Liver diseases Flashcards
What is the anatomy of the liver?
- It is the largest organ in the body
- It contains a left and right lobe
- Each of those lobes are divided into 8 segments which are called lobules
Each lobule is made up of:
- Central vein
- Blood capillaries called Sinusoids
- Bile ducts
- Hepatocytes and other cells
- The capillaries will eventually join to form veins
- The bile ducts will eventually join to form common bile duct. The common bile duct will drain into the gallbladder where the bile is stored and concentrated before it’s released into the duodenum following a fatty meal.
What does the hepatic portal vein carry?
It carries nutrient rich blood, coming from the GI tract.
It is carrying those absorbed nutrients towards the liver where it can be examined and made sure theres nothing toxic in there before they travel around the body.
What do the bile ducts do?
The bile ducts will basically gather and form the common bile duct which then has this gallbladder which will store the bile.
Talk about the vascular structure of the liver.
- About 25% of the resting cardiac output is gone to the liver.
- 25% is coming from the hepatic artery - which is carrying oxygen rich blood to this large organ.
- 75% is coming from the gut, which is carrying the nutrient rich blood to the liver.
- Blood will leave through the hepatic vein back into the vena cava and back into the heart.
Talk about the hepatic lobules.
- The lobules are hexagonal structures
- In the middle you have a central vein
- On the outside you have a portal triad - consists of a branch of the hepatic artery, branch of the portal vein coming from the gut and a branch of the bile duct.
- The nutrients and oxygen that are coming in to the liver, they are coming from the hepatic artery and portal vein. Hence it comes in from the outside of the hexagon structures. It works it way from smaller blood vessels and smaller blood vessels into the capillaries eventually called the Sinusoid capillaries. Eventually these will join again and again up into the central vein, taking the oxygenated blood away.
- The main fundamental unit in the liver is called the hepatocytes. That’s the basic cell structure and these make up everything and store everything in the liver.
- Between the cells you have Bile Canaliculi, and these are very small branches of the bile duct, that will gather finally into the bile duct and take the bile that’s made by the hepatocytes, away.
What other important cells are in the hepatic lobule?
- Macrophages
- Kupffer cells -> Involved in phagocytosis of anything forgein. Kupffer cells can also become inflammatory cells during inflammation, which is an earlier sign of liver disease
- Fibrocyte -> Important in supporting the hepatocytes and also during disease, as it progresses you get fibrosis (scarring) and these cells, particularly the hepatic stelai cells are responsible for this.
- Hepatic stelai cell -> Important in supporting the hepatocytes and also during disease, as it progresses you get fibrosis (scarring) and these cells, particularly the hepatic stelai cells are responsible for this.
Important physiologically but can cause issues during disease.
Talk about the metabolism of the liver.
Our energy comes from food.
Main food types are:
1. Carbohydrates
- Stores glucose as glycogen
- Glycogenolysis in fasting
- Gluconeogenesis in fasting
- Lipids
- Synthesis of cholesterol (85% of cholesterol comes from our liver - we make it ourselves)
- Lipoproetins - VLDL, LDL, HDL (These carry the cholesterol around the body) - Proteins
- Amino acid synthesis (non-essential amino acids: hence we can make them ourselves)
- Breakdown of amino acids to ammonia and the urea for excretion
The liver is very important in storing energy
What are the many functions of the liver?
- Metabolism
- Immunity
- Storage of nutrients
- Detoxification of drugs
- Synthesis
- Catabolism
- Activation
- Transport of numerous proteins
- Excretion
Talk about detoxification and degradation in the liver.
- Conversion of harmful ammonia to urea takes place.
- This is a major elimination route of nitrogenous waste - Detoxification of drugs and xenobiotics (food contaminants etc):
- Phase I reactions facilitated by Cytochrome P450 enzymes
- Phase II reactions - conjugation with other compounds to become more hydrophilic e.g gluconosyltransferases
- Age, nutrition and genetics influence drug metabolism (these can affect our ability to detoxify)
Talk about the endocrine activities of the liver.
- Modification of some hormones
- Vitamin D3 (from the skin) is converted to 25-OH vitamin D3 in the liver
- Thyroid hormone -> conversion of T4 to more potent T3
- Insulin-like growth factors produced by hepatocytes modify action of growth hormone - Major organ for degradation of hormones
- Insulin and glucagon
- Oestrogen, glucocorticoids, growth hormone, PTH
- Gastrin and other GO hormones (although kidney degrades more of these)
What is stored in the liver?
- Fats (can be a problem in obesity, as were not only storing fat in our adipose but also the liver - leading to a fatty liver (early stage of liver disease- reversible))
- Glycogen
- Trace elements - Copper, Iron
- Vitamins
- Vitamin A
- Vitamin D
- Vitamin K
- Some water soluble B Vitamins for shorter periods
What is synthesised in the liver?
- Hormones
- Insulin-like growth factor
- Thrombopoietin - stimulates platelets - Plasma proteins
- Coagulation factors
- Transport for cholesterol (lipoproteins)
- Transport for steroid and thyroid hormones
- Angiotensinogen - important in salt conservation - Iron transport and metabolism proteins
- Transferrin (transports iron in the blood), haptaglobin (will bind free haemoglobin in the blood), hemopexin (will bind free haem in the blood), hepcidin (inhibits iron uptake by the gut) - Acute phase proteins
- Important in inflammation
- E.g. Opsonin, complement proteins etc. - Bile acids
- Primary - colic acid and chenodeoxycholic acid
- Secondary - deoxycholic acid and lithocholic acid
What is bile?
- Bile is actively secreted by the liver and actively diverted to gallbladder between meals
- It is stored and concentrated in the gallbladder
It is an aqueous alkaline fluid containing:
1. Bile Salts
2. Cholesterol
3. Lecithin
4. Bilirubin
- After meal, bile enters duodenum, after being stored and concentrated in the gallbladder
What are bile salts?
- They are derivatives of cholesterol
- Both Bile salts and Lecithin act as emulsifiers
- Converts large fat globules into a liquid emulsion as micelles
Micelles:
- This will allow the lipase in the gut to get in, which increases the surface area, allowing the lipase to start work.
- In the middles of the micelles we have the lipid, and on the outside we have the aqueous layer (hydrophilic area).
- In the outer layer we can have bile salts which have both a lipid soluble and water soluble portion.
- Allowing the formation of Hydrophobic core and Hydrophilic shell
- After participation in fat digestion and absorption, most are reabsorbed into the blood
Talk about excretion in the liver.
- Bile salts can also be excreted. Bile salts are made in the liver, stored in the gallbladder, and then will travel down, and 95% of it will be reabsorbed in the terminal ileum and travels back through the hepatic portal vein to the liver to be reused.
- However 5% of them will be lost in the faeces.
Excretion of cholesterol and bilirubin (breakdown product of haem from RBC breakdown) through bile secretion:
- Bilirubin:
1. When our RBCs have done their job, they will get broken-down
2. The Haem and the Haemoglobin will be broken down into Bilirubin.
3. This occurs in the macrophages in the reticular endothelial systems.
4. These macrophages will break down the heme with an enzyme called hemeoxygenase-1.
5. The unconjugated Bilirubin that’s formed, is all complexed in the liver and conjugated to glucuronic acid.
6. This conjugated Bilirubin will then be secreted into the Bile and will travel in the intestine.
7. In the intestine, in the colon part, the glucuronic acid is removed by the bacteria.
8. So this bilirubin which is free at this stage then, is now converted to urobilinogen.
9. Some of this is reabsorbed from the gut and will enter the portal blood.
10. When reabsorbed, it will be transported to the kidneys, and the yellow colour (urine) of kidneys is due to your urobilin, as it is converted to urobilin and excreted.
11. A portion of it will continue and stay in the colon and get excreted and the urobilinogen that stays in the colon is oxidised by the intestinal bacteria and becomes a brown colour, and is converted to stercobilin.
12. Some of it will get reabsorbed into the enterohepatic circulations, where it gets reabsorbed and back into the liver and get excreted again.
- Bile contains water, electrolytes, bile acids, cholesterol, phospholipids and bilirubin
What is the immunological function of the liver?
Carried out by the Reticuloendothelial system
Macrophages (Kupffer cells attached to endothelium) phagocytose and degrade bacterial/other antigens carried from the gastrointestinal system in the portal vein
Hepatic stellate cells:
- Perisinusoidal
- Antigen-presenting role
- Major cell involved in liver fibrosis
Other immune cells - play a role in the inflammatory response
What are the main causes of liver disease?
- Alcohol
- Obesity
- Undiagnosed hepatitis infection
- Drug or other chemical toxicity
Name a few examples of liver diseases.
- Alcohol-related liver disease
- Drug toxicity
- Hepatitis (inflammation)
- Non-alcoholic fatty liver disease (NAFLD)
- Cirrhosis
- Cancer
- Gallstones
- Cholangitis
- Hemochromatosis (iron overload, inherited)
- Wilsons disease (copper overload, inherited)
- Gilbert’s disease (inability to metabolise bilirubin properly)
What are the 2 classifications of liver disease?
- Acute liver disease:
- Usually self-limiting
- Results in hepatocyte inflammation and damage
- Occasionally severe resulting in liver failure
- Generally caused by drugs or viruses - Chronic liver disease:
- Inflammation present for over 6 months
- Results in permanent damage with structural changes resulting in cirrhosis
- Most common cause is alcohol abuse
Talk through the progression of liver damage.
What are the causes of different viral liver diseases?
Viruses cause hepatitis - inflammation.
- Hepatitis A:
- Fecal-oral route
- Acute inflammation that generally resolves spontaneously
- Vaccine is available - Hepatitis B:
- Body fluids
- Mother to baby
- Acute infection that progresses to chronic inflammation, cirrhosis and cancer
- Vaccine available - Hepatitis C:
- Body fluids
- Chronic and may progress to cirrhosis and cancer
- No vaccine available - Hepatitis D:
- Body fluids
- Requires concomitant infection with Hepatitis B to survive - Hepatitis E
- Contaminated food and water, usually self-limited - Hepatitis G
- Body fluids
- Chronic infection similar to HCV
How do drugs influence liver disease?
Hepatocytes can become temporarily inflamed or permanently damaged by drugs/medications
Some drugs require overdose to cause liver damage e.g. Paracetamol
Other drugs may cause damage even when appropriately prescribed e.g:
- Statins
- Some common antibiotics e.g. Amoxicillin, Tetracycline
- Methotrexate
Some natural products can also cause liver damage:
- Herbal remedies
- High doses of Vitamin A
- Some wild mushrooms
How does alcohol influence liver disease?
Alcohol is the most common cause of liver disease/cirrhosis
Alcohol is directly toxic to liver cells
Alcohol causes inflammation which progresses to fatty liver and eventually fibrosis
Fibrosis alters structure and blood flow leading to portal hypertension and eventually liver failure.
Damage occurs >40g/d in men and >20g/d in women (1 unit= 9g)
UK ALCOHOL GUIDELINES:
- <14 Units per week
- Don’t save them up
- Spread over at least 3 days
- No alcohol in pregnancy
What is cholestasis?
Cholestasis is the lack of bile. It is the slowing or stalling of bile flow from your liver.
Can be due to 2 reasons:
- Due to hepatocytes:
- Failure of bile production and secretion
- Causes include hepatitis from viruses, alcohol and drugs
- Pregnancy - Dur to bile duct:
- Failure of outflow via bile ducts due to obstruction
- Gallstones, carcinoma, cholangitis (progressive scarring of bile ducts)
What are the main symptoms of acute liver disease?
- Possibly asymptomatic
- Generalised malaise (general discomfort/unhappiness)
- Anorexia
- Fever
- Possibly jaundice (later on)
What are the main symptoms of chronic liver disease?
- Fatigue and weakness
- Loss of weight
- Nausea/vomiting
- Loss of appetite
- Cachexia - wasting of muscle in arms and legs
- Abdominal swelling
- Right upper quadrant abdominal pain and tenderness
- Jaundice
- Bleeding from gums/nose and easy bruising
Can be specific depending on type of disease e.g. Gallstones
Individuals with cirrhosis develop progressive symptoms as liver fails:
- Inability to metabolise waste as liver fails
- Failure to produce proteins required for body function e.g. clotting
- Symptoms include easy bruising, gynecomastia, impotence, confusion, ascites, portal hypertension, oesophageal varices.
What are the different signs and complications of liver disease?
- Jaundice
- Ascites
- Portal hypertension and oesophageal varices
- Hepatic encephalopathy
- Haematological changes
- Circulatory changes
- Skin changes
- Endocrine abnormalities
- Renal failure - due to reduced renal blood flow
What is Jaundice?
It is the yellow discolouration of skin and mucous membranes (sclera - the white outer layer of the eyeball)
Causes include:
- Haemolysis (Haemolytic jaundice)
- Hepatocellular damage (hepatic jaundice)
- Cholestasis (obstructive jaundice)
What is portal hypertension and oesophageal varices?
Oesophageal varices are swollen veins in the oesophagus
Blood flow is reduced in the liver when theres disease and therefore pressure builds up in the portal vein.
When theres high blood pressure, it pushes blood into surrounding blood vessels, including thin-walled veins in the oesophagus close to the surface (also upper stomach).
If the pressure is too high, they can rupture and bleed. Uncontrolled bleeding leads to shock and death.
