Hepatic Flashcards
True or false: The horse does not have a gall bladder so bile flows freely almost continuously and unconcentrated in a direction opposite to blood.
True
Where are the spaces of Disse and what do they do?
Spaces of Disse lie beneath pores in the endothelial lining of the sinusoids. These connect with lymphatic vessels and freely absorb plasma but not RBCs.
A cleft, lies between the hepatocytes and the cells lining the sinusoids. It contains fluid similar to the composition of blood but does not contain erythrocytes.
What do stellate cells do?
Store fat soluble vitamins such as vitamin A.
What are the different zones of the liver lobule and what are the features of each?
Zone 1 (periportal) is located adjacent to the branching hepatic arteries and portal veins. It is the most oxygenated and hence most metabolically active. Responsible for oxidative liver functions such as gluconeogenesis and ß-oxidation of fatty acids and is the primary site for deposition of haemosiderin.
Zone 2 is the one typically affected by toxins such as creeping indigo.
Zone 3 is located adjacent to the central veins and has the highest cytochrome P450 mixed-function oxidase activity and the least favourable situation for oxygenation. It is most susceptible to toxins and hypoxic damage.
Where does the bile duct empty?
Major duodenal papilla (with the pancreatic duct)
When liver parenchyma cells are destroyed they are replaced with fibrous tissue that eventually contracts around the blood vessels. What is the effect of this?
Portal hypertension which can impede flow from the intestines and spleen resulting in leakage of fluid from the capillaries into the lumen and walls of the the intestine.
Which coagulation and fibrinolysis factors are formed in the liver?
Factors II, V, VII-XIII, fibrinogen, antithrombin III, protein C, plasminogen, plasminogen activatior inhibitor.
What is the role of hepcidin?
Reduces dietary iron absorption by reducing iron transport across the gut mucosa and reduces iron exit from macrophages and the liver.
What influence to glucocorticoids, glucagon and thyroid hormone have on the liver?
They increase gluconeongenesis, glycogenolysis and promote peripheral protein catabolism.
What is the role of the liver in eliminating ammonia?
- Synthesis of non-essential amino acids from α keto acids and ammonia via reversal deamination. Involves formation of glutamate from α-ketoglutarate and ammonia.
- Glutamate is used to form other amino acids and also participates in the conversion of more ammonia into glutamine which is delivered to the kidney to be converted back to ammonia and excreted (glutamine is non-toxic except in the brain where it causes cerebral oedema).
- Ammonia not excreted by the kidneys is returned to the liver where it synthesises urea via the Krebs-Henseleit cycle for excretion via the kidneys.
How are the majority of short-chain fatty acids (SCFA) delivered to the liver?
Incorporated into phospholipid or triglyceride by enterocytes and delivered via the portal blood.
What are the differences between VLDLs and HDLs and what happens to them once packaged?
VLDLs primarily contain triglycerides whereas HDLs primarily contain protein and phospholipids. They are released into hepatic sinusoids and once in the systemic circulation adipose tissue takes them up or endothelial lipases alter their composition by removing triglyceride, forming intermediate low density lipoproteins.
What are the roles of glucocorticoids and insulin on fatty acids in the liver?
Glucocorticoids increase fatty acid mobilisation from the periphery.
Insulin decreases adipose tissue release of fatty acids by activating lipoprotein lipase and inhibiting hormone sensitive lipase.
Insulin also acts on the liver to increase fatty acid synthesis from glucose.
What is the role of bile acids?
Amphoteric molecules that act as detergents to facilitate excretion of cholesterol and phospholipid from the liver into bile and facilitate digestion and absorption of lipid and lipid soluble compounds such as vitamin A, D, E and K from the intestinal tract.
What is the difference between conjugated and unconjugated bilirubin?
Macrophages in the spleen, bone marrow and liver engulf pigments, convert them to biliverdin, and then convert that to bilirubin and release it as free bilirubin - this is unconjugated for which is bound to albumin and delivered to the liver. Within the hepatocyte, the bilirubin is conjugated with glucuronide and is now water soluble and excreted into the bile canaliculi as conjugated bilirubin.
In normal circumstances, little conjugated bilirubin escapes into the circulation but with severe liver disease, increased amounts will escape and be freely filtered in the urine.
Microflora in the GIT reduce conjugated bilirubin to urobilinogen and stercobilinogen which impart a yellow-brown colour to faeces. Urobilinogen is absorbed by intestinal mucosa and returned to the liver.
A small amount of conjugated bilirubin in the intestinal lumen is hydrolysed to unconjugated bilirubin and reabsorbed. The live extracts most of the urobilinogen however a small amount spills over into the urine where it is concentrated and therefore detectable.
What are the phases of hepatic detoxification?
Phase 1: polar groups are added to the compound or existing polar groups are exposed by oxidation, hydroxylation, deamination or reduction. Some substrates are capable of saturating the enzymes responsible for this (usually of the P450 system) causing accelerated removal rates (eg barbiturates, bute, chlorinated hydrocarbons); others are inhibitors of these microsomal enzymes thus prolonging effects (eg chloramphenicol, cimetidine, organophosphates, morphine and quinidine)
Phase 2. The product of phase 1 is conjugated usually with glucuronate or sulphate.
True or false: substances for detoxification are usually water-soluble and biotransformation renders them more susceptible to renal or biliary excretion.
False. Substances for detoxification are usually water INSOLUBLE and biotransformation renders them more susceptible to renal or biliary excretion.
Biotransformation sometimes results in the formation of toxic metabolites from a non-toxic parent compound. Which group of horses may be more at risk of toxic effects when metabolising these compounds?
Young horses may have less ability to metabolise aromatic hydrocarbons for example.
What is the role of Kupffer cells?
They phagocytose and cleans the portal blood of bacterial endotoxins and other products absorbed from the GIT before they reach the systemic circulation and help cleanse the hepatic arterial blood of fibrin degradation products, tissue plasminogen activators, haemoglobin, microbes, foreign antigens and other particulate debris and help recycle iron from senescent or injured RBCs hence they accumulate haemosiderin.
What role does the liver have in vitamin D metabolism or synthesis?
Vitamin D is first converted in the liver to 25-hydroxycholecalciferol and exported to the kidney where it is transformed into 1,25 dihydroxycholecalciferol, the active form.
What role does the liver have in the foetus and how does this change with adulthood?
In the foetus, the liver is a site of haematopoiesis.
In adults it is an extra-medullary site only for intense conditions of erythrocyte regeneration or if a large portion of the bone marrow is destroyed.
In most conditions, what proportion of hepatic mass must be lost before the hepatic function is impaired?
80%+
Why do clinical signs rarely accompany focal hepatic injury?
Because sufficient hepatic reserve exists in unaffected regions to compensate.
The multifocal or generalised disease is more likely to result in clinically significant hepatic disease.
What is bridging necrosis?
Necrosis of contiguous hepatocytes that spans adjacent lobules in a portal to portal, portal to central or central to central fashion.