animias

1. animias

2. Anemia • Defined as a reduction in one or more of the major RBC measurements: • Hgb: measures the concentration of the major oxygen carrying pigment in whole blood • Hct: percent of a sample of whole blood occupied by intact RBCs • RBC Count: number of RBCs contained in a specified volume of whole blood • All factors are dependent on the RBC mass and the plasma volume

3. Signs and Symptoms of Anemia • Dependent on the degree of anemia, the rate at it evolved, and the oxygen demand • Normally, RBCs carry oxygen linked to Hgb from the lung to tissue capillaries, where oxygen is released • Symptoms result from decreased oxygen delivery or acute blood loss (hypovolemia) • Compensatory mechanisms allow one to tolerated lower levels of Hgb/Hct • Increase in stroke volume, HR ( increased CO) • Enhanced oxygen extraction by the tissues

4. Anemia: History • Is the patient bleeding? • NSAIDs, ASA • Past medical history of anemia? Family history? • Alcohol, nutritional questions • Liver, renal diseases • Menstrual history if applicable • Ethnicity • Environmental/work toxins (ie lead)

5. Symptoms of Anemia • Decreased O2 delivery • Hypovolemia if acute loss • Exertionaldyspnea, fatigue, palpitations, “bounding pulses” • Severe: heart failure, angina, MI • “Pica”– craving for paper products • Pagophagia– craving for ice

6. Signs of Anemia • Tachycardia, • Pallor • Jaundice • Koilonychia or “Spoon nails” • Splenomegaly, lymphadenopathy • Petechiae, ecchymoses • Atrophy of tongue papillae • Guaiac

8. Pallor Koilonychia or “Spoon nails

9. Approach to Anemia • Classification: • Kinetic Approach –mechanism responsible • Decreased RBC production • Increased RBC destruction • Blood Loss • Morphologic Approach – alteration in RBC size • Macrocytic • Normocytic • Microcytic

10. Kinetic Approach • Decreased RBC Production • Lack of nutrients (Fe, B12, Folate) due to diet, malabsorbtion • Bone Marrow Disorders • Bone Marrow Suppression • Drugs, chemotherapy, radiation • Low levels of trophic hormone levels which stimulate RBC production • Epo, Thyroid Hormone, Androgens • Chronic disease/inflammation • Causes decreased Fe absorbtion from GIT, decreased Fe release from macrophages, reduction of Epo

11. Kinetic Approach • Increased RBC Destruction • Inherited and acquired hemolytic anemias • Inherited: Hereditary Spherocytosis, sickle cell disease, thalassemia • Acquired: • Blood Loss • One of the most common causes of anemia • Not only lose RBCs, but also the Fe in these cells, which leads to Fe deficiency

12. Morphologic Approach • Macrocytic • Reticulocytosis • Drugs interfering with nucleic acid synthesis • Abnormal nucleic acid metabolism of erythroid precursors • Abnormal RBC Maturation • liver disease, hypothyroidism • Normocytic • Microcytic • Reduced iron availability • Reduced Heme synthesis • Reduced globin production

13. Lab Evaluation • CBC • Reticulocyte Count: • High: hemolysis or blood loss • Low: deficient production of RBCs (reduced marrow response to anemia) • RBC Indices: • MCV – mean corpuscular volume (Hct/RBC) • MCH – mean corpuscular Hgb (Hgb/RBC) • MCHC – mean corpuscular Hgb concentration (Hgb/Hct)

14. Hemolytic Anemia

15. Hemolytic Anemia • Anemia due to shortened survival of circulating RBCs (Normal: 110-120 days) • Hemolysis <100 days • With intact bone marrow: • Anemia  Compensatory increase in Epo secretion  Enhances RBC production (reticulocytosis)  Reduces degree of anemia • This is most commonly seen with hemolytic anemia, but not specific to hemolysis (can also be seen with acute blood loss)

16. Reticulocyte Count • Relative reticulocyte count • % of all RBC (normal 0.8-1.5%) • Absolute reticulocyte count • Relative reticulocyte count x RBC count • Normal 50,000-75,000/µl • Examples: 1.1% x 4.96 x106 = 55,000/ml 12..2% x 2.05 x106 = 250,000/ml

17. Causes of Hemolysis - Intrinsic • Generally, a hereditary disorder • Intrinsic hemolysis is caused by defects in Hgb, RBC membrane or metabolic factors needed to generate ATP • Examples • Thalassemia (defect in alpha or beta globin chains) • Spherocytosis (missing RBC membrane proteins) • G6PD deficiency (abnormality in reducing power (NADPH))

18. Causes of Hemolysis - Extrinsic • Acquired disorder • Causes include: • Ab directed against RBC membrane components • AIHA (Auto Immune Hemolytic Anemia), delayed transfusion reaction • Stasis/trapping/destruction in spleen (hypersplenism) • Trauma • Prosthetic heart valve • Exposure to compounds with oxidant potential • Sulfonamide in those with G6PD • Destruction of RBC by pathogens • Malaria, babesiosis

19. Site of Hemolysis • Dependant on the severity and type of cell alteration (alteration in RBC membrane) • Severe damage  immediate lysis in the circulation (INTRAVASCULAR) • Less severe damage  cell destruction is via the monocyte-macrophage system in the liver, spleen, BM, lymph node (EXTRAVASCULAR)

20. Intravascular Hemolysis • Intravascular hemolysis  Release of Hgb into the plasma • Free Hgb binds to haptoglobin  Hgb-haptoglobin complex is taken up by liver  Decrease in plasma haptoglobin • Free Hgb breaks down to alpha-beta dimers  filtered by glomerulus  Hemoglobinuria

21. Intravascular Hemolysis • Causes: • Shear stress • Mechanical heart valve • Heat damage • Complement-induced lysis • Paroxysmal cold hemoglobinuria • Osmotic lysis • Lysis from bacterial toxins • Clostridium

22. Extravascular Hemolysis • Damaged RBCs are destroyed by liver and spleen

23. Features of Hemolysis • Rapid fall in Hgb • Increased LDH, decreased Haptoglobin • Jaundice (elevated indirect bilirubin) • Splenomegaly • H/o pigmented gallstones • Abnormally shaped RBCs • Reticulocytosis

24. Labs • LDH: elevated • Indirect bilirubin: elevated (due to catabolism of Hgb) • Haptoglobin: decreased • Binds to Hgb and taken up by liver • In a series of reports: • Elevated LDH, low Haptoglobin was 90% specific • Normal LDH, Haptoglobin >25 was 92% sensitive for ruling out hemolysis • Reticulocyte Count: elevated • Normal is 0.5-1.5% • Anemia leads to increase Epo production leading to a reticulocytosis (4-5% increase above baseline)

25. Iron deficiency anemia

26. role of iron in the body Iron have several vital functions • Carrier of oxygen from lung to tissues • Transport of electrons within cells • Co-factor of essential enzymatic reactions: • Neurotransmission • Synthesis of steroid hormones • Synthesis of bile salts • Detoxification processes in the liver

27. IRON METABOLISM Iron is present in the diet in many forms. Haem is the most important source. Vegans may need to supplement their dietary intake with non-organic iron. A normal adult requires 15-20 mg of iron per day to remain in balance.

28. Iron is normally absorbed by active transport across the wall of the duodenum and upper part of thejejunum. If large amounts of iron are ingested the active transport mechanism is overtaken by passive diffusion.. Disease of the upper small gut can lead to malabsorption of iron, e.g. coeliac disease or tropical sprue.

29. Iron is best absorbed in the ferrous (reduced) form (Fe++). Absorption is improved by reducing substances, e.g. ascorbic acid (vitamin C). Absorption is also increased by certain iron chelators and by alcohol.

30. Iron absorption is normally relative to the needs of the body. About 10% of dietary iron is usually taken up by the body but this can increase several-fold in iron deficiency, or reduce if the body has a surplus.

31. Most iron in the body is in the form of haem; present in large amounts in red cells, muscle and liver where it is essential for oxygen supply. Iron is also present in many enzyme systems, e.g. electron transport systems. The transport and storage of iron mainly involves three proteins: transferrin transferrin receptor (TfR) ferritin

32. Transferrin actively binds and transports iron in the body and can be estimated by measuring the serum total iron binding capacity (TIBC). Transferrin increases in iron deficiency and decreases with iron overload, liver disease, infection, malignancy and protein deficiency.

33. Excess iron is stored mainly in macrophages as haemosiderin; an insoluble protein-iron complex formed by lysosomal degeneration of ferritin. Ferritin is the water soluble protein-iron complex formed when iron combines with apoferritin. Iron in ferritin is in the ferric form (Fe+++) and must be reduced before it can be utilised.

34. LABORATORY INVESTIGATION OF IRON DEFICIENCY ANAEMIA • Full Blood Count • Serum Ferritin • Serum Iron & Total Iron Binding Capacity • Serum Transferrin • Bone Marrow

35. FULL BLOOD COUNT can be suggestive but not diagnostic of iron deficiency. Negative iron balance produces microcytosis (low MCV) and hypochromasia (low MCH). Red cell morphology varies from mild anisocytosis to marked anisopoikilocytosis. Thrombocytosis is common. Leucocytes are usually normal.

36. SERUM FERRITIN is now a standard diagnostic test for IDA; only iron deficiency will give a low result. Normally the level of serum ferritin reflects the body iron stores (100 μg/L = 800 mg of iron). A value <15 μg/L is diagnostic of IDA.

37. Circumstances in which the serum ferritin is normal or high in the presence of IDA: • Liver dysfunction; ferritin is released when hepatocytes are damaged • Increased haem turnover; haemolysis and trauma (including surgery) • Inflammatory lesions; malignancy, infection and inflammation

38. SERUM IRON (SI) and TOTAL IRON BINDING CAPACITY (TIBC) In iron deficiency the SI is low (<10 μmol/L) and the TIBC is usually raised (>70 μmol/L).

39. The SI shows marked diurnal variation. It may also be low in the presence of infection or inflammation. The TIBC is also affected by nutrition and may be low in malnourished persons despite iron deficiency. For these reasons the serum ferritin is now preferred. SI and TIBC are useful when the ferritin is falsely high, e.g. liver damage.

40. In the plasma, iron is bound to transferrin and the TIBC depends on the concentration of this protein. The transferrin to which iron is not bound is known as the unsaturated iron-binding capacity (UIBC). SI + UIBC = TIBC

43. Iron in the body 75% The total body iron in a 70-kg man is about 4 g. This is maintained by a balance between absorption and body losses in the proximal small intestine (duodenum) 10-20% 5-15%

44. At physiological pH, ferrous iron (Fe2+) is rapidly oxidized to the insoluble ferric (Fe3+) form • Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron • If iron are low • hepcidin in the duodenal epithelium is decreased • causes an increase in ferroportin activity • stimulating iron uptake

45. Laboratory findings • CBC; WBC and differential cell count normal or • variable depend on patient condition, • Hb, Hct • RBC morphology => hypochromicmicrocytic cells • platelet => adequate or depend on patient condition • 2. RBC indices => MCV, MCH, MCHC • 3. Reticulocyte count => low related to degree of anemia • 4. Serum iron (SI) , Total iron binding capacity (TIBC) • 5. Serum ferritin • 6. Serum transferrin receptor (sTfR) • 7. % Transferrin saturation

46. Laboratory diagnosis Suspicious Hypochromic microcytic anemia Low Si and ferritin Raised TIBC and sTfR Lab. diagnosis Investigation of cause • 1. For female • Menorrhagia • Pregnancy • 2. For male or • female (1. not found) • GI bleeding • Stool occult blood test • GI endoscopy • Investigation of other causes Treat cause and iron uptake

47. Anemia of Chronic Disease

48. Anemia of Chronic Disease • A normocytic, normochromic chronic anemia due to chronic infections (TB) or chronic inflammations (RA, neoplatic conditions) as well as chronic illnesses (diabetes, liver disease) • Usually mild, progressive and asymptomatic

49. Anemia of Chronic Disease • Etiology • disruption of iron metabolism • defect in red cell production • shortening of erythrocyte life span • Incidence second most common to iron deficiency

50. Diagnostics • Normal to increased iron stores with concurrent low serum iron • serum iron-decreased • TIBC-decreased • serum ferritin-increased • Hemoglobin-decreased • Hematocrit- decreased • MCV? normal • Reticulocytes-decreased