Investigation of liver disease

The liver

A meaty organ that sits on the right side of the belly. Weighing about 3 pounds, the liver is reddish-brown in color and feels rubbery to the touch. Normally you can't feel the liver, because it's protected by the rib cage.

The liver has two large sections, called the right and the left lobes. The gallbladder sits under the liver, along with parts of the pancreas and intestines. The liver and these organs work together to digest, absorb, and process food.

The liver's main job is to filter the blood coming from the digestive tract, before passing it to the rest of the body. The liver also detoxifies chemicals and metabolizes drugs. As it does so, the liver secretes bile that ends up back in the intestines. The liver also makes proteins important for blood clotting and other functions.

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Liver functions

  • Catabolism and excretion of bilirubin
  • Maintenance of glucose homeostasis
  • Metabolism of cholesterol and triacylglycerols
  • Production of some clotting factors
  • Detoxification of drugs
  • Filters blood
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Liver Function Tests

  • Bilirubin
  • Albumin
  • Prothrombin time (clotting test)

While these are the main liver function tests, the other tests listed abouve can help to determine whether the liver is working efficiently.

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ALT & AST

Enzymes involved in the transfer of amino groups. Released into the bloodstream when hepatocytes are damaged.

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Alkaline phosphatase (ALP)

The enzyme present in membrane of hepatocytes close to biliary ducts.  The enzyme blood levels increase when the pressure inside biliary ducts increase.

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Gamma glutamyl transpeptidase (GGT)

Enzyme present in membrane of hepatocytes close to biliary ducts. The transfer of gamma-glutamyl groups between peptides.  

Enzyme synthesis is induced by alcohol and by some drugs, e.g. some antiepileptic drugs.

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Albumin

Synthesised in the liver, they are a carrier of proteins/peptides/drugs in the blood. It maintains oncotic pressure in blood vessels. 

Low serum albumin concentration in severe liver disease

Concentration decreases with server liver disease.

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Bilirubin

A Waste product of haemoglobin and cytochromes: unconjugated bilirubin. Conjugated in the liver with glucuronic acid: conjugated bilirubin and excreted in the bile. 

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Ammonia

Only measured in neonates (new born babies) with severe illness/irritability/low consciousness level. 

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Glucose

Not a routine laboratory liver function test. May be low in severe liver disease.

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Hepatitis

Drugs/Toxins such as paracetamol overdose and alcohol as well as an autoimmune infection.

Ischaemic (not enough blood to the liver) can cause secondary to acute shock, severe hypotension.

Increases hepatocyte destruction ‘hepatitic pattern which causes the release of cell enzymes into the blood. 

Other abnormalities: 

  • Increased serum ALP  2 x ULN 
  • Increased serum bilirubin (depends on severity)
  • Bilirubin appears in urine 

In massive hepatitis (fulminant)

·       Hypoglycaemia – glucose conc. In blood ..
·       Hypoalbuminaemia

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Cholestasis

Impairment of bile flow, anywhere from liver canaliculus to duodenum causing a partial or complete obstruction:

  • Gall stones
  • Extra-hepatic 

 A cholestatic pattern is when alkaline phosphatase (ALP) and bilirubin are elevated. Increased back-pressure on cells of canaliculi and then hepatocytes. 

Incomplete obstruction, the stool is pale (bile pigments not reaching the gut). 

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Mixed hepatitis/cholestasis

Damage to both hepatocytes and cells of bile ducts.

       During sepsis – bacteria in the blood, which causes organ damage

       Drugs e.g. immunosuppressants

       Autoimmune liver disease

       Any hepatitic or cholestatic disorder already mentioned.

Aminotransferases and ALP mildly-moderately raised.

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Liver Tumours

  •  Benign or malignant
  •  Single or multiple nodules/masses. Usually infiltrative
  •  Primary or secondary (metastases from tumour in different part of body)

Usually normal liver function tests until quite advanced, large increase ALP.

  • Hepatocarcinoma: usually raised AFP
  • Alpha-feto-protein (AFP) produced by tumour
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Alcoholic liver disease

Chronic alcohol intake causes:

  •  Increased Gamma glutamyltranspeptidase (GGT) (due to ­ enzyme synthesis)
  •    increased red cell volume (macrocytosis)

If individual stops intake, GGT goes back to normal in 3-4 weeks. Not a very sensitive test. Not specific either as GGT can be increased in most types of liver disease.

Other consequences of chronic alcohol intake:

  • Fatty liver: deposition of fat in liver, associated with raised serum triaylglycerols
  • Raised plasma urate ( a metabolite for nucleotide breakdown)
  •  Acute hepatitis (acute alcohol intake)
  • Liver cirrhosis 
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