test #24 4.13 Flashcards
slow acetylators metabolize which 4 drugs slowly?
P450 acetylation of dapsone, hydralazine, procainamide, and isoniazid
methylation is an important drug biotransformation for..
azathioprine and 6-mercaptopurine
gilbert syndrome can affect drug metabolism..
bc some drugs require gluronidation for biotransformation.
dysfunctional glucoronyl transferase
drug hydrolysis occurs with..
esterases and amidases
normal amount of amniotic fluid
1000ml.
fetal anomalies associated w/ impaired swallowing (2)? increase urination? (polyhydramnios)
impaired swallowing: duodenal, esophageal, or intestinal atresia (GI obstruction) & anencephaly
increased fetal urination: high cardiac output due to (1) anemia or (2) twin-to-twin transfer
posterior urethral valve
congenital obstruction to urine flow
rachischisis
neural tube defect where vertebral column does not close over spinal cord. (posterior neuropore fails to close).
MI w/ normal coronary artery? think (3)
(1) coronary arteritis, (2) hypercoagulability w/ acute thrombosis, (3) coronary vasopasm
describe libman-sacks endocarditis
verrucous (wart-like) endocarditis, 25% of patients on EITHER side of valve. sterile, finely granular, fibrinous, eosinophilic. may result from immune complex deposition. can progress to valve fibrosis & regurg or stenosis.
Churgg-Strauss
polyarteritis nodosa-associated condition w/ lung vasculitis, severe asthma, and eosinophilia (in atopic patients). have necrotizing granulomas
flexor retinaculum aka
transverse carpal ligament.
carpa tunnel is associated with what scenarios?
(1) chronic repetitive stress (typing, knitting)
(2) fluid retention (renal failure, hypothyroidism, pregnancy
(3) diabetes mellitus, acromegaly, rheumatoid arthritis
dialysis associated amyloidosis
B2-microglobulin. can lead to median nerve compression (often bilateral)
endoneural inflammation infiltration with segmental demyelination seen in..
guillain-barre syndrome
endoneural arteriole hyalinization occurs in..
diabetic microangiopathy
insulin secretion is stimulation by which 3 systems
(1) blood glucose
(2) parasympathetic: secrete
insulin at smell/sight of food
sympathetic can inhibit or stimulate depending on receptor
(1) alpha- INHIBIT insulin release
(2) beta- STIMULATE insulin release
diphenhydramine, dimenhydrinate, chorpheniramine
commonly used antihistaminic agent (blocks H1). commonly have (1) anti-muscarinic (2) anti-alpha-adrenergic effects
ephedrine
indirect general sympathetic agonist, releases stored catecholamines.
used for nasal decongestion, urinary incontinence, hypotension
alpha receptor agonist on insulin?
inhibit insulin release
beta receptor agonist on insulin
promote insulin release
loratadine, fexofenadine, cetirizine
second generation H1 blockers. less sedating bc less CNS penetration.
still anti-Muscarinic
alpha-2 agonists (2)
clonidine & methyl-dopa
clonidine use
alpha-2 agonist, does not decrease renal blood flow. hypertensive urgency, ADHD
alpha-methyldopa
alpha-2 agonist. hypertension in pregnancy
classic anti-inflammatory effects
TGF-beta, IL-10
generally TGF-beta shuts it all down. and IL-10 shuts down cell-mediated and enhances humoral.
TGF-beta: (1) inhibit Th2 lymphocyte differentiation, (2) cytotoxic T cell activities, and (3) B-cell immunoglobulin secretion.
also suppress NK, LAK, and cytotoxicity of mononuclear phagocytes
IL10 (1) inhibits IL-2 and IFN-gamma production by Th1 cells, (2) enhances IL-4 and IL-5 production by Th2 lymphocytes. (3) inhibits TNF-alpha and IL-12 by monocytes and (4) decreases NK cell IFN-gamma production. (5) inhibit monocyte MHC class II and B7 expression (impairing antigen presentation)
TNF-alpha
proinflammatory cytokine. made by T cells and monocytes. induces NFKb (important factor in production of inflammatory mediators. IL-1, IL-4, IL-5, IL-12.
persistent lymphedema (chronic dilatation of lymphatic channels) predisposes to..
lymphangiosarcoma.
rare malignant neoplasm of endothelial lining of lymphatic channels.
pyogenic granuloma
polypoid form of capillary hemangioma. often grow rapidly, as exophytic red nodules attached by a stalk on gingival or oral mucosa or skin. bleed easily, may be ulcerated. resemble hypertrophic granulation tissue.
port-wine stain
birthmark of malformed, dilated blood vessels in superficial dermis. permanent.
kaposi sarcoma (histology)
HHV-8. hyperplasia or neoplasm of spindle-like cells w/ markers for (1) smooth muscle (2) vascular endothelium lining
liver hemangiosarcoma. caused by… (3)?
MALIGNANT tumor of endothelial origin. associated w/ exposure to..
(1) arsenic - pesticide
(2) vinyl chloride (plastics in industry)
(3) thorotrast - former radioactive contrast
PDA murmur
continuous, but will still hear distinct S1 / S2. can hear inspiratory splitting. best heart left infraclavicular. maximal intensity at S2.
Lutembacher syndrome
ASD presenting as continuous murmur when there is mitral valve obstruction due an elevated pressure gradient across atria. very uncommon
what travels through the optic canal (3)
CNII (optic n), opthalmic artery, central retinal vein.
what travels through superior orbital fissure (6)
CN III, IV, V1, VI, opthalmic vein, sympathetic fibers
what travels through foramen rotundum
CN V2 (travels in pterygopalatine fossa and then through inferior orbital fissure [[not in orbit]]
what travels through foramen ovale
CN V3
what travels through foramen spinosum
middle meningeal artery
what travels through internal auditory meatus? (2)
CN VII, and VIII
what travels through jugular foramen? (4)
CN IX, X, XI, jugular vein
what travels through hypoglossal canal?
CN XII
what travels through foramen magnum (3)
spinal roots of CN XI, brain stem, vertebral arteries
where do the branches of the trigeminal n leave the skull (3)
standing room only.
V1: superior orbital fissure
V2: foramen rotundum
V3: foramen ovale
foramen lacerum
occluded by cartilage. internal carotid artery courses just superior to the foramen lacerum in the carotid canal
ways to damage radial n
proximal: uses crutches improperly, passing out on chair. midshaft fracture of humerus (travels w/ deep brachial artery)
distal: medial epicondyle fracture.
path: medial to surgical neck of humerous, inferior to teres major within axilla. enters posterior arm between long head of triceps brachii and posterior humerus.
roots and cord of radian n.
C5-T1. posterior cord.
suprascapular n.
supraspinatus and infraspinatus. abduct and laterally rotate arm
damage to long thoracic nerve. how is it often damaged?
damage serratus anterior. winging of scapula (medial border).
damage long thoracic w/ lymph node dissection, radial masectomy
fracture of surgical neck of humerus / anterior dislocation of glenohumeral joint
axillary nerve injury. paralysis of deltoid and teres minor.
problems w/ abduction, extension, flexion, lateral rotation of arm at sohulder
spinal accessory innervates
trapezius and sternocleidomastoid
what % of small cell carcinoma occur in nonsmokers
1%
what extrapulmonary feature is large cell carcinoma of lung associated w.
gynecomastia and galactorrhea
what extrapulmonary feature is adenocarcinoma associated with (2)
hypertrophic osteoarthropathy and clubbing
most common lung cancer in population (female and nonsmokers)?
adenocarcinoma
endometrium days 1-14 (proliferative/follicular phase)
estrogen stimulates proliferation of stratum functionale. nonbranching, nonbudding, UNIFORM glands evenly distributed throughout uniform stroma. glands are TUBULAR, NARROW, STRAIGHT, lined w/ pseudostratified elongated mitotically active epithelial cells. spiral artery in deep layers.
gland:stroma ratio < 1:1
begins w/ menses and ends w/ ovulation
endometrium days 15-28 (secretory phase)
progesterone promotes development of secretory endothelium. glands larger, more COILED, cells lining glands have cytoplasmic vacuoles. glycogen-rich MUCUS released. stroma = EDEMATOUS. prominent spiral arteries extend to endometrial surface.
gland:stroma ratio ~1:1
begins w/ ovulation and ends w/ onset of menses.
how does c. tetani cause disease
tetanospasmin toxin binds to presynaptic membrane of motor neurons, migrates retrograde axonal transport to cell bodies, into spinal cord & brain stem. block glycine and gaba release from central system.
cardiac output with ficks principle
co = o2 consumption / arteriovenous O2 difference
how much blood must flow through pulmonary / systemic circulation to account for the difference in oxygen content between arterial and venous circulations
respiratory quotient
ratio of CO2 to O2 across alveolar membrane. estimates metabolic rate. usu 0.8.
ovary findings in turner’s
various degrees of ovarian dysgenesis (complete absence to streaked [connective tissue w/ no or minimal follciles]
hirsuitism and primary amenorrhea
polycystic ovarian syndrome
disseminated candida infxn? test?
rarely, in very immunosuppressed, any organ. pneumonia, esophagitis, right sided endocarditis, abscesses, candidemia (sepsis)
cold - yeast. heat - mold.
on light microscope: budding yeasts w/ pseudohyphae.
innoculation into serum 37 C (98.6) for 3 hours: form true hyphae (see yeast transforming to mold) on scope
adult lead poisioning
less common, miners or industrial workers, especially battery manufacturing
presentation of lead poisioning
weakness, abdominal pain, constipation. severe: neuro. blue “lead lines” at junction of teeth and gingivae. peripheral blood smear: coarse basophillic stippling on background of hypochromic microcytic anemia.
inhibition of ALAD and ferrochelatase
accumulate protoporphyrin and d-ALA
mees lines – white lines on finger nails
arsenic poisioning
purple / blue ilnes on gingiva
lead poisioning
basophillic stippling in lead poisioning
ribosomal aggregates
enzyme deficiency in acute intermittent porphyria. symptoms.
porphobillinogen deaminase.
build up porphobillinogen, d ALA, and (coporphobillinogen in urine)
symptoms = 5 P’s
painful abdomen, port-wine coloured urine, polyneuropathy, psychological disturbances, ppt by drugs, alcohol, and starvation.
rx: glucose + heme, to stop ALAS (rate-limiting step) reduces production of d-ALA & porphobillinogen
porphyria cutanea tarda
deficient in uroporphyrinogen decarboxylase
first step in heme synthesis requires. blocked in?
glycine, succinyl-CoA —-> d-ALA
enzyme: d-ALA synthase
cofactor: B6
defective in x-linked sideroblastic anemia
steps in heme synthesis blocked by lead poisioning (2)
- d-ALA —> porphobillinogen
via d-ALAD (d-ALA dehydratase)
build up d-ALA
- protoporphrin + Fe2+ —> heme
via ferrochelatase
both steps in mitochondria!
defective step in acute intermittent porphyria
conversion of porphobillinogen —> hydroxymethylbilane.
via porphobilinogen deaminase
(will have corporbillinogen in urine)
defective step in porphyria cutanea tarda
uroporphyrinogen III —-> coproporphyrinogen III
via uroporphryrinogen decarboxylase
build up uropohryin (tea coloured urine
tea-coloured urine + blistering photosensitivity
porphyria cutanea tarda. defective uroporphyrinogen decarboxylase.
abdominal pain w/o abdominal tenderness
acute intermittent porphyria
leukoerythroblastosis
immature granulocytes w/ nucleated tear drop-shaped RBCs. results from myelopthisic processes
Pica
abnormal compulsive consumption of nonfood and/or non-staple food. can occur in any stage of pregnancy. associated w/ iron-deficiency anemia.
can LEAD to anemia bc of decreased nutritional intake.
vs. normal pregnancy craving: overeat normal foods
anorexia nervosa
excessive DIETING. weight loss of 25% of body weight. or 15% below normal weight for age / height. distorted body image.
bulimia
episodic & secretive BINGE eating followed by self-induced vomiting / fasting / laxatives.
olfactory craving
common appetite disturbance of pregnancy. craving certain smells. often, dangerous items like gasoline, automobile exhaust, liquid
what kind of polymerase is telomerase
reverse transcriptase (RNA-dependent DNA pol) TTAGGG to 3’ end.
consists of TERT reverse transcriptase and built in TERC RNA template (read repeatedly)
bloom syndrome
premature aging. associated w/ shortened telomeres
what cofactor is needed for oxaloacetate —> PEP (via PEP carboxykinase
GTP (made from succinyl-CoA to succinate in TCA)
metabolites made in TCA! 5
- isocitrate –> a-KG makes NADH
- a-KG –> succinyl-CoA makes NADH
- succinyl-CoA –> succinate makes GTP
- succinate –> fumarate makes FADH2
(fumarate –> malate makes nothing) - malate –> oxaloacetate makes NADH
(malate can leave mitochondria to become oxaloacetate –> PEP consuming GTP
how can oxaloacetate get from mitochondria to cytoplasm for gluconeogenesis?
(1) PEP carboxykinase in mitochondria can convert oxaloacetate —> PEP
(2) oxaloacetate transamination to aspartate
(3) oxaloacetate reduction to malate
PEP, aspartate, and malate can all leave mitochondria. oxaloacetate cannot.
medications that can cause seizures
bupropion, clozapine, isoniazid, ciprofloxacin, imipenem
rare but important side effect of ticlopidine
neutropenia, presents w/ fever and mouth ulcers!
must monitor CBC biweekly for first 3 months!
fever and mouth ulcers in patient treated w/ meds post-stroke
ticlopidine
nipple inversion in breast cancer suggests
tumor invades central region of breast
skin retraction “focal dimpling”
cancer infiltrates suspensor Cooper ligaments
peu de orange – lympedema and putting and thickening of skin
dermal lymphatic invasion/obstruction, seen w/ invasive breast carcinoma. often inflammatory type. 50% survival in 5 years.
diphenoxylate & meperidine
mu-optiate agonist. anti-diarrheal. SLOWS gastric motility.
since high doses –> euphoria. add atropine in med to discourage abuse
sulfasalazine
combination of (1) sulfapyridine (antibacterial) and (2) 5-aminosalicylic acid (anti-inflammatory.
activated by colonic bacteria.
used for crohn’s and ulcerative colitis.
kaolin-pectin & attapulgite
make stool less watery, symptomatic relief
rx for secretory diarrhea
can be due to many things. rx: octreotide, bismuth salicylate, probiotics help
psychogenic polydipsia
(1) serum Na+ low
(2) urine concentrates w/ water deprivation (after dehydration)
(3) <10% increase in urine concentration after ADH
DHT binds to..
testosterone receptor; has higher affinity than testosterone
which drug decreases leydig cell synthesis of testosterone
ketoconazole (block 17,20 desmolase) & spironolactone (17-alpha-hydroxlase)
ketoconazole’s endocrine effects
weak anti-adrenergic. blocks leydig production of testosterone and adrenal production of steroid hormones.
blocks 17,20 desmolase
anastrozole
aromatase inhibitor
flutamide & cyproterone acetate, and spironolactone
block testosterone intxn w/ receptor
treat metastatic prostate cancer
flutamide
spironolactone’s endocrine effects
(1) blocks testosterone receptor (2) blocks 17,20 desmolase (steroid synthesis)
(3) blocks 17-alpha-hydroxylase
adenoma to carcinoma sequence
AK-53 & DCC
normal mucosa –> cancer
APC –> K-ras –> p53
APC –> makes adenomatous polyp.
K-Ras –> increase polyp size
p53 + DCC –> malignant transformation
mutation in WT-1
Wilms tumor
normal fxn of BRCA
suppresses cell cycle
role of APC
implicated in sporadic colon cancer (normal mucosa –> polyp –> cancer) & FAP (autosomal dominant inheritance of mutated APC gene.
needed to maintain low levels of beta-catenin (oncogenic) & maintain intercellular adhesion
fall from free & catch tree trunk as falling
damage lower trunk C8-T1: klumpke’s palsy
musculocutaneous n injured when…
w/ upper trunk lesions, like head and shoulder are violently stretched apart
long thoracic n injury
axially node dissection w/ radical masectomy
common side effect of all nitrates
headaches & cutaneous flushing
causes of secondary hyperaldosteronism
high aldosterone due to high renin.
(1) renal artery stenosis, associated w/ fibromuscular dysplasia, or atheroscerlosis.
(2) malignant hypertension (leading to microvascular damage and renal ischemia).
(3) renin-secreting tumors (juxtaglomerular cells)
cancers associated with Rb
retinoblastoma and osteosarcoma
cancers associated w/ BRCA
breast and ovarian
cancer associated w/ APC
colon cancer (FAP and sporadic), and melanoma
keep beta-catenin low & maintain intercellular adhesion
most common cancers in li-fraumeni
inherited autosomal dominant. p53 (tumor suppressor). need to have sporadic mutation in second.
breast, brain, adrenal cortex.
bile soluble means..
it will die in bile! like s. pneumoniae
differentiate s. bovis & enterococci
both survive in bile. s. bovis DIES in NaCl
hypertrophic cardiomyopathy (HCM) associated w/ mutations in..
sarcomere proteins
myosin heavy chain, myosin binding protein, cardiac troponin T, tropomyosin
inherited dilated cardiomyopathy
1/3rd are inherited. majority due to autosomal dominant defect in cytoskeletal protein (like distrophin) or mitochondrial enzymes
where is ADH / vassopressin made
supraoptic / paraventricular nuclei of hypothalamus
transient central diabetes insipidus
damage to posterior pituitary. magnocellular neurons in hypothalamus hypertrophy and undergo axonal regeneration –> allows for release of fxnal ADH eventually.
permanent central diabetes insipidus
damage to hypothalamus or supraoptic-hypophysial tract. not enough magnocellular neurons to make enough ADH
main feature of G1, S, and G2 phase
G1: synthesis of RNA, protein, lipid and carbohydrate
S: DNA replication
G2: ATP synthesis
active Rb
hypophosphorylated ‘unleashed’. prevents G1—>S transition
evidence of frontal lobe damage
inappropriate behavior, impaired judgement, poor executive fxn. incontinence and gait disturbances
damage to inferior parietal lobe of DOMINANT hemisphere? non-dominant?
dominant (usu left): Gerstmann’s syndrome: right/left confusion, dysgraphia, dyslexia, dyscalculia.
nondominant: apraxia, contralateral neglect
marantic endocarditis
non-bacterial thrombotic endocarditis associated w/ underlying visceral malignancy. often: mucinous adenocarcinomas of pancreas & adenocarcinoma of lung (relate to procoagulant effects of circulating mucin)
(bc cancer-related wasting of body “marasmus”)
tumor-associated release of procoagulants also thought to be responsible for migratory thrombophlebitis (Trousseau syndrome)
Trousseau syndrome
migratory thrombophlebitis sometimes seen w/ underlying malignancy (GI).
like marantic endocarditis: mucin-related GI malignancy –> hypercoagulable state –> NBTE
achalasia
failure of LES to relax. absence of myenteric (auerbach’s plexus) –> high LES opening pressure and uncoordinated peristalisis. progressive dysphagia to solids and liquids. “bird beak” on barium swallow
which pharyngeal muscle is important to initiate wave of peristalisis
cricopharnyngeus muscle, push bolus down.
cricopharyngeal dysfunction
failure of cricopharyngeal muscle to relax during swallowing. causes choking or food sticking sensation and pain with swallowing
brain metastasis
multiple well-circumscribed masses and junction of gray and white matter.
gross oligodendrogliomas
well circumscribed gray messes. areas of necrosis and hemorrhage not common
gross glioblastoma
frequently cross midline, in white matter. foci of necrosis and hemorrhage common
