Liver Pathology Flashcards
Outline the main functions of the liver.
- Temporary nutrient store
- Removes toxins from the blood
- Removes old/ damaged RBCs
- Regulates nutrient and metabolite levels in the blood.
- Secretes bile into the small intestines via the bile ducts and gall bladder
What are the 4 lobes of the liver?
Major; left and right
Minor; caudate and quadrate
What are the different ducts of the liver?
- Common hepatic
- Cystic
- Common bile
Describe the structure of liver lobules.
Roughly hexagonal structures consisting of hepatocyte cells.
At each of the six corners there is a portal triad.
What is the purpose of the hepatic artery?
To supply oxygen-rich blood to the liver.
Describe the blood in the hepatic portal vein.
Nutrient-rich, toxin-ladened, oxygen-poor blood from the gut.
Describe blood in the hepatic portal artery.
Oxygen-rich
Where do the two supplies of blood in the liver (from the hepatic portal vein and artery) meet and describe each
Triad - Branches of three vessels; hepatic portal vein, hepatic artery along with the bile drainage ductless all run together to infiltrate all parts of the liver.
Sinusoids - Special liver capillaries where blood mixed with liver cells etc.
By-products leave as bile in canalicui which merge to form bile ducts.
Outline the functions of hepatocytes.
- Bilirubin metabolism
- Intermediary metabolism of carbohydrates, lipids, proteins and minerals
- Synthesis of plasma proteins
- Detoxification, inactivation or conversation of hormones and xenobiotics.
What cells produce bile?
Hepatocytes
What is bile?
A yellow, green alkaline solution containing bile salts, bile pigments, cholesterol, neural fats, phospholipids and a variety of electrolytes.
It is composed of water, ions, bile salts, bile acids and organic molecules.
How much bile does the liver produce daily ?
1/2 to 1 litres
How do bile salts emulsify fats?
Large fat globules enter the small intestines and are physically separated into millions of small fat droplets to be digested and absorbed.
What is the main component in Gallstones?
Cholesterol
What is the purpose of bile salts and when is this useful?
They emulsify fats and salts which allows absorption across the walls of the small intestines into the lacteal lymph capillaries.
Describe the structure of the gall bladder.
A thin-walled muscular sac on the inferior surface of the liver.
Describe how the gallbladder carries out its function.
When the muscular wall contracts, bile is expelled into the bile duct.
What does the gallbladder store?
Bile that is not immediately needed for digestion.
What does the gallbladder do to bile that it is storing?
Concentrates it
What is cholesterol needed for?
Cell membranes Vitamin D Hormones (progesterone and testosterone) Myelin Components of bile salts
Describe where different %’s of bile in the body come from
85% endogenous or manufactured by our own cells (mostly in the liver).
15% from food we eat.
What substrate does the liver use to produce cholesterol?
Acetyl-CoA
What type of cholesterol is termed “bad”?
LDL - low density lipoproteins
What type of cholesterol is termed “good”?
HDL - high density lipoproteins
What dietary factors raise HDL levels?
Mono-unsaturated fats such as olive and canola oil
What dietary factors raise LDL levels?
Trans and saturated fats
What components does the liver metabolise?
Steroid and polypeptide hormones.
Drugs and foreign compounds.
Bilirubin.
What components does the liver store?
Iron
Glycogen
Vitamin A, D, E and B12
Outline how detoxification occurs within the liver.
Typically a 2 stage process whereby reactive groups are added to xenobiotes and then conjugates are added to make it soluble. This allows excretion via the kidneys.
What is the purpose of the liver carrying out detoxification?
Allows excretion via the kidneys.
Can detoxification in the liver create harmful substances?
Sometimes the original compound could be toxic, sometimes it could be the Phase I or Phase II metabolite. This process may convert unharmful substances to harmful products or vice versa.
What happens in detoxification Phase I in the liver?
Addition of a reactive group to a rug or xenobiotic molecule via oxidation, reduction or hydrolysis in order to render it more water soluble.
In terms of detoxification Phase I, what systems and molecules can be used if oxidation takes place?
- Cytochrome P450 monooxygenase system
- Flavin-containing monooxygenase system
- Alcohol dehydrogenase and aldehyde dehydrogenase
- Monoamine oxidase
In terms of detoxification Phase I, what systems and molecules can be used if reduction takes place?
NADPH-cytochrome P450 reductase
In terms of detoxification Phase I, what systems and molecules can be used if hydrolysis takes place?
Esterases and Amidase
Epoxide hydrolase
Describe what happens in Phase II of detoxification in the liver.
Conjugates a Phase I metabolite with a charged endogenous species to allow for efficient excretion via the kidney.
In Phase II of detoxification, what different ways can conjugation occur?
Methylation, sulphation, acetylation, glucoronidation, glutathione, glycine.
Which phase of detoxification in the liver is most likely to produce toxic metabolites ?
Phase I
In what disease is increased alkaline phosphatase commonly observed?
Cholestatic liver disease and some bone diseases.
Where can alkaline phosphatase be found?
Microvilli of the bile caniculi of the liver.
Liver, bone, placenta and intestinal epithelium.
What affect does cholestasis have on alkaline phosphatase have in the liver?
Stimulates its production
What is cholestasis?
Blocked flow of bile from the liver to the duodenum?
When do levels of Alkaline phosphatase naturally alter?
Through development and ageing and also in the 3rd trimester of pregnancy.
Name some markers of liver failure.
Cholestasis, cirrhosis, hepatic tumours or abscesses, infiltrate hepatic disease, hepatitis.
As well as; bone diseases, healing fractures, osteomyelitis, inflammatory bowel disease, Paget’s disease and Osetomalacia.
What do high levels of ALT (alanine aminotransferase) indicate?
Hepatocellular damge
What do high levels of Aspartate aminotransferase (AST) indicate?
Hepatocellular damage, hepatitis, liver necrosis, cholestasis, chronic hepatitis, other liver diseases.
Pancreatitis, haemolysis, major crush injuries, severe tissue hyperaemia, myocardial infarction, can occur following surgery or trauma, skeletal muscle disease.
Where is ALT found?
Cytosol
Where is AST found?
Cytosol and mitochondrion.
What is GGT an indicator of ? (Gamma Glutamyl Transferase)
Hepatobilary disease
What may cause raised GGT levels if a patient doesn’t have hepatobiliary disease?
Anticonvulsant drugs Rifampicin Enzyme induction Cholestasis Alcoholic liver disease Hepatitis Cirrhosis Other liver diseases Excessive alcohol consumption Enzyme-inducing drugs Congestive cardiac failure Pancreatitis
What is a good measure of protein synthesis in the liver?
Albumin levels
What happens to albumin levels in chronic liver disease?
They decrease
What may decreased albumin levels indicated?
Chronic liver disease
Why is it often difficult to identify hypoalbuminaemia?
Albumin has a long half life of 20 days
What molecules does albumin bind to?
Bilirubin, thyroid hormones, cortisol, testosterone, metals and drugs.
What procoagulant factor is NOT present in the liver?
Von Willebrand Factor
What causes hypoalbuminaemia?
Decreased liver synthesis of albumin as liver is the only source of albumin.
What is Caeruloplasmin?
A carrying protein synthesised in the liver.
What happens in terms of Caeruloplasmin during liver failure?
Lack of Caeruloplasmin causes Wilson’s disease and results in copper being carried free in the body in a form where it can participate in numerous harmful reactions.
What is jaundice?
Colours of skin, yellowing of whites of the eyes
What causes jaundice?
Problems with the liver and gall bladder.
What is indicated if AST and ALT levels are elevated but normal levels of alkaline phosphatase are present?
Hepatitis
What is indicated if AST/ALT levels are normal but there is elevated alkaline phosphatase?
Obstructive jaundice
What is Bilirubin a degradation product of ?
Heme
Describe the properties of unconjugated bilirubin.
Fat soluble and toxic
Describe the properties of conjugated bilirubin.
Water soluble and non-toxic
How much Bilirubin does a person produce per day?
300mg
How much bilirubin can a healthy liver metabolise and excrete ?
3000mg
Why is bilirubin not a sensitive test of liver function?
The liver can metabolise and excrete 10x the bilirubin that is actually produced daily.
What causes hyperbilirubinaemia?
Increased production of bilirubin
Impaired metabolism
Decreased excretion
What are the 3 stages of liver disease?
Prehepatic
Hepatocellular
Post-hepatic
Describe the prehepatic stage of liver disease.
- Increased rate of haemolysis.
- Increased breakdown of haemorrhage pigment found in RBC haemoglobin.
- Sickle cell anaemia, speherocytosis, thalassaemia and glucose-6-phosphate dehydrogenase deficiency Gilbert’s syndrome.
What is Gilbert’s syndrome?
Failure to conjugate bilirubin.
Describe the hepatocellular phase of liver disease.
Acute or chronic hepatitis, hepatotoxicity, cirrhosis, drug-induced hepatitis and alcohol liver disease.
Describe the post-hepatic phase of liver disease.
Gallstones in the bile duct, parasites in the bile duct, strictures in the bile duct, biliary atresia, pancreatitis, cholestasis, thrombosis.
What is Hepatorenal syndrome?
A rapid deterioration in kidney function due to liver failure.
Who is likely to get hepatorenal syndrome ?
Those with Cirrhosis
What are the possible treatments for hepatorenal syndrome?
Dialysis may prolong life but liver transplant is necessary.
Why is hepatorenal syndrome thought to occur?
Due to an altered intestinal blood supply altering blood supply to the kidneys via alterations in vessel tone. This therefore causes prerenal kidney failure.
What is Hepatopulmonay syndrome?
Shortness of breath and dyspnoea at rest found in 10-15% of Cirrhosis patients.
What causes Hepatopulmonary syndrome?
Alterations in the hepatopulmonary bloody flow
Does hepatopulmonary syndrome cause changes to the lung tissue?
No
Describe the microscopic changes caused by hepatopulmonary syndrome and why these occur.
Intrapulmonary and arteriovenous dilations form due to increased hepatic production/ decreased hepatic clearance of vasodilators.
What is hepatic encephalotomy?
A neuropsychiatric abnormality that occurs as a result of liver failure.
What causes hepatic encephalotomy?
When the liver is impaired with toxic substances normally removed by the liver. These accumulate in the blood and brain functioning is altered.
What exacerbates Hepatic Encephalotomy?
Portal hypertension resulting in blood bypassing liver resulting in further toxin accumulation.
What are the symptoms of hepatic encephalotomy?
Impaired cognition, a flapping tremor and a decreased level of consciousness probably leading to coma.
Describe stage I of hepatic encephalotomy.
Mild confusion Agitation Irritability Sleep Disturbance Decreased attention
Describe stage II of hepatic encephalotomy.
Lethargy
Disoritentation
Inappropriate behaviour
Drowsiness
Describe stage III of hepatic encephalotomy.
Somnolence but arousal
Incomphrensible speech
Confusion
Aggression when awake
Describe stage IV of hepatic encephalotomy.
Coma
What is Hepatitis?
Damage to liver cells
What is Cirrhosis?
Increased fibrous tissue formation leads to shrinkage of the liver and decreased hepatocellular function.
Obstruction of bile flow also occurs.
Compare the lengths of time that acute and chronic liver hepatitis last.
Acute < 6 months
Chronic > 6 months
What is acute hepatitis ?
Acute injury directed against hepatocytes.
What is chronic hepatocytes ?
Chronic inflammation of the liver.
Name some of the causes of Cirrhosis.
- Diffusion of fibrosis with nodular regeneration.
- Chronic injury to the liver.
- Viral (hepatitis B or C)
- Toxic (alcohol , methotaxol)
- Metabolic (haemochromatosis, Wilson’s disease)
- Biliary
- Autoimmune hepatitis
