1. Some Biochemistry I. Metabolism of the Red Blood Cell A. Glycolysis B. Hexose Monophoshate Shunt II. Heme Synthesis and Degradation III. Anemia A. Hemolytic B. Megaloblastic C. Iron Deficiency

2. Case 1:Peter T. History –Back Pain –Biliary Colic –Gallstones (bilirubin pigment) Presenting symptoms Malaise Palpable spleen Anemia Jaundice

3. Peter T. Laboratory Results Red Blood Cells, x 10 12 /L 2.9 (5) Reticulocytes, % 15 (0.5-1.5) Hemoglobin, g/dl 8.0 (14-18) Serum Bilirubin, µmol/L 78 (2-44) Serum bilirubin is unconjugated Urobilinogen in urine

4. Bilirubin Unconjugated Made in tissues Insoluble in plasma Bound to albumin Elevated in hepatic disease Elevated with hemolysis Conjugated Made in the liver Soluble Direct Elevated in biliary disease

5. Peter T: Red Blood Cells Spherocytes Osmotic fragility

6. Osmotic Fragility Harrison’s Figure 108-1

7. Red Blood Cell Shape Maintenance of electrolyte gradients –Fine architecture of the membrane –Supply of ATP ATP K+K+ Na + K+K+

8. Peter T: Post splenectomy Laboratory Values return to normal Patient feels better Red Blood Cells, x 10 12 /L 5.4 (5) Reticulocytes, % 1 (0.5-1.5) Hemoglobin, g/dl 15.7 (14-18) Serum Bilirubin, µmol/L 8.5 (2-44)

9. Case 2: R.P. History Malaria Primaquine prescribed Black urine Weakness Abdominal and back pain Presenting Symptoms Yellow sclerae Weak Anorexic Vomiting

10. R.P. Laboratory Results Serum bilirubin is unconjugated Urobilinogen in urine Red Blood Cells, x 10 12 /L 3.5 (5) Reticulocytes, % 12 (0.5-1.5) Hemoglobin, g/dl 9.2 (14-18) Serum Bilirubin, µmol/L 340 (2-44)

11. R.P.: Red Blood Cells Contain small dark inclusion bodies Polymerized hemoglobin 2Hb-SH +oxidizing agent Hb Hb S S

12. Glutathione Tripeptide consisting of glutamic acid, cysteine (-SH group) and glycine. Protects cells from oxidative damage Requires NADPH for conversion from oxidized to reduced form.

13. Glutathione and NADPH G S S G 2 G SH NADPH NADP 2G SH + Hb Hb 2Hb SH + G S S G S S 2G SH +primaquine reduced primaquine + G S S G

14. R.P.: Ten Days Later Urine is normal color R.P. feels better Discharged from hospital Red Blood Cells, x 10 12 /L 5 (5) Reticulocytes, % 4 (0.5-1.5) Hemoglobin, g/dl 14.5 (14-18) Serum Bilirubin, µmol/L 23 (2-44)

15. Case 3: George III History Attacks of severe pain, excited overactivity, paralysis and delirium. Began in 1765 (age 27) Became frequent by 1788 Presenting symptoms 1811, violently insane blind

16. pedigree

17. Harrison’s Fig. 346-1 Heme synthesis

18. Marks Fig. 41.5 Heme synthesis. Marks

19. Harrison’s Fig. 346-2 Gene

20. Porphyria Cutanea Tarda

21. George III

22. Precipitating Factors Drugs Increase in Heme Synthesis Fasting or low carbohydrate intake

23. Treatment Heme Glucose

24. Case 4: Herbert B. History Progressive anorexia Liquid foods to avoid abdominal pain Presenting Symptoms Loss of weight Weakness Shortness of breath Sore tongue Difficulty with swallowing Epigastric pain Numb, tingling hands Palpitations

25. Herbert B.: Laboratory Results

26. Herbert B: Red Blood Cells

27. B12 and folate Methionine Synthase “ folate trap” Harrison’s Fig.107-2

28. Methylmalonyl CoA mutase L- Methylmalonyl CoA Succinyl CoA B 12 Methylmalonate in urine From ß-oxidation To TCA cycle and/or Heme biosynthesis

29. B 12 absorption Harrison’s Fig. 107-1

30. Herbert B.: Treatment IM injections of B 12 monthly

31. Herbert B.: Summary Loss of weight Weakness Shortness of breath Sore tongue Difficulty with swallowing Epigastric pain Numb, tingling hands Palpitations

32. Case 5: Vincent M. History Abnormal blood values Low dietary intake of iron Presenting Symptoms Short of breath Difficulty climbing stairs Can not work

33. Vincent M.: Laboratory Results Hematocrit % 13.5 (47) Hemoglobin g/dl 5.4 (16)

34. Vincent M.: Physical Exam No abdominal mass Stool and urine are negative for blood

35. Iron Metabolism Harrison’s Fig. 105-1

36. Factors Affecting Iron Absorption Positive –Heme vs. non heme –MFP factor or meat factor –pH- reduction of ferric to ferrous iron –Organic acids-ascorbic, malic and lactic Negative –Phytates –Polyphenols –Fiber –Calcium

37. Treatment Iron supplements Nutrition education

38. Some Biochemistry I. Metabolism of the Red Blood Cell A. Glycolysis B. Hexose Monophoshate Shunt II. Heme Synthesis and Degradation III. Anemia A. Hemolytic B. Megaloblastic C. Iron Deficiency

39. Marks Fig. 41.7 Bilirubin Metabolism

40. Normal Blood Smear

41. Glycolysis Harrison’s Figure 108-3

42. Red Blood Cell Membrane Harrison’s Figure 108-2

43. Anemia Harrison’s Figure 61-4

44. Bilirubin Metabolism Peter T. R.P. Types Figure 45-1 Harrison’s 14th ed.

45. Glucuronide Formation Harrison’s14th ed Figure 45-2

46. Hereditary Spherocytosis