Lecture 41 - Anemias

Hematological Diseases

Diseases of Red Cells

Diseases of Platelets & Coagulation Proteins

Diseases of White Cells

Leukemias

anemias Bleeding /Thrombosis Myeloproliferative Diseases

Multiple Meyloma

Red blood cells = Erythroid cells = Erythrocytes • Most abundant cells in blood • RBC count: 4.5-6.5 x 1012 / L • Red cells: disc shape, biconcave • Do not have a nucleus • Colored red because of presence of hemoglobin

Red Blood Cells - Site of Production Bone marrow process called = Erythropoeisis (Erythropoeisis = synthesis of red blood cells’precursors marrow)

Formation of Red Cells - Erythropoiesis

stem cell

polychromatophilic erythroblast

late stem cell

proerthroblast (pronormoblast)

orthocromatophilic orthochromatic erythroblast erythroblast (Normoblast) extruding its nucleus

basophilic erythroblast

reticulocyte (polychromat ophilic erthrocyte)

mature red cells

Erythropoiesis • •

the development of mature red blood cells (erythrocytes). The first cell that is morphologically recognizable as specifically leading down the red cell pathway is the proerythroblast .

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As development progresses, the nucleus becomes smaller and the cytoplasm becomes more basophilic

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As the cell begins to produce hemoglobin, the cytoplasm attracts both basic and eosin stains, and is called a polychromatophilic erythroblast . The cytoplasm eventually becomes more eosinophilic, and the cell is called an orthochromatic erythroblast

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This orthochromatic erythroblast will then extrude its nucleus and enter the circulation as a reticulocyte . Reticulocytes are so named because these cells contain reticular networks of polyribosomes.

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As reticulocytes loose their ribosomes they become mature red blood cells.

Erythropoiesis

Functions of Blood: • Distribution of nutrients, hormones and O2 • Transport medium for metabolic wastes • Transport medium for specialized defense cells

Blood = connective tissue

extracellular matrix: Plasma

specialized cells: (Formed elements) RBCs  WBCs Platelets

RBCs = Erythrocytes Most abundant blood cell: 1000 RBCs/1 WBC No nucleus = anucleate

Lifespan ~ 120 days

Erythropoiesis – Growth Factors

Erythropoiesis – Growth Factors • Erythropoietin – (EPO) is the hormone produced by kidney to stimulate RBC production

Regulation of Red Cell Production Kidney

Bone Marrow Epo mRNA Epo

Multi-potent stem cell Erythroid stem cell

Oxygen sensor 3-4 days

Blood vessel

Peripheral blood RBC survival 120 days

RBC Shape Disc shape

RBC in capillaries

Fig 20­2

Hemoglobin: A complex protein, composed of heme + globin (2α + 2β) chains Carries oxygen from lungs to tissues and CO2 from tissues to lungs

Hemoglobin (Hb) β

Fe ion in heme group reversibly binds O2

How many oxygen molecules can 1

α

haem globin chains

Haem= protoporphyrin ring+ iron

Heme Synthesis

+ globin

Red Cell Metabolism (Anaerobic Glycolysis)

Anemia - Definition Reduction below normal of Hb and/or hematocrit appropriate for age and ethnic group Males: 135 – 165 g/L Females : 12-14 g/L

Anemia- Physiologic Definition

Decrease in oxygen carrying capacity and thus oxygen availability to tissues

Anemias Clinical Consequences Of Anemia Depends On: ** Hemoglobin concentration (the reduction in the oxygen carrying capacity of the blood) **The rapidity with which the anemia has developed **Age of the patient ** The compensatory mechanisms of the body ** The underlying cause of the anemia

Anemia Acute

symptoms develop quickly over a short period of time

Chronic

as chronic IDA ( iron defficiency ) , Pernicious anemia patients can tolerate lower levels of Hb

Symptoms and signs of Anemia Fatigue , palpitations , headaches Dizziness Dyspnea on exertion Pallor of skin and mucous membranes Chest pains and angina Features specific to underlying cause

Adapting to Anemia The body can adapt to decrease in O2 carrying capacity by: Hb gives O2 more readily to tissues by increase in 2,3DPG

Adapting to Anemia As a compensatory measure, heart rate increases ( tachycardia ) as well as respiratory rate (tachypnea). This occurs at rest or with small exertion

Oxygen Dissociation Curve of Hb

Anemia-Classification 1: Based on cause 2: Morphologic: red cell size: microcytic / normocytic/ macrocytic 3: Pathophysiologic: decreased production, increased destruction, blood loss and sequestration 4: Inherited (congenital) , acquired

Classification of anemia based on cause : 1) Anemia due to blood loss from stomach, G.I tract, trauma, etc. 2) Nutritional anemia Iron deficiency anemia Megaloblastic anemia 3) Hemolytic anemia Red cell membrane disorders Red cell enzyme disorders Hemoglobinopathies 4) Bone marrow disease bone marrow failure (Aplastic anemia) bone marrow infiltration (leukemia / malignancy) 5) Anemia due to systemic illness liver / kidney disease / ACD

Blood Loss • Acute or chronic • Can be – internal: joints, trauma, hematomas – external: GI, renal, menses, bleeding disorder

• symptoms are mainly secondary to hypovolemia • Clinical features – pallor - usually noticed by observer who has not seen child recently – may be hard to recognize if chronic

Blood Loss- Evaluation • CBC (if blood loss is acute, anemia is usually normocytic, normochromic) • If bleeding causes chronic iron deficiency, anemia would be hypochromic, microcytic • PT, PTT • Blood type and cross match

Treatment • If bleeding massive or life-threatening: – IV access, start fluids – control active bleeding – IV albumin while waiting for blood (no longer in practice)

• If in shock: give O negative blood

Anemia- Morphologic Classification • microcytic: iron deficiency, lead toxicity and thalasemia • normocytic: blood loss, hemolysis, chronic disease, infiltrative, sequestration • macrocytic: Vit B12 and folate def, liver disease, hemolysis, uremia, drugs, hypothyroid, aplastic anemia, dyserythropoeisis

Anemia-Decreased Production • decreased substance/nutrient: iron, B12, folate, protein (ascorbic acid) • bone marrow suppression: congenital abn (aplastic), infection (parvovirus), drugs, asphyxia, chronic disease • bone marrow replacement: malignancy, bony (osteopetrosis), infiltrative (mylofibrosis) • dyserythropoiesis: sideroblastic anemia

Anemia-Loss • sequestration – spleen, hemangiomas

Hemolytic Anemia Hemolysis : short red cell life span (normal = 120 days) = premature red cell breakdown

Hemolytic Anemias Inherited / Congenital causes 1. Membrane Disorders: – Spherocytosis, Elliptocytosis

1 2 3

2. Hemoglobin Disorders: – Hemoglobinopathies - Sickle cell, HbC etc. – Thalassemia Syndromes - α, β, δ

3. Enzyme disorders: – G6PD, PK deficiency

Hemolytic Anemias Acquired causes • Autoimmune (cold & warm antibody) • Mechanical, drugs & toxins • Transfusion reaction

Laboratory Evaluation of Anemia • Complete blood count • Reticulocyte count • Peripheral smear

CBC Hematology Analyzer

CBC : Complete Blood Count

MCV=

mean cell volume

determines size of red cell MCH = (mean cell hemoglobin) MCHC = (mean cell hemoglobin concentration) (MCH & MCHC determine color or amount of Hb in red cell)

Blood Smear / film