red cells menwomen hemoglobin (g/l)140-180120-160 hematocrit (%)40-5236-48 red cell count (10 12...
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Red cellsMen Women
• Hemoglobin (g/l) 140-180 120-160• Hematocrit (%) 40-52 36-48• Red cell count (1012/l) 4.5-6.5 3.9-5.6
• Reticulocyte count (%) 0.5-1.5• Mean cell volume (fl) 80-95• Mean corpuscular hemoglobin (pg) 27-33• Mean corpuscular hemoglobin concentration (gm/dL) 33-37
Red cellspathological conditions: I. decrease in the circulating red cell mass
(poss. with structural abnormalities)very common - anaemia
II. increase in the circulating red cell massless commonpolycythemia =erythrocytosis=polyglobulyreactive – low levels of oxygen in the PB (heart disease, high altitude)neoplastic – polycythemia vera = chronic myeloproliferative disease
Anaemiadecrease in the total circulating red cell mass
(hematocrit, hemoglobin concentration)
Classification: A. underlying mechanism
blood loss
increased destruction
decreased production
B. morphology of erythrocytes
size (micro-, macro-, normocytic)
shape (spherocytosis, stomato-,...)
color (degree of hemoglobinization:normo- hypo-, hyperchromic)
Acute
• Hypovolemia – shock
• Anemia – normocytic normochromic
• Shift of water – hemodilution –↓ hematocrite
• Compensatory increase of red cell production
• Reticulocytes
• Chronic
• hypochromic sideropenic anemia
Blood loss•acute or chronic•internal or external
Iron deficiency anemia• body iron = functional + storage;
• F - 2g, M - 6g
• 1. Lack in diet, low absorption
• 2. Increased requirement
• !!!3. Chronic blood loss!!! - GIT, GYN
The internal iron cycle
Plasma iron bound to transferrin transported to the marrow,transferred to developing red cells, incorporated into hemoglobin.Mature red blood cells released into the circulation, after 120 daysingested by macrophages in RES, iron extractedfrom hemoglobin, returned to the plasma.
PB: ery pale + small
BM: erythroid hyperplasia, loss of iron
alopecia, koilonychia, atrophy of tongue, gastric mucosa
Plummer-Vinson syndrome: siderop.an., atrophic glossitis, esophageal webs
Hypochromic microcytic anemia of iron deficiency
Small red cells - narrow rim of peripheral hemoglobin. Scattered fully hemoglobinized cells - blood transfusion,
Iron deficiency anaemianail beds palenails flattened, brittle
Iron deficiency anaemiakoilonychianails concave, ridged, brittle
Iron deficiency anaemiaangular cheilosisfissuring and ulceration
Iron deficiency anaemiaflattening and loss of papillaebald , fissured tongue
Increased destruction=lysis of red cells=hemolysis• intravascular – rare (mechanical injury – artificial
valves or microthrombi, exogenous toxic agents, complement fixation (transfusion of mismatched blood)
• Extravascular - more common, when red cells considered foreign or less deformable
Hemolytic anemiaAbnormality: intracorpuscular or extracorpuscular hereditary (intra) or acquired (extra)
Hemolytic anemia• premature destruction of red cells
• accumulation of the products of the hemoglobin catabolism
• BM – increased erythropoiesis, extreme: extramedullary hematopoiesis
• PB: reticulocytosis
• high bilirubin –gallstones; jaundice, blr in urine
• chronic duration: hemosiderosis
• splenomgaly
Increased destruction of ery=hemolysisI. Intrinsic
A. hereditary • membrane – cytoskeleton, lipid synthesis• enzymes – deficiencies - G6PD, glutathione
synthetase, pyruvate kinase• hemoglobin - deficient synthesis of globin,
structurally abnormal HbB. acquired
• membrane defect: paroxysmal nocturnal hemoglobinuria
• II. Extrinsic• antibodies, trauma, infection, chemical injury
sequestration
Pathophysiology of hereditary spherocytosis
Mutations weakening interactions involving α-spectrin, β-spectrin, ankyrin, band 4.2, or band 3 cause the normal biconcave red cell to lose membrane fragments and become sphericalspherocytic cells: less deformable than normal, become trapped in the splenic cords, phagocytosed by macrophages.
Red cell membrane cytoskeleton Alterations leading to spherocytosis and hemolysis
Table 13-2. Adult Reference Ranges for Red Blood Cells*
A red cell squeezing from the red pulp cordsinto the sinus lumen. Note the degree of deformability required for red cells to passthrough the wall of the sinus.
Splenic sinus
Hereditary spherocytosis (peripheral smear)
anisocytosis and several dark-appearing spherocytes with no central pallor. Howell-Jolly bodies (small dark nuclear remnants)
Hereditary stomatocytosis
Akanthocytosis
Hereditary elliptocytosis
Hereditary elliptocytosis
Enzyme deficiency: G6PD deficiency effects of oxidant drug exposure (PB)
Red cells with precipitates of denatured globin (Heinz bodies)splenic macrophages pluck out these inclusions → "bite cells"
Pathophysiology of sickle cell anemia
Sickle cell anemia (PB)
Splenic remnant in sickle cell anemia
Pathogenesis of β-thalassemia major
aggregates of unpaired α-globin chains not visible Blood transfusions correct the anemia reducethe stimulus for marrow expansion,but add to systemic iron overload
Decreased productiondisorders of proliferation and differentiation stem cells erythroblasts
Impaired: DNA synthesis – B12, folic acid hemoglobin synthesis - heme
(lack of iron)
- globin others
Vitamin B12
absorption
Megaloblastic anaemia
Acute leukaemia
Megaloblastic anaemia - perniciouslemon-yellow appearancepallor (anaemia) + jaundice (ineffective erythropoiesis)
Pernicious anaemia (38 ys.)premature greying, blue eyes, vitiligo
Megaloblastic anaemiaspontaneous bruising
Pernicious anaemiaspinal cord demyelination
Stomachnormal atrophy - pern. an.
Coeliac disease - jejunum
normal villi subtot. villous atrophy
Aplastic anemia Markedly hypocellular marrow
contains mainly fat cells.
Raynaud phenomenonautoimmnune haemolytic anaemia
Sideroblastic anaemia (Perl´s stain)collars of iron granules around the nucleus
Anemia of chronic disease
*Infections
*immunologic
*neoplasms
Mechanism: defect in reutilization of iron (transfer, cytokines]
! abundant storage iron
Anemia: normo, normo or hypo, micro
Aplastic anemia• Failure or suppression of myeloid stem cell
• PANCYTOPENIA
• primary OR secondary - drugs , chemicals
infections
irradiation
inherited
BM: hypocellular, PB: pancytopenia, symptoms
spleen normal
Fanconi anemia
AR,
defective DNA repair
anomalies – bones, kidney, spleen
Pure red cell aplasia
• Isolated absence of red cell precursors
acute OR insidious
drug, virus thymoma
aplastic crisis
Other forms of marrow failure
• Myelophthisic an. - space occupying lesions
(meta, TBC]
• diffuse liver disease, chronic renal failure