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Anemia - General aspects

Anemia - General aspects. Department of Hematology Rui Jin Hospital. Anemia. Most important Related to many diseases Diagnosed properly Treated properly. What is anemia?. A reduction below normal in the - concentration of hemoglobin - red blood cells in the blood

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Anemia - General aspects

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  1. Anemia- General aspects Department of Hematology Rui Jin Hospital

  2. Anemia • Most important • Related to many diseases • Diagnosed properly • Treated properly

  3. What is anemia? • A reduction below normal in the - concentration of hemoglobin - red blood cells in the blood - hematocrit （红细胞比容） • The blood hemoglobin concentration often preferred - accuracy and reproducibility - value most indicative of the patho-physiologic consequences of anemia

  4. Normal range - adult

  5. Conditions associated with a significant disproportion between the hematocrit and RBC? • Spurious anemia (假性贫血) - relative increase in plasma volume hydremia of pregnancy overhydration in oliguric renal failure or congestive heart failure chronic diseases and hypoalbuminemia congestive splenomegaly recumbency (斜卧)

  6. Pronormoblast Normoblasts

  7. Regulation of erythropoiesis • How many are produced? • 25 billion /24 hours • The entering cells are reticulocytes which should be 1% of the total population of circulating erythrocytes • Erythrocytes last 120 days and are destroyed by the spleen • Red cell production should equal red cell destruction

  8. Anemia: Etiologies • Production defects • Blood loss • Blood destruction

  9. RBC loss without RBC Destruction • Hemorrhage - Due to trauma - Due to disorders: e.g.cancer, ulcers, tuberculosis, and irritable bowel syndrome (including ulcerative colitis and Crohn’s disease) • Menstrual flow • Gynecological disorders (e.g. endometriosis) • Pregnancy, especially at gestation • Parasitism - Hookworms

  10. RBC Destruction Intrinsic Abnormalities • Thalassemia • G6PD • Sickle Cell Anemia • Hereditary Spherocytosis Extrinsic Abnormalities • Infections • Malaria (Plasmodiumm species) • Mycoplasma (支原体） • Disseminated Intravascular Coagulation • Lead poisoning

  11. Conditions Associated with Anemias Due to Reduced Erythrocyte Production • Anemias due to decreased erythropoietin production • Renal disease • Endocrine deficiency (pituitary, adrenal, thyroid, testis) • Starvation • Hemoglobinopathy (reduced oxygen affinity) • Anemias due to inadequate marrow response to erythropoietin • Deficiency state (iron, vitamin B12, folate) • Anemia of chronic disease (inflammation, infection, or malignancy) • Sideroblastic anemia • Primary marrow disorders-pure red cell aplasia, myelodysplasia, myelofibrosis, leukemia • metastasis to bone marrow, osteogenic sarcoma

  12. 贫血的病理生理(pathophysiology of anemia) ●RBC的主要功能是输送氧气 ●正常血液一克Hb能携带1.34ml氧 ●贫血的病理生理基础是血液携氧能力减低，组织缺氧 ●机体对缺氧进行代偿和适应机制如下

  13. 贫血的病理生理 • 心脏搏出量增加 • 贫血患者因RBC减少，血液粘度减低和选择性的周围血管扩张，周围血管阻力减低 • 心率加速，循环速度加快 • 为防止对机体供氧量减少，心脏排血量增加

  14. 贫血的病理生理 • 增加组织的灌注 ：贫血时血液供应重新分配，供血减少区域为皮肤组织和肾脏，故皮肤苍白，对缺氧敏感的心肌、脑和肌肉供血量增加 • 肺的代偿机能 ：贫血时呼吸加快、加深、呼吸增强，但这并不能得到更多的氧，这可能是对组织缺氧的一种反应

  15. 贫血的病理生理 • 氧解离曲线右移 • 在缓慢发生的贫血，RBC内2、3二磷酸甘油酸（2、3－DPG）的合成增加 • 2、3－DPG使Hb与氧的亲和力减低 • 促进Hb O2解离曲线右移，使组织在氧分压降低的情况下能摄取更多的氧

  16. Clinical manifestation • First symptom - decreased work tolerance - shortness of breath - palpitations - other signs of cardiorespiratory adjustments to anemia - at times, they feel fine, but their friends or family notes the pallor

  17. The manifestations depend on • The reduction in the oxygen-carrying capacity of the blood • The degree of change in total blood volume • The rate at which these two factors developed • The capacity of the cardiovascular and pulmonary systems to compensate for the anemia • The associated manifestations of the underlying disorder

  18. Cardiorespiratory system • Noticeable only after exertion or excitement • Dyspnea and awareness of vigorous or rapid heart action noted at rest • Shortness of breath, tachycardia, dizziness or faintness, and extreme fatigue • Congestive heart failure, angina pectoris, intermittent claudication （间歇性跛行）

  19. Cardiorespiratory system • Left ventricular hypertrophy • Heart murmurs - systolic in pulmonic area • Electrocardiographic changes - depression of the ST junction - U-shaped deformation of the S-T segment - inverted T waves

  20. The skin • Pallor – most evident sign - dilation of the peripheral vessels - degree and nature of the pigmentation - nature and fluid content of the subcutaneous tissues - jaundice, cyanosis… • Detected most accurately in the mucous membranes of the mouth and pharynx, conjunctivae, lips, and the nail beds, palms of the hands

  21. Tell anemia from the color of the skin… • A waxy, dead whiteness - acute blood loss • A distinctly sallow （灰黄色）color - chronic anemia • A lemon-yellow pallor - pernicious anemia（恶性贫血） • Marked pallor associated with petechiae or ecchymoses（瘀斑） - acute leukemia

  22. Neuromuscular system • Headache • Vertigo • Tinnitus　（耳鸣） • Faintness • Scotomata （盲点） • Lack of mental concentration • Drowsiness • Restlessness • Muscular weakness

  23. Gastrointestinal system • Underlying diseases: ulcer, cancer • Glossitis and atrophy of the papillae of the tongue • Painful, ulcerative, and necrotic lesions in the mouth and pharynx (aplastic anemia, acute leukemia) • Dysphagia (chronic iron-deficiency anemia)

  24. Others • Retinopathy: 20% - flame-shaped hemorrhages • Slight proteinuria • Fever of mild degree • Hemolytic anemia - jaundice - hemoglobinemia, pain in the abdomen or back

  25. Evaluation and diagnosis • Medical History • Physical examination • Laboratory tests • Morphologic features

  26. Medical history • The duration of the symptoms and their onset (insidious/acute) • Family history of jaundice, splenectomy, bleeding disorders, and hemoglobin-associated abnormalities • Occupation, drugs, solvents and other chemicals

  27. Others • Stool habits: neoplasms of the colon and rectum, hemorrhoids • Women: blood lost during menstruation • Child or adolescent: growth rate • Dietary history • Fever: infection, lymphoma, collagen disease, etc. • Bruises, ecchymoses, and petechiae

  28. Physical examination • Icterus 黄疸 (hemolytic) • Sternal tenderness (leukemia) • Lymph nodes enlargements (infection, lymphoma, leukemia, metastatic carcinoma) • Cardiac murmurs (bacterial endocarditis) • Liver, spleen, and kidneys

  29. Morphologic feature • Blood smear • Bone marrow examination

  30. Classification • Impaired erythrocyte production - hypoproliferative iron-deficient erythropoiesis erythropoietic deficiency hypoplastic anemia infiltration - ineffective megaloblastic microcytic • Increased erythrocyte production - hemolytic anemia

  31. Anemia? Survival Destruction? Production? The key test is the …..

  32. The reticulocyte count • Increased reticulocytes (greater than 2-3% or 100,000/mm3 total) are seen in blood loss and hemolytic processes, although up to 25% of hemolytic anemias will present with a normal reticulocyte count due to immune destruction of red cell precursors. • Retic counts are most helpful if extremely low (<0.1%) or greater than 3% (100,000/mm3 total).

  33. Another step of diagnosis Anemia Erythrocyte indices blood smear MCV>100 MCV 80-100 MCV<80 Macrocytic Normocytic Microcytic (大细胞性) (正常细胞性) (小细胞性)

  34. Macrocytic anemias • Vitamin B12 or folate deficiency • Accelerated erythropoiesis - hemolytic anemia • Erythroleukemia (红白血病) • Increased membrane surface - hepatic disease, obstructive jaundice • Refractory anemias - myelodysplastic anemias

  35. Normal, RBC's. They have a zone of central pallor about 1/3 the size of the RBC.). A few small fuzzy blue platelets are seen. In the center of the field are a band neutrophil on the left and a segmented neutrophil on the right.

  36. Note the hypersegmented neurotrophil and also that the RBC are almost as large as the lymphocyte. Finally, note that there are fewer RBCs.

  37. Vitamin B12 deficiency • Dietary deficiency (rare) • Lack of intrinsic factor - pernicious anemia - gastric surgery • Functionally abnormal intrinsic factor • Biologic competition - small-bowel bacterial overgrowth • Drug-induced vitamin B12 malabsorption • Chronic disease of the pancreas • Zollinger-Ellision syndrome • Hemodialysis

  38. Folate deficiency • Dietary deficiency • Increased requirements - alcoholism and cirrhosis - pregnancy - infancy • Congenital folate deficiency • Extensive intestinal resection

  39. Diagnosis • Smear - Macrocytic (High MCV) RBCs, +/- hypersegmented neutrophils, +/- modest neutropenia • B12 - Low serum B12 level • Folate - Serum folate level -- can normalize with a single good meal

  40. Neurological presentation of B12 deficiency • Paresthesias of fingers & toes • Reduced vibration sense (256-Hz) • Ataxia 共计失调 (Combined system disease) • Perversion of taste & smell • Optic atrophy • Dementia (痴呆), Memory Loss & Depression • “Megaloblastic Madness” – Paranoid Schizophrenia • Specific MRI abnormalities

  41. Treatment • B12 deficiency - B12 1 mg/month IM, or 1-2 mg/day po • Folate deficiency - Improved diet, 5mg tablets • Monitor for a response to therapy • Pernicious Anemia – monitor for GI cancers

  42. Food • B12 deficiency • Meat • Eggs • Folate deficiency • Green vegebables • Nuts • Cereal • Fruit • Yeast

  43. Microcytic anemias • Disorders of iron metabolism - iron-deficiency anemia - anemia of chronic disorders • Disorders of globin synthesis - thalassemias - hemoglobin E and C disease • Sideroblastic anemia

  44. The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

  45. Iron Deficiency Anemia vs. anemia of chronic disorders • Smear - hypochromic and microcytic (low MCV) RBCs, usually not seen unless Hct  30% - platelet count is often elevated • Ferritin: a measure of total body iron stores, but also an acute phase reactant - <15g/l = Fe deficiency - 150 g/l = Not Fe deficiency - 15-150 g/l = Not conclusive • Bone marrow - absent Fe stores Gold standard for IDA

  46. Thalassemias • Genetic defect in hemoglobin synthesis -  synthesis of one of the 2 globin chains ( or ) - Imbalance of globin chain synthesis leads to depression of hemoglobin production and precipitation of excess globin (toxic) - “Ineffective erythropoiesis” - Ranges in severity from asymptomatic to incompatible with life (hydrops fetalis) - Found in people of African, Asian, and Mediterranean heritage

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