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1264 Cards in this Set
- Front
- Back
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Roles of hormones
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"Reproduction, growth, homeostasis, EPU"
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Alpha Cells Secrete
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Glucagon
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Beta Cells secrete
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insulin
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insulin begins as
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preproinsulin
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First step of processing of preproinsulin
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"Cleaving off the signal peptide, becomes proinsulin"
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where is proinsulin processed
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Golgi
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Why is the C-peptide important
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can monitor amount of insulin secretion. made in 1:1 ratio. cleaved of A and B chains to make proinsulin into insulin
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where is preproinsulin synthesized
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cytosol
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what is one of the primary regulators of insulin secretion
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ATP/ADP levels in beta cells open/close K channels which then effect Ca channels which release the vesicles
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What cells are affected by insulin
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Only cells that have insulin receptors
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what glucose transporters are in pancreatic B cells
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GLUT2
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What is the primary effect of insulin
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Enhances translocation of GLUT4 to the membrane of target cell
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In general what physiologic processes does insulin produce
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anabolic paths for storage with decreased catabolism
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Glucagon is inhibited by
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Glucose and insulin
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how to catecholamines and glucocorticoids affect glucagon secretion
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counteract insulin affects
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What cell signalling pathway interacts with glucagon secretion
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G protein coupling with PKA and cAMP
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Whats up with glucagon in type I diabetes
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since no insulin is produced glucagon is not inhibitted
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What Glucose transporters have the lowest Km
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1 and 3
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What is the state of phosphorilated PFK2 in the liver
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Inactive
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"What is the state of Fructose 2,6 Bisphosphotase when there is no phosphorylation in the muscle"
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Active
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What is the result of glucocorticoids on a cell
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"regulate transcription, resulting in slow changes that can have prolonged effects"
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Leptin has what effect
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satiey
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Orexigenic or Anorexigenic: Gherlin
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Orexigenic
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Orexigenic or Anorexigenic: PYY
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Anorexigenic
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gamma bond of ATP releases how much energy
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"7.3 kcal
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"why is 1,3 biphosphoglycerate important"
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"substrate level phosphorylation
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When is substrate level phosphorylation especially important
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RBC since they do not have a TCA cycle
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What is the equation for BMR
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Weight (kg) x 24 kcal/kg/day
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TEE?
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Total Energy Expenditure=BMR+activity
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What is the go to fuel for muscle
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Fatty acids
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RBCs use what for fuel
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ONLY glucose
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What can't the brain use for fuel
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Fatty acids
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What is the livers role in metabolism
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"Maintains all the other organs, produces KB, converts glucose to fat or glycogen for storage"
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Where are fuels going in the fed state
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"brain and rbc are using glucose for energy. adipose and liver are storing glucose, muscle is using glucose and other tissues are using proteins"
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what shift happens in fasting
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"production of ketone bodies, muscle is using more FA and KB, adipose is releasing FA and liver is going thru GNG to feed RBC and brain. Urea cycle kicks in"
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Starved state has what effects
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Urea cycle stops and brain is using KB exclusively. All glucose made from GNG is going to RBCs
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how many protons are pumped by oxidizing NADH
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"10, 4 from I, 2 from III, and 4 from IV"
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How many protons are pumped by oxidizing FADH
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"6, 2 from III and 4 from IV"
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F0 of ATP synthase is located where
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imbedded in the inner membrane of mitochondria
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what subunit is turning in ATP synthase during proton transport
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Gamma
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"in one full turn of gamma, how many protons are pulled thru, and how many ATP are made"
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12 H+ and 3 ATP
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How does ADP get into the matrix
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"Use of an antiporter with ATP
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how is P being replenished in the matrix
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A symporter Phosphate translocase moves H2PO4 and H+
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how do reducing equivalents get into the mitochondria
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Malate Aspartate shuttle
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Malate Dehydrogenase
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OAA+NADH-->malate
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Aspartate Aminotransferase
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"Transamination of OAA to Asp
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What does the brain do to get reducing equivalents
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"Glycerol 3 phosphate shuttle
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What is Oligomycin
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"blocks proton channel of atp synthase. enhances ETC at same time until proton pumps fail, slows overall o2 consumption"
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what is DNP (dinitrophenol)
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disconnects proton pump from ETC. Disrupts proton gradient. ADP builds up and forces ETC but no ATP made
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Thermogenin
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uncouples proton gradient produces heat
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what enantomer form are most monosacharides in
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D-form
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Which configuration is glucose most commonly found in
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Alpha. OH on C1 is opposite C6
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Galactose+ Glucose=
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Lactose
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Fructose+ Glucose=
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Sucrose
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Dietary Fiber has what type of glycosidic bond
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"B 1,4"
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Glut5
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Fructose transporter
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Glut1
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glucose and galactose
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SGLT1
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Na and Glucose cotransporter
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how does a cell reestablish Na concentration in regards to SGLT1
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Na K ATPase pump
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What is the net production of glycolysis
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2 ATP and 2 NADH (.5 ATP thru TCA)
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Hexokinase is inhibitted by
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Glucose 6 Phosphate
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Glucokinase is inhibitted by
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Fructose 6 Phosphate
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What is positive feedback for PFKII
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"Insulin, Ca"
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What pushes F26Bp towards F16Bp
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Glucagon
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What inhibits PFKI
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"ATP, Citrate"
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What induces PFKI
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"AMP, F2,6Bp"
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What is the rate limiting step of glycolysis
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PFKI
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Inhibitors of PK (pyruvate kinase)
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"Alanine, ATP"
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Activator of PK
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"F1,6P (insulin in the liver)"
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At what steps of glycolysis is ATP produced
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"phosphoglycerate Kinase, pyruvate kinase"
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What steps of glycolysis require energy
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"Hexokinase/glucokinase, PFK"
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What can pyruvate become
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"Alanine, lactate, OAA, acetyl CoA"
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when is NADH produced in glycolysis
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"Glyceraldehyde 3 phosphate--> 1,3 bisphosphoglycerate"
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How is Glucokinase regulated
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"sequestered in nucleus with a regulatory protein, glucose dissociates the RP. F6P activates the RP"
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1 Trip thu TCA gives
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"3 NADH, FADH, GTP"
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What is the driving force of TCA
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"Low NADH/NAD+ ratio, Low ATP/ADP"
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What enzymes are regulated in TCA
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"citrate synthase, isocitrate dehydro, a-ketodehydeo, succinate dehydro"
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where does the pyruvate dehydro rxn happen
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mitochondria
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What moves pyruvate into the mitochondria
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monocarboxylate transporter (antiporter with OH)
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PDH complex has what vitamin as a part of it
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"Thiamine (B1), B2, and B3"
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What regulates PDH
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"substrate activation, product inhibition, PDH kinase/phosphotase, kinase and phos are further regulated by products and substrates of PDH"
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PDH deficiency
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Leads to Lactic acidosis
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what is the substrate of the PPP
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G6P is converted to a pentose sugar while producing NADPH via oxidative path or F6P via the non oxidative path
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What glucosylates glycogenin
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itself!
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insulin does what to glycogen synthesis enzymes
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"activates the phosphotases, no phosphorylated enzymes= glycogen synthesis"
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What enzyme is not present in muscle regarding glycogen
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Glucose 6 phosphatase. that way g6p can only go thru glycolysis
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UDP Glucose Pyrophosphorylase
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makes G1P into UDP Glucose
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Glycogen Synthase
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"creates 1,4 glycogen bonds when not phosphorylated"
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4:6 Transferase
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makes 1:6 glycogen bonds to create branching in glycogen after about 11 glucoses are added in a chain
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Why does glycogen need to branch
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so there are many available reducing ends to add and subtract glucose molecules from
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When glucogon is high what regulatory enzyme is turned on regarding glycogen
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Kinase. when glycogen enzymes are phosphorylated glycogen breakdown predominates
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what interconverts G6P and G1P
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phosphoglucomutatse
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"4,4 transferase"
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"takes off branches 3 Gs from branch point and creates 1,4 bonds"
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"what is special about the action of 1,6 glucosidase"
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"removes the branch point as glucose, not G6P"
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What is the interaction between PK and epi in muscle tissue
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Epi will not cause phosphorylation of PK
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What is the deficiency in McArdle's Disease
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Glycogen phosphorylase
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what 2 chromosomes are most hemoglobin genes on
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11 and 16
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What 2 types of hemoglobin are hb gower
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epsilon and zeta
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Hb F is which 2 globins
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alpha and gamma
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what is HbA2
|
alpha and delta. low abundance adult hb
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"What Hb has the highest affinity for O2, why?"
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"HbF, so it can steal O2 from mothers blood stream"
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What creates methemoglobin
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oxidizing iron to become Fe3+
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F helix is proximal or distal
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Proximal Histadine
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what does the distal histidine do
|
stabilizes the O2 interaction and prevents oxidation and reduces affinity for CO
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What increase Fe absorbtion
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Vit C
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What breaks down iron compounds after theyve been absorbed
|
heme oxygenase. to be absorbed Fe3+ in diet must be reduced. reductase upregulated by Vit C
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What must happen to iron to be carried by transferrin
|
transferrin only carries Fe3+ so it must be oxidized again by ferroxidase
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"If a pt has a high TIBC, what does that mean"
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the pt is iron deficient
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What are agents that inhibit heme production
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"Heme, Heavy Metals"
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What would happen in a ferrochetalase deficiency
|
"heme would still bind Fe, but at much slower rates"
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Which step in heme synthesis is the most sensitive to enzyme dysfunction
|
"Step 4, takes the unstable compounds and turns them into heme, without enzyme 4 many unstable dangerous metabolites can be formed"
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What is the difference between ALAS1 and 2
|
"ALAS1 makes heme for tissues other than blood, ALAS2 makes heme for blood"
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How do cells ensure there is no disproportionate levels of heme to globin
|
globin synthesis is induced by presence of heme and inhibitted thru HCI if no heme is available
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What would be a good way to treat a pt with toxic levels of heme metabolites
|
inhibit ALA synthase (hematin or glucose) which will slow the production at the rate limiting step
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Porphyria Cutanea Tarda
|
"Dom inher.
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Acute Intermittent Porphyria
|
colored stool and urine. agitation/madness. mis-Dx as psych issue
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what contributes to heme being able to release O2 to tissues
|
"physical strain on molecule, likes to be puckered but O2 flattens it out."
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which steps of heme synthesis happen in the mitochondria
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1st and last 3
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2.3 BPG levels _____ in people living in higher altitudes
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Higher
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"explain why 2,3 BPG levels vary in people of different altitudes"
|
"2,3 BPG decreases hb affinity for O2, allowing more effective O2 delivery to peripheral tissues."
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"besides altitude what can increase 2,3 BPG levels"
|
"Anemia, Cardiopulmonary insufficiency"
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Explain the Bohr effect
|
"as O2 binds to hb, H+ is released. If the blood becomes acidotic it pushes O2 off hb, decreasing affinity."
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alpha thalassemia
|
"deletion of 1 or more alpha globin genes. 1 deletion-silent. hydops fetalis, all 4 deleted, hemoglobin H, 3 deletions"
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B-thalassemia
|
"varied phenotype. minor-severe. in severe cases too much a-globin, forms insoluable aggregates."
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what is the regulated step of Hb degradation
|
"heme oxygenase cleaves pyrrole ring, requires O2 and NADPH. Releases CO and Fe3+. product: biliverdin"
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what can physiologic levels of CO tell a clinician
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Rate of heme breakdown
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what are the steps of bilirubin conjugation
|
"Bili is carried to liver on albumin
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what moves conjugated bili out of hepatocytes
|
multidrug resistance protien 2
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what does direct bilirubin measure
|
conjugated bilirubin
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What is a characteristic of prehepatic jaundice
|
"no bili in urine, increased unconjugated bili"
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intrahepatic jaundice will result in what lab results
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increased urobilinogen in urine and decreased in stool.
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Posthepatic jaundice presents:
|
"lots of conjugated bili in urine, no urobili in stool or urine"
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What does Haptoglobin do
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binds loose ab hb dimers in blood
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"What are the caloric values of carbs, protein, fat, and ethanol"
|
"4, 4, 9, 7"
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what is the relationship between length of FA and melting point
|
longer chains make for higher melting points
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how do double bonds affect melting point
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"more double bonds, lower melting point"
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ARDS is a result of:
|
lack of phosphatidylcholine (lecithin)
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What vitamin is important for myelin
|
B12
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the major component of cholesterol is
|
Acetyl CoA
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How do Lipase and Colipase work together
|
colipase makes space for lipase to work in the micele to make monoacylglycerol
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what happens to MAG and FA in absorptive cells in the intestines
|
reassembled as TG and packaged into chylomicrons and sent to the lymphatics
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Small and medium chain fatty acids are special why
|
Don't need micelles or chylomicrons. long and very long do
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which lipoprotein is located on chylomicrons
|
ApoB48
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HDL gives up which proteins to chylomicrons
|
ApoCII and ApoE
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How do chylomicrons get into cells
|
LPL is upregulated by insulin and binds to ApoCII in the capillary lumen. digests TG in the chylomicron to FA and glycerol
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Describe the actions of hormone sensitive lipase
|
"Epi, Glucagon, corticoids activate PKA which P-ates HSL. HSL removes FA from glycerol 1 by 1"
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how do LC and VLC FA get into the mitochondria
|
"LC are P-ated and bound to CoA, carnitine shuttle moves it in. VLC are reduced to LC in peroxisomes"
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Describe the process in which LCFA gets P-ated
|
ATP releases 2P and binds AMP to LFCA via Thiokinase. CoA is added and AMP is released
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How does the Carnitine Transport System work
|
CPTI on outer membrane swaps the CoA for carnitine. FA-Carn then enters antiporter carnitine acyl carnitine translocase into the matrix. CPTII on inner membrane swaps carnitine for CoA
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What inhibits CPTI
|
Malonyl CoA (FA synthesis intermediate)
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What is produced from each round of B-oxidation
|
"1 NADH, 1 FADH2, 1 Acetyl CoA"
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If there is an error in MCFA dehydrogenase what will happen
|
B-ox cannot happen and will result in low ketones and eventually liver damage from ammonia build up
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What happens if a FA has an odd # of carbons
|
"get propionyl CoA, eventually becomes Succinyl CoA. Uses biotin and B12"
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|
Gaucher's Disease
|
Marcophages cant break down glucocerebroside. get accumulation
|
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What is the first barrier in GNG
|
Pyruvate-OAA-PEP
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What are the components of the 1st regulated step of GNG
|
"Pyruvate+Biotin,CO2, ATP, Pyruvate Carboxylase. PCarb is allosteric by acetyl CoA"
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What is the total energy input for the first step of GNG
|
"1 ATP, 1 GTP for each Pyruvate-->PEP"
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How does B oxidation tie into GNG
|
"lots of acyl CoA around, will allosterically activate rxn Pyruvate -->OAA"
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what enzyme catalyzes the reverse reaction of hexokinase
|
Glucose 6 Phosphatase
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|
What is the GNG equivalent of PFKI
|
"Fructose 1,6 Bisphosphatase"
|
|
|
How are ketone bodies formed
|
"2 acetyl CoA attach, HMG CoA in mitochondria adds another acetyl CoA. lose an acetyl CoA, get acetoacetate as an end product."
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how do you get B hydroxybuterate
|
oxidize acetoacetate with NADH.
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how do ketone bodies make energy
|
"from BHB, creates NADH, succinyl CoA and 2 Acetyl CoA for TCA. Acetoacetate creates succinyl CoA and 2 Acetyl CoA"
|
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Apo A1
|
"On HDL Receptor ligand for liver, activates PCAT"
|
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B100
|
"on LDL, VLDL."
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B48
|
On chylomicrons
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|
CII
|
Activates LPL
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|
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CIII
|
inhibits LPL and Apo E
|
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Apo E
|
Ligand for liver receptor
|
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How does the protein transfer between Chylo and HDL occur
|
"HDL give Apo E and Apo CII to chylo. after chylo gives up TG, it gives Apo CII back to HDL. Keeps Apo E so it can dock at the liver"
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Describe the path of cholesterol from VLDL
|
VLDL has Apo B100. Gets E and CII from HDL. GIves off TG as CII binds LPL. Becomes LDL. LDL gives back CII and E to HDL. B100 signals to tissues to uptake the LDL.
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What is an ACAT reaction
|
makes cholesterol Esters
|
|
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What is HDLs path
|
starts as A1 with some fat and interacts with ABCA. Takes on cholesterol. Pancake stage. PCAT begins making cholesterol esters. rounds up. brings these back to the liver.
|
|
|
how does HDL interact with VLDL besides protein exchange
|
VLDL gives HDL phospholipids in exchange for TG. PCAT is taking phospholipids and making esters. so HDL needs more PL.
|
|
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What is evidence of Metabolic Syndrome
|
"Pear shaped, High TG, Low HDL, HTN, Hyperglycemia, Albuminuria"
|
|
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What are the risk factors for CHD
|
"Age, Fam Hx, Smoking, HTN, Low HDL, Diabetes, Obesity"
|
|
|
3 things you need for FA synthesis are
|
"Acetyl CoA, Energy, Reducing power (NADPH)"
|
|
|
What is the first step of FA synthesis
|
Convert Acetyl CoA to Malonyl CoA
|
|
|
How can the body prevent wasting of materials and energy during FA Syn
|
while transferring reducing eq to NADPH pyruvate is created. OAA->Malate->pyruvate
|
|
|
Where is the most regulation in FA Syn
|
"Acetyl CoA->Malonyl CoA
|
|
|
what vitamin is essential for Acyl Carrier Protein
|
B5
|
|
|
What happens in the priming step of FA syn
|
Acetyl group attaches to the SH and then is transferred to the cysteine nub
|
|
|
What occurs in the first reaction of FA syn
|
"Malonyl attaches to the SH and in a condensation reaction bonds to the acyl group on the cys nub, CO2 is released."
|
|
|
to go through one cycle of FA Syn what is consumed and produced
|
2 NADPH are used. 1 CO2 and 1 H2O are produced
|
|
|
What is a restriction of FA synthase
|
Can only make FA 18 carbons or shorter
|
|
|
Where is FA elongase located
|
On the ER
|
|
|
How do you make double bonds on new FA
|
FA CoA desaturase. uses O2. makes double bond and oxidizes NADH.
|
|
|
what is FA CoA desaturase limitation
|
can only make double bonds up to carbon 9
|
|
|
What regulates Acetyl CoA Carboxy
|
Citrate activates and palmitoyl CoA inhibits. Phosphorylation by glucagon will inhibit.
|
|
|
How do we prevent a futile cycle of FA Syn and B-oxi
|
"synthesis happens in cytosol, b-ox in the mitochondria. malonyl CoA also prevents b-oxi substrates from entering mitochondria"
|
|
|
what enzyme is lacking in adipose to prevent futile cycling of TG syn and breakdown
|
no glycerol kinase to break them down.
|
|
|
what illnesses are related to diet
|
"scurvy, goiter, rickets, diabetes, CHD, osteoarthritis, osteoporosis"
|
|
|
Some Fat soluable Vitamins
|
A D E K
|
|
|
What are the most important D vitamins
|
Ergocalciferol (D2) and cholecalciferol (D3)
|
|
|
Vitamin D deficiency=
|
Osteomalacia
|
|
|
What is Vit D's job
|
regulates Ca via absorbtion
|
|
|
What is released by parathyroid glands and what does it to to regulate Ca
|
"PTH, stimulates osteoclasts"
|
|
|
Vitamin K function
|
"Coagulation Proteins, bone mineralization"
|
|
|
Sources of Vit K
|
"Green leafy veg, intestinal bacteria"
|
|
|
Vit K deficiency
|
"very rare, clotting delays. megadosing of A and E can counteract K"
|
|
|
What does thiamine do
|
"B1 is par of TPP, removes carboxyl groups in glucose metab. Used in B-oxi and nervous system"
|
|
|
Thiamine Deficiency
|
"BeriBeri-muscle weakness, heart failure. Wet beriberi has edema. ETOH associated"
|
|
|
Riboflavin
|
"B2. part of FADH, in TCA and B-oxi. aids in deamination"
|
|
|
Riboflavin Deficiency
|
Angular Stomatitis-cracks in the mouth
|
|
|
Sources of Riboflavin
|
"Liver and yogurt, some milk"
|
|
|
Niacin
|
can lower LDL via HMG reductase inhibition. Part of NADH.
|
|
|
Sources of Niacin
|
"Tryptophan, meat, grains (minus corn)"
|
|
|
Deficiencies of Niacin
|
"Pellegra. the 4Ds dementia, diarrhea, dermatitis, Death"
|
|
|
Pantothenic Acid
|
B5. part of CoA
|
|
|
Sources of Pantothenic acid
|
"liver, in lots of food"
|
|
|
Pantothenic Acid Deficiency
|
"None, unless induced"
|
|
|
Biotin
|
Can be made in the bowel by bacteria. used in carboxylation rxns.
|
|
|
Biotin Deficiencies
|
"Leiners disease-seborrheic dermatitis, baldness, waxy skin."
|
|
|
B6
|
"Three forms. Pyridoxal, pyridoxine, pyridoxamine."
|
|
|
B6 function
|
transamination. blood cell synthesis. influences homocysteine levels
|
|
|
Deficiency of B6
|
"Microcytic hypochromic anemia, atherosclerosis"
|
|
|
Folate
|
"Converted to THFA, used in one carbon metabolism in DNA syn"
|
|
|
Folate deficiency
|
"megaloblastic anemia, spina bifida"
|
|
|
B12
|
works with folate. mylelin sheath. works with TCA
|
|
|
What is the difference between major minerals and trace elements
|
"Major minerals are needed in concentrations >100mg, trace elements <100 mg"
|
|
|
What is the most key aspect to mineral absorption
|
Stomach acidity keeps the minerals ionized and soluable
|
|
|
What causes Na deficiency
|
"disease state (vomiting, diarrhea, sweating)"
|
|
|
What is are some comorbitities with hyponatremia
|
"dehydration, edema, neurological issues"
|
|
|
Functions of Na
|
"fluid balance, nerve transmission, muscle contraction, blood pH, nutrient absorption"
|
|
|
What occurs in hypernatremia
|
hypervolemia-->HTN
|
|
|
What can loop diuretics decrease
|
"K, Mg levels"
|
|
|
Hypokalemia
|
"Abnormal cardiac rhythm, muscle cramps"
|
|
|
Hyperkalemia
|
"Rare, except in cases of renal disease. Heart arrhythmias"
|
|
|
Hypocholoremia
|
can result in metabolic alkalosis.
|
|
|
Hypophosphotemia
|
elevated PTH. Vit D deficiency. results in osteomalacia
|
|
|
Hyperphosphotemia
|
"kidney disease, low PTH level. too much Vit D. "
|
|
|
What should be a concern when P is high and Ca is low
|
Excessive bone loss
|
|
|
Hypomagnesaemia
|
"bleeding problems, stiffness, cramps"
|
|
|
Zinc Deficiencies
|
"Hypogonadism, hair loss, skin lesions, growth retardation, heart disease"
|
|
|
Selenium
|
part of glutathione peroxidase
|
|
|
Chromium
|
involved in homeostasis of glucose levels
|
|
|
what are the five factors determining state of nutrition
|
"biological, social, psychological, presence of disease, energy expenditure"
|
|
|
What does the EAR represent
|
dietary intake that will meet 50% of the requirement at their particular stage of life
|
|
|
what is the RDA
|
the dietary intake that will meet 97-98% of dietary requirements
|
|
|
what are the drug classes that sensitize the body to insulin
|
bigaunides and thiazolidinediones
|
|
|
what drug classes increase insulin secretion
|
"Sulfonylureas, meglitinides"
|
|
|
What do alpha-glucocosidase inhibitors do
|
"slow the absorbtion of starches, create alot of gas"
|
|
|
what is byetta
|
"gila monster saliva, curbs appetite, affects leptin"
|
|
|
januvia
|
another diabetes drug
|
|
|
What is the difference between Gprotein coupled receptors and enzyme coupled receptors
|
GPCRs act indirectly and send a signal molecule to the enzyme. ECR have either enzymatic activity on receptor or right next to the receptor
|
|
|
what are the 3 small 2ndary messagers
|
"DAG-lipid sol, Ca and cAMP-water sol"
|
|
|
what are the 8 mechanisms of large 2ndary messengers
|
"scaffold, transform, amplify, relay, spread, anchor, modulate, integrate"
|
|
|
What are the 3 amino groups that usually get Pated
|
"serine/threonine, tyrosine"
|
|
|
What do SH2 domains bind
|
P-ated tyrosine
|
|
|
what do SH3 domains bind
|
non P-ated proline rich areas
|
|
|
What does PTB bind
|
P-ated Tyrosine
|
|
|
What do Pleckstrin Homology domains bind
|
phosphoinositides
|
|
|
Explain the inositol phosphilipid signal path
|
"PLCB activated
|
|
|
What is PKC
|
Ser/Thr kinase
|
|
|
What is Calmodulin
|
"Ca Carrier. binding causes conformation changes, can influence transcription factors"
|
|
|
What are the 4 major classes of adhesion molecules
|
"selectins, intergrins, ICAMs, cadherins"
|
|
|
What is the most important class of cell-cell molecules
|
Cadherins
|
|
|
What mediates the strength of cadherin adhesions
|
number of cadherin molecules (like velcro)
|
|
|
What does the intracellular domain of a cadherin do
|
"initiates signalling, creates scaffolds"
|
|
|
what does the extracellular domain of cadherins do
|
"binds ligands, receptor for adhesion molecules"
|
|
|
What happens to cadherin molecules in the absence of Ca
|
the wobble and lose their adhesion to other molecules
|
|
|
Besides adhesion what is another role of cadherins
|
"regulate space between cells, anchor cytoskeleton elements"
|
|
|
what molecule is important to cadherin attachment to the cytoskeleton
|
B-catenin
|
|
|
If there is a gene mutation in B catenin:
|
easy disaggregation resulting in local invasion and distant metastasis
|
|
|
What cancers are closely related to cadherin disfunction
|
"breast, esophagus, colon, ovary, prostate"
|
|
|
What is the other function of B-catenin
|
gene regulatory protein signalling for cell replication
|
|
|
in colon cancer what happens in B-catenin signalling
|
cell believes that WNT is continuously signalling and B-catenin is not destroyed therefore promoting call replication
|
|
|
What is the primary ligand for selectins
|
carbohydrates
|
|
|
what adhesion molecules are Ca dependent
|
cadherins and selectins
|
|
|
What are the functions of selectins
|
"homing receptors for lymphocytes to enter lymph nodes, facilitates binding of neutrophils to endothelial cells (rolling interactions)"
|
|
|
what 3 endothelial ligands bind L-selectin
|
"glycam, madcam, CD34"
|
|
|
What do E selectins bind (ELAM)
|
"Lewis A or Lewis X family molecules on granulocytes, monocytes, or memory T cells"
|
|
|
Why is E selectin important
|
brings effector lymphocytes to sites of inflammation
|
|
|
Where is P selectin stored in platelets
|
Wiebel-Palade bodies
|
|
|
Why are p selectins stored
|
because platelets cannot synthesize proteins
|
|
|
What disorder in humans is related to selectins
|
Leukocyte adhesion deficiency 2. susceptible to bacteria infections
|
|
|
What do integrins do
|
coordinate and integrate extracellular signals with motility and shape changes of cell
|
|
|
What is the structure of integrins
|
Heterodimers with alpha and beta chains. types are named by the beta chain.
|
|
|
"extracellularly, what to integrins bind"
|
RGD in fibronectin especially
|
|
|
what is the trick to recognizing a cytoskeletal component that binds integrins
|
"ends with IN (talIN, actIN, tropomyosIN, actinIN, vinculIN)"
|
|
|
What is another name for B1 integrins
|
VLA (very late activating) also CD49 (a-g subtypes)
|
|
|
where are VLAs expressed
|
"constitutive on leukocytes, can be induced elsewhere"
|
|
|
What is the primary function of B1 selectins
|
homing of lymphocytes to areas of inflammation
|
|
|
What is the other name for B2 integrins
|
"LFA- lymphocyte function associated antigen
|
|
|
LFA1 has the CD#:
|
CD11aCD18
|
|
|
what does LFA1 bind
|
ICAM on APCs
|
|
|
What is a deficiency in B2 integrins
|
"LAD1 no B2 integrins, succumb to bacterial infection"
|
|
|
What are hallmarks of apoptosis
|
"condensed chromatin, no inflammation, distinct organelles, blebs. cell shrinkage, multiple nuclei, "
|
|
|
Biochemically what happens in apoptosis
|
"Its energy dependent, caspases cleave proteins (lamins, scaffolds, cytoskeleton), dna breakdown, phosphatidyl serines flip for phagocytic recognition."
|
|
|
What induces apoptosis intrinsiclly
|
mitochondrial walls weaken and release cytochrome C.
|
|
|
What are Bcl-2 and Bcl-x
|
anti-apoptotic molecules on the mitochondrial membrane. inhibit apaf-1 and prevent pore formation on mitochondria
|
|
|
what are the pro-apoptotic members of the bcl2 family
|
"Bax, Bim, Bak"
|
|
|
How does cytochrome C induce apoptosis
|
activates caspase 9 by forming a complex with apaf1
|
|
|
How is extrinsic apoptosis intiated?
|
Fas ligand binds to a Fas receptor (TNF superfamily)
|
|
|
How does the Fas pathway work
|
"3 or more Fas molecules become linked by Fas ligand, FADD binds pro-caspase-8, pro-caspase-8's cleave each other and waterfall occurs"
|
|
|
What can inhibit Fas pathway
|
FLIP
|
|
|
How does the TNF-R path work?
|
Same as Fas but uses TRADD forms and binds FADD and so forth.
|
|
|
What are the main initiator caspases
|
8 and 9
|
|
|
What are the main executioner caspases
|
3 and 4
|
|
|
What does caspase 3 directly activate
|
"endonucleases, split DNA into large chunks (300 kbp) then 180 bp"
|
|
|
p53 has what role in apoptosis
|
"arrests cell cycle after G1 if DNA is damaged, if not repaired, p53 signals for apoptosis"
|
|
|
What is morphology as it relates to pathology
|
"What a cell looks like- shrink, swell, disintegrate"
|
|
|
What factors are important in determining reversible vs irreversible damage
|
"how long the damage is occuring, how severe is the damage, how hardy is the cell"
|
|
|
what are ways cells and tissues adapt to an injurious stimuli
|
"atrophy, hypertrophy, hyperplasia, metaplasia"
|
|
|
What is hypertrophy
|
"increased CELL size, stress on cell makes it work harder (muscle tissue)"
|
|
|
What happens in sub cellular hypertrophy
|
"organelles grow in size to meet demands. ER- increased detox, increased protein load. Mitochondria- increased energy demand"
|
|
|
What is hyperplasia
|
"Increased # of cells, usually in response to hormone changes (endometrium)"
|
|
|
why would hyperplasia occur physiologically
|
in response to hormones or damage to a tissue (remove part of the liver)
|
|
|
Atrophy is
|
Decreased cell size
|
|
|
when is atrophy physiologic
|
during development of embryo
|
|
|
pathologic atrophy can be caused by
|
"decreased use, blood supply, nutrition, nerve stimulation, or increased physical pressure on a cell"
|
|
|
metaplasia is
|
a hardier cell type replaces another sensitive cell type (columnar -> squamous)
|
|
|
what are indicators of necrosis
|
"cellular swelling, swelling and disintegration of organelles, "
|
|
|
What are some mechanisms of cell injury
|
"depletion of ATP, mitochondrial damage, influx of Ca, ROS, membrane permeability"
|
|
|
What occurs during ATP depletion
|
"decreased Na pump activity, water remains in cell and it swells. decreases pH thru glycolysis, cant pump Ca out, cant synthesize proteins for functioning."
|
|
|
Why does mitochondrial damage injure cells
|
"release cytochrome C leading to apoptosis, and decreases cell ATP."
|
|
|
How does Ca homeostasis injure a cell
|
"Ca accumulates in ER and mitochondria, damage membranes, cell explodes"
|
|
|
Necrosis displays what core signs
|
"membrane integrity is lost, inflammation, proteins are broken down and destroyed, necrotic cells are removed."
|
|
|
What is the morphology of necrosis
|
"eosiniphilic, myelin figures, nuclear changes"
|
|
|
what is karyolysis
|
nucleus broken down into fine fragments
|
|
|
what is pyknosis
|
nucleus shriveling up
|
|
|
what is karyorrhexis
|
nucleus breaks into large fragments
|
|
|
what occurs in a ischemia-reperfussion injury
|
increases ROS
|
|
|
Hallmarks of coagulative necrosis
|
"Can see cell outline but nothing else, ghostlike. occurs esp in MI and kidneys. cant see organelles, nucleus, or striations (in case of heart)"
|
|
|
hallmarks of caseous necrosis
|
"cheesy appearence, occurs in TB in the lungs and lymph nodes."
|
|
|
Fat necrosis
|
"fat destruction, pancreatic enzymes degrade fat, trauma to fatty areas"
|
|
|
liquefactive necrosis
|
"seen in bacterial and fungal infections. can occur in brain and kidney. complete digestion of the cells, results in scar tissue and cavity formation"
|
|
|
dystrophic vs metastatic calcification
|
dystrophic occurs at site of injury with normal Ca levels. metastatic occurs on healthy tissue with high Ca levles
|
|
|
Serous injury
|
"straw colored clear fluid, low in protein, EX blisters"
|
|
|
Fibrinous injury
|
"high protein content, accumulation of fibrin at injury site"
|
|
|
supperative injury
|
"abscess and pus, dead white blood cell accumulation, abscess is a walled off infection"
|
|
|
ulceration
|
eroded epithelium. gastric or epidermis
|
|
|
What is the definition of a free radical
|
Any chemical species that can independently exist with one or more unpaired electron in its outer shell
|
|
|
Why is O2 an ROS
|
it has 2 unpaired electrons
|
|
|
what is the most potent ROS
|
Hydroxyl radical
|
|
|
What are sources of ROS
|
"ETC, peroxisomes, radiation, toxins, pollution, drugs"
|
|
|
What are the beneficial effects of free radical
|
"Regulate metabolism, biomolecule turnover, microbe protection"
|
|
|
How is superoxide radical made
|
spontaneous reaction
|
|
|
How does the body get rid of superoxide
|
"superoxide dismutase converts it to H2O2, a less reactive ROS"
|
|
|
How does the body get rid of H2O2
|
1 of 2 rxns. Catalase or Glutathione peroxidase (selenium cofactor)
|
|
|
If H2O2 is not reduced what can happen pathologically
|
"Fenton Rxn- with iron to make hydroxyl radicals
|
|
|
When is hypochlorous acid good
|
Respiratory burst from phagocytes results in its production
|
|
|
What is the consequence of increased oxidative stress
|
peroxidation of cell membranes followed by increased Ca influx and cell death
|
|
|
How can oxidative stress be measured
|
"MDA, 4-HAD
|
|
|
Why are both E and C needed as antioxidants
|
"E is good for scavanging lipids, C is in the cytosol and can regenerate E."
|
|
|
How is NADPH related to oxidative stress
|
helps reduce glutathione so glutathione peroxidase can function
|
|
|
how is metHb dealt with
|
NADPH can directly or indirectly reduce it to Hb.
|
|
|
What in general do cytokines do
|
"activate cells, induce proliferation, increase cytotoxicity"
|
|
|
what are the 3 functions of complement
|
"recruit inflammatory cells, opsonization, perforation"
|
|
|
what are some mechanical elements of innate immuntity
|
"skin, peristalisis, flushing, coughing, mucus, cilia, fever"
|
|
|
what is a cellular element of innate immunity
|
"phagocytes (monocytes, neutrophils)"
|
|
|
What signals phagocytes in innate immunity
|
Pattern Recognition receptors (with aid of TLRs and Ab/complement)
|
|
|
What occurs during innate immunity after a PPR is activated by a PAMP
|
"Increased cytokines, chemokines (IL8), lysozyme, upregulation of other receptors (MHC)"
|
|
|
What does TLR4 recognize
|
LPS
|
|
|
What does TLR 6 bind
|
CpG DNA in prokaryotes
|
|
|
What does TLR5 bind
|
Flagellin
|
|
|
TLR3 binds
|
dsRNA
|
|
|
ICAM is a ligand for
|
integrins
|
|
|
What is the definition of a pathogen
|
an organism that has the potential to cause disease
|
|
|
what kind of immunity are B cells associated with
|
humoral
|
|
|
T cells are players in which kind of immunity
|
CMI and Humoral
|
|
|
What do T cells require to activate
|
a antigen presented by an APC
|
|
|
Why are dendritic cells special
|
they pick up antigens in periphery and run them to the closest node for clonal selection
|
|
|
what are the 2 roles of antibodies
|
"neutralize (as in toxins or attachment of pathogens), and target things for destruction"
|
|
|
What receptor is important for phagocytosis
|
Mannose
|
|
|
what ramps up phagocytes
|
IFN-gamma
|
|
|
whats a downside to innate immunity through cytokines and phagocytosis
|
"sloppy, lots of collateral damage"
|
|
|
what happens in secondary lymphoid tissue
|
"mature lymphocytes live there, wait for antigens and return from patrolling. antigen is also concentrated."
|
|
|
what does CMI require that humoral immunity does not
|
an APC
|
|
|
What is humoral immunity reactive to
|
free floating antigens/pathogens
|
|
|
What immunity targets pathogens within cells and viruses
|
CMI
|
|
|
What does CMI always require
|
APC and T-helper cells
|
|
|
What do marginal zone B cells react to
|
blood borne polysaccharide antigens
|
|
|
what do follicular B cells react to
|
respond to protein antigens
|
|
|
B1 B cells are special why
|
"line GI track, do not react to ingested protein but still can attack pathogens"
|
|
|
what is similar between Surface Ig and TCR
|
"both have antigen binding domains, both have variable and hypervariable regions. "
|
|
|
Differences between SIg and TCR
|
"ones on T ones on B cells, TCR have 2 chains, SIg have 4. 2 binding sites on SIg, TCR binds to MHC"
|
|
|
What is active immunity
|
"made own antibodies, via natural (infection) or artificial (vaccination) means"
|
|
|
What is passive immunity
|
"immunity came from elsewhere.
|
|
|
what are the cardinal features of adaptive immunity
|
"Specific, Diverse, Adaptable, Memory, clonal expansion, specialized, limited, discriminant"
|
|
|
Clonal Selection Theory States
|
A cell with a specific antibody exists before pathogen insult. once the antigen binds its antibody that cell then replicates and clones are produced
|
|
|
What factors make an antigen more immunogenic
|
"Larger size, protein or complexed with a protein, complex molecule"
|
|
|
What is an immunogen vs an antibody
|
immungens are antibodies that illicit an immune response
|
|
|
What type of receptor can bind conformational epitopes
|
B cells
|
|
|
What 3 things are required for B cells to begin secreting Ig
|
"stimulated by an antigen
|
|
|
what are the 2 kinds of light chain domains
|
kappa and lambda
|
|
|
what 2 Ig types have 4 constant domains
|
M and E
|
|
|
what holds A and M polymers together
|
J chains
|
|
|
IgA does:
|
"opsonization, neutralization, transporting across epithelium, can activate complement thru alt path. Found in secretions"
|
|
|
IgG does
|
"opsonization, neutralization, Sensitization for NK cells, complement, mast cell sense, crosses placenta, found in serum high concentrations"
|
|
|
IgM does
|
complement like whoa and agglutination
|
|
|
What gene components are in heavy chains
|
"V D J C, C is the tail named for Ig type"
|
|
|
What genes are in light chains
|
just V and J with a C. Kappa has more diversity than lambda
|
|
|
how does ELISA work
|
"antigens in wells, blood added, AbAb added with reactive enzyme, more IgG for antigen, the darker the well. titer is inverse of weakest dilution with a reaction"
|
|
|
Western blot works by
|
figuring out what components of a pathogen a pts antibodies are reacting too
|
|
|
What are the 3 functions of complement
|
"Opsonization, Lysis of invading organsism, Chemoattraction of inflammatory cells"
|
|
|
How is the Lectin pathway initiated
|
Mannose binding protein binds to mannose on cell surface and then acts like C1
|
|
|
What is the most step in all complement pathways
|
cleavage of C3 and the binding of C3b to the cell surface
|
|
|
Why is C3 so important
|
"opsonin, amplification. C3a is a chemoattractant"
|
|
|
What is classical C3 Convertase
|
C4b2a bound to the membrane surface
|
|
|
What is Classical C5 convertase
|
C3b2a4b
|
|
|
What is the attack complex
|
"C5b bound with C6 and C7, 8 binds once complex bind membrane and C9 creates the pores"
|
|
|
What non Ig molecule can iniate the classical path
|
C-reactive protein
|
|
|
How is C1 regulated
|
C1INH keeps C1 from over acting
|
|
|
What parts of compliment are anaphalaxins
|
C3a and C5a
|
|
|
what important role does C5 play
|
"smooth muscle contraction, degranulation of mast cells, histamine release, increased vascular permeability"
|
|
|
What happens if you lack end game complement components
|
Severe susceptibility to Neisseria
|
|
|
How does Alternative path get started
|
"C3 is hydrolized spontaneously by water binding a thioester bond. becomes iC3 which binds B, D cleaves B, you get iC3Bb, Cleaves C3 and C3b binds membrane"
|
|
|
What is soluable C3 Convertase
|
iC3Bb
|
|
|
what is alternative C3 convertase
|
C3b3bBb
|
|
|
How is C3 regulated in the alternative path
|
Properdin speeds up C3 Convertase binding
|
|
|
What is an antagonist for properdin
|
Factor H inactivates C3b by Factor I
|
|
|
"If someone is deficient in factor I, what happens"
|
iC3Bb cleaves and cleaves and cleaves until all the C3 is depleted. lots of ear infections
|
|
|
To what does CR1 bind
|
C3b or C4b
|
|
|
"Where can you find CR1, what does it do"
|
"Macrophages, neutrophils, RBC, binds tagged membrane for destruction and filtration (RBC-Spleen). enhanced function if FcR binds to Ig or when IFNg is around."
|
|
|
What receptor is important in the context of EBV
|
CR2 on Bcells and Dendritic cells
|
|
|
What is the function of CR2
|
"binds degradation products of C3, activates B cells"
|
|
|
CR3 and CR4 are what class of adhesion molecules
|
Beta-integrins
|
|
|
"What do CR3 and 4 bind, what do they do"
|
Bind iC3b (inactive C3b) lead to phagocytosis
|
|
|
What are characteristics of Bacterial colony morphology
|
"Color, size, shape, smell, hemolysis"
|
|
|
What are differences in membranes between eukayotic and prokayotic cells
|
"Bacteria dont have cholesterol, have peptidoglycan wallas"
|
|
|
Describe the structure of bacterial cell wall
|
cross linked sugars by amino acids NAM and NAG
|
|
|
what does lysozyme do to cell walls
|
cleaves B 1-4 glycosidic bonds in NAM and NAG
|
|
|
Teichoic and lipoteichoic acid are found where
|
in the gram+ cell wall.
|
|
|
what causes a systemic immune response like endotoxins in Gram+
|
Lipoteichoic Acid
|
|
|
What is important in the outer cell membrane of Gram- bacteria
|
LPS- endotoxin
|
|
|
"What is the ""bad part"" or LPS"
|
Lipid A
|
|
|
What is used to classify gram- bacteria
|
O antigen on the LPS
|
|
|
What is the function of bacterial Capsule
|
"Protects from innate IS, antigenic factors, protects against phagocytosis, adheres to surfaces"
|
|
|
Biofilm is
|
a slime layer that is less discrete than a capusle but has similar job
|
|
|
What is the name for the doubling time in bacteria
|
Generation Time
|
|
|
What factors affect bacterial growth
|
"Carbon, Nitrogen, Iron, pH, temp, osmolarity, Oxygen"
|
|
|
What are sterile sites in the body
|
"Blood, UT, Sinuses, uterus, prostate, CSF, lungs"
|
|
|
What conditions determine if an infection will occur
|
"Pathogenicity, Immune status, Route of entry, Dose of infectious agent"
|
|
|
What are factors determining virulence
|
"Structure- capsule, lps, pili.
|
|
|
How do eukaryotes get iron
|
"siderophores steal it from transferrin and lactoferrin, others have receptors for host transferrin"
|
|
|
How does disease occur from infection
|
"By products of growth- gas, acid
|
|
|
Exotoxins
|
"Proteins secreted by gram + and -.
|
|
|
How do endotoxins lead to septic shock
|
toxin is released systemically and the immune reaction is overloaded with Immune response
|
|
|
How can bacteria evade immune response
|
"degrade chemotaxins, opsonins, live inside cells, capsule can mask bound complement, phase variation"
|
|
|
What is the mechanism of endotoxins
|
"LPS binds to LPSBP, binds to CD14 or TLR, Macrophage releases cytokines"
|
|
|
what mediators are the big players in septic shock
|
"TNF-a and IL 1. cause hypotension, vascular permeability"
|
|
|
What are 4 types of entry of exotoxins
|
"AB structure, Type III, Poreforming, Superantigens"
|
|
|
How do AB toxins work
|
"A is active subunit, B is binding and mediates A's entry"
|
|
|
What is an example of AB toxin
|
"Diptheria from C. Diptheria. catalyzes ADP ribosylation of histidine on EF2, prevents protein synthesis.
|
|
|
What are examples of single subunit internalized exotixins
|
"Adenylate cyclase toxin-purtussis
|
|
|
Membrane Active Toxins
|
"Hemolysins
|
|
|
Membrane lytic enzymes
|
Clostridium perfringens- results in necrosis
|
|
|
Membrane active enzymes
|
"Staph aureus- exfoliative exotoxin- scalded skin syndrome
|
|
|
Superantigens
|
"Staph- TSST1
|
|
|
conjugative plasmid is
|
can encode for ways to transfer the plasmid to another organism
|
|
|
what is the lysogenic cycle
|
"after a bacteria is infected by a phage, the viral genome can become dormant in the chromosome and bacteria is a lyogen, with a prophage. can undergo lysogenic conversion."
|
|
|
Penicillin is a
|
"beta lactam, inhibits cell wall synthesis"
|
|
|
How do Beta lactams work
|
Bind penicillin binding proteins and prevent cross linking
|
|
|
How do bacteria resist the effects of a beta lactam
|
"lactamases cleave the lactam rings, porins mutate in gram-, cant get to wall, can change the PBP"
|
|
|
What is the difference in vanco
|
inhibits cell wall synthesis by binding D-ala
|
|
|
How is vanco resisted
|
d-ala d-ala is switched to d-ala d-lac
|
|
|
How does bacitracin work
|
prevents cell wall components from moving thru the cell membrane
|
|
|
what antibiotics interfere with protein synthesis
|
"aminoglycosides, tetracycline, macrolides"
|
|
|
Aminoglycosides
|
premature release of mRNA
|
|
|
Tetracycline
|
inhibits tRNA from binding ribosomes
|
|
|
Macrolides
|
Prevents peptide elongation
|
|
|
Antibiotics that are nucleic acid synthesis disrupters
|
"Quinolones, rifampin"
|
|
|
Quinolones
|
Block DNA gyrase
|
|
|
Rifampin
|
Inhibit DNA dependent RNA polymerase
|
|
|
Drugs that inhibit metabolism
|
"sulfonamides, trimethoprim. mess with folate metabolism"
|
|
|
What is the ultimate goal of intracellular signalling in IR
|
"activation of NFAT (tcells)
|
|
|
What does increased synthesis of those TFs
|
"Increased, CD40L, IL2, and IL2R expression"
|
|
|
What 2 things does ZAP do
|
activates PLC and RAS
|
|
|
What does PLC do
|
cleaves PIP2 into IP3 and DAG
|
|
|
How do immunosuppressives work on the immune system
|
Block calcineurin from activating NFAT
|
|
|
What do the ITAMs phosphorylate
|
P59Fyn which then P-ates ZAP
|
|
|
How long is the acute phase in inflammation
|
72 hrs
|
|
|
Why are some proteins negatively regulated in inflammation
|
"material rationing, hiding iron from bacteria"
|
|
|
What is CRP
|
"Induced APP, works with complement and increases cell survival during insult"
|
|
|
What does CRP bind to in invading organisms
|
Ca dependent binding to PCh on cell membranes of bacteria and fungus
|
|
|
What are the big 3 markers of acute inflamation molecularly
|
"ESR, CRP, SAA"
|
|
|
What are the components of inflammations
|
"redness, swelling, pain, and heat"
|
|
|
How does SAA work in the context of inflammation
|
Binds to apolipoproteins and can decrease foam cells in the system by eliminating cholesterol esters
|
|
|
what is alpha 2 macroglobulin
|
"panprotease inhibitor, lots of things can bind, cleaves them and they are phagocytized. also important in coagulation"
|
|
|
what is the function of haptoglobin
|
scavanges loose Hb from the blood
|
|
|
What parts of the immune system present in acute inflammation
|
"PMN, macrophages"
|
|
|
What cells are absent in acute inflammation
|
lymphocytes
|
|
|
What mediator is going to lead to a lot of vasoconstriction in inflammation
|
histamine
|
|
|
What are characteristics of transudate
|
"albumin, low SG, usually clear, mostly fluid"
|
|
|
What is exudate
|
"high protein content, high SG"
|
|
|
How do macrophages make NO
|
iNOS makes arginine to NO
|
|
|
What eicosanoids mediate vasoconstriction
|
TXA2 and LT
|
|
|
What eicosanoids mediate dilation
|
Prostoglandins
|
|
|
What are effects of IL1 and TNF in inflammation
|
"Decrease appetite, APP, hypotension, also increase leukocyte adherence, pro-coag, increase IL1, 8, 6"
|
|
|
Why is vessel constriction important in an injury site
|
"slows flow, more contact with inflammatory cells"
|
|
|
what is the order of reactions in conventiional intrinsic coagulation
|
"12, 11, 9, 8, 10, 5, 2, 1, 13"
|
|
|
what initiates extrinsic path
|
cell damage activates VII which cleaves X
|
|
|
how is ca tied to coagulation
|
creates a bridge between the negative cell surfaces and the negative surfaces of the platelets
|
|
|
How is vitamin K used in coagulation
|
"wakes up factors 2, 7, 9, 10, C and S."
|
|
|
how does warfarin (coumarin) affect vit k in coagulation
|
K cannot be recycled by reduction in the presence of warfarin
|
|
|
How is fibrinogen activated
|
thrombin removes the alpha and beta subunits and the fibrin monomers bind noncovalently
|
|
|
how does fibrin cross linking occur
|
Factor XIII forms covalent bonds between lysine and glutamine groups on fibrin
|
|
|
What effect does APC have
|
inactivates V and VIII
|
|
|
how is APC activated
|
endothelial cells give of thrombomodulin which activates APC
|
|
|
What happens in Factor V mutations
|
"Factor V leidin, APC cannot inactivate factor V"
|
|
|
How does alpha 2 macroglobulin act in coagulation
|
traps factors and cuts them
|
|
|
what are serpines in coagulation
|
suicide inhibitors of clotting factors
|
|
|
how does heparin work
|
changes the conformation of ATIII and enhances inhibitory effects
|
|
|
What does ATIII affect
|
"2, 9, 10, 11, 12 (intrinsic path)"
|
|
|
What does PTT test
|
intrinsic and common path of coagulation. testing for heparin effects
|
|
|
what does PT test
|
"extrinsic path, Factor VII and the effects of coumadin."
|
|
|
What bacteria are catalase positive
|
staph
|
|
|
How can you tell the difference between strep and staph
|
strep are catalase negative and staph is catalase positive
|
|
|
pt has a catalase + and coagulase + bacteria what is it
|
staph aureus
|
|
|
what strains of staph are coagulase -
|
staph epidermis and staph saprophyticus
|
|
|
Identifying characteristics of staph aureus
|
"gold colonies, beta hemolytic, coagulase +, protein A (binds Fc) capsule, grows in high salt"
|
|
|
What is a key pathogenic feature of staph aureus
|
can cause osteomyelitis
|
|
|
staph aureus toxins present how
|
"exfoliatin toxin- scalded skin syndrome
|
|
|
why arent PCNs effective against staph
|
have beta lactams in 90% of strains
|
|
|
what is typically used to fight staph
|
"pcn derivatives, vanco against mrsa"
|
|
|
What immune factors combat staph infections
|
opsonizing IgG
|
|
|
what does staph epidermidis look like
|
"white non hemolytic colonies, coagulase negative. high mw slime"
|
|
|
what is the key factor for identifying epidermidis vs saprophyticus
|
sapro is resistant to novobiocin
|
|
|
what are the medically important strains of strep
|
"A, B and enterococcus"
|
|
|
what does alpha hemolysis mean
|
incomplete hemolysis
|
|
|
what is beta hemolysis
|
complete hemolysis
|
|
|
Key factors in GAS
|
"(strep pyogenes), very sensitive to bacitracin, M protein and lipoteichoic acid in pilli. epitopes are similar to cardiac muscle"
|
|
|
what does streptolysin S do
|
"lysis leukocytes, platelets, and RBC"
|
|
|
Strepolysin O does
|
all what S does plus its immunogenic
|
|
|
How do you diagnose a GAS
|
"Gram +, catalase -, sensitive to bacitracin"
|
|
|
How can u treat GAS
|
PCN works
|
|
|
Strep agalactiae is different how
|
resistant to bacitracin
|
|
|
why is strep agalactiae important
|
#1 cause of neonatal sepsis and meningitis
|
|
|
Dx of enterococcus
|
"Gram+ in pairs, non hemolytic, grow in high salt, high temp, and survive bile"
|
|
|
how do you treat entero
|
"usually need more than one, usually resistant to vanco"
|
|
|
Strep pneumo
|
alpha hemolytic
|
|
|
Enterobact
|
"are everywhere, cause sepsis, UTI, GI, pulm. all ferment glucose, oxidase negative"
|
|
|
E. Coli
|
UTI king. ones that cause GI probs have a extra plasmid.
|
|
|
Shigella
|
bloody diarrhea
|
|
|
salmonella
|
gastroenteritis
|
|
|
klebsiella
|
necrotizing pneumo
|
|
|
Mac plates
|
"inhibit gram+, lacotose fermenters will be pink, non lactose will be colorless"
|
|
|
EMB plates
|
"inhibit gram +, ecoli are green, others are pink"
|
|
|
How does Ecoli bind to the gut
|
pilli
|
|
|
what organism has a lot of capsule
|
klebsiella
|
|
|
what stimulates early proliferation of CLPs
|
IL7
|
|
|
what happens if you lack IL7
|
SCID- Bubble boy
|
|
|
How does heavy chain recombination occur in B cells
|
"occurs between proB and preB stages. VLD chains rearrange, DJ first VDJ second. "
|
|
|
When does light chain rearrangment happen and how
|
"in preB stage after successful heavy chain mix. and mu+heavy chain is expressed w a surrogate light chain. small preB starts, K than L light chain rearrangement"
|
|
|
How does negative selection of B cells occur
|
"in bone marrow if it reacts to self antigen can be killed, anergy, or will edit its receptor"
|
|
|
once B cells migrate out what happens
|
can start expressing IgD along with IgM
|
|
|
How do T cells mature
|
"Begin as double negative (no CD4 or 8) beta chain made first in TCR, with rearrangment, after alpha is rearranged and added. Become double positive, by random occurance meet MHC 1 or 2 and then express 4 or 8 depending on what they hit"
|
|
|
if thymocytes fail to recognize MHC what happens
|
signaled for death (fail to positive select)
|
|
|
CD1
|
thymocytes and langerhans cells
|
|
|
CD3
|
associated with TCR
|
|
|
CD4
|
"Thelper cells, hook MH2"
|
|
|
CD5
|
costimulation on T cells
|
|
|
CD8
|
CTL recognize MHC1
|
|
|
CD10
|
preB cells
|
|
|
CD19
|
all B cept Plasma
|
|
|
CD20
|
all B cept plasma
|
|
|
CD21
|
EBV receptor on B and dendritic
|
|
|
CD23
|
B cells
|
|
|
CD79
|
all B cells
|
|
|
What is the intial contact of rolling T cells
|
L-selecting binds CD34 on HEV (or glycam)
|
|
|
What is the second contact in rolling T cells
|
LFA1 onto ICAM
|
|
|
what is the costimulatory signal
|
CD28:B7.1 (CD28 on TCell)
|
|
|
what happens if Tcell doesnt get costim signal
|
anergy
|
|
|
what is CD40L
|
"binds CD40 on macrophages and B cells, causes them to PAD and get ramped up. also stims class switching to IgG"
|
|
|
What does IL2 do
|
"made by t cells, autocrine signal. will PAD"
|
|
|
How do Th1 cells form
|
IFN-gamma/IL12 signals
|
|
|
What do TH1 cells do
|
make IFN gamma. important for chronic inflammation. make TNF
|
|
|
What do TH2 cells do
|
"IL4 induces, make IL4,5, and 13. important for allergy and parasites. produce more IL10 than TH1"
|
|
|
what happens when a CD4 cell meets a Bcell with antigen on an MHC
|
CD40 and CD40L interaction. CD4 cell secretes cytokines that make B cell PAD and secrete/class switch
|
|
|
what makes an antigen T cell independent
|
"all sugar, no protein, can stimulate Bcells on their own, no memory tho"
|
|
|
what effects do TH! cells have on macrophages
|
"Increase NO, ROS, Proteases, MHCII, B7, CD40, TNFR.
|
|
|
What do macrophages release upon signalling from a TH1 cell
|
more IL 12 which makes more TH1 cells.
|
|
|
what is needed to activate NK cells
|
IL2
|
|
|
What secrete interleukins?
|
"Leukocytes, also they stimulate leukocytes"
|
|
|
What cytokines regulate innate immunity
|
"Type I IFN, TNF-a, IL 1, IL 6, IL, 12, IL 10"
|
|
|
What are the 2 groups of Type I IFN
|
A and B
|
|
|
What secrete INFa
|
Mononuclear Phagocytes
|
|
|
What secrete IFNb
|
Lots of cells
|
|
|
What are Type I IFNs important for
|
Viral infections
|
|
|
What transduction path to Type I IFNs follow
|
JAK STAT
|
|
|
what is an ISRE and what stimulates it
|
"interferon sequence response element, IFN"
|
|
|
What is the response to Type I IFN
|
"upregulation of: oligoadenylate synthase, dsRNA serine/threonine Kinase, RNAses, Increase MHC I, upregulate IL 12r (increases Th1 proliferation, enhance NK cell cytotoxicity"
|
|
|
What is the main goal of an IFN response
|
inhibit proliferation of viruses and enhance their destruction
|
|
|
How can IFN be used therpeutically
|
"Cancer, Virus treatment"
|
|
|
What are the toxic effects of IFN
|
"Flu like, fever, chills, malaise, myalgia, headache, depression"
|
|
|
What are Pro inflammatory cytokines
|
"TNF, IL1, IL6, chemokines"
|
|
|
What is the primary response to gram - bacteria
|
TNFa
|
|
|
What releases TNFa
|
"activated mononuclear phagocytes (can also be released by Th1, NK, and Mast cells)"
|
|
|
What augments production of TNFa
|
IFNg
|
|
|
What does TNFa do
|
"upregulates selectins, VCAM and ICAM, increases chemokine secretion by macros, promotes clot formation, induces fever (thru prostoglandins), cachexia, and increases APP"
|
|
|
Prolonged TNFa secretion results in
|
sepsis
|
|
|
What are the hallmark symptoms of sepsis
|
"hypotension, shock, disseminated intravascular coagulation, crazy blood sugar levels"
|
|
|
What do CC affect
|
"monocytes, lymphocytes, eosinophils"
|
|
|
What do CXC affect
|
neutrophils
|
|
|
What is the function of chemokines
|
"Recruit cells, promote angiogenesis"
|
|
|
what produces IL 12
|
"mononuclear phagocytes, macrophages, dendritic cells,"
|
|
|
what does IL 12 do
|
"activates NK, lymphocytes, stims IFNg production, Th0->Th1, increases cytotoxicity"
|
|
|
what does IL 10 do
|
opposes everything IL 12 stands for. inhibits macros and dendritics
|
|
|
what makes IL 10
|
activated macros
|
|
|
What helps shut down T cell activity
|
IL 10
|
|
|
What is the principle purpose of IL 2
|
Moving T cells from G1 to S and maintaining T-regs
|
|
|
What makes IL 2
|
"CD4 (Th0, Th1) and lesser so CD8"
|
|
|
What stimulates IL 2 release
|
stimulation by an antigen
|
|
|
What antiapoptotic factor does IL 2 affect
|
increases Bcl2 in T cells
|
|
|
What other factors does IL 2 increase
|
IFNg and IL 4
|
|
|
What IL is redundent with IL2
|
IL 15
|
|
|
What occurs in IL 2 toxicity
|
Hypotension and edema
|
|
|
what does IFNg do
|
"Stims B cell class switching (IgG2), inhibs Th2 growth, activates macros, Increases MHC, activates NK cells"
|
|
|
G-CSF
|
"used in myelosuppressive chemo, fights granulocytopenia and regens neutrophil populations"
|
|
|
What are the side effects of G-CSF
|
"splenic rupture, allergic reactions"
|
|
|
GM CSF
|
"used after bone marrow transplant, helps repopulate neutrophils and monocytes"
|
|
|
What are the side effects of GM CSF
|
"bone pain, fever, edema"
|
|
|
Peptostreptococcus
|
"Gram + cocci, normal flora in mouth and colon. can be pathogenic in lots of places."
|
|
|
Clostridium
|
"Gram + bacilli, forms spores"
|
|
|
Bifidobacterium
|
Gram + non spore forming.
|
|
|
What can cause brain absesses
|
"peptostreptococcus, fusobacterium, prevotella"
|
|
|
Actinomyces
|
"Gram + bacilli, long filiments, can be mistaken as fungus. aerotolerant. found in mouth and skin. worry about invasion after oral surgery"
|
|
|
Baceroides
|
"Gram - rods, found in colon, worry about endocarditis and abd infections"
|
|
|
B. Fragilis
|
can cause endocarditis
|
|
|
Prevotella melaninogenica
|
"capsule, gram- rod, found in mouth, causes inf above diaphragm"
|
|
|
Prevotella bivia/disiens
|
"gram- rods, GYN infections"
|
|
|
Porphyromonas
|
Gingivitis and dental abscess
|
|
|
Fusobacterium
|
"gram - rods, pointed ends, mouth, colon, vagina. in mixed infections"
|
|
|
Lactobacillis
|
"Gram- rod, falc or obligate anaerobe. non pathogenic"
|
|
|
mobiluncus
|
"Gram+ but shows up Gram-, bacterial vaginosis"
|
|
|
Veillonella
|
"Gram - cocci, in mouth, associated with bite wound infections"
|
|
|
C. Perfringens
|
"Gram+ rod, spores, double hemolysis, cellulitis, myonecrosis, food poisoning"
|
|
|
what toxin do all strains of C. perf produce
|
alpha toxin
|
|
|
what does C. perf Beta toxin do
|
"necrotizing, produced by Type C strain"
|
|
|
What do C. perf Group A do
|
"food poisoning, produce enterotoxin, causing diarrhea"
|
|
|
What does tetanus toxin do
|
"Inhibits GABA, produces spastic paralysis"
|
|
|
Risus Sardonicus
|
Tetanus smile/grimace
|
|
|
Tetani back spasms
|
opisthotonus
|
|
|
C. botulinum produces
|
flaccid paralysis by inhibiting acetylcholine release
|
|
|
What is C diff toxin A
|
"diarrhea, and chemotaxis of neutrophils by increases cytokines"
|
|
|
What is C diff toxin B
|
damages cells by disrupting actin
|
|
|
How does chlamydia stay alive in the cell
|
controls vacuole movement to avoid lysosomal fusion
|
|
|
What is super creepy about listeria
|
once it invades the cell it disrupts actin and then uses the actin to move cell to cell
|
|
|
What is Type 3 secretion?
|
Make a pore in the membrane and then can control gene expression. shigella does this
|
|
|
The body requires ______ to clear intracellular bacteria infections
|
exogenous therapy (antibiotics)
|
|
|
What does chlamydia pneumo bind to avoid destruction
|
"binds complement receptor rather than IgR. Cr's don't produce Oxidative burst, IgR does"
|
|
|
What cell type do Rickettsia orgs usually invade
|
endothelial cells
|
|
|
Rickettsia prowazekii
|
"louse borne typhus, vasculitis, usually appears in disaster areas"
|
|
|
Rickettsia tsutsugamushi
|
"Scrub typhus, mite transmitted"
|
|
|
Coxiella burnetti
|
"CV disease, Q-fever, livestock contamination, resists lyso enzymes. can lead to endocarditis"
|
|
|
Ehrulichia chaffeenis
|
"monocytic ehrlichiosis, lone star tick, leucopenia"
|
|
|
Chlamydia trachomatis
|
"GU tract, prevent lysosomal fusion, move vacuole to golgi or ER"
|
|
|
Chlamydia Pneumo
|
"community acquired pneumo, athlersclerosis, might have alzheimers connection"
|
|
|
Chlamydia psittocosis
|
"causes psittacosis, sever pneumo"
|
|
|
mold
|
filamentous form
|
|
|
yeast
|
single celled form
|
|
|
dematiaceous fungi
|
"black/brown fungus, opportunistic, phaeohyphomycosis"
|
|
|
Hyphae
|
filaments/tubular structures in molds
|
|
|
coenocytic
|
nonseptated
|
|
|
pseudohyphae
|
formed by incomplete budding of yeast cells
|
|
|
mycelium
|
mass of intertwined hyphae
|
|
|
vegetative mycelium
|
absorbs nutrients
|
|
|
aerial mycelium
|
reproductive
|
|
|
Conidia
|
asexual spores
|
|
|
conidiophores
|
support chains of conidia (aspergillus)
|
|
|
sporangiospores
|
sac like structure (in zygomycetes)
|
|
|
Blastoconidia
|
budding yeast cell
|
|
|
Arthroconidia
|
conidia formed by fragmentation of hyphae
|
|
|
Cutaneous mycoses
|
dermatophytes (ringworm)
|
|
|
Superficial Mycoses
|
Tinea versicolor
|
|
|
Systemic mycoses
|
"internal organs, opportunistic"
|
|
|
Endemic mycoses
|
dimorphic
|
|
|
How is candida variable
|
"its yeast when its normal flora, when it becomes an infection it becomes a mold"
|
|
|
What happens in a systemic mycosal infection
|
"inhale/ingest a mold, then becomes a yeast in the system"
|
|
|
Echinocandins
|
"cell wall synthesis. inhibit B 1,3 glucan bonds. good against candida and aspergillus"
|
|
|
Types of ergosterol synthesis inhibitors
|
"allylamines, azoles, polyenes"
|
|
|
Allylamine
|
"inhibit squalene epoxidase, build up squalene and cell dies. step in ergosterol syn. accumulate in nails. terbinafine"
|
|
|
Polyenes
|
"amphotericin B, bind to ergosterol and form pores"
|
|
|
Azoles
|
P450 related (liver tox) ketoconazole (dimorphics) and non-ketoconazoles (cutaneous)
|
|
|
triazoles
|
greater specificity for fungal enzymes. less effects. fluconazole. broad spectrum.
|
|
|
Amphotericin B has what side effects
|
"liver toxicity, generates free radicals, renal impairment"
|
|
|
Nystatin
|
alternative to amphotericin B
|
|
|
Flucytosine
|
needs to enter cells and then disrupts DNA synthesis. used against cryptococcus. usually coupled with another drug
|
|
|
Griseofulvin
|
binds keratin and prevents infection
|
|
|
What are the top 3 killers
|
"HIV, TB, Malaria"
|
|
|
What is the life cycle of Borellia burgdorferi?
|
"2 years, larva, nymph, adult. nymph stage is the infective stage"
|
|
|
What is the lyme disease rash called
|
Erythemia Migrans
|
|
|
Symptoms of Lyme disease
|
"Heart Block, acrodermatitis, lymphocytoma, morphea"
|
|
|
What does Ehrlichia chaffeenis infect
|
monocytes
|
|
|
What does Anaplasma phagocytophilium infect
|
granulocytes
|
|
|
What disease shows a maltese cross on blood smear
|
babesiosis
|
|
|
What is a key factor in classifying a zoonotic infection
|
transmitted among vertebrates only
|
|
|
what is a key radiologic factor in the dx of anthrax
|
mediastinal widening
|
|
|
What are the steps in wound repair
|
"Injury, thrombus formation, acute inflammation, cellular invasion, synthesis of repair components"
|
|
|
What are the 4 steps of the hemolytic stage of healing
|
"Platelet aggregation, cytokine secretion, clot formation, "
|
|
|
Cytokines released by platelets
|
"PDGF, EGF, TGFb, IL1, LTB4"
|
|
|
what is FDB
|
fibrin degradation products. chemotaxin for neutrophils
|
|
|
what peptide do neutrophils bind
|
n formyl methionine on microbes
|
|
|
what form of PDGF is important in athlerosclerosis
|
BB
|
|
|
TGFb
|
"can be stim, inhib, or both depending on siyuation"
|
|
|
TGFa
|
repithelialization
|
|
|
EGF
|
reepithelialization
|
|
|
FGF
|
prolif of fibroblasts
|
|
|
VEGF
|
"angiogenesis, autocrine signalling"
|
|
|
KAF
|
"keratinocyte growth factor, reepitheliazation"
|
|
|
what do laminin and vitronectin do
|
"cell migration, form endothelium, angiogenesis"
|
|
|
"What cells are required to provide strength, regulation and structure during angiogenesis"
|
Pericytes and smooth muscle cells
|
|
|
What causes angiogenesis
|
"Injury, tumor secreting growth factors"
|
|
|
Vasculogenesis
|
"BV assembly during embryonic development, make from ECP/angioblasts"
|
|
|
Angiogenesis
|
BV formation in adults. form from already existed vessels or recruited EPC from bone marrow.
|
|
|
What stimulate EPC
|
"chronic inflammation, fibrosis, tumor growth, ischemic tissue"
|
|
|
Hemangioblasts
|
link hematopoietic and vascular systems during development
|
|
|
Angioblasts
|
"Proliferate and migrate to periphery. differentiate into endothelium, pericytes, lymphatics, SMC"
|
|
|
What steps are required for angiogenesis
|
"Vasodilation by NO, increased vasc permeability by VEGF, Degrade ECM, Migrate EPCs"
|
|
|
Where are VEGF receptors
|
"on epithelium, VEGFR2"
|
|
|
Ang 1 recruits
|
periendothelial cells (Tie2)
|
|
|
Ang1/Tie2
|
Maturation and maintains quiesence once maturation occurs
|
|
|
Ang2Tie2
|
"loosens preexisting endothelium, making them more responsive to other signals"
|
|
|
What is unique about tumor vessels
|
very irregular and leaky and grow continuously
|
|
|
Angiogenic Switch
|
"When tumors switch to angiogenic phenotype, when it is turned on prognoses is poor"
|
|
|
What does a malignant cell need to grow
|
"Growth signals, insensitivity to inhibition, invasion and metastasis, limitless growth potential, evasion of apoptosis"
|
|
|
VGEFR1
|
physiologic angiogenesis receptor
|
|
|
VGEFR2
|
receptor in tumor angiogenesis
|
|
|
VGEFR3
|
important in lymphatics
|
|
|
Carcinomas spread via
|
lymphatics
|
|
|
Sarcomas spread via
|
hematogenous routes
|
|
|
What are the 3 main causes of chronic inflammation
|
"persistant infection, persistant toxins, autoimmune disease"
|
|
|
What are the main cells of chronic inflammation
|
macrophages and lymphocytes
|
|
|
What is the hallmark of chronic infection
|
tissue destruction
|
|
|
how does the maturation of macrophages occur
|
monoblasts are released from marrow into the blood (monocytes) then into the tissues (macrophages)
|
|
|
what are the 3 ways macrophages accumulate in an infection site
|
"recruitment, proliferation, immobilization"
|
|
|
what do glucocorticoids do
|
"stop transcription of IL6 and IL1, and suppress COX and PLP"
|
|
|
"Pentoxifulline, thalidomide"
|
suppress release of TNFa
|
|
|
Infliximab
|
"blocks TNFa, can lead to lymphomas though."
|
|
|
3 possible outcomes of infection
|
"Resolution, Regeneration, Repair"
|
|
|
Resolution
|
"Original architecture stays intact, infection is cleared with no morphology changes"
|
|
|
Regeneration
|
"Cells proliferate to replace lost tissue, no changes in structure compared to original tissue"
|
|
|
What cell types cannot regenertate
|
"Permanent Cells, such as mycocardium and CNS cells. Scarring occurs and lose function in that area"
|
|
|
Repair
|
Body brings in materials to fix an area.
|
|
|
What creates a scar
|
loss of cellularity in an area and is filled in by collagen
|
|
|
What is Fibrosis
|
large amounts of collagen being laid down in an area of damage. TGFb important in the formation of fibrotic areas
|
|
|
Matrix metalloproteinases
|
zinc dependent enzymes that allow degradation events
|
|
|
in the healing of wounds by 2nd intention what occurs
|
"massive amounts of granulation tissue, lots of collagen deposition that can result in contracture"
|
|
|
What local factors influence healing
|
"persistent infection, blood supply, movement, irradiation, drugs (NSAIDS, Steroids)"
|
|
|
What systemic factors influence healing
|
"age, nutrition, metabolic disease, malignancies, systemic drugs."
|
|
|
LOX makes
|
leukotrienes
|
|
|
COX makes
|
thromboxanes and prostaglandins
|
|
|
What chemicals can produce erythema
|
PGE2 and PGI2
|
|
|
What do prostaglandins do
|
"produce fever, increase renal blood flow, GFR, mucus secretion in GI, inhibit stomach acid and thrombosis."
|
|
|
TXA2
|
induces platelet aggregation
|
|
|
at low doses what do NSAIDs inhibit
|
selectively inhibit TXA2 (stop platelet aggregation)
|
|
|
What happens as the NSAID dose increases
|
begins to inhibit PGI2 (therefor promotes clotting)
|
|
|
What are the 4 As of NSAIDs
|
"Analgesic, Anti-inflammatory, Antipyretic, Antiplatelet."
|
|
|
What are general contraindications of all NSAIDs
|
"ASA hypersensitivity, Liver dysfunction, Renal dysfunction, Alcoholism, Pregnancy/Breastfeeding"
|
|
|
Salicylates
|
"have all 4 As, increase resp, change acid/base, irreversible cox, high protein binding"
|
|
|
What are the contraindications of salicylates
|
"gout, bleeding disorders, chicken pox, flu"
|
|
|
what occurs in salicylate tox
|
"tinnitus, vertigo, confusion, delerium, GI bleed, N/V, heptatotoxicity"
|
|
|
What is different about diflunisil
|
"no antipyretic, used for severe, inflammation, much more anti-inflam capacity, can't be used with asthmatic pts"
|
|
|
Para-aminopheno derivatives
|
"tylenol, low anti-inflammatory capacity. lower protein bound, can be used where ASA can't."
|
|
|
Entercoccus spp
|
Amp +/- gent
|
|
|
S. Aureus
|
Nafcillin
|
|
|
MRSA
|
Vanco +/- gent
|
|
|
S pneumo
|
PCN
|
|
|
PCN resistant S pneumo
|
Vanco+ceftriaxone
|
|
|
N. gonorrhoeae
|
PCN
|
|
|
N. meningitidis
|
Cefuroxime
|
|
|
C. diff
|
Metronidazole
|
|
|
Chlamydia
|
Macros
|
|
|
T pallidum (syphillis)
|
PCN
|
|
|
Bacteriodes
|
Metronidazole
|
|
|
E coli
|
3rd gen cephs
|
|
|
Propionic Acid Dervis
|
"Ibuprofen, naproxen"
|
|
|
Ibuprofen
|
"4 A's, reversible platelets, Comp Inhib Cox, No interactions. ADR: headache, ocular issues"
|
|
|
Naproxen
|
"Inhibs PMN migration, has ototoxicity, 4 As, reversible platelets"
|
|
|
Heteroaryl Acetic Acid
|
"Ketorolac, Tolmetin, Diclofenac"
|
|
|
Ketorolac
|
"4 As, reversible, Potent COX inhib, drowsiness"
|
|
|
Tolmetin
|
"4 As, little occult blood loss, RA, OA, No competition, Sever GI side effects and tinnitis"
|
|
|
Diclofenac
|
"3 As, no platelets, RA, OA, Spond, reduces Arach acid, High FP effect, sin rash, some competition"
|
|
|
Enolic Acid
|
"Piroxicam, Phenylbutazone"
|
|
|
Piroxicam
|
"4 As, RA, gout, OA. Inhibs neutros, some competition, GI ADRs"
|
|
|
Phenylbutazone
|
"very toxic, RA, acute gout, lots of competition, Nephritis, hepatitis, anemia"
|
|
|
Indomethacin
|
"3 As, RA, Spond, acute gout, close ductus arteriosis, most potent COX inhib, Significant bleeding, depression, psychosis"
|
|
|
Sulindac
|
"Prodrug for indomethacin, easier on pt"
|
|
|
Celecoxib
|
"selective Cox2 inhib. 3 As no platelet, P450 mets, very little ulceration"
|
|
|
Type 1 Hypersensitivities
|
"Rapid, IgE, no IL12 and no IFNg, no macros"
|
|
|
What Il do Th2 cells produce
|
"4,5,6,10,13"
|
|
|
What does IL4 do
|
Induces class switching to IgE
|
|
|
What Il activates eosinophils
|
IL5
|
|
|
What is the first mediator of a Type 1 response
|
"Histamine, H1 is for allergies"
|
|
|
What occurs during the second wave
|
"chemokines, cytokines, PGD2, LC4/D4, occur leading to neutrophil invastion, brochospasm, constriction and innflammation"
|
|
|
Uticaria
|
Hives
|
|
|
What is the infective state of protazoa
|
Cyst form
|
|
|
What is the pathogenic state of protazoa
|
trophozite
|
|
|
What are the 2 types of playhelminths
|
Cestodes (tape) and trematodes (flukes)
|
|
|
What is a common sign of parasite infection
|
Charcot-Leyden Crystals
|
|
|
What are the major HLA groups looked at in matchin
|
"A, B, DR. Maternal and paternal total of 6 matches"
|
|
|
How do we know graft rejection is immunologic
|
animals sensitized to donor MHC react to a transplant as they would a repeat pathogen
|
|
|
Hyperacute Rejection
|
"AB mediated. Host must be sensitized, very very quick. Type II Hypersensitivity with vasculitis."
|
|
|
Acute Rejection
|
"Necrosis, hemorrhage, endothelitis, CD4 and 8 and macros. Necrotizing vasculitis. Swollen endothelium and parenchyma"
|
|
|
Chronic Rejection
|
"Thickening of vasculature, Smooth muscle prolif, narrowing of intima by fibrosis. no necrosis, has atrophy."
|
|
|
Acute GVH
|
"Necrosis, Jaundice, diarrhea, rash"
|
|
|
Chronic GVH
|
"Fibrosis, Atrophy, Jaundice, Eso Strictures"
|
|
|
What is the immune response in GVH
|
Donor T cells release cytokines which activate host macros and NK cells to do damage to the host.
|
|
|
How does cyclosporine work
|
blocks IL2 transcription by binding cyclophilin and then it blocks calineurin and NFAT cant dephosphorylate
|
|
|
How does Tacrolimus work
|
"Binds FK binding protein, binds calcineurin like cyclo"
|
|
|
Sirolomus
|
"Binds immunophilins and inhibs calcineurin, blocks B cell prolif"
|
|
|
Mycophenolate mofetil
|
"stops synthesis of purines, stops b a t mitosis."
|
|
|
Corticosteroids
|
"Interferes with cell cycle of lymphoid system, inhibs inflammation"
|
|
|
DNA Viruses
|
"Host polymerase, very durable, replicate in nucleus, genome is template for mRNA"
|
|
|
+ strand RNA
|
"genome is mRNA, encodes RNA dependent RNA polymerase. Transcription makes template for mRNA and genome. Makes a poly protien"
|
|
|
Infectious Genomes:
|
DNA and + strand RNA viruses have genomes that can initiate an infection alone
|
|
|
- Strand RNA
|
"RNA dependent RNA poly is a core protein, genome is template for mRNA, transcription makes template for genome"
|
|
|
Retroviruses
|
"+ strand RNA is transcriped into DNA. RNA dependent DNA pol is a core enzyme, transcription of cDNA makes genome and mRNA"
|
|
|
PCN
|
URI
|
|
|
Nafcillin
|
PCN resistant Staph
|
|
|
Amoxicillin
|
URI
|
|
|
Ticarcillin
|
Pseudomonas
|
|
|
Piperacillin
|
4th gen PCN
|
|
|
Imipenem
|
Beta-lactam
|
|
|
Vancomycin
|
Gram +
|
|
|
Aztreonam
|
Gram -
|
|
|
Cefazolin
|
1st gen Ceph
|
|
|
Cefoxitin
|
2nd Gen Ceph
|
|
|
Cefacor
|
2nd Gen Ceph
|
|
|
Ceftriaxone
|
3rd gen Ceph
|
|
|
Cefotaxime
|
3rd gen Ceph
|
|
|
Nalidixic Acid
|
Quinolone
|
|
|
Ciprofloxacin
|
Fluoroquinolone
|
|
|
Ofloxacin
|
Fluoroquinolone
|
|
|
Gatifloxacin
|
3rd gen FQ
|
|
|
Levofloxacin
|
3rd gen FQ
|
|
|
Sulfamethoxazole
|
Sulfonamide
|
|
|
Sulfisoxazole
|
Sulfonamide
|
|
|
Sulfasalazine
|
Sulfonamide
|
|
|
Sulfacetamide
|
Sulfonamide
|
|
|
Doxycycline
|
Tetracycline
|
|
|
Minocycline
|
Tetracycline
|
|
|
Gentimycin
|
AMG
|
|
|
Tobramycin
|
AMG
|
|
|
Amikacin
|
AMG
|
|
|
Streptomycin
|
AMG
|
|
|
Spectinomycin
|
AMG-related
|
|
|
Erythromycin
|
Macrolide
|
|
|
Azithromycin
|
Macrolide
|
|
|
Clarithromycin
|
Macrolide
|
|
|
Clindamycin
|
Misc
|
|
|
Metronidazole
|
Misc
|
|
|
Quinupristine
|
Misc
|
|
|
Linezolid
|
Misc
|
|
|
Chloramphenicol
|
Misc
|
|
|
What in general are AMGs for
|
Serious Gram - infections
|
|
|
What drugs inhibit the 50s subunit in bacteria
|
"Macrolides, chloramphenicol, linezolid"
|
|
|
What antibacterials are contraindicated for pregnancy
|
"AMG, tetracyclines, FQ, Sulfonamides"
|
|
|
What are the DOC for Pseudomonas
|
"3 and 4th gen PCN, Ticarcillin, pipercillin"
|
|
|
What lactamase inhib is paired with pipercillin
|
tazobactam
|
|
|
What is paired with clavulanic acid
|
amoxicillin
|
|
|
What can you use for a gram - infection with a PCN allergy
|
Aztreonam
|
|
|
What is the DOC for drug resistant gonorrhea
|
Ceftriaxone (3rd gen)
|
|
|
what are the 2nd gen FQs
|
"Cipro, ofloxacin, lomefloxacin"
|
|
|
What is an important consideration in prescribing Quinolones
|
can lead to cation toxicity if taking mineral supplements and competes for the P450 system with other drugs
|
|
|
In general 2nd gen FQs are used for
|
"Gram -, STD, and neutropenic pts"
|
|
|
What is the difference between the 2nd and 3rd gen FQs
|
Better Gram+ coverage in 3rd gen
|
|
|
Levofloxacin is a
|
3rd gen FQ
|
|
|
What consideration needs to be taken with 1st generation quinolones
|
want to acidify urine to promote secretion
|
|
|
What typically are sulfanamides restricted to
|
opthalmology and uncomplicated UTI E.coli (complexed with trimethoprim)
|
|
|
What is the MOA of sulfanamides
|
block folic acid synthesis
|
|
|
What drugs can have the ADR of kernicterus
|
Sulfonamides
|
|
|
Pneumocystis jiroveci
|
Sulfamethoxazole and Trimethoprim
|
|
|
Prostatitis in young males
|
oflaxacin
|
|
|
Prostatitis in older males
|
trimethoprim/sulfonamide
|
|
|
What is the MOA of tetracyclins
|
Bind the 30s subunit. block tRNA from binding the A site
|
|
|
What is the spectrum of tetracyclins
|
"pretty broad, DOC for lyme disease, rickettsiae."
|
|
|
What is the MOA of AMGs
|
binds to the AUG site of the 30s stops all protein synthesis.
|
|
|
What is the worst part about AMG
|
Ototoxicity
|
|
|
What is the primary spectrum for AMG
|
gram -. complexed usually with PCN
|
|
|
What is used to treat TB
|
Streptomycin
|
|
|
Typically what is used to treat pcn resistant chlamydia
|
Eryrthromycin
|
|
|
What is the DOC for C diff
|
Metronidazole
|
|
|
What drugs are good against Vanco resistant gram+
|
"Quinupristine, Linezolid"
|
|
|
What strain of HIV predominates in the US
|
HIV-1 Group M Clade B
|
|
|
What is Group N HIV
|
Recent combination of SIV and HIV-1
|
|
|
Into what family and genus of virus does HIV fall
|
"Retrovirus, Lentivirus"
|
|
|
What is unique about HIV 2
|
Less virulent and infected pts show resistance to HIV1. slower progression to AIDS. Has 5 clades
|
|
|
In the early stages of infection what can describe HIV
|
macrophage trophic virus R5
|
|
|
When does HIV start producing syncitia
|
later stages when it is T cell trophic
|
|
|
When is HIV more cytopathic
|
Late stage
|
|
|
What is the receptor that makes HIV trophic for T cells in the late stage
|
CXCR4 receptor (X4 virus)
|
|
|
How many copies of the genome exist in a virus
|
2
|
|
|
What surrounds the genome
|
nucleocapsid protein p7 also contains the RT
|
|
|
What is the capsid protein
|
p24 surounds the nucleocapsid
|
|
|
What does the matrix protein do
|
p17 is involved in the assembly of the virus
|
|
|
what are the 2 parts of the envelope
|
"gp120, the globular head and outermost part
|
|
|
what does gp120 do
|
is responsible for attachment
|
|
|
what does gp41 do
|
mediates fusion of the virus and host cell
|
|
|
what does env encode for
|
gp120 adn gp41
|
|
|
what does pol encode
|
"enzymes for replication
|
|
|
what does gag encode
|
"Structural proteins, matrix, capid, nucleocapsid"
|
|
|
what genes overlap
|
"gag and pol, gag makes own protein, gag=pol polyprotein"
|
|
|
how is env transcribed
|
"makes gp160... cleaved then into gp120, gp41"
|
|
|
what does tat encode
|
transactivates transcription (turns on ts)
|
|
|
what does rev encode
|
promotes mRNA export to cytoplasm
|
|
|
nef
|
"contributes to virulence. if missing nef, virus is attenuated, needed to progress to AIDS"
|
|
|
vif
|
"helps assembly, blocks antiviral proteins"
|
|
|
vpu
|
"inhibits tetherin, allows virus to be released from cell"
|
|
|
vpr
|
transports cDNA to nucleus
|
|
|
what does the LTR do
|
"promoter, enhancer sequences for host TS factors"
|
|
|
how does HIV attach to a cell
|
"gp120 binds CD4 and allows CCR5 to bind gp120 via V3, which allows gp41 to interact with plasma membrane and allow fusion"
|
|
|
what can prevent infectivity of HIV
|
if the virus doesnt cleave the polyprotein
|
|
|
What creates quasispecies within an individual
|
Lots of mutations
|
|
|
What can the mutations in HIV do
|
"Escape IR, resist ARV, change R5-X4, allow syncytia formation"
|
|
|
What receptors do T cells express that are attachment site for HIV
|
"R5, X4"
|
|
|
NRTI
|
nucleoside RT inhibitors
|
|
|
What must occur to activate an NRTI
|
must be phosphorylated by a cellular kinase
|
|
|
NRTI MOA
|
"binds to RT and inhibits RT, results in chain termination. Zidovudine"
|
|
|
NNRTI (non nucleoside RT inhibitor
|
No phosphorylation needed. binds to RT at non-active site and inhibits. Nevirapine
|
|
|
Protease inhibitors
|
"Binds HIV protease, virus cant mature. Saquinavir."
|
|
|
Fusion inhibitors
|
"enfuvirtide, binds gp41 and virus cant fuse"
|
|
|
CCR5 inhibitor
|
"Maraviroc, binds CCR5. alters conformation, can drive virus to become X4"
|
|
|
Integrase inhibitors
|
"Raltegravir, does what it says"
|
|
|
What happens in the primary infection
|
"high viral loads, flu/mono like symptoms. infecting CD4 cells and CD8 cells kill off productive CD4"
|
|
|
During reinfection what areas are hit the hardest
|
MALT and GALT. areas with a lot of T cells
|
|
|
How are T cells depleted
|
"Directly via the virus, apoptosis induced by the virus, or from CTL cells"
|
|
|
What is being screened for in an acute infection
|
"antibodies to p24, viral load (PCR), p24"
|
|
|
what happens if HIV is opsonized by AB
|
"Nothing, is phagocytized but survives in the cell"
|
|
|
What is ARC
|
"AIDS related complex- CD4 is 500-200. lymohadenopathy, fever, weight loss, malaise. some OI"
|
|
|
What are AIDS defining illnesses
|
"Thrush, Karposi, Dementia"
|
|
|
What is the biggest obstacle in developing an HIV vaccine
|
"target would be gp120, but is very variable"
|
|
|
How would using humoral immunity help defend against HIV infection
|
T cells would be activated earlier and be able to make the set point of the virus very low and manageable
|
|
|
What are indicators for testing for HIV
|
"other STDs, Opportunistic infections, odd lab findings"
|
|
|
What does the CDC recommend for testing
|
"Routine testing for 13-64 yo in health care settings, opt out rather than opt in, no seperate consent for test, no counseling, repeat testing at discression of dr"
|
|
|
What are the big 4 symptoms of acute HIV
|
"Fever, Lymphadenopathy, Pharygitis, Rash"
|
|
|
What other things are in the differential for HIV
|
"Group A step, Mono, Malignancy"
|
|
|
What are indicators for beginning ART
|
"Hx of AIDS defining OI, CD4 350-500, pregnant women, HIV associated nephropathy, Hep B"
|
|
|
What is the main goal of ART
|
restoration and or preservation of immunologic function
|
|
|
what is the typical regimen for ART
|
NNTRI/PI and 2 NRTIs
|
|
|
what does it mean to be a preferred therapy
|
"Optimal efficacy and durability, favorable tolerability and toxicity"
|
|
|
What is the preferred therapy
|
efavirenz/tenofovir/FTC (atripla)
|
|
|
what is the preferred therapy for pregnancy
|
LPV/ZDV/3TC
|
|
|
what are non infectious body fluids
|
"urine, feces, vomitus, saliva, sweat, tears"
|
|
|
what are infectious body fluids
|
"blood, vaginal secretions, semen, breast milk"
|
|
|
What happens in lymph nodes during HIV infection
|
"Germinal centers are hyalinized, ,follicles involute, B cell activation leads to hypergammaglobulinemia"
|
|
|
What is PGL and how does it present
|
"persistent generalized lymphadenopathy. 2 non inguinal nodes, non tender, follicular hypoplasia"
|
|
|
What kind of lymphoma is common in AIDS
|
"Non-hodgkin's, 80% systemic, 20% CNS"
|
|
|
What occurs in stage 4 HIV
|
"OI, pneumocystis infections, neoplasms, HHV8, bedridden"
|
|
|
What diseases do you become susceptible to at CD4 500
|
"KS, Lymphoma, TB"
|
|
|
What diseases do you become susceptible to at CD4 250
|
"Pneumocystis, toxo, Candida"
|
|
|
What diseases do you become susceptible to at CD4 100
|
"CMV, Crypto, mycobacterium, encephalopathy"
|
|
|
PML
|
progressive multifoccal leukoencepphalopathy. autoimmune demyelinating disorder
|
|
|
What problems arise in the kidneys in HIV
|
Focal segmental glomerulonephritis
|
|
|
Oncogenes
|
Growth promoting
|
|
|
Tumor Suppressor
|
Growth stopping
|
|
|
what kind of mutation typically occurs to create tumors
|
over expression of growth factors due to gene amplification
|
|
|
C-erb-B1
|
80% of lung cancer
|
|
|
What happens when Ras is mutated
|
cannot cleave GTP and signal transduction cannot be stopped
|
|
|
What GAP do
|
enhances Ras GTPase activity
|
|
|
What happens if Myc is mutated
|
amplifies replication signal
|
|
|
What happens in a Cyclin D or CDK4 mutation
|
when they bind together in G0-G1 phase they are permanently activated and cannot stop cell cycle by continuous inactivation of Rb
|
|
|
Oncogenes: Dominant/Recessive?
|
Dominant
|
|
|
Tumor Suppressor Genes: Dominant/Recessive?
|
Recessive
|
|
|
What does p53 do
|
"Monitors cell and DNA, can inhibit replication and helicase, inhibits Rb, triggers apoptosis, induces p21"
|
|
|
What does TGF-b do
|
suppress c-myc
|
|
|
Desmoplasia
|
"abnormal collagen deposition in a neoplasm, makes tumor rigid"
|
|
|
what are the characteristics of a benign neoplasm
|
"Focal, confined, uniform, matured cells, diploid"
|
|
|
what are characteristics of a malignant neoplasm
|
"rapid growth, immature cells, anueploid, can metastasize"
|
|
|
Hamartoma
|
proliferation of cells native to an organ type
|
|
|
Choristoma
|
"Developmental, proliferation of cells not native to the organ. (pancreatic tissue growing in stomach)"
|
|
|
at what size does a tumor become palpable
|
"1 cm, about 30 doublings"
|
|
|
why are more than one form of chemotherapy used
|
there is always a chance that there is at least 1 resistant cell that will be selected for if only 1 therapy is used.
|
|
|
What is Primary/Induction Therapy
|
"Used mostly for liquid tumors, used when disease is systemic"
|
|
|
Adjuvant therapy
|
When disease has spread outside of the locally controlled area. Used after surgery
|
|
|
what do you have to be concerned with combination therapy
|
"use different MOA, dont combine toxicities, different metobolism"
|
|
|
ADR: Antracyclines
|
Cardiac tox
|
|
|
ADR: Taxanes
|
Neuro tox
|
|
|
ADR: Alkylating
|
"Cardiac tox, 2dary malignancy"
|
|
|
ADR: cisplatin
|
renal and neuro tox
|
|
|
ADR: cyclophosphamide
|
Hemorrahagic Cystitis
|
|
|
Cell type+OMA=
|
benign (exception- melanoma)
|
|
|
Cell of origin for Sarcoma
|
mesenchymal cell
|
|
|
Cell of origin for carcinoma
|
epithelial cell
|
|
|
what is differentiation
|
Extent to which tumor resembles the tissue of origin
|
|
|
What level of differentiation comes with a poor prognosis
|
the less differentiated the worse the prognosis
|
|
|
Anaplasia
|
"lack of differentiation, usually more aggressive"
|
|
|
what are you going to see microscopically on a malignant neoplasm
|
"crowded glands, high N/C, irregular shapes, generally ugly looking"
|
|
|
How long is a course of radiation therapy
|
everyday for 1-9 weeks
|
|
|
IMRT
|
intensity modulator radiation therapy. MCL changes throughout tx to modulate radiation.
|
|
|
IGRT
|
image guided. can visualize tumor as you treat.
|
|
|
What is a brag peak
|
term in proton therapy. proton deposits most of its energy in the treatment site and then leaves the tissue. no residual radiation
|
|
|
what does vWF bind
|
GP Ib/IX/IV
|
|
|
What is contained in platelet granules
|
"ADP, serotonin, platelet factor 4"
|
|
|
What allows the platelets to bind together
|
GP IIb IIIa receptor connects with fibrinogen after a conformation change
|
|
|
Thrombocytopenia is
|
low platelets
|
|
|
What are the general causes of thrombocytopenia
|
"too much destruction, too little proliferation, sequestering in the spleen. hemodilution/spurious"
|
|
|
what is the 2nd step after a blood smear
|
"bone marrow, look at megakaryocytes. none- cancer/aplasia. normal- platelet destruction"
|
|
|
If everything looks normal what is next in dDx
|
"DIC, TTP, SLE, ITP (very last thing)"
|
|
|
What are causes of decreased platelet production
|
"leukemia, cancer, fibrosis, infection, TB, drugs, chemicals"
|
|
|
Congenital Thrombocytopenia
|
"absent radius syndrome. low platelets, weird skeletal things"
|
|
|
May Hegglin Anomaly
|
"Auto Dominant, purpura, giant platelets, Dhole bodys in neutros"
|
|
|
Wiskott Aldrich
|
"IgM deficiency, allergies/eczema"
|
|
|
what can cause increased platelet destruction
|
"autoimmune, lymphoma, drugs, infections, DIC, TTP, HUS"
|
|
|
ITP
|
IgG autoantibodies against GP IIb/IIIa
|
|
|
TTP
|
"vWF multimers are supposed to be cleaved by ADAMTS13, pt has huge vWF clumps and start forming thrombi"
|
|
|
How does TTP present
|
"Thrombocytopenia, Microangiopathic hemolytic anemia, headaches, renal dysfuntion, fever, schistocytes"
|
|
|
HUS
|
"hemolytic uremic syndrome. looks like TTP, caused by gastroenteritis"
|
|
|
NAIT
|
"neonatal alloimmune thrombocytopenia. mom is PLA neg and baby is positive, moms antibodies cross placenta"
|
|
|
Type II HIT
|
"heparin induced, antibodies bind to PF4-Heparin complex and cause thrombosis"
|
|
|
What 4 factors are used in platelet aggregation testing
|
"epi, collagen, ADP, Ristocentin"
|
|
|
Type I vWF disease
|
decrease in all polymeric forms of vWF
|
|
|
Bernard Soulier Syndrome
|
"Auto recess. Def of GP Ib IX. platelets cant stick to walls. Large platelets, severe bleeding, rsitocetin decreased"
|
|
|
Glazmann Thromboasthenia
|
"weak platelets, auto rec, GP IIb IIIa disorder, platelets dont adhere to eachother. ristocetin is normal, others are decreased."
|
|
|
Storage pool disease
|
can either lack granules or cant release them
|
|
|
Petechiae
|
platelet/vessel disorder
|
|
|
mucosal bleeding
|
platelet/vessel
|
|
|
bleeding from superficial cuts
|
platelet disorder
|
|
|
delayed bleeding
|
coag disorder
|
|
|
hemarthroses
|
coag disorder
|
|
|
hematomas
|
coag disorder
|
|
|
PT measures
|
"extrinsic pathway, VII, warfarin"
|
|
|
Vit K is necessary for
|
"II, VII, IX, X, C and S"
|
|
|
PTT measures
|
"intrinsic path, VIII, IX, XI, XII, V, X, heparin"
|
|
|
Hemophilia A
|
"VIII disorder, long PTT"
|
|
|
Hemophilia B
|
"IX, long PTT"
|
|
|
Hemophilia C
|
"Auto recessive, XI disorder, long PTT"
|
|
|
PT is normal
|
"vWF, hemo A or B, thrombocytopenia"
|
|
|
PT increased
|
Vit K def
|
|
|
PTT normal or high
|
"vWF, vit K"
|
|
|
PTT is high
|
Heme A or B
|
|
|
Normal plate count
|
"vWF, hem A/B, Vit K def"
|
|
|
Low Plt
|
thrombocytopenia
|
|
|
What is the definition of cachexia
|
"Wasting syndrome resulting in altered metabolism, weight loss, loss of lean body mass, decreased albumin, increase CRP"
|
|
|
what area the clinical manifestations of cachexia
|
"nonvoluntary weight loss, anorexia, early satiety, hypermetabolism, loss of lean body mass/fat, anemia, weakness"
|
|
|
Progestagens
|
"inhibit cytokines, prevent NPY down regulation"
|
|
|
Thalidomide
|
blocks cytokine production
|
|
|
how does EPA counteract cachexia
|
"competes with arachadonic acid for COX and LOX, prevents synthesis of series 2 and 4 PG and TX. less inflamation less cachexia"
|
|
|
What physical exercise is recommended for cachexia pts
|
"resistance training 3 days/wk, 12 large muscle groups, 3 sets of 8"
|
|
|
Aflatoxin is linked to
|
HCC
|
|
|
Aromatic amines is linked to
|
Bladder cancer
|
|
|
Asbestos is linked to
|
Mesothelioma
|
|
|
Benzene is linked to
|
leukemia
|
|
|
Beryllium is linked to
|
Lung cancer
|
|
|
Vinyl Cloride is linked to
|
Angiosarcoma
|
|
|
What is a consequence of tumor cells having more laminin receptors
|
allow tumor cells to readily attack to organs
|
|
|
What is a major biochemical marker of cancer
|
"Keratin, IDs tumor as a carcinoma"
|
|
|
What are the signs of a neoplasm in a lymph node
|
"large painless, unilateral"
|
|
|
What factors are involved in the intrinsic path
|
"8,9,11,12"
|
|
|
PTT tests
|
intrinsic system by activating factor 12
|
|
|
What deficiency will PT/PTT not pick up
|
"factor 13, neither test looks at crosslinking of fibrin"
|
|
|
What factors is Vit K responsible for
|
"2, 7, 9, 10, S, C"
|
|
|
What will happen if bowel flora is suppressed
|
"less vit K synthesis, additive effect with coumadin"
|
|
|
What can you do to reverse a coumadin overdose
|
"wait it out, vit k, FFP, prothrombin factor"
|
|
|
What anticoag drug keeps a normal thrombin time
|
"coumadin.
|
|
|
In case of a major heparin overdose what is the Tx
|
protamine sulfate
|
|
|
DIC
|
"rapid coag with consumption of clotting factors resulting in thrombi, schistocytes, purpura. get secondary fibrinolysis"
|
|
|
What does DDimer measure
|
"fibrin degradation products. evidence that cross linking has occured. found elevated in DVT, PE"
|
|
|
How do you manage DIC
|
"Hydration, replacement therapy (for anything low ie plt), heparin, activated protein C (esp in cases of gram- infection)"
|
|
|
How does the liver relate to DIC
|
a failing liver will not remove excess clotting factors and a cascade can be set off more easily
|
|
|
DDVAP
|
"vasopressin analog, enhances vWF release, used for hemophilia and vW disease."
|
|
|
How is thrombocytopenia managed
|
"Corticosteroids, discontinue meds, IgG, IgRho, Plt transfusion"
|
|
|
How does Ig therapy fix thrombocytopenia
|
blocks removal of plates by the spleen
|
|
|
What are the 4 Ts of Heparin induced thrombocytopenia
|
"Thrombocytopenia, Timing (7-13 days post exposure), Thrombosis, Other causes of thrombocytopenia are not evident"
|
|
|
What occurs with TTP
|
"renal impairment, feer, neuro signs, hemolytic anemia, thrombocytopenia, "
|
|
|
What happens in TTP which does not happen in DIC
|
clumping of platelets and affecting kidney filtration. Lab tests are usually normal
|
|
|
What causes warfarin related skin necrosis
|
Protein C deficient Pt gets warfarin
|
|
|
What are the 4 major causes of anemia
|
"Marrow disorders, substrate deficiency, accelerated loss, decreased erythropoietin"
|
|
|
what is a normal Hb
|
"Men 14-16, women 12-15"
|
|
|
What is the normal ratio RBC:HgB:Hct
|
1:3:9
|
|
|
What is Hct
|
% of blood volume that is red cells
|
|
|
MCV
|
"how big cells are
|
|
|
"MCH, MCHC"
|
mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. heme per cell and heme per hct
|
|
|
RDW
|
"red cell distrobution width, 12-14"
|
|
|
WBC
|
5000-10000
|
|
|
Platelets
|
"150,000-450,000"
|
|
|
What changes in blood are seen in pregnancy
|
"RBC mass increase, RBC volume increase, but plasma increases more so may have low Hct"
|
|
|
what is a normal retic count
|
"25,000- 75,000"
|
|
|
when is a normal retic count not normal
|
"when the patient is anemic, retic count should be elevated."
|
|
|
What does a low retic count suggest
|
"bone marrow isnt working. Aplastic, suppressed, dysplastic"
|
|
|
what does a high retic count mean
|
marrow is working while pt is anemic (can be 6-7x higher)
|
|
|
What is the definition of a microcytic anemia
|
Less than 6 microns
|
|
|
What are the diseases with microcytic anemia
|
"Iron def
|
|
|
visually how can u call a cell hypochromic
|
if the central pallor is greater than 1/3 of the diameter of the cell
|
|
|
What are the 3 forms of iron in the body
|
"stored, useable, and transport"
|
|
|
As you begin to bleed where is iron lost first
|
plasma iron decreases briefly then iron is pulled from ferritin.
|
|
|
if bleeding continues and iron is depleted from storage what occurs
|
"TIBC goes up, and plasma ferritin goes down"
|
|
|
What gets fixed first during tx of iron deficient anemia
|
"serum iron, then transferrin, then ferritin."
|
|
|
B thalassemia trait
|
"usually asymptomatic, can have skeletal deformities due to massive marrow proliferation. MCV/RBC<13 suspicious. Codocytes (target cells)"
|
|
|
what happens biochemically in B thalassemia
|
"use up all the beta chains left with excess alpha chains, they glob together and precipitate out. inclusion bodies, splenomegaly"
|
|
|
Loss of 1 alpha trait
|
no complications
|
|
|
Loss of 2 alpha traits
|
still no symptoms can be cis or trans
|
|
|
lose 3 alpha genes
|
"hemoglobin H, splenectomy, transfusions"
|
|
|
Lose 4 alpha genes
|
"hydrops faetalis, not compatible with life"
|
|
|
Normocytic anemia
|
"Iron deficiency after a massive bleed, renal failure (less erythropoietin) marrow failure (slowed production)"
|
|
|
ACD
|
"disorder of iron homeostasis.
|
|
|
What are possible causes of ACD
|
"Arthritis, infections, cancer, lupus, bowel disease, sarcoid, vasculitis"
|
|
|
How do you stage renal failure
|
"based on glom filt rate.
|
|
|
What do you look for when you have pure RBC aplasia
|
Thyoma
|
|
|
Dacrocytes
|
"found in complete marrow aplasia, racket cells"
|
|
|
Fanconi's anemia
|
"aplastic, auto recess, defective DNA repair, cannot remove free radicals. fixed by marrow transplant"
|
|
|
Differential for macrocytic
|
"B12
|
|
|
Pernicious Anemia
|
"Anti intrinsic factor antibodies
|
|
|
hemolytic anemia
|
"immune regulated: Ab attack RBC. Coombs test. Looks for Ab either on the cells or in the blood.
|
|
|
what causes non immune regulated hemolytic anemia
|
"Artificial implants, heart valve abnormal, DIC, sickle cell, G6PD deficiency, "
|
|
|
Lab tests for hemolytic anemia
|
"bilirubin, indirect will be high. haptoglobin- will be low"
|
|
|
what are options in restoring iron
|
"ferrous sulfate, ferrous gluconate"
|
|
|
What can occur in iron overload
|
"GI pain, metabolic acidosis"
|
|
|
how do you treat iron overload
|
"gastric lavage, chelation using deferoxamine"
|
|
|
what happens in hemochromotosis
|
"intestines lose ability to stop absorbing iron, organ failure occurs"
|
|
|
why are cells macrocytic in folate deficiency
|
"get back up of FH3CH3, cells expand "
|
|
|
How are B12 and folate linked
|
cobalamin (B12) demethylates folate and is used to make methionine- used in myelin
|
|
|
what interacts with folate absorbtion
|
methotrexate and trimethoprim
|
|
|
Filgrastim
|
"G-CSF, increases production of neutrophils"
|
|
|
Mechlorethamine
|
"Alkylating, used in Lymphoma, ADR myelosuppression"
|
|
|
Mechlorethamine
|
"Alkylating, used in Lymphoma, ADR myelosuppression"
|
|
|
When do alkylating agents work
|
"anytime, cross link and alkylate the DNA (guanine mostly)"
|
|
|
When do alkylating agents work
|
"anytime, cross link and alkylate the DNA (guanine mostly)"
|
|
|
Cyclophosphamide
|
"alkylating, Burkitts, breast. Hemorrhagic Cystitis"
|
|
|
Cyclophosphamide
|
"alkylating, Burkitts, breast. Hemorrhagic Cystitis"
|
|
|
Ifosfamide
|
"alkylating, Burkitts, breast, Neurotoxicity"
|
|
|
Ifosfamide
|
"alkylating, Burkitts, breast, Neurotoxicity"
|
|
|
Chlorambucil
|
"Leukemia/Lymphoma, alkylating"
|
|
|
Chlorambucil
|
"Leukemia/Lymphoma, alkylating"
|
|
|
Busulfan
|
"Alkyl sulfonates, CML,
|
|
|
Busulfan
|
"Alkyl sulfonates, CML,
|
|
|
Carmustine
|
"Nitrosourea, HL, NHL, Brain, high lipid soluble, Renal tox"
|
|
|
Carmustine
|
"Nitrosourea, HL, NHL, Brain, high lipid soluble, Renal tox"
|
|
|
Cisplatin/Oxaliplatin
|
"Metal salt, G1, S phases. Damages renal tubes"
|
|
|
Cisplatin/Oxaliplatin
|
"Metal salt, G1, S phases. Damages renal tubes"
|
|
|
Doxorubicin
|
"Anthracyclines, Antibody, S/G2, Cardiac tox!!!!"
|
|
|
Doxorubicin
|
"Anthracyclines, Antibody, S/G2, Cardiac tox!!!!"
|
|
|
Bleomycin
|
"G2, HL, Testicular, lung, PULMONARY FIBROSIS"
|
|
|
Bleomycin
|
"G2, HL, Testicular, lung, PULMONARY FIBROSIS"
|
|
|
Methotrexate
|
"leads to polyglutination and cell death, S phase, need to alkalize urine"
|
|
|
Methotrexate
|
"leads to polyglutination and cell death, S phase, need to alkalize urine"
|
|
|
Mercaptopurine
|
S phase
|
|
|
Mercaptopurine
|
S phase
|
|
|
Cytarabine
|
"pyrimadine analog, S phase"
|
|
|
Cytarabine
|
"pyrimadine analog, S phase"
|
|
|
5 flurouracil
|
"S phase, bone marrow suppression"
|
|
|
5 flurouracil
|
"S phase, bone marrow suppression"
|
|
|
Vincristine/Vinblastine
|
"M phase, bind tubulin, cant go thru m phase. Neurotox"
|
|
|
Vincristine/Vinblastine
|
"M phase, bind tubulin, cant go thru m phase. Neurotox"
|
|
|
Etoposide
|
"Topoisomerase inhib. allows double strand breaks, S, G2 phase, 2ndary leukemia"
|
|
|
Etoposide
|
"Topoisomerase inhib. allows double strand breaks, S, G2 phase, 2ndary leukemia"
|
|
|
Paclitaxel
|
"polymerizes microtubules, M phase cant progress, G2/M. sever neurtopenia"
|
|
|
Paclitaxel
|
"polymerizes microtubules, M phase cant progress, G2/M. sever neurtopenia"
|
|
|
Asparaginase
|
"ALL, hypergycemia"
|
|
|
Asparaginase
|
"ALL, hypergycemia"
|
|
|
Tamoxifen
|
"inhibits estrogen receptors, no cell growth signalling"
|
|
|
Tamoxifen
|
"inhibits estrogen receptors, no cell growth signalling"
|
|
|
Leuprolide
|
"anti GnRH, stops LH, FSH release, used for prostate CA"
|
|
|
Leuprolide
|
"anti GnRH, stops LH, FSH release, used for prostate CA"
|
|
|
What cells are myeloid lineage
|
"Granulocytes, momocytes, platelets and erythrocytes"
|
|
|
what cells are lymphoid lineage
|
"B cells, T cells, NK cells"
|
|
|
What Il stimulates stem cells
|
1 and 6
|
|
|
What stimulates eosinophils
|
IL 5
|
|
|
In what cases do you worry about leukostasis
|
"AML WBC>100,000
|
|
|
what is a general blast marker
|
CD34
|
|
|
What disease is missing Factor VIII
|
Hemophilia A
|
|
|
What disease is missing factor IX
|
Hemophilia B
|
|
|
If you are vit K deficient what factors are affected
|
"2, 7, 9, 10"
|
|
|
What is occuring in acute leukemia
|
cells are not maturing completely
|
|
|
What defines AML
|
marrow is >20% blasts
|
|
|
what are the 2 major translocations in AML
|
t(15:17) and t(8:21)
|
|
|
what chemo agents typically cause a secondary AML
|
alkylating agents
|
|
|
what are factors in determining a prognosis in AML
|
"age, previous heme path, cytogenetics, performance status, MDR, high WBC at dx"
|
|
|
what is the typical chemo regimen for AML
|
7 and 3 anthracycline and cytarabine induction regimen.
|
|
|
what are the 3 stages of CLL
|
"chronic, accelerated, blast crisis"
|
|
|
What is Virchow's triad
|
"Coag State
|
|
|
what causes hemopoietic cells to become megakaryocytes
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thrombopoietin
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what produces TPO
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liver and kidney
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what is the receptor for TPO
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CMPL
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What is missing in Glanzmann thrombastenia
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"Gp IIb/IIIa
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What is missing bernard soulier syndrome
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"GpIb
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what sequence is important in plt binding
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"RGD: arginine, glycine, aspartate"
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alpha granule contains
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"PF4, beta thromboglobulin, PDGF, vWF"
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dense granules contain
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ADP
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what is gray platelet syndrome
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no alpha granules
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What do Omega 6 FA make
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"Series 4 Leukotrienes
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what are microparticles
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tiny pieces of plts that are procoagulant. have encrypted tissue factor
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"besides fibrinogen, what else can thrombin activate"
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"V, VIII, XI, VII, XIII"
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what does activated protein C do
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inactivates V and VIII
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what is a defining morphology of hodgkins
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reed sternberg cells
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what markers are on a stem cell in marrow
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CD34
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A genetic hit to a germinal center B cell gives rise to what forms of lymphoma
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"follicular, LBL, HL, Burkitt"
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Which bcl gene can lead to excessive cell production
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BCL1
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What bcl gene can lead to not enough apoptosis
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BCL2
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Changes in BCL1 are seen in what lymphoma
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mantel cell lymphoma
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Changes in BCL2 are seen in what lymphoma
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follicular lymphoma
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what is LDH used for
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marker for cell turnover in lymphoma. lower levels show response to therapy
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what does every lymphoma pt get
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marrow biopsy
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when is HL likely to occur
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20-30s and 60-70s
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what are B symptoms
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"fever, night sweats, weight loss"
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what factors attribute to a bad HL prognosis
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"low albumin, low Hbg, male, stage IV, high WBC"
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what is an important risk factor in NHL
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Autoimmune disease and immunosuppression
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SPEP is used for
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finding imunoglobulins to determine subtype of lymphoma
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what diseases are associated with NHL
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"Sjorgrens, RA, SLE"
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what is the prognostic index for follicular lymphoma and what goes into it
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"FLIPI, number of sites, LDH, age over 60, Stage, low Hgb"
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what is typical treatment for folicular lymphoma
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watch and wait then rituximab
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what does rituximab do
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hones into CD20 and interferes w cell function
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what is APLES
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"the IPI for DLBCL, Age, performance, extranodal sites, LDH, stage"
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What is the genetic translocation for M3 AML
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t(15:17)
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t(8:21) occurs in what leukemia
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M2 AML
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In what leukemia do you find auer rods
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APML (M3)
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what do you use to treat APML
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"ATRA, except t(11:17)"
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what markers are seen in ALL
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"TdT, CD10, CD19"
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what markers are seen in CLL
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"CD20, 23, 5"
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What stain is used in CML
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LAP
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"CD20, no CD5 means"
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B cell prolymphocytic leukemia
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TRAP stain is used to dx
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Hairy Cell Leukemia
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CD20 +"
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Lymphocyte Predominant HL
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CD10 BCL6
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Burkitt's
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CD3 with no 4 or 8
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Sezary syndrome
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Clover leaf and flower nuclei is a sign of
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Adult T cell prolymphocytic leukemia
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neutrophil infiltration into marginal zones
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Nodal Marginal Zone Lymphoma
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"lipid vacuoles, large macrophages, starry sky"
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Burkitt's
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"Lacunar RSC, collagenic fibrous bands"
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Nodular Sclerosing HL
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Popcorn cells (RSC)
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Lymphocyte predominant HL
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"Variation of follicle size, tingible Body macros"
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Nonspecific follicular Hyperplasic
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"asteroid bodies, schauman bodies, calcium oxalate crystals"
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Sarcoid
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"Macrophages with C shaped nuclei, monocytes with round nuclei"
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Kikuchi
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"Follicular hyperplasia, w granuloma of palisading macrophages"
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Cat scratch or lymphogranuloma venerum
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onionskin and lollipops
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Castleman's
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Foamy Macrophages
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Whipples
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Bland Macrophages
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Virus associated Hemophagic syndrome
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t(9:22)
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"CML
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7q21 deletion
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Splenic marginal zone lymphoma
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7q21 deletion
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Splenic marginal zone lymphoma
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t(14:18) bcl2 and cmyc
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Follicular lymphoma
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t(11:14) cyclin D
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Mantle cell lymphoma
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t(8:14)
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Burkitt's
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Trisomy 8
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Hepatosplenic T cell lymphoma
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What is used against Follicular lymphoma
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R-CVP
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what is used against LBCL
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R CHOP
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against HL what therapy agents are used
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ABVD or the Stanford 5
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what is at risk for and what is a richter transformation
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"CLL, changes into LBCL"
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Definition of myeloproliferative disorder
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clonal expansion of a multipotent hematopoietic progenitor cell which leads to overproduction of one or more elements of blood
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myelodysplasia
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abnormal growth of myeloid line
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How do you dx P vera
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"exclusion, rule out hypoxia, renal disease, abnormal EPO receptor, if EPO level is low- look at PV"
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what is erythromelagia and how is it treated
|
"erythema, pain, warmth, digital infarcts, NSAID"
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What is myelofibrosis
|
"stem cell anomaly that leads to the overgrowth of one type of myeloid, in response there is an overgrowth of T cells and fibroblasts"
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what is going to happen to marrow in AMM
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hypervascular and fibrous scar tissue. start to see secondary sites of hematopoiesis
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What are the hallmarks of AMM
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"Marrow fibrosis, myeloid metaplasia, extramedularry hematopoiesis, 20% transform into AML"
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What are the clinical features of AMM
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"asymptomatic, splenomegaly, leukoerythroblastic smear, red bumpy skin"
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What must be ruled to to dx as AMM
|
"CML, myelophthesis, leukemia, MPD"
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Treatment for AMM
|
"treat sx, hydroxyurea, BMT, thalidomide"
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Essential Thrombocytosis
|
"usually asymptomatic, jak+/-, rule out iron def, inflammation, CML (use LAP)"
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How is ET treated
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"anagrelide- poor tolerance
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|
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myelodysplastic syndromes
|
"ineffective erythropoiesis, like cytopenia, 33% becomes AML"
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what are the qualities of a primary MDS
|
"idiopathic, simple genetic change, low IPSS, better tx response"
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Secondary MDS have these qualities
|
"due to chemo, complex cytogenetics, High IPSS, poor outcomes"
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|
|
RAEB-1
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refractory anemia excess blasts. blasts <10%
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RAEB-2
|
refractory anemia excess blasts. blasts >10%
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RA
|
"reactive anemia >5% blasts and <15% sideroblasts, no auer rods"
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|
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RARS
|
>15% sideroblasts
|
|
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RCMD
|
dysplasia in >10% abnormal in >1 cell lines
|
|
|
what mutation has a better outcome in MDS
|
"5q mutation, lenalidamide therapy"
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|
|
Dx MDS
|
"Low blood count, macrocytic, r/o b12/folate def."
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|
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Dx MDA
|
"Low blood count, macrocytic, r/o b12/folate def."
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|
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tx MDS
|
"no standard. EPO, transfusion, GCSF, azacitidine"
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|
|
What should a gamma spike look like in a healthy person
|
nice constant smooth slope
|
|
|
what does monoclonality mean
|
one type of Ig is over produced
|
|
|
what is linked to a worse outcome in MM
|
light chains in the urine
|
|
|
MGUS
|
"stable M spike, no light chains, no bone involvment, no renal faiure. can progress to MM"
|
|
|
Smoldering Myeloma
|
"M spike in between MM and MGUS, no bone, CA, or renal involvement. can transfrom to MM"
|
|
|
Solitary myeloma
|
"one tumor of plasma cells in the bone somewhere. no M spike, asymptomatic, Rad therapy"
|
|
|
Plasma Cell Leukemia
|
"russel and dutcher bodies, looks like CLL, hyperviscous blood, no skeletal, cold agglutination-raynaud's. very aggressive"
|
|
|
What are signs of MM
|
"low albumin, weak bones, kidney failure. CBC, BUN/creat, Ca, Ig level, UPEP, SKeletal survey, BM biopsy"
|
|
|
How do you treat stage II and III MM
|
"chemo, aggressive tx, BM transplant, bisphosphonates for bones (watch kidneys)"
|
|
|
What IL goes up in MM
|
IL 6
|
|
|
Components of Osteosclerotic Myeloma
|
"POEMS, demylenation, organomegaly, endocine, megakaryocytes, skin"
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