Red Blood Cells, Anemia, and Polycythemia

Dr joe okurut
Mmed phy mak
Phd candidate neurology
Function of Red Blood Cells

Transport of Hemoglobin

Transport of Carbon Dioxide

Acid-base buffer
Definitions
Hematocrit: % volume of blood that is red cells
Men ~45%
Women ~40%

Hemoglobin:
34 gm/100 ml red cells
15-16 (male) gm Hb/100 ml blood
13-14 (female) gm Hb/100 ml blood

Oxygen carrying capacity:

gm Hg/100 ml blood * 1.34 ml O2/gm Hb
~21 ml O2/ 100 ml blood for men
~19 ml O2/ 100 ml blood for women
 Normal Values
WBC count x 103 7.8 ± 3
RBC count x 106 5.4 ± 0.7 male
x 106 4.8 ± 0.6 female
Hemoglobin 16 ± 2 male
14 ± 2 female
hematocrit 47 ± 5 male
42 ± 5 female
RBC indices
MCV fl 90 ± 9
MCH pg 32 ± 2
MCHC % 33 ± 3
RDW-sd fl 42 ± 5
Platelet count x 103 140-440
 Normal Distribution of RBC Volumes

% Occurrence
Normal Red Cells

70 80 90 100 110 120 130

MCV
 Increased RBC Volumes

% Occurrence

70 80 90 100 110 120 130

MCV
 Increased Distribution of RBC Volumes

% Occurrence

70 80 90 100 110 120 130

MCV
Regulation of Red Cell Mass

Balance between production and destruction

~ 1% produced/day ~ 1% destroyed/day

Produced in bone marrow

sternum, pelvis, vertebrae, ribs

Production regulated by erythropoietin

Sites Of Hemopoietic Activity

Bone marrow
Yolk sac
Vertebra
Liver

Sternum

Rib

Spleen
Femur

Tibia

1 3 20
FETAL MONTHS ADULT
 Genesis of Blood Products

CFU-T T-Cell

B-Cell
CFU-B
Pluripotent Lymphoid
Stem Cell Stem Cell
eosinophil
CFU-Eosin

basophil
CFU-Bas
neutrophil
monocyte

CFU-GM macrophage

Myeloid platelets
Stem Cell CFU-MEG

BFU-E
erythrocyte
Copyright © 2006 by Elsevier, Inc.
Normal and Abnormal Production of RBCs

Figure 32-3; Guyton & Hall

Erythropoietin
Hormone released from kidney in response to low renal oxygenation

Stimulates stem cells to form pronormoblasts

Promotes release of reticulocytes

Red cell production increases within 24 hours

Erythropoietin life span is 4-12 hours

Increase in red cell number in 5 days

Erythropoietin
Produced in peritubular interstitial cells of the kidney

Produced in the liver ~10%

No preformed stores of erythropoietin

Erythrocytosis suppresses erythropoietin production

but does not abolish it

Erythropoietin is always present in the plasma

Destruction of Red Blood Cells

< 100 days survival hemolysis

Decrease in enzyme activity, ATP levels, and MCH
Decreased deformability (spherocytosis)
Binding by IgG
Ingested by macrophage in spleen
extravascular hemolysis
Iron release to transferrin
Hemoglobin excreted as bilirubin
 Iron Metabolism

• 7 mg/1000 calories ~ 10% absorbed, 1-1.5 mg/day

• absorption enhanced by meat, poultry, fish
• inhibited by carbonates, tannate (tea), oxalate (spinach,
rhubarb), phosphates (vegetables), clay
• duodenum and upper jejunum major site absorption
• HCl promotes absorption
• loss 1 mg/day males average
• menstruating women additional 14 mg/period loss
Daily Iron Requirements

Fetus

5
menstruation
Red cells
mg/day

Pregnancy
 Iron Metabolism
Muscle
Macrophage Parenchymal cells

1-7
C
RB

da
ys
of
th
a
De

Fe++ (ferrous) GUT

Circulating RBCs
Transferrin

Functional Iron
Marrow Hepatocytes
Storage Iron
Copyright © 2006 by Elsevier, Inc.
 Iron Transport and Storage
• Transferrin
• Two iron binding sites
• Responsible for pink color of plasma
• 1/3 of sites are occupied, TIBC = 300 ug/ml, 30%
saturation, 100 ug/ml
• Ferritin
• 30% of total iron
• Hemosiderin
• Water insoluble
Reticulocyte Index
Retic = relative percent of cells that are reticulocytes
Need to correct to get absolute percentage

RI= Retic (%) * Hc(patients)/Hc (normal)

Hc = 50 Hc = 25
Retic = 1% (50,000/ul) Retic = 2% (50,000/ul)
 Anemia

Hypoproliferative Maturation Hemorrhage/

RI = low Disorders Hemolysis
RI = low RI = high

Marrow Damage Cytoplasmic Blood loss

defects
Stimulation Thalassemia Intravascular hemolysis
Renal disease
Inflammation Nuclear maturation Autoimmune
Metabolic disease
defect
Folate deficiency Metabolic membrane
Iron deficiency Vit B12 deficiency
Hemoglobinopathy
 Classification of Anemias
MCV Hgb Content Causes
(fl) (MCHC) (g/dl)

Normocytic Normochromic Bone marrow failure, renal

(80-100) (32-36) disease, hemolytic anemia

Macrocytic Normochromic Megaloblastic anemia

(>100) (32-36)

Microcytic Hypochromic Iron deficiency, chronic

(<80) (<32) diseases
 Hypoproliferative
• Aplastic anemia
• Primary
• idiopathic
• Secondary
• Drugs - chemotherapy, antibiotics, antidepressants,
ethanol
• Chemicals - benzene
• Radiation
• Immune suppression of stem cell
• Malignancy (non-hematopoietic tumors and
transformation of hematopoietic stem cells)
• Therapy
 Hypoproliferative
• Reduced erythropoietin response
• Acute inflammatory state
• acute, chronic bacterial infections
• AIDS
• Renal Disease
• Hypometabolic state
• protein deprivation
• endocrine deficiency
• hypothyroidism
• hypopituitarism
• Therapy
 Hypoproliferative
• Iron deficiency
• almost always blood loss
• exceptions (children, adults poor absorption)
• Men and post menopausal women
• GI blood loss
• depletion of stores
• decrease iron - microcytic, hypochromic
• major deficiency misshapen RBCs
 Anemia

Hypoproliferative Maturation Hemorrhage/

Disorders Hemolysis

Marrow Damage Cytoplasmic Blood loss

defects
Thalassemia Intravascular hemolysis
Stimulation Iron Deficiency
Renal disease Autoimmune
Inflammation
Metabolic disease Nuclear maturation
Metabolic membrane
defect
Folate deficiency
Vit B12 deficiency Hemoglobinopathy
 Maturation defects

• Thalassemia
• South European, African, Asian
• defect in hemoglobin synthesis
• microcytic, hypochromic
• transfusions, folic acid
Megaloblastic Anemias
Large fragile red blood cells
Impaired DNA synthesis
Increased utilization
Folic Acid Deficiency
Inadequate diet, Dialysis, cirrhosis, vegetarian
Impaired absorption
Folate very heat labile
Vitamin B12 Deficiency
Inadequate diet
Dialysis
Impaired absorption
Intrinsic factor (glycoprotein secreted by gastic parietal cells)
(Pernicious anemia)
 Anemia

Hypoproliferative Maturation Hemorrhage/

Disorders Hemolysis

Marrow Damage Cytoplasmic Blood loss

defects
Thalassemia (globin defect) Intravascular hemolysis
Iron Deficiency Iron Deficiency
Immune
Nuclear maturation
Stimulation Membrane
defect hereditary spherocytosis
Renal disease Folate deficiency
Inflammation Vit B12 deficiency Hemoglobinopathy
Metabolic disease
 Hemolytic, Blood Loss

• Hereditary
• Sickle cell (hemoglobin)
• Spherocytosis (membrane)
• Acquired
• Microangiopathic hemolytic anemia
• Immune responses, mismatch typing
• Blood Loss
Polycythemia
Three Pathophysiological Categories of Polycythemia
1.Relative Polycythemia (Red Blood Cell Mass Normal, Plasma Volume Decreased)
2.Secondary Polycythemia (Red Blood Cell Mass Increased)
3.Polycythemia vera (Red Blood Cell Mass Increased)

Polycythemia Secondary Polycythemia

Vera
Pathophysiology Stem Cell Disorder Tissue hypoxia increasing EPO
production or due to renal or hepatic
disease causing inappropriate increase
in EPO production
CBC Hct and often WBC and Only Hct is increased
platelets are increased

EPO level Decreased or low normal Normal or increased

Treatment Phlebotomy Treatment not required