test #28 4.19 Flashcards
examples of delayed-type hypersensitivity reactions
(1) contact dermatitis
(2) granulomatous inflammation
(3) tuberculin skin test
(4) candida extract skin reaction
delayed-type HSR mediated by..
T-lymphocytes (not Ab or complement).
reaction takes 1-2 days, bc antigen taken up by dendritic cells, present to CD4+ cells on MHC II.
Th1 cells secrete IFN-gamma, recruit & stimulate macrophages –> monocytic infiltrate.
[also occurs when ‘walling off’ TV
increased WBC post-corticosteroids
falsely elevated. due to demargination (release from vascular walls) of cells
2 disorders of mast cells
urticaria pigmentosum. systemic mastocytosis
what two factors drive angiogenesis
VEGF and FGF
- vascular ENDOTHELIAL growth factor
- fibroblast growth factor
VEGF: angiogenesis in variety of tissues: normal, chronically inflammed, healing, neoplastic. increases endothelial cell motility and proliferation –> new capillaries.
FGF-2: made by many cells. significantly involved in (1) promotion of endothelial cell proliferation, migration, and differentiation. also: impt in (2) embryogenesis (stimulating angioblast production)
[FGF: angiogenesis, embryonic develoment, hematopoiesis, wound repair]
somatomedin C
IGF-1
synthesized by growth-hormone influenced hepatocytes. stimulate cell growth and multiplication.
barrier to angiogenesis
laminin in basement membranes
non-viral-dependent nucleotides analogues
cidofovir (activated by cellular kinase) & tenofovir
rx for thymidine kinase-deficient (acyclovir-resistant) varicella?
fosacarnet: (PYROPHOSPHATE analog viral DNA polymerase inhibitor)
cidofovir: broad spectrum NUCLEOTIDE. analogue of cytidine monophosphate (activated by CELLULAR kinase)
factitious disorder vs. malingering
both CONSCIOUSLY creates symptoms.
factitious: for 1’ gain (sick role/medical attn)
malingering: for 2’ gain (avoid work, compensation)
munchausen syndrome
chronic factitious disorder
conversion disorder
unconscious; somatic.
post-stressor.
sudden neurological symptoms (loss of sensory/motor) with NO physical evidence.
somatic disorder vs. factitious & malingering
somatic disorder syndromes (i.e. conversion, hypochondriaisis, somatization) are UNCONSCIOUS
factitious & malingering: CONSCIOUS
somatization disorder (vs. conversion disorder)
somatoform disorder, several symptoms
usu begins <30 y/o. impact social/occupation.
4 pain
2 GI
1 sexual
1 neuro
with no physical exam / imaging evidence
(differs from conversion, which has specific NEURO and POST-STRESSOR)
hypochondriasis
somatoform disorder
preoccupation/fear of having serious illness despite medical evaluation & assurance.
often, mistinterpretation of normal bodily symptoms (gas = colon cancer). associated w/ Dr. shopping
body dysmorphic disorder
think body is pathologically flawed, when in fact, it is not.
chromosome 3p deletion
VHL
von-Hippel Lindau
autosomal DOMINANT.
cerebellar hemangioblastomas, clear cell renal carcinoma, and pheochromocytoma.
RCC develops in 40% of patients.
tumor supressor
cerebellar hemangioblastoma, clear cell renal carcinoma, pheochromocytoma
VHL (tumor supressor chr. 3)
location of RB
chr. 13
osteosarcoma and retinoblastoma
location of NF-1
chr. 17
WT-1 location
chr. 11
location of chemoreceptor trigger zone (area postrema)
dorsal surface of medulla, caudal end of fourth ventricle.
adhesion molecules
integrin, cadherin, selectin, Ig superfamily members
laminins bind to
collagen, fibronectin, laminin in ECM
fibronectin
large glycoproteins produced by fibroblasts & some epithelial cells. binds to integrin, matrix collagen, glycosaminoglycans. mediations cell adhesion
heparan sulfate
proteoglycan component of ECM.
associated w/ reticular fibers and basal laminae. helps w/ endothelial cell attachment to BM.
does not bind to cell surface integrins.
hyaluronic acid
glucuronic-acid containing glycosaminoglycan in ECM.
contributes to water retention in ECM -> lubricant properties. viscous, gel-like consistency.
elastic fibers
core of elastin protein surrounded by fibrillin
keratan sulfate
galactose-containing glycosaminoglycan. role in maintaining type I collagen fibril organization in cornea.
aromatase deficiency
present early:
- mom virilization (androgens)
female:
- ambiguous/male genitalia
- primary amenorrhea & tall (no estrogen to fuse epiphyseal plate
male
- tall w/ osteoperosis
aromatase rxns (2)
androstenedione -> estrone
testosterone -> estrogen
aromatase deficiency vs. 21-b hydroxylase deficiency in girls
aromatase deficiency
- has mom virilization
- no hypotension w/ salt wasting & hyperkalemia
auscultation site determined by..
position closest to where sound waves reverberate. NOT at position of valve
glomerular splitting of basement membrane (2)
MPGN II and Alport syndrome
Alport syndrome
triad:
1. glomerulonephritis
2. sensorineural deafness
3. eye problems
mutation in alpha-side chain of collagen type IV.
thinning and splitting of basement membrane
X-linked dominant.
nasal mucosal ulcerations “saddle nose” w/ glomerulonephritis
granulomatosis w/ polyangiitis (wegner’s)
HSP 4 signs
IgA / C3 deposits everywhere 1. palpable purpura 2. abdominal pain 3. arthralgia usu self-limiting, but can get.. 4. glomerulonephritis & end-stage renal failure
usu post-infectious
drugs w/ negative chronotropic effects
(1) b-blockers
(2) non-DHP calcium blockers
(3) digoxin (independent vagal effects)
(4) amiodarone
(5) sotalol (class III w/ b-blocking effects)
(6) cholinergic agonists
what cell type exerts master control over iron metabolism?
HEPCIDIN, made by liver parenchymal cells
fate of Fe2+ in GI system
absorbed via DMT-1 channel in duodenum, bind to intracellular FERRITIN..
(1) stay in enterocyte, and pass in stool when sloughed off
(2) exist basolaterally via FERROPORTIN -> bind to transferrin in blood -> taken up by cells via transferrin receptor
PATH determined by hepcidin!
hepcidin
acute phase reactant. binds to ferroportin in enterocytes & macrophages & degrades it.
BLOCKS release of Fe2+. prevents iron overload.
anemia of chronic disease
increased levels of hepcidin (from liver) down regulate ferroportin. trap Fe2+ in macrophages and enterocytes.
filtered load =
GFR x Px
excretion rate =
V x Ux
RPF estimated w/
PAH clearance – fully cleared
GFR estimated w/
creatinine clearance (similar to inulin)
normal filtration fraction
20% (GFR/RPF)
when does glucose begin to appear in urine? when are glucose transporters maximally saturated?
- begin at 200mg/dL
- saturated at 375mg/dl
normal GFR
100ml/min
180L/day
when GFR is normal (100ml/min), large decreases in GFR, causes ___ in serum creatinine
small increases in serum creatinine
when GFR is very low (<60ml/min), small changes in GFR causes ___ in serum creatinine
LARGE increases in serum creatinine
serum creatinine can be normal after loss of how much GFR
even after 50% loss!
general rule of thumb with changes in GFR & serum creatinine
everytime GFR halves, serum creatinine doubles.
increase in cardiac output during exercise
5 L/min to 20 L/min
early in exercise, how is CO maintained?
increase BOTH HR and SV
late in exercise, how is CO maintained
increase only HR
stroke volume maxes out
pulse pressure is directly related to? inversely related to
PP = systolic - diastolic
directly related to CO
inversely related to arterial compliance
three sympathetic hemodynamic effects in exercise.
why does MAP only increase 2-40mmHg?
(1) increased CO
(2) venoconstriction to increase preload
(3) vasoconstriction to muscles not participating in exercise
only modest increase in MAP bc of MAJOR decrease in SVR due to…
local vasodilation in skeletal muscle (via adenosine, adenosine, K+, ATP, CO2, lactate)
in exercise, skeletal muscle can get 85% of CO
infection of liver capsule w/ violin string adhesions of peritoneum to liver.
Fitz-Hugh-Curtis syndrome, resulting from PID
manifestation of pelvic inflammatory disease
endometritis, salpingitis, tubo-ovarian abscesses, pelvic peritonitis
can result in infertility
how does pregnancy increase risk of gallstones?
ESTROGEN: increase HMG-CoA reductase activity, bile = SUPERSATURATED w/ cholesterol
PROGESTERONE: reduce bile acid secretion, slow gall bladder emptying = HYPOMOTILE
together: ppt cholesterol crystals
staphylococcus bacteremia associated with..
intravascular devices
i.e. indwelling central venous catheters
in dehydration, fluid is primary reabsorbed by..
always PCT (~65% reabsorption), even in dehydration
collecting ducts can take ~20% free water
Fenoldopam
SELECTIVE D1 agonist.
vasodilate most ARTERIAL beds (esp coronary, renal, splanchnic, peripheral)
overall decreased SVR.
increased flow to kidney allows for Na+ and H20 excretion
ONLY drug to reduce BP while increasing blood flow to KIDNEY
rx for HTN emergency w/ concomittant renal insufficiency
fenoldopam
diazoxide
anti-HTN
K+ activator, relax smooth muscle –> ARTERIAL vasodilation
mechanism of hydralazine. must be given w/?
increase cGMP -> smooth muscle relaxation
arterioles > vein. afterload reduction
must give w/ beta-blocker, as it causes reflex increased contractility, HR, & fluid retention
first-line rx for HTN in pregnancy?
hydralazine (increase cGMP) with methyl-dopa (a2 agonist)
methyl-dopa
HTN in pregnancy. alpha-2 agonist
use of hydralazine & diazoxide
though arteriole vasodilator, often cause significant increase in HR and contractility & Na+ and fluid retention
nimodipine
DHP calcium channel blocker, used for post-subarachnoid hemorrhage (to prevent vasospasm)
nicardipine
DHP calcium channel blocker. vasodilates arterioles & myocardium.
can cause tachycardia
ways to get EHEC 0157:H7
- eating undercooked contaminted ground beef.
- person-to-person
- raw unpasterized milk
- swimming in / drinking sewage contaminated water
1st line disease modifying for rheumatoid arthritis?
methotrexate.
Leflunomide and TNF-alpha inhibitors for rheumatoid arthritis
also disease modifying agents, can use in combo w/ methotrextate
leuflunomide – decreases pyrimidine synthesis
methotrexate side effects
stomatitis (painful mouth ulcers) and hepatotoxicity (hepatitis, cirrhosis)
hydroxychloroquine
unclear mechanism. accumulates in cell, and increases pH, reducing fxn.
antimalarial and used in SLE
impt side effect of hydroxychloroquine
RETINAL DAMAGE
formula for volume of distribution
amount of drug given (mg) / plasma concentration of drug (mg/L)
what causes a drug to stay in blood (low volume of distribution) (3)
large molecular weight
bound extensively to plasma proteins
highly charged
(~3-5L)
if drug has small molecular weight, but hydrophillic
will also distribute to interstitial space (~15L)
if drug has small molecular weight, and uncharged
can also cross cell membranes – ~41 volume of distribution
Vd for drugs that are avidly bound in tissues?
higher than total body water (>40L)
G. lambia in stool
O&P (smear w/ iodine stain)
ellipsoidal cysts w/ smooth defined walls and 2+ nuclei
loperamide
opiate antimotility drug, can be used in traveller’s diarrhea w/ no fever / blood in stool
rx for inflammatory traveler’s diarrhea (stool w/ mucus & blood)
ciprofloxacin
rx for ancylostoma, ascaris, enterobius?
mebendazole
rx for tapeworms (cestode) echinococcus granulosa
albenzadole
mechanism of enfuvirtide
binds to gp41, blocks conformational change needed for fusion
side effects of nnrtis (nevirapine, efavirenz, delavirdine)
hepatic failure (first 6 wks). also steven-johnsons
propionyl-CoA made from catabolism of…
VOMIT
valine, odd-chain fatty acids, methionine, threonine, isoleucine, threonine
propionyl-CoA carboxylase deficiency
build up proprionyl-CoA
poor feeding, vomiting, hypotonia, lethargy, dehydration
exacerbated by VOMIT:
valine, odd chain fatty acids, methionine, isoleucine, threonine & cholesterol
L-asparaginase therapy
antineoplastic, gets rid of asparagine in serum (so rapidly dividing leukemic cells can’t use it, as their synthesis of asparagine is impaired)
histidine metabolism
deaminated to urocanic acid, converted to N-forminino-glutamate (FIGlu). forimino group donated to THF to form glutamate and forminino-THF.
oxidative decarboxylation of histidine forms histamine –> released by mast cells in type I HSR
proline is a nonessential amino acid oxidized into..
glutamate
prognosis of minimal change disease
rapid response to corticosteroids
rx for all symptoms organophosphate poisioning?
pralidoxime (restore AchE)
atropine only stops muscarcinic effects, not nicotinic.
bronchi differences in chronic bronchitis due to smoking vs. asthma?
both have: thickening of bronchial epithelium, basement membrane, and bronchial walls, as well as edema, inflammatory infiltrates, submucosal mucous gland enlargement, and bronchial smooth muscle hypertrophy
smoking: patchy squamous metaplasia & neutrophil infiltrate
asthma: eosinophil / mast cell infiltrate
rupture of chordae tendineae can occur with..
endocarditis or MI
diseases that cause myocardial fibrosis
dermatomyositis, muscular dystrophy, carcoidosis, scleroderma
vegetations associated w/ bacterial endocarditis represent..
FIBRIN & PLATELET deposition at site of bacterial colonization.
often at site of endothelial damage
myxomatous degeneration of valve
often mitral valve in MVP.
in the setting of CT diseases, like Marfan’s.
can predispose to endocarditis.
coarctation of aorta in infants pre-ductal pr post-ductal? cyanotic?
preductal. though there is right-to-left shunting, not enough to cause cyanosis.
5T’s of congenital cyanotic diseases
(1) tetrology of fallot
(2) tricuspid atresia
(3) total anomalous pulmonary return
(4) truncus arteriosus
(5) transposition of the great vessels
what is tricuspid atresia?
congenital cyanotic heart disease.
one ventricle feeds both aorta & pulonary artery
pulmonary alveolar proteinosis (PAP) (presentation & histology)
presents: gradually worsening of dyspnea and productive cough
histology: bilateral patchy pulmonary opacification due to intraalveolar accumulation of protein & phospholipid (constituents of surfactant)
characterestic presentation of idiopathic pulmonary fibrosis
insidious-onset progressive exertional dyspnea, pulmonary function tests w/ restrictive profile
surgical biopsy: extensive interstitial fibrosis, paraseptal and subpleural cystic airspace enlargement (honeycomb lung)
restrictive pulmonary function test
FVC low
FEV1/FVC normal (>80%)
routes of hepatic abscess in US? in developing nations
- portal vein
- arterial supply
- ascending biliary tract infection
- direct invasion from adjacent source
- penetrating injury
developing nations: parasitic infxn
most likely cause of hepatic abscess in US
hematogenous spread of staph aureus
valve abnormality in turner’s
bicuspid
nonstenotic bicuspid aortic valve murmur
aortic ejection sound. early systolic, high frequency click over cardiac apex and/or right second interspace
most common cardiac abnormality in Turner’s?
bicuspid aortic valve. can also have coarctation
calcitonin
decreases serum Ca2+ levels.
decreases bone resorption of Ca2+ by osteoclast inhibition, but not a dominant hormone
levels increase when given exogenous Ca2+
PTH regulates Ca2+ by.. (3)
(1) release from bone
(2) increased vitamin D to reabsorb more in gut
(3) increased renal absorption
vitamin D under control of..
high PTH mainly.
also low Ca2+ and low PO4-
when are calcitonin levels LOW?
when serum Ca2+ is low
xeroderma pigmentosum has mutation in what type of enzyme
UV-specific ENDOnuclease
not EXOnuclease
NADPH is required for..
fatty acid, cholesterol, and steroid synthesis
parinaud syndrome
paralysis of conjugate vertical gaze due to lesion in superior colliculi (i.e. pinealoma)
(pineal gland is anterior-superior to superior colliculi)
erythematous, papulovesicular, weeping, encrusted lesions that may evolve into thickened scaly plaques
eczematous dermatitis.
prone to bacterial superinfection – yellow crust
5 types:
- allergic contact dermatitis
- atopic dermatitis
- drug-related eczematous dermatitis
- photo-eczematous dermatitis
- primary irritant dermatitis
spongiosus
seen in exzematous dermatitis (i.e. contact dermatitis)
epidermal accumulation of edematous fluid in intercellular spaces.
intercellular bridges become distinctive. epidermis = spongy.
edema can become so marked –> intraepidermal vesicles by tearing desmosomes apart
acanthosis
increase in thickness of stratum SPINOSUM.
associated w/ psoriasis
dyskeratosis
abnormal, premature keratinization of individual keratinocytes. strongly eosinophilic and may have small basophilic nuclear remnant.
found in squamous cell carcinoma
hyperparakeratosis
retention of nuclei in stratum corneum (suggests incomplete keratinization)
normal on mucus membrane, but abnormal (actinic keratosis) in other areas
hypergranulosis
excessive granulation in stratum granulosum of epidermis. seen in lichen planus
lesser omentum
composed of hepatogastric and hepatodudenal ligament (along lesser curvature –> liver)
greater omentum
along grater curvature
adjustable gastric banding must pass through
lesser omentum, to enclose cardia
falciform ligament of liver
attaches liver to anterior body wall (contains ligamentum teres)
what ligament must be divided to have access to posterior stomach and anterior pancreas
gastrocolic ligament (connects greater curvature of stomach to transverse colon)
part of the greater omentum
what is contained in splenorenal ligament (2)
(2) splenic artery & vein
(3) tail of pancreas
