135 - Liver and Pancreatic Secretions Flashcards
Where is CCK produced?
In the duodenum
Why is CCK released?
In response to chyme (partially digested food) released into the duodenum from the stomach
CCK action 1 2 3 4
1) Gall bladder contraction.
2) Digestive enzyme release by pancreas.
3) Acts on CNS, promotes feeling of fullness
4) Assists in insulin release
Ionic composition of serum
Mostly Na+ and Cl-.
Some HCO3
Ionic composition of gastric juice
Mostly H+ and Cl-.
Ionic composition of bile
Mostly Na+ and Cl-.
More HCO3- than serum
Ionic composition of pancreatic juice
A lot of Na+, Cl- and HCO3-.
Enteropeptidase substrate
Trypsinogen
Major components of bile
Water (80-90% of bile in the liver and gallbladder) Bile pigments Bile salts Fatty acids Cholesterol Lecithin Inorganic salts
Bile salts
Detergent derivatives of cholesterol
Lecithin
Generic name for phospholipids.
Acts as a detergent.
Bile pigments
Products of breakdown of Hb. Mostly bilirubin diglucuronide in bile.
Gall stones
Bile salts are normally right at the limit of ability to keep cholesterol in micelles.
If too much cholesterol or too little bile salts, then cholesterol precipitates as gall stones.
Often stained with bilirubin derivatives
Stercobilin precursor
Urobilinogen
Constituents of bile that aren’t bile salts
Fatty molecules taken up by hepatocytes (not subject to renal excretion) that are modified in liver and excreted into the bile.
Bile acid chemistry
Various derivatives of cholesterol, cholic acid.
What generates cholic acid from cholesterol?
CYP450 system
Desoxycholic acid
Bile acids are recycled in the body.
Bacteria can modify cholic acid to desoxycholic acid.
Humans can not produce desoxycholic acid.
Amphipathic
Hydrophilic end and a hydrophobic end.
Detergents.
Cholic acid amphipathicity
Is a kind of crinkled shape.
One face of the molecule has a - charge (with a COOH and 3xOH groups).
The other face is uncharged.
Are triacyl glycerols hydrophobic or hydrophilic?
Neither. They are amphipathic (detergents)
TAG digestion 1 2 3 4 5
1) Emulsion droplet in gut
2) Lipase and colipase secreted from pancreas.
3) Bile acid released from gallbladder/liver
4) TAG digested into fatty acids and 2-monoacylglycerol micelles
5) Enter enterocytes, form triacylglycerols, packaged into chylomicrons
Colipase
Mr12,000 protein. Procolipase from pancreas is converted to colipase in the intestine. It binds to lipase activating the lipase and preventing bile salt inhibition of lipase
Where in gut are fats absorbed?
Upper gut.
Where are cholesterol and bile salts absorbed in the hut?
Lower gut
Orlistat
Inhibits lipase.
Makes fats indigestible
Steatorrhoea
In the absence of bile, fats become indigestible and are instead excreted in faeces (steatorrhea). Faeces lack their characteristic brown colour and instead are white or grey, and greasy. Steatorrhea can lead to deficiencies in essential fatty acids and fat-soluble vitamins because they remain associated with other lipids.
Effect of orlistat
Artificial steatorrhoea
Amount of cholesterol made by an average liver per day
0.8g per day
Amount of cholesterol secreted by the liver each day as bile salts
20-30g
Essential enzyme in cholesterol synthesis
HMG-CoA
Amount of cholesterol excreted in faeces each day
0.8g
Old way that some foods lowered cholesterol
Bile salts + complex fibre (or cholestryramine, a synthetic anion binding polymer) lead to insoluble complex excreted with faeces.
Problems with cholestyramine treatment for cholesterol
Discomfort in the gut.
Normal ability of negative-feedback regulated cholesterol synthesis to make up for the excreted cholesterol. T
The side effects of cholestyramine are stomach upset, heartburn, constipation, belching, gas, nausea, loss of appetite, aggravated hemorrhoids, change of taste, headache and itching
Newer way to regulate cholesterol in food
Natural plant sterols can be added to margarine to compete with bile salt absorption receptors. 2 to 3 grams a day of a supplemented margarine can reduce total and LDL cholesterol levels 9 to 20 percent. A potentially negative side effect is that sterols reduce the ability to absorb β-carotene and vitamin E.
Regulation of cholesterol synthesis in the liver
Cholesterol from reabsorbed bile salts negatively feedbacks, inhibits cholesterol synthesis.
How are bile salts reuptaken?
Actively in ileum
Pancreatic acinar cell stimulus for release of digestive enzymes
1
2
3
1) Enteric nerves (ACh) stimulate receptors.
2) CCK from duodenum
3) Secretin from duodenum
Where in the pancreas is most bicarbonate released?
Pancreatic duct cells (not acini)
Examples of pancreatic zymogens 1 2 3 4
Chymotrypsinogen
Trypsinogen
Procarboxypeptidase
Proelastase
Trypsinogen activation
Intestine enteropeptidase removes tail, trypsin is activated.
Regulation of trypsin activation
The pancreas makes a trypsin inhibitor (shown in red), that binds to any traces of active trypsin present before it is secreted into the intestine.
Function of trypsin
Activates chymotrypsin, elastase, carboxypeptidase, colipase
Example of a protein that isn’t completely digested in the glu
Gluten
Pancreatitis
Inappropriate activation of pancreatic zymogens.
Most common causes of pancreatitis
Gallstones and alcohol abuse
When do most alcoholics with pancreatitis present?
Pancreatitis from alcohol usually occurs in long-term alcohol drinkers and is often chronic by the time the person seeks medical attention (usually for severe pain). A decrease in pain may signal advanced destruction of the pancreas
Demographic most at risk of gallstones
Women over 50 years of age
Enzymes elevated in pancreatitis
Serum amylase and lipase
