The haematological system and skin - Physiology Flashcards
Name the key players in iron metabolism
- DMT-1
- Ferritin
- Transferrin
- Transferrin receptor
- Haemosiderin
- Ferroportin
- Hepcidin
- HFE
Describe the absorption of iron
Enzyme on brush border (ferric reductase) converts (Ferric iron) Fe3+ to Fe2+ (Ferrous iron)
DMT1 uptakes Fe2+ into enterocytes
The iron within enterocytes can either be stored as ferritin, or transferred into the bloodstream via the protein ferroportin.
Once in the blood, iron is bound to the transport protein transferrin, and is mostly transported to bone marrow for erythropoiesis.
Some iron is taken up by macrophages in the reticuloendothelial system as a storage pool.
Fe2+ transfers enterocytes and
What increases the absorption of iron? (name 6)
- Fe2+
- Haem iron
- Acids
- Ascorbate
- Solubilising agens - sugars, amino acids
- Pregnancy
- Increased erythropoiesis
- Haemochromatosis
- Increased DM1
What decreases the absorption of iron? (name 6)
- Fe3+
- Non-organic iron
- Alkalis
- Phytates and phosphates
- Tea
- Tetracyclines
- High iron diet
- Infections
- High body iron store
Describe the absorption of folate metabolism
Native folates present as polyglutamate
Converted to mono glutamate by folate conjugate in burst border membrane
This is absorbed in duodenum (HCPI) and methylated to methyl-THF
Where does erythropoiesis occur?
Bone marrow
Name 5 requirements of erythropoiesis
- Normal stem cell
- Normal maturation
- Healthy bone marrow microenvironment
- Growth factors (erythropoietin, GM-CSF)
- Essential components: iron, vitaminB12, folate, amino acids
Name the 4 types of RBC cell in the maturation of a RBC
- Erythroblasts
- Nucleated rBC
- Reticulocyte
- Mature red cells
What makes red blood cells pliable?
Biconcave shape due to RBC membrane allows it to squeeze through capillaries
Describe the RBC membrane that makes it RBC pliable
RBC have protein skeleton (spectrin, band-3 protein, actin, protein 4.1 and ankyrin) which maintain the RBC biconcave shape and deformability
The proteins contains several sulfhydyl (-SH) groups which are essential for the maintenance of their tertiary structure and therefore the structural integrity of the red cell
How many polypeptide chains is haemoglobin composed of?
Four
Name the three types of haemoglobin that occur in normal adult blood
Haemoglobin A
Haemoglobin A2
Haemoglobin F
Describe the haemoglobin chain pairing for the following
a) HbA in adult
b) HBA in foetal
c) HbA2
a) pairing 2 alpha chains and 2 beta chains
b) Pairing 2 alpha chains and 2 gamma chains
c) pairing 2 alpha chains and 2 delta chains
Describe the haemoglobin chain pairing for the following
a) HbA in adult
b) HBA in foetal
c) HbA2
a) pairing 2 alpha chains and 2 beta chains
b) Pairing 2 alpha chains and 2 gamma chains
c) pairing 2 alpha chains and 2 delta chains
Why is there different haemoglobin in foetus and adult?
Foetal haemoglobin has a higher affinity so oxygen flows from the maternal to foetus circulation more regularly across the placenta
What is the life span of RBCs?
120 days
Group A blood type: antigens on red cell surface and antibodies in plasma
Antigens on red cell: A
Antibodies in plasma: Anti-B
Group B blood type: antigens on red cell surface and antibodies in plasma
Antigens on red cell: B
Antibodies in plasma: Anti-A
Group AB blood type: antigens on red cell surface and antibodies in plasma
Antigens on red cell: A+B
Antibodies in plasma: none
Group O blood type: antigens on red cell surface and antibodies in plasma
Antigens on red cell: (Small H)
Antibodies in plasma: Anti-A + Anti-B
Who can donate blood?
Are fit and healthy
Weight between 50-158kg
Are aged between 17 and 66
Are over 70 and have given full blood donation in the last 2 years
Alternatives to blood transfusion
Erythropoietin (EPO)
(Anabolic) steroids
Vitamin B12
Iron
Folate
Monitoring
Red cell transfusion - indications
Severe haemorrhage
Severe anaemia refractory to other therapy or needing rapid correction
Types of red cells for transfusion
Fresh whole blood
Packed red cell
Platelet storage - temperature and shelf life
Temperature
- 22 degrees celsius and
Shelf life
- Short of 5-7 days
Platelet support - indications
- Thrombocytopenia <50 x 10^9/L – in the presence of significant bleeding or prior to an invasive procedure
- Thrombocytopenia <10 x 10^9/L or higher – in patients with infection or bleeding.
- Prophylactic platelet transfusions in post-chemotherapy or stem cell transplant or bone marrow failure patients or patients with severe thrombocytopenia who are to have red cell transfusions
- Functional platelet disorder (numbers may be normal) with bleeding e.g., inherited platelet disorder, DIC
- Dilutional’ thrombocytopenia e.g., from massive bleeding
- Thrombocytopenia which is multifactorial and associated with bleeding e.g., liver disease
Fresh frozen plasma - temperature of storage and shelf life
Temperature
- -30 degree celsius
Shelf lide
- 1 year
Fresh frozen plasma - indications
- DIC
- Massive transfusion
- Thrombotic thrombocytopenia purpura
- Liver disease with abnormal clotting
- Some rare factor deficiencies where factor concentrate is not available
Cryoprecipitate - indications
- DIC
- Liver disease
- Following massive transfusion
Albumin solution - indications (contains no coagulation factors)
Used in the treatment of hypovolaemia
(particularly when caused by burns and shock associated with multiple organ failure)
What increases the risk of an alloantibody formation against red cell antigen
Pregnancy
Red cell transfusion
Why is anti-D prophylaxis given?
To prevent the development of immune anti-D and hence haemolytic disease of the foetus
Who is anti-D prophylaxis given to?
RhD negative women who are pregnant
RhD negative patient after exposure - accidental or deliberate
When is Anti-D prophylaxis given?
Pregnancy: after a potentially sensitising event (e.g., birth of rHD positive foetus , abortion or antepartum haemorrhage), prophylactically at 28 weeks, on delivery of an RhD positive babe
Accidental exposure
Deliberate exposure
How is anti-D prophylaxis given?
IM into the the deltoid muscle
Alternatives of blood products for anaemia
Treat underlying cause
Iron tablets
IV iron
Vitamin B12
Folic acid
Erythropoietin
Alternatives of blood products for thrombocytopenia
Platelets only if unavoidable
Corticosteroids
Transexemic acid
Maximise clotting - avoid aspiring, NSAIDs
Alternatives for plasma transfusion
Recombinant factors
Vitamin K
Prothrombin complex concentrate (PCC)
Fibrinogen concentrate
Where does haem synthesis occur?
Partly in mitochondria and partly in the cytoplasm
Rate limiting reaction of haem synthesis
Condensation of succinyl CoA and glycine to form enzyme-bound alpha-amino-beta ketoadipate
Decarboxylation of alpha-amino-beta-ketoadipate to form beta-aminolevulinate (ALA)
Rate limiting reaction of haemolytic synthesis - location
Mitochondria
Porphyria - presentation
Acute neurovisceral features (with or without ski lesions)
Sun-induced urticaria or erythema
Active skin lesions: erosion +/- bullae
Formation of the platelet plug - adhesion, activation and aggregation
- Damage to a blood vessel causes exposure of collagen. vWF binds to collagen
- Platelets adhere to the damaged endothelium via vWF. When platelets adhere, they activate and deregulate - their shape changes and they release chemicals that cause vasoconstriction and draw more platelets to the damaged area. This positive feedback loop continues
- The aggregation of platelets result in formation of a platelet plug that temporally seals the break in the vessel wall
- Following formation of the platelet plug, coagulation is activated to form a fibrin mesh which stabilises the platelet plug
Coagulation pathway - factors involved in intrinsic pathway
XII, XI, IX, VIII
Coagulation pathway - factors involved in extrinsic pathway
VII and tissue factor
Coagulation pathway - factors involved in common pathway
X, V, prothrombin, fibrinogen
Coagulation pathway - describe the intrinsic pathway
XII activated to XIIa –>
XI activated to XIa –>
IX activated to Ixa: VIIIa –>
activates common pathway
Coagulation pathway - describe the extrinsic pathway
VII becomes activated to VIIa and forms a complex with tissue factor
Coagulation pathway - describe the common pathway
Factor X becomes activated and converted prothrombin to thrombin and that converts fibrinogen to fibrin
What stops the coagulation process from forming thrombi throughout the circulation?
Coagulation inhibitors
- Antithrombin
- Protein C
- Protein S
Fibrinolysis
Fibrinolysis - process
Plasminogen converted to plasmin
Plasmin breaks down fibrin clot into fibrin degradation products (D-dimers)
Prothrombin time (PT)
a) Activators
b) Coagulation pathway
c) Factors
d) Normal clotting time
e) Abnormal in e.g.,
a) Tissue factor + calcium
b) Extrinsic + Common
c) Extrinsic - VII
Common - V, X, Prothrombin, fibrinogen
d) 10-13 secs
e) Liver disease, warfarin DIC
Activated partial thromboplastin time (APTT)
a) Activators
b) Coagulation pathway
c) Factors
d) Normal clotting time
e) Abnormal in e.g.,
a) ‘Contact activator’ phospholipid + calcium
b) Intrinsic + common
c) Intrinsic = XII, XI, IX, VIII
Common: V, X, Prothrombin, Fibrinogen
d) 24-38 seconds
e) Haemophilia A/B, DIC, lupus anticoagulant
Thrombin time
a) Activators
b) Coagulation pathway
c) Factors
d) Normal clotting time
e) Abnormal in e.g.,
a) Thrombin
b) Fibrinogen to fibrin
c) Fibrinogen
d) 14-16 secs
e) Low fibrinogen states
Haematopoiesis - location in foetus
Yolk sac, liver, spleen and lymph nodes
Haematopoiesis - location in babies and children
All bone marrow
Haematopoiesis - location in adults
Bone marrow of axial skeleton and proximal long bones
Red cell and erythropoietin (expo) feedback - process
Low blood oxygen
Stimulates liver and kidneys
To release erythropoetin in blood stream
Stimulates red bone marrow to release more red cells in blood stream
This increases oxygen-carrying capacity
This increase inhibits erythropoietin
