24A15: Exam Report

Outline how the measurement of the following can be used in the assessment of liver function (25% of marks each):
(i) Albumin
(ii) Prothrombin time (PT) (iii) Glucose
(iv) Ammonia.

56% of candidates passed this question.

A good answer should cover the following points:

  • Normal range
  • How and why the value is affected by liver failure and potential con-founders.

As an example in the case of albumin

  • The normal range is 35- 50g/L
  • It is produced in the liver and thus the measured value will decrease in synthetic liver dysfunction
  • The half life of albumin is long (20 days) and therefore it is a better marker of chronic dysfunction
  • Potential con-founders include
    • Inflammation (negative phase protein)
    • Malnutrition
    • Increased loss (nephrotic syndrome etc).

Marks were not allocated for information not relevant to the question asked (such as the
function of albumin).

21B07: Exam Report

Outline how the measurement of the following can be used in the assessment of liver function (25% marks of each)
• Albumin
• PT
• Glucose
• Ammonia

54% of candidates passed this question.

This was a new question and overall, most candidates provided some detail on each component as requested.

Those answers that used a simple template for each section generally scored better than those who wrote in a paragraph style for each section.

Areas expected to be covered included the following; a definition of the variable to provide context, a normal value and the range of influences that effect the variable both related to liver function and or extrinsic to the liver (attempting to introduce the concepts of sensitivity and specificity for each test).

Stronger answers provided some context as to whether the variable was sensitive to acute or chronic changes in liver function and which synthetic/metabolic component of the liver the variable represented.

N2i / 24A15 / 21B07: Outline how the measurement of the following can be used in the assessment of liver function (25% marks of each)
• Albumin
• PT
• Glucose
• Ammonia

Summary

  • Table
  • Definition of the variable
  • A normal value
  • Range of influences that affect variable related to liver function and/or extrinsic to liver
  • If variable sensitive to acute or chronic changes in liver function
  • Which synthetic/metabolic component of the liver the variable represented
  • Sensitivity and specificity to liver disease

Definition

Normal value

Affected by

Sensitivity / specificity to liver disease

Changes in acute or chronic liver disease?

Albumin

Definition

Single polypeptide chain of 585 amino acids. MW 69 kDa. 

Synthesised exclusively by the liver (15 g/day)

Normal value

Plasma concentration 35 – 50 g/L

Affected by

Albumin concentration ↓ by:

  • ↓ Albumin production (liver impairment, malnourishment)
  • ↑ Breakdown (malnourishment)
  • ↑ Movement from intravascular to extravascular compartments (altered vascular permeability in sepsis, burns)
  • Acute phase response following major stress

Sensitivity / specificity to liver disease

Low specificity

Changes in acute or chronic liver disease?

Chronic (intravascular half-life albumin 20 days)

Prothrombin time (PT)

Definition

Time required for fibrin clot formation in a citrated plasma sample following addition of Ca2+ & thromboplastin

Represents the extrinsic pathway of coagulation (mainly clotting factor VII), then final common pathway (X, V, II, fibrinogen) – all synthesised by the liver

Normal value

16-18 secs

Sensitivity of commercial thromboplastin varies therefore use international normalised ratio (INR) (ratio of pt’s PT compared with average PT of control sample)

Affected by

PT prolonged by:

  • ↓ Hepatic synthesis of vit K dependent factors from liver disease
  • Vit K def
  • Warfarin
  • DIC due to consumption of clotting factors
  • Major haemorrhage (consumptive coagulopathy)

Sensitivity / specificity to liver disease

High sensitivity

Included in the MELD score

Low specificity

Changes in acute or chronic liver disease?

Acute and chronic 

Half-life of clotting factors short,  therefore ↓ hepatic synthetic function > ↓  production > rapid ↑  INR

Glucose

Definition

A carbohydrate with 6 carbons. Used for ATP production (esp RBC and brain).

 

Liver is the major glucostat organ and site of gluconeogenesis, glycogenolysis, glycogenesis.

 

Approx 100 g glycogen in liver

Normal value

Plasma concentration 4 -6 mmol/L

Affected by

Glucose concentration ↓ by:

  • ↓ Hepatic function resulting in ↓ glycogenolysis and ↓ gluconeogenesis
  • Exogenous insulin
  • Starvation
  • Insulinoma

Sensitivity / specificity to liver disease

Low specificity 

Changes in acute or chronic liver disease?

Acute

Ammonia

Definition

NH3

Sources:

  • Oxidative deamination of amino acids in liver
  • A.a. metabolism in muscles
  • Kidneys via renal ammoniogenesis
  • Bacterial metabolism in colon

Ammonia is toxic > liver converts NH3 into non-toxic urea via urea cycle

Normal value

Plasma concentration 10 – 65 umol/L

Affected by

Ammonia concentration ↑ by:

  • Severe hepatic dysfunction
  • Porto-systemic shunt
  • Medications (e.g. valproate)
  • Inherited defects in urea cycle 

Sensitivity / specificity to liver disease

Low specificity

Changes in acute or chronic liver disease?

Acute and chronic

Limited utility in CLD, as normal values do not rule out encephalopathy

Author: Madeline Coxwell Matthewman