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RED BLOOD CELL FORMATIONRED BLOOD CELL FORMATION

Dr. B.L. Mtinangi.Dr. B.L. Mtinangi.Department of PhysiologyDepartment of Physiology

HKMUHKMUNovember, 2015November, 2015

RED BLOOD CELL FORMATIONRED BLOOD CELL FORMATIONRbc’s are circular, biconcave, disk-like, Rbc’s are circular, biconcave, disk-like,

dumbbell shaped, non nucleated living dumbbell shaped, non nucleated living cell.cell.

Mean Cell Volume (MCV) is the average Mean Cell Volume (MCV) is the average volume of each red cell (82-92cub micron)volume of each red cell (82-92cub micron)

Mean Cell Haemoglobin (MCH) is the Mean Cell Haemoglobin (MCH) is the average Hb in each cell (27-32 picogram)average Hb in each cell (27-32 picogram)

Mean Cell Haemoglobin Concentration Mean Cell Haemoglobin Concentration (MCHC) this indicates the degree of (MCHC) this indicates the degree of saturation of Rbc with Hb (32 to 38%)saturation of Rbc with Hb (32 to 38%)

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RBC’s CONT.RBC’s CONT. During Anaemia MCHC is less, it is known During Anaemia MCHC is less, it is known

as hypochromic anaemia andas hypochromic anaemia and If MCHC is normal it is normochromic If MCHC is normal it is normochromic

anaemiaanaemiaBiconcave shape gives certain advantages:Biconcave shape gives certain advantages: Maximum surface area for gas diffusionMaximum surface area for gas diffusion Diffusion distance is minimisedDiffusion distance is minimised Rbc can mould their shape while passing Rbc can mould their shape while passing

through narrow capillariesthrough narrow capillaries

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RBC’s FORMATIONRBC’s FORMATIONThere is some daily loss of Rbc’s ie There is some daily loss of Rbc’s ie

the average life span of Rbc’s is the average life span of Rbc’s is about 120 daysabout 120 days

To keep the Rbc’s count normal or to To keep the Rbc’s count normal or to balance this lossbalance this loss

Sufficient number of Rbc’s must be Sufficient number of Rbc’s must be produced dailyproduced daily

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FORMATION OF RbcFORMATION OF RbcFormation/generation (ERYTHROPOIESIS) Formation/generation (ERYTHROPOIESIS)

starts in the third week of INTRAUTERINE starts in the third week of INTRAUTERINE life.life.

Third week to third month erythropoiesis Third week to third month erythropoiesis occurs in the mesoderm of the york sacoccurs in the mesoderm of the york sac

Third month to fifth month it occurs in the Third month to fifth month it occurs in the liver and spleen (HEPATIC PHASE)liver and spleen (HEPATIC PHASE)

Fifth month onwards it occurs in the red Fifth month onwards it occurs in the red bone marrowbone marrow

HAEMATOPOIESISHAEMATOPOIESIS

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FORMATION OF Rbc CONTFORMATION OF Rbc CONT..Post natal (after birth) red blood Post natal (after birth) red blood

cell formation (erythropoiesis) cell formation (erythropoiesis) occur in the RED BONE MARROWoccur in the RED BONE MARROW

Main sites for erythropoiesis:Main sites for erythropoiesis:Ribs, vertebra, sternum, cranium Ribs, vertebra, sternum, cranium Pelvis. Shaft of the femur and Pelvis. Shaft of the femur and

tibiatibia

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BLOOD FORMING TISSUESBLOOD FORMING TISSUESMyeloid tissues produces Rbc,Wbc Myeloid tissues produces Rbc,Wbc

and Platelets.and Platelets.Lymphoid tissues include the lymph Lymphoid tissues include the lymph

node, thymus and spleen. All node, thymus and spleen. All produce Lymphocytes produce Lymphocytes

RBC maturation

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Rbc DEVELOPMENTAL STAGESRbc DEVELOPMENTAL STAGES Pluripotent stem cell ( Uncommitted stem Pluripotent stem cell ( Uncommitted stem

cell) develop intocell) develop into Committed stem cell into Pronormoblast or Committed stem cell into Pronormoblast or

Myeloblast or Megaloblst or LymphoblastMyeloblast or Megaloblst or LymphoblastPronormoblast (Proerythroblast) develop into Pronormoblast (Proerythroblast) develop into

Early normoblast then to Intermidiate Early normoblast then to Intermidiate normoblast then to Late normoblast then normoblast then to Late normoblast then into immature Rbc (Reticulocyte) then into immature Rbc (Reticulocyte) then within 2 to 3 days develop into mature Rbc within 2 to 3 days develop into mature Rbc

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FORMATION OF Rbc CONT.FORMATION OF Rbc CONT.One committed stem cell produces One committed stem cell produces

16 mature Rbc116 mature Rbc1

10% to 15% of Rbc undergo 10% to 15% of Rbc undergo premature destruction during premature destruction during developmentdevelopment

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NORMAL VALUESNORMAL VALUESTotal normal Rbc count:Total normal Rbc count: men 4.5 to 6.4 mill/cummmen 4.5 to 6.4 mill/cumm women 3.9 to 5.6 mill/cummwomen 3.9 to 5.6 mill/cummNormal Haemoglobin (Hb) Normal Haemoglobin (Hb)

concentration:concentration: men 13 to 17g/dlmen 13 to 17g/dl women 11 to 16g/dlwomen 11 to 16g/dl

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FACTORS INFLUENCING FACTORS INFLUENCING ERYTHROPOIESISERYTHROPOIESIS

1. Erythropoietin.1. Erythropoietin. Is a hormone produced in Is a hormone produced in

JuxtaGlomerular Apparatus(JGA) in JuxtaGlomerular Apparatus(JGA) in the macula densa (kidney)the macula densa (kidney)

Is a glycoprotein with MW 36000Is a glycoprotein with MW 36000Stimulate proliferation and Stimulate proliferation and

differentiation of erythroblastdifferentiation of erythroblastStimulate Hb synthesisStimulate Hb synthesisPromote Rbc maturation Promote Rbc maturation

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2. VITAMINS2. VITAMINSVITAMIN B12VITAMIN B12 Is essential for erythropoiesis ie it Is essential for erythropoiesis ie it

stimulates erythropoiesisstimulates erythropoiesis Present only in meat, fish and diary Present only in meat, fish and diary

productsproducts Absent in vegetablesAbsent in vegetables In the GIT it combines with the intrinsic In the GIT it combines with the intrinsic

factor which protect & transport it to the factor which protect & transport it to the terminal ileumterminal ileum

Absorbed in the terminal ILEUMAbsorbed in the terminal ILEUM Required for DNA and RNA SYNTHESISRequired for DNA and RNA SYNTHESIS

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3. FOLIC ACID3. FOLIC ACIDFolic acid is another vitamin that is Folic acid is another vitamin that is

essentialessentialStimulates erythropoiesisStimulates erythropoiesis

Required for DNA and RNA synthesisRequired for DNA and RNA synthesis

Present in vegetables and fruitsPresent in vegetables and fruits

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4.IRON4.IRONIRON:IRON: Found in the meat and vegetableFound in the meat and vegetable Required for Haemoglobin synthesisRequired for Haemoglobin synthesis Daily intake is about 10 to 20 mgDaily intake is about 10 to 20 mg 5% to 10% of iron daily intake is absorbed ie 5% to 10% of iron daily intake is absorbed ie

(0.5 to 2mg/day)(0.5 to 2mg/day) 2/3 of Iron is found in the Rbc2/3 of Iron is found in the Rbc It circulate in the blood as TransferrinIt circulate in the blood as Transferrin Stored in the bone as Ferritin and Stored in the bone as Ferritin and

HaemosiderinHaemosiderin

Red Blood Cell Turnover

A summary of:Bilirubin formation, circulation and

elimination

Senescent (old) Red blood cell destruction

Hb is degraded to Haem & GlobinGlobin is reutilised as Amino AcidHaem an Iron component is

degraded to a porphyrin ringPorphyrin ring is converted to

choleglobin

CONTCholeglobin in the presence of an

enzyme haem oxygenase is converted to BILIVERDIN

Biliverdin in the presence of an enzyme biliverdin reductase is converted to BILIRUBIN

Bilirubin is released into plasma

CONTIn the plasma Bilirubin is bound to

ALBUMIN and transported to the liverIn the liver bilirubin is conjugated

with GLUCURONIC ACID to conjugated bilirubin (bilirubin glucuronide)

CONT.Conjugated bilirubin is transported to

the intestine through the bile ductIn the intestine bilirubin is further

conjugated by the bacteria to STERCOBILINOGEN

Stercobilinogen is oxidized to stercobilin after exposure to air in the feces

CONTThe reminder 5% is absorbed

(enterohepatic circulation) and transported to the kidney as UROBILINOGEN

Urobilinogen is oxidized to UROBILIN after exposure to air in the urine

ANAEMIAANAEMIAAnaemia is defined as the reduction of:Anaemia is defined as the reduction of: HaemoglobinHaemoglobin Total red cell countTotal red cell count Haematocrit (Packed cell volume – Haematocrit (Packed cell volume –

PCV)PCV)According to age and sexAccording to age and sex

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CAUSES OF ANAEMIACAUSES OF ANAEMIACauses could be due to:Causes could be due to: Nutritional deficiences, eg iron, folic Nutritional deficiences, eg iron, folic

acid, vitamin B12 ect ectsacid, vitamin B12 ect ects Excessive destruction of Rbc eg due Excessive destruction of Rbc eg due

to malaria, sickle cell disease etc etcto malaria, sickle cell disease etc etc External/ internal bleedingExternal/ internal bleeding Infestations eg hookwormInfestations eg hookworm Bone marrow failureBone marrow failure

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Thank you