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Medicine - Year 2 > The haematological system and skin - Physiology > Flashcards

The haematological system and skin - Physiology Flashcards

1
Q

Name the key players in iron metabolism

A
  • DMT-1
  • Ferritin
  • Transferrin
  • Transferrin receptor
  • Haemosiderin
  • Ferroportin
  • Hepcidin
  • HFE
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2
Q

Describe the absorption of iron

A

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

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3
Q

What increases the absorption of iron? (name 6)

A
  • Fe2+
  • Haem iron
  • Acids
  • Ascorbate
  • Solubilising agens - sugars, amino acids
  • Pregnancy
  • Increased erythropoiesis
  • Haemochromatosis
  • Increased DM1
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4
Q

What decreases the absorption of iron? (name 6)

A
  • Fe3+
  • Non-organic iron
  • Alkalis
  • Phytates and phosphates
  • Tea
  • Tetracyclines
  • High iron diet
  • Infections
  • High body iron store
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5
Q

Describe the absorption of folate metabolism

A

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

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6
Q

Where does erythropoiesis occur?

A

Bone marrow

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7
Q

Name 5 requirements of erythropoiesis

A
  • Normal stem cell
  • Normal maturation
  • Healthy bone marrow microenvironment
  • Growth factors (erythropoietin, GM-CSF)
  • Essential components: iron, vitaminB12, folate, amino acids
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8
Q

Name the 4 types of RBC cell in the maturation of a RBC

A
  1. Erythroblasts
  2. Nucleated rBC
  3. Reticulocyte
  4. Mature red cells
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9
Q

What makes red blood cells pliable?

A

Biconcave shape due to RBC membrane allows it to squeeze through capillaries

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10
Q

Describe the RBC membrane that makes it RBC pliable

A

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

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11
Q

How many polypeptide chains is haemoglobin composed of?

A

Four

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12
Q

Name the three types of haemoglobin that occur in normal adult blood

A

Haemoglobin A

Haemoglobin A2

Haemoglobin F

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13
Q

Describe the haemoglobin chain pairing for the following

a) HbA in adult

b) HBA in foetal

c) HbA2

A

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

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14
Q

Describe the haemoglobin chain pairing for the following

a) HbA in adult

b) HBA in foetal

c) HbA2

A

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

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15
Q

Why is there different haemoglobin in foetus and adult?

A

Foetal haemoglobin has a higher affinity so oxygen flows from the maternal to foetus circulation more regularly across the placenta

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16
Q

What is the life span of RBCs?

A

120 days

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17
Q

Group A blood type: antigens on red cell surface and antibodies in plasma

A

Antigens on red cell: A

Antibodies in plasma: Anti-B

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18
Q

Group B blood type: antigens on red cell surface and antibodies in plasma

A

Antigens on red cell: B

Antibodies in plasma: Anti-A

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19
Q

Group AB blood type: antigens on red cell surface and antibodies in plasma

A

Antigens on red cell: A+B

Antibodies in plasma: none

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20
Q

Group O blood type: antigens on red cell surface and antibodies in plasma

A

Antigens on red cell: (Small H)

Antibodies in plasma: Anti-A + Anti-B

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21
Q

Who can donate blood?

A

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

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22
Q

Alternatives to blood transfusion

A

Erythropoietin (EPO)

(Anabolic) steroids

Vitamin B12

Iron

Folate

Monitoring

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23
Q

Red cell transfusion - indications

A

Severe haemorrhage

Severe anaemia refractory to other therapy or needing rapid correction

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24
Q

Types of red cells for transfusion

A

Fresh whole blood

Packed red cell

25
Q

Platelet storage - temperature and shelf life

A

Temperature
- 22 degrees celsius and

Shelf life
- Short of 5-7 days

26
Q

Platelet support - indications

A
  • 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
27
Q

Fresh frozen plasma - temperature of storage and shelf life

A

Temperature
- -30 degree celsius

Shelf lide
- 1 year

28
Q

Fresh frozen plasma - indications

A
  • DIC
  • Massive transfusion
  • Thrombotic thrombocytopenia purpura
  • Liver disease with abnormal clotting
  • Some rare factor deficiencies where factor concentrate is not available
29
Q

Cryoprecipitate - indications

A
  • DIC
  • Liver disease
  • Following massive transfusion
30
Q

Albumin solution - indications (contains no coagulation factors)

A

Used in the treatment of hypovolaemia
(particularly when caused by burns and shock associated with multiple organ failure)

31
Q

What increases the risk of an alloantibody formation against red cell antigen

A

Pregnancy

Red cell transfusion

32
Q

Why is anti-D prophylaxis given?

A

To prevent the development of immune anti-D and hence haemolytic disease of the foetus

33
Q

Who is anti-D prophylaxis given to?

A

RhD negative women who are pregnant

RhD negative patient after exposure - accidental or deliberate

34
Q

When is Anti-D prophylaxis given?

A

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

35
Q

How is anti-D prophylaxis given?

A

IM into the the deltoid muscle

36
Q

Alternatives of blood products for anaemia

A

Treat underlying cause

Iron tablets

IV iron

Vitamin B12

Folic acid

Erythropoietin

37
Q

Alternatives of blood products for thrombocytopenia

A

Platelets only if unavoidable

Corticosteroids

Transexemic acid

Maximise clotting - avoid aspiring, NSAIDs

38
Q

Alternatives for plasma transfusion

A

Recombinant factors

Vitamin K

Prothrombin complex concentrate (PCC)

Fibrinogen concentrate

39
Q

Where does haem synthesis occur?

A

Partly in mitochondria and partly in the cytoplasm

40
Q

Rate limiting reaction of haem synthesis

A

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)

41
Q

Rate limiting reaction of haemolytic synthesis - location

A

Mitochondria

42
Q

Porphyria - presentation

A

Acute neurovisceral features (with or without ski lesions)

Sun-induced urticaria or erythema

Active skin lesions: erosion +/- bullae

43
Q

Formation of the platelet plug - adhesion, activation and aggregation

A
  1. Damage to a blood vessel causes exposure of collagen. vWF binds to collagen
  2. 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
  3. The aggregation of platelets result in formation of a platelet plug that temporally seals the break in the vessel wall
  4. Following formation of the platelet plug, coagulation is activated to form a fibrin mesh which stabilises the platelet plug
44
Q

Coagulation pathway - factors involved in intrinsic pathway

A

XII, XI, IX, VIII

45
Q

Coagulation pathway - factors involved in extrinsic pathway

A

VII and tissue factor

46
Q

Coagulation pathway - factors involved in common pathway

A

X, V, prothrombin, fibrinogen

47
Q

Coagulation pathway - describe the intrinsic pathway

A

XII activated to XIIa –>

XI activated to XIa –>

IX activated to Ixa: VIIIa –>

activates common pathway

48
Q

Coagulation pathway - describe the extrinsic pathway

A

VII becomes activated to VIIa and forms a complex with tissue factor

49
Q

Coagulation pathway - describe the common pathway

A

Factor X becomes activated and converted prothrombin to thrombin and that converts fibrinogen to fibrin

50
Q

What stops the coagulation process from forming thrombi throughout the circulation?

A

Coagulation inhibitors
- Antithrombin
- Protein C
- Protein S

Fibrinolysis

51
Q

Fibrinolysis - process

A

Plasminogen converted to plasmin

Plasmin breaks down fibrin clot into fibrin degradation products (D-dimers)

52
Q

Prothrombin time (PT)

a) Activators

b) Coagulation pathway

c) Factors

d) Normal clotting time

e) Abnormal in e.g.,

A

a) Tissue factor + calcium

b) Extrinsic + Common

c) Extrinsic - VII
Common - V, X, Prothrombin, fibrinogen

d) 10-13 secs

e) Liver disease, warfarin DIC

53
Q

Activated partial thromboplastin time (APTT)

a) Activators

b) Coagulation pathway

c) Factors

d) Normal clotting time

e) Abnormal in e.g.,

A

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

54
Q

Thrombin time

a) Activators

b) Coagulation pathway

c) Factors

d) Normal clotting time

e) Abnormal in e.g.,

A

a) Thrombin

b) Fibrinogen to fibrin

c) Fibrinogen

d) 14-16 secs

e) Low fibrinogen states

55
Q

Haematopoiesis - location in foetus

A

Yolk sac, liver, spleen and lymph nodes

56
Q

Haematopoiesis - location in babies and children

A

All bone marrow

57
Q

Haematopoiesis - location in adults

A

Bone marrow of axial skeleton and proximal long bones

58
Q

Red cell and erythropoietin (expo) feedback - process

A

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

Medicine - Year 2 (27 decks)

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