Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
86 Cards in this Set
- Front
- Back
|
What regenerates NAD+ in RBCs
|
lactate production
|
|
|
What is NADH used for in RBCs
|
reduce ferric form of hemoglobin
|
|
|
what is the ferric form of hemoglobin called
|
methemoglobin
|
|
|
what is the major allosteric effector for oxygen binding to hemoglobin
|
2, 3-biphosphoglycerate (2, 3-BPG); produced via side pathway of glycolysis
|
|
|
hexose monophosphate shunt
|
generates NADPH to protect RBCs membrane lipis and proteins from oxidation through regeneration of reduced glutathione
|
|
|
what does heme originate from
|
succinyl coenzyme A and glycine
|
|
|
porphyrias
|
mutations in any of the steps of heme synthesis
|
|
|
polymorphonuclear leukocytes
|
granulocytes; neutrophils, eosinophils, and basophils
|
|
|
mononuclear leukocytes
|
lymphocytes (B-cells, T-cells, NK cells) and monocytes
|
|
|
how do the different granulocytes stain
|
neutrophils pink, eosinophils red, basophils blue
|
|
|
respiratory burst
|
initiated by neutrophils, creates oxygen radicals that rapidly destroy forgein materials found at site of infection
|
|
|
eosinophil granules
|
contain hydrolytic enzymes and cationic proteins which are toxic to parasitic worms
|
|
|
basophil granules
|
histidine/histamine (allergic response), proteases, B-glucuronidase, and lysophospholipase; degrade microbial structures and assist in remodeling damaged tissue
|
|
|
how are different subclasses of T-cells identified
|
surface membrane proteins; correlate with fxn
|
|
|
Fxn of B-cells
|
secrete antibodies in respponse to antigen binding
|
|
|
Fxn of NK cells
|
target virally infected and malignant cells for destruction
|
|
|
MCV
|
average volume of RBC (80-100 fL)
|
|
|
MCHC
|
average concentration of hemoglobin in each individual erythrocyte (32-37 g/L)
|
|
|
What is ATP used for in RBCs
|
ion transport, phosphorylation of membrane proteins, priming rxns of glycolysis
|
|
|
rapaport-luebering shunt
|
glyclysis uses to generate 2, 3-BPG
|
|
|
what is 2, 3-BPG used for in other cells
|
required for phosphoglycerate mutase rxn of glycolysis; regenerated during each rxn, so only trace amounts required in most cells (except RBCs)
|
|
|
what occurs in pyruvate kinase deficiency
|
1/2 ATP formed in glycolysis compared to normal; tend to gain Ca++ and lose K+ and water
|
|
|
How are anemia affects moderated in pyruvate kinase deficiency
|
increased 2, 3-BPG concentration makes RBCs in circulation highly efficient in realeasing O2 to tissue
|
|
|
What state must iron be in hemoglobin to bind O2
|
ferrous (+2) state
|
|
|
NADH-cytochrome b5 methemoglobin reductase system
|
cytochrome b5 reduces Fe3+, then oxidized cytochrome b5 is reduced by flavin-containing enzyme using NADH as the reducing agent
|
|
|
enzyme that catalyzes first step of hexose monophosphate shunt
|
glucose 6-phosphate dehydrogenase (G6PD); lifetime of RBC correlates with G6PD activity
|
|
|
conditions with excess methemoglobin
|
enzymatic deficiency in cytochrome b5 reductase or inherited hemoglobin M (stabilizes Fe3+)
|
|
|
what happens when someone with G6PD deficiency is given antimalarial drugs like primaquine
|
develop anemia
|
|
|
Heme formation step 1
|
glycine and succinyl CoA condense to form d-aminolevulinic acid (d-ALA)
|
|
|
requirement for d-ALA aynthase in step 1 of heme formation
|
requires participation of pyridoxal phosphate (rxn is an aa decarboxylation rxn…glycine decarboxylated)
|
|
|
Heme formation step 2
|
2 molecules of d-ALA condense to form pyrrole, porphobilinogen
|
|
|
Heme formation step 3
|
4 pyrrole rings condense to form linear chain and then a series of porphyrinogens
|
|
|
Heme formation step 4
|
porphyrinogens initially contain acetyl (A) and propionyl (P); acetyl groups decarboxylated to methyl groups
|
|
|
Heme formation step 5
|
1st 2 propionyl side chains decarboxylated and oxidized to vinyl groups, forming a protoporyrinogen
|
|
|
Heme formation step 6
|
methylene bridges are oxidized to form protopophyrin IX
|
|
|
Heme formation step 7 (final step)
|
Fe2+ incorporated into protoporphyrin IX; catalyzed by ferrochelatase (heme synthase)
|
|
|
what increases uptake of nonheme iron in digestive tract
|
vitamin C (ascorbic acid)
|
|
|
what form is iron absorbed/transported
|
absorbed as Fe2+, then converted by the ferroxidase ceruloplasmin to ferric state for transport
|
|
|
transferrin
|
iron plus apotransferrin; usually only 1/3 saturated with iron
|
|
|
iron binding capacity of blood
|
300 ug/dL (mostly due to transferrin)
|
|
|
morphology of vit B6 deficiency
|
microcytic, hypochromic RBCs; iron stores elevated
|
|
|
Pathology of lead poisoning
|
d-ALA and ferrochelatase are inactivated by lead; lack of hemoglobin and energy producation
|
|
|
Where is most iron stored
|
liver, spleen, and bone marrow
|
|
|
ferritin
|
apoferritin in complex with Fe3+; generally little in blood unless excess iron
|
|
|
hemosiderin
|
form of ferritin complexed with additional iron that cannot be readily mobilized; occurs when excess iron absorbed from diet
|
|
|
heme regulation
|
negative feedback; heme stimulated hemoglobin synthesis by stimulating protein globin synthesis
|
|
|
degredation of heme
|
degraded to bilirubin which is conjugated with glucuronic acid and excreted in bile
|
|
|
bilirubin processing in liver
|
reacts with UDP-glucuronate to form bilirubin monoglucuronide which is converted to diglucuronide and excreted into bile
|
|
|
iron lost per day in men
|
1 mg/dl; due to desquamation of skin, bile, feces, urine, and sweat
|
|
|
what should you suspect if male has iron-deficient anemia
|
GI tract bleeding (ulcers, colon cancer, etc)
|
|
|
RBC and spleen relationship
|
RBCs pass through spleen ~120 times per day taking ~30 s each time
|
|
|
iron deficiency vs vit B6 deficiency anemias
|
both have microcytic, hypochromatic, but iron level will differ
|
|
|
what results in a branched membrane cytoskeleton in RBCs
|
actin can bnd multiple spectrins
|
|
|
ankyrin
|
interacts with B-spectrin and integral membrane protein band 3; band 4.2 helps stabilize
|
|
|
band 4.1
|
anchors spectrin skeleton with membrane by binding integral membrane protein glycophorin C and actin complex
|
|
|
how do RBCs handle mechanical stress
|
spectrin network rearranges with some beoming uncoiled and extended while others compress
|
|
|
what is 2, 3-BPG made from
|
1, 3-biphosphoglycerate
|
|
|
buffer in tissues
|
CO2 converted into carbonic accid which dissociates into bicard and H+ ions
|
|
|
CO2 interaction with hemoglobin
|
forms carbamate adducts with the N-terminal amino groups of deoxyhemoglobin and stabilized deoxy form
|
|
|
population of hematopoitic stem cells
|
1 to 10 per 10^5 bone marrow cells
|
|
|
what secretes growth factors and regulates hematopoitic development
|
stromal cells (fibroblasts, endothelial cells, adipocytes, macrophages)
|
|
|
most hematopoietic growth factor receptors
|
cytokine receptor superfamily; JAK signal propagation
|
|
|
JAK phosphoylates what
|
STAT which dimerize and translocate to nucleus to affect gene transcription
|
|
|
SHP-1
|
tyrosine phosphatase necessary for proper dvlpmnt of myeloid and lymphoid lineages; dephosphorylates JAK2, inactivating it
|
|
|
Protein inhibitors of activated STAT (PIAS)
|
inactivated STAT
|
|
|
what occurs with a defective erythropoietin receptor
|
over production of RBCs since receptor can not be deactivated - sustained activation of JAK2 and STAT5; SHP-1 generally deactivates
|
|
|
fanconi anemia
|
bone marrow failure and increased susceptability to malignancy
|
|
|
RBC developmental precursors
|
1) stem cell to mixed myeloid progenitor cell (CFU-GEMM) 2) burst forming unit (BFU-E) 3) colony forming unit (CFU-E) 4) normoblast (first recognizable RBC) 5) reticulocyte
|
|
|
where do reticuloctes mature
|
in spleen where ribosomes and mRNA are lost
|
|
|
what type of anemia do folate and vit B12 defiencies cause
|
megaloblastic; nucleus extruded before cell divisions completed; fewer RBCs produced
|
|
|
What happens to unconjugated bilirubin in sickle cell
|
increases, causing gallstones
|
|
|
HbC
|
glu-lys replacement; promotes water loss by activating K+ transporter; homozygous have mild hemolytic anemia, heterozygous unaffected clinically
|
|
|
thalassemias
|
excess of one hemoglobin chain over another
|
|
|
HbF
|
lower affinity for 2, 3-BPG than adult hemoglobin aka greater affinity for O2
|
|
|
HbF composition
|
2 alpha and two gamma chains
|
|
|
HbA composition
|
2 alpha and two beta chains
|
|
|
point mutations in A-gamma and G-gamma promoters
|
have ameliorating (helpful) effect on sickle cell/b-thalassemia diseases due to increased gamma chain synthesis
|
|
|
embryonic megaloblast
|
1st embryonic RBC produced 15 days post fertilization; nucleus retained
|
|
|
when does erythropoiesis shift to liver
|
6 weeks, then also created in spleen
|
|
|
when does erythropoiesis shift to bone marrow
|
few weeks before birth; by 8-10 week post-birth, bone marrow is exclusive site of production
|
|
|
hemoglobin genes on chromosome 16
|
embryonic zeta gene, 2 copies alpha-gene
|
|
|
hemoglobin genes on chromosome 11
|
embryonic epsilon gene, 2 copies fetal beta gene, G-gamma, A-gamma, and two adult genes: detla and beta
|
|
|
order of hemoglobin genes on chromosomes
|
in order of expression during development
|
|
|
what controls switching of hemoglobin genes
|
transcription factor independent of environmental factors
|
|
|
hereditary spherocytosis cause
|
defect in ankyrin, B-spectrin, or band 3 are 75% cases; alpha-spectrin and band2 remainder
|
|
|
what immunizations should someone with splenectomy get
|
pneumococcus, meningococcus, Haemophilus influenzae type b
|
