7. Liver pathology Flashcards
Name 3 plasma analyses indicating liver damage
- plasma ALT
Increased levels suggest inflamed/damaged hepatocytes, i.e. hepatitis (viral, acute alcohol intake, fatty liver disease, drugs/toxins), acute liver injuries - plasma Alkaline Phosphatase (present in canaliculi, bile ducts and bone)
Increased levels suggest:
i. bile duct/hepatocyte disease with cholestasis (eg. biliary obstruction, cirrhosis, liver metastases, some drugs)
ii. bone disease (eg. bone metastases/fractures, osteomalacia, hyperparathyroidism, Paget’s bone disease)
NB. raised levels normal during childhood due to bone dev. - plasma Gamma GT (present in bile duct cells)
Increased levels suggest bile duct obstruction (or liver cirrhosis, liver metastases or drus) or alcoholism (production induced by alcohol)
describe the metabolism and excretion of bilirubin
i. aged RBCs (120 day lifespan) broken down by liver/spleen macrophages…
ii. haem breakdown produces hydrophobic unconjugated bilirubin…
iii. transported to liver bound to albumin…
iv. bilirubin conjugated to glucoronic acid (now water-soluble) in hepatocytes (by UDP glucuronyl transferase)…
v. secreted into bile canaliculi in bile and conversion to urobilinogen in gut…
- excretion as stercobilin in faeces (90%)
- reabsorbed in blood and converted to urobilin in kidney for excretion in urine (10%)
P presents with:
- moderate jaundice
- normal stool colour
- dark urine
- no pruritis
What is the likely type of jaundice and what would plasma/urine investigations show
HEPATIC jaundice: hepatocyte failure to conjugate and/or secrete bilirubin (eg hepatitis, cirrhosis)
- increased plasma (un)conjugated bilirubin
- normal urine urobilinogen
- bilirubinuria (conjugated bilirubin present in urine) - causes dark urine
P presents with:
- mild jaundice (lemon-tinge)
- v. dark stool colour
- normal urine colour
- no pruritis
What is the likely type of jaundice and what would plasma/urine investigations show
PRE-HEPATIC jaundice: increased haemolysis causing increased total bilirubin (e.g. sickle cell anaemia, haemolytic anaemia)
- increased plasma bilirubin
- increased urinary urobilinogen
- no conjugated bilirubin in urine
P presents with:
- severe jaundice (green-tinge)
- pale stool colour
- dark urine
- pruritis
What is the likely type of jaundice and what would plasma/urine investigations show
POST-HEPATIC jaundice: failure of biliary tree to convey conjugated bilirubin to duodenum (e.g. bile duct gallstones, pancreatic head carcinoma)
- increased plasma bilirubin
- decreased urinary urobilinogen
- bilirubinuria (conjugated bilirubin present in urine)
which is urine dark in hepatic and post-hepatic jaundice but not pre-hepatic
In hepatic and post-hepatic, increased conjugated bilirubin in blood (due to hepatocyte/biliary tree failure) - water soluble so excess excreted in urine causing dark colour.
In pre-hepatic, there is increased urinary urobilinogen but not conjugated bilirubin.
why is pruritis a symptom of post-hepatic jaundice
gallbladder or biliary tree disease… conjugated bilirubin back up into blood… bile salt deposition into skin
what is hepatitis - suggest 3 clinical effects
Inflammation and/or necrosis of hepatocytes causing loss of function.
Liver failure results in:
1- increased susceptibility to infections (esp. bacterial but also fungal)
2- increased susceptibility to toxins and drugs
3- increased serum ammonia - failure of ammonia (produced via amino acid deamination and colonic bacteria) clearance via urea cycle… hepatic encephalopathy
name 3 investigations indicating hepatitis
- sig. increased serum ALT
- increased serum bilirubin
- conjugated bilirubin in urine
which signs/symptoms suggest hepatitis
- jaundice
- dark urine
- right upper quadrant pain
- fever
- anorexia
- malaise
what is liver cirrhosis? Describe the pathophysiology.
Liver cirrhosis = shrunken and hard nodular liver due to destruction and replacement by fibrosis of liver tissue… impairs liver function and alters vessel architecture in liver.
Process: cellular stress/injury… stellate cells lose vitamin A storage capacity and differentiate into myofibroblasts… deposit collagen within liver perisinusoidal space… liver fibrosis.
what is the effect of pressure/occlusion of hepatic sinusoids and bile canaliculi in liver cirrhosis
- pressure and occlusion of hepatic sinusoids…
- portal hypertension… ascites, portosystemic shunting (diversion of nutrient-rich blood away from liver)
- increased pressure in portosystemic anastamoses, e.g. at oesophagogastric junction (… oesophageal varices), anorectal junction (… haemorrhoids) and ligamentum teres of falciform ligament (… caput medusae)
- pressure on bile canaliculi… decreased ability to excrete toxins, bilirubin, etc. … bilirubinuria
why does cirrhosis cause easy bleeding/bruising
hepatocyte replacement by fibrous tissue… decreased albumin and clotting factor production
name the 2 main causes for biliary duct obstruction
- gallstones (migrating from bladder into common bile duct)
2. carcinoma of head of pancreas
why do gallstones form and what are the symptoms
- form when bile acids and excess cholesterol crystallise and precipitate (4/5) or from excess levels of bilirubin (1/5)
- most remain in bladder and are asymptomatic but can cause biliary colic if they move into gallbladder neck or ducts: RUQ pain that radiates to top of right shoulder, lasting up to 6hrs, often precipitated by eating fatty meal
