test #43 4.30 Flashcards
S4 heart sound results from
suddent rise in end diastolic ventricular pressure caused by atrial contraction against a ventricle that has reached the limit of its capacitance.
stiff ventricle
presystolic sound, precedes S1
when are the papillary muscles placed under tension
during ventricular systole
describe axoneme in flagella and cilia
circular array of microtubule doublets anchored at basal body and surrounding 2 central microtubules (9+2)
doublets connected by ATP-splitting dynein arms
primary ciliary dyskinesia
autosomal recessive
impaired ciliary & flagellar motility due to dynein protein defect
about 1/2 develop kartagener: male infertility, situs inversus, recurrent sinusitis/otitis, and bronchiectasis.
reaction formation
behavior pattern in which person does opposite of what he feels/desires
usu: person uses excessive havior to cover up how she/he really feels bc feeling that might be perceived as unacceptable by others in society.
wants to do crack, gives talks about how people who do crack should be shunned
(diff from altruism bc here, hope is to cover up a desire)
or angry at wife, tells her she looks great
short-term, immature, eventually breaks down
describe polyol pathway
glucose -> sorbitol
consume NADPH -> NADP+
via: aldose reductase
sorbitol -> fructose
consume NAD+ -> NADH
via: sorbitol dehydrogenase
note: retina, renal papilla, schwann cells have much less sorbitol dehydrogenase activity: prone to osmotic damage w/ glucose overload
lens has significant sorbitol dehydrogenase, but can still be overwhelmed.
note: oxidative stress from NADPH depletion also plays a role
primary energy source for sperm
fructose
where is the polyol pathway particularly prominent
seminal vesicles, make fructose for sperm
how does hyperglycemia lead to cataracts
overwhelm sorbitol dehydrogenase ability to convert sorbitol to fructose
sorbitol generates osmotic prssure, influx of water into lens cells –> hydropic lens fibers that degenerate. lens opacification.
oxidative stress from NADPH depletion also plays a role!
2 ways damage induced w/ hyperglycemia in lens, retina, schwann cells, renal papillae..
sorbitol accumulation -> osmotic damage
NADPH depletion: oxidative damage
xylulose
end product of glucoronic acid metabolism, and intermediate in pentose phosphate pathway
presentation of klinefelters
hypogonadism, eunuchoid habitus, small firm testes, genotype 47 XXY. have barr body
hormonal abnormalities in klinefelter
high LH, FSH.
low inhibin, testosterone
sperm count is decreased
seminferous tubules progressively destroyed & hyalinized –> small firm testes.
results in low inhbin & low testosterone (leydig cells also hurt)
results in high LH and FSH
congenital absence of GnRH-neurons called
Kallmann syndrome
decreased LH, FSH, testosteone, and sperm count
why is sperm count low w/ exogenous steroids
high LOCAL concentration of androgens needed for spermatogenesis.
exogenous steroids decrease LH production, reducing local testosterone in testes.
ends up w/ testicular atrophy over time.
hormonal problems in cryptoorchidism
high FSH, normal LH, normal testosterone, decreased sperm
sertoli cells susceptible to heat, poor inhibin, high FSH
when is aortic regurg heard loudest (peak murmur intensity)
greatest pressure difference,
when incompetent aortic valve closes
early diastolic, high-pitched, blowing descrendo.
mid to late diastole, intensity of murmur would be less bc magnitude of the gradient diminished.
left sternal border, patient leaning forward (valve to wall), end expiration
peak murmur intensity of mitral regurg
greatest pressure diff in ventricle and atria.
early systole. opening of aortic valve
peak murmur intensity of aortic stenosis
greatest pressure diff in aorta and ventricle.
peak of systole
crescendo-descrescendo
peak murmur intensity of mitral stenosis
greatest pressure diff in atria and ventricle
mid-diastole. low pitch rumble after the opening snap
low grade vs. high grade tumors
low grade: well differentiated. morphologically and architecturally similar to normal cells in tissue of origin
high grade: poorly differentiated, lack most characteristic feature of original tissue.
complete lack of differentiation: anaplastic
features of anaplastic (high-grade, poorly differentiated) tumors
pleomorphic cells w/ large, hyperchromatic nuclei, grow in disorganized fashion. contain numerous mitoses, and giant multinucleated cells.
- loss of cell polarity, complete disruption of normal tissue architecture, cells coalsce into sheets / islands in a disorganized, infiltrative fashion
- significant variation in shape & size (cellular pleomorphism) and nuclei (nuclear pleomorphism)
- disproportionately large nuclei (high NC ratio) often deep staining (hyperchromatic) w/ abdunfant coarsely clumped chromatin and nucleoli
- numerous, abnormal, mitotic figues
- giant, multinucleated tumor cells
bronchial epithelium
columnar
relative risk reduction
absolute risk (control) - absolute risk (treatment)
divided by
absolute risk control
musculocutaneous n
C5-7
major upper arm flexors
biceps brachii, coracobrachialis, brachialis muscles.
continues as lateral cutaneous nerve of forearm, sensory to lateral forearm
sensory innervation to the foot
mostly superficial peroneal n.
deep only: region between 1st & 2nd digits
impt strxr near medial malleolus
saphenous n & great saphenous vein; course anteriorly
posterior tibial artery, tibial n, tendons of flexor digitorum longus, flexor hallucis longus, tibialis posterior; course posteriorly
anastrozole, letrozole, exemestane
aromatase inhibitor
describe how the lens is attached to eye
lens is attached to suspensory ligaments, which are attached to the ciliary muscle.
ciliary muscle relaxes->
suspensory fibers are taut
lens flatten
ciliary muscle contracts ->
suspensory fibers are loose
lens thicken
age related changes in lens –? ]
presbyopia, inability of lens to focus on near objects
lens is hardened; loose elasticity as proteins undergo progressive degeneration
also, ciliary muscle less strong.
when contract ciliary muscle
loosen suspensory ligaments
lens no longer thickens
loose accomodation
presbyopia is most people? in myopic people?
most: loose ability to read fine print, eye strain after reading, need to hold objects farther from eye.
myopic (near-sighted): will retain ability to see up close w/o refractive correction & experience some improved distance vision
cause of skin aging (wrinkles: rhytides)
reduced elasticity, decreased amounts if supporting subdermal fat
- thinning of dermis and epidermis w/ flattening of dermoepidermal junction,
- decreased FIBROBLASTS
- reduced synthesis & increased breakdown of collagen & elastin
what position allows for S3 hearing?
low frequency
lie in left lateral decubiitus, fully exhale (bring heart close to chest wall)
what forms s-adenosyl-methionine SAM?
added adenosine from ATP to methionine
role of s-adenosyl-methionine SAM
methyl donor (methyltransferases take its methy & give to others)
becomes s-adenosyl-homocysteine –> homocysteine + adenosine
what is the precursor to homocysteine
s-adenosyl-homocysteine
which forms after SAM gives away a methyl
what are 2 fates of homocysteine
cystathione or methionine
cystathione -> cysteine
what converts homocysteine to cystathione
cystathione synthetase
+ B6 & serine
how does B12 help form homocysteine -> methionine
homocysteine -> methionine requires conversion of n5-methyl-THF to THF.
N5-methyl-THF -> THF requires B12.
w/o B12, accumulate N5-methyl-THF ‘folate trap’. can’t make methionine
methylmalonylCoA -> succinyl-CoA requires
methylmalonyl-CoA mutase, B12 cofactor.
fibroadenoma histology
cellular, myxoid stroma, encircles (and sometimes compresses) epithelium-lined glandular & cystic spaces.
sclerosing adenosis
proliferative breast disease
increased acini & intralobular fibrosis. associated w/ calcifications. often confused w/ cancer.
central acinar compression & distortion (by surrounding fibrotic tissue) & peripheral duct diitation
increase risk 1.5-2x of cancer.
paget’s disease of nipple
malignant cells spread from DCIS into nipple (w/o crossing basement membrane)
still in epidermis. will see large cells in epidermis w/ clear halo “paget cells”
unilateral erythema & scale crust
mammary duct ectasia
ductal dilation, inspissated breast secretion, chronic granulomatous inflammation in periductal / interstitial areas
medullary breast carcinoma (invasive)
fleshy, cellular, lymphocytic infiltrate.
good prognosis, associated w/ BRCA1
solid sheets of vesicular, pleomorphic, mitotically active cells w/ significant lymphoplasmacytic infiltrate around & within the tumor & a pushing, non-infiltrating border.
units of the breast anatomy
deep -> out
lobule, terminal duct, major duct, lactiferous sinus, nipple
intraductal papilloma
benign breast tumor, occurs in lactiferous duct, typically beneath areola
serous/blood nipple discharge,
slight risk w/ carcinoma
phyllodes tumor
large bulky mass of connective tissue & cysts. biphasic. may become malignant.
invasive ductal carcinoma
worst, most invasive.
most common of all breast cancer
firm, fibrous, rock-hard mass. sharp margins, small, glandular, duct-like cells.
gross: stellate
invasive lobular carcinoma
often e-cadherin mutation in in situ form –> “floating”
oderly row of cells
often bilateral, multiple lesions
inflammatory invasive breast cancer
dermal lymphatic invasion by carcinoma.
peau d’orange: due to lymphedema –> pitting, skin thickening.
neoplastic cells block lymphatic drainage
50% survival in 5 years
presents like acute mastitis that won’t get better w/ antibiotics
what causes nipple inversion? skin retraction
nipple inversion: tumor invades central part of breast
skin retraction: cancer infiltrates coopers suspensory ligament –> focal dimpling
legionella infection leading to legionnaire’s disease
very HIGH fever in a smoker w/ 1. diarrhea,
- confusion,
- cough (slightly productive)
lab: hyponatremia
radiographic evidence of pneumonia, high fever, GI symptoms; suspect
legionella (legionaire’s disease)
HYPONATREMIA
testing for legionella
antigen in urine
lab: hyponatremia
rx for legionella
respiratory fluoroquinolines: levofloxacin.
or new macrolide: azithromycin
sputum stain of legionella? detection
will be negative, unless using silver stain
ANTIGEN in URINE
water sources of legionella
aersolized water: air conditioning, hot water tanks
no person to person
pontiac fever vs. legionaire’s disease
legionnaire: severe pneumonia, fever, GI, CNS
pontiac: mild flu-like. no pneumonia
pneumonia w/ mild anemia
consider mycoplasma: cold hemolytic anemia
chest radiography that looks must more severe than patient
consider mycoplasma
diffuse bilateral infiltrate
M. kansasii
atypical mycobacterium
causes disease like TB
similar to legionella bc water contaminant.
a particular contaminant of municipal drinking water system. not frequently found in nature.
M. avium intracellulare
disseminated non-TB disease in AIDS.
hemodynamic findings in cardiac tamponade
pulsus paradoxus & arterial hypotension
usu when pericardial pressure > 10mmHg
pulsus paradoxus
exaggeration in normal drop in systolic pressure w/ inspiration
>10mmHg drop
gross diagnosis of pulsus paradoxus
grossly diagnose w/ radial pulse disappearing w. inspiration
pulsus alternans
in patients w/ left ventricular dysfunction
beat-to-beat variation in magnitude of pulse pressure in presence of regular cardiac rhythm
dicrotic pulse
pulse w/ 2 distinct peaks (one in systole, one in diastole)
best palpated in carotids
in patient w/ severe systolic dysfunction
pulsus parvus et tardus
aortic stenosis
low magnitude pulse w/ delayed peak
hyperkinetic pulse
rapid ejection of large stroke volume against decreased afterload
during fever / exercise in normal
or patient w/ high-output condition (AV fistula, PDA)
halothane, enflurane, isoflurane, sevoflurane..
halogenated inhalation anestheics
think: massive hepatic necrosis!
esp: halothane
presents 2d-4wks post exposure w/ liver tenderness, hepatomegaly, increased LFT
80% mortality; no therapy
rare, but severe
microvesicular fatty change in liver
reyes syndrome
children 5-10 w/ salicylate
drug induced cholestasis
oral contraceptive, anabolic steroid, chlorpromazine
hepatic granulomatosis
associated w/ methyldopa, hydralazine, quininde
base excision repair
- make apurinic/apyrimidinic site (remove base)
- glycosylase - cleave 5’end phosphodiester bond
- endonuclease - cleave 3’ end phosphodiester bond
- lyase - fill in single gap
- DNA polymerase
- ligase
UV on DNA? ionizing radiation?
UV: thymidine dimers
ionizing radiation: double stranded DNA break & oxidative changes
deamination of cytosine
leads to uracil
demaination of adenine
xanthine
deamination of guanine
hypoxanthine
methylation of uracil
thymine
where is total pulmonary vascular resistance lowest?
at functional residual capacity
end of tidal volume
what are the determinants of pulmonary vascular resistance?
both alveolar & extraalveolar pulmonary vascular resistance, which have opposite relationships w/ increasing lung volumes
what increases alveolar pulmonary vascular resistance?
increased lung volume stretches alveoli –> reduces diameter & lengths vessel –> increasing resistance
what increases extraalveolar pulmonary vascular resistance?
decreased lung volumes reduce radial traction holding vessels open & increases intrathoracic pressure –> compresses extraalveolar vasculature –> increasing resistance
effect of competitive antagonist on maximum drug effect
just requires higher dose of drug (shifts to right)
does not change Vmax
effect of noncompetitive // or irreversible competitive antagonist on maximum drug effect
reduces vmax
bosentan (2 effects)
oral endothelin receptor antagonist, blocks pulmonary hypertension
- decrease pulmonary arterial pressure
- lessens progression of vascular & right ventricular hypertrophy
endothelin
potent vasoconstrictor and stimulant of endothelial proliferation.
mycobacterium leprae infects..
cold temp: skin, nerves (schwann cells), eyes & testes
transmission: armadillo
what should be checked before giving etanercept
PPD
TNF-alpha inhibitor.
TNF-alpha needed to keep latent TB in check.
worry about reactivation TB
what must be checked before given methotrexate & leflunomide?
liver function test
can cause hepatotoxicity
hydroxychloroquine can cause..
irreversible retinal damage
must have baseline & follow up opthalmologic exam
rx for CHF and HTN?
best: ACE inhibitors
inhibit myocardial remodeling * associated deterioration of ventricular contractile function.
B blocker also good: improves mortality in patients w/ systolic CHF & MI
rx for HTN and diabetes
best: ACE inhibitors
rx for essential HTN (w/o diabetes or CHF)
hydrochlorothiazide
rx for HTN and benign prostatic hyperplasia
can give terazosin
alpha-blocker
what agents produce bad myocardial remodeling?
angiotensin II
- give ace inhibitors
aldosterone
- give spironolactone
positive long term effects of b-blockers
improve mortality in patients w/ systolic CHF & MI
w/ HTN
what produces ring-enhancing lesions in brain (4)
multiple
- toxoplasmosis
- neurocystercersosis from taenia solium eggs
- CNS lymphoma
single:
4. glioblastoma (usu solitary & butterfly)
distinguish w/ story & biopsy
prepubertal eggs are stuck in..
prophase meiosis I
primary oocyte
postovulatory eggs are stuck in..
metaphases meiosis II
when does gametogenesis begin
4 weeks ovulation.
primordial germ cells migrate from yolk sac to developing gonadal region & undergo mitosis
progression of germ cells in females
primordial germ cells –> oogonia (46, 2N)
begin meiosis I –> primary oocyte (46, 4N)
stays until puberty. ovulation, finish meiosis I: secondary oocyte & polar body, both (23, 2N)
halt at metaphase of meoisis II until fertilization, when it divides into mature oocyte & second polar body
when is a woman’s full complement of oocytes developed?
by 5 months gestational age.
from that point on, oocytes deplete
coagulative necrosis on histology
structure maintained.
NO NUCLEUS
in heart, occurs w/ >30min ischemia
fibrinoid necrosis
histologic pattern of injury seen in blood vessel walls
- polyarteritis nodosa (vasculitis
- malignant HTN
- diabetes
results from 1. immune complex deposition and/or 2. plasma protein (fibrin) leaking through damaged intima
histology: circumferential ring of pink, amorphous material
when does dystrophic calficiation occur
in areas of necrosis that escape removal by phagocytes
microscopic: amorphous BASOPHILIC material on H&E
where are cysts found in ADPKD
kidney, liver
differentiate cysts in liver & kidney from solid mets on CT
cysts: homogenous w/ regular outlines, nonenhacing on CT
solid med: irregular, enhancing
life span of ARPKD
manifest in INFANT
die shortly after birth, or
first years of life
Kearns-Sayre syndrome
mitochondrial disease:
aka
oculocraniosomatic neuromuscular disease w/ ragged red fibers
mitochondrial myopathy
pleomorphism, nuclear abnormalities, abundant mitoses, disordered maturation, changes in cell polarity occur in what cell change?
BOTH dysplasia and carcinoma
what differentiates dysplasia from carcinoma?
dysplasia: reversible
carcinoma: IRREVERSIBLE
once breach BM -> irreversible
dysplasia
abnormal cell growth confined to epithelium
cells: uniform and organized, but nuclei: pleomorphic, loss of alignment on BM, no longer grouped right, hyperchromatic, increased NC ratio, bizarre mitoses
high-grade dysplasia is synonymous with
carcinoma in situ
dysplasia throughout epithelium. does not penetrate.
once breach = invasive carcinoma
low grade vs. high grade dysplasia
low grade: does not involve entire thickness of epithelium.
high grade: entire = carcinoma in situ
epithelial malignancy progression
low grade dysplasia -> high-grade dysplasia/carcinoma in situ -> invasive carcinoma
what types of plaques are more prone to rupture
- think fibrous cap
- rich lipid core
- high degree of inflammation (metalloproteinases: destabilize mechanical integrity)
all promote rupture & superimposed thrombosis
important determinant of whether a coronary plaque –> myocardial necrosis
RATE of arterial occlusion
slow: allow development of adequate collateral circulation
blood supply to upper 1/3 ureter?
lower 2/3?
upper 1/3rd: renal artery
- transplanted w/ kidney!
lower 2/3rd: branches of aorta & iliac: gonadal & vesical artery
kidney transplant
usually leave old kidney. anastomose..
-donor renal artery & vein -> external iliac artery & vein
also transplant upper 1/3 of ureter
3 microscopic changes in alzheimers
- neurofibrillary tangles
- senile plaques
- amyloid angiopathy
biochemical changes in Alzheimers
decreased Ach in
- hippocampus
- nucleus basalis of meynert
due to deficiency of choline acetyltransferase (ChAT)
basal nucleus of meynert
participates in memory & cognition
base of forebrain, widely projects to neocortex
in alzheimers, see deficiency in ChAT (low Ach)
what is depleted in huntington’s
NMDA receptors depleted in striatum –> loss of GABA release
EML4-ALK fusion protein associated w/
non-small cell lung cancer
chromosomal rearragement
constitutive active tyrosine kinase
usu nonsmoking adenocarcinoma who lack k-ras gene or EGF-R mutation
rx: crizotinib
what structures derive from ventral pancreas bud? dorsal?
main pancreatic duct
uncinate process, and piece of head
dorsal?
everything else, inclu: accessory pancreatic duct
pancreatic divisum
ventral and dorsal bud don’t fuse (should in 8th wk of fetal life)
not a big deal. pancreas drain via 2 ducts now.
accessory pancreatic duct will not degenerate, so that pancreas can still drain dorsal via minor papilla.
ventral: drain via main pancreatic duct; major papilla
embryonic origin of pancreas
from foregut outpouching
endodermal
anti-snRNP antibodies
mixed connective tissue disease
how to snRNP cleave introns
cleave 5’ end of intron & joining that end to branch point. then cleave 3’ end
ligate remaining exon mRNA w/ phosphodiester
peroxisomes
cytoplasmic organelles containing oxidative enzymes
catalase, D-amino oxidase, uric acid oxidase.
most abundant in liver & kidney.
detox of ingested materials.
ALSO breakdown FATTY ACIDS
proteosome vs. lysosomes
both degrade proteins
proteosome: intracellular protein degrade
lysosome: mostly extracellular
PCOS hormones
high everything, except FSH normal/low
(high: testosterone, LH, estrogen)
LH/FSH ratio > 3
long term risk of PCOS
high unopposed estrogen –> endometrial hyperplasia / adenocarcinoma
histology of ovaries in PCOS
exam: bilaterally enlarged
histology: multiple enlarged, sclerotic, cystic follicles
vaginal adenosis
replacement of squamous epithlelium w/ glandular columnar epithelium
associated w. female offspring exposed to DES (diethylstilbestrol)
precursor for clear cell adenocarcinoma of vagina
DES (diethylstilbestrol) exposure in utero
vaginal adenosis
precursor: clear cell adenocarcinoma of vagina
histology of abetalipoproteinemia
normal intestinal mucosal architecture,
but enterocytes contain clear / foamy cells:
more promiment at tips
dietary lipids are processed in enterocytes as..
chylomicrons B-48
endogenosly produced lipids are secreted from hepatocytes as..
VLDL B-100
what is missing in abetalipoproteinemia
autosomal recessive, loss of function in MTP gene.
MTP (microsomal triglyceride transfer protein) = chaperone protein needed for
- proper folding of apo B
- loading lipids into chylomicrons & VLDL
presentation of abetalipoproteinemia
first year of life: malabsorption (abdominal distention, foul smelling stools).
lab: very low plasma triglycerides and cholesterol. chylomicons, VLDL, and apoB missing.
poor absorption of fat soluble vitamins & essential fatty acids.
RBC: thorny projections: acanthocytes
neuro abnormalities: progressive ataxia, retinitis pigmentosa
mutation in MTP gene causes
microsomal triglyceride transfer protein
abetalipoproteinemia
no chylomicrons, VLDL
histology of whipple’s disease
distended macrophages in lamina propria of small intestine
macrophage: PAS+ diastase resistance granules & rod shapped tropheryma whippelii bacilli
granules in whipple are..
PAS +
diastase resistane
greatest risk of abestos exposure
greatest risk: bronchogenic carcinoma!
mesothelioma is rare! if had mesothelioma, most likely related to abestos exposure
abestosis
fibrocalcific plaques on parietal pleura. subsequence diffuse pleural thickening & fibrosis of lower lobe.
histology: interstitial fibrosis & asbestos bodies
most common cause of death in asbestos workers
bronchogenic carcinoma
2nd: mesothelioma
what increases risk of mesothelioma
asbestos exposure
smoking does NOT
direct alkylating agents associated w/
acute leukemia
nitrosamines and amide exposure associated w/
stomach carcinoma
beta-napthylamine exposure assoaciated w/
(in aniline dyes & rubber)
bladder carcinoma
neonatal complications w/ gestational diabetes
- premature
- fetal macrosomia
- neural tube defects: caudal regression
- hypoglycemia
- hypocalcemia
- polycythemia
- respiratory distress
- transient hypertrophic cardiomyopathy
neonates exposed to high glucose in utero develop..
glucose crosses, insulin doesn’t
baby makes more insulin from pancreas.
after birth, continue to make extra insulin –> HYPOGLYCEMIA
will eventually downregulate
redistribution of fat from extremities to trunk associated with (2)
- glucocorticoids
- cushing syndrome - HAART therapy - protease inhibitors
(highly active antiretroviral therapy)
- lipodystrophy
lipodystrophy
redistribution of body fat from extremities to trunk
occurs w/ protease inhibitors in HAART therapy
pathogenesis of drug-induced lipodystrophy
protease inhibitor: impair hepatic chylomicron uptake & triglyceride clearance
excess accumulation of fat in abdominal viscera, breast, posterior neck “buffalo hump”, supraclavicular area
dysmetabolic profile: hyperglycemia, hyperlipidemia, hyperinsulinemia
short-term relief of osteoarthritis
intra-articular glucocortoids
(NOT oral)
which has very low chance of producing cushing syndrome
in the first month after a vasectomy
can still find viable sperm in ejaculate
can have sperm proximal to ligation
20% still have viable sperm after 3 months and at least 20 ejaculations
need sperm sample to confirm azoospermia
path of vas deferens
up abdominal wall, around top part of bladder, down posterior wall of bladder, connects to prostate near seminal vesicle
vas deferens does not affect
- sexual desire, satisfaction
2. ejaculate volume: semen mostly seminal vesicle & prostate fluid
monitor DIC occurance
D-dimers and serum fibrinogen
dead fetus in utero for 6 wks can cause
release of thomboplastin (tissue factor) from placenta – consumptive coagulopathy
findings of DIC (5)
- prolonged PTT and PT
- thrombocytopenia & microangiopathic hemolytic anemia
- low fibrinogen
- elevated fibrin split products (D-dimer)
- low factor V and VIII
