Chemical Pathology - LFTs Flashcards
What are markers of liver cell damage?
- ALT
- AST
- ALP
- GGT
- Bilirubin
What are markers of synthetic function?
- Clotting (INR)
- Albumin
- Glucose
What is the best marker of liver function in acute liver injury?
Prothrombin time
What are some causes of transaminitis (Transaminases in the 1000s)?
- Acute viral hepatitis
- Toxins (e.g. paracetamol)
- Ischaemic hit
Where are AST and ALT found?
Liver, cardiac and skeletal muscle, and the kidney + brain
What are some causes of a raised AST and ALT?
Hepatic (e.g. hepatitis, transaminitis)
What conditions are indicative of a raised ALT > raised AST?
- Chronic liver disease (e.g. NASH)
- Chronic hepatitis C
- Hepatic obstruction
- Advanced fibrosis/cirrhosis
What are some causes of an AST:ALT ratio of 2:1?
Alcoholic liver disease
What are some causes of an AST:ALT ratio of 1:1?
Viral hepatitis
Where is GGT found?
- Hepatocytes
- Biliary cells
- Kidney
- Pancreas
What type of picture is seen with a raised GGT and ALP?
Cholestatic/obstructive
- Gallstones
- Head of pancreas tumour
What are some causes of a raised GGT?
- Chronic alcohol use
- Bile duct disease
- Metastases
Where is ALP found?
High concentrations in liver, bone (osteoblastic activity), intestine + placenta
What are some physiological and pathological causes of an isolated rise in ALP?
Physiological:
- Pregnancy
- Childhood (growth spurt)
Physiological:
>5x upper normal limit
- Paget’s disease
- Osteomalacia
- Liver (cholestasis, cirrhosis)
<5x upper normal limit
- Primary tumours, infiltrative liver disease
- Hepatitis
- Renal osteodystrophy
Why is ALP normal in multple melanoma?
Plasma cells suppress osteoblasts (ALP produced by osteoblasts)
What is albumin indicative of?
Liver synthetic function
What are some causes of a low albumin levels?
- Chronic liver disease
- Malnutrition
- Protein-losing enteropathy
- Nephrotic syndrome
- Sepsis
What are some causes of low urea?
- Severe liveer disease
- Malnutrition
- Pregnancy
Where is urea synthesised?
The liver
What are some causes of a raised urea (>10x the upper normal limit)?
- Upper GI bleed
- Dehydration/AKI
What are some causes of prehepatic jaundice?
- Haemolytic anaemia
- Ineffective erythropoeisis
What are some bilirubin findings of prehepatic jaundice
- No conjugated bilirubin
- No urine bilirubin
- Normal/increased urobilinogen
- Normal/increased unconjugated bilirubin
- Splenomegaly
What are some causes of hepatic jaundice?
- Hepatocellular dysfunction
- Impaired conjugation (Gilbert’s syndrome)
- Impaired bilirubin uptake
What are som bilirubin findings of hepatic jaundice?
- Increased conjugated bilirubin
- Increased unconjugated bilirubin
- Increased urobilinogen
- Urine bilirubin present
- Dark urine
- Increased AST/ALT
- Splenomegaly
What are some causes of post-hepatic jaundice?
Obstruction
- Stones
- Pancreatic cancer
What are some urine and stool findings of post-hepatic jaundice?
- Incerased conjugated bilirubin
- Absent/decreased urobilinogen
- Urin bilirubin present
- Dark urine (increased urobilinogen)
- Pale stool (decreased stercobilinogen)
- Increased ALP
How much albumin is synthesised daily in the average adult?
200mg/kg
What does albumin do?
Binds many hormones, calcium + other metabolites
What can contribute to a reduced albumin?
- Acute illness/systemic inflammation
- Malnutrition
What is a poor prognostic factor in critically ill patients?
Hypoalbuminaemia
Which clotting factors are synthesised in the liver?
- Factors V, VII, IX, X, XII, XIII
- Fibrinogen
- Prothrombin
What is the INR?
International normalised ratio
- Prothrombin time standardised for age and population
- Expressed as ratio of normal
What are some other causes of deranged clotthing (aside from hepatocellular dysfunction)?
- Iatrogenic (therapeutic warfarinisation)
- Hereditary thrombophilia
- Acquired consumption (DIC)
What is jaundice?
Elevated serum bilirubin manifesting as yellowing of the skin or sclera (icterus)
What is bilirubin?
A breakdown produce of heme (majority produced by breakdown of haemoglobin)
What is the process of bilirubin, urobilinogen and stercobilinogen production?
- Normal bilirubin metabolism: conjugation in hepatocytes + secretion into bile ducts then GI tract
- Conjugated bilirubin metabolised in GI tract into urobilinogen
- Urobilinogen partially reabsorbed and excreted in kidneys (as urobilin) + the rest is converted into stercobilin
What is basic pathophysiology of pre-hepatic jaundice?
Raised bilirubin production
What is the basic pathophysiology of hepatic jaundice?
Decreased ability to conjugate bilirubin
What is the basic pathophysiology of post-hepatic jaundice?
Decreased ability to excrete conjugated bilirubin
Why is there no urine bilirubin in prehepatic jaundice?
- Unconjugated bilirubin (from heme breakdown in spleen), is tightly bound to albumin
- Too larger to pass through glomerulus
- Expect: raaised LDH, reduced haptoglobin
What are some causes of hepatomegaly with a smooth margin?
- Viral hepatitis
- Biliary tract obstruction
- Hepatic congestion secondary to HF/Budd-Chiari
What are some causes of hepatomegaly with a craggy border?
- Hepatic metastatic disease
- Polycystic disease
- Cirrhosis (will shrink)
