Introduction To Blood And Red Blood Cells Flashcards
What are the normal circulating blood Volume?
5.5l in 70kg man(+/- 71-75ml/kg)
Ave. woman: +/- 4.5l
Baby: 300ml (+/- 8oml/kg)
What are the constituents of blood?
Plasma
White Blood cells(Leukocytes)
Red Blood Cells(Erythrocytes)
Platelets(Thrombocytes)
In men the cells account for approx. 1.
of the blood volume and plasma 2.
In woman the ratio is x:y
- 46%
- 54%
- 42:58
What do haemopoietic stem cells do.
Give rise to all the blood cells
They are self-renewing
They are ‘Nested’ in the bone marrow storma:
-Fat cells,endothelial cells,connective tissue etc
-Produces growth factors which are necessary for stem cell survival
The Sites of Haemopoeisis(Fetus)
0-2 Months: Yolk Sac
2-7 Months: Liver and Spleen
5-9 Months: Bone Marrow
The Sites of Haemopoeisis(Infants)
Bone marrow(Practically in all the bones)
The sites of haemopoeisis(Adults)
Vertebrae Ribs Sternum Skull Sacrum and Pelvis Proximal ends of the femur
When does extramedullary haemopoiesis occur and what is it associated with?
- When the spleen and liver resume their haemopoietic role
- It is associated with:
1. Myelofibrosis
2. Myeloid Leukaemia
3. Compensatory red cell production in severe aneamias(Chronic haemolysis, megablastic anemia, Thalassaemia)
What are the Growth Factors(Hormones which stimulate blood cells to either:
Proliferate(Multiply)
Mature
Function Properly
Differentiate(Develop into a different cell type)
Examples of Growth Factors
Erythropoietin(EPO), Thrombopoietin
Granulocyte-Macrophage Colony Stimulating Factor(GM-CSF)
Granulocyte-Colony Stimulating Factor(G-CSF)
Steps in the Erythrocyte Production
- Stem Cell(Hemocytoblast)
- Commited cell(Proerythoblast)
- Phase 1: Ribosome Synthesis-Early erythroblast>Late erythoblast
- Phase 2: Hemoglobin Accumulation-Late erythoblast>Nomoblast
- Phase 3: Ejection of nucleus- Nomoblast>Reticulocyte
- Erythocyte
Haemoglobin content of precursor cells:
Stem cells and pronormoblasts: No haemoglobin
Early normoblasts: Some
Late normoblasts and mature red cells: Saturated with haemoglobin
Erythropoietin( EPO) Gene
Location
Production Site
Product
Location:Chromosome 7
Production site/Gene expression:
- Fetus: Liver
- Adult: Kidney(Peritubular intestinal cells) and Liver
Product: Heavy Glycosylated hormone(EPO)
Erythropoietin effects can be classified as Haematological and Non-haematological
Stimulates growth and differentiation
NB for survival of erythroid progenitors:
- Need continual exposure to EPO for survival
- Withdrawal results in Apoptosis
Non-haematological effects of EPO
- Neuroprotection
- Renal Protection
- Retinal Protection
- Wound Healing
- Angiogenesis/Vascular Protection
- Cardioprotection
The Red Blood Cell (General Information)
Structure:
- Biconcave(thinner in the centre)
- Diameter: 7.5 um( Range 6-9)
- No nucleus and mitochondria
- Volume: 82-99 fl
Can pass through narrow capillaries as narrow as 3um(Lungs)
Hypertonic Solution: Shrink
Hypotonic Solution: Becomes enlarge and ruptures
The Red Blood Cell Morphology( Blood Smear)
- Central Pallor( 1/3 of diameter)
- No Inclusions
- Almost the same size as the nucleus of a small lymphocyte
Red Blood Cell Count
Males: 4.6-6.2 x 1012/l
Females: 4.2-5.4 x 1012/l
The orginazation of the Red Blood Cell Membrane
- Highly elastic
- Responds rapidly to applied stress
- Capable of undergoing large membrane extensions
- Stronger than steel i.t.o. structural resistance
Cytoskeletal Proteins
Basic mesh of skeleton composed of interpenetrating hexagons:
-Spectrin: Forms thee side and raadii
-Spectrin self association site: Where two or more
spectrin dimers articulate
-Junctional complexes: Points of convergence of
multiple tetramers
Haemoglobin concentrations in the Adult and conditions which affect red cell count and [Hb]
Males: 16.0+/-2.0 g/dl
Females: 14.0 +/-2.0 g/dl
Age
Gender
Altitude
Disease Status
Function as well as the components of Haemoglobin
Function:
- Transport of oxygen and carbon dioxide
- Important buffer system
Components:
- Haem(Pigment)
- Globin(Protein)
What does haem consist of?
It consists of a porphyrin pigment(Protoporphyrin) to which iron is bound
What are porphrins
They are chemical compounds containing a nucleus that consists of four pyrrole rings joined by methene bridges
Where is the iron required for haem synthesis supplied from?
Food/Diet
Hemoglobins in the Normal Adult
HbA - 98%: 2A +2B
HbF - ~1& : 2A +2Y
HbA_2 - <3.5%: 2A + 2D
Factors which causes as shift to the curve:
Left:
- HbF
- Decreased 2.3 DPG
- Decreased H+
Right:
- HbS
- Increassed 2,3 DPG
- Increassed CO2
- Increassed H+
Functions of Red Cells
RBC transports oxygen from the lungs to the tissues
Transports Carbon dioxide from tissues to the lungs’
Play an important role on the pH homeostasis
Contribute to the viscosity of the Blood
Main RBC metabolic activities/House keeping functions of RBCs
- Embden-Meyerhof glycolytic Pathway
- Pentose Phosphate Pathway
- Reduction of MetHb
- Rapoport-Luebering Shunt
Embden-Meyerhof glycolytic Pathway
-Provides energy in the form of ATP
-Glucose is transported actively across the RBC
membrane by an insulin-independent mechanism
-About 90% is metabolised anaerobically,10% Pentose phosphate pathway
Embden-Meyerhof glycolytic Pathway
-Provides energy in the form of ATP
-Glucose is transported actively across the RBC
membrane by an insulin-independent mechanism
-About 90% is metabolised anaerobically,10% Pentose
phosphate pathway
Pentose Phosphate Pathway
-Has a reducing power
-Linked to the redox reactions through the glutathione
cycle
Reduction of MetHb
- Occurs under normal conditions
- The coupled reaction with NAD+
Rapoport-Luebering Shunt
-Provides the 2,3 DPG for the control of Hb oxygen affinity
Main enzymes that regulate/control additional reactions
- Glutathione Reductase
- Glucose-6-phosphate dehydrogenase
- Methaemoglobin Reductase
- DPG(Diphosphoglycerate) Mutase and DPG
Phosphatase - Carbonic Anhydrase
- ATPase
Glutathione Reductase
Catalyse reduction of glutathione disulphide to its reduced form,Glutathione
Functions:
- Protects RBC againsts oxidative stress
- Stabalise RBC membrane and Hb
Glucose-6-phosphate dehydrogenase
Leads to the production of NADPH in pentose phosphate pathway,required by glutathione reductase to reduce glutathione disulphide
Methaemoglobin Reductase
Converts methaemoglobin(Oxidised Fe3+ Hb),Produced at 3%/day) to haemoglobin
Function:
-Reduces Fe atom( in heam) from funtionally dead Fe3+ state for O2 transport
DPG(Diphosphoglycerate) Mutase and DPG Phosphatase
2,3 DPG metabolism though the Rapoport-Luebering shunt
Carbonic Anhydrase
Catalyse the following reactions:
- CO2 + H2O H2CO3
- Function: CO2 Transport
ATPase
Part of sodium/potassium pump
Funtions: Maintains Na+ and K+ balance
-Intracellular: Increased K and Decrease Na+
-Extracellular: Vice Versa
Lifespan of RBcs
+/- 120 Days
- RBCs have no nuclues, metabolism gradually deteriorates as enzyme are degraded and not replaced: Cells become non visible
- RBCs are phagocytosed and destoyed extravascularly by macrophages of the reticuloendothelial system(Bone marrow, spleen and liver).
Discuss the Breakdown of RBCs
- RBCs are brokendown into haem and globin by macrophages of the reticuloendothelial system’
- Globin: Broken down to amino acids,which are recycled.
- Haem: Dissociates into iron and porphyrin
- Iron: Binds to transferin in plasma and is recycled
- Porphyrin: Converted to biliverdin and then to bilirubin
Discuss the breakdown of RBCs(Cont.)
In plasma, Bilirubin(Fat soluble) combines with albumin(Unconjugated bilirubin)
Complex is transported to the the liver where bilirubin is freed from the albumin, and conjugated to glucuronic acid( Conjugated bilirubin)
Bilirubin-glucuronide is water soluble and is excreted into the small intestine via the bile
In the intestine bacteria convert bilirubin to urobilinogen which is sometimes converted to stercobilinogen and stercobilin and excreted in the faeces(Brownish colour)
The remainder is reabsorbed from the intestine and excreted by the kidney in urine as urobilinogen and urobilin
Intravascular haemolysis plays little to no part in normal RBC destruction
Plasma
90-92% of plamsa consists of water *Contains inorganic substances which are dissolved in plasma *Organic substances present in plasma *Plasma proteins
Inorganic Substances of Plasma
Sodium, Na Potassium, K Calcium, C Magnesium, Mg Chlorine, Cl Bicarbonate, HCO3
Organic substances of Plamsa
Proteins Amino Acids Glucose Lactate Lipids Vitamins
Plasma Proteins
Large Molecules
Pass though with difficulty through capillary membranes and tend to remain intravascular
Functions of Plasma Proteins(7)
- Exert oncotic pressure of 3.3 kPa across the capillary
wall-play a role in retaining water within capilaries
2.Transport: Carries various substances, incl.
hormones, enzymes, lipids, vit b12, bilirubin
3.Viscosity: Gives blood viscosity which helps to
create and maintain arterial pressure.
4.Buffers: Can accept both hydrogen and basic ions-
Responsible for 15% of bloods buffering capacity
5.Contains antibodies(gamma-glubulins) and other
antimicrobial protiens
6.Coagulation of blood( Through coagulation factors) - Production: Under certain circumstances to
synthesize enzymes, hormones and structural
proteins
Plasma(Definition)
Is anticoagulated and therefore contains viable clotting factors
If blood is anticoagulated and centrifuged: The fluid fraction will still contain viable clotting factors and is referred to plasma
Serum(Definition)
Plasma without coagulation factors, Plamsa that has been allowed to clot
If blood is allowed to clot and then centrifuged; the fluid(acellular) fraction on top is called serum