LR

RGI.14 Intestinal Enzymes, Liver, Hepatitis, Cirrhosis and Large Intestine Notes

Intestinal Enzymes

  • Large quantities of alkaline fluid and mucus are produced by Brunner’s glands and crypts (2 liters/day).
  • These secretions (succus entericus) contain almost no enzymes.
  • Enterocytes (intestinal columnar epithelial cells) produce digestive enzymes that remain attached to the microvillar surface.

Peptidases

  • Aminopeptidase: An exopeptidase that attacks small peptides at the amino end (-NH2), splitting off single amino acids.
  • Dipeptidase: Splits dipeptides into two amino acids.

Maltase, Sucrase, and Lactase

  • Break down disaccharides into monosaccharides.

Small Intestine Cytology

  • Columnar Epithelial Cells (Enterocytes or Absorptive Cells):
    • Function: Absorption.
    • Location: All parts of mucosa.
  • Goblet Cells: Produce mucus in all parts of mucosa.
  • Paneth Cells: Produce lysozyme and antimicrobial β-defensins in Crypts of Lieberkühn.
  • Enteroendocrine Cells: Secrete secretin and cholecystokinin (CCK) in duodenal crypts.
  • Brunner’s Glands: Secrete thin alkaline mucus in submucosa.

Intestinal Enzymes & Secretions

  • Aminopeptidase:
    • pH: 8.0
    • Source: Epithelial cells
    • Substrate: Peptides (exopeptidase)
    • Product: Amino acids
  • Dipeptidase:
    • pH: 8.0
    • Source: Epithelial cells
    • Substrate: Dipeptides
    • Product: Amino acids
  • Maltase:
    • pH: 8.0
    • Source: Epithelial cells
    • Substrate: Maltose
    • Product: Glucose
  • Sucrase:
    • pH: 8.0
    • Source: Epithelial cells
    • Substrate: Sucrose
    • Product: Glucose & fructose
  • Lactase:
    • pH: 8.0
    • Source: Epithelial cells
    • Substrate: Lactose
    • Product: Glucose & galactose
  • Enterokinase:
    • pH: 6.9
    • Source: Epithelial cells
    • Substrate: Trypsinogen
    • Product: Trypsin (active)
  • Mucus:
    • pH: 7
    • Source: Goblet cells
    • Substrate: Intestinal mucosa
    • Product: Protection
  • Succus Entericus:
    • pH: 7.6
    • Source: Crypts & Brunner’s glands
    • Substrate: Chyme
    • Product: Digestive medium

Lipid Digestion & Absorption

  • Absorption mainly takes place in the jejunum and ileum.
  • Bile contains bile salts which have a detergent effect on fat droplets, forming minute bile salt micelles.
  • These micelles allow pancreatic lipase to break down triglycerides into glycerol and fatty acids.
  • In the smooth endoplasmic reticulum, triglycerides are re-synthesized, covered with a protein coat, and discharged as chylomicrons into the intercellular space where they are taken up by the lacteals of the lymphatic system.

Liver

  • Accessory organ of the gastrointestinal tract, similar to the pancreas.
  • Largest internal organ, weighing 1.5 kg.
  • Center for metabolic regulation.
  • Located in the right and central abdomen under the diaphragm, potentially extending to the left region.

Liver Functions

  1. Production of Bile
  2. Metabolism and Storage of Nutrients
  3. Controlling Blood Composition: Regulating plasma proteins and blood sugar.
  4. Detoxification: Processing alcohol, drugs, and other substances.
  5. Destruction of Red Blood Cells: Occurs after approximately 120 days.
  • The liver receives venous blood from the intestine via the hepatic portal vein.
  • Nutrients absorbed from the gut are directly conveyed to the liver cells for breakdown, storage, or redistribution.
  • Structures and functions related to the liver are termed ‘hepatic’.

Portal System

  • The liver receives blood from two sources:
    • Hepatic artery
    • Hepatic portal vein
  • The left gastric vein, and the superior and inferior mesenteric veins drain into the hepatic portal vein.

Liver - Structure & Histology

  • Divided into a large right lobe, a smaller left lobe, and two smaller subsidiary lobes on the visceral side.
  • Composed of hexagonal lobules bounded by connective tissue.
  • Lobules consist of liver cells called hepatocytes arranged in plates.
  • These plates are two cells thick with blood running in sinusoids between them.

Hepatic Blood Supply

  • The liver receives blood from the hepatic artery and hepatic portal vein.

Liver Histology

  • At each of the six corners of the hexagonal lobule is a portal area.
  • Each portal area has branches of the hepatic portal vein, a bile duct, and the hepatic artery.
  • At the center of each lobule is the central vein, a branch of the hepatic vein.
  • Blood flows from the portal area to the central vein within sinusoids, carrying oxygenated blood from the hepatic artery and deoxygenated nutrient-rich blood from the hepatic portal vein.

Hepatic Bile Transport

  • Bile is carried between hepatocytes via bile canaliculi.
  • These empty into bile ducts, leading to the common hepatic duct and gallbladder.
  • The flow of bile in the canaliculi is opposite that of blood in the sinusoids.

Bile Flow

  • Bile is secreted continuously by hepatocytes, eventually reaching the common hepatic duct.
  • From there, it either goes directly into the duodenum or is diverted to the gallbladder via the cystic duct.
  • Bile secretion ranges between 600 - 1000 ml/day.
  • The gallbladder has a capacity of 40 - 70 ml but can store up to 12 hours of secretion by concentrating it five-fold.
  • When the small intestine is empty, the papilla of Vater (or duodenal papilla) is closed by the sphincter of Oddi, forcing bile up the cystic duct to the gallbladder for storage.

Gallbladder Physiology

  • Bile secretion is increased by two hormones:
    • Cholecystokinin (CCK): Produced by duodenal enteroendocrine cells, especially when chyme has high fat content.
      • Causes contraction of the gallbladder.
      • Relaxes the sphincter of Oddi at the major duodenal papilla.
    • Secretin: Secreted by enteroendocrine cells in response to acid in the duodenum.
      • Causes bile duct cells to secrete bicarbonate and water, increasing the volume and flow of bile into the intestine.

Bile Composition

  • Human bile is alkaline, with a pH of 6.8 - 8.5, but it can be acidic in some mammals.
  • It is a yellow, brown, or olive-green liquid.
  • Bile contains:
    • Bile salts (steroids that emulsify fats), such as sodium glycocholate and sodium taurocholate.
    • Quantities of their precursor cholesterol.
    • Bilirubin (a bile pigment).
    • Water, lecithin (a phospholipid), and several ions.

Role of Bile

  • Bilirubin is a byproduct of hemoglobin breakdown from erythrocyte destruction.
  • Bacteria in the large intestine convert bilirubin to stercobilin, giving feces its characteristic color.
  • Excess bilirubin in the blood causes jaundice.
  • Bile is responsible for most of the cholesterol secretion in the body.
  • Bile salts keep cholesterol dissolved within the bile.
  • High cholesterol concentrations may lead to cholesterol crystallization and gallstone formation.
  • Bile salts play a role in lipid emulsification.

Gallstones

  • Gallstones may obstruct bile flow from the gallbladder, leading to obstructive jaundice.
  • Moving through the cystic duct can cause intense pain.
  • Occur in 7% of males and 15% of females between ages 18 – 65.
  • Under 40 years, there is a 3:1 female to male susceptibility ratio; in the elderly, it is 1:1.
  • Classical treatment involves surgical removal of the gallbladder.
  • Recent treatments include drugs, ultrasound (lithotripsy), and laser treatment to dissolve the stones.

Hepatitis

  • Inflammation of the liver results in hepatocyte damage and cell death.
  • May occur with limited or no symptoms, but often leads to:
    1. Jaundice (yellowish discoloration)
    2. Anorexia (poor appetite)
    3. Malaise (general feeling of illness).
  • Acute hepatitis is generally followed by complete recovery.
  • Prolonged inflammation may lead to fibrosis and cirrhosis.
  • Common causes include viral infections, autoimmune disorders, excessive alcohol, and certain drugs and toxins.
  • In younger adults, it is a significant cause of premature death.

Large Intestine

  • Almost all nutrient absorption occurs in the small intestine.
  • The large intestine primarily reabsorbs water and ions secreted earlier in the digestive process.
  • Bacteria in the large intestine produce significant amounts of vitamins K and B12.
  • The ileocecal valve regulates chyme admission into the large intestine and prevents reflux.

Large Intestine - Structure

  • Divided into six anatomical sections:
    • Ileocecal valve → cecum (appendix) → ascending colon → transverse colon → descending colon → sigmoid colon → rectum → anus
  • The cecum is large in some mammals but small in humans and terminates in the vermiform appendix (10 cm long), which contains lymphoid tissue.
  • Appendicitis is caused by an inflamed appendix, initially perceived as central abdominal pain shifting to the right iliac fossa.
  • Obstruction of the appendix lumen is the usual precipitating cause of acute appendicitis.

Colon

  • About 1.5 meters long and divided into four sections (ascending, transverse, descending, sigmoid).
  • Constricted at intervals forming pockets or bulges called haustra.
  • Lacks villi internally.
  • The mucosa has closely packed tubular glands with many goblet cells.
  • The muscularis externa has a thick circular muscle layer.
  • The longitudinal muscle is arranged into three bands called taeniae coli.

Rectum

  • The colon terminates at the rectum, which has:
    • More numerous goblet cells in the mucosa.
    • A thicker muscularis externa with a complete longitudinal muscle layer.
  • The rectum is about 12 cm long and curves downward and forward.

Rectum and Anal Canal

  • Suddenly turns 90 degrees backward and down through the pelvic diaphragm.
  • Becomes the recto-anal junction.
  • The anal canal is short (4 cm) and marks the junction between the endoderm and ectoderm.
  • It is guarded by internal (smooth muscle) and external (striated muscle) anal sphincters.

Large Intestine - Physiology

  • Of the 500 – 1000 ml/day volume of chyme entering the cecum, only 100 - 200 ml is lost in the feces.
  • Most fluid reabsorption occurs in the proximal half of the colon, called the absorbing colon.
  • Approximately 75% of feces is water; the remaining 25% solids are approximately:
    • 1/3 bacteria, 1/3 undigested cellulose, 1/3 mostly fat.
  • Feces are propelled by slow peristaltic contractions until they reach the rectum, which is usually empty.

Large Intestine - Physiology

  • As fecal matter accumulates, it moves into and distends the rectum, stimulating stretch receptors.
  • This may stimulate the defecation reflex in the spinal cord.
  • Defecation is under the control of parasympathetic nerves (internal sphincter) and somatic motor nerves (external sphincter).
  • The defecation reflex does not normally occur until the external anal sphincter relaxes under conscious control.
  • All fluid secretions added daily to the GIT amount to approximately 7.2 liters, plus about 1.5 liters of ingested food.

GIT - Secretion and Reabsorption

  • Secretions (ml/day):
    • Saliva: 1,200
    • Gastric: 2,000
    • Pancreatic: 1,200
    • Bile: 700
    • Succus entericus: 2,050
    • Colon: 60
    • Total secretions: 7,210
    • Ingested approximately: 1,500
    • Total fluid: 8,710
  • Reabsorbed (ml/day):
    • Small intestine: 8,000
    • Large intestine: 500
    • Feces approximately: 210