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

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

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

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

Peter T: Red Blood Cells Spherocytes Osmotic fragility

Osmotic Fragility Harrison’s Figure 108-1

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

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

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

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

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

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.

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

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

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

pedigree

Harrison’s Fig Heme synthesis

Marks Fig Heme synthesis. Marks

Harrison’s Fig Gene

Porphyria Cutanea Tarda

George III

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

Treatment Heme Glucose

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

Herbert B.: Laboratory Results

Herbert B: Red Blood Cells

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

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

B 12 absorption Harrison’s Fig

Herbert B.: Treatment IM injections of B 12 monthly

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

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

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

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

Iron Metabolism Harrison’s Fig

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

Treatment Iron supplements Nutrition education

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

Marks Fig Bilirubin Metabolism

Normal Blood Smear

Glycolysis Harrison’s Figure 108-3

Red Blood Cell Membrane Harrison’s Figure 108-2

Anemia Harrison’s Figure 61-4

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

Glucuronide Formation Harrison’s14th ed Figure 45-2

Hereditary Spherocytosis