Non-salivary Secretions of the GI Tract

What are the Functions of the Small Intestine?

Specialisation of the Intestinal Wall

What is Brunner’s Gland?

1. Compound tubular submucosal glands found in the duodenum

2. Main function is to secrete mucus and HCO₃^-

3. Progressive neutralisation of low pH (acidic) chyme from stomach

How does Stem Cell Renewal replace Epithelial Cells?

1. Intestinal stem cells proliferate (mitosis) in the crypt region

2. Intestinal stem cells then differentiate into the other enterocyte cells

3. Harsh environment requires a rapid turnover of epithelial cells every 5-7 days

4. Vulnerable to radiation, chemotherapy

What is the Hepatopancreatic Sphincter?

Secretions from the duodenal wall mix with pancreatic and biliary secretions regulated by the hepatopancreatic sphincter (sphincter of Oddi).

Hepatopancreatic Sphincter- Enteroendocrine Secretions

Enteroendocrine secretions

1. CCK (I cells) – stimulates pancreatic and gallbladder secretion

2. Secretin (S cells ) – stimulates pancreatic and biliary bicarbonate secretion

3. GIP (K cells) – may inhibit acid secretion / stimulate insulin release

Hepatopancreatic Sphincter- Exocrine Pancreatic Juice

Exocrine pancreatic juice (1.5 L): bicarbonate / digestive enzymes

Hepatopancreatic Sphincter- Bile

Bile (0.5-1 L) : bile salts for lipid emulsification (liver hepatocyte synthesis, gall bladder storage)

What are Intestinal Bacteria?

• Bacteria secrete vitamins B and K for subsequent absorption

• Bacteria act on chyme and produce hydrogen, CO2 and methane gas

• Bacteria produce stercobilin as a breakdown product of bilirubin to give faeces brown colour.

Why does the Large Intestine have Limited Secretions?

Which cells in the intestinal cell wall are responsible for secretion of hormones into the GI tract?

Enteroendocrine cells

What are the Exocrine Secretions of the Pancreas?

Exocrine acinar clusters (95%) secreting pancreatic juice

• water, electrolytes, sodium bicarbonate and pro-enzymes

What are the Endocrine Secretions of the Pancreas?

Endocrine pancreatic islets (5%)  (Islets of Langerhans) secreting

• glucagon (alpha)

• insulin (beta)

• somatostatin (delta)

• pancreatic polypeptide (F cell)

The Exocrine Pancreas

The Exocrine Pancreas- Acinar Secretions

Acinar Secretions

• Rich in enzymes, Na⁺, Cl^- and H₂O

• Triggered by acetylcholine from the Vagus nerve

• Triggered by CCK in response to fat/protein in chyme

The Exocrine Pancreas- Ductal Secretions

Ductal Secretions

• Rich in bicarbonate, Na⁺ and H₂O

• Triggered by secretin in response to highly acidic chyme

The Exocrine Pancreas- Pancreatic Juice

• Unlike saliva, pancreatic juice remains isotonic

• Pancreatic juice is an enzyme rich, slightly alkaline liquid

Examples of Pancreatic Enzymes

How are Proteolytic Enzymes Activated?

1. Proteolytic enzymes are produced as inactive precursors called zymogens

2. Small intestinal brush border enterokinase enzyme cleaves hexapeptide to form active trypsin from trypsinogen

3. Trypsin cleaves and activates other proteolytic enzymes

4. Process prevents pancreatic autodigestion (+ activity of trypsin inhibitor)

CFTR and Bicarbonate Secretions

1. Duodenal H⁺ causes enteroendocrine cells to produce secretin

2. Secretin binds to the secretin receptor (SCTR) at the basolateral membrane

3. Secretin binding triggers cyclic adenosine monophosphate (cAMP) second messenger pathways

4. cAMP upregulates activity of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl^- and HCO₃⁻ channel at the apical membrane

5. Secretin stimulates high volume of HCO₃⁻ rich pancreatic juice to buffer acid

Phases of the Pancreatic Secretion

How does the pancreas prevent pancreatic digestion by proteolytic enzymes?

Enzymes are released as pro-enzymes

How is Bile Stored?

How is Bile Secreted?

Direct secretion of bile

• Via common bile duct joining the pancreatic duct to drain into the duodenum at the hepatopancreatic ampulla

What are Hepatocytes?

What is Bile?

Bile is a greenish liquid containing water, salts, cholesterol, bile pigment bilirubin and electrolytes.

Function of Bile- Fat Digestion and Absorption

Fat digestion and absorption

• Bile salts (amphipathic) emulsify fats for digestion by pancreatic lipase and form micelles for absorption

Function of Bile- Elimination of Waste Products

Elimination of waste products

• Bilirubin (pigment) from haem in red blood cell degradation (breakdown product stercobilin gives faecal brown colour)

How is Bile Secretion Regulated?

What is Enterohepatic Circulation?

Excretion of Bilirubin in Bile

1. Haem from old/faulty RBC converted to bilirubin (orange) and transported to liver bound to albumin

2. Conjugated (made hydrophilic) with glucuronic acid and excreted in bile

3. Gut bacterial hydrolysis (b glucuronidase) deconjugates bilirubin to form urobilinogen

4. Urobilinogen reduced to stercobilin, excreted in faeces (brown colour)

What is the physiological benefit of sinusoidal capillaries in the liver?

Large pores to allow passage of large molecules

Dysfunction in Intestinal Secretions- Coeliac Disease

Dysfunction in Enzyme Activation Process- Pancreatitis

Dysfunction in Ductal CFTR Cl- Channel- Cystic Fibrosis

Dysfunction in the Gall Bladder- Gallstones

What is Jaundice?

• The build up of bilirubin in extracellular fluid (serum bilirubin >30-60 mmol.L^-1) 

• Yellow discoloration of skin and sclera

• May occur when underlying disease processes disrupt the production and excretion bilirubin

Causes of Jaundice- Pre-hepatic

Pre-hepatic

• excessive RBC breakdown and build up of unconjugated bilirubin eg haemolytic anaemia

Causes of Jaundice- Hepatocellular/Congenital

Hepatocellular/congenital

• altered hepatocyte function eg Crigler-Najjar syndrome

Causes of Jaundice- Post-hepatic

Post-hepatic

• obstruction to normal bile drainage, build up of conjugated bilirubin eg gallstones

A young patient presents to their ED in the evening with severe stomach pains. Blood tests suggest serum bilirubin is 4 umol/L. The patient explains they are usually uncomfortable in the evenings. What is the likely diagnosis?

Coeliac Disease