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L1- Histology of Blood Cells

Blood cells

  • Blood composition
  • Red blood corpuscles
  • Role of liver and spleen in the formation and destruction of erythrocytes
  • Hematopoiesis

Introduction

Blood is a fluid which is continuously circulating inside the blood vessels by the pumping action of the heart, acting as a link between various cells and systems of the body

Blood composition

The blood consists of a fluid part representing 55% of its volume which is the plasma and cellular elements representing 45%

The cellular elements are :

A-The red blood cells

B-White blood cells

C-Platelets

Red Blood Corpuscles

Shape and size

These are non-nucleated circular biconcave discs which are about 2.2 microns thick, 7.2 microns in diameter and about 90 cubic microns in volume.

They contain the red respiratory pigment hemoglobin

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Structure of erythrocytes

– The RBCs are surrounded with a plastic semipermeable membrane which is lipoprotein in nature. This allows the changes in size of the corpuscles and help them to be squeezed through the narrow capillaries

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-The most important constituent of the red blood corpuscles is hemoglobin. Its concentration inside RBCs is 34%.

-The chief cation inside is potassium.

-The corpuscles contain also carbonic anhydrase enzyme the which plays an important role in carbon dioxide transport

Hemoglobin

-It is made of four subunits. Each subunit is formed of heme and a polypeptide .

-Heme is an iron protoporphyrin. The latter is formed of glycine and succinyl-Co A.

-In each molecule of Hb there are four atoms of iron and two pairs of polypeptide called collectively globins.

-Each gram of hemoglobin unites loosely with 1.33 ml oxygen.

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Hemoglobin molecule

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Normal Hemoglobin content

-16 gm% in adult males

-14 gm% in adult females

-It is estimated by Sahli apparatus.

Types of Hemoglobin

-The Hb of normal adult is called Hb A.

-Slight changes in its polypeptide chains produce abnormal types of Hb

-The commonest abnormal Hb include:

a-Hb A2 : It is harmless and represents 2.5% of Hb  in normal adults

b-Hb F: It presents in the fetus. Its O2 carrying capacity is greater than Hb A.

c-Hb S : It is insoluble Hb that is easily precipitated especially at low O2 tensions

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Sickle cells containing Hb S

Functions of RBCs

1-The main function of RBCs is to contain hemoglobin. Hemoglobin carry oxygen and take up carbon dioxide from tissues.

2-Hemoglobin in the red blood corpuscles is an important buffer and helps to keep the pH of blood.

3-The red cells keep the hemoglobin inside them and prevent its loss in the urine

4-If the hemoglobin was free in the plasma, this would increase the colloidal osmotic pressure of the plasma from 25 to 70 mmHg. The pressure in capillaries should increase to 80 mmHg. The work of the heart must increase markedly.

Red cell count

-The red cell count in an adult male is 5 millions per cubic millimeter. In adult female is 4.5 millions per cubic millimeter.

-The red cell count varies with age. It is high in newly born infants. In old age the red cell count drops.

-Athletes and people living at high altitude have a higher count.

Hematocrite Value (Ratio) or Packed cell volume

-It is the percentage ratio of red cells in blood .

-It is measured by dividing the height of the red cell column by the height of the total blood column.

-Normal values are 46% for adult males and 42% for adult female

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Blood or hematological indices

Once  the hematocrite, red cell count, and hemoglobin content are known, further information about the red cells can be calculated:

1-Mean corpuscular hemoglobin

2-Mean corpuscular volume

3-Mean corpuscular hemoglobin concentration

Mean corpuscular hemoglobin (MCH)

It is the amount of hemoglobin in a single red cell measured in absolute units.

It equals:

Hemoglobin content X 10

—————————-

Red cell count in millions

= 30 picogram

-The normal range of MCH is 25 – 32 pg

-Values less than 25 pg indicate hypochromic anemia.

-Values above 32 pg indicate hyperchromic anemia.

Mean corpuscular volume (MCV)

It is a measure of the average volume of a single red corpuscle in absolute units.

It equals

Hematocrite value X 10

—————————

Red cell count in millions

= 90 cubic microns or fl

-The normal range is 80 – 95 cubic micron.

-Values less than 80 indicate microcytic cells.

-Values above 95 indicate macrocytic cells.

Mean corpuscular hemoglobin concentration (MCHC)

It is a measure of hemoglobin in 100 ml of packed red cells (not blood).

It equals

Hemoglobin content x 100

——————————-

Hematocrite

= 33%

-The normal range is 32 – 38%

-Values below 32% indicate hypochromic anemia.

-Values above 38% indicate hyperchromic anemia

-This index is more diagnostic for detection of iron deficiency than MCH

Formation of red cells (Erythropoiesis)

The number of red cells is kept fairly constant by a balance between the rate of formation and the rate of destruction

Origin (Site of formation) of RBCs

-During the first 6 months of fetal life, the formation of RBCs is extramedullary i.e. outside the bone marrow in the liver and spleen.

-During the last 3 months of fetal life and after birth they are formed in the bone marrow.

-Until adolescence, the bone marrow of all bones produce red corpuscles.

-After the age of 20 years, the active red marrow is found only in the upper ends of long bones (femur and humerus) and flat bones (vertebrae, sternum and ribs).

-The production of red cells in the bone marrow of membranous bone declines as age increases.

Regulation of Erythropoiesis

I-Oxygen supply to tissues

The increased red cells production as a result of tissue hypoxia is due to the release of a hormone erythropoietin

Erythropoietin

It is formed as a result of tissue hypoxia especially the kidneys.

It increases the production of red cells in the bone marrow. It stimulates the synthesis of messenger RNA necessary for formation of new cells.

II- Diet

A-Proteins:

Proteins of high biological value are essential in the diet to build the globins of protein.

B-Iron:

It is important for the formation of hemoglobin, myoglobin of red muscles, and certain enzymes as cytochromes, peroxidases, catalase.

Iron metabolism

Iron requirements:

The average daily intake is about 15-20 mg per day. The amount of iron absorbed is equal to the amount lost i.e. 0.6 mg daily i.e. about 4% of the daily intake.

Iron absorption and transport:

-Iron is absorbed in the duodenum by enterocytes and transferred to the plasma. There, it is bound by transferrin, and becomes available for uptake throughout the body by any tissue with transferrin receptors.

-Liver parenchyma is especially rich in transferrin receptors, and stores large quantities of iron.

In muscle tissue, iron is used to make myoglobin, and in bone marrow.

erythrocytes use iron to make Hb.

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Iron Metabolism

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Amount of Iron in the body

Excess iron in the plasma is deposited especially in the liver cells where it combine with apoferritin to form ferritin.

The iron in ferritin is called storage iron.

Ferritin is in equilibrium with plasma iron. When the plasma iron falls iron is released from ferritin

C-Vitamins:

They are needed for the formation of red blood cells:

A-Vitamin B12

B-Folic acid

Vitamin B12

-It is important fort transformation of RNA into DNA.

-Lack of the vitamin leads to failure of nuclear maturation and cell division. Failing to divide, erythroblastic cells form megalocytes.These cells are fewer in number, larger in size and are more fragile

D-Trace elements:

Copper and cobalt act as cofactors for the formation of hemoglobin

Cobalt enters in the formation of vitamin B12 and stimulates production of the renal erythropoietin factor

III- Bone marrow

A healthy bone marrow is essential for the production of red cells.

The marrow is destroyed by X-rays, atomic radiations, cancer cells infiltration, and certain drugs.

IV- The liver

Liver is important for Erythropoiesis because:

A-It acts as store for vitamin B12

B-It acts as a store for iron

C-It shares formation of erythropoietin

D-It plays an important role in globins’ synthesis

V-Hormones

They regulate the metabolic processes in various tissues including the bone marrow

-Thyroxin

-Glucocorticoids

-Androgens

VI-The kidney

It is important for the formation of Erythropoietin which stimulates erythropoiesis

Anemia is a prominent symptom in chronic renal failure

Fate of red cells

-The life san of red cells is 120 days.

-The cells become older and more fragile and rupture during their passage through some tight spots of circulation.

-Many old red cells rupture during their passage in the spleen.

Destruction of hemoglobin

-The hemoglobin released from the red cells is picked up by the cells of the  reticuloendothelial  system mainly in the spleen.

-Hemoglobin breaks into globin and iron protoporphyrin

-The iron protoporphyrin ring is opened and iron is carried in the blood in the form of transferrin.

-The latter is either carried to the bone marrow for building new red cells or to the liver to be stored.

-The protoporphyrin is converted into the bile pigment bilirubin which is secreted by the liver

Some physico-chemical properties of blood

1- Erythrocyte sedimentation rate

The height of column of clear plasma on top is the measure of ESR. It is read after the first and second hours

Normal value:

1)In males  after  :

-first hour is 6 mm

-second hour is 8 mm

2)In females after :

-first hour is 10 mm

-second hour 16 mm

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Westergren tube for ESR

Clinical significance of ESR

-Physiological Changes

-Pathological Changes

When plasma globulins are increased, the negative charges are decreased and red cells tend to stick together and form rouleaux. This occurs in:

-Chronic infections especially TB

-Rheumatic fever

-Malignant tumours

-Coronary infarction

2- Osmotic resistance of red cells

Hypotonic solutions lead to water diffusion into RBCs causing their swelling and then rupture (Hemolysis).

Normally RBCs begin hemolysis in solutions of concentrations about 0.5%

In Hereditary spherocytosis RBCs stat hemolysis at 0.7% NaCl solution.

3- Blood viscosity

It plays an important role in cardiovascular hemodynamics.

The viscosity of blood is mainly produced by red blood cells  and plasma proteins.

The plasma viscosity is 1.5 as regard to water

The blood viscosity is 3 as regard to water

Pathology of RBC

Anemia

Polycythemia


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