blood constituents, haematopoiesis and transfusion Flashcards
What is blood made of?
Plasma 55%
Buffy coat (leukocytes and platelets) <1%
Erythrocytes 45%
Adults have 5l of blood
Haematocrit- 0.45 (% RBCs)
If too high- stroke etc
1000x more than WBCs as have to transport O2
What is haematopoiesis?
The process by which blood cells are formed
Least mature- multipotential hematopoietic stem cell (pluripotent)- needed to make all blood cells, in bone marrow, needed for bone marrow transplants
Most mature- macrophage, plasma cell etc, more limited life span
What stems from common myeloid progenitors?
Erythrocytes (RBCs) Mast cells Myeloblasts Basophils Neutrophils Eosinophils Monocytes Macrophages Megakaryocytes Thrombocytes (platelets)
What stems from common lymphoid progenitors?
Natural killer cells (large granular lymphocytes)
Small lymphocytes
T and B lymphocytes
Plasma cells
What can be seen in a whole blood smear?
Small cell fragments- platelets
Many RBCs- anuclear
WBCs- lobed nucleus
Where does haematopoiesis take place?
Bone marrow
In children- all bones
In adults- axial skeleton and proximal ends of long bones (if not in bone marrow due to eg. Cancer or anaemia, can resume in liver/spleen)
~bone marrow in pelvis contains precursor cells (taken for transplants)
In embryo- waves of haematopoiesis come from yolk sac
What is the bone marrow niche?
Stem cells Endothelial cells Fibroblasts Stromal cells Fat cells
Cues to enable changes in haematopoiesis via cell surface receptors on stem cells that tell them how to divide
What are stem cells?
Pluripotent
Self replicating
Some progeny differentiate into mature cells
As stem cells taken out, they differentiate in vitro or in blood (why we need bone marrow transplants)
What is the lifespan of mature cells in blood?
RBCs- 120 days
WBCs- 6-24hrs (neutrophils), a day (monocytes)
Platelets- 7-10 days
Old/dying cells are removed by liver and spleen via reticuloendothelial system
How is haematopoiesis controlled?
Hormones (often glycoproteins) act via intracellular signalling cascades eg. phosphorylation to transmit signals from receptors to nucleus- changes transcription to differentiate into correct cell
Erythropoietin drives RBC production
Granulocyte colony stimulating factor is used to treat neutropenia (stimulates WBCs)- elevated after infection
Thrombopoietin used to treat thrombocytopenia (stimulates platelets)
What are RBCs?
No nucleus/mitochondria
Bags of Haemoglobin (if free Hb- renal failure)
Rely on glycolysis for ATP (lactose goes to liver)
Rely on pentose phosphate pathway to make reducing NADPH and prevent oxidative damage (ROS)
Biconcave disc, high SA:vol for gas transfer, flexible, 4 x 10^12/l RBCs, can’t cross endothelia
Stem cell-> early progenitor-> nucleated precursor-> reticulocyte (48hrs)-> RBC
Kidney- Hif- detects O2- can drive EPO
Reticulocytes- if high- haemorrhage, if low- deficiencies
What is haemoglobin?
4 chains- 2 beta, 2 alpha
Tetrameric structure
Each monomer has haem group containing Fe where O2 binds
Cooperative binding- 1 O2 binding facilitates other binding, release of O2 facilitates others
Low O2- H+, CO2, 2,3-diphosphoglycerate causes release of O2 to periphery
Mutations lead to eg. Sickle cell anaemia, thalassaemia
What is anaemia?
Not enough RBCs, not enough Hb Not many specific symptoms Acute- blood loss Chronic- insufficient haematinics eg. Vit B12, B6 and folate Genetic causes- mutations
What are symptoms of anaemia?
Fatigue Dizziness Pallor (mucous membrane esp) Headaches Increased cardiac output Tachycardia Systolic murmur
What is polycythaemia?
Increase in RBCs due to-
Raised EPO
Hypoxia
Polycythaemia vera- mutation of JAK2
Reduced plasma volume due to-
Dehydration, smoking, industrial working, hypoxic lung disease
Can lead to- high Hb-> more viscous blood-> thrombosis (arterial and venous)
What are platelets?
Tiny anucleate cells Made from megakaryocytes Circulate in resting state Bind to damaged vessel walls Stops bleeding- primary haemostasis
What happens when platelets become activated?
Become spiky and migratory
Secrete mediators to aggregate
How many platelets are normal?
140-400 x10^9/l
Thrombocytopenia
<80 =increased risk of bleeding
<50 =teeth extraction concern
<20 =spontaneous bleeding/bruising (intracranial worry)
Thrombocytosis
Eg. Due to Polycythaemia Vera or essential thrombocythaemia
Increased rates of arterial/venous thrombosis
Treated w aspirin or similar
What are neutrophils?
Phagocytosis and kill bacteria
Lysosomes fuse w phagosomes (acidification/activation of proteases)
Release cytokines- temperature, redness, swelling
Increased no during infections
Spot/boils- pus- dead neutrophils
Neutropenia- eg. After chemo
Can stimulate neutrophil production w GMCSF
What are monocytes/macrophages?
Macrophage- in tissue, look for infections (phagocytosis and release mediators to recruit other immune cells)
Monocyte- in circulation, differentiate into macrophages
What are lymphocytes?
Fight viral infections
Lymphocytosis- high nos
B cells- make antibodies, make memory cells
T cells- cytotoxic/helper cells, protect against cell invasion (non-self)
How might one become immunodeficient?
Lack of lymphocytes
Eg. HIV infects CD4 T cells
Patients die of opportunistic infections
What are plasma proteins?
Eg. Albumin (main component of plasma)
Albumin- regulates blood vol and osmosis
Others- carrier proteins, coagulation proteins, complement proteins, immunoglobulins
What are immunoglobulins?
Antibodies produced by plasma cells (differentiated B cells)
Classes- IgG, IgA, IgM etc
Basis of vaccination
What are coagulation factors?
Inactive proteins in circulation Eg. convert soluble fibrinogen into insoluble fibrin polymer Overactivity= thrombosis Failure= bleeding, haemophilia Eg. Factor I (fibrinogen), Factor XIII
What is blood transfusion?
RBCs in a sugar solution
Increased O2 capacity
Can also transfuse platelets
Recombinant proteins used over plasma to reduce infection risk
WBCs rarely given
Specific proteins given (eg. Clotting factors)
What are blood groups?
RBCs carry surface antigens (mostly sugars) that differ between people (inherited)
38 blood group systems
Mainly- ABO and Rhesus
Lewis, Kell and MNS- low risk
What are the ABO blood groups?
A B AB O Result in different sugar modifications on RBC surface O is recessive so O= OO A= AA or AO B= BB or BO AB= AB
O is most common in Caucasians
O= universal donor
AB= universal recipient
What antibodies recognise RBC antigens?
IgM antibodies
These don’t cross the placenta
Baby can have different blood type to you
What are the Rhesus blood groups?
Complex system of C D and E antigens (>50)
D= most likely to provoke immune response
D is dominant so D positive (DD or Dd) and D negative (dd)
85% of population= D +ve
If D -ve= antibodies against D
What is Rhesus D disease?
If dd woman has D+ partner, mum can have harmful antibodies against baby= Rhesus D disease (jaundice-> death of baby)
Blood mixes when placenta comes away after second birth so memory antibodies
How is Rhesus D disease prevented?
The mother is given anti-D antibodies to mop up the D from the baby (prevents sensitisation
Men are vaccinated with D to make anti-D for therapy
Why might someone need a blood transfusion?
Hypovalaemia- blood loss
Severe anaemia- inadequate tissue oxygenation
Anaemia that can’t be corrected by bone marrow function
When should blood transfusion not be used?
Iron/B12/folate deficiency
Minor blood loss esp. if fit and healthy
Asymptomatic anaemia
What are the risks of blood transfusion?
ABO incompatibility- fatal
Delayed transfusion reactions
Febrile reactions (fever), urticarial reactions
Fluid overload, pulmonary oedema
Infections (bacterial, viral, malarial, prions)
Iron overload= long term (damage liver and heart)
