Laboratory Investigation of Liver and GI tract Disease Flashcards Preview

CLINICAL PATHOLOGY > Laboratory Investigation of Liver and GI tract Disease > Flashcards

Flashcards in Laboratory Investigation of Liver and GI tract Disease Deck (46)
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1

What are the major functions of the liver? 

  • Carbohydrate, fat and protein metabolism 
  • Synthesis of plasma proteins (e.g albumin) 
  • Hormone metabolism 
  • Metabolism and excretion of drugs + foreign compounds 
  • Storage - glycogen, Vitamin A and B12, plus iron and copper 
  • Metabolism + Excretion of bilirubin 

2

List some of the common diseases affecting the liver 

  • Hepatitis → Damage to hepatocytes 
  • Cirrhosis →  Increased fibrosis, liver shrinkage, decreased hepatocellular function, obstruction of bile flow 
  • Tumours → Frequently secondary (colon, stomach, bronchus) 

3

What is the general biochemical assesment of liver function? 

Liver Function Test (LFT) 

Standard profile includes: 

  • Bilirubin 
  • Albumin 
  • Alanine aminotransferase (ALT) or Aspartate aminotransferase 
  • Alkaline phosphatase 
  • Gamma glutamyltransferase

4

What is the general prinicple of liver function tests?  

  • A type of blood test 
  • Is not diagnostic but is used as an aid for 
    • Screening for presence of liver disease 
    • Assesing prognosis 
    • Measuring efficacy of treatments for liver disease 
    • Differential diagnosis →  Predominantly hepatic/cholestatic 
    • Monitoring disease progression 
    • Assesing severity →  especially in patients with cirrhosis 

5

Describe the metabolism of bilirubin

  • Bilirubin is a yellow-orange pigment derived from haem 
  • RBCs are broken down in the spleen 
  • Bilirubin is unconjugated (and not soluble) its transported via albumin in the circulation 
  • Bilirubin will be transported to the liver where it is conjugated into a more soluble form via UDP-glucuronyl transferase 
  • Bilirubin →  bilirubin diglucuronide 
  • Bilirubin will be excreted in the gut where it is broken down into urobilinogen 
  • Urobilinogen will be converted to stercobilin (brown in faeces) via gut flora 
  • Some urobilinogen will escape into extrahepatic circulation where it is excreted in urine 

6

What is Jaundice? 

Jaundice is the yellow discoloration of tissue due to bilirubin deposition (hyperbilirubinaemia) 

Clinical jaundice may not be evident until the serum/plasma bilirubin concentration is 2x the upper reference of normal, >50 micromol/L

7

What are causes of Jaundice? 

  • Haemolysis (increased bilirubin production)
    • Acquired autoimmune haemolytic jaundice, drug induced + spherocytosis
  • Hepatocellular damage (impaired bilirubin metabolism)
    • Toxins or infections
  • Cholestasis (decreased bilirubin excretion)
    • Cirrhosis, tumour or gallstones

8

Describe Neonatal Jaundice 

  • Occurs due to immaturity of the bilirubin conjugation enzymes 
  • Normally common and transient will resolve in the first 10 days 
  • Pathological if there are high levels of unconjugated bilirubin → toxic to newborn 
    • Due to HYDROPHOBICITY cross blood-brain barrier and cause kernicterus (brain damage due to toxic bilirubin affecting neurons) 

9

When does neonatal jaundice become urgent? 

Pale stools in babies with biliary atresia → urgent surgical treatment is essential !!!

10

How can you treat neonatal jaundice? 

Phototherapy with UV light = converts bilirubin to water soluble non-toxic form 

11

Describe Gilberts Syndrome 

  • Results in prehepatic jaundice, Benign liver disorder 
  • Caused by a genetic defect UDP-glucuronyl transferase 
  • Frequency à 10% of the population
  • Characterised by mild, fluctuating increases in unconjugated bilirubin
    • Caused by decreased ability of the liver to conjugate bilirubin
  • Males more frequently affected then females

12

What does a standard liver function test include? 

  • Total bilirubin
  • Alanine aminotransferase (ALT)
  • Alkaline phosphatase (ALP)
  • Albumin

13

Describe the lab investigations of bilirubin in plasma/blood 

Measured in serum/plasma sample as: 

  • Total bilirubin = unconjugated and conjugated bilirubin 
  • Direct = conjugated bilirubin (delta bilirubin) 
  • Indirect = unconjugated bilirubin (calculated) 

Delta bilirubin is formed by the irreversible covalent addition of bilirubin to albumin that occurs in the presence of prolonged conjugated hyperbilirubinaemia 

14

Describe lab investigations of bilirubin in urine 

  • Bilirubin in measured in urine using a dipstick 
  • Presence of bilirubin in urine indicates presence of conjugated hyperbilirubinaemia 
  • Excess conjugated bilirubin will darken urine (e.g hepatitis or impaired flow of bile in patients with biliary obstruction) 

15

What is the signifiance of urobilinogen in urine? 

  • If urobilinogen is present in the urine it demonstrates that bilirubin is reaching the gut 
  • Excess urobilinogen may indicate liver disease such as viral hepatitis and cirrhosis or haemolytic conditions associated with increased red cell destruction 

16

What are liver transaminases? And what are they used to detect? 

  • Most commonly markers of hepatocyte injury 
  • Include ALT (alanine transaminase) + AST (aspartate transaminase) 
  • Transaminases catalyse the transfer of an amino group 
  • e.g ALT catalyses the transfer of an amino group from alanine to alpha-ketoglutarate 
  • ALT is used to identify liver damage from hepatocyte inflammation or necrosis 
    • ALT → Predominantly locallised to the liver 
    • AST →  has a wide tissue distribution located in the heart, skeletal muscle, kidney, brain, erythrocytes, lung + liver 

17

What do elevated levels of transaminases mean? 

  • Values >20x the upper limit of normal (ULN) may occur with severe liver damage.
    • Acute viral hepatitis, hepatic necrosis induced by drugs or toxins, ischaemic hepatitis induced by circulatory shock

  • Small increases (<5x ULN) may occur in cholestasis due to secondary damage to hepatocytes
    • Fatty liver, chronic viral hepatitis, prolonged cholestatic liver disease, cirrhosis (in compensated cirrhosis values may be normal)

18

Describe alkaline phosphatase (ALP) 

  • Enzyme removes phosphate groups from proteins and NAs at an alkaline pH (9-10.5) 
  • Enzyme isoforms mainly produced in the liver and bone but also placental intestinal forms

19

How is alkaline phosphatase used in liver diagnosis? 

  • ALP levels will increase when there is bile duct obstruction (due to ALP synthesis) 
  • Obstruction may be due to
    • extrahepatic (stones, tumour or stricture)
    •  intrahepatic (infiltration or space occupying lesion)
      • ALP values >3 x ULN found in intra- & extrahepatic cholestasis
      • ALP values <3 x ULN found in hepatocellular disease

20

When can alkaline phosphatase also increase but isnt liver related? 

Increases when there is a increase in osteoblastic activity as ALP is also released by bones

For example in

  • Healing fractures 
  • Vitamin D deficiency 
  • Paget's Disease 

21

How can ALP isoenzymes be seperated? 

  • The source of an elevated ALP can be determined by gel electrophoresis 
  • It is possible to separate ALP isoenzymes into liver, bone and intestinal fractions 
  • The placental isoenzyme of ALP can be identified as it is heat stable at 65 degrees for 10 minutes unlike the other isoenzymes

22

Describe gamma glutamyl transferase (GGT)

GGT is a membrane bound enzyme which transfers the gamma glutamyl group from peptides such as glutathione to other peptides and L-amino acids

  • Wide tissue distribution, but liver isoenzyme activity predominates in serum 
  • Used in combination with ALP (increase in value confirms ALP of hepatic origin) 

23

What are the increases in gamma glutamyl transferase due to? 

  • Increased levels may be due to enzyme induction by alcohol or drugs e.g. anticonvulsants.
  • Increased levels occur in cholestasis and hepatocellular disease
  • Can be increased in non-hepatic disorders, e.g. pancreatitis, myocardial infarction and diabetes mellitus

24

Describe how albumin is to assess liver function

  • Concentration widely regarded as an indec of hepatic synthetic function 
  • Can be normal in early acute hepatitis due to its long half-life (21-days) 
  • Acute or chronic destructive liver diseases of moderate severity show decreased severe albumin 
    • Decreases also consistent with 
      • Haemodilution (e.g. in pregnant women) 
      • Impaired synthesis (e.g. malnutrition) 
      • Increased loss (e.g. nephrotic syndrome) 
      • Inflammatory leak 

But values may be well compensated in liver disease 

25

Describe NAFLD 

NAFLD more prevalent than alcoholic liver disease

  • Prevalence
    • 20% in general population
    • Up to 70% in type 2 diabetes
  • Stages
    • Hepatic steatosis (fat >5% liver volume)
    • Greater risk of progressing to fibrosis, cirrhosis, HCC
  • Major risk factors
    • Obesity
    • Diabetes/ insulin resistance
  • Hypertension

26

Provide a brief overview of the GI tract 

  • Continuous tube running from mouth to anus 
  • Partitioned into many sections with distinct structure, anatomy and function 
  • Associated organs include liver, gall bladder and pancreas 
  • GI tract is encased in layers of voluntary and involuntary muscle (contraction in waves) 
  • Has a large arterial system linking different sections to the circualtion (30% of C.O.) 

27

What are gastric ulcers? 

  • Caused due to a break in the protective stomach mucosal lining 
    • Signs + Symptoms 
      • Pain in abdomen 
      • Waking up with pain in abdomen 
      • Bloating, retching and feeling sick 
      • Feeling full after a normal sized meal 

28

What are the common causes of gastric ulcers? 

  • H.Pylori  (80% of cases) 
    • Helix shaped gram negative bacteria survives in gastric acid by secreting urease
  • Use of aspirin and NSAIDs (20% of cases) 
    • Non-steroidal anti-inflammatory drugs

29

How is H.Pylori detected? 

  • Urea breath test 
    • Patient drinks a solution containing urea labelled with a uncommon isotope (non-radioactive carbon-13) 
    • The detection of isotope labelled CO2 in exhaled breath detected that urea was split by urease secreting H.Pylori 

30

What is vitamin B12 and why is it required? 

  • Water soluble vitamin whcih plays a role in the formation of RBCs acting as a co-factor for DNA and cell metabolism
  • Involved in the conversion of homocysteine to methionine  
  • Also known as cobalamin 
  • Not produced by the body but taken up via the diet through meat and dairy products 

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