroids
mucosal surfaces of mouth / genital (labia majora not considered mucosal).
white thickening of mucosal surface.
many diff causes. often EBV w/ immunosuppression
vaginal candidiasis presentation? cutaneous?
vaginal: white, curd-like malodorus discharge.
cutaneous: skin folds. erythema and satellite pustules.
6 P’s: pruitic, purple, polygonal, planar papules & plaques.
mucosal presentation: wickham striae (reticular white lines)
histology: sawtooth infiltrate of lymphocytes at dermal-epidermal junction
extrinsic causes of ATN?
aminoglycosides, amphotericin B, radiographic contrast dye, heavy metals.
myoglobinuria, hyperuricemia, bence-jones protein in multiple myeloma