red cells menwomen hemoglobin (g/l)140-180120-160 hematocrit (%)40-5236-48 red cell count (10 12...

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