Flashcards in EXAM #1: REVIEW Deck (104)
What cells produce endogenous G-CSF? What is their normal role?
Macrophages secrete G-CSF from sites of inflammation, which circulates to the bone marrow and stimulates the production of granulocytes
List the morphological, structural, and staining changes that happen to RBCs as they mature.
1) Cell size decreases
2) N:C ratio decreases
3) Nucleoli decrease in number and disappear
4) Cytoplasmic staining goes from dark blue to light blue
What is the normal percentage of "bands?"
List the four major purposes of RBC metabolism. What is required to accomplish these purposes?
1) Reduce iron--NADH for methemoglobin reductase
2) Maintain ion gradients (K+/Ca++)-- ATP
3) Reduce protein SH-goups--NADPH
4) Maintain cell shape--ATP
What are the two regulated steps of glycolysis in RBCs? What inhibits these enzymes?
Both are inhibited by lowered pH
Draw and label the pertinent metabolic pathways in a RBC.
What is the effect of 2,3 BPG on Hb's oxygen affinity?
2,3 BPG will lower Hb's affinity for oxygen
When cells are acidotic, 2,3 BPG synthesis is inhibited. What is the effect on Hb's oxygen affinity?
Increased oxygen affinity
What is the Bohr effect?
Decreased Hb oxygen affinity in acidotic conditions
What activates Glucose 6-phophate dehydrogenase?
Draw the role of glutathione peroxidase and glutathione reductase in antioxidant defense.
What are two enzyme defects that cause non-spherocytic anemia? What is the mode of inheritance?
- G6PD= X-linked recessive-->lack of NADPH
- Pyruvate Kinase Deficiency= autosomal dominant and recessive-->lack of NADH/ATP
List the four cytoskeletal protein components of a RBC.
1) Spectrin= filamentous scaffold
2) Ankryin= peripheral membrane protein*
3) Band 3= integral membrane protein
4) Glycophorin= integral membrane protein
*Most common cause of Hereditary Spherocytosis (autosomal dominant)
What enzyme reduces Fe+++ to Fe++ for absorption?
Outline how iron gets from the plasma to the cytoplasm of the cell.
1) Clathrin-mediated endocytosis of Transferrin-Fe++
2) ATPase acidifies the endosome (forming lysosome)
3) Conformational change in Transferrin releases Fe++
4) Fe++ -->Fe+++
5) Fe+++ reduced back to Fe++
6) DMT-1 transports Fe++ into the cytoplasm
Describe the post-transcriptional regulation of ferretin translation.
1) 5' UTR contains the Iron Response Element
2) Iron Regulatory Proteins bind the IRE to block translation
3) Free iron in the cytoplasm binds to IRPs and displaces them; thus, translation begins quickly
What is the effect of free iron on ALA synthetase?
Increased translation of ALA synthetase
What is the effect of free iron on transferrin receptor transcription?
Free iron DECREASES the synthesis of the transferrin receptor by binding to IRPs and STABILIZING the mRNA
*Note that this is opposite of the case for Ferretin and AlA Synthetase--likely test question*
List the most common causes of iron deficiency in the following age groups: infants, children, adults, and the elderly.
Children= poor diet
Adults= PUD in males and menorrhagia in females
- Western= colon polyps/ carcinoma
- Developing= hookworm
What are the three stages of iron deficiency anemia?
1) Iron depletion
2) Deficient erythropoesis with normal Hb
3) Inadequate Hb
What are the common causes of iron overload?
1) Chronic blood transfusion
2) Inappropriate parenteral transfusion
3) Ineffective hematopoiesis
4) Hereditary uptake disorder e.g. hemochromatosis
What is the genetic defect in Hemochromatosis?
Mutation in the HFE gene that codes for Hepcidin; thus, Ferroportin is NOT inhibited and increased iron is released from enterocytes into the plasma
Draw the heme synthesis pathway. Label the enzymes that are associated with pathology.
What is X-Linked Sideroblastic anemia?
- X-Linked disorder caused by defective protoporphyrin synthesis, which leads to a microcytic anemia
- Specifically, caused by mutant ALA synthase encoded by the on ALAS2 gene on the X-Chromosome
What products of heme synthesis accumulate in AIP? What is the clinical consequence?
ALA and PBG, which cause the urine to turn a dark red color
What are the three classifications of anemia based on etiology?
1) Under production
3) Blood loss
What is the normal distribution of leukocytes?
How is a reticulocyte count corrected?
Pt. Hct/45 x Reticulocyte count= corrected reticulocyte count
What is the major difference in lab values that differentiates between IDA and ACD?
IDA= low serum ferretin and high TIBC
ACD= high serum ferretin and low TIBC