Liver disorders Flashcards
Function units of the liver?
Thousands of lobules which form the four lobes. Lobules are hexagonal structures composed of hepatocytes
True or False - the liver can regenerate
True
What proportion of cells can the liver lose before it stops functioning?
3/4
What are the blood supply’s to the liver?
Two sources;
- oxygenated blood via hepatic artery
- venous blood via hepatic portal vein (carries nutrients and toxins)
What are sinusoids?
Vascular channels allowing exchange between blood and hepatocytes
Where is bile produced and flow to?
Produced in hepatocytes, drains into canaliculi
- Exits lobules via bile ducts
- Exits liver via hepatic duct
- Enters duodenum via common bile duct
What are the liver functions
- Synthesis of plasma proteins and clotting factors
- Storage of minerals and vitamins
- Metabolism of carbohydrates, fats, proteins
- Elimination of bilirubin
- Metabolism of steroid hormones
- Metabolism of alcohol
- Metabolism of drugs
- Production of bile salts
How is bilirubin conjugated?
1) Reticulo endothelial system - RBC become heme which become bilirubin. Transported to hepatic portal vein bound to albumin
2) Liver: Bilirubin is conjugated (water soluble), excreted via common bile duct
3) GI tract: Brown colour of feaces
How to diagnose liver disorders?
- Pt history
- Pt signs & symptoms
- Physical exam
- Laboratory tests
- Other: liver biopsy, abdomen ultrasound, CT scan, MRI
What are the categories for impaired liver function?
- Hepatocellular injury
- Cholestasis
- Liver failure
What is a hepatocellular injury?
- Injury to hepatocytes leads to cell necrosis
- Causes decreased synthetic/metabolic activity of the liver and the release of intracellular contents
- Causes hyperbilirubinemia, high levels of bilirubin in the blood, causing jaundice
What are the likely causes of a hepatocellular injury?
- Non-alcoholic fatty liver disease
- Viral hepatitis
- Alcohol, drug toxicity
- Haemochromatosis
- Autoimmune disease
What is cholestasis?
- Reduction of bile flow
- Usually obstruction: Maybe intra- or extra- hepatic
- Causes a build-up in the blood of substances that are normally excreted in the bile
- Bile accumulates and plugs ducts which rupture and damage liver cells
- Causes Alk Phos to be released in blood
- Build up of bile acids cause itching
What are the likely causes of cholestasis?
- Gall stones (cholelithiasis)
- Abdominal masses/malignancies
- Some drugs
- Pregnancy
- Primary biliary cholangitis
What is liver failure?
Massive liver destruction and loss of functional capacity
What are the likely causes of liver failure?
- Sudden e.g. fulminant hepatitis
- Chronic progressive damage e.g. chronic alcoholic cirrhosis
What is jaundice & what does it do?
- 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 dark due to high bilirubin
- Usually first and only sign of liver disease
What is kernicterus?
- High bilirubin in neonates
- In neonates bilirubin can cross blood brain barrier and damage neurons in the brain causing permanent, fatal brain damage
How does kernicterus occur?
- Premature babies have immature liver function and are unable to form conjugated bilirubin
- Have immature blood brain barrier
How to treat kernicterus?
With blue light therapy
What are the 3 main types of jaundice?
- Pre-hepatic (hemolytic) jaundice
- Intrahepatic jaundice
- Posthepatic (obstructive) jaundice
What is pre-hepatic (hemolytic) jaundice?
- 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
What are causes of pre-hepatic (hemolytic) jaundice?
- Haemolytic anemias
- Blood transfusion reactions
- Incompatible Rh factor in neonates
What is intrahepatic jaundice?
- Damage to liver cells (hepatocyte injury) impedes conjugation of bilirubin and/or its secretion
- Failure to process or secrete bile
- Reflux of bile between hepatocytes
- Accumulation of unconjugated bilirubin in bloodstream
What are causes of intrahepatic jaundice?
- Hepatitis
- Hepatotoxicity
- Cirrhosis
- Alcoholic liver disease
- Primary biliary cholangitis (autoimmune Disease that destroys bile ducts in liver)
- Neonatal jaundice
What is post-hepatic (obstructive) jaundice?
- Bile flow between liver & intestine is obstructed, impairing bile formation or bile flow
- Causes a build-up in the blood of bilirubin and bile acids, and the synthesis and release of enzymes from the apical membrane of duct cells
What are causes of post-hepatic (obstructive) jaundice?
- Strictures (biliary atresia) of bile duct
- Obstruction by gallstones
- Tumours of bile duct or pancreas
What is hepatitis?
- Inflammation of the liver
- If inflammation persists it causes fibrosis then cirrhosis
What are causes of hepatitis?
- Viral infection (hepatitis virus)
- Alcoholism
What is acute hepatitis?
- Hepatitis for less than 6 months
- Sharp, sudden onset with hepatocyte damage
- Jaundice
- Dark urine
What is chronic hepatitis?
- Hepatitis for more than 6 months
- Long term, steady, ongoing hepatocyte damage
- Jaundice may occur
- Urine is unaffected
What is alcohol induced liver disease?
Spectrum of conditions:
- Fatty liver (steatosis) - Liver cells contain fat deposits; the liver is enlarged
- Alcoholic hepatitis - Liver inflammation and liver cell necrosis
- Cirrhosis - Scar tissue partially blocks sinusoids and bile canaliculi
What is non-alcoholic fatty liver disease (NAFLD)?
- Absence of alcohol use and hepatitis viral infection
- Associated with insulin resistance/metabolic syndrome/obesity
- Ranges from Steatosis, inflammation with steatosis, hepatocyte necrosis, cirrhosis
- Elevated liver enzymes
What is cirrhosis?
- Chronic end-stage liver disease which leads complete liver failure
- Nodules of regenerated parenchymal cells with widespread fibrosis and often ascites
- Characterised by portal hypertension (increased vascular resistance in the liver and increased splanchnic/portal blood pressure), often leading to ascites
What are caused of cirrhosis?
- Alcohol abuse
- Viral hepatitis
- NAFLD
- Biliary disease
What are clinical manifestations of cirrhosis?
- Fibrosis of nodules causing disrupted vascular flow & biliary ducts in liver
- Leads to portal hypertension and associated complications such as ascites and varices, biliary channel obstruction and bile stasis
- Results in hepatomegaly, weight loss, cachexia, weakness, anorexia, RUQ pain
What is portal hypertension?
Increased pressure in hepatic portal system due to cirrhosis
What are manifestations of portal hypertension?
- Splenomegaly, spleen engorge with blood, decreasing number of RBCs, WBCs, and platelets
- Ascites, increase in fluid in peritoneal cavity
- Collateral channels and shunts develop between portal and systemic blood systems, causing oesophageal varices, haemorrhoids, and paraumbilical veins (caput medusa)
What are ascites?
Fluid in peritoneal cavity
What are causes of ascites?
- Obstruction of lymphatic flow
- Portal hypertension
- Lowered albumin levels
- Impaired liver function causes increase ADH & aldosterone resulting in fluid retention
What are oesophageal varices?
- Varices in submucosa & lumen of oesophagus
- Thin walled so may haemorrhage into stomach which causes bleeding varices
What is liver failure?
- Most severe stage of liver disease
- Can result from sudden liver damage (fulminant hepatitis) or chronic liver disease
- 80-90% liver function lost
What is normal production of bile acids & bile salts?
- Liver produces bile acids & salts which are secreted in bile
- Important for normal fat digestion
- Bile salts act as emulsifiers & allow efficient action of lipases on triglycerides
What is impaired production of bile acids & bile salts?
- Difficulties in digesting fat, indigestion causing fat to be excreted in faeces
- Causes fat intolerance, steatorrhoea (pale greasy stools)
What is normal alcohol & drug metabolism?
- Liver detoxifies drugs and alcohol
- Detoxification reactions use cytochrome p450 enzymes or microsomal enzymes
What is impaired alcohol & drug metabolism?
Deficient detoxification reactions causing toxic degradation of cells in the body
What is normal metabolism of cholesterol & steroid hormones?
The liver forms lipoproteins, syntheses cholesterol, and metabolises steroid hormones
What does impaired metabolism of cholesterol & steroid hormones cause?
- Lowered serum cholesterol levels
- Gynecomastia, testicular atrophy in males
- Amenorrhea in females
What is normal metabolism of carbohydrates?
- Glycogenesis during the absorptive state
- Maintains blood glucose during post-absorptive state through glycogenolysis and gluconeogenesis
What is impaired metabolism of carbohydrates?
- Impaired carbohydrate metabolism increasing risk of hypoglycaemia
How does impaired liver function affect storage of vitamins?
Impaired fat absorption and reduced storage of fat-soluble vitamins may lead to deficiencies
What is normal metabolism of proteins?
- Liver synthesises plasma proteins (albumin) & some clotting factors (prothrombin, fibrinogen)
- Liver deaminates proteins & forms urea
What is impaired metabolism of proteins?
- Decreased blood albumin and oedema
- Low albumin contribute to ascites
- Bleeding tendency
- Elevated levels of blood ammonia which are highly toxic to cells & may cause hepatic encephalopathy
What is normal albumin and body fluid distribution in the liver?
- Albumin maintains normal fluid distribution between interstitial and intravascular compartments
What is impaired albumin and body fluid distribution in the liver?
- Long term deficiency in albumin (usually with long- term liver failure)
- Causes accumulation of fluid in interstitial space (called third spacing)
- Results in oedema and ascites
What is hepatic encephalopathy?
- Result of complete liver failure
- Stages: changes in personality, memory, lethargy- progressing to confusion, stupor, convulsions, coma
What leads to a coma in hepatic encephalopathy?
- Hypoglycemia due to failure of normal blood glucose homeostasis by the liver
- A build up of ammonia causing severe liver impairment, ammonia not converted to urea causing increased blood ammonia which is toxic to tissues especially to the brain (encephalopathy)
What are some liver function tests?
- Combination of markers of function with markers of liver damage
- Raised levels of ALT & AST suggest hepatic process
- Raised levels of Alk Phos indicate biliary disease
- Raised levels of GGT indicate hepatitis and cholestasis
What is intrahepatic cholestasis?
Widespread blockage of small ducts/canaliculi; may be caused by oedema that occurs with hepatitis
What is extra-hepatic (post hepatic) cholestasis?
Blockage of bile from the gallbladder to the duodenum
What is gallstones (cholelithiasis)?
- ~80% crystallised cholesterol
- ~20% calcified stones
What are the signs & symptoms of gallstones (cholelithiasis)?
- Localised pain
- Nausea and vomiting after eating a fatty meal
How are gallstones (cholelithiasis) diagnosed?
- Ultrasound/imaging
