Liver function tests (LFT)

Liver
function tests

Content

       Liver
function tests

       Normal
reference ranges of various lab parameters

       Various
disease conditions correlated with liver function tests

Objective

After completion of this lecture, student will be able
to:

       Explain
the various liver function tests

       Explain
the normal reference ranges of various lab parameters

       Explain
the various disease conditions correlated with liver function tests

Functions of liver

Introduction

       Tests include:

                a)
Tests to assess liver synthetic capabilities

                b) Tests to assess cholestatic
disease and hepatocellular injury

Tests to assess liver
synthetic capabilities

       Used to assess functional
capabilities of liver

       Its synthetic products are measured
[albumin, fibrinogen, prothrombin, hepatoglobin, transferin and other proteins]

       Most commonly used tests include

                                -albumin

                                -prothrombin
time

       Occasionally

                                -total protein

                                -globulin (with
albumin)

       Albumin:

                Reference range: 3.5 to 5 gms/dl

                -Synthesised from AA derived
from gut/breakdown of RBC

                -Maintains oncotic pressure

                -Binds numerous hormones,
anions, drugs and fatty acids

                -Liver synthesise 122 gm /day if
needed it can double the synthesis

                -Serum half-life is 20 days

                -Albumins measurements are slow
to fall after the onset of hepatic dysfunction due to long half –life

                -Complete cessation of albumin
production results in only 25% decrease in serum concentration after 8 days

                -Albumin concentration remains
unaltered in many liver disease when liver function is preserved – if disease
progress its synthetic capacity impaired [severe hepatitis, cirrhosis]

       Non hepatic causes: Hypoalbuminemia: Malnutrition, malabsorption,
overhydration, nephrotic syndrome, protein losing enteropathy, burns and
chronic illness

       At very low concentration (2-2.5gm/dl)
patients can develop peripheral edema, ascities or pulmonary edema

       Non hepatic causes:

               -Hyperalbuminemia:

                -Dehydration

                -Anabolic steroids

                     Does not cause any symptoms

       Prothrombin time:

                -It is one of the coagulation
factor

                -Liver synthesises SIX
coagulation factors: I, II, V, VII, IX and X

                Normal range: 10 to 13 seconds

                -PT is not specific for liver
disease

Causes for prolongation of PT:

                – Inadequate vitamin K in the
diet

                – Poor / inadequate nutrition

                – Drugs – warfarin, salicylates,
moxalactum, cefoperazone, tetracycline

       If PT remains prolonged despite
parenteral vitamin K (10mg), it is considered a sign of substantial hepatic
dysfunction

       Treat the patient with vitamin K if
no bleeding

       If bleeding present, treat with
fresh frozen plasma

       Total protein:

                Reference range: 5.5 to 9gm/dl

                -Refers to sum of albumin and
globulin

                -Any symptoms increase either
albumin/ globulin also increases total protein

                -Its value is limited if albumin
and globulin results are already known

       Globulin:

                Reference range: 2 to 3gm/dl

                -Refers to total measurements of
immunoglobulins (antibodies) in serum

                -Synthesised by T lymphocytes

                -Ig – IgA, IgD, IgE, IgE, IgG
and IgM

       Causes:

                -Malabsorption

                -Protein binding enteropathy

                -Hepatocellular dysfunction does
not lower globulin concentration unless associated with malabsorption

                -Elevation of globulins is a
sign of inflammation – may present in hepatitis

                -In chronic hepatitis  – albumin decreases and globulin increases

                -In primary biliary cirrhosis –
Increase in IgM

                -Alcoholic patients – increase
IgA

       Non – hepatic causes:

                -Chronic infections, chronic
inflammatory states, multiple myeloma

                -In non-hepatic condition –
globulin increases than albumin concentration and thus G;A ratio will be >1
(normal – 0.6)
 

Tests to assess cholestatic
disease and hepatocellular injury

       Liver disease:

                                -Cholestatic

                                -Hepatocellular
damage

                                -Mixed

       Cholestatic –
primary interference with the metabolism or secretion of bilurubin

       Hepatocellular damage – damage to hepatocytes or inflammation of hepatocytes

       Mixed type is due to:

                                                   back pressure



                Cholestatic                <—————->hepatocellular
damage

                                                        swelling

       Elevation of liver enzymes are
common findings in clinical practice

       The significance of the elevation
has to be assessed whether or not mild non-specific elevation (e.g., viral /
drug / liver disease)

Useful tests

                                                Enzymes                              Reference range

                                                ALP                                        30 – 120
U/L

                                                GGT                                       0 – 30U/L

                                                AST                                        0 – 35
U/L

                                                ALT                                         0 – 35
U/L

                                                LDH                                        110 –
220 U/L                    

                                Bilurubin

                                                total                                                       2
– 18 mmol/L

                                                direct
(conjugated)                         0 – 4
mmol/L

                                               

                                Albumin                                                             3.5 – 5.0 gms/dl

                                Globulin                                                             2.0 – 3.0 gms/dl

                                Prothrombin
time                                          10 – 13 seconds

Liver enzymes are most useful in differentiating
hepatocellular damage from cholestasis

Extra-cellular (present
in cells lining biliary canaliculi)                                                     

1. ALP                     

2. GGT     

Intra-cellular
enzymes
(present in cytosol of liver cells)                                                

1. AST                     

2. ALT                     

3. LDH

CHOLESTASIS

Intra-hepatic (obstruction
in bile ducts within liver)

Causes:

      metastasis

Extra-hepatic (obstruction
in bile ducts outside the liver)

Causes:

      gall
stones

      cancer
of head of pancreas

      inflammation

 á
ALP & GGT Bone disorder (pagets disease, osteomalacia, 10, 20
malignancy of bone)

                á GGT (100-140 U/L) without
any abnormality in liver  à Chronic alcoholism or phenytoin  

       If
chronic alcoholism is associated with hepato-cellular damage, ALT increase
along with GGT

       Chronic
alcoholism can lead to fatty infiltration, alcoholic hepatitis and cirrhosis

Hepatocellular damage

       In
hepatocellular damage, AST, ALT and LDH increases

       Both
AST and ALT runs parallel

       Measure
ALT as it is very specific to liver

Causes:

      Paracetamol overdose, ischemic / hypoxic
hepatitis

                            
Marked elevation of ALT and LDH, both of the same order (800-3000 U/L)

                            
The ratio of ALT / LD is 0. 8 – 1.2

      Viral hepatitis

     
both ALT and LDH increases

     
ALT elevation is significantly > LDH

     
ALT/LDH ratio is 1.2-2.0

      Infections mono-nucleousis (Epstein Bar
virus)

      Liver
and Spleen maybe swollen

      Simultaneous
increased level of ALP, GGT, LDH and ALT between (200-600 U/L) occur

      Rhabdomylosis

      LD
level will be markedly elevated (800-20,000 U/L) than ALT

      ALT:
LDH ratio is  <  0. 8

      Due
to muscle destruction CK level also increase (2,000 – 1,00,000 U/L)

      Increase
CK does not occur in liver damage (liver does not contain CK)

Drugs involved in liver disorders

       Predominantly hepatocellular

      Allopurinol,
aspirin, cytotoxic, diclofenac, anti TB drugs, methotrexate, paracetamol,
phenytoin, propylthiouracil and quinidine

      
Predominantly
cholestasis

      Augmentin,
CBZ, chlorpromazine, chlorpropamide, flucloxacillin, dicloxacillin,
indomethacin, phenothiazines and tolbutamide

       Mixed

      Methyldopa,
halothane, norfloxacin, PAS, ranitidine, sulindac, valproate co-trimaxozole

Summary

       Liver function tests include tests
which assess the liver synthetic capabilities and  hepatocellular injury

       Hepatocellular dysfunction does not
lower globulin concentration unless associated with malabsorption

       Hepatocellular damage – damage to
hepatocytes or inflammation of hepatocytes

       The significance of the elevation
has to be assessed whether or not mild non-specific elevation (e.g., viral /
drug / liver disease)

 

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