Liver Disorders Flashcards
What type of blood supply does the liver have
Unique dual blood supply:
-2/3 from portal vein(venous,from digestive tract and spleen)
-1/3 from hepatic artery(arterial,from aorta)
Facts about the liver
-it has regenerative abilities,75%of liver can be removed without obvious loss of function
-its functional unit are called lobules
Kupffer cell
Macrophages,remove debris and pathogens from circulation by phagocytosis
Liver cells
Called hepatocytes and are involved In bile production
They flow into bile canals,flow in opposite direction to the blood flow
Liver functions list
1)Carbohydrate metabolism
-Stores excess glucose as glycogen.
-It also converts non-carbohydrates into glucose
2)Fat metabolism
-Breaks down fats into fatty acids and glycerol
-It also synthesizes cholesterol and bile acids, which aid in fat digestion
3)Protein metabolism
-Breaks down amino acids and synthesizes proteins
-It also removes ammonia from the blood, converting it into urea
4)Endocrine
Produces a variety of hormones, including insulin-like growth factor 1 (IGF-1) and angiotensinogen
5)Iron storage
-Iron is essential for the production of red blood cells
6)Storage of vitamin B12
-Vitamin B12 is necessary for the production of red blood cells
Detoxification
-Filters harmful substances from the blood, such as drugs,
Liver function tests(LFTs)
There is no single bio marker,profile of biochemical and heamatological liver function tests needed to establish liver disease and make a specific diagnosis.
-second line investigation involves determining whether its hepatic or cholestatic
Hepatic(hepatocyte injury)
Primarily medial management
Liver biopsy/other investigations
Choleststic(biliary system)
Imaging techniques
Surgical intervention
Type of liver function test
Aminotransferases which indicates Hepatic damage, increased in blood when released from dead/injured hepatocytes
Alkaline phosphatase which indicates Cholestatic disease: accumulation o f bile causes increased ALP production by
hepatocytes
Gamma-glutamyl transpeptidase (GGT) which indicates Cholestatic disease: Cell surface enzyme
expressed by biliary cells. Role in cysteine/protein metabolism
Albumin which indicates Synthetic function
Prothrombin time which indicates Clotting (dynamic indicator): the liver produces clotting factors
Bilirubin which indicates Cholestasis: if the biliary system is not working circulating bilirubin will increase
Aspartate aminotransferase (AST)
Present in cytosol/mitochondria of hepatocytes
Lacks specificity: could also indicate a problem in a different organ/system
Alanine aminotransferase (ALT)
Present in cytosol of hepatocytes
More specific for liver – activity much lower in extrahepatic tissue
How do aminotransferases indicate hepatic damage
Hepatocellular damage
• Infective agents, autoimmune disorders, toxins
• ALT/AST may increase by up to 100 times upper limit of reference range
• ALT/AST useful in monitoring progress of hepatocellular damage
Cholestasis
• AST/ALT increases slightly but no more than 2-3 times upper limit of reference range
AST/ALT ratio > 2 suggestive of alcohol misuse
What is cholestasis
Condition where flow of bile from the liver to the duodenum is impaired.can whether be caused by an obstruction in the duct system due to eg malignancy or caused by disturbances in bile formation
Alkaline phosphatase (ALP)
• Not specific for liver
• Occurs on hepatocyte surface and microvilli of bile ducts
• Hepatocellular damage
ALP normal/slightly raised; no more than 2 times upper limit of reference range
• Cholestasis
ALP is increased > 3 times upper limit of reference range
ALP concentration useful for monitoring progress of cholestasis
Increase in serum ALP may be caused by
Liver
• Obstruction of bile duct or ductules
• Portal hypertensions or reduced blood flow due to left heart failure
Other causes
• Paget’s disease
• Malignancy in the bone
• Benign transient hyperphosphatasaemia (GIT infections)
Gamma-glutamyl transpeptidase (GGT)
• Also called gamma-glutamyl transferase
• GGT activity in plasma mainly attributable to the liver isoenzyme
• Raised in both hepatocellular disease and cholestasis
BUT
• Poor specificity for liver disease
• Direct relationship between GGT and alcohol
• Weight, drugs
Plasma proteins
• Albumin is the major protein synthesised by the liver
• 12 g/day
• Correlates with liver function
• ↓ serum [albumin] in chronic liver disease
• ↑Plasma globulins in alcoholic cirrhosis, autoimmune hepatitis
Prothrombin time (PT)
The rate at which prothrombin is converted to thrombin in the presence of activated clotting factors, calcium and thromboplastin.
• Increase is early feature of acute liver disease or vitamin K deficiency
• International normalised ration (INR), normal: 0.8-1.1
𝐼𝑁𝑅 = 𝑃𝑇 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡′𝑠 𝑏𝑙𝑜𝑜𝑑 \𝑃𝑇 𝑜𝑓 𝑛𝑜𝑟𝑚𝑎𝑙 𝑐𝑜𝑛𝑡𝑟𝑜𝑙
Bilirubin
• Yellow-green coloured pigment
• Derived from haem
• Haemolysis causes ↑ serum bilirubin
• Daily production of unconjugated bilirubin 250-350 mg
Measurement of serum/plasma bilirubin is one of the true “liver function” tests
How is bilirubin formed
-In the spleen erythrocytes get destructed
-This causes haemoglobin to be released;the glob in chain is hydrolysed to amino acids and the heam group is either a)carried by transferrin to be stored in bone marrow or liver or used for erythropoiesis
B)turned into protoporphyrin and there bilirubin
bilrubin metabolism
-there is 2 types of bilirubin;unconjugated(not water soluble) and conjugated(water soluble)
-unconjugated bilirubin becomes bound to albumin and taken to liver cells
-in liver cells bilirubin is conjugated with glucuronic acid ie. Conjugated bilirubin
-conjugated bilirubin is excreted in bile in small intestine where bacterial action converted it to urobilinogen and stercobilinogen
How does bilirubin become unconjagated
Binds to albumin
Bilirubin metabolism
Watch Lucture capture
Hyperbilirubinaemia
• Excess bilirubin production
• Impaired hepatic uptake of unconjugated bilirubin
• Impaired conjugation of bilirubin
• Decreased excretion of conjugated bilirubin in bile
Non-hepatic raise in unconjugated bilirubin
• Crigler-Najjar syndrome
Rare autosomal recessive condition. No or reduced bilirubin glucoronidation Kernicterus: Brain damage in infants
• Gilbert syndrome
Common, ~ 7% of the population
Autosomal dominant
Reduction in enzyme responsible for bilirubin conjugation Benign but recurrent episodes of mild jaundice
Non-hepatic raise in conjugated bilirubin
• Dubin-Johnson syndrome
Uncommon, benign condition; autosomal recessive. Decreased biliary canalicular transport of conjugated bilirubin.
• Rotor syndrome
Autosomal recessive, unknown gene mutation moderate fluctuation of jaundice.
Good prognosis.
Jaundice
-bilirubin] > 34 μmol/
-types of jaundice:
1)Pre-hepatic caused by:
-Haemolysis
-Ineffective erythropoiesis
2Hepatic caused by
-Hepatitis (drug / viral)
-Gilberts syndrome
-Crigler-Najjar syndrome
Dubin-Johnson syndrome
Rotor syndrome
Cirrhosis
Tumours
Biliary atresia
3)Post-hepatic
Gallstones
Cholangitis
Jaundice clinical symptoms
• Discolouration of skin / white area of eye
• Dark coloured urine due to bilirubin loss (cholestatic cause) • Rarely causes serious symptoms in adults
• Kernicterus (brain damage in children)
Management of jaundice
• Treat underlying cause
• Phototherapy
• e.g. in newborn when [bilirubin] is ≈ 200 μmol/L
• Exchange transfusion
• e.g. in newborn [bilirubin] is > 300 μmol/L
Acute liver disease
• Poisoning: drugs e.g. paracetamol • Infection: hepatitis A, B and C
• Majority of cases resolve completely
• In case of acute hepatic failure:
• Medical emergency
• Acid-base imbalance, electrolytes, hypoglycaemia, hypoalbuminaemia, oedema, ascites
• Renal failure due to toxins
• May lead to chronic liver disease
Investigation of Acute liver disease
• Hepatic damage: AST / ALT raised
• Cholestasis: ALP and serum [bilirubin] raised • Measure AST /ALT / ALP to monitor treatment
Chronic liver disease
• Alcoholic liver disease
• Chronic active hepatitis
• Primary biliary cirrhosis
• Non-alcoholic fatty liver disease
• Cirrhosis
Liver Cirrhosis
• Final stage of chronic liver disease
• Irreversible
• Jaundice, encephalopathy and ascites in later stages • Death due to liver failure
