Chemical Pathology - LFTs

Question 1

What are markers of liver cell damage?

Answer 1

• ALT
• AST
• ALP
• GGT
• Bilirubin

Question 2

What are markers of synthetic function?

Answer 2

• Clotting (INR)
• Albumin
• Glucose

Question 3

What is the best marker of liver function in acute liver injury?

Answer 3

Prothrombin time

Question 4

What are some causes of transaminitis (Transaminases in the 1000s)?

Answer 4

• Acute viral hepatitis
• Toxins (e.g. paracetamol)
• Ischaemic hit

Question 5

Where are AST and ALT found?

Answer 5

Liver, cardiac and skeletal muscle, and the kidney + brain

Question 6

What are some causes of a raised AST and ALT?

Answer 6

Hepatic (e.g. hepatitis, transaminitis)

Question 7

What conditions are indicative of a raised ALT > raised AST?

Answer 7

• Chronic liver disease (e.g. NASH)
• Chronic hepatitis C
• Hepatic obstruction
• Advanced fibrosis/cirrhosis

Question 8

What are some causes of an AST:ALT ratio of 2:1?

Answer 8

Alcoholic liver disease

Question 9

What are some causes of an AST:ALT ratio of 1:1?

Answer 9

Viral hepatitis

Question 10

Where is GGT found?

Answer 10

• Hepatocytes
• Biliary cells
• Kidney
• Pancreas

Question 11

What type of picture is seen with a raised GGT and ALP?

Answer 11

Cholestatic/obstructive
- Gallstones
- Head of pancreas tumour

Question 12

What are some causes of a raised GGT?

Answer 12

• Chronic alcohol use
• Bile duct disease
• Metastases

Question 13

Where is ALP found?

Answer 13

High concentrations in liver, bone (osteoblastic activity), intestine + placenta

Question 14

What are some physiological and pathological causes of an isolated rise in ALP?

Answer 14

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

Question 15

Why is ALP normal in multple melanoma?

Answer 15

Plasma cells suppress osteoblasts (ALP produced by osteoblasts)

Question 16

What is albumin indicative of?

Answer 16

Liver synthetic function

Question 17

What are some causes of a low albumin levels?

Answer 17

• Chronic liver disease
• Malnutrition
• Protein-losing enteropathy
• Nephrotic syndrome
• Sepsis

Question 18

What are some causes of low urea?

Answer 18

• Severe liveer disease
• Malnutrition
• Pregnancy

Question 19

Where is urea synthesised?

Answer 19

The liver

Question 20

What are some causes of a raised urea (>10x the upper normal limit)?

Answer 20

• Upper GI bleed
• Dehydration/AKI

Question 21

What are some causes of prehepatic jaundice?

Answer 21

• Haemolytic anaemia
• Ineffective erythropoeisis

Question 22

What are some bilirubin findings of prehepatic jaundice

Answer 22

• No conjugated bilirubin
• No urine bilirubin
• Normal/increased urobilinogen
• Normal/increased unconjugated bilirubin
• Splenomegaly

Question 23

What are some causes of hepatic jaundice?

Answer 23

• Hepatocellular dysfunction
• Impaired conjugation (Gilbert’s syndrome)
• Impaired bilirubin uptake

Question 24

What are som bilirubin findings of hepatic jaundice?

Answer 24

• Increased conjugated bilirubin
• Increased unconjugated bilirubin
• Increased urobilinogen
• Urine bilirubin present
• Dark urine
• Increased AST/ALT
• Splenomegaly

Question 25

What are some causes of post-hepatic jaundice?

Answer 25

Obstruction - Stones - Pancreatic cancer

Question 26

What are some urine and stool findings of post-hepatic jaundice?

Answer 26

- Incerased conjugated bilirubin - Absent/decreased urobilinogen - Urin bilirubin present - Dark urine (increased urobilinogen) - Pale stool (decreased stercobilinogen) - Increased ALP

Question 27

How much albumin is synthesised daily in the average adult?

Answer 27

200mg/kg

Question 28

What does albumin do?

Answer 28

Binds many hormones, calcium + other metabolites

Question 29

What can contribute to a reduced albumin?

Answer 29

- Acute illness/systemic inflammation - Malnutrition

Question 30

What is a poor prognostic factor in critically ill patients?

Answer 30

Hypoalbuminaemia

Question 31

Which clotting factors are synthesised in the liver?

Answer 31

- Factors V, VII, IX, X, XII, XIII - Fibrinogen - Prothrombin

Question 32

What is the INR?

Answer 32

International normalised ratio - Prothrombin time standardised for age and population - Expressed as ratio of normal

Question 33

What are some other causes of deranged clotthing (aside from hepatocellular dysfunction)?

Answer 33

- Iatrogenic (therapeutic warfarinisation) - Hereditary thrombophilia - Acquired consumption (DIC)

Question 34

What is jaundice?

Answer 34

Elevated serum bilirubin manifesting as yellowing of the skin or sclera (icterus)

Question 35

What is bilirubin?

Answer 35

A breakdown produce of heme (majority produced by breakdown of haemoglobin)

Question 36

What is the process of bilirubin, urobilinogen and stercobilinogen production?

Answer 36

- 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

Question 37

What is basic pathophysiology of pre-hepatic jaundice?

Answer 37

Raised bilirubin production

Question 38

What is the basic pathophysiology of hepatic jaundice?

Answer 38

Decreased ability to conjugate bilirubin

Question 39

What is the basic pathophysiology of post-hepatic jaundice?

Answer 39

Decreased ability to excrete conjugated bilirubin

Question 40

Why is there no urine bilirubin in prehepatic jaundice?

Answer 40

- Unconjugated bilirubin (from heme breakdown in spleen), is tightly bound to albumin - Too larger to pass through glomerulus - Expect: raaised LDH, reduced haptoglobin

Question 41

What are some causes of hepatomegaly with a smooth margin?

Answer 41

- Viral hepatitis - Biliary tract obstruction - Hepatic congestion secondary to HF/Budd-Chiari

Question 42

What are some causes of hepatomegaly with a craggy border?

Answer 42

- Hepatic metastatic disease - Polycystic disease - Cirrhosis (will shrink)