1. Regulation of pancreatic secretions
1- Ach released from the vagus or enteric NS stimulates the secretion of enzymes from the acinar cells.
2- CCK secreted from the duodenal & jejunal mucosa when chyme contacts the mucosa, the hormone goes by the blood to the pancreatic acini & stimulates the cells to secrete their enzymes.
3- Secretin secreted by the intestinal mucosa in response to acid enters the duodenum & jejunum, it acts on the ductal epithelium & stimulates the production of large amounts of HCO3- & H2O.

2. Phases of pancreatic secretion
1- Cephalic phase:
The same stimuli that activate the vagus N & stimulates gastric secretions also stimulates pancreatic enzymes.
2- Gastric phase:
When food enters the stomach, Ach is released & Stimulates pancreatic enzymes.
3- Intestinal phase:
When the acidic chyme enters the duodenum, secretin is released & stimulates the secretion of large amounts of water & bicarbonate.

3. The liver Anatomical considerations:
The liver is organized in lobules, blood flows through the sinusoids from branches of the portal vein to the central vein of each lobule.

4. The endothelium of the sinusoids have large fenestrations, there is only one layer of hepatocytes between the sinusoids, so the total area of contact between the hepatocytes & the plasma is very large.

5. The central vein coalesce to form hepatic vein which drains into inferior vena cava (IVC).

6. Liver functions Storage of glycogen, iron, vit. B12, A & D.
Filtration of blood.
Carbohydrate metabolism: conversion of galactose & fructose into glucose (gluconeogenesis).
Fat metabolism: oxidation of fatty acid to supply energy, formation of lipoproteins, synthesis of cholesterol (80% converted into bile salts) & phospholipids & conversion of proteins & CHO into fat.

7. 5. Protein metabolism:
Deamination of amino acids, formation of urea for removal of ammonia, formation of polypeptides, synthesis of the non-essential AA.
6. formation of clotting factors.
7. Catabolism & excretion of drugs & hormones like thyroxine, cortisol, aldosterone, estrogen, & it is one of the major routes for excretion of Ca++.

8. Bilirubin metabolism
Briefly, when the red blood cells have lived out their
life span (on average, 120 days) and have become too
fragile to exist in the circulatory system, their cell
membranes rupture, and the released hemoglobin is
phagocytized by tissue macrophages (also called the
reticuloendothelial system) throughout the body. The
hemoglobin is first split into globin and heme, and
the heme ring is opened to give (1) free iron, which is
transported in the blood by transferrin, and (2) a
straight chain of four pyrrole nuclei, which is the substrate
from which bilirubin will eventually be formed.
The first substance formed is biliverdin, but this is
rapidly reduced to free bilirubin, which is gradually
released from the macrophages into the plasma. The
free bilirubin immediately combines strongly with
plasma albumin and is transported in this combination
throughout the blood and interstitial fluids. Even when
bound with plasma protein, this bilirubin is still called
“free bilirubin” to distinguish it from “conjugated bilirubin,”
which is discussed later.
Within hours, the free bilirubin is absorbed through
the hepatic cell membrane. In passing to the inside of
the liver cells, it is released from the plasma albumin and
soon thereafter conjugated about 80 per cent with glucuronic
acid to form bilirubin glucuronide, about 10 per
cent with sulfate to form bilirubin sulfate, and about 10
per cent with a multitude of other substances. In these
forms, the bilirubin is excreted from the hepatocytes by
an active transport process into the bile canaliculi and
then into the intestines

9. Jaundice (Icterus)
Increase concentration of free or conjugated bilirubin > 2 mg / dL causes jaundice.
The skin, sclera & mucous membranes become yellow.

10. Causes of jaundice
1- Excess production of bilirubin (hemolytic anemia).
2- Decrease uptake of bilirubin by the hepatocytes.
3- Defect in conjugation.
4- Disturbance in secretion of the conjugated bilirubin into the bile canaliculi.
5- Intrahepatic or extrahepatic bile duct obstruction.
1, 2, unconjugated bilirubin is increased.
4, conjugated bilirubin is increased.
Conjugated= direct , unconjugated= indirect

11. Biliary secretions Functions of the bile:
The liver secretes about 600 – 1200 ml of bile / day.
Functions of the bile:
1- It plays important role in fat digestion & absorption.
This is the function of bile acids which are present in the bile.
2- The bile serves as a mean for excretion of waste products from the blood like bilirubin & excess cholesterol synthesized by the liver.

12. The bile is secreted by the hepatocytes into the bile canaliculi, then the bile flows peripherally into the terminal bile ducts, then into larger ducts until it reaches the hepatic duct & common bile duct (CBD), from here the bile either empties into the duodenum or diverted through the cystic duct into the gall bladder to be stored.

13. The ductal cells add another substance to the bile which is a watery solution of Na+ & HCO3- stimulated by secretin, it neutralizes the acid from the stomach.

14. Bile salts Functions of the BS are:
The precursor of BS is cholesterol.
There are 2 principal BS;
A- Cholic acid.
B- Chenodeoxycholic acid.
Functions of the BS are:
1- They help to emulsify the large fat particles of the food into small particles, then it can be attacked by the lipase enzyme of the pancreas (lecithin is more important than BS in emulsification).
2- They aid in the transport & absorption of digested fat end products through the intestinal mucosa by forming soluble complexes with fat called Micelles.
triglycerides is digested in the stomach by lingual lipase
Digestion of Fats in the Intestine. A small amount of
that is secreted by lingual glands in the mouth and
swallowed with the saliva. This amount of digestion is
less than 10 per cent and generally unimportant.
Instead, essentially all fat digestion occurs in the small
intestine as follows.
Emulsification of Fat by Bile Acids and Lecithin. The
first step in fat digestion is physically to break the fat
globules into very small sizes so that the water-soluble
digestive enzymes can act on the globule surfaces.This
process is called emulsification of the fat, and it begins
by agitation in the stomach to mix the fat with the
products of stomach digestion.
Then, most of the emulsification occurs in the duodenum
under the influence of bile, the secretion from
the liver that does not contain any digestive enzymes.
However, bile does contain a large quantity of bile salts
as well as the phospholipid lecithin. Both of these,
but especially the lecithin, are extremely important for
emulsification of the fat. The polar parts (the points
where ionization occurs in water) of the bile salts and
lecithin molecules are highly soluble in water, whereas
most of the remaining portions of their molecules are
highly soluble in fat. Therefore, the fat-soluble portions
of these liver secretions dissolve in the surface
layer of the fat globules, with the polar portions projecting.
The polar projections, in turn, are soluble in the
surrounding watery fluids, which greatly decreases the
interfacial tension of the fat and makes it soluble as
well.
When the interfacial tension of a globule of nonmiscible
fluid is low, this nonmiscible fluid, on agitation,
can be broken up into many very minute particles
far more easily than it can when the interfacial tension
is great. Consequently, a major function of the bile
salts and lecithin, especially the lecithin, in the bile is
to make the fat globules readily fragmentable by agitation
with the water in the small bowel.This action is
the same as that of many detergents that are widely
used in household cleaners for removing grease.
Each time the diameters of the fat globules are significantly
decreased as a result of agitation in the small
intestine, the total surface area of the fat increases
manyfold. Because the average diameter of the fat
particles in the intestine after emulsification has
occurred is less than 1 micrometer, this represents an
increase of as much as 1000-fold in total surface areas
of the fats caused by the emulsification process.
The lipase enzymes are water-soluble compounds
and can attack the fat globules only on their surfaces.
Consequently, it can be readily understood how important
this detergent function of bile salts and lecithin is
for digestion of fats.

16. Emptying of Gall Bladder
When fatty food enters the duodenum, CCK is released & stimulates contraction of GB & relaxation of sphincter of Oddi, so the bile starts to enter the duodenum & digest the fat.
Ach also stimulates GB emptying but to lesser extent.

17. Enterohepatic circulation of BS
About 94% of BS are reabsorbed from the intestine specially in the terminal ileum, only 6% are lost daily in the stool.
The absorbed BS are returned to the liver through the portal vein & then re-excreted by the liver into the bile.

18. Gall stone Causes: 1- Too much absorption of water from the bile.
2- Too much absorption of BS from the bile.
3- Too much cholesterol in the bile.
4- Inflammation of the epithelium of GB.

20. Secretions of the small intestine
1- Secretion of mucus by the Brunner’s glands.
These are compound mucus glands located in the duodenum between the pylorus & the ampulla of Vater, they secrete alkaline mucus for the protection of the duodenal mucosa from digestion by the acid of the stomach.

21. 2- Crypts of Lieberkühn. These are pits among intestinal villi, they secrete; a- Mucus by the goblet cells. b- Water & electrolytes from the enterocytes in the crypts & they are reabsorbed by the villi with the products of digestion.
The circulation of fluid from the crypts to the villi provides a vehicle for the transport & absorption of nutrients from the chyme.

22. 3- Secretion of digestive enzymes by the brush border of the villi.
a- Several peptidases for the splitting of small polypeptides into AA.
b- Disaccharidases which breaks disaccharides into monosaccharides.
c- Small amounts of lipases for the digestion of fat.

23. The most important regulatory mechanisms for small intestinal secretions is the local enteric NS, CCK & secretin also have role but to lesser extent.
The Brunner’s glands are inhibited by sympathetic stimulation, therefore, sympathetic stimulation causes peptic ulcers.

24. Secretions of the large intestine
Most of the mucosal cells here are goblet cells which secretes mucus.
When there is irritation of the colonic mucosa like in infections, there is secretion of large amounts of water & electrolytes resulting in diarrhea.
Parasympathetic stimulation causes increase motility & mucus secretion.