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. MegaloblasticC. Iron Deficiency

Case 1:Peter T.

History– Back Pain

– Biliary Colic

– Gallstones (bilirubin pigment)

Presenting symptomsMalaise

Palpable spleen

Anemia

Jaundice

Peter T. Laboratory Results

Red Blood Cells, x 1012/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

Bilirubin

UnconjugatedMade in tissues

Insoluble in plasma

Bound to albumin

Elevated in hepatic disease

Elevated with hemolysis

ConjugatedMade in the liver

Soluble

Direct

Elevated in biliary disease

Peter T: Red Blood Cells

• Spherocytes• Osmotic fragility

Osmotic FragilityHarrison’s Figure 108-1

Red Blood Cell Shape

Maintenance of electrolyte gradients– Fine architecture of the membrane– Supply of ATP

ATP

K+

Na+Na+

K+

Peter T: Post splenectomy

• Laboratory Values return to normal

• Patient feels better

Red Blood Cells, x 1012/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)

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 1012/L 3.5 (5)

Reticulocytes, % 12 (0.5-1.5)

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 1012/L 5 (5)

Reticulocytes, % 4 (0.5-1.5)

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. 346-1

Heme synthesis

MarksFig. 41.5

Heme synthesis. Marks

Harrison’s Fig. 346-2

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 ResultsPatient Normal

Red blood cells, x 1012/l 1.9 5

Gastric secretion

volume, liters per 24 h 0.3 2.5

pH 7.0 1.5

Urine methylmalonate, mgper 24 h

45 <4

Herbert B: Red Blood Cells

B12 and folate

MethionineSynthase

“ folate trap”

Harrison’sFig.107-2

Methylmalonyl CoA mutase

L- Methylmalonyl CoA Succinyl CoAB12

Methylmalonate in urine

From ß-oxidation

To TCA cycleand/or Heme biosynthesis

B12 absorption

Harrison’sFig. 107-1

Herbert B.: Treatment

IM injections of B12 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. 105-1

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. MegaloblasticC. Iron Deficiency

MarksFig. 41.7

Bilirubin Metabolism

Normal Blood Smear

Glycolysis

Harrison’sFigure 108-3

Red Blood Cell MembraneHarrison’s Figure 108-2