#5 3/9 Flashcards
Histology of (1) zona glomerulosa (2) zona fasiculata (3) zona retiularis (4) adrenal medulla
(1) rounded/arched cluster (2) foamy-appearing cells in columns (3) basophilic cells in anastomosing cords (4) basophilic cytoplam
Adrenal medulla releases…
80% Epi, 20% Norepi
Aldosterone secretion from zona glomerulosa regulated by… (2 things)
(1) Angiotensin II (2) extracellular K+ levels
TNF-alpha inhibitors treat…
Rheumatoid arthritis (STUDY MORE) etanercept, inflixamab & adalimumab
First-line drug for established rheumatoid arthritis
methotrexate
NSAID side effects (3)
GI ulcer and bleeding, fluid retention (block prostaglandin-mediated vasodilation of afferent arteriole)
Kallmann’s syndrome
Failure of GnRH-secreting neurons to migrate from olfactory lobes to hypothalamus (migration problem)
Thyroid development
(1) lower end of pharynx (2) migration along thyroglossal duct, from foramen cecum on dorsal surface of tongue to superior border of thyroid isthmus (can become sublingual if impaired
Parafollicular C-cells originate from
ultimobranchial bodies
Clinical presentation of hypothyroidism in children
lethargy, feeding problems, constipation, macroglossia, umbilical hernia, large fontanels, dry skin, hypothermia, prolonged jaundice
How does an enzyme speed up the reaction rate?
reduce the energy of the transition state (activation energy); cannot alter Gibbs free energy
deltaG describes..
direction of a chemical rxn & concentrations of reactants and products at equilibrium
deltaG0 describes..
change in free energy that accompanies formation of 1 mol of products from substrate under standard condition
exothermic = -deltaGo (spontaneous)
endothermic = +deltaGo
Differentiate mucor/rhizopus from aspergillus on microscopy & affected population
irregular BROAD non-septate hyphae branching at WIDE angles (vs. septate hyphae that branch at 45 degrees).
Aspergillus: chronic granulomatous disease & immunocompromised
Mucor/Rhizopus: diabetic ketoacidotic & leukemic
Both can cause sinusitis in immunosuppressed
Dimorphic Fungi
Body Heat Changes Shape: blastomycoses, histoplasma, coccidiomycoses, sporothrix
Thyrotoxicosis on serum calcium
hypercalcemia due to increased bone resorption
Familial hypocalciuric hypercalcemia (inheritance and defect)
autosomal dominant, defective calcium-sensing receptor on parathyroid cells & kidney
Hydrochlorothiazide electrolyte abnormalities:
elevated: glucose, lipid, uric acid, calcium
decreased: potassium, magnesium, sodium
Hypothyroid effect on skeletal muscle
myopathy: pale muscle fibers, decreased striation, deposition of mucinous material. atrophy or type II muscle fibers (increase in creatine kinase)
Elevated creatinine kinase isoform localize: CK-MB, CK-BB, CK-MM
CK-MB: cardiac muscle
CK-BB: nervous system
CK-MM: skeletal muscle
Common causes of elevated creatine kinase (4)
hypothyroidism, HMG-CoA reductase (statins), autoimmune disease (polymyositis, dermatomyositis), muscular dystrophy (Duchenne)
evolution of EPS side effects & Rx
4 hr: acute dystonia (muscle spasm, stiff, oculogyric crisis) rx: diphenhydramine
4 day: akathisia rx: propanolol
4 wk: bradykinesia rx: benztropine
4 mo: tardive dyskinesia rx: discontinue
localize thyroid hormone receptor
inside nucleus (also, retinoids, peroxisomal proliferating activated receptors, and fatty acids)
resistance to rifampin
genetic mutation in DNA-dependent RNA polymerase (RAPID when monotherapy)
use of rifampin (3)
(1) prophylactic monotherapy for H. flu and N. meningitidis; combo: (2) mycobacterium TB (3) leprosy
Rx: MAC
macrolide (clarithromycin or azithromycin)
rifampin
ethambutol
Rx: penicillin-resistant pneumococcus
ceftriaxone & vancomycin combination
Rx: staphylococcal endocarditis
IV penicillin & rifampin or aminoglycoside (synergistic)
Use of colchine & mechanism of action
rx: for acute gout & prophylaxis
binds & stabilizes tubulin, inhibiting leukocyte chemotaxis and degranulation
also reduces LTB4
- 1st line Rx: acute gout
- preferred Rx in elderly/renal failure
- NSAID (anti-inflammatory, analgesic, anti-pyretic)
- intra-articular glucocorticoids
Side effect of colchine
GI
Use of leukotriene modulators (zileuton, montelukast, zafirlukast)
preventing recurrent of asthma & allergic rhinitis
ADH signal transduction
V2 receptor on principal cells in collecting duct -> increased cAMP -> fusion of endosomes with aquaporin 2 to luminal side -> increased water reabsorption
- highest & lowest tubular fluid osmolarity location (in presence of ADH? in absence?)
- osmolarity in PCT
highest: bottom of loop of henle (1200mOsm when ADH is high)
lowest: DCT (100mOsm)
PCT equivalent to serum (300mOsm)
in absence of ADH, most dilute in collecting ducts (as low as 50mOsm)
Cause of focal brain lesions in HIV+patients
& other causes in any pt
toxoplasma, CNS lymphoma (B cell; related to latent EBV infxn)
& primary brain tumor (globlastoma multiforme), metastatic carcinoma, abcesses (cryptococcus, TB)
Irreversible neuronal damage (neuronal shrinkage, eosinophilic cytoplasm) leads to
glial hyperplasia; reactive gliosis (NOT fibroblast)
Vertebral level: bifurcation of abdominal aorta
& common iliac vein merge to IVC
L4
vertebral level: renal vein entering IVC
L1-2
interomediolateral nucleus (lateral horn) levels
T1-L2
appetite suppressants (fenfluramine, phentermine, dexfenfluramine) for >3 months causes..
pulmonary HTN -> cor pulmonale -> sudden death from arrhythmia
cerebral berry aneurysm associated with which genetic disorders?
ADPKD and Eherlos-Danlos
medial calcinosis (affected vessels and prognosis)
calcific deposits in muscular artery >50y/o. affects femoral, tibial, radial, ulnar. and arteries to genital tract. do not narrow lumen, so asymptomatic
prominent finding in neonate/fetus with Turner (45X,O) along with others (think: lymph, cardiac, kidney)
- lymphedema of hands and feet
- abnormal nuchal lymphogenesis (subcutanoue nuchal edema and cystic hydroma)
- webbed neck/low posterior hairline
- cardiac abnormalities: coarctation of aorta, bicuspid aortic valve
- horseshoe kidney
adult presentation of Turner syndrome
(45 X,O) short stature, broad shield-like chest, webbed neck, primary ovarian failure – streaked)
fetus with Down Syndrome
trisomy 21; flat face, abnormal ears, slanted palpebral fissures, redundant skin at nape of neck, hypotonia, pelvic dysplasia, single transverse palmar crease
Edwards syndrome
trisomy 18; edwards: prominent occiput, micrognathia, small mouth, low-set and malformed ears, rocker-bottom feet. CHARACTERESTIC: clenched hands with index overriding the middle finger, 5th overriding 4th
1st most common autosomal trisomy in liveborn infants? 2nd? 3rd?
trisomy 21, downs
trisomy 18, edwards
trisomy 13, patau (most severe)
Patau syndrome
trisomy 13; patau: holoprosencephaly, microcephaly, polydatyl, rocker-bottom feet. mult facial abnormalities (hypotelorism, micropthalmia, cleft lip, cleft palate, absent or malformed nose)
47 XXX
clinically silent, decreased IQ, no increase risk of stillbirth
Klinefelter syndrome
47 XXY; mild mental retardation or normal intelligence. tall male with gynecomastia, small testes, and infertility. no increase risk of stillbirth
glucose-6-phosphate dehydrogenase catalyzes what rxn?
glucose-6-phosphate –> 6-phosphogluconate (with NADP+ –> NADPH. rate limiting step in HMP shunt
glucose through hexose monophosphate (HMP) shunt creates…
(1) oxidative: NADPH as a reducing equivalent
- requires glucose-6-phosphate
(2) reductive: ribose 5-phosphate for nucleotide synthesis & intermediates for glycolysis
- requires transketolase (thiamine-dependent)
How do RBCs protect against oxidative injury?
HMP shunt, generates NADPH to maintain glutathione in a reduced state (via gluathione reductase)
G6PD histology & precipitants
X-linked; Heinz bodies (denatured hemoglobin from oxidative damage), destroyed in spleen
PAINS: primaquine, aspirin, isoniazid nifuratoin, sulfonamides
Ascorbic acid
vitamin C; hydroxylation of proline and lysine residues in collagen: CT maintenance and wound-healing
Clinical presentation of orotic aciduria and Rx
impaired de novo pyrimadine synthesis: hypochromic megaloblastic anemia, neurologic abnormalities, growth retardation, excretion of orotic acid in urine; uridine supplementation, inhibit carbamoyl phosphate synthetase II
Resting potential of skeletal myocytes? cardiac myocytes?
- 75mV for skeletal
- 90mV for cardiac (reduced risk of arrhythmia)
Plataeu phase of cardiac myocyte action potential
phase 2: opening of L-type DHP-sensitive Ca++ channels and closure of some K+ channels
Orchiectomy vs. Orchipexy
removal of abdominal testes vs. surgery that allows descent
Effect of having one testicle on (1) androgen levels (2) inhibin B levels
(1) androgen not effected (compensation)
2) inhibin decrease (FSH increase
High levels of cortisol on GnRH secretion
hypogonadotropic hypogonadism (suppressed GnRH hormone)
Lipofuscin pigment
‘wear and tear’ pigment; finely granular yellow brown pigment granules composed of lipid containing residues of lysosomal degradation (part of normal aging: heart, liver, kidney…)
Pathologic ventricular hypertrophy is characterized by… (2)
(1) morphologic changes (increased sarcomere content & volume of myocyte) and (2) gene transcription changes, i.e: ANP
ANP vs. BNP (who secretes it, in response to what)
ANP: secreted by atria & sometimes hypertrophic
BNP: predominately ventricles
both in response to volume overload –> natriuesis & diuresis
Laplace’s law
distending pressure (pressure required to keep a sphere open) proportional to surface tension and inversely proportional to radius
P= 2T/r
as the radius of a sphere with constant ST decreases, pressure increases
Surfactant (2 effects)
prevent smaller airways from collapsing during expiration & regulates alveolar expansion (all at similar rates)
Chlamydia trachomatis cell wall
Lacks peptidoglycan in cell wall (muramic acid) and has cysteine residues instead (does have a cell wall, but can’t be treated with penicillin/cephalosporins)
(2) organisms that lack a cell wall
Ureaplasma urealyticum & mycoplasma (increased cholesterol)
causes of urethritis
gonococcal & (NGU) chlamydia trachomatic, ureaplasma urealyticum, mycoplasma, trichomonas. Rx: NGU: azithromycin
chlamydia anomaly
chlamydia has PBPs and genes for peptidoglycan synthesis, but does not have peptidoglycan on cell wall
MRSA survives penicillin by..
modification of PBPs
Class IA antiarrhythmics (procainamide) are good for what type of arrhythmia
arising from centers of normal automaticity (rather than areas demonstrating abnormal automaticity)
Class IV antiarrhythmics (verapamil) are good for…
atrial tachycardia (i.e. supraventricular tachycardia, bc slows conduction through AV node)
BAD for ventricular tachycardia; exacerbates
use of adenosine
paroxysmal supraventricular tachycardia
digoxin as an antiarrythmic
slow conduction through AV node
Labetolol mechanism & use
blocks alpha and beta adrenergics (decreased PVR, HR, contractility, slow AV conduction). used for refractory HTN, hypertensive urgency / emergency, and patients with pheo
Rx: ventricular tachycardia
amiodarone (class III) (used to be lidocarine class IB)
Niacin/nicotinic acid/B3 side effects…
acute flare of gouty arthritis (hyperuricemia),
facial flushing (cutaneous vasodilation Rx: aspirin)
hyperglycemia (acanthosis nigricans)
heptatitis
Mechanism of Niacin/nicotinic acid/B3
decrease hepatic synthesis of TGs and VLDL, increasing HDL
Drugs that increase risk of gouty attacks
HCTZ, cyclosporine, pyrazinamide, Niacin
Statin side effects
hepatitis, myopathy
First-line Rx: hypertriglyceridemia & side effects
fibrates; gallstones & myopathy (worse w/ statins)
Ezetimibe effect
inhibit intestinal absorption of cholesterol
Bile acid-binding resins (cholestyramine) side effects
GI upset
Hypertriglyceridemia
malabsorption
Acute monoarticular arthritis in septic arthritis vs. gout / pseudogout
septic arthritis (gonococcus) has high WBC (100,000) while gout / pseudogout has <20,000
MDD diagnosis vs. Dysthymic
5 symptoms of SIG-E-CAPS for at least 2 wks w/ depressed mood or anhedonia
vs. dysthmic disorder: depressed mood for >2yrs w/ 2 symptoms
both respond to antidepressants
Borderline personality disorder
instability in relationships and marked impulsivity
splitting: swing from scorning to idealizing
suicidal / self-mutilating
Manifestation of transplant rejection
- hyperacute
- acute
- chronic
- vascular fibrinoid necrosis; neutrophil infiltrate; thrombosis; infarction
- dense interstitial T-cell infiltrate (cell-mediated) OR vasculitis (Ab: in between hyperacute/chronic)
- obliterative intimal smooth muscle hypertrophy and fibrosis
Lung mass w/ hyponatremia =
SIADH, EUVOLEMIC
transient subclinical hypervolemia –> production of natriuretic peptides –> excretion of sodium
Hyponatremia urine osmolarity DDx (2)
- inappropriately concentrated >100mOsm = SIADH
- maximally dilute <100mOsm = polydypsia (appropriately low ADH)
Course of adult polycystic kidney disease
asymptomatic; progressively worsening uremia. has renal, pancreatic, and hepatic cysts
Risk during pelvic surgery (esp hysterectomy)
ligation of ureter, which runs posterior to uterine artery (ligated during hysterectomy for invasive cervical cancer)
Vesicoureteral reflex can occur after what surgeries (2)
prostatectomy or bladder surgery
Differentiate (3) Lambert-Eaton from Myasthenia Gravis
LEMS has…
(1) hyporeflexia or areflexia
(2) autonomic symptoms (dry mouth, impotence)
(3) better with stimulation / at the end of the day
Myasthenia gravis is associated with what endocrine abnormality, and how does MG happen?
thymoma / thymic hyperplasia
MG is NOT inherited acquired autoimmune disease
Polymyositis (3 characterizations)
idiopathic inflammatory myopathy characterized by (1) bilateral proximal muscle weakness (2) elevated creatinine kinase (3) electromyographic abnormalities
Polymyalgia rheumatica (PMR) (2 characterestics)
sudden onset of stiffness, pain, and tenderness of musculature (esp shoulders, hips, neck, torso)
- classically elevated ESR
Amyotrophic lateral sclerosis
(1) upper motor neuron disease – hyperreflexia, spasticity
(2) lower motor neuron disease – atrophy, fasiculation
Guillain-Barre syndrome; onset and progression
acute post-infectious polyneuropathy (often after Campylobacter jejuni). progressive ascending paralysis
Half of all LEMs have…
malignancy (small cell carcinoma usu)
Localized amyloidosis in cardiac atria (isolated atrial amyloidosis; form of senile cardiac amyloidosis)
Natiuretic peptide
IAA risk increases w/ age ( >90% by 90)
senile cardiac amyloidosis: transthyretin, also in brain
primary systemic amyloidosis deposits
immune globulin light chains (primarily lambda); in mesodermal tissue (heart, muscle, tongue)
BRCA-1 gene location and action
AD, chr. 17, tumor supressor; control cell cycle & role in gene repair & transcription
APC gene mutation associated w/..
decreased expression of D-cadherin adhesion molecule
genome recombination
two defective virus co-infect same host cell yielding cytopathic wild-type genome. exchange of genes between two chromosomes via crossing over within homologous regions
viral reassortment
exchange of whole genome sequences
transformation
uptake of naked DNA by prokaryotic cell
phenotypic mixing
co-infection of a host cell by two viral trains, resulting in a virion w/ nucleocapsid proteins from one strain and genome of other strain (alters infectivity)
viral interference
one virus inhibits the replication/release of a second virus infecting the same cell
sign of NE extravasation & antidote
cold, hard, pale IV site –> intense alpha-1 vasoconstriction –> local tissue necrosis. infuse phentolamine (reversible alpha-1 blocker)
lidocaine is less effective in…
acidic, ischemic tissue (becomes charged)
