PHYSIOLOGY BLOOD UNIT 4

Blood Unit 4

Red Blood Cells (Erythrocytes)

Red Blood Cells

• Shape & size
- Circular Biconcave Disc
- Non-nucleated
- Diameter 7-8 um x 2.5 mm , 1 mm
- Flexible
- Number =4.5-5 x106
- No nucleus, No Mitochondria, No Ribosome
- DEPEND ON Glucose Metabolism For Its Energy Source

Composition

- 62.5% water
- 35% Hb
- 2.5 %
1. Sugar
2. Lipids
3. Protein
4. Enzymes
5. Vitamins
6. Ions

Normal Values

- At birth 6-7 million/cumm
- Adults Male- 5-6 million/cumm
- Adults Female- 4.5 to
5.5 million/cumm
- Lifespan is 120 days
- 5 million/cumm is 100% RBC count clinically

Variation in Size

- Anisocytosis- Size
- Poikilocytosis- Shape
- Spherocytosis- Spherical

Genesis of RBC

• All blood cell are formed from Pluripotent hematopoietic stem cells ? committed cells:
• Committed stem cells for RBC
• Committed stem cells for WBC
• Growth of different stems cells are controlled by different growth factors

Stages of differentiation of RBC

- Stages of RBC development
   • Committed stem cell - Proerthroblast
      - basophil erythroblast
      - polychromatophil erythroblast
      - orthochromatic erythroblast
      - Reticulocytes
      - Mature erythrocytes
• Rapid RBC production  increases reticlocytes in the circulation

Proerythroblast

• No hemoglobin
• Nucleus 12 um
• Contain nucleoli

Basophil erythroblast

• Early normoblast
• Nucleoli disappear
• Show mitosis
• Cytoplasm deep blue
- Increase in RNA
• Hemoglobin starts appearing - Little Hb

Polychromatophil erythroblast

• Late normoblast
• Nucleus smaller
• Coarse Chromatin
• Hemoglobin increase
- Eosinophil Stain
• RNA - Basophil stain

Orthochromatic Erythroblast

• Normoblast
• Nucleus smaller
- Pyknosis
• Nuclear lysis and
• Nuclear extrusion

Reticulocyte

• Reticulum
• Remnant of ER & GA
- Synthesize Hb
• Few Mitochondria
• Young RBCs (34% Hb)
• 1 % of Red Cells

Transfer of RBC to Circulation

RBC pass from the bone marrow into the blood capillaries by Diapedesis (squeezing through the pores of the capillary membrane).

Erythropoiesis

- RBC development is characterize by:
   - decrease in cell size
   - disappearance of nuclus
   - appearance of haemoglobin

RBC Formation before birth

• Mesoblastic stage
    - Nucleated RBCs - Yolk sac and Mesothelial layers of the placenta -3rd week
• Hepatic stage
    - At 6 weeks - Liver form blood cells
    - Spleen + lymphoid tissues form blood cells.
• Myeloid stage
    - From the third month onwards - the bone marrow gradually becomes the principal source of the RBCs
    - Last month - Bone marrow exclusively

RBC Formation after birth

• The bone marrow - all bones - 5 years
• Marrow of the long bones (except for the proximal humerus and tibia)
    - No more red blood cells after = age 20 years.
• Most red cells continue to be produced in the marrow of the membranous bones, such as - Vertebrae, Sternum, Ribs, and Ilium.

Regulation of RBC production 

• Erythropoiesis is stimulated by erythropoietin hormone produced by the kidney in response to hypoxia (low oxygen in the blood)
• Hypoxia caused by:
   - Low RBC count (Anaemia)
   - Hemorrhage
   - High altitude
   - Prolong heart failure
   - Lung disease

Erythropoietin

• Glycoprotein
• 90% from renal cortex 10% liver
• Stimulate the growth of early stem cells
• Does not affect maturation process
• Can be measured in plasma & urine
• High levels of erythropoietin
   -anemia
   -High altitude
   -Heart failure
   -Lung Disease
(Result in polycythemia)

RBC Indices

• RBC indices include:
   - Mean Corpuscular Volume (MCV)
   - Mean Corpuscular Hemoglobin (MCH)
   - Mean Corpuscular Hemoglobin Concentration (MCHC)
   - RBC Distribution Width (RDW)
   - Colour Index (CI)

MCV

• Mean cell volume
• MCV is average size of RBC
• MCV  =   Hct x 10/RBC (millions)
• If 80-100 fL, normal range, RBCs considered normocytic
• If < 80 fL are microcytic
• If > 100 fL are macrocytic
• Not reliable when have marked anisocytosis

MCH

• MCH is average weight of hemoglobin per RBC.
• MCH = Hgb x 10/RBC (millions)

MCHC

• MCHC is average hemoglobin concentration per RBC
• MCHC = Hgb x 100 Hct (%)
• If MCHC is normal, cell described as normochromic
• If MCHC is less than normal, cell described as hypochromic
• There are no hyperchromic RBCs

RDW

• Most automated instruments now provide an RBC Distribution Width (RDW)
• An index of RBC size variation
• May be used to quantitate the amount of anisocytosis on peripheral blood smear
• Normal range is 11.5% to 14.5% for both men and women

CI

• Ratio of Hb to RBC
• Insignificant index as normal range is very wide for RBC
• CI- Hb%/RBC%
• Normal Range is 1 (0.85-1.15)

Anemia

• Anemia (An-without,emia-blood)is a decrease in the RBC count, hemoglobin and/or
Hematocrit values resulting in a lower ability for the blood to carry oxygen to body tissues .

Grading

• Mild Anemia- Hb 8-12 gm%
• Moderate Anemia- Hb 5-8 gm%
• Severe Anemia- Hb less than 5 gm%

TYPES OF ANEMIA

Based on clinical picture
* Iron deficiency anemia.
* Megaloblastic anemia.
* Pernicious anemia.
* Hemorrhagic anemia.
* Hemolytic anemia.
  -Thalassemia anemia
  -Sickle cell anemia
* Aplastic anemia
* Erythroblastosis Foetalis
* G-6PD Anemia- Decrease in Glutathione Production

• Iron deficiency anemia
   - excessive loss of iron .
   - Women are at risk. ---- For menstrual blood and growing fetus.
• Megaloblastic anemia
   - Less intake of vitamin B 12  and folic acid.
   - Red bone marrow produces abnormal RBC.
• Pernicious anemia
   - Inability of stomach to absorb vitamin B 12 in small intestine.
• Hemorrhagic anemia
  - Excessive loss of RBC through bleeding,stomach ulcers,menstruation
• Hemolytic anemia
  - RBC plasma membrane ruptures.
  - may be due to parasites,toxins,antibodies.
• Thalassemmia
  - Less synthesis of hemoglobin .Found in population of Mediterranean sea.
• Sickle cell anemia
  - Hereditary blood disorder, characterized by red blood cells that assume an abnormal, rigid, sickle shape.
• Aplastic anemia
  - destruction of red bone marrow .
  - caused by toxins,gamma radiation.
• Normochromic, normocytic anemia (normal MCHC, normal MCV).These include:
  - anemias of chronic disease
  - hemolytic anemias (those characterized by accelerated destruction of RBC's)
  - anemia of acute hemorrhage
  - aplastic anemias (those characterized by disappearance of RBC precursors from the marrow)
• Hypochromic, microcytic anemia (low MCHC, low MCV).These include:
  - iron deficiency anemia
  - thalassemias
  - anemia of chronic diseases
• Normochromic, macrocytic anemia (normal MCHC, high MCV).These include:
  - vitamin B12 deficiency
  - folate deficiency

RISK FACTORS

• Poor socio economic class
• Multiparity
• Teenage pregnancy
• Menstural problem

SIGNS OF ANAEMIA 

• Brittle nails
• Koilonychia (spoon shaped nails)
• Atrophy of the papillae of the tongue
• Angular stomatitis
• Brittle hair
• Dysphagia and Glossitis
• Plummer vinson/kelly patterson Symptoms & Signs