T1 L5: Secretions of intestines liver gallbladder & pancreas

• Functions of the small intestine

  Motility: segmentation and peristalsis

  Digestion: majority of chemical digestion

  Absorption: nutrients, electrolytes and water; vitamin B12 absorption in the ileum

  Aided by:

  • intestinal juice (mucus/HCO3-)
  • pancreatic juice (digestive enzymes)
  • bile (bile salts)
• Specialisation on the intestinal wall

  Cells in the intestinal wall (enterocytes) have both absorptive and secretory functions:

  • Absorptive cells: absorb nutrients; surface microvilli
  • Goblet cells: secrete mucus
  • Entereoendocrine cell: secrete secretin, cholecystokinin or GIP
  • Paneth cell: secrete lysozymes and can phagocytose microbes
• Brunner's Gland


  Compound tubular submucosal glands found in the duodenum

  Main function is to secrete mucus and HCO3-

  Progressive neutralisation of low pH chyme from stomach

  
• Stem cell renewal replaces epithelial cells

  Initial stem cells proliferate in the crypt region

  Intestinal stem cells then differentiate into the other enterocyte cells

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

  so vulnerable to radiation and chemotherapy

  
• Hepatopancreatic sphincter 


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

  Enteroendocrine secretions:

  • CCK (I cells): stimulate pancreatic and gallbladder secretion
  • Secretin (S cells): stimulates pancreatic and biliary bicarbonate secretion
  • GIP (K cells) - may inhibit acid secretion/stimulate insulin release

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

  Bile (0.5-1.5L): bile salts for lipid emulsification (liver hepatocyte synthesis, gall bladder storage)

  
• Intestinal bacteria

  secrete vitamins B and K for subsequent absorption

  act on chyme and produce hydrogen, CO2 and methane gas

  produce stercobilin as a breakdown product of bilirubin to give faeces brown colour
• Limited secretions in the large intestine

  Very limited secretion occurs in large intestine

  Primary function is the final absorption of water and formation of faecal matter

  Two types of cells:

  • Absorptive cells - absorption of water
  • Goblet cells - secretion of mucus

  
• Exocrine secretions of the pancreas

  Pancreas has both exocrine and endocrine role

  Exocrine acinar clusters (95%) secreting pancreatic juice

  (water, electrolytes, sodium bicarbonate and pro-enzymes)

  Endocrine pancreatic isles (5%) (Islets of Langerhans) secreting:

  • glucagon (alpha)
  • insulin (beta)
  • somatostatin (delta)
  • pancreatic polypeptide (F cell)

  
• The exocrine pancreas

  1. Acinar Secretions:
  2. rich in enzymes, Na+, Cl-, H2O
  3. triggered by acetylcholine from vagus nerve
  4. triggered by CCK in response to fat/protein in chyme
  5. Ductal secretions:
  6. rich in bicarbonate, Na+ and H2O
  7. triggered by secretin in response to highly acidic chyme
  8. unlike saliva, pancreatic juice remains isotonic throughout
  9. pancreatic juice is an enzyme rich, slightly alkaline liquid

  
• Pancreatic enzymes

  1. amylase
  2. lipases
  3. nucleases
  4. proteolytic enzymes
  5. trypsin inhibitor

  
• Activation of proteolytic enzymes

  produced as inactive precursors called zymogens

  small intestinal brush border enterokinase enzyme cleaves hexapeptide which forms active trypsin from trypsinogen

  trypsin cleaves and activates other proteolytic enzymes

  process prevents pancreatic autodigestion (+ activity of trypsin inhibitor)
• CFTR and bicarbonate secretion

  Secretin stimulates high volume of HCO3- rich pancreatic juice to buffer acid

  • enteroendocrine
  • secretin
  • SCTR
  • cAMP
  • CFTR
  • HCO3-

  
• Phases of pancreatic secretion

  1. Cephalic Phase
  2. Parasympathetic vagal stimulation of the ENS causes ACh to be released
  3. Gastric Phase
  4. Vagal reflexes in cephalic phase drive enzyme rich pancreatic secretions
  5. Distension of the stomach triggers gastrin release, further driving enzyme rich secretions
  6. Intestinal Phase
  7. If chyme acidic (pH<3)...
  8. free H+ triggers secretin release from S cells driving bicarbonate rich pancreatic juice
  9. If protein present in chyme...
  10. drives CCK secretion by I cells driving enzyme rich pancreatic juice
• Biliary secretions

  Bile made by hepatocytes in liver

  Storage of bile:

  • secreted via common hepatic duct > cystic duct > gallbladder

  Direct secretion of bile:

  • via common bile duct > pancreatic duct > hepatopancreatic ampulla > drain into duodenum

  
• Hepatocytes as functional units

  Hepatocytes are cuboidal cells and are the functional unit of the liver

  • are clustered into lobules possessing a central vein (1)
  • line highly permeable sinusoidal blood vessels (3) on one side and bile canaliculi (2) on the other side for bile drainage

  
• Function of Bile

  Greenish liquid containing water, salts, cholesterol, bile pigment bilirubin and electrolytes. Two functions:

  1. Fat digestion and absorption:

  • amphipathic bile salts emulsify fats for digestion by pancreatic lipase and form micelles for absorption

  2. Elimination of waste products:

  • Bilirubin from haem in red blood cell degradation. Breakdown product stercobilin gives faecal brown colour.

  
• Regulation of bile secretion

  1. CCK
  2. when high fat & protein in duodenum
  3. Relaxation of sphincter of oddi
  4. Contraction of gallbladder
  5. Secretin
  6. when acidic chyme
  7. Liver ductal secretion of HCO3- and H2O
  8. Vagal and enteric Acetylcholine stimulation (minor)
  9. bile flow, gall bladder contraction

  
• Enterohepatic circulation

  Continuous recycling of bile salts occurs several times per day

  Bile salts are energetically expensive to produce

  Liver is the site of metabolism for many drugs

  Enterophepatic recycling frequently occurs to slow drug elimination

  Hydrophobic drugs can therefore be therapeutically beneficial at lower concentrations, eg NSAIDs

  
• Excretion of bilirubin in bile - compete the flow diagram

  1. Haem→ bilirubin
  2. bound to albumin
  3. transported to liver
  4. conjugated with glucuronic acid
  5. excreted in bile
  6. gut bacterial hydrolysis deconjugates bilirubin → urobilinogen
  7. urobilinogen → stercobilin
  8. Excreted in faeces

  
• Dysfunction in intestinal secretions - Coeliac Disease 


  Pathophysiology:

  • Autoimmune destruction of enterocytes in small intestine
  • Reduced intestinal secretions prevents uptake of nutrients

  Trigger: unknown

  Symptoms: diarrhoea, stomach pains and indigestion following gluten intake; tiredness & weight loss due to inefficient uptake of nutrients

  Treatment: no cure; management of symptoms through avoiding gluten in food

  
• Dysfunction in enzyme activation process - Pancreatitis 


  Pathophysiology: inflammatory disease where pancreatic enzymes are activated within the pancreas and surrounding tissues; resulting in autodigestion

  Triggers: common causes are gallstones and alcohol abuse where obstruction of the pancreatic duct occurs

  Symptoms: severe dull pain around stomach that develops suddenly

  Treatment: Management in hospital with fluids, painkillers and oxygen; treatment of underlying cause

  
• Dysfunction in ductal CFTR Cl- channel - Cystic Fibrosis 


  Pathophysiology:

  • Cl- CFTR channel is absent resulting in defective ductal fluid secretion
  • mucus becomes progressively thickened, blocking enzyme activity

  Trigger: Autosomal recessive inheritance

  Symptoms: recurrent chest infections; weight loss

  Treatment: no cure; management with antibiotics and anti-inflammatory agents

  
• Dysfunction in the gall bladder - Gallstones 


  Pathophysiology: formed following disruption to bile and/or cholesterol excretion

  Trigger:

  • Excessive water and bile salt reabsorption from bile
  • Excessive cholesterol in bile causing precipitation (high fat diet)
  • Inflammation of the epithelium (low grade chronic infection)

  Symptoms: usually asymptomatic; severe rapidly intensifying abdominal pain

  Treatment: surgical removal if large; management with painkillers if not

  
• Jaundice

  Pathophysiology: build up of bilirubin in extracellular fluid

  Symptoms: Yellow discoloration of skin and sclera

  Trigger: May occur when underlying disease processes disrupt the production and excretion of bilirubin.

  Three types:

  1. Pre-hepatic Jaundice: excessive RBC breakdown and build up of unconjucated bilirubin, eg haemolytic anaemia
  2. Hepatocellular/congenital Jaundice: altered hepatocyte function, eg Crigler-Najjar Syndrome
  3. Post-hepatic Jaundice: obstruction to normal bile drainage, build up of conjugated bilirubin, eg gallstones