Impaired liver function Flashcards
- Outline the main functions of the liver and the consequences of impaired function.
Metabolic Functions of the Liver • Bile production • Bilirubin excretion • Drug and hormone metabolism – Biotransformation into water-soluble forms – Detoxification or inactivation
Liver Functions • Carbohydrate metabolism- glycogenesis, gylcogenolysis, gluconeogenesis • Protein metabolism – Amino acid synthesis – Production of clotting factors – Hormone (thrombopoietin) that stim.s production of platelets – Production of Albumin – Synthesis of Angiotensinogen • Synth of Bile for emulsification of fats (and vit K absorption across gut) • Fat Metabolism – Breakdown of fat to produce glycerol (for gluconeogenesis) – Cholesterol synthesis – Lipogenesis- produce triglycerides – Produce lipoproteins (LDL, HDL, VLDLs) • Breaking down toxic substances, drugs alcohol • Conjugation of Bilirubin – Storage of vitamins (A, D, B12, K), and minerals (iron, copper) – Convert ammonia into urea (urea cycle) – Steroid Metabolism • Conversion of steroid hormones into active forms • Destruction of steroid hormones (oestrogen, testosterone, aldosterone, cortisol)
Consequences of liver damage
• Hepatocellular: injury to hepatocytes leads to cell necrosis. This causes decreased synthetic/metabolic activity and the release of intracellular contents (e.g. the enzymes AST and ALT)
• Cholestasis: impaired bile formation by hepatocytes or impaired bile flow by blockage of the bile ducts/ductules causes a build-up in the blood of substances that are normally excreted in the bile (e.g. bilirubin and bile acids) and the synthesis and release
of proteins from the apical membrane of duct cells (e.g. ALP)
Diagnosis of Liver Disease
– Patient history
– Patient signs & symptoms
– Physical examination (e.g. hepatomegaly)
– Laboratory tests (blood, urine)
– Other diagnostics: liver biopsy, abdominal
ultrasound, computed tomography (CT) scan,
magnetic resonance imaging (MRI)
Abnormal Function: Bilirubin Metabolism
- Jaundice (icterus) is a yellow discolouration of the skin and sclera due to abnormally high levels of serum bilirubin accumulating in these tissues
- Bilirubin is toxic to cells
- Urine is usually dark because of the excess bilirubin being excreted via the kidneys (NB faeces may be pale)
- Jaundice is usually the first, and sometimes the only sign, of liver disease
Abnormal Function: Bilirubin Metabolism
• In neonates, bilirubin can cross the blood brain barrier & cause kernicterus
• Toxic damage by bilirubin to neurons in the brain > permanent, fatal brain damage
How?
1. In premature babies, immature liver function unable to form conjugated bilirubin > accumulation of bilirubin (fat-soluble, readily enters cells)
2. Immaturity of blood-brain barrier
• Bilirubin is photosensitive and isomerises to soluble form, which can be passed by the kidneys, with blue light therapy
Types of Jaundice
3. Posthepatic (obstructive) jaundice
Three types of jaundice:
#1. Pre-hepatic (hemolytic)
• Increased rate of breakdown of RBCs
• excess unconjugated bilirubin is produced faster than the liver is able to conjugate it for excretion
• Unconjugated bilirubin is insoluble and is not excreted in the urine e.g. haemolytic anemias, blood transfusion reactions,
incompatible Rh factor in neonates
#2. Intrahepatic
a) Damage to liver cells stop conjugation of bilirubin and/or its secretion
b) Failure to process or secrete bile
c) Reflux of bile between hepatocytes
d) accumulation of unconjugated bilirubin in bloodstream
• raised concentrations of both conjugated and unconjugated serum bilirubin, and typically stools and urine are of normal
colour. However, pale stools and dark urine can occur transiently in many acute hepatic illnesses e.g. hepatitis, hepatotoxicity, cirrhosis, alcoholic liver disease,
primary biliary cirrhosis, neonatal jaundice
• Bile flow is obstructed between the liver and the intestine Due to strictures (biliary atresia) of bile duct, or obstruction by
gallstones, tumours of bile duct or pancreas
• Conjugated bilirubin is water soluble and is excreted in the urine, giving it a dark colour (bilirubinuria). At the same time, lack of bilirubin entering the gut results in pale, “putty” coloured stools and an absence of urobilinogen in the urine
hepatitis
• Inflammation of the liver
• If inflammation persists > fibrosis > cirrhosis
• Often caused by viral infection (hepatitis virus)
• Over half of all deaths from end-stage liver
disease in New Zealand are due to chronic
hepatitis B (50%) or C (5%) virus infection
• Also often caused by alcoholism; the majority of alcoholic hepatitis patients can go on to develop cirrhosis
• Acute: lasts for < 6 months; high bilirubin with jaundice; dark coloured urine; sudden, sharp onset with hepatocyte damage
• Chronic: lasts for >6 months; jaundice may
occur but urine unlikely to be affected; long
term, steady, ongoing hepatocyte damage
Alcoholic Liver Disease
• Fatty liver (steatosis)
– Liver cells contain fat deposits; the liver is
enlarged
• Alcoholic hepatitis
– Liver inflammation and liver cell failure
• Cirrhosis
– Scar tissue partially blocks sinusoids and bile canaliculi
Fatty liver disease (steatosis)
• Hepatic steatosis; fat content of the liver >10%
• Macrovesicular fatty changes; may lead to
inflammation (and then to fibrosis / cirrhosis)
• Elevated liver enzymes
Non-alcoholic fatty liver disease
• Absence of alcohol use and hepatitis viral infection
• Associated with insulin resistance/metabolic
syndrome/obesity
• Elevated liver enzymes
• Probably associated with changes in gut microbiota
• Growing in incidence; now affects up to 30% of adults
Production of Bile Acids and Bile Salts
• Liver produces bile acids & salts which are
secreted in bile
• Important for normal fat digestion
• Bile salts act as emulsifiers and allow efficient action of lipases on triglycerides
• Patients with liver disease have difficulties in digesting fat, indigestion fat excreted in faeces
• Results in fat intolerance, steatorrhoea (pale greasy stools)
Cholestasis
• A reduction or stoppage of bile flow
• Bile flow in the liver slows down.
• Bile accumulates and forms plugs in the ducts.
– Ducts rupture and damage liver cells
• Alkaline phosphatase released into blood
• The liver is unable to continue processing
bilirubin.
– Increased bile acids in blood and skin causes Pruritus (itching)
• Biliary obstruction (blockage of bile movement)
• Intrahepatic = widespread blockage of small ducts/canaliculi; may be caused by oedema that occurs with hepatitis
• Extrahepatic (posthepatic) cholestasis:
blockage of bile from the gallbladder to the
duodenum
Gallstones (cholelithiasis)
• Usually (~80%) made of cholesterol
• Cholesterol is hydrophobic and precipitates in crystals unless it is held in solution by bile salts (which form micelles with cholesterol at the centre)
• Others (~20%) are calcified stones containing bilirubin pigments; usually seen in conditions with excessive unconjugated bilirubin production e.g. cirrhosis or
chronic haemolysis
• Risk factors: overweight; age >60; female; rapid weight loss; pregnancy/birth control; family history
• Fairly common (up to 20% of women and 10% of men); may remain asymptomatic (at least, until they block the duct!)
• Presents with localised pain, nausea and vomiting after eating a fatty meal; diagnosed by ultrasound/imaging, acute or chronic cholecystitis (inflamed gall bladder)
Cirrhosis
• Chronic liver disease
• Characterised by portal hypertension
(increased vascular resistance in the liver and
increased splanchnic/portal blood pressure),
often leading to ascites
• Nodules of regenerated parenchymal cells with widespread fibrosis and often ascites
• Occurs in 10 – 20% of heavy drinkers
• Eventually leads to complete liver failure
Veins Draining Into the Hepatic Portal
System
- Portal hypertension causes pressure in these veins to increase. Veins such as the paraumbilical veins causing caput medusae
- Collateral channels and shunts develop, such as oesophageal varices, that are thinned walled, can break and haemorrhage.
- Organs like the spleen engorge with blood causing splenomegaly
