Liver, Gall Bladder & Pancreas Pathology

Question 1

What does the liver do?

Answer 1

Carbohydrate metabolism:
storage of glycogen & main source of plasma glucose

Fat Metabolism
Processes dietary fats to lipoproteins

Protein Metabolism
Major site for protein synthesis – particularly plasma proteins. Important groups include:
Albumin, coagulation factors, transport proteins for iron & copper
Several signs & symptoms of liver disease reflect failure of synthesis of these vital plasma proteins.
Bile Synthesis
Bile secretion which includes bilirubin, cholesterol, electrolytes and bile salts.
Storage
Stores glycogen, iron, copper & fat soluble vitamins
Detoxification
Liver detoxifies certain drugs & many metabolites and steroid hormones.

Question 2

What is Jaundice?

Answer 2

Caused by abnormalities in bilirubin metabolism & excretion
Clinical jaundice is evident when levels are above 50mol/ L and will manifest as yellow discoloration of the sclera and skin.
Jaundice can be caused by impaired bilirubin metabolism at different levels, and can be divided into three main biochemical types:

Unconjugated hyperbilirubemia
Conjugated hyperbilirubemia
Mixed pattern

Question 3

What is Unconjugated hyperbilirubinemia ?

Answer 3

excessive unconjugated bilirubin in the blood
E.g. due to red blood cell destruction which causes excessive bilirubin or abnormal hepatocyte metabolism
cause  hemolytic anemia, Gilbert’s syndrome

Question 4

What is Conjugated hyperbilirubinemia?

Answer 4

excessive conjugated bilirubin in the blood
Cause obstruction of bile secretion

Question 5

What is Mixed Jaundice?

Answer 5

Disease which causes generalized damage to hepatocytes
leads to mixed pattern of conjugated & unconjugated hyperbilirubinemia

Question 6

What is What is Bilirubin

Answer 6

Bilirubin is derived from a normal breakdown of hemoglobin entering the liver via the splenic vein and portal vain
Unconjugated bilirubin is bound to albumin (cannot be excreted in urine) and circulates to the liver, where it is normally internalized and conjugated to glucuronic acid.
Unconjugated bilirubin is lipid soluble. In neonates, high levels can enter the brain & cause damage- kernicterus.
Conjugated bilirubin (Water soluble) is excreted in bile to reach the gut.
In the gut, bacteria split the conjugate into urobilinogen, most of which exits in the feces.
20% is reabsorbed into the blood and re- excreted by the liver.
A small amount of reabsorbed bilirubin is excreted in the urine

Question 7

What is Gilbert’s syndrome?

Answer 7

An inherited condition
5 to 10% of the population
unconjugated hyperbilirubinemia as a results of a defect in the process of conjugation of bilirubin

Question 8

What is Biliary obstruction (conjugated hyperbilirubinemia) and its clinical presentation?

Answer 8

aka cholestatic or obstructive jaundice
Accumulation of conjugated bilirubin in the blood

Clinical Presentation:
Jaundice
Pale stools
as bile cannot enter the gut via the biliary system
Disturbed fat absorption – which leads to impaired vitamin K absorption.
Itching
from accumulated bile salts
Dark Urine
containing bilirubin, because conjugated bilirubin is water soluble

Question 9

What are the Two main causes of conjugated hyperbilirubinemia?

Answer 9

1. Intrahepatic Causes:
   hereditary enzyme defects
   hepatocellular defects
2. Extrahepatic Obstruction
   Gallstones
   Strictures of the common bile duct
   Pancreatic cancer
   Compression of bile ducts by external masses e.g. enlarged lymph nodes, tumors.

Question 10

How is hepatitis transmitted?

Answer 10

Hepatitis A & E
transmitted through feaco-oral route

Hepatitis B, C, D & G
Transmitted via a parenteral route

Similarities of Acute Viral Hepatitis:
Hepatocytes swell & undergo death by apoptosis
Increased lymphoid cells in portal tracts
mild cholestasis may be see

Question 11

What are the Signs & Symptoms of Acute Viral Hepatitis?

Answer 11

Symptoms:
Nausea, anorexia, low grade fever & general malaise

Signs
Hepatomegaly, jaundice, increased conjugated bilirubin levels

Question 12

What is the cause of hepatitis A?

Answer 12

feco- oral route or drinking / recreational water contaminated by sewage.
Does not cause chronic hepatitis

Question 13

What is the cause of hepatitis B?

Answer 13

transmitted in blood, semen & saliva through close physical contact
most acute infections are self limiting
can progress to chronic hepatitis

Question 14

What is the cause of hepatitis C?

Answer 14

clinically similar to Hep B infection
can progress to chronic hepatitis, and later cirrhosis

Question 15

What is the cause of hepatitis D?

Answer 15

Can only cause diseases if Hep B is also present
particularly prevelant in drug abusers & dialysis patients
Seldom resolves, and often progresses to chronic hepatitis & cirrhosis

Question 16

What is the cause of hepatitis E?

Answer 16

clinically similar to Hep A
No progression to chronic hepatitis.

Question 17

Acute hepatitis can also be caused by?

Answer 17

Epstein – Barr Virus
Rubella (childhood)
Herpes Simplex infections (Childhood)

Question 18

What is chronic hepatitis?

Answer 18

Several disease of the liver are characterised by progressive hepatic damage over a period of many months of years can be grouped together as chronic inflammatory liver diseases.

The most important long term consequences of chronic hepatitis are:
progressive liver cell loss
fibrosis
regeneration of hepatocytes

Question 19

What are the classifications of hepatitis?

Answer 19

Caused by Viral Infections
Chronic Hepatitis B, C & D

Caused by Autoimmune Disease
Autoimmune hepatitis, primary biliary cirrhosis

Caused by toxic / metabolic change
Chronic drug hepatitis, Wilson’s disease.

Question 20

Chronic Hepatitis can be staged & graded according to histology of the liver - what are the clinical findings?

Answer 20

inflammation may be in the portal tracts, edges of the portal tracts or within the hepatic lobule.

increasing severity of inflammation is associated with necrosis of hepatocytes.

Fibrosis initially develops around the portal tracts

Fibrosis then progresses to bridge between portal tracts & later may be associated with true cirrhosis

Question 21

What is cirrhosis?

Answer 21

Irreversible form of liver disease
is the end stage of many processes.
The normal architecture of the liver is diffusely replaced by nodules of regenerated liver cells, separated by bands of collagenous fibrosis.

Fibrosis is caused by growth factors liberated from inflammatory cells, Kupffer cells & hepatocytes
Myofibroblasts secrete collagen
Hepatocyte nodules lack normal vascular & bile drainage connections

Question 22

What are the key characteristics of cirrhosis?

Answer 22

Long standing destruction of liver cells
Associated chronic inflammation that leads to:
fibrosis
regeneration of hepatocytes to cause nodules

Question 23

What are the Main consequences of Cirrhosis?

Answer 23

Reduced hepatocyte function
Portal Hypertension
due to disturbance of blood flow through the liver
Reduced immune competence & therefore increased susceptibility to infection
Increased risk of developing liver cancer
Increased risk of developing portal vein thrombosis.

Question 24

What is the relationship of alcohol and the liver?

Answer 24

most common cause of chronic liver disease
Alcohol is a hepatotoxin
maximum advised intakes (without risk od liver damage)
50 -60g / day in males
30-40g / day in females

Alcohol causes fatty liver, acute hepatitis and cirrhosis.

Question 25

What is Acute Alcoholic Hepatitis?

Answer 25

Ingestion of large amounts of alcohol causes hepatitis with focal necrosis of hepatocytes.
Fatty changes occur
resembles viral hepatitis
If alcohol is abstained, the inflammation resolves without harm.
Continued ingestion of alcohol leads to fibrosis around central veins & there is continued hepatocyte necrosis
eventually may progress to Alcoholic cirrhosis.

Question 26

What is Alcoholic Fatty Liver?

Answer 26

Fatty liver is the build up of fat inside the hepatocytes
Leads to hepatomegaly

Question 27

What is Non- Alcoholic Fatty Liver Disease (NAFLD)?

Answer 27

Term for a range of conditions that leads to a build up of fat in the liver
usually seen in obese individuals (with high cholesterol)
Early stages don’t usually cause any harm, but can lead to cirrhosis if not managed.
However, high levels of fat are an increased risk of diabetes, heart attacks & stroke
Most people only ever develop the first stage without progression

Question 28

What are the 4 stages of Non- Alcoholic Fatty Liver Disease (NAFLD)?

Answer 28

1. Simple fatty liver (steoatosis)
   harmless build up of fat in the hepatocytes
2. Non- Alcoholic Steatohepatitis (NASH)
   More serious form NAFLD  inflammation of the liver
3. Fibrosis
   caused by persistent inflammation.
4. Cirrhosis

Question 29

What is portal hypertension?

Answer 29

Portal Hypertension is high blood pressure in the portal vein
The portal vein receives blood from digestive organs (intestines, stomach, spleen, pancreas) and carries it to the liver.
The liver filters the blood before returning it back to the heart.
In Liver disease, blood can be be blocked through the liver which raises the pressure in the portal vein.
A consequence of portal hypertension, is blood is redirected to other parts of the body; especially the eosophagus & stomach where new vessels form called VARCIES (blood vessels also form in the abdomen & rectum).
These vessels become enlarged & twisted and are at risk of rupture.
Treatment is needed to prevent rupture (which can be fatal)

Question 30

What are the Causes of Portal Hypertension?

Answer 30

Prehepatic
blockage of vessels before the hepatic sinusoids
M/C  portal vein thrombosis due to sepsis or polycythaemia

Hepatic
Blockage in the sinusoids
M/C  hepatic disease causing cirrhosis

Post Hepatic
blockage in the central veins, hepatic veins or vena cava.
M/C  Congestive heart failure, Pericarditis, cardiomyopathy

Question 31

What are Portal Hypertension Complications?

Answer 31

Portal hypertension leads to vasodilation in the splanchnic vessels, reducing blood volume and activating the Renin- angiotensin- aldosterone system.
This causes sodium & water retention
Lead to serious kidney problems
Build up of fluid in the abdomen  ASCITES
Internal Bleeding
due to enlarged Esophageal varices

Question 32

What is Cholelithiasis?

Answer 32

Stones in the gall bladder and / or bile duct system
Most common disease affecting the biliary system.
Stones from bile, cholesterol, calcium salts & bilirubin

Question 33

In Cholelithiasis, what are the 2 main types of stones?

Answer 33

Cholesterol stones (80% of stones- most common)
Pigment stones (20% of all stones)

Question 34

What are the Risk factors for cholesterol stones?

Answer 34

Reduced bile acids in bile due to oestrogen or malabsorption in Crohn’s Disease.
Increased cholesterol in bile caused by:
obesity, female gender, increasing age.

Question 35

What is Cholecystitis?

Answer 35

Acute inflammation of the gallbladder, most often caused by obstruction of the cystic bile duct by a stone.

Question 36

What is the pancreas?

Answer 36

the pancreases is an exocrine gland

Digestive enzymes are secreted and travel via pancreatic ducts to the duodenum

Question 37

What is chronic pancreatitis?

Answer 37

Most commonly caused by chronic alcohol abuse

continued chronic inflammation and fibrosis scarring, loss of pancreatic parenchyma.

Can lead to the development of malabsorption diabetes mellitus as the pancreatic parenchyma are destroyed.

Question 38

What is Acute Pancreatitis?

Answer 38

Severe, acute inflammation and necrosis of the pancreas leads to liberation of powerful digestive enzymes
this results in extensive enzyme mediated local tissue necrosis,
particularly fat necrosis

Question 39

What are Predisposing factors in acute pancreatitis?

Answer 39

Mechanical Obstruction:
Gallstones
Trauma

Metabolic / Toxins:
Alcohol
Drugs
Hypercalcemia
Hyperlipidemia

Vascular
Atherosclerosis

Infections
Mumps
Epstein- Barr Virus