test #33 4.22 Flashcards
antiarrhythmic prolonging QT & bradycardia (prolonged PR)
sotalol
beta-blocker w/ class III antiarrhythmic properties
how do beta blockers work?
(1) slow AV nodal conduction
(2) prolonging phase 4 depolarization
triglyceride breakdown. fate of fatty acid & glycerol?
triglyceride –> fatty acid & glycerol (via lipases)
FATTY ACID –> fatty acyl-coA
via fatty acid CoA synthetase
carnitine carries fatty acyl-CoA into mitochondria
fatty acyl-CoA –> beta oxidation
GLYCEROL (IN LIVER)
glycerol –> glycerol 3-phosphate
(via glycerol kinase)
glycerol 3-phosphate -> DHAP
DHAP can go into (1) energy via glycolysis or (2) glucose via gluconeogenesis
glycerol also can be used for triglyceride synthesis in any tissue
liver-specific enzyme for energy generation & glucose synthesis
glycerol kinase (converts glycerol into glycerol 3 phoshpate)
glycerol 3-phosphate -> DHAP -> either glycolysis or gluconeogenesis
ONLY in liver.
acetyl-CoA carboxylase
first committed step in fatty acid SYNTHESIS!
acetyl-CoA –> malonyl-CoA
(acetyl-CoA carboxylase)
eventually make palmitate
occurs in cytoplasm
where does fatty acid oxidation occur? synthesis?
oxidation in mitochondria
synthesis in cytoplasm
fatty acid synthesis movement from mitochondria to cytosol?
oxaloacetate + acetylCoA –> citrate
citrate shuttled out
converted into oxaloacetate + acetylCoA again (via ATP citrate lyase)
acetyl-CoA –> malonyl CoA–> fatty acid
oxaloacetate –> malate –> pyruvate, back into mito
which is the only organ that can use glycerol as energy source?
LIVER
how do adipocytes make glycerol for triglyceride synthesis?
synthesizes glycerol phosphate from DHAP
nail clubbing suggests? nail spooning [koilonychia] suggests
clubbing: PROLONGED hypoxia
associated w/ large-cell lung cancer, TB, CF, suppurative lung disease: empyema, bronchiectasis, chronic lung abscesses
(not asthma, bc brief, episodic?)
spooning: Fe2+ deficiency anemia
nail clubbing:
drumstick appearance, flattening of nail folds, shininess of nail and distal portion of finger.
pressing of nail: spongy, fluctuant (unstable) sensation –> softening of nail beds
potential pathophysiology of digital clubbing
failure of platelet precursors to fragment completely within pulmonary circulation
increased peripheral megakaryocytes & platelet clumps –> impact finger & toe –> release PDGF and VEGF –> increased fibrovascular proliferation –> clubbing!
also, elevated levels of prostaglandin E2 implicated.
c-ANCA targets
lysosomal enzymes
wegners: granulomatosis w/ polyangiitis
wegner’s (granulomatosis w/ polyangiitis)
what’s involved (3)
necrotizing granulomatous vasculitis
- upper respiratory: ear, nose, sinus, throat: chronic sinusitis, mucosal ulceration (due to mucosal granulomas that later ulcerate)
- pulmonary symptoms: cough/hemoptysis, focal necrotizing granuloma in lung, can coalesce and undergo cavitation
- renal disease: RPGN: crescentic
RPGN due to wegner’s differs bc
pauci-immune.
RPGN 1: immunoglobulin against basement membrane
RPGN 2: immune complex mediated
nephritic 2-3 days after upper respiratory infection? nephritic 2-3 wks after URI?
2-3 days: IgA nephropathy
2-3 wks: PSGN: postinfectious strep glomerulonephritis
A is earlier
indirect jaundice post-stress (i.e. hiking, fasting)
gilbert syndrome! weak UDP-glucoronyl-transferase. usu not a big deal, unless stressed.
normal serum total bilirubin
.2-1 mg/ml
< 0.2mg direct bilirubin
which TB virulence factor allows for intracellular bacterial proliferation
sulfatide
horseshoe nuclei
langhan’s giant cells
classic locations for disseminated TB
- basal meninges (tuberculous meningitis
- lumbar spine (Pott disease)
- psoas muscle (psoas abscess)
- serous membranes like pericardium and pleura
disseminate TB vs milary
milliary -> extreme form; small scattered seed-like foci of infection throughout body.
preventative measure for all kidney stones?
drink fluids
most stones result from supersaturation
low calcium diet on Ca2+ kidney stone formation?
INCREASES risk.
serum Ca2+ is low, compensatory increase in intestinal Ca2+ absorption and Ca2+ release from bone –> increase risk of stone formation
high protein diet on kidney stone formation?
increases risk.
increases body’s acid load, stimulate calcium release from bones & Ca2+ excretion into urine.
recommend low protein diet for individuals w/ calcium and uric acid stones
high dietary Na+ on kidney stone formation?
increased Ca2+ release from bone.
recommend low Na+ diet
recommendation for patients w/ calcium stones and hyperoxaluria?
pyridoxine. B6 decreases endogenous oxaloacetate formation –> less stone
difficulty abducting right arm past horizontal position & prominence of scapular angle
serratus anterior
long thoracic n.
likely injured during masectomy
past horizontal abduction –> need seratus anterior to rotate glenoid cavity superiorly.
which structures can be damaged in thyroidectomy (2)
- recurrent laryngeal, when ligate inferior thyroid
2. superior laryngeal, when ligate superior thyroid artery.
anterior dislocation of shoulder OR fracture of neck of humerus can injure..
axillary n. delt & teres minor & sensation to upper lateral arm
stretch between head and shoulder injures..
upper trunk of brachial plexus. erb’s palsy
damaged musculocutaneous & suprascapular
– shoulder adducted, arm pronated, elbow extended
where does clavicular fracture typically occur
middle 1/3rd, due to strength of ligamentous structures at either end.
first infection w/ VZV is called? reactivation is called? spread via?
spread via respiratory secretions
1st infxn: varicella, chicken pox
reactivation: herpes zoster (shingles)
presentation of herpes zoster (reactivation)
1st. burning and/or pain unilaterally in dermatome.
2-3 days: erythematous maculopapular rash in affected dermatome.
papule transform into vesicles that later coalesce.
rupture of vesicles -> ulcers that crust. CONTAGIOUS until lesions are DRY.
skin biopsy of herpes zoster infection
intranuclear inclusions in keratinocytes & multinucleated giant cells. (positive Tzanck)
acantholysis (loss of intercellular connections) & intraepidermal vesicles
dermal inflammatory infiltration and leukocytoclastic vasculitis may be present.
acantholysis forming suprabasal blisters –>
pemphigus vulgaris
IF: IgG deposits in reticular pattern around keratinocytes.
Ab target is desmoglein 3
dermatitis herpetiformis
pruritic grouped vesicles on extensor surfaces.
light micropscopy: accumulations of neutrophils on tips of dermal papillae
verruca vulgaris
WARTS like in HPV infection
skin biopsy of molluscum contagiosum
pox virus
– eosinophillic cytoplasmic inclusions.
definition of GI ulcer (vs. erosion)
breaches of alimentary tract mucosa that extend THROUGH muscularis mucosae –> into submucosa or beyond
gastric ulcers & risk of malignancy?
can frequently be malignant in nature; associated w/ poorly defined excavated ulcer bordered by irregular heaped-up mucosa
(vs. duodenal ulcer, usu not malignancy-related)
duodenal ulcers & risk of malignancy?
not associated!
esophageal ulcer & risk of malignancy
both associated!
(1) esophageal adenocarcinoma– associated w/ ulcerated exophytic lesion at GE-junction)
(2) squamous cell carcinoma–associated w/ plaque-like thickening of mucosa that may eventually excavate & ulcerate
colon ulcer & risk of malignancy?
associated!
distal colon: annular lesions w/ “napkin-ring” constriction of bowel, w/ heaped up edges & ulcerated central region.
also, ulcerative colitis generally increased risk of colorectal cancer.
rx for trigeminal neuralgia
carbamazepine (increase Na inactivation)
painful episodes can last for months! unclear pathogenesis
side effect of carbamazepine
aplastic anemia & agranulocytosis
haloperidol can be given for
4
schizophrenia, acute psychoses, acute mania, tourette
how to avoid confounding
confounding: confusion of two supposedly causal variables, such that part/all of observed effect thought to be due to one variable is actually due to other.
deal by matching on possible confounders: age, race
selection bias
choosing groups that reflect general population
which muscles of mastication close jaw? open?
close: masseter, medial pterygoid, temporalis
open: lateral pterygoid
what leaves through foramen ovale (4)?
V3 of trigeminal
lesser petrosal nerve
accessory meningeal artery
& emissary veins
what leaves through foramen spinosum (3)?
meningeal/recurrent branch of V3
middle meningeal artery
middle meningeal vein
foramen lacerum
carotid canal just above this.
- meningeal branch of ascending pharyngeal artery.
- artery & n. of pterygoid canal.
otherwise, occluded by cartilage
jugular foramen
- CN IX, X, XI,
- inferior petrosal and signoid sinus
- posterior meningeal artery
exit points for trigeminal n. branches (3)
standing room only
superior orbital fissure, foramen rotundum, foramen ovale
(not spinosum!)
presentation of arsenic poisioning?
arsenic containing insecticide.
GI symptoms: nausea, vomiting, abdominal pain, diarrhea. decreased level of consciousness, hypotension, tahycardia.
GARLIC ODOR in breath
MEES lines: fingernails w/ white lines
rx: dimercaprol or succimer.
displaces arsenic ions from sulhydryl groups of enzymes.
dimercaprol itself = toxic (nephrotoxic & HTN)
dimercaprol / succimer use (3)? mechanism?
displaces ions from sulhydryl groups of enzymes.
use for mercury, arsenic, gold, lead
rx for acute lead or mercury posioning?
choice: CaNa2-EDTA
cyanide poisioning presentation? rx (3)
presentation: almond scented breath, trismus, apnea
rx: (1) amyl nitrite (2) sodium thiosulfate (3) hydroxocobalamin
(1) nitrite: forms methemoglobin, binds to cyanide ions (forming nontoxic cyanomethemoglobin) –> prevents cyanide binding to mitochondrial enzymes
(2) thiosulfate: sulfur donor, increase thiocyanate for excretion
(3) hydroxocobalamin: bind to CN and excrete in urine
deferoxamine
rx: iron poisioning. facilitates urine excretion
rx for methemoglobinemia
methylene blue. reducing agent, converts iron in heme form Fe3+ to Fe2+
lyonization
process of randomly inactivating an X chromosome in normal females –> heterochromatin – Barr body at periphery of nucleus on micropscopy.
all human females -> mosaics of X-chromosome (methylation of cytosine -> methycytosine)
why do RBCs make 2,3 BPG?
made in glycolysis.
normally:
glucose»_space;> 1,3 bisphosphoglycerate –> 3phosphoglycerate (1 ATP made)»_space;» pyruvate.
in RBC, will convert 1,3 bisphosphoglycerate –> 2,3 bisphosphoglycerate (via a mutase) –> 3 phosphoglycerate»_space;> pyruvate
basically sacrifice making ATP, in order to make 2,3 DPG. important in reducing hemoglobins affinity for oxygen for delivery to peripheral tissue!
varicose veins
dilated tortuous veins that predominately involved superficial veins of leg.
risk factors: chronically increased lower-extremity venous pressure: long periods of standing, >50y/o, multiple pregs. genetic defects that affect venous wall/valvular integrity.
repercussions of varicose veins?
prolonged increase in intraluminal pressure results in loss of vessel-wall tensile strength. result in venous dilation –> causing veins to fail. resulting backflow exacerbates venous HTN –> worse valve competency.
complications: painful superficial thromboses, stasis dermatitis, skin ULCERATION (medial malleolus), poor wound healing, superficial infection.
claudication usu associated w/
pain & weakness associated w/ exertion.
due to peripheral artery disease.
phlegmasia alba dolens
painful white leg, “milk leg”
consequence of iliofemoral venous thrombosis in peripartum women.
pregnancy disposes to deep vein thrombosis due to pressure of uterus on deep pelvic veins –> stasis. also, hypercoagulable.
location of varicose veins
SUPERFICIAL venous system. not deep. less associated w/ thromboembolism & PE.
describe giardia morphology? most important in preventing it in GI system?
pear-shaped, bilaterally symetric organism. 4 pairs of flagella. 2 nuclei.
IgA helps prevent & clear infection. impair adherence.
how do eosinophils kill helminth larvae?
antibody dependent cellular cytotoxicity (ADCC). involves major basic protein.
familial syndrome associated w/ bronchiectasis?
kartagener’s syndrome. immotile cilia due to dyenin arm defect.
infertility, recurrent sinusitis, and bronchietasis
most common congenital upper limb deformity. 2nd most?
most common: synfactyly – failure of digits to separate
2nd: constriction band syndrome: interrupts fetal blood supple to distal limbs, causes amputation of fingers/toes
osler-weber-rendu disease aka
hereditary hemmorhagic telangiectasia
increased bleeding time and PTT (normal PT) suggests?
von willebrand disease
- BT bc binds to platelets
- PTT bc stabilizes/carries factor VII
absence of vWF –> functional factor VIII and platelet deficiency.
factor VII deficiency itself will NOT affect bleeding time.
(aka factor VII needs vWF, but vWF does not need factor VII)
if bleeding time is up, MUST mean there is a platelet issue
inheritence of von willebrand disease
autosomal DOMINANT w/ variable penetrance
most common heritable bleeding disorder.
DIC elevates
bleeding time, PT, and PTT (consumptive).
also elevated d-dimers
degradation product of cross-linked fibrin
factor XIII
transglutaminase. crosslinks fibrin polymers. STABILIZE clots.
deficiency: causes delayed bleeding, but does NOT prolong bleeding time, PT, or PTT.
why is amphotericin so terrible
binds cell membrane cholesterol
has higher affinity for ergosterol than cholesterol, but does affect cholesterol a little.
main: nephrotoxic, hypomagnesium, hypokalemia.
main toxicity:
- acute infusion related reaction
- chills, fever, rigor, hypotension
- antipyretics & antihistamine can help - dose-dependent nephrotoxicity
- bc decreases GFR - electrolyte abnormalities
- hypomagnesemia and hypokalemia - anemia
- due to suppressed EPO synthesis - thrombophlebitis
- at site of injection
oxidase +, comma shaped, gram negative bacteria (3). how are they unique?
- camplyobacter jejuni
- grows in 42 C - vibrio cholera
- grows in alkaline conditions - helicobacter pylori
- produces ureas
[pseudomonas is also oxidase +, but is a rod)
which 2 bacteria increase cAMP in intestine?
- ETEC (heat labile toxin)
- vibrio cholera
when should the neural tube close
4th week of fetal development
failure of neural tube closure increases 2 things in amniotic fluid
AFP and acetylcholinesterase
duodenal atresia occurs due to
abnormal apoptosis. duodenal lumen fails to recanalize
adverse effects of L-DOPA on brain
anxiety and agitation
also insomnia, confusion, delusions, hallucinations
test for supraspinatus pathology?
empty-can supraspinatus test.
simultaneous abduction and flexion of arm at shoulder & apply force downwards
long head of biceps brachii? short head?
long head: passes through glenohumeral joint to insert on supraglenoid tubercle of scapula.
short-head on coracoid
levator scapulae inserts on..
superomedial border of scapula and on tranverse processes of C1 - C4
primary biliary cirrhosis
chronic liver disease.
characterized by autoimmune destruction of intrahepatic bile ducts & cholestasis
usu middle age women, insiduous onset.
pruritus is first symptom, fatigue.
physical exam: hepatosplenomegaly, xanthomatous lesions of eyelind or in skin / tendons
lab: elevated ALP, cholesterol, and IgM
associated w/ autoimmune diseases
describe changes w/ skin aging.
aging of human skin by 30-35. gradual thinning, reduction in subcutaneous fat, blood vessels, hair follicles, sweat ducts, & sebaceous gland.
decreased dermal collagen & elastic fibers
wrinkles due to..
reduced synthesis of collagen fibrils.
loss of intrinsic reticular supoprt – inelastic skin sags and demonstrates wrinkles
severe triglyceridemia can cause…
pancreatitis
2 mechanisms of fibrates
(1) activate PPAR-alpha
(2) increased LPL activity –> triglyceride clearance
how does PTH activate osteoclasts (3)
stimulate osteoblasts to (1) express RANK-L (2) secrete M-CSF
also decrease osteoprotegrin release (decoy receptor for RANK-L)
thyroid hormone on bone formation
t3 increases bone turnover by mainly increasing OSTEOCLASTIC RESORPTION
(reason why patients w/ thyrotoxicosis have mild hypercalcemia)
where is ventillation highest? perfusion? V/Q ratio?
BOTH ventilation & perfusion higher at BASE
V/Q RATIO greater at APEX
- ventillation greater at base b/c alveoli are less distended, more compliant (weight of lung)
- perfusion greater at base bc of gravity
perfusion GREATLY increases as move to base. ventilation increases slightly
why do fibrates increase cholesterol stone in gallbladder?
inhibit 7-alpha-hydroxylase, increased cholesterol in bile – ppt out
first step in cholesterol synthesis
via thiolase
condense two acetyl-CoA into acetoacetyl-CoA –> substrate for HMG-CoA reductase
which hepatitis viruses transmitted fecal-oral?
NAKED ones. hep A and hep E
hepatitis E is concerning in what population
high mortality rate in pregnant women.
most people –> self-limited. not associated w/ chronic liver disease OR carrier state.
gait abnormality & urinary incontenience. LATER progresses to progressive dementia and emotional blunting
NORMAL PRESSURE HYDROCEPHALUS.
- wacky, wobbly, wet
gradual diminshed reabsorptive capacity of arachnoid villi.
(distinguish from alzheimers due to the order of symptoms!)
sometimes reversible w/ relief of CSF volume
agenesis
absent organ due to absent primordial tissue
aplasia
absent organ DESPITE presence of primordial tissue
hypoplasia
incomplete organ development ; primordial tissue present
deformation
extrinsic deformation occurs AFTER embryonic period
uterine pressure on fetus in breech position –> congenital hip dislocation. clubbed feet.
disruption
secondary breakdown of previous normal tissue or structure (i.e. amniotic band syndrome – amniotic bands compress/ampute fetal limbs
malformation
instrinsic disruption; during embryonic period (weeks 3-8)
i.e. holoprosencephaly, congenital heart disease, anencephaly, polydactyly, syndactyly
sequence
abnormalities resulting form a single primary embryological event (i.e. oligohydramniosis –> potter sequence)
holoprosencephaly
MALFORMATION: primary defect in cells or tissues that form an organ. division of prosencephalon happens during 5th wk of embryonic period.
associated w/ patau, edwards, and fetal alcohol syndrome
most calcium stones result from what serum state / urine state
normocalcemia, hypercalciuria
usu idiopathic hypercalciuria
what can cause hyperoxaluria?
diet high in oxaloacetate: chocolate, nuts, spinach
also, diets low in Ca2+ makes more free oxaloacetate for absorption and subsequent renal excretion (occurs in crohn’s disease & other intestinal malabsorption)
what can cause hyperuricosuria?
high protein diet, large amounts of purines metabolized into uric acid.
morning stiffness in osteoarthritis
happens! just shorter than in rheumatoid arthritis (~10-15min)
RA: can last hours
most common cause of epiglottitis?
haemophilus influenza B:
drooling, dysphagia, difficulty breathing, fever, cherry red epliglotis
inspiratory stridor (narrowed larynx)
cerebellar tumor in child w/ primitive cells?
medulloblastoma! primitive neuroectoderm
