Blood cell physiology

Question 1

Lymphocyte function

Answer 1

humoral (B cell) and cellular (T cell) immunity

B cells differentiate into plasma cells when activated by Ag –> synthesize and secrete immunoglobulins

Question 2

Hematopoietic stem cell progenitors

Answer 2

Lymphoid multipotent cell

Myeloid multipotent cell

Question 3

Lymphoid multipotent cell progenitor

Answer 3

Lymphocyte-colony-forming cell

Question 4

LCFC progenitor

Answer 4

lymphoblast –> B and T lymphocytes

Question 5

Myeloid multipotent cell progenitors

Answer 5

Erythrocyte-colony-forming cell
Megakaryocyte-forming cell
MGCFC --> monocyte-CFC, granulocyte-CFC
Eosinophil-colony-forming cell
Basophil-colony-forming cell

Question 6

MCFC progenitor

Answer 6

promonocyte –> monocyte

Question 7

GCFC progenitor

Answer 7

neutrophilic myelocyte –> neutrophilic granulocyte

Question 8

Neutrophil function

Answer 8

phagocytose bacteria

Question 9

Eosinophil function

Answer 9

phagocytose Ag-Ab complexes and parasites

allergic responses

Question 10

Basophil function

Answer 10

anticoagulation (platelet-activating chemotactic factors, heparin)
increases vascular permeability (histamine)
bind IgE in allergic reactions
anaphylaxis

Question 11

Monocyte function

Answer 11

gives rise to macrophages

Question 12

Megakaryocyte function

Answer 12

gives rise to membranous cytoplasmic fragments –> platelets

blood clot and coagulation formation (produce von-Willebrand factor, thrombospondin, platelet-derived GF)

Question 13

Fe distribution men

Answer 13

4g
65-70% hemoglobin
10% myoglobin
20-25% storage in reticuloendothelial cells, liver

Question 14

Fe distribution women

Answer 14

2-3g

Question 15

Food that increases Fe absorption

Answer 15

forms soluble iron chelates
ascorbic acid
sugars
amino acids

Question 16

Foods that decrease Fe absorption

Answer 16

phosphates
oxalates, phytates
tannates

Question 17

Iron absorption

Answer 17

1) ferric reductase from +3 to +2 on brush border
2) enter enterocyte via DMT1
3) storage into ferritin or transported out via ferroportin
4) hephaestin coverts +2 to +3, bound to transferrin

Question 18

Iron utilization

Answer 18

1) transferrin receptor endocytoses transferrin-iron complex
2) acidic pH of vesicle releases iron, receptor/transferrin recycled
3) Fe incorporated into Heme (made by mit) or stored as ferritin

Question 19

Fe recycle

Answer 19

1) RBC turnover in the spleen
2) macrophages destroy heme poryphyrin ring via heme oxygenase, releases Fe and protoporphyrin
3) Macrophages transport Fe to plasma transferrin, carry back to bone marrow

• macrophages also maintain a storage pool of iron

Question 20

Iron storage

Answer 20

Ferritin

• multi-subunit protein shell surrounding up to 4500 Fe
• easily mobilized

Hemosiderin

• insoluble complex derived from ferritin, lost surface protein and has aggregated
• higher concentration of Fe than ferritin but releases it more slowly

Question 21

Regulation of iron absorption

Answer 21

Hepcidin

• produced in the liver in response to iron demands
• controls flow out of enterocytes, macrophages, RE and liver cells by binding to ferroportin
• Hepcidin-ferroportin complex taken up by cell and degraded

Question 22

Role of B12 in metabolism

Answer 22

Cofactor for:

• homocysteine –> methionine: generates THF from methyl-THF; active form needed for DNA synthesis
• methylmalonyl-CoA–>succinyl-CoA

Question 23

Folate absorption

Answer 23

Present in food in the form of reduced polyglutamates
Requires transport and action of pteroylglutamyl carboxypepsidase associated with mucosal membranes
Mucosae of duodenum and upper jejunum are rich in dihydrofolate reductase, can methylate most or all of folate absorbed

Question 24

Anemia in B12 and folate deficiency

Answer 24

megaloblastic anemia
larger variation in size
erythroblasts in bone marrow show slowed maturation
hypersegmented neutrophils

Question 25

Normal Hb structure

Answer 25

64.5 kDa 4 globins, 4 heme groups 2 alpha, 2 beta each Hb binds 4 oxygen molecules

Question 26

Hb synthesis

Answer 26

1) protoporphyrin combines with Fe in mit to form heme 2) globin synthesized on polyribosomes 3) globin + heme in cytoplasm

Question 27

Hb gamma chain

Answer 27

synthesis starts in 1st trimester rises to a peak in 2nd and 3rd falls off just before birth gives rise to major Hb in fetus and newborn (HbF - alpha2gamma2)

Question 28

Epsilon and zeta chains of Hb

Answer 28

synthesized in embryonic yolk sac, disappears in first trimester

Question 29

Erythropoietin site of production

Answer 29

Peripheral interstitial cells in the kidney

Question 30

Integral membrane proteins of RBCs

Answer 30

Glycophorin C - anchoring | Band 3 - link plasma membrane to cytoskeleton

Question 31

Peripheral membrane proteins of RBCs

Answer 31

spectrin protein 4.2 ankyrin form lattice framework parallel to membrane dynamically changes shape to accommodate passage of RBCs

Question 32

G6PD

Answer 32

provides reducing power (NADPH) - prevents membrane lipid oxidation - detoxifies oxidants - prevents globin oxidation & denaturation - the only source for reduced glutathione (only protection for oxidative stress)

Question 33

PK in RBC

Answer 33

pyruvate kinase key glycolytic enzyme catalyzes transphosphorylation from PEP to ADP --> yields pyruvate + ATP

Question 34

Red marrow

Answer 34

50% of adult marrow dividing stem cells, precursors of mature blood cells in adults - only in heads of femur and humerus & sternum, ribs, cranium, pelvis, vertebrae (flat)

Question 35

Yellow marrow

Answer 35

50% Of adult marrow inactive dominated by fat cells may be reactivated

Question 36

Components of a bone marrow biopsy

Answer 36

``` framework of reticulin fibers specialized supporting fibroblasts meshwrok of vascular sinuses cords of hematopoietic cells adipocytes (increases with age) ```

Question 37

Key cells in erythropoiesis

Answer 37

1) proerythroblast 2) basophilic erythroblast (early normoblast) 3) polychromatic erythroblast (intermediate normoblast) 4) (late) normoblast 5) reticulocytes 6) mature RBCs

Question 38

RBC maturation

Answer 38

5-7 days to form released into bloodstream as reticulocytes then matures in 24-48 h

Question 39

Lymphocyte maturation

Answer 39

T - differentiate and mature in thymus | B - develop in bone marrow

Question 40

Factors that affect hepcidin production

Answer 40

``` Iron stores, circulating iron - bone morphogenetic protein senses iron - transferrin receptor, HFE (iron sensors on cell surfaces) Erythropoiesis & hypoxia - erythropoietin, erythroferrone Inflammation -IL6 ```

Question 41

effects of hypoxia on iron availability

Answer 41

1) kidney produces epo 2) erythroblasts produce erythroferrone 3) downregulate hepcidin in hepatocytes 4) increased iron availability

Question 42

TIBC in different disease states

Answer 42

Goes up in iron deficiency (transferrin goes up) Iron overload - increases up to 50% but not 100% Anemia of chronic disorders - reduced TIBC

Question 43

Serum ferritin in different states

Answer 43

Anemia of chronic disorders - increased, iron trapped in cells Low ferritin = diagnostic of iron deficiency