Gastro physiology Flashcards
What are the functions of the liver (6)
- Gluconeogenesis, glycogenolysis
- Protein metabolism
- Break down protein converting ammonia to urea, 50% of which is excreted by the kidneys - Fat metabolism
- Converts free fatty acids to ketones
- Synthesis of VLDL
- Processes chylomicron remnants from the blood
- Formation & secretion of bile
- Processes fat soluble vitamins - Synthesis
- IGF-1/ somatomedin
- plasma proteins: acute phase proteins, albumin, clotting factors, steroid binding & other hormone-binding proteins - Inactivation
- Toxins
- Steroids (chemical modification and excretion of thyroxine) - Immunity
- Kuppffer cells
How is glutamate produced and what is it.
Glutamate is an excitatory neurotransmitter. Which serves as a substrate for the production of A ketodehydrogenase.
Formed by converting GLUTAMINE to GLUTAMATE
- This is done by the enzyme GLUTAMINASE.
- This enzyme is abundant in renal tubular cells (which is why ammonia is made in the kidney).
- GLUTAMINE is found in the glia.
- Glutamic acid/ glutamate is taken up by the brain.
What causes the abnormally high blood ammonia levels found commonly in hepatic coma
- porto-systemic shunting of blood
- reduced capacity for urea synthesis in the liver i.e. ammonia can’ t be converted to urea
- bacterial production of ammonia in the gut
- decreased hydrogen ion excretion by the kidney
What is the composition of bile
97% water
0.7% bile salt
0.2% bile pigment
Bile salts
- Na, K
Bile pigments
- Responsible for yellow colour
- From glucuronides, bilirubin & biliverdin by breakdown of RBCs
Other substances
- Cholesterol
- Inorganic salts
- Fatty acids
- Lecithin
- Fat
- Alkaline phosphatase
What would you see predominantly if you analyzed bile chemically
Bile salts
What does the cholesterol solubility of bile depend on
Presents of bile salts and lecithin
How much bile do we secrete a day, where from and what causes secretion of more
liver secretes 500ml of bile daily some excreted in faeces & urine, some gets reabsorbed & re-secreted (enterohepatic
circulation)
Reabsorption of bile salts from the intestine leads to further secretion of bile
What are the 4 types of bile acids
- Primary (formed in the liver)
- Cholic acid 50%
- Chenodeoxycholic acid 30% - Secondary (made elsewhere e.g in the colon and converted by bacteria)
- Cholic acid -> Deoxycholic acid (15%)
- Chenodeoxycholic acid -> lithocholic acid (5%)
How are bile acids converted to bile salts
Conjugated with taurine & glycine to form bile salts
What is the function of bile salts
They are amphipathic (hydrophilic and hydrophobic) and form micelles.
- To reduce surface tension
- Assist in fat emulsification, digestion and absorption in the small intestine (in conjunction with phospholipids & monoglycerides)
What is required for the formation of micelles
A certain concentration of bile salts is required for the formation of micelles.
Bile salts contain bile acids, which are made from cholesterol.
Does steatorrhoea follow resection of the terminal ileum and if so why.
Steatorrhoea may follow resection of the terminal ileum
BECAUSE
95% of the bile salts are absorbed in the terminal ileum & recycled by the enterhepatic circulation
Where are bile salts absorbed and how are they re-circulated.
- 95% small intestine (mainly terminal ileum). This is done by a Na-bile salt co transported, powered by Na-K basolateral ATPase
- Some are absorbed by non-ionic diffusion along the way.
- The remaining 5-10% then enter the colon where they are converted to deoxycholic acid and lithocholic acid.
- Lithocholate is relatively insoluble, mostly excreted in stools; only 1% is absorbed.
- Deoxycholate is absorbed
- The absorbed bile salts are transported back to the liver in the portal vein -> re-excreted in bile (enterohepatic circulation)
- Those lost in stool are replaced by synthesis in liver
What happens when enterohepatic circulation is interrupted e.g terminal ileum resection, Chron’s
- 50% of ingested fat will appear in the feces because liver cannot increase rate of bile salt production fast enough
- severe malabsorption of fat-soluble vitamins
What are bile salts synthesised from and where are they concentrated
Synthesised from cholesterol and concentrated in the GB
What are the clinical manifestations of excess bile salts
Make the skin jaundice and skin itchy
What are the primary bile salts and what are they conjugated with in the liver.
The primary bile salts are cholate & chenodeoxycholate & are conjugated with glycine or taurine in the liver
Where is Bilirubin formed
formed in the reticuloendothelial system & BM; when RBCs breakdown (life span ~120days)
When do we get an increase in un-conjugated bilirubin
When there is excessive destruction of RBC’s (haemolysis)
How do we make Bilirubin and how to we get rid of it.
Macrophages engulf old erythrocytes and degrade them.
Erythrocytes release Hb, which is broken down into haem and globin.
Globin is broken down into amino acids.
The haem is broken down into unconjuagted bilirubin and iron.
Iron is re used for erythropoiesis.
Un-conjugated bilirubin needs to be removed. It is lipid soluble, needs to be bound to albumin to travel in blood (some does float freely unbound).
Un-conjugated bilirubin is carried to the liver.
In the liver bilirubin is conjugated by the addition of glucoronic acid.
This conjugated bilirubin is now water soluble.
This occurs in the sER and is done by glucuronyl transferase.
Conjugated bilirubin can now be excreted in bile (against a concentration gradient) then into the small intestine.
In the ileum/ beginning of large bowel it is converted by gut bacteria into URObilinogen (this is also lipid soluble)
URObilinogen 10-15% reabsorbed by the blood and bound to albumin. Some of this makes it back to the liver and enters the enterohepatic circulation (secreted as bile)
The other 5% is transported to the kidneys where it is converted to urobilin and peed out.
85-90% is oxidised to form sterocobolin (brown) excreted as poop.
What level of billirubin is required for jaundice to occur
34
Where does excess bilirubin accumulate
Blood
Skin
Sclera
Mucus membranes
What causes hyperbilirubinemia (physiological not diseases)
- Too much production (haemolytic anaemia)
- Not enough uptake into liver cells
- Not conjugated properly
- Conjugated bilirubin can’ t be released into bile canaliculi
- Obstruction of bile flow inside & outside of liver
Do people with obstructive jaundice have a tendancy to bleed and if so why
Patient who has obstructive jaundice due to gallstone may have an increased tendency to bleed
BECAUSE
In obstructive jaundice, decreased absorption of vitamin K occurs in the gut