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 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
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
K+
K+
ATP
Na+
Na+
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
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)
• Serum bilirubin is
unconjugated
• Urobilinogen in urine
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
NADPH
G S S G
2G SH + Hb
S
NADP
2G
Hb
S
2G SH +primaquine
SH
2Hb SH + G S S G
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
Heme synthesis
Harrison’s
Fig. 346-1
Heme synthesis. Marks
Marks
Fig. 41.5
Gene
Harrison’s Fig. 346-2
Porphyria
Cutanea
Tarda
George III
Precipitating Factors
• Drugs
• Increase in Heme Synthesis
• Fasting or low carbohydrate intake
Treatment
• Heme
• Glucose
• Analgesics
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
Patient
Normal
1.9
5
volume, liters per 24 h
0.3
2.5
pH
7.0
1.5
45
<4
Red blood cells, x 10 12/l
Gastric secretion
Urine methylmalonate, mg
per 24 h
Herbert B: Red Blood Cells
B12 and
folate
Harrison’s
Fig.107-2
Methionine
Synthase
“ folate trap”
Methylmalonyl CoA mutase
From ß-oxidation
B12
L- Methylmalonyl CoA
Succinyl CoA
Methylmalonate in urine
To TCA cycle
and/or Heme biosynthesis
B12
absorption
Harrison’s
Fig. 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: Susan
History
• Heavy menstrual
bleeding
• Low fat diet-avoids
red meat
• “mature” multivitamin, mineral
supplement
Presenting Symptoms
• Feels “great”
• Ice chewing
Susan: Laboratory Results
Susan
Normal
11.3
12.0 - 15.0
Hematocrit (%)
30
36 – 44
Ferritin (ng/ ml)
4.3
13 - 300
Hemoglobin (g/dl)
Susan: Physical Exam
• Physical exam unremarkable
• Normal PAP and mammogram
• Urine and stool 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:325 mg (60 mg iron) PO with each
meal tid
• 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
Bilirubin Metabolism
Marks
Fig. 41.7
Normal Blood Smear
Glycolysis
Harrison’s
Figure 108-3
Red Blood Cell Membrane
Harrison’s Figure 108-2