Week 5 Physiology

Blood makes up 8% of body wt, approx 5.6L in a 70Kg person, 55% is plasma

 

Platelets.

  • Small granulated bodies that aggregate in sites of vascular injury
  • Made by megakaryocytes
  • No nuclei
  • 300 000/microL
  • T1/2 = 4d
  • Splenectomy increases platelet count, cos spleen sequesters platelets

 

Red cells.

  • Biconcave, no nuclei at maturation,
  • T1/2 120d
  • 5million/ microL, 900g circulating Hb
  • Spleen removes old or damaged RBCs, contains platelets and is important in immunity

 

Haemoglobin.

  • 4 subunits – Haemoglobin A(Adult) – 2 alpha, 2 beta
  • Haem is an iron containing porphyrin
  • 2.5% on adult blood is Haem A2 – 2 alpha, 2 delta
  • O2 + Hb = oxyhaemoglobin – its formation affected by pH, temp, 2,3 DPG (needs F2+)
  • Drug exposure leads to Fe3+ –> methHb –> NADH methHB reductase then converts it back to normal Hb
  • Carbon monoxide has much higher affinity for Hb than O2 so it will displace O2 from Hb and form carboxy Hb  and reduce O2 carrying capacity of blood.
  • Fetal Hb – 2 alpha, 2 gamma – have more affinity for O2 than adult Hb
  • Haem made from succinyl coA and glycine
  • Hb breakdown
  • Hb split to haem and globin –> haem turn to biliverdin–> biliverdin –> unconjugated Bilirubin –> travels with albumin –> liver conjugates –> bile –> colon –> reabsorbed –> excreted in urine as urobilinogen

 

Blood types

  • ABO
    • Dominant inheritance
    • Congenitally we have a combination of A or B or no antigens(agglutinogens) on surface of RBC, we also develop antibodies(agglutinins) to the antigens not present on the RBC as infants.
  • Rhesus
    • Antigen in some RBC – usually D but can also refer to C or E
    • Important cos sensitization in Rh- mothers can cause fetal anaemia in subsequent Rh + baby(erythroblastosis fetalis, hydrops fetalis, kernicterus).
    • 85% of caucasians are Rh +, 99% asians are Rh +

 

Transfusion reactions.

Types

  • Acute haemolytic reaction
    • Occurs when the native blood has preformed antibodies against any protein in the transfused blood. Plasma is too dilute in the transfused blood for this to happen in the opposite way.
    • Eg mismatch blood groups, Rh sensitivity, Kell etc.
    • Cause widespread haemolysis –> fever, hypotension, flushing, wheezing, anxiety, DIC
  • Non haemolytic febrile reaction
    • Only fever usually, sometimes hypotension/vomiting
  • Allergic reaction
    • Maculopapular rash/urticaria
    • Anaphylaxis – hypotension without fever, dyspnoea, wheeze, anxiety
  • Bacterial cotnamination, endotoxaemia
    • High fever, shock, tachycardia, weak pulse
  • Volume overload
  • Transfusion related acute lung injury
    • Pulmonary oedema in absence of fluid overload
    • Rapid onset SOB, hypoxaemia, rales
    • No fever

 

Plasma proteins & their functions.

  • Albumin, fibrinogen, globulin etc
  • Oncotic pressure
  • Coagulation
  • Carry other molecules around
  • Immunity
  • Mostly made in liver

 

Haemostasis.

Injury –> transient vasocontriction –> vasodilation –> exposure of vWF, tissue factor –> platelets attach to area of injury, activate and shape change –> release granules with Calcium, coagulation factors, thromboxane, serotonin –> aggregation of further platelets–> temporary primary clot–> tissue factor starts extrinsic pathway to fibrin formation, which also starts intrinsic pathway to fibrin pathway–> cross linking–> RBC also get caught up –> secondary definitive haemostatic plug.

 

Anti-clotting mechanisms.

  • Once clotted –> fibrinolysis  by tissue plasminogen
  • Anti clotting by anti thrombin III, protein C, Protein S, thrombomodulin (from endothelium–> activate protein C –> inactivate factor V and VIII and inhibit tissue plasminogen inhibitor so there’s more plasmin), fibrinogen degradation proteins inhibit thrombin.

 

Viva questions:

  • What is the structure of Haemoglobin ?
  • What blood grouping systems are you aware of ? Which ones are the most important, and why ?

Know ABO and Rhesus well, plus know the names of a few others e.g. Kell, Duffy, Kidd etc.).

  • What types of transfusion reactions are you aware of ?
  • What are the major steps involved in haemostasis ?
  • Tell me about the role of platelets.
  • What are the intrinsic and extrinsic systems ?
  • Draw the clotting cascade
  • Describe the fibrinolytic system (e.g. “ What stops blood from clotting within normal blood vessels ?”).