D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 8 - BLOOD & BLOOD DISORDERS I
Chapter 7
1.
Blood Cell Formation (fig. 7 - 1 & ppt. 1):
• hemopoiesis:
- stem cells & progenitor cells - in red bone marrow, stem cells represent source
of all other cells (resemble embryonic cells - not committed to any particular path of
differentiation; each division regenerates stem cell + a progenitor cell that is committed to
a particular line of differentiation
• erythropoiesis - RBC development (from an erythrocyte progenitor) entails
hemoglobin (Hb) synthesis and eventual loss of nucleus and most cytoplasmic organelles; all
RBC enter bloodstream as reticulocytes, which have some ribosomes persisting in
cytoplasm; these mature into erythrocytes in about 3 days; usually 1% of circulating
red cells are reticulocytes; a higher percentage may suggest a recent challenge to
erythropoiesis (ppt. 2)
- nutrients required: iron, vitamins B6, B12 (fig. 7 - 20 & ppt. 3) and folic
acid (+ amino acids); also requires erythropoietin
- erythropoietin mechanism (fig. 7 - 2 & ppt. 4): hypoxia stimulates release of
renal product that causes erythropoietin formation from a plasma protein; erythropoietin
promotes erythropoiesis in bone marrow (ppt. 5)
- red cell lifespan: erythrocytes last about 120 days; replaced by marrow;
disposal by spleen & liver
- recycling hemoglobin of 'spent' red cells (fig. 7 - 19 & ppt. 6): protein
portion (globin) is degraded to amino acids that are recycled; heme group is split into iron
& porphyrin; iron is stored (ferritin), transported to bone marrow (transferrin) (ppt. 7);
porphyrin is converted to bilirubin that is excreted via bile
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- p. 2 -
• leukopoiesis (ppt. 1): granulocytes (neutrophils, eosinophils & basophils) &
monocytes derive from single progenitor; lymphocytes derive from precursors
(immature cells) that migrate to lymphoid tissues; recall that B cells mature in bone
marrow, but T cells mature in thymus; monocytes mature into macrophages when
they enter the tissues, e.g. inflammation sites
- lifespan of WBC: much shorter, lasting from a few hours, days or weeks
(granulocytes), up to 3 months for monocytes; replacement stimulated by various
growth factors, including some originating from inflammation sites
• thrombopoiesis (ppt. 1): progenitor produces giant multinucleated cell
called megakaryocyte, which releases fragments (platelets or thrombocytes) into the
bloodstream; some stored in red pulp of spleen; platelets have only a few days'
lifespan; development stimulated by thrombopoietin from liver
2.
Red Cell Disorders:
• anemias: (= no blood) - reduction in red cell count, or in hematocrit that
compromises oxygen transport; characterized by pallor, weakness, lethargy, &
exercise intolerance; caused by excessive rate of red cell loss or deficiency of red cell
formation (figs. 7 - 18, 7 - 21 & ppts. 8 - 10)
- methods of assessing red cell status of blood: red cell count (average 4 5.5 x 106/cu. mm.), hematocrit (packed cell volume = 45% average) & hemoglobin
(12 - 18 gm./dl.)
- derived values, aid in diagnosing type of anemia (table 7 - 3 & ppt. 11):
- mean corpuscular volume (MCV) (hematocrit divided by red cell count) normal value = normocytic, elevated = macrocytic, depressed = microcytic
- mean corpuscular hemoglobin concentration (MCHC) (hemoglobin
divided by hematocrit) - normal value = normochromic, elevated = hyperchromic,
depressed = hypochromic
- reticulocyte count: > normal suggests challenge to erythropoiesis, e.g.
excessive RBC destruction or significant blood loss
Bio 307/607 lec 8
- p. 3 -
• important causes: iron deficiency - needed for adequate hemoglobin
formation, iron forms part of the heme group (O2 transporting part of hemoglobin);
recycling results in average iron loss of 1 - 2 mg./day (higher in females who are
menstruating) (fig. 7 - 19 & ppt. 7); impaired intake or absorption of iron (unusual in
Western countries) or excessive loss are likeliest causes of iron deficiency; resulting
anemia exhibits small cells (microcytic) and deficient hemoglobin level (hypochromic) (ppt.
11)
- vitamin B12 deficiency - required for DNA synthesis in erythropoiesis;
absorption of B12 is dependent upon intrinsic factor from gastric mucosa (fig. 7 - 20
& ppt. 3), so diseases of stomach (impaired production) or intestinal malabsorption
(impaired uptake) may eventually cause a deficiency; resulting anemia (pernicious
anemia) exhibits large, immature (megaloblastic) cells
- folic acid deficiency - required for DNA synthesis in erythropoiesis;
diseases of malabsorption are likeliest causes; a megaloblastic anemia, similar to
pernicious anemia results
- hemolytic anemias (fig. 7 - 24 & ppt. 10): usually caused by
hemoglobinopathies, e.g. HbS, transfusion reactions, autoantibodies, or, rarely, snake
venom
- high rate of destruction of RBC exceeds marrow's replacement
capability
- sickle cell anemia is most familiar form in the West; genetically
determined abnormality of hemoglobin formation results in HbS, which causes
'sickling' and increased destruction of red cells (hemolysis); higher incidence among
African Americans (0.2%); results from single gene mutation
- thalassemia (disordered synthesis of globin chains) is another type of
anemia (often called Mediterranean anemia) that is caused by hemoglobin defects
(mainly found in people of Mediterranean origin)
- metabolic defects of red cells --> damaged membranes, abnormal enzymes
--> increased fragility (genetic mutations)
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- p. 4 -
- autoimmune hemolysis, hypersplenism, impaired RBC metabolism,
trauma from damaged or obstructed vessels or diseased heart valves
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- p. 5 -
• polycythemias (=large cell # in blood - fig. 7 - 25 & ppt. 12)
- absolute forms (elevated red cell levels in normal plasma volume) relate
to overproduction of RBC by marrow due to elevated erythropoietin, e.g., renal
tumor (secondary polycythemia) or by unregulated elevation of erythropoiesis, e.g.,
bone marrow tumor (primary polycythemia)
- relative polycythemias entail an elevated hematocrit resulting from plasma
losses due to burns, dehydration, diuresis, or diarrhea