In this article we will discuss about: 1. Meaning and Special Features of RBC 2. Basic Functions of RBC 3. Structure 4. Genesis 5. Variations 6. Deficiency.
Meaning and Special Features of RBC:
Red blood corpuscles (RBCs) also known as erythrocytes, contains hemoglobin, hence red in color.
RBCs are:
i. Biconcave disc-shaped
ii. Mature red cell have:
a. No nucleus
b. No endoplasmic reticulum
c. No mitochondria
d. No centriole
e. No ribosome
iii. Glucose can be transported into the red cell without insulin.
Advantages of Biconcavity of RBC:
1. Biconcavity increases the surface area of RBC, which facilitates the diffusion of O2
2. RBC can squeeze itself into the capillary more easily.
Basic Functions of RBC:
1. Transport of oxygen and carbon dioxide.
2. Maintenance of pH of blood ― Hemoglobin in RBC acts as an acid-base buffer.
3. Determination of blood group ― Blood group antigens present on the surface of the RBC help in determination of blood group.
Shape and Size:
Functional morphology
Shape – Biconcave disc
Size – Diameter is 7.8 micrometer
Thickness is 2.5 micrometer at thickest point and 1 micrometer at the center.
Surface area – 120-140 µm2
Volume:
80 µm3
Normal Count:
Men – 5,200,000 RBC/cubic millimeter of blood.
Women – 4,700,000 RBC/cubic millimeter of blood.
Birth – 6 to 7 million RBC/cubic millimeter of blood.
Quantity of Hemoglobin in Cells:
RBC has the ability to concentrate hemoglobin up to 34 gm/100 ml of cells. Normal hemoglobin level in ―
Men – 15 gm of hemoglobin/100 ml of cells.
Women – 14 gm of hemoglobin/100 ml of cells.
Structure of RBC:
Cell Membrane:
RBC cell membrane is a lipoprotein bilayer.
The inner side of the cell membrane has the following proteins:
1. Actin
2. Spectrin ― Both are contractile proteins and help in keeping up the shape of RBC.
Absence of spectrin leads to hereditary spherocytosis. Spherocytes are RBCs smaller and denser than normal RBCs.
3. Glycophorin ― It is a protein in RBC cell membrane and contains blood group antigens.
Cell Contents:
Water – 60-63%
Hemoglobin – 34%
Others – 3-6%
Production of Red Blood Cells:
Embryonic life – Yolk sac
Mid-trimester – Liver, spleen and lymph nodes
Last trimester and after birth – Bone marrow
Up to 5 years – Bone marrow of all bones
6-20 years – Red bone marrow of long bones and membranous bones
After 20 years – Shaft of humerus and tibia gets deposited with fat. Proximal end of these bones produce RBC. Flat bones like sternum, ribs, iliac and vertebrae produce RBC.
Genesis of RBC:
1. Pleuripotent Hematopoietic Stem cells (PHSC):
These cells are capable of forming any kind of blood cell.
2. Committed Stem Cells:
PHSC become committed to a particular line of cells called committed stem cells.
3. Colony Forming Unit:
Erythrocyte (CFU-E) ― committed stem cells that produce erythrocytes is called colony forming unit-erythrocyte.
4. Proerythroblast:
It is 15-20 µm in size. First cell that can be identified belonging to red blood cell series. It divides multiple numbers of times to form basophil erythroblast.
5. Basophil Erythroblast (Early Normoblast):
It is 12-16 µm in size. These cells stain with basic dyes. Hemoglobin is absent.
6. Polychromatophil Erythroblast (Intermediate Normoblast):
It is 10-14 µm in size. Hemoglobin appears in this stage. It has basophilic cytoplasm with acidophilic hemoglobin.
7. Orthochromatic Erythroblast (Late Normoblast):
It is 8-10 µm in size. Hemoglobin increases. Acidophilic cytoplasm with basophilic nucleus.
8. Reticulocyte:
About 1% of total red cells are reticulocytes. It is 7.5 µm in size. It is also called as young red cells. With Brilliant crystal blue, RNA appears as reticulum.
Nucleus condenses and gets extruded from the cell. Endoplasmic reticulum is reabsorbed. Remnants of Golgi apparatus, mitochondria, and few other cytoplasmic organelles are present. Reticulocyte response: anemic persons on treatment show increased release of reticulocytes in response to therapy. This is called as reticulocyte response.
9. Mature Erythrocyte:
Reticulocytes by the process of diapedesis pass from bone marrow into blood capillaries.
Basophilic materials disappear in 1 to 2 days and mature erythrocytes are formed. Because of short life their concentration is less than 1%.
Factors Necessary for Erythropoiesis:
1. Growth Inducers and Differentiation Inducers:
i. Growth Inducers:
Multiple proteins that induce growth and reproduction of different stem cells are called growth inducers, e.g. interleukin-3.
ii. Differentiation Inducers:
They cause one type of committed stem cells to differentiate into one or more steps in final blood cells. Hypoxia-reduced oxygen levels results in growth induction, differentiation and production of erythrocytes.
2. Hormones:
Erythropoietin:
Erythropoietin is a glycoprotein hormone with a molecular weight of 34,000.
Function:
To regulate erythropoiesis.
Stimulus for erythropoietin (EPO) secretion occurs, in:
i. High altitude
ii. Cardiopulmonary disorders.
Other Factors that Stimulate EPO Secretion are:
i. Epinephrine
ii. Norepinephrine
iii. Prostaglandins.
Site of Formation of EPO:
Interstitial cells in the peritubular capillaries of kidneys ― 85%
Perivenous hepatocytes of liver ― 15%
Actions of Erythropoietin:
i. EPO acts on stem cells to differentiate into committed stem cells.
ii. Promotes ‘Hb’ synthesis by acting on 8 aminolevulinic acid synthetase.
iii. Promotes every stage of maturation from pronormoblast to mature red cells.
iv. Promotes release of RBCs from marrow to circulation.
Half-Life of EPO:
5 hours
Effect of EPO on Erythropoiesis:
Exposed to hypoxia → Minutes to hours → Epo production beings 24 in hours → Maximum production after 5 days → RBC formed.
EPO activates hematopoietic stem cells in bone marrow, to become pro-erythroblast. EPO also speeds up each step in the production of new red cells. Production continues as long as a person remains in low oxygen state.
3. Renal Failure:
When both kidneys fail, the person becomes anemic as kidneys produce 90% of EPO.
4. Androgens:
Males have higher RBC count than females because androgens are potent stimulators of:
i. Erythropoietin production
ii. Erythropoiesis.
5. Estrogens:
Estrogens have inhibitory effect on erythropoiesis.
6. Thyroxine:
Thyroxine deficiency leads to anemia.
7. Hypo Function of Adrenal Cortex and Pituitary Gland:
Leads to mild-to-moderate anemia:
i. Nutritional Factors:
First class proteins are necessary for globin formation.
ii. Minerals:
Iron, copper, cobalt and zinc are necessary for erythropoiesis. Iron is necessary for haem production.
iii. Vitamins:
Vit B12, Vit C, and folic acid.
Vit C: Promotes iron absorption from the gut.
Vit B12 and folic acid are necessary for synthesis of DNA.
8. Maturation of Red Cells:
Maturation of red cells is by:
i. Vitamin B12
ii. Folic acid
Thymidine triphosphate forms one of the essential building blocks of DNA.
9. Maturation Failure:
Absence or lack of B12 (or) folic acid → Diminished/No thymidine triphosphate → Diminished DNA synthesis → Failure of nuclear maturation → Larger than normal size red cells-macrocytes → Flimsy cell membrane short life.
10. Intrinsic Factor of Castle:
Parietal cells of gastric gland secrete → Intrinsic Factor (IF) → IF + B12 → Binds to receptor on mucosal cells of lieum → Pinocytosis B12 is absorbed.
11. Applied Physiology:
Absence of IF leads to maturation failure caused by lack of B12. This condition is called pernicious anemia.
Variations of RBC:
In Number:
Increase in number of red cells is called polycythemia.
It may be:
i. Physiological
ii. Pathological
Cause:
i. Physiological:
High altitude, muscular exercise, temperature, decreased oxygen tension, emotion and after meals.
ii. Pathological:
a. Primary Polycythemia (or) Polycythemia Vera:
In primary polycythemia there is genetic aberration in hemocytoblastic cells. It occurs in myeloproliferative disorders. RBC count is >8 million/mm3, PCV 60-70%, blood volume increases to twice the normal, viscosity of blood becomes 10 times that of water (Normal = 3 times that of water).
b. Secondary Polycythemia:
Hypoxia causes production of red cells in large number. The causes could be physiological, e.g. high altitude, pathological, e.g. congenital heart disease.
Effects of Polycythemia on Circulatory System:
Polycythemia Increase in viscosity → Increase in peripheral resistance → Increase in arterial pressure → Hypertension
Deficiency of RBC:
I. Anaemia:
Decrease in the number of red cell count or decrease in the quantity of hemoglobin leading to decrease in oxygen carrying capacity is called anemia.
Classification of Anaemia:
1. Morphological Classification:
i. Normocytic Normochromic:
Size and hemoglobin content of RBC is normal, e.g. haemorrhage.
ii. Microcytic Hypochromic:
RBCs are smaller in size and pale, e.g. iron deficiency anemia.
iii. Macrocytic (or) Megaloblastic:
RBCs are larger in size and hemoglobin is less, e.g. B12 (or) folic acid deficiency.
2. Etiological Classification:
i. Nutritional Deficiency:
Anemia is due to deficiency of iron, folic acid, vitamin B12, vitamin C and proteins.
ii. Aplastic Anemia:
Marrow failure with reduction in stem cell number occurs in aplastic anemia. It occurs due to exposure to radiation, excessive X-ray, and industrial chemicals.
iii. Hemolytic Anemia:
Red cells are destroyed quickly. Anemia occurs due to excess hemolysis of RBC and bone marrow tries to compensate by increasing red cell production. When hemolysis is more than production, hemolytic anemia occurs.
Causes of Hemolytic Anemia:
Congenital:
1. Red cell membrane defect:
i. Hereditary spherocytosis
ii. Hereditary elliptocytosis.
2. Enzyme defect, e.g. glucose-6-phosphate deficiency, pyruvate kinase deficiency.
Hemoglobin Abnormalities:
Sickle cell anemia, thalassemia.
Acquired:
Erythroblastosis fetalis
Infection, e.g. malaria
Drugs and chemicals, e.g. dapsone.
Investigations:
Reticulocyte count is high, plasma bilirubin is increased.
Sickle Cell Anemia:
It is common among blacks in West Africa and America. Abnormal hemoglobin called “Hb-S” is present in these people. The defect occurs in 6th position of β-chain of hemoglobin. Instead of glutamic acid, valine is present in sickle all anemia. Hypoxia causes this hemoglobin to precipitate into long crystals in RBC called tectoids. These tectoids causes sickling of red cells.
Microcytic Hypochromic Anemia:
Pathophysiology:
1. Defective iron absorption
2. Decreased transferring in blood
Less of iron to form ‘Hb’ → Decreased hemoglobin synthesis → Decreased cell volume → Small sized cell – microcytes with pale colored RBC – hypochromic
Sickle Cell Crisis:
Hyoxia → Sickling of RBC Sickled → RBC blocks the circulation → Tissue hypoxia
Sickle cell crisis leads to death within few hours. Sickle cell trait is the heterozygous state of sickle cell anemia. People with sickle cell trait are resistant to Plasmodium falciparum malaria its treatment includes hydroxyurea and bone marrow transplantation.
II. Thalassemia:
In thalassemia there is:
i. Defect in synthesis of globin part of hemoglobin
ii. Defect in α-chain synthesis is α-thalassemia
iii. Defect in β-chain synthesis is β-thalassemia
iv. β-thalassemia can be:
a. β-thalassemia major:
1. Less common
2. Homozygous transmission
3. Complete absence of β-chain → Severe anemia ― (i) HbF is increased (ii) Short lifespan: 17
b. β-thalassemia minor:
1. More common
2. Heterozygous transmission
3. Partial absence → Mild anemia ― (i) HbF is normal (ii) Survive longer and transmit to 18 years the gene to offspring
Blood Loss Anemia:
In acute haemorrhage, body replaces the fluid portion of plasma in 1 to 3 days. This leads to normocytic normochromic anemia. Replacement of RBC takes 4-6 weeks.
In chronic blood loss, intestinal mucosa cannot absorb adequate iron, leading to microcytic hypochromic anemia.
Symptoms:
Anemia causes weakness, fatigue, lassitude, dyspnoea on exertion and palpitation.
Compensatory changes that occur in anemic persons are:
i. Tachycardia
ii. Increased cardiac output
iii. Redistribution of blood flow
iv. Increased content of 2, 3, DPG – that favors oxygen release into the tissues to meet the tissue hypoxia.
v. Hemic murmur – A non-conducted systolic murmur is heard at the apex.
Features of Iron Deficiency Anemia:
i. Pallor (seen in conjunctiva)
ii. Spoon-shaped nails (koilonychias)
iii. Brittle nails
iv. Atrophy of papilla in tongue
v. Dysphagia (Plummer-Wilson syndrome).
Features of Megaloblastic Anemia:
i. Glossitis
ii. Angular stomatitis
iii. Paresthesia of fingers and toes. Demyelination of lateral and posterior column fibers of spinal cord.
Investigations:
i. Hemoglobin estimation
ii. RBC count
iii. Peripheral blood smear
iv. Red cell indices
v. Reticulocyte count
vi. If necessary, bone marrow smears
vii. Estimation of iron content in serum
viii. Serum iron binding capacity.
Treatment:
Treatment depends on the severity of anemia.
Severe anemia is treated by giving packed cell transfusion. This will prevent volume overload and hence congestive cardiac failure.
Mild and moderate anemia is treated by giving iron and B12.
I. Nutritional/Actors:
First class proteins are necessary for globin formation.
II. Minerals:
Iron, copper, cobalt and zinc are necessary for erythropoiesis.
i. Iron is necessary for haemo production
ii. Iron deficiency is due to:
a. Inadequate intake
b. Inadequate absorption
c. Excess loss
d. Hookworm infestation.
III. Vitamins:
Vit B12, Vit C, folic acid.
Vit C: Promotes iron absorption from the gut.
B12 and folic acid are necessary for synthesis of DNA.