GASTROINTESTINAL system

2025-2026
Session 7
Liver ,Gall bladder and Pancreas
Prof. Dr. Hadeel A. Karbel
F.I.B.M.S(path.), [Link].B
 objectives
• to appreciate the causes and consequences of liver disease
• to appreciate the effects of disorders of the biliary tree, including gall stones
• to appreciate the causes and consequences of pancreatic disease
• describe the causes of and effects of jaundice
• distinguish pre-hepatic, hepatic and post-hepatic jaundice
• describe the effects of excessive alcohol consumption on the liver,
and the key features of alcoholic liver disease.
• describe the consequences of cirrhosis of the liver.
• outline how liver diseases may lead to portal hypertension.
• Liver function tests:
• The liver has a wide range of functions including bile
production, carbohydrate, lipid, and protein
metabolism, protein synthesis, Vitamin D synthesis,
detoxification, vitamin and mineral storage, and
phagocytosis. Any hepatic disease can subsequently
cause a wide range of effects and this can arise from a
variety of means including infection, inflammation,
and cancer.
Hepatic failure
• The most severe clinical consequence of liver disease is hepatic
failure.
• It generally develops as the end point of progressive damage to the
liver, either through insidious piecemeal destruction of hepatocytes
or by repetitive waves of symptomatic parenchymal damage.
• 80% to 90% of hepatic function must be lost before hepatic failure
ensues.
 Causes of Liver Failure:
Viral hepatitis
• Main cause worldwide
Alcohol
• Main cause in the UK
Drugs
• Paracetamol, halothane, NSAID,RIFAMPICIN,antidepressent
Industrial solvents
Mushroom poisoning
Wilsons disease
Shock and multi-organ failure
 • Describe the functions of the Liver in relation to blood
proteins
Albumin
Albumin is the most abundant plasma protein. Albumin is essential in maintaining the
oncotic pressure needed for proper distribution of body fluids.
Coagulation Factors
• The liver produces several coagulation factors:
• I – Fibrinogen
• II – Prothrombin
• V ,VII , IX , X , XI
• As well as Protein C, Protein S and Antithrombin.
Thrombopoietin
• A glycoprotein hormone that regulates the production of platelets by bone marrow.
Amino Acid Synthesis
• Transamination; a chemical reaction that transfers an amino group to a ketoacid to form new
amino acids
 Interpret basic Liver function tests
Hepatocellular Damage
• If hepatocytes are damaged, their ruptured membranes will allow Aminotransferases
into the blood stream. Their presence there is indicative of liver damage (ALT/AST).
Aspartate transaminase ; found in the liver, heart, skeletal muscle, kidneys, brain
ALT (Alanine transaminase)
Cholestasis (Bile ducts)
• Bilirubin – Unable to excrete bilirubin, plasma concentration rises
• Alkaline Phosphatase (ALP) – Enzyme in cells lining the liver’s biliary ducts. Plasma
levels rise with an obstruction.
Synthetic function
• Albumin – Levels reduced in chronic liver disease
• Prothrombin time (Clotting) – Measures the clotting tendency of blood
 Describe the causes of and effects of jaundice
•

• In the normal adult, the rate of systemic bilirubin production is equal to

the rates of hepatic uptake, conjugation, and biliary excretion.
• Jaundice occurs when the equilibrium between bilirubin production and
clearance is disrupted;

• The increased levels of bilirubin (Hyperbilirubinaemia) results in a

yellowish pigmentation of the skin, conjunctival membranes
over the sclera and other mucus membranes.
Jaundice is clinically detectable at >40µmol/L (Normal range
<22µmol/L)
Distinguish pre-hepatic, hepatic and post-hepatic
jaundice
Pre-Hepatic Jaundice
• Excessive Bilirubin Production, usually due to an increased breakdown of red blood cells
(haemolysis)
• Liver unable to cope with excess bilirubin
• Lab Findings
• Unconjugated hyperbilirubinaemia

• Reticulocytosis: a condition where there is an increase in reticulocytes, immature red

blood cells. It is commonly seen in haemolytic anaemia , haemorrhage
• Anaemia

• ↑ LDH (Lactate dehydrogenase)in living cell (esp. blood cells and heart)

• decreased Haptoglobin (protein) which indicate of haemolysis

Causes

Inherited
• Red Cell Membrane defects
• Haemoglobin abnormalities
• Metabolic defects
Causes cont.
• Congenital Hyperbilirubinaemias
• Gilbert’s syndrome a relatively common (7% of the
population), benign, somewhat heterogeneous inherited
condition manifesting as mild, fluctuating unconjugated
hyperbilirubinemia. The primary cause is mild reduction in
hepatic levels of glucuronosyltransferase attributed to a
mutation in the encoding gene
• Crigler-Najjar syndrome ß Rare
inherited disorder affecting the metabolism of bilirubin,
• type I there is almost complete absence of
glucuronosyltransferase.
• Type II, reduced levels of glucuronosyltransferase.
•Acquired
•Immune
•Mechanical ß E.g. RBC’s running
across metal heart valves
•Acquired membrane defects
•Infections
•Drugs
•Burns
 Hepatic
Jaundice
Reduced capacity of liver cells to secrete conjugated
bilirubin into the blood
Lab Findings:
• Mixed unconjugated and conjugated
hyperbilirubinaemia
• ↑ Liver enzymes (ALT/AST)
• Abnormal Clotting
Causes
Congenital Autoimune hepatitis:
Gilbert’s Syndrome
Crigler-Najjar syndrome
Hepatic Inflammation
• Viral (Hepatitis A, B, C and E, Epstein Barr Virus (EBV))
Alcohol
Drugs
• Paracetamol
Cirrhosis
• Alocohol
• Chronic hepatitis
• Metabolic disorders
Haemochromotosis : indicates accumulation of iron in the body from any cause.
Wilson’s disease: a genetic disorder in which copper builds up in the body. Alcohol which
worse the condition

Hepatic tumours
• Hepatocellular carcinoma
• Metastases
 Post-Hepatic Jaundice
Obstruction to drainage of bile, causing a back up of bile acids into the
liver. Can be intrahepatic or extrahepatic. The passage of conjugated
bilirubin is blocked.
Lab Findings
Conjugated hyperbilirubinaemia
Bilirubin in urine (dark)
• ⬆ Canalicular enzymes (ALP)
• ⟷/⬆ liver enzymes (ALT/AST)
 Causes
Intrahepatic : Hepatitis
Drugs
Cirrhosis
Primary biliary colic
Congenital hyperbilirubinemia.

• Dublin-Johnson syndrome results from an autosomal recessive defect

in the transport protein responsible for hepatocellular excretion Affected
persons exhibit con- jugated hyperbilirubinemia. Other than having a
darkly pigmented liver and hepatomegaly, patients are other- wise
without functional problems
Causes cont.

Extrahepatic
• Gallstones/Biliary stricture
• Carcinoma
• Head of pancreas
• Ampulla
• Bile duct
• Porta hepatis lymph nodes
• Liver metastases
• Pancreatitis
• Sclerosing cholangitis
 Types of jaundice
Type Pre-Hepatic Hepatic Post-Hepatic

Cause Excessive bilirubin Reduced capacity to Obstruction to biliary

production conjugate/excrete system
bilirubin

Bilirubin ↑ Unconjugated Mixed unconjugated Conjugated

hyperbilirubinaemia and conjugated hyperbilirubinaemia
hyperbilirubinaemia Bilirubin in urine (dark)
None in faeces (pale)
Hepatitis
• Hepatitis is the inflammation of the liver, which can be acute or
chronic, and can be caused by viral infection, autoimmune disorders,
alcohol or drugs (paracetamol, rifampicin, methyldopa). Acute
hepatitis causes variable levels of hepatocyte breakdown (increased
levels of AST and ALT seen), whereas chronic hepatitis will cause a
fibrotic liver with associated synthesis failure (reduced albumin levels
and clotting factors).
Viral hepatitis
• Hepatitis A virus (HAV) is a non-enveloped RNA virus and is
transmitted faecal-orally.
• Hepatitis B virus (HBV) is an enveloped DNA virus that is transmitted
parentally, sexually, and congenitally.
• Hepatitis C virus (HCV) is an enveloped RNA virus and is transmitted
commonly through infected blood.
• Hepatitis D virus (HDV) is an enveloped RNA virus that is transmitted
by intimate contact or blood products, only in individuals who already
have HBV infection.
 Describe the effects of excessive alcohol consumption on the liver, and the
key features of alcoholic liver disease
Pathology
• Fatty liver
• Alcohol metabolism generates NADH from NAD+
• Increased NADH induces fatty acid synthesis
• Decreased NAD+ results in decrease fatty acid oxidation
• Accumulation of fatty acids in the liver
• Glycerol à TAGs (triacylglycerol).
• TAGs accumulate, giving fatty liver

• Alcoholic Hepatitis
• Inflammation of hepatocytes
• Cirrhosis
• Liver cell necrosis followed by nodular regeneration and fibrosis, resulting in
increased resistance to blood flow and deranged liver function.
Liver cirrhosis
• Cirrhosis results from enlarged fatty liver, the chronic necrosis of the
hepatocytes followed by chronic inflammation leading to fibrosis of
the liver (natural healing process) and nodule formation. This
interferes with blood flow and impairs liver function.
• The type of nodular formation can give clues to underlying cause:
• Micronodular cirrhosis is where the nodules are less than 3mm in size
and suggest ongoing alcohol damage or biliary tract disease.
• Macronodular cirrhosis is where the nodules are of variable size and
commonly suggests a chronic viral hepatitis.
Causes Clinical Features
• Alcohol
• Liver dysfunction
• Wilson’s Disease
• Jaundice
• a1-antitrypsin deficiency
• Anaemia
• Biliary cirrhosis
• Bruising
• Haemochromotosis
• Palmar erythema
• Hepatitis B or C
• Dupuytren’s contracture:
• Autoimmune hepatitis
The underlying mechanism involves
the formation of
abnormal connective tissue within
the palmar fascia
 Investigations
• - / é ALT/AST
• é ALP or normal
• é Bilirubin
• ê Albumin
• Deranged clotting
Na+ levels may be low due to effect cirrhosis on free water clearance.
 Complications
• Portal hypertension complication. Like ascites, esophageal varices etc..

• Cardiopulmonary complication like cirrhotic cardiomyopathy,

hepatopulmonary syndrome.

• Coagulopathy…increasing bleeding risk.

• Metabolic complication , hepatic encephalopathy, jaundice, D.M., nutritional

deficiency

• Hepatocellular carcinoma.
•Management for liver cirrhosis
involves cessation of alcohol and
treating individual symptoms.
•The only real option however is a
liver transplant.
Outline how liver diseases may lead to portal hypertension
and appreciate the associated pathology these may lead to

• Portal hypertension is defined as portal venous pressure > 20mmHg.

It can be caused by
• Obstruction of the portal vein (extrahepatic obstruction)
Congenital, thrombosis or extrinsic compression
• Obstruction of flow within the liver
Cirrhosis, hepatoportal sclerosis, Schistosomiasis, sarcoidosis)
• Post hepatic obstruction Budd- Chairi syndrome. Cardiac causes like
right side heart failure.
Portal hypertension may lead to
1. Ascites
Any rise in pressure from the liver will result in backflow down
the Portal vein. Since there are no valves in the portal venous
system this will affect the splanchnic vasculature draining into it.
The hypertension coupled with reduced albumin levels forces
fluid out into the peritoneal cavity resulting in ascites
2. Splenomegaly –

Due to subsequent increased B.P. in the spleen, Any

rise in pressure from the liver will result in backflow down
the Portal vein.
The spleen will also enlarged as it attempts to drain into the
portal vein but cannot.
3. Porto-Systemic Anastomoses
There are several anastomoses between the hepatic portal
and systemic veins. As such, when the pressure is
increased in the portal venous system, blood is backed up
through these anastomoses. The increased blood pressure
causes the vessels to dilate, protrude into the lumen,
rupture/ulcerate and haemorrhage.

• Oesophageal varices
• Rectal varices
• Caput Medusae
• There is distention of the
abdomen (ascites) and
periumbilical dilatation of
subcutaneous veins (caput
medusae).
Portal → Systemic
Gastroesohageal junction
(azygos system).(esophageal vein
& left gastric vein.
Rectal Varices
Superior rectal → Inferior rectal
Caput Medusae
Paraumbilical → Small epigastric
of abdominal wall

Colic/Splenic/Portal →
Retroperitoneal veins of posterior
abdominal wall or diaphragm
 Describe the causes and consequences of
gallstones
• Bile acids return to the liver in between meals and are secreted by canaliculi cell
walls a long time before they are next needed. Until they are needed, they are
stored in the gall bladder.

• To reduce the volume that needs to be stored, bile acids are concentrated by the
transport of salt and water across the gall bladder epithelium. However, the
concentration process increases the risks of precipitation, leading to Gall Stones.
• often asymptomatic,
• move into the neck of the gall bladder or biliary tree, causing very painful biliary
colic or even obstruction, followed by inflammation (Cholecystitis) and infection of
the Gall Bladder

• Pain from Gallstones can be worse after eating, as the secretion of Cholecystokinin
(CCK) will cause the gall bladder to contract.
location of obstruction
determines symptoms If blocking
1. cystic duct → biliary colic and malabsorption of fats.
2. common bile duct → biliary colic, &post-hepatic jaundice as a feature
3. Distal to the common bile duct → acute pancreatitis.

• The only real treatment for gall stones is surgery, yet some may pass out
naturally as they are broken down
• complications of a cholelithiasis are: obstructive jaundice, acute
pancreatitis, ascending cholangitis, and gall bladder carcinomas.
• Charcot’s triad is used to describe ascending cholangitis: the symptoms are
fever, intermittent pain, and jaundice.
Infections are likely to arise both from ascending cholangitis and due to stasis.
 Acute pancreatitis
Acute pancreatitis is a reversible inflammatory disorder that varies in severity,
ranging from focal edema and fat necrosis to widespread hemorrhagic
parenchymal necro- sis.

The pathogenesis behind it is from the ductal obstruction or direct acinar

damage
• the release of proteases (causing tissue destruction), lipases (causing fat
necrosis), and elastases (destroys blood vessels leading to haemorrhage)
inside the Pancreas
main causes are gall stones (70%), alcohol (25%)
Roughly 5% of patients with gallstones develop acute pancreatitis, and
gallstones are implicated in 35% to 60% of cases overall.
Proposed pathogenesis of acute pancreatitis.
Clinical features: severe abdominal pain, vomiting, dehydration, and
(subcutaneous haemorrhage.
Clinically, :↑ amylase levels become &hyperglycaemic , ↓calcium levels.
In any chronic pancreatitis due to alcoholism, there is
parenchymal destruction, fibrosis and loss of acini.
It can present sometimes with:

Cullen’s sign, where the release on enzymes from the pancreas results in
superficial oedema and bruising around the umbilicus,
Grey-Turner sign, where there is retroperitoneal damage, leading to bruising
of the flanks.
Treatment is mainly supportive and any haemorrhage from the release of
elastases must be stopped. There is a 10% mortality with the acute
condition.
 Describe the presentation of carcinoma of the
pancreas
• 90% of pancreatic carcinomas are Ductal Adenocarcinomas, and they
account for ~5% of cancer deaths
• Clinical Presentation:
• Initially symptomless, but then lots of symptoms all at the same time:
Obstructive jaundice, pain, vomiting, Malabsorption, diabetes

• the main treatment is surgery yet this also has a poor prognosis.