test #25 4.13 Flashcards
skin rash, photosensitivity, arthralgia, renal disease in young women. general pathogenesis of disease
SLE. generally: autoantibodies bind autoantigens, immune complex deposition in vessel walls –> complement activation –> tissue inflammation and injury.
acute: fibrinoid necrosis
chronic: fibrosis & narrow lumen
anti-Smith (anti-snRNPs) and anti-dsDNA
highly specific for SLE, but absence does not rule out!
60% have anti-dsDNA, 20-30% have anti-snRNP/smith. virtually all have anti-ANA, but not specific for lupus
transposition of the great vessels
failure of aorticopulmonary septum to spiral normally during fetal development. aorta to right ventricle. pulmonary artery to left ventricle.
incompatible w/ life unless PDA, septal defect, or patent foramen ovale to allow for mixing.
failure of proliferation
unilateral aplasia of fibula
failure of oblieration
branchial cleft cyst
failure of apoptosis
autoimmune disease due to persistence of autoreactive T/B cells
failure of migration
hirschsprung, Kallman’s
failure of fusion
hypospadius
where can the saphenous vein be harvested?
just inferolateral to the pubic tubercle
when left anterior descending is occluded by plaque, which vein is often harvested?
left internal mammary artery (left internal thoracic artery).
when multiple coronary arteries are needed, which veins are used?
saphenous vein grafts. longest in body, located superficially. courses up from medial foot –> medial malleolus –> up medial aspect of leg and thigh. joins femoral vein in proximal anterior thigh 3-4cm infeolateral to pubic tubercle. in femoral triangle (inguinal ligament, sartorius, adductus longus)
most common type of hair less in males and females? genetics?
androgenetic alopecia (male pattern baldness). POLYGENIC inheritance w/ variable penetrance.
relationship between type of androgen receptor gene on X chromosome (X-linked recessive component)
NOT autosomal dominant as once thought
common polygenic medial conditions
androgenetic alopecia, epilepsy, ischemic heart disease, schizophrenia, glaucoma, hypertension, malignancy, DM type II
persistent vegetative state
severe brain damage that results in wakefulness without awareness. 50% of cases will regain consciousness in 6 months, but with severe subsequent disability
acute salicylate intoxication
2 different acid base abnormalities simultaneously.
(1) respiratory alkalosis: SOON AFTER INGESTION. directly stimulate medullary respiratory center –> hyperventillation, increased loss of CO2.
(2) few hours later, anion gap metabolic acidosis, due to accumulation of organic acids in blood. (high doses, salicylates increase lipolysis, uncouple oxidative phosphorylation, inhibit TCA –> accumulate ketoacid, alctate, pyruvate.
winter’s formula
PaCO2 = (1.5 x HCO3- + 8) +/- 2
used to see if respiratory compensation for metabolic acidosis is appropriate or not.
(i.e. respiratory compensation or independent respiratory alkalosis)
adverse effect in drugs w/ selective vasodilation of arterioles (hydralazine and minoxidil)
reduced arterial pressure, stimulates baroreceptor-mediated activation of sympathetics –> increased heart rate, contractility, increased RENIN –> Na+ and fluid retention
when given, add diuretics and sympatholytics
persistent cough and angioedema with a anti-HTN drug?
ACE inhibitors
angioedema
rapid swelling of dermis, subcutaneous tissue, mucosa, and submucosa
how can c. botulinum be prevented?
thoroughly heating food prior to consumption (toxin is heat labile)
classic paralysis in c. botulinum
descending paralysis, first manifesting w/ cranial n. involvement (diplopia, dysphagia, difficulty speaking).
note, both nicotinic and muscarinics aren’t getting Ach
hemicholinium
blocks choline entry into neuron
bromoacetylcholine
inhibits chAt (choline acetyltransferase) blocking synthesis of acetate + choline –> ACh
vesamicol
noncompetitively blocks vesicular Ach transporter.
transference
unconscious shifting of emotions or desires associated with one person to another. often arise from childhood parent child relationship
single most preventable cause of death and disease in US
smoking!
most effective preventative intervention
increased risk for macrovascular (MI, stroke), microvascular (retinopathy, nephropathy), complications of diabetes.
risk of MI-associated mortality decreases immediately upon smoking cessation
omeprazole
inhibit H+/K+ ATPase, decreasing concentration of HCl in stomach lumen
primary active transport
lidocaine
block voltage gated Na+ channels in sensory neurons, purkinje fibers, and ventricular cells
drug to reduce nicotine cravings while decreasing pleasurable effects of cigarettes?
varenicline PARTIAL AGONIST of a4b2 nAChR.
prevents nicotine binding & reduces symptoms of withdrawal by mildly stimulating receptor –> limited release of dopamine, less stimulation of reward parthways than nicotine would.
reduce cravings and rewarding effects of use
reinforcing effects of nicotine mediated by..
stimulate alpha-4-beta-2 nAChR in CNS
biopsy of skin lesion w/ celiac disease & appearance
dermatitis herpetiformis. groups of small vesicles (papulovesicular) on extensor surfaces.
biopsy: neutrophil & fibrin & IgA at tips of dermal papilla –> forming microabscesses.
gluten-free items? gluten-containing
gluten free: oats & rice.
gluten-containing: wheat, rye & barely
abetalipoproteinemia
inherited inability to form chylomicrons - absence of B48. presents in first year of life w/ malabsorption, failure to thrive, progressive ataxia, abnormal RBCs (acanthocytes)
skin manifestations of crohn’s disease & ulcerative colitis. what additional feature foes crohn’s have?
- erythema nodosoum (tender subcutaneous nodules) &
- pyoderma gangrenosum (deep ulcers w/ violaceous borders).
- apthous ulcers
normal gut flora. how is c. diff growth normally prevented?
very few aerobes: pseudomonas.
10% facultative anaerobes: e. coli, klebsiella, streptococcus, lactobacillus, staphylococcus, bacillus.
most strict anaerobes: bifidobacterium fusobacterium, clostridium, eubacterium, peptococcus, peptostreptococcus
suppress overgrowth of c. diff & others by competing for nutrients & adhesion sites (normal intestinal biomass)
oral thrush, interstitial pneumonia, and severe lymphopenia in first year of life suggests..
vertical transmission of HIV-1 from mom to baby
risk of HIV vertical transmission with no prenatal antirtroviral therapy
13-39%
most effective maternal prophylaxis to prevent vertical transmission of HIV-1? (who have not had antiretroviral treatment previously
ZIDOVUDINE (nucleoside analogue, retroviral reverse transcriptase inhibitor). reduces risk by 2/3rds.
intiiate at 14 wks & continued. IV during labor. oral 6 wks postpartum.
enfurvirtide
fusion inhibitor, blocks conformation changes in gp41 subunit required for fusion.
which vessels supply the trochanteric anastomosis that feed the femoral head and neck (4)? which is the major one? which is susceptible in femoral neck fracture
superior & inferior gluteal arteries. medial & lateral femoral circumflex arteries.
major: medial femoral circumflex. susceptible to damage w/ femoral neck fractures due to close association w/ posterior aspect of femoral neck.
lateral femoral circumflex: courses anterior to femoral neck.
obturator artery significance
gives rise to an artery that supplies blood to region of femoral head proximal to epiphyseal growth plate. impt in kids, minimal significance in kids
cataracts in galactosemia?
due to galactose –> galactitol (via aldose reductase) due to either galactokinase or galactose 1-phosphoate uridyl transferase deficiency
beta-galactosidase deficiency
lysosomal enzymes responsible for breakdown of glycosoaminoglycans. results in accumulation of keratin sulfate in lysosomes.
short stature, normal intelligence, altantoaxial instability, valvular heart disease
enzyme also impt for breakdown of lactose
collagen’s simple repetitive amino acid sequency
-(Gly-X-Y)-333.
glycine > proline > lysine
GLYCINE every 3rd position (most abundant amino acid in collagen). smallest, fits into tight spaces when form triple helix
many X and Y are PROLINE (ring structure introduces bend in polypeptide chain).
other X and Y form hydrophobic & charged regions to enable crosslinking to other molecules. LYSINE
how does NaHCO3 help TCA overdose
correct QRS prolongation, reverse hypotension, and treat ventricular dysrhythmia
all effects of TCA due to blocked fast Na+ channels
HbsAg
noninfective envelope coat glycoprotein of Hep B. forms tubules and spheres w/ 22nm diameter
HbcAg
nucleocapsid core protein of Hep B
HbeAg
nucleocapsid core protein + precore protein (which mediates secretion)
marker of replication & transmissibility
Hbx (transcriptional transactivator of viral genes from X region
necessary for Hep B replication. also downregulates regular hepatocyte replication, important for development of hepatocellular carcinoma
what maintains CO in aortic regurg
increased left ventricular end diastolic volume
bone marrow diagnosis for multiple myeloma
> 30% plasma cells in bone marrow
symptoms of multiple myeloma and demographic. pathogenesis?
usu older (70 y/o).
CRAB:
hypercalcemia, renal failure, anemia, bone pain / lytic lesions
increased susceptibility to infxn
neoplasm of plasma cells. secrete IL-1 (osteoclast activating) and IL-6. hypercalcemia.
M-spike on serum protein electrophoresis (usu IgG or IgA)
Bence jones protein casts (immunoglobulin light chain ppt)
rouleoux on smear
renal failure due to amyloidosis, hypercalcemia deposits, bence jones protein casts, plasma cell infiltration.
diseases w/ m-spike on serum protein electrophoresis (3)
(1) multiple myeloma (2) waldenstrom’s macroglobulinemia (3) MGUS (monoclonal gammopathy of undetermined significance)
waldenstrom’s macroglobulinemia
hyperviscosity symptoms, M spike, no lytic bone lesions
MM lytic bone lesions
MGUS (monoclonal gammopathy of undetermined significance)
precursor to multiple myeloma. M spike w/ 30% plasma cells in bone marrow)
factors important for insulin resistance? mechanism?
free fatty acids, glucocortiocids, glucagon, catecholamines.
downstream SERINE phosphorylation of (1) beta-subunit of insulin receptor and (2) of IRS-1
instead of TYROSINE phosphorylation
rx for seizures (DTs) in alcohol withdrawal
benzodiazepine (diazepam / chlordiazepoxide)
most important side effect of benzodiazepines
sedation!
avoid first generation anti-histamines (diphenhydramine, dimenhydrinate, chlorpheniramine, hydroxyzine, promethazine)
also avoid: alcohol, barbituates, neuroleptics
diphenhydramine, chlorpheniramine, diphenhydrinate, hydroxyzine, promethazine
1st generation antihistamines
PABA-containing sunscreen
most potent & widely-used UVB (290-320 nm) radiation absorbers.
do NOT absorb UVA (320-400) (absorbed by avobenzone [specifically] and zinc-oxide containing [broadly]
which UV radiation is major cause of ultraviolet radiation burns, histologic skin damage, UVR-induced immunosuppression, skin photo-aging, and photocarcinogenesis
UVB
generates ROS that damages skin
what type of sunscreen blocks UVAI and II only
avobenzone
which sunscreens provide broad-spectrum UVB, UVAI, and UVAII block
zinc-oxide containing
rx for multiple myeloma
bortezimib (proteosome inhibitor)
allows for accumulation of protein in plasma cells –> apoptosis
cytoplasmic inclusions in oligodendrocytes
PML
gower’s sign & calf enlargement in a male between 3-6
Duchenne muscular dystrophy. X-linked recessive. frameshift mutation of dystrophin. links actin to ECM
Charcot-Marie-Tooth disease (aka heriditary motor and sensory neuropathy)
mutation of genes responsible for synthesis of MYELIN (& other components of peripheral n.)
decreased nerve conduction.
presentation: weakness of foot dorsiflexion due to involvement of common peroneal n.
hyperkalemic periodic paralysis
ion channel myopathy
rx for congenital adrenal hyperplasia (i.e. 21B-hydroxylase deficiency)
low doses of corticosteroids, suppressing ACTH.
most common locations for colon cancer?
rectosigmoid > ascending > descending
right vs. left sided colon cancer
right: exophytic. presents as iron deficiency anemia, associated w/ HNPCC (microsite instability)
left: infiltrate wall, narrow lumen, obstruction. associated w/ APC
role of prostacyclin PGI2(4)
made by vascular endothelium. inhibits platelet aggregation, vascular tone, bronchial tone, and uterine tone.
in balance w/ thromboxane A2 (enhances platelet aggregating and vasoconstricts)
kulchitsky cells
gut ECL cells
hageman factor
factor XII of clotting cascade.
kalikrein
converts kininogen into bradykinin
which two brain regions are first damaged during global cerebral ischemia
FIRST: HIPPOCAMPUS (pyramidal cells)
and thenCEREBELLUM (purkinje cells)
microscopy differences between crohn’s and ulcerative colitis
crohn’s - noncaseating granulomas.
ulcerative colitis - crypt abscesses. no granuloma.
ependymal epithelium in choroid plexus
simple ciliated columnar.
describe choroid plexus capillaries
unlike elsewhere in CNS, capillaries are FENESTRATED. columnar epithelium (ependymal cells) have TIGHT junctions –> selective
pseudotumor cerebri
classically overweight young females. communicating hydrocephalous. related to decreased CSF outflow at arachnoid villi
inheritance of glucose-6-phosphate dehydrogenase decfiency
x-linked recessive (most common human enzyme deficiency).
oxidative step of pentose-phosphate pathway:
needed to convert glucose-6-phosphate —> 6-phosphogluconate (generate NADPH).
NADPH then given to glutathione (via glutathione reductase)
2 steps in pentose phosphate pathway (HMP shunt)
oxidative:
glucose-6-phosphate —> ribulose-5-phosphate
(rate limiting enzyme: glucose-6-phosphate dehydrogenase, 6-phosphogluconate is first pdt)
makes NADPH for glutathione reduction
nonoxidative
ribulose-5-phosphate —> ribose 5 phosphate
(via transketolase, requires THIAMINE B1 exclusively)
drugs that trigger oxidative stress & hemolysis in RBCs (dark urine in glucose-6-phosphate dehydrogenase)
primaquine, anti-malarial, anti-TB, nitrofurantoin, dapsone, bactrim, sulonfamides. FAVA beans
how is the H2O2 (made by partial reduction of O2) in RBCs cleaned up
with glutathione peroxidase (reduces H2O2 with reduced glutathione) to make water
class I antiarrhythmics generally have affinity for which types of receptors?
what are their relative Na+ channel bindings? how does this related to their indications / contraindications?
inactivated & active Na+ channels (not those in resting). therefore, use dependent (not enough time to be in ‘resting’ state’
relative Na+ channel binding strength 1C > IA > IB.
IC (morzicline, flecainide, propafenone) binds so strongly, will have accumulating affects w/ each cardiac cycle (takes long to dissociate), esp in tachyarrhythmia. so much so that block of conduction velocity in myocytes can be greater than AV node block —> leading to pro-arrhythmic effects. CONTRAindicated in ischemic / structural defective tissue, bc will bind too avidly
IB (lidocaine, mexelitine, phenytoin) has less ‘use dependence’ bc binds less avidly, and dissociates rapidly (minimal cumulative effect). but, in ischemic tissue, reduce potential difference increases time Na+ channels are inactivated, allows for IB binding. useful for treating ischemia-induced ventricular arrhythmia.
HR determined by
rate of If (funny current) depolarization in pacemaker cells
