General HO 0502Q Flashcards
HIT
more common w/ unfractionated heparin.
leads to paradoxical thrombosis.
avoid HMW and LMW heparin.
argatroban
direct thrombin inhibitor - bind thrombin active site. does not require AT III for action.
used to treat HIT.
other DTIs: hirudin, lepirudin
dx of febrile URI followed by sudden appearance of red, flushed cheeks 2-5 days later in child?
erythema infectiosum (parvovirus B19) - rash related to IC deposition once serum IgM and IgG levels are high enough
where does parvovirus B19 replicate?
BONE MARROW.
tropic for erythroid precursor cells (bld group P Ag [globoside] serves as receptor)
what appears as parvovirus face rash disappears?
reticular lacelike pattern on trunk and extremities
JAK2
non-receptor tyrosine kinase assoc. with EPO receptor (type I cytokine receptor)
which Abs are essential for classical complement pathway after binding C1?
IgG and IgM.
which Ab is more effective in activating complement cascade?
IgM (pentameric structure)
dysphagia and disfigured fingernails (spoon nails/koilonychia) are specific for….?
iron deficiency anemia
*dysphagia often due to esoph. webs (Plummer Vinson syndrome)
common features of all types of anemia
malaise fatigue pallor decreased exercise capacity CHF
tx of iron deficiency anemia
oral iron prep
*may add vit C to improve oral iron absorption
what supplement reduces erythroid precursor apoptosis in folate deficiency?
THYMIDINE
activates thymidine kinase salvage pathway.
increases dTMP levels.
X-linked recessive inheritance
affected males always produce unaffected sons, carrier daughters.
carrier females have 50% chance of producing affected son, carrier daughter.
ex: G6PD deficiency
ferritin
intracellular iron-binding protein.
stores iron inside enterocyte.
iron is eventually excreted in stool as enterocytes are sloughed.
ferroportin
iron transporter on basolateral enterocyte surface.
allows iron to enter circulation.
transferrin
iron-binding transport protein that binds free iron in circ.
eventually becomes internalized after interacting with transferrin receptor on cell.
what regulates the diff routes taken by iron?
HEPCIDIN - acute phase reactant made in LIVER by hepatocytes
hepcidin action on ferroportin
causes internalization and degradation of ferroportin.
results in decreased basolateral iron transport in intestine. inhibits release of iron by macrophages
what increases hepcidin synthesis?
high iron levels.
inflamm conditions.
lactoferrin
secreted by renal tubular cells.
binds free iron in urine for possible metabolic use.
*very limited role in iron metabolism
AL amyloidosis
assoc. with multiple myeloma and other monoclonal plasma cell dyscrasias.
derived from monoclonal Ig light chains.
deposit in kidney, heart, tongue, nervous system.
serious adverse effect of ganciclovir
NEUTROPENIA
increased incidence w/ co-admin of zidovudine. both drugs affect DNA synthesis of hematopoietic stem cells and result in BM suppression
mitotic index is Burkitt lymphoma
high value.
aka proliferation fraction (Ki-67)
how does radiation induce DNA damage?
through dsDNA breaks and formation of oxygen free radicals.
common cause of extramedullary hematopoiesis
severe chronic hemolytic anemia
skel abnormalities due to EM hematopoiesis
expanding mass of progenitor cells in BM thins out bony cortex and impairs bone growth…
pathologic fx
maxillary overgrowth and frontal bossing (chipmunk facies)
Bruton’s agammaglobulinemia
X-linked deficiency of all antibodies and low B cell counts due to defect in B cell maturation.
T cell numbers and functions are intact.
absent germinal centers.
paracortical zone of LN
internal to cortex.
mainly has T cells and dendritic cells.
dendritic cells present Ag to T cells here.
causes of non-EBV infectious mono
CMV
HIV
toxoplasmosis
procarcinogens enter body and are metabolized by…?
most chemicals are metabolized by P450 MONOOXYGENASE in hepatic microsomes and endoplasmic reticulum in various tissues
factor Xa inhibitors
anticoagulants with specific activity against factor Xa WITHOUT antithrombin activity
lab changes seen with factor Xa inhibitors
increase PT and aPTT.
NO CHANGE to TT.
what effect does heparin and other drugs that directly inhibit thrombin formation have on TT?
prolonged TT
steroid abuse
erythrocytosis abn testicular size, function hepatic abnormalities deepened voice male pattern baldness acne
*competitive athletes
androgen effect on RBC
stimulates RBC production (higher Hct)
MTX for ectopic preg
DOC for <6WGA
toxic to rapidly dividing cells of trophoblast
MTX molecule
similar to folic acid structure.
converted to POLYGLUTAMATE form inside target cell (keeps it in cell)
what modification allows folate and recycled DHF to be stored within cells?
polyglutamation
what is PABA (para-aminobenzoic acid)?
folic acid precursor in prokaryotes
what drug is a chemical analogue of PABA?
sulfonamide Abx - inhibit dihydropteroate synthetase to prevent bact conversion of PABA to folic acid
PI3K/Akt/mTOR pathway
intracellular signaling pathway - antiapoptosis, cellular proliferation, angiogenesis
mutations in any component contribute to cancer pathogenesis
aplastic anemia presentation
pancytopenia
low reticulocyte count
NO splenomegaly
aplastic anemia labs
“dry” BM aspirate.
marrow replaced by fat cells and fibrous stroma
myelophthisic anemia
caused by SPACE-OCCUPYING lesions in BM. all hematopoietic lines affected.
*common cause: metastatic carcinoma with fibrosis
Hb action in lungs
binds O2, releases protons
Hb action in tissues
releases O2
acquires protons
where in body does Hb become completely saturated with O2?
LUNGS
high pO2 in alveoli increases O2 binding to Hb, causes release of protons.
what is the mech of Hb release of oxygen in the TISSUES?
high proton conc (due to high Co2, converted to bicarb and protons by carbonic anhydrase) in tissues protonates amino groups of Hb subunits – subunits form salt/ionic bridges that STABILIZE DEOXY Hb and decreases Hb affinity for O2
what stabilizes deoxyHb (favors decreased Hb affinity for O2)?
- salt bridges between N-terminal histidine residues in each globulin
- ionic bonding of 2,3 DPG to two beta subunits
Rb protein
prolif signals activate cyclin-dependent kinase 4, which hyperphosphorylates Rb to make it INACTIVE. this allows unregulated transition from G1 to S phase of cell cycle
*hypophosphorylated = active. hyperphosphorylated = inactive.
E2F transcription factor
released by hyperphosphorylated Rb to allow cell progression from G1 to S phase
what happens when E2F TF is bound?
hypophosphorylated Rb + E2F complex INHIBITS transcription of genes for G1-S transition
what would increased activity of DHF reductase and DNA polymerase indicate?
increased DNA synthesis
what kind of cells are the ATYPICAL LYMPHOCTES seen in infectious mono?
activated CD8+ cytotoxic T cells
destroy virally infected B cells
what is CD14?
surface marker of monocytes, macrophages.
receptor for LPS, which activates macrophage.
scenarios for CO poisoning
- emission for cars in poorly ventilated spaces
2. faulty home heater
tx of CO toxicity
100% or hyperbaric oxygen
CO action
inhaled CO rapidly diffuses across alv memb to bind heme-bound iron (carboxyHb)
CO decreases O2 content of bld by occupying O2 bindings sites
CO also alters Hb conformation to relaxed form (inhibits release of O2 in tissues)
how does CO change oxygen dissociation curve?
CO also alters Hb conformation to relaxed form (inhibits release of O2 in tissues)
LEFT shift in curve.
tissue hypoxia via deficient O2 unloading
2,3 DPG
binds Hb in pocket formed by the two beta chains - forms ionic bonds with beta subunits of DEOXY form
what type of Hb cannot interact with 2,3 DPG?
fetal Hb (serine instead of histidine. no beta chains) - much higher affinity for O2. needs to extract O2 from maternal Hb in placenta.
process of liver uptake of unconj bilirubin
PASSIVE - organic anion transporting polypeptide (OATP)
process of liver secretion of conj bilirubin
ACTIVE - MRP2 organic ion transporter/ATP-binding cassette protein
some passive through hepatocyte OATP
what is unconj bilirubin complexed to in circ?
serum albumin - UCB is insoluble in water. tightly complexed to albumin in circ. CANNOT be excreted in urine.
which form of bilirubin is freely excreted in urine?
conjugated bilirubin - water soluble, non toxic. loosely bound to albumin.
mechs that produce unconj hyperbilirbuinemia
- excessive production of bili
- reduced hepatocyte uptake
- impaired conjugation
mechs that produce conj hyperbilirubinemia
- decreased hepatocellular excretion
2. impaired bile flow
host cell receptor : virion/virion protein binding
- CD4 : HIV gp120
- CD21 : EBV gp350
- erythrocyte P Ag : parvovirus B19
EBV transmission
oropharyngeal secretions
herpesvirus entry into host cell requires…?
initial contact with GAG chains on host cell surface proteoglycans
resistance to activated prot C
factor V Leiden = atypical venous thrombosis
ondansetron for chemo-induced nausea/vomiting
inhibits serotonin 5HT3 receptors which are located peripherally in presynaptic nerve terminals of vagus n. in GI tract - also present centrally in chemoreceptor trigger zone (area postrema) and solitary nucleus
filgrastim
G-CSF analog that stimulates proliferation/differentiation of granulocytes.
used to minimize granulocytopenia after myelosuppressive chem.
prevention of tumor lysis syndrome (electrolyte disturbances, acute renal failure)
ALLOPURINOL
along with hydration and alkalinization of urine
major clin manifestations of factor V Leiden
- DVT
- cerebral vein thrombosis
- recurrent pregnancy loss
pathogenesis of thrombophilia in factor V Leiden
- increased coagulation (thrombin prod)
2. decreased anticoagulation (activated prot C resistance)
what is used to prevent primary/secondary coronary artery events and ischemic strokes in pts who have had a TIA?
daily low-dose aspirin
presentation of TIA
sudden onset of focal numbness and tingling, fully resolved in minutes.
ddx: seizure, migraine, anxiety, hypoglycemia
at low doses, aspirin mainly inhibits….?
COX1
what is Samter’s triad?
- asthma
- aspirin hypersensitivity (nasal sx, bronchospasm, facial flushing)
- nasal polyposis
- occurs in asthmatics treated w/ ASA
- due to overproduction of leukotrienes that occurs when ASA blocks COX and diverts precursors into lipooxygenase pathway
salicylism
caused by very high dose ASA.
vertigo, tinnitus, hearing loss.
also stimulates resp drive (hyperpnea).
why is there an even greater increased risk of GI bleeding with high dose ASA?
loss of gastric cytoprotection in addition to impaired plt aggregation
multidrug resistance gene (MDR1) in human tumor cells
codes for P glycoprotein, a transmemb ATP-dependent efflux pump protein that has broad specificity for hydrophobic cmpds.
reduces influx of drugs into cytosol AND increases efflux from cytosol - thereby preventing action of chemotherapeutic agents
differential cyanosis restricted to lower body (in child) suggests….?
PDA with late-onset reversal of shunt.
*whole body cyanosis occurs with shunt reversal in pts with septal defects or TOF
does coarctation of aorta cause cyanosis?
NOOOOO - it can limit lower extremity exercise tolerance but does not cause cyanosis
what causes differential cyanosis?
reduced arterial oxygen saturation in distal aorta compared to that in aorta proximal to left subclavian artery – right to left shunting of bld through PDA into junction between aortic arch and descending aorta
most common cause of aortic stenosis
degenerative (senile) calcification of aortic valve leaflets
pulsus parvus et tardus
small and slow rise in carotid pulse during systole
*seen in aortic stenosis
how does hydroxyurea help sickle cell disease?
increase HbF by unknown mech
which sickle cell pts are treated with hydroxyurea?
pts with frequent pain crises
Gardos channel blockers in sickle cell tx
calcium-dependent (Gardos) potassium channel regulates K and H2O transport through RBC memb.
blocked channel = prevent RBC dehydration = reduce HbS polymerization.
BM in megaloblastic anemia
HYPERCELLULAR but megaloblastic erythroid precursors are quickly destroyed in BM before entering circ
hyperplastic arteriolosclerosis mechanism in hypertensive crisis
laminated SMCs and reduplicated BMs.
renal arteriolar stenosis decreases glom perfusion and GFR, thus activating RAAS.
presentation of aplastic anemia
pancytopenia.
NO SPLENOMEGALY.
BM in aplastic anemia
HYPOcellular. replaced by fat cells, fibrous stroma.
what should be ruled out first in a pt with iron deficiency anemia?
bld loss, esp in GI tract…. esp in adult males and postmenopausal women
*upper GI endoscopy + colonoscopy
hemorrhagic disease of newborn
cutaneous, GI, and intracranial bleeding.
PRETERM INFANTS at risk.
prevent with VIT K (parenteral at birth + supp in formulas)
what does breast milk from women with healthy diets lack?
vit K and D
*D deficiency manifests around 6 mos.
K deficiency can be life-threatening w/in first week of life.
when do maturing erythrocytes lose their ability to synthesize heme?
when they lose their mitochondria
where in the body is heme synthesized?
everywhere but mainly in RBCs and hepatocytes
what do hepatocytes use heme in?
P450 system
what is the major determinant of prognosis for bladder carcinoma?
tumor penetration of bladder wall
do sickle cell TRAIT RBCs sickle when sodium metabisulfite is added?
yes….
all other parameters normal.
HbS in sickle cell trait
35-40% HbS
> 50% HbA**
