Investigation of Liver and GI tract disease Flashcards
What is the largest organ in the body?
The liver
Where is the liver located?
Located in the upper right quadrant of the abdomen
How much does the liver weigh ?
Weighs approximately 22 g/kg of body weight
What’s the blood supply of the liver?
Has dual blood supply
- 2/3 comes from the gut via the portal vein
- 1/3 from the hepatic artery (rich in oxygen)
Where does the blood leave the liver through?
Blood leaves through the hepatic vein
How many loves does the liver have and which one is bigger?
The liver has two lobes
Right lobe is slightly larger than left
What are these lobes composed of?
Composed of multiple liver lobules
What do the lobes consist of and what do they do?
These consist of plates of hepatocytes radiating from a central vein
Which carries blood from the liver
What is the liver acini?
the smallest functional unit of the liver
What do the bile canaliculi merge and form?
The bile canaliculi merge and form bile ductules
What are the major functions of the liver?
Carbohydrate metabolism Fat metabolism -Cholesterol and fatty acid synthesis Protein metabolism Synthesis of plasma proteins Hormone metabolism -Peptide and steroid hormones Metabolism and excretion of drugs and foreign compounds Storage – glycogen, vitamin A and B12, plus iron and copper Metabolism and excretion of bilirubin
What does hepatitis do to the liver?
Causes damage to hepatocyte
What does cirrhosis do to the liver?
- Increased fibrosis
- Liver shrinkage
- Decreased hepatocellular function
- Obstruction of bile flow
Why does it take a while for liver function to decrease?
Liver has a big functional reserve so takes a while for liver function to decrease
What are LFT’s indicators of?
Insensitive indicators of liver function
Sensitive indicators of liver damage
What do LFT’s look for?
Look for pattern of results - a single result rarely provides a diagnosis on its own
What context must LFT’s be interpreted within?
Interpretation must be performed within the context of the patient’s risk factors, symptoms, medications, current condition/illness and physical findings
What can LFT’s be used for?
- Screening the presence of liver disease
- Assessing prognosis
- Differential diagnosis: predominantly hepatic or cholestatic
- i.e. destruction of liver cells or blockage - Monitoring disease progression
- Measuring efficacy of treatments for liver disease
- Assessing severity
- Especially in patients with cirrhosis as this is a chronic disease
What results do standard LFT’s provide?
- Total bilirubin
- Alanine aminotransferase (ALT)
- Alkaline phosphatase (ALP)
- Albumin
When do albumin concentrations tend to decrease in?
Albumin concentrations only tend to decrease in chronic liver disease
What is bilirubin?
Bilirubin is the breakdown of the haem of haemoglobin
What is bilirubin broken down by?
Broken down by spleen
What state is bilirubin produced in and what’s it bound to when its transported?
Bilirubin produced is unconjugated
-Has to be transported bound to protein – albumin
Where does unconjugated bilirubin get transported to and enters what cells?
Unconjugated bilirubin gets transported to liver, enters hepatocytes
Why does bilirubin become conjugated and for what?
Becomes conjugated to make it more soluble for excretion
What causes bilirubin to become conjugated?
UDP-glucoronyl transferase
Where does conjugated bilirubin get excreted to and what’s it broken down to in the gut?
Conjugated bilirubin gets excreted to gut where it is broken down to urobilinogen and stercobilin
What causes the brown colour of faeces?
stercobilin
What can urobilinogen escape to and where can it be seen then?
Urobilinogen can sometimes escape to extra-hepatic circulation so some may be seen in kidneys
What does jaundice describe?
Jaundice describes the yellow discolouration of tissue due to bilirubin deposition
What is hyperbilirubinemia?
An increase in total bilirubin
When is clinical jaundice evident?
When the serum/plasma bilirubin concentration is 2x the upper reference of normal
What are the causes of jaundice?
- Haemolysis
- Hepatocellular damage
- Cholestasis
What effect does haemolysis have on bilirubin?
Increased bilirubin production
What effect does hepatocellular damage have on bilirubin?
Impaired bilirubin metabolism
What effect does cholestasis have on bilirubin?
Decreased bilirubin excretion
What is bilirubin measured in samples as?
Bilirubin is measured in serum/plasma samples as:
- Total bilirubin - Unconjugated and conjugated bilirubin (& delta bilirubin)
- Direct – Conjugated bilirubin (& delta bilirubin)
- Indirect – Unconjugated bilirubin (calculated)
What is delta bilirubin formed by and what does it occur in the presence in?
Delta bilirubin is formed by the irreversible covalent addition of bilirubin to albumin
-Occurs in the presence of prolonged conjugated hyperbilirubinemia
How can bilirubin be measured in urine?
Bilirubin can be measured in urine using a simple dipstick
Why is unconjugated bilirubin not normally found in urine?
As unconjugated bilirubin is protein bound it is not normally found in urine
-It is insoluble
What does bilirubin in urine indicate presence of?
Presence of bilirubin in the urine therefore indicates the presence of conjugated hyperbilirubinaemia
What darkens the urine and what cases is this seen in?
Excess conjugated bilirubin will darken the urine
-This is seen in cases of hepatitis or impaired flow of bile in patients with biliary obstruction
What does the presence of urobilinogen demonstrate and what can this be detected by?
If urobilinogen is present in the urine it demonstrates that bilirubin is reaching the gut
-It can be detected by a urine dipstick
What does excess urobilinogen in the urine indicate?
Excess urobilinogen in the urine may indicate liver disease such as viral hepatitis and cirrhosis or haemolytic conditions associated with increased red cell destruction.
What happens to our stool if bilirubin doesn’t reach the gut?
When bilirubin does not reach the gut, stercobilin is not produced and stools appear pale in colour
What is the alanine aminotransferase enzyme(ALT) and what is it a key enzyme in?
ALT is a intracellular cytoplasmic enzyme that catalyses the transfer of an amino group from alanine to α-ketoglutarate
-Key enzyme in gluconeogenesis
What is ALT the most specific marker for and what is it expressed by other than the liver
ALT is the most specific marker for liver injury although it is also expressed by the kidneys and cardiac and skeletal muscle
What is ALT used to identify and arising from what?
ALT is used to identify liver damage arising from hepatocyte inflammation or necrosis
What can happen to the levels of ALT with severe liver damage?
Values >20x the upper limit of normal (ULN) may occur with severe liver damage
What happens to levels of ALT in cholestasis and due to what?
Small increases (<5x ULN) may occur in cholestasis due to secondary damage to hepatocytes.
What is asparate aminotransferase enzyme(AST)?
AST is a intracellular cytoplasmic and mitochondrial enzyme that catalyses the transfer of an amino group from aspartate to α-ketoglutarate
What is the only indication for measuring ALT and AST and to suggest what disease?
The only indication for measuring ALT and AST is to determine the AST:ALT ratio:
-<0.8 – suggestive of non-alcoholic fatty liver disease (NAFLD); >1.5 – alcoholic liver disease (ALD)
Where are AST and ALT released from?
AST and ALT are released from the cytosol (AST is also being released by mitochondria)
What is alkaline phosphatase(ALP)?
ALP is a membrane bound glycoprotein enzyme that removes phosphate groups from proteins and nucleic acids
When does ALP have a maximum catalytic activity?
It has maximum catalytic activity at pH 9-10.5
Where are ALP isoenzymes found?
ALP isoenzymes are found in a number of tissues
What is ALP a major value in the diagnosis of?
ALP is of major value in the diagnosis of cholestatic disease along with GGT as cholestasis stimulates enhanced synthesis of liver ALP
When is ALP elevated other than diseases?
ALP is elevated in children and correlates well with the rate of bone growth (child-specific reference ranges). Also increased during pregnancy due to an increase in placental ALP
What can the source of elevated ALP be determined by?
The source of an elevated ALP can be determined by gel electrophoresis
What is it possible to separate ALP isoenzymes into?
It is possible to separate ALP isoenzymes into liver, bone, and intestinal fractions
How can placental isoenzyme of ALP be identified?
The placental isoenzyme of ALP can be identified as it is heat stable at 65C for 10 minutes, unlike the other isoenzymes
What is Gamma glutamyl transferase(GGT)?
GGT is a membrane bound enzyme that transfers the gamma glutamyl group from peptides
What is GGT a marker for?
A relatively specific marker for liver injury found on the canalicular membrane of hepatocytes, but also found on the cell membranes of other tissues
What is elevated plasma GGT in response to?
Plasma GGT is elevated in response to consumption of alcohol and other drugs
What does an increased ALP and GGT suggest?
↑ ALP and ↑ GGT – suggestive of hepatic cause
What does an increased ALP and normal GGT suggest?
↑ ALP and N GGT – suggestive of bone source of ALP
What does normal ALP and increased GGT suggest?
N ALP and ↑ GGT – suggestive of excess alcohol intake
What is the half life of albumin?
Half life around 20 days
How many grams of albumin does the liver synthesis around a day?
liver synthesises around 12g every day
What happens to the levels of albumin in chronic liver disease?
Decreases in chronic liver disease
What is albumin and what is its roles?
Albumin is an essential plasma protein and has many roles including maintaining the plasma oncotic pressure and binding several hormones, drugs, anions and fatty acids
What is the GI tract?
The GI tract is a 7-10 m continuous tube that runs from the mouth to anus
What is the GI tract partitioned into?
Partitioned into many sections with distinct structure, anatomy and function
Different parts of the GI tract
LOOK AT DIAGRAM ON PPT SLIDE
What is the GI tract encased in?
The GI tract is encased in layers of voluntary and involuntary muscle (contraction in waves)
What does the GI tract have a large sysem of?
Has a large arterial system linking the different sections to the circulation
What percentage of the cardiac output innervates the GI tract?
30%
What is the enteric endocrine system?
Hormone signalling allows different parts of the GI tract to ’switch on’ and ‘switch off’
What are gastric ulcers caused by?
Gastric (or peptic) ulcers are caused by a break in the protective mucosal lining of the stomach
What are signs and symptoms of gastric ulcers?
- Pain in the abdomen that may come and go (may be eased with antacid)
- Waking up with a feeling of pain in the abdomen
- Bloating, retching and feeling sick
- Feeling particularly ‘full’ after a normal size meal
What are the causes of gastric ulcers?
Causes of gastric ulcers are infection with helicobacter pylori (80% of cases) or the use of NSAIDs(20% of cases)
What is H.Pylori?
H. pylori is a helix-shaped gram-negative bacteria
Dimensions of H.pylori
Diameter of 0.5 μm and length of 3 μm
What does H.pylori cause damage to?
Causes damage to the mucosal layer of gut
What does H.pylori cause in the duodenum?
In the duodenum, it causes hypersecretion of acid
What is the urea breath test used to identify?
The urea breath test is rapid and non-invasive procedure used to identify infections by H. pylori
Steps involved in urea breath test
First take a basal breath test
Then patient drinks a solution containing urea labelled with an uncommon isotope (radioactive carbon-14 or non-radioactive carbon-13)
Take second breath test
If H.pylori is present, it will split the urea and release the uncommon isotope
The detection of isotope-labelled carbon dioxide in exhaled breath indicates that the urea was split and that that urease, and therefore H. pylori, is present in the stomach
Why must Vitamin B12 be obtained from diet?
Vitamin B12 cannot be produced by the human body and so must be obtained from the diet
What does vitamin B12 play a role in?
Essential role in the nervous system and the formation of red blood cells as a co-factor for DNA synthesis
What do we need for the absorption of vitamin B12 by the small intestine?
Needs intrinsic factor for its absorption by the small intestine
What is the intrinsic factor?
a 45 kDa glycoprotein made by the parietal cells of the stomach
What does the B12-IF complex do when it enters the intestine?
The B12-IF complex enters the intestine where it binds to receptors on the musocal cells of the ileum and is absorbed into the blood stream
Why would it take a long time for B12 deficiency to present itself?
The liver can store 3-5 years worth of vitamin B12, meaning that it can take a long time for vitamin B12 deficiency to present itself
What are signs and symptoms of B12 deficiency?
Macrocytic anaemia (increased MCV, decreased haemoglobin)
Weakness and tiredness
Pale skin
Glossitis – inflammation of the tongue
Nerve problems such as numbness or tingling (severe deficiency)
What is severe deficiency of vitamin B12 caused by?
Severe deficiency of vitamin B12 is usually caused by pernicious anaemia, an autoimmune attack on the gastric mucosa
What is there a loss of in pernicious anaemia?
Loss of intrinsic factor as there is loss of parietal cells
What is coeliac disease?
Coeliac disease is an autoimmune disorder, primarily affecting the small intestine
What does coeliac disease result from?
The disease results from immunological hypersensitivity to ingested to gliadin
What does coeliac disease do to the villi in the small intestine?
Flattens the villi in small intestine
What do classic symptoms of coeliac disease include?
GI problems such as diarrhoea, abdominal distention, malabsorption and loss of appetite
What is used for the diagnosis of coeliac disease?
A duodenal biopsy is the gold standard diagnosis of coeliac disease
What are tissue transglutaminase antibodies?
Enzyme that deaminates glutamine residues to glutamic acid on the gliadin fragment
what antibodies to TTG are found in approx. 96% of patients with coeliac disease?
IgA antibodies to TTG are found in approximately 96% of patients with coeliac diseas
What other antibody to TTG do we test for in coeliac disease?
Also test for IgG antibodies to TTG
When do we test for endomysial antibodies?
Do this test if patient does not have IgA
What is the endomysium?
The endomysium is the supporting structure that surrounds the middle third of the oesophagus
What are endomysial antibodies indicative of?
Endomysial antibodies are indicative of coeliac disease
What test is more sensitive for coeliac disease?
Endomysial antibody test is not as sensitive as the TTG antibody test
What are the signs and symptoms of IBS and IBD?
abdominal pain or discomfort with diarrhoea or constipation
How can IBD be treated and why?
can be treated with anti-inflammatory drugs because IBD is autoimmune
What is calprotectin, where’s it found and what’s it released upon?
Calprotectin is a small zinc and calcium containing protein found in neutrophils and released upon inflammation
What happens to neutrophils in the presence of active intestinal inflammation neutrophils?
In the presence of active intestinal inflammation neutrophils migrate to the intestinal mucosa from the circulation
What does disturbance In mucosa architecture due to inflammatory processes result in?
Any disturbance in the mucosa architecture due to the inflammatory process results in leakage of neutrophils and hence calprotectin is excreted in feces
What is the faecal immunochemical test(FIT)?
‘Dipstick’ test for blood in stool
What does FIT allow an early detection of?
Colon cancer
Why may we get erroneous test results in FIT?
Erroneous test results due to improper specimen collection, failure to follow the recommended sample collection procedure, handling or storage, or an insufficient concentration of starting material
What does FIT measure?
Quantitative measurement of Hb in faeces
FIT result <9.5 µg Hb/g faeces
These patients have a low risk of colorectal cancer.
FIT ≥10 µg Hb/g faeces
Further investigations are required in line with local guidelines.
