20B12: Exam Report

Describe the physiology (50% marks) and pharmacology (50% marks) of albumin.

19% of candidates passed this question.

The question required an equal treatment of the physiology and pharmacology of albumin. The physiology discussion needed to include synthesis, factors affecting synthesis, distribution in the body (including the proportion divided between the plasma and interstitial space), functions, breakdown, and elimination half-life. Discussion of the pharmacology should have included available preparations (4% and 20% Albumin) and pharmaceutics, distribution, elimination (both the protein and crystalloid components), mechanism of action to expand the plasma compartment, longevity in the plasma compartment, indications, and adverse effects. Oedema, circulatory overload, immunological reactions, and relative contraindication in brain injury were important to mention. There was some confusion regarding the infectious risks of albumin. An outline of the manufacturing process from donated plasma and pasteurisation was expected.

Q4i / 20B12: Describe the physiology (50% marks) and pharmacology (50% marks) of albumin.

Definition

A naturally occurring protein found in blood plasma. Recombinant human albumin is a product that is manufactured to be structurally equivalent to native human serum albumin. 

Classification

6 subfamilies – vit D binding proteins occupy family 1-2 

Physiology

Synthesis

  • In liver
  • Synthesized as preproalbumin -> N-terminal peptide removed -> proalbumin -> cleared in Golgi vesicle -> albumin 

Factors Affecting Synthesis

  • Nutrition 
  • Liver function 
  • infection /sepsis/inflammation 

Distribution

  • 40% intravascular space 
  • 60% extravascular space 
  • The balance between plasma and interstitial space is established at varying rates with respect to the two subcompartments of the extravascular albumin pool 
  • Factors affecting distribution: HTN, CCF, trauma, exercise, DM, Burns, CPB

Function

  • Carriage 
    • Steroids
    • Fatty acids
    • Thyroid hormones 
    • Drugs 
  • Modulator of oncotic pressure 
  • Maintenance of microvascular integrity 
  • Maintenance of acid-base balance
  • Antioxidant
  • Anticoagulant 

Breakdown

  • Broken down by cysteine protease 
  • Elimination half life – 16hrs

Pharmacology

Pharmaceutics

  • 4% or 20% 
  • Separated from donated blood via chromatography 
  • Contains 40G albumin 
  • 70k Da
  • 140 Na+ 
  • Hypoosmolar 

Indication

  • Volume replacement: peri-operative period, burns patient, trauma 
  • Resuscitation in severe sepsis

Mechanism of Action

  • As a natural colloid already abundant in plasma, infused Albumin takes the same route
  • Normal translocation of albumin over endothelium to interstitium occurs
  • 60% of albumin is located extravascularly
  • Albumin is transported back to circulation by lymphatic system
  • Albumin 5% expands Plasma volume by 80% the infused volume
  • Infusion of 10ml/kg albumin 5% increases serum albumin by 10% for 6-8hrs

PK

  • A – IV only
  • D
    • After IV administration – rapid distribution within the vascular pool 
    • 90% remains in intravascular compartment at 2hrs 
  • M – by cellular proteolysis 
  • E – degradation via liver 15%, renal 10%, leakage via GIT 10%, muscle + skin 40-60%. Degraded into amino acids -> amino acid pool
  • As albumin is infused, its serum concentration falls rapidly – 50% dec by end of 1st day as albumin distributes to ECF  

AE: Allergy Infection Risk

  • Bacteria, parasites and intracellular viruses are not transmitted because they are destroyed by freeze-thaw steps or removed by filtration
    • Pathogenic plasma-borne viruses such as HIV, HCV, Hep B, Hep A, Parovirus B19, and West Nile virus – at risk of transmission

Contraindications

  • head injury (SAFE Study), previous immunological reactions, circulatory overload, oedema

Manufacturing Process

  • From Australian-sourced plasma
  • Pooled from thousands of donations (minimises the infection risk)
  • Whole plasma is fractionated to prepare Albumin
  • Fractionation involves
    • Physical separation (by precipitation)
    • Chromatography (separates molecules based on chemical and physical properties
    • Removal of pathogens by:
      • Pasteurisation (vapour heat 60C for 10hrs)
      • Use of solvents and detergents
      • Exposure to low pH conditions
      • Nanofiltration
  • Partitioning allows purification of immunoglobulins, clotting factors and albumin from plasma
  • Then stored in secure & monitored environments

Author: Zoe Guo / Krisoula Zahariou