Structure and Function of Blood Flashcards
What are the different types of blood cells?
RBC
WBC
Platelets
What is haematopoiesis?
Production of blood cells
Derived from a relatively small pool of pluripotent stem cells capable of making all the different types of blood cells
Where is the site of haematopoiesis in the embryo?
Yolk sac then liver then marrow
3rd to 7th month
Where is the site of haematopoiesis at birth?
Mostly bone marrow, liver and spleen when needed
Where is the site of haematopoiesis from birth to maturity?
Number of active sites in bone marrow decreases but retains the ability for haematopoiesis
Where is the site of hematopoiesis in adults?
Not all bones contain bone marrow
Haematopoiesis restricted to the skull, ribs, sternum, pelvis, proximal ends of femur
What has to happen to a stem cell to make blood?
Proliferation
Differentiation
Self renewal
Most stem cells are in a quiecent state
How will a neutrophil progress?
Myeloblast to promyelocyte to myelocyte through to metamyelocyte forms eventually to band forms and neutrophils that are seen in blood
Do cells get bigger or smaller as they divide?
Smaller
Describe the maturation progression of erythrocytes?
Pronormoblast Basophilic Polychromatophilic Orthochromatic Reticulocyte Mature red cell
What is the precursor to platelets?
Megakaryocyte
What are the different forms of granulocytes?
Eosinophils
Basophils
Neutrophils
What is the structure of neutrophils?
Lobulated polymorphic nucleus
Neutral staining granules
What is the function of neutrophils?
Short life in circulation - transit to tissues
Phagocytose invaders
Kill with granule contents and die in the process
Attract other cells
Increased body stress - infection, trauma, infarction
What is the structure of eosinophils?
Bi-lobed
Bright orange/ red granules
What is the function of eosinophils?
Fight parasitic infection
Hypersensitivity; allergic reactions
Elevated in patients with allergic conditions; asthma, atopic rhinitis
What is the structure of basophils?
Infrequent in circulation
Large deep purple granules obscuring nucleus
What is the function of basophils?
Circulating version of tissue mast cells
Mediated hypersensitivity reactions
Fc receptors bind IgE
Granules contain histamine
What is the structure of monocytes?
Large single nucleus
Faintly staining granules, often vacuolated
What is the function of monocytes?
Circulate for a week and enter tissues to become macrophages
Phagocyte invaders; kill them and present antigen to lymphocytes
Attract other cells
More long lived than neutrophils
What is the structure of lymphocytes?
Mature; small with condensed nucleus and a rim of cytoplasm If activated (atypical) - large with plentiful blue cytoplasm extending round neighbouring red cells
What is the function of lymphocytes?
Numerous types; B, T, NK
Cognate response to infection
What is the precursor cell to basophils, eosinophils, neutrophils and monocytes?
Myeloblast of which that is a lineage of common myeloid progenitor
What is the precursor cell to dendritic cells and macrophages?
Monocytes of myeloblast of common myeloid precursor
What is the precursor cell to platelets?
Megakaryocytes of myeloid progenitor
What is the immediate precursor cell to erythrocyte?
Reticulocyte
What is the precursor cell to B, T and NK cells?
Common Lymphoid progenitor
What cells will originate from common myeloid progenitor cells?
Megakaryocyte
Erythrocyte
Mast cell
Myeloblast
How are primitive precursor cells recognized?
Immunophenotyping; expression of antigens on cell surface
Bio-assays; culture in vitro and show lineage of progeny in different growth conditions
Where are common sites for bone marrow aspiration?
Posterior iliac crests
What is the name of a normal marrow biopsy?
Trephine
What are the required properties of RBC?
Full of Hb to carry oxygen No nucleus to allow flexibility and Hb molecules No mitochondria High surface area/ volume ratio Flexible to squeeze through capillaries
What are the consequences of red blood structure?
Full of Hb; high oncotic pressure, oxygen rich environment (oxidation risk)
No nucleus; can’t divide or replace damaged proteins, limited life span
No mitochondria; limited to glycolysis
High SA/ volume ratio; need mechanism to keep water out
Flexible; specialised membrane required that can ensue mutations
What molecules in the RBC membrane allow for flexibility?
Alpha and beta spectrin connected by tropomyosin actin complex
What mechanism is present in RBC to ensure water is kept out?
Na/K+ ATPase pump (sodium out, potassium in)
What type of protein is Hb?
Tetrameric globular protein
What is the structure of Hb?
2 alpha and 2 beta chains
Heme group is Fe2+ in a flat porphyrin ring
One haem per subgroup
One oxygen binds to one Fe2+ (will NOT bind to oxidised Fe3+)
What is the function of haemaglobin?
Delivers oxygen to tissues
Buffer for H+
CO2 transport
What regulates red cell production?
Erythropoietin via hypoxia sensors in kidney
What is the lifespan of a red blood cell?
120 days
What happens to a red blood cells once it has reached its life span
Taken up by macrophages
Globin chains recycled to amino acids
Haem group broken down to iron and bilirubin
Bilirubin taken to liver to be conjugated and excretes in bile
How is iron stored?
As ferritin or hemosiderin
Can be released to transferrin with the aid of ceruloplasmin
What is the basic breakdown of haem?
Haem
Porphyrin
Biliverdin
Bilirubin
What is the pathway of ATP production in red blood cells?
EXAM CONTENT
Embden-Meyerhof Pathway
Net gain of ATP and NADH
2 pyruvate
What is the function of NADH in RBC?
Prevent oxidation of Fe2+ to Fe3+
What is Fe3+ called?
Met Hb; oxidised Hb that has no capacity to carry O2
What are the reactive oxygen species that can be found in RBC?
Superoxide
Hydrogen Peroxide
Free radicals that have an unpaired free electron and can interact with other molecules (protein, DNA) and damage their structure
What enzyme converts superoxide to hydrogen peroxidase?
Superoxide dismutase
What enzyme converts hydrogen peroxidase to water?
Peroxidases catalase
What is the function of glutathione (GSH)?
Protects us from hydrogen peroxide by reacting with it to form water and oxidised glutathione product (GSSG)
How can glutathione be replenished?
NADPH
How is NADPH generated?
EXAM content
Hexose Monophosphate Shunt
What is the rate limiting enzyme in the hexose monophosphate shunt that forms NADPH?
G6PD
Can you have mutations in G6PD?
Yes; x-linked condition
Why is a G6PD deficiency harmful?
Prevents neutralisation of damaging oxidative stress (hydrogen peroxide) to RBC
RBC will not live as long and will be hemolyzed
How does CO2 get from the tissues to the lungs?
10% dissolved in solution
30% bound to Hb as carbamino-Hb
60% converted to bicarb
What converts carbon dioxide to bicarb?
Carbonic anhydrase
What exchange exports HCO3- from RBC?
Chloride/ bicarb shift
Cl- enters cell to preserve potential; cell swells
When does the oxygen dissociation curve need to shift to the right?
Anaemic, metabolic acidosis, hypercapnia
What is the structure of Hb in the foetus?
2 alpha, 2 gamma subunits
How much oxygen will 1g of fully saturated Hb contain?
1.34 ml
What do most dissociation curves follow?
Michaelis-Menten kinetics
What dissociation curve does oxygen show?
Sigmoidal
Allosteric effect/ cooperative binding
What dissociation curve does myoglobin show?
Hyperbolic
What shunt forms t2,4-BPG?
Rapapoport Lubering shunt
In what conditions is the Rapapoport-Lubering Shunt activated?
Chronic anaemia; will burrow into Hb interacting with how oxygen binds allowing increased oxygen tissue delivery
What will shift the curve to the right?
Increased H+/ decreased pH
Increased 2,3-BPG
Increased temp
Increased CO2
What are the clinical parts of the oxygen dissociation curve?
- 3 in venous blood
13. 3 in arterial blood
What is the benefit of myoglobin and fHb?
At same pO2; they will bind to more O2
What are the conditions that result in a dysfunctional red cell membrane structure?
Hereditary Spherocytosis
What are the 3 main pathways in the biochem of red cells?
Embden-Meyerhof Pathway; anaerobic glycolysis that generates ATP and NADH (reverses metHb to Fe2+)
Hexose Monophosphate Shunt; generates NADPH, protective against oxidative stress and regenerates glutathione
Rapapoport-Lubering Shunt; generates 2,3-BPG which shift oxygen dissociation curve to right and allows more o2 to be released
