Structure and Function of Blood Flashcards by Joanna Mitchell

What are the different types of blood cells?

RBC
WBC
Platelets

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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

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Where is the site of haematopoiesis in the embryo?

Yolk sac then liver then marrow

3rd to 7th month

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Where is the site of haematopoiesis at birth?

Mostly bone marrow, liver and spleen when needed

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Where is the site of haematopoiesis from birth to maturity?

Number of active sites in bone marrow decreases but retains the ability for haematopoiesis

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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

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What has to happen to a stem cell to make blood?

Proliferation
Differentiation
Self renewal
Most stem cells are in a quiecent state

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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

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Do cells get bigger or smaller as they divide?

Smaller

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Describe the maturation progression of erythrocytes?

Pronormoblast 
Basophilic 
Polychromatophilic
Orthochromatic 
Reticulocyte
Mature red cell

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What is the precursor to platelets?

Megakaryocyte

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What are the different forms of granulocytes?

Eosinophils
Basophils
Neutrophils

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What is the structure of neutrophils?

Lobulated polymorphic nucleus

Neutral staining granules

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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

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What is the structure of eosinophils?

Bi-lobed

Bright orange/ red granules

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What is the function of eosinophils?

Fight parasitic infection
Hypersensitivity; allergic reactions
Elevated in patients with allergic conditions; asthma, atopic rhinitis

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What is the structure of basophils?

Infrequent in circulation

Large deep purple granules obscuring nucleus

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What is the function of basophils?

Circulating version of tissue mast cells
Mediated hypersensitivity reactions
Fc receptors bind IgE
Granules contain histamine

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What is the structure of monocytes?

Large single nucleus

Faintly staining granules, often vacuolated

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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

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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

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What is the function of lymphocytes?

Numerous types; B, T, NK

Cognate response to infection

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What is the precursor cell to basophils, eosinophils, neutrophils and monocytes?

Myeloblast of which that is a lineage of common myeloid progenitor

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What is the precursor cell to dendritic cells and macrophages?

Monocytes of myeloblast of common myeloid precursor

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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?

5. 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