Major functions of the liver (6 points)
Synthesis of plasma proteins (albumin and clotting factors)
Formation of blue (600ml-1L per day)
Synthesis of cholesterol, triglycerides and phospholipids
Storage of glycogen, iron, vitamin B12 and folic acid
Destuction of RBCs
Describe how bilirubin is metabolised
Bilirubin is formed by the destruction of RBCs in the spleen. Haem broken down by haem oxygenase to bilverdin which is reduced to bilirubin by bilverdin reductase.
Bilirubin is transported in the blood by albumin to the liver where it is conjugated and excreted into the intestines with bile. Intestinal bacteria metabolise bilirubin to urobilinogen which is then exreted in the faeces or urine.
What is Jaundice?
Yellowing of the sclera, or skin due to an excess of bilirubin (bile pigment) in the blood.
When plasma bilirubin concentration exceeds 34uM/L yellowing becomes obvious
3 causes of jaundice
1. Pre-hepatic: the ability of the liver to metabolise bilirubin is exceeded e.g.in haemolytic anaemia
2. Hepatic: diseases can disturb the uptake of bilirubin from blood and the liver's ability to conjugate or secrete bilirubin
3. Post-hepatic or obstructive: prevention of passage of bile into the duodenum. Causes of obstruction can be luminal (gall stones), mural (cancer, inflammatory strictures), external (mass, compression of pancreas)
What is Calot's triangle and why is it clinically significant?
An anatomic space bordered by the common hepatic duct medially, cycstic duct inferiorly and the inferior edge of the liver superiorly. (The cystic artery normally passes through the triangle.
Important during laparoscopic cholecystectomies.
Composition of bile
Consists of water, electrolytes, bile acids, cholesterol, phopholipids and conjugated bilirubin.
Bile acids synthesized in hepatocytes from cholesterol derivatives.
The presence of Na+ and K+ low pH means bile acids exist as salts.
Describe the structure of the liver
Largest internal organ in the body, divided into right and left lobes by the middle hepatic vein. Liver surrounded by thin connective tissue.
Further subdivided into eight segments by inflow and outflow hepatic veins which receive their own portal pedicle.
Has two blood supplies:
The hepatic artery, a branch of the coeliac trunk (25%)
The portal vein, drains most of the GI tract and spleen (75%)
Describe the microstructure of the liver
Acinus is the functional unit of the liver.
Hepatocytes form sheets that radiate outwads from the central vein to the portal vein and hepatic artery branches.
Central vein transports clean blood to the hepatic vein
Bile flows from hepatocytes into bile canaliculi, into biliary ducts which drain into the main bile duct.
Sinusoids - permeable blood vessels (fenestrated epithelium) carry blood from hepatic artery and portal vein to the central vein.
What is a common cause of varices?
The portal vein is formed by the joining of superior mesenteric and splenic veins. Normally has low pressure (5-8mmHg). Rise in portal pressure causes venuous system to dilate and collaterals occur within the systemic venous system.
Main sites of collaterals are:
gastro-oesophageal junction (oesophageal varices)
rectum (rectal varices)
anterior abdominal wall vai umbilical vein (re-opens, forms caput's medusae)
Causes of portal hypertension
Prehepatic: Extra hepatic blockage due to portal vein thrombosis.
Intrahepatic:most common cause is cirrhosis, can be schistomiasis or sarcoidosis
Posthepatic: prolonged severe heart failure e.g. IVC obstruction, constrictive pericarditis.
What is cirrhosis?
Chronic injury to the liver results in inflammation and necrosis of the liver cells followed by fibrosis and nodule formation.
Disrupts the architecture of the liver and interferes with the blood supply to the liver and its function.
Common causes: alcohol, Hepatitis
Describe the structure and function of the gall bladder
Pear-shaped fibromuscular sac lying on on the visceral surface of the liver at the junction of the right and left lobes of the liver.
Wall of the gall bladder consists of highly folded columnar epithelium, lamino propria and a fibromuscular layer.
Hepatic ducts and cycstic duct merge to form the common bile duct which passes into the duodenum at the ampulla of Vater
Receives, stores and concentrates bile in the liver.
Why are portal-systemic anastamoses clincally important?
Areas where the collateral vessels of the portal venuous system contacts the systemic venuous system. Formed in the submucosa of the inferior oesophagus, anal canal, in the paraumbilical region, ascending ans descending colon and the liver.
Clinical significance: Allow alternate routes of blood into the inferior vena cava if portal circulation through the liver is diminished or obstructed. Varices form in these areas with portal hypertension.
Physiology of the gall bladder
Influenced by the autonomic nervous system
Major controlling factor during digestion is cholecystokinin - CCK
CCK is released from the mucosa of the duodenum in response to the presenc of food.
Stimulates contraction of the gall bladder and relaxing of the sphincter of oddi by modulating action of vasoactive intestinal peptide (VIP)
Function of bile
Bile acids act as detergents. Main function is to solubilise lipids.
How are gall stones identified on an ultrasounds?
Gall stones in the gall bladder cast acoustic shadows which can be seen on the ultrasound
What are gall stones?
Crystalisations or precipitates of bile acids and cholesterol
Precipitation of calcium salts, fatty acids and calcium bilirubinate can cause pigment stones (less common, seen in people with haemlytic disorders)
What three factors can affect the formation of gall stones?
1. Oversaturation of bile with cholesterol. Can be caused by reduced HMG-CoA activity, reduced bile salts or rapid weight loss.
2. Composition of bile salts. Influences the ability of bile to maintain cholesterol in solution.
3. Motility of the gall bladder. Stasis of the gall bladder or abnormal motility increases mucin secretion, promotes precipitation of cholesterol.
List four complications of gall stones
1. Acute cholecystitis
2. Biliary colic
3. Biliary enteric fistula
4. Increased risk of adeocarcinoma
Features of acute cholecystitis
Gall stone blocks the cystic duct which prevents the gall bladder from emptying.
Obstruction causes glandular secretion leading to progressive distension, compromising the vascular supply.
Retained bile causes inflammatory response, and the gall bladder may also become infected.
Normally self-resolving within 2 months but can progress to biliary sepsis. A chronically inflamed gall bladder can fistulate through to the duodenum. Gall stones enter small bowel and cause obstructions.
Describe the structure of the pancreas
Divided into head, neck and tail.
Head surrounded by the first three parts of the duodenum
Superior mesenteric vein runs behind the neck of the pancreas and merges with the splenic vein to form the portal vein.
Pancreatic duct joins the duodenum at the ampulla of Vater.
List two exocrine functions of the pancreas
1. Produces and secretes digestive enzymes (amylase, lipase, trypsin)
2. Secretes bicarbonate ions in response to a meal (regulated by secretin)
Name the main types of islet cells in the pancreas and the hormones they produce
1. Alpha cells: glucagon
2. Beta cells: insulin
3. DD cells: somatostatin
4. PP cells: pancreatic polypeptide
5. Enterochromaffin cells: serotonin
Mechanism of enzyme production/secretion in pancreas
CCK is released by the duodenum in response to the presence of food.
Acinar cells in the pancreas produce inactive zymogens which are released into the duodunum via the pancreatic duct in response to CCK.
Secretin produced by duodenal cells in response to acidic chyme promote secretion of HCO3- by ductal cells but also stimlate acinar cells to secrete enzymes
Common causes of pancreatitis
Gall stones obstructiong the common bile duct within the head of the pancreas causing external presure on the pancreatic duct.
Complication: can form a pseudocyst where fluid collects in the lesser sac.
What is Glisons's capsule?
Thin layer of connective tissue that surrouonds the liver
Explain the terms hepatic lobule and hepatic acinus
Both used to describe the structural arrangement of the liver
Lobule: A small division of the liver defined histologically. Each lobule forms a hexagon with a vein in the centre. Branches of the portal triad lie at the periphery of each lobule.
Acinus: The functional unit of the liver. Blood drains from the portal triad into a centrall vein
What is the difference between the anatomical and functional lobes of the liver?
Anatomical lobes: the liver is divided into right and left lobes anatomically by the middle hepatic vein. The right lobe is large while the left is much smaller Functional lobes: the liver is divided into 8 functional segments supplied by individual branches of the portal triad. Each branch supplies its own portal pedicle which means that a diseased portion of the liver can be resected without having major effects on the blood supply to other parts.
Name three common causes of liver cirrhosis
Hepatitis Metastatic cancer Portal hypertension