Digestive System - Pancreas, Liver, Gall Bladder, and the Large Intestine

Pancreas

• Location: Behind the stomach, approximately 6 inches in length.
• Exocrine Portion:
  • Clusters of glandular epithelial cells (acini) produce pancreatic juice.
  • Pancreatic juice passes into the duodenum via the pancreatic duct.
• Endocrine Portion:
  • Approximately 1% of the pancreas.
  • Islets of Langerhans secrete hormones, including insulin and glucagon, which control blood glucose levels.

Key Anatomical Features of the Human Pancreas

• Key Components:
  • Spleen
  • Gallbladder
  • Common bile duct
  • Pancreas (head, body, neck, tail, uncinate process)
  • Duct of Wirsung
  • Ampulla of Vater
  • Duodenum
  • Islet of Langerhans (alpha, beta, delta, and PP cells).
  • Acini
  • Duct

Exocrine Acini Structure and Function

• Acinar Cells: Contain nucleus and zymogen granules; responsible for inactive enzyme production.
• Centroacinar Cells: Produce bicarbonate ions (HCO3-).
• Ductal Cells: Facilitate HCO3-/Cl- exchange with interstitial fluid.

Pancreatic Juice

• Volume: Approximately 1-1.5 liters per day.
• Composition:
  • Bicarbonate Ions: Alkaline pH inactivates pepsin from the stomach, neutralizes acid, and protects the small intestine (pH 8).
  • Enzymes:
    • Pancreatic Amylase: Digests starch into maltose.
      starch \rightarrow maltose
    • Pancreatic Lipase: Digests fats into 2 free fatty acids and monoglyceride.
      fats \rightarrow 2 \ free \ fatty \ acids + monoglyceride
    • Protein-Digesting Enzymes (Proteases): Examples include trypsinogen and carboxypeptidase, produced in inactive forms.
  • Note: Pancreatic enzymes are only activated once within the duodenum.
• Pancreatitis:
  • Inflammation of the pancreas (acute and chronic).
  • Activated proteases auto-digest the pancreas.

Relation of the Pancreas to the Liver, Gallbladder, and Duodenum

• The image illustrates the anatomical relationship between the liver, gallbladder, pancreas, and duodenum, highlighting the common bile duct and pancreatic duct.

The Liver

• Largest internal organ (~1.5 kg).
• Blood Supply: Receives approximately 25% of cardiac output.
• Functions: Responsible for essential metabolic and synthetic functions (>200 functions).
• Consequences of Liver Damage: Results in widespread consequences; death can occur within 24 hours if the liver stops working.
• Regenerative Capacity: Can survive on 1/3 of the liver due to its extensive reserve and regenerative capacity.

Liver Conditions

• Includes normal liver, fatty liver, polycystic liver disease and cirrhosis.

Signs of Liver Damage

• Liver Function Tests: Measure enzymes concentrated in liver cells:
  • Alanine Aminotransferase (ALT).
  • Aspartate Aminotransferase (AST).
  • Gamma-Glutamyl Transferase (GGT).
• Changes in Blood Bilirubin Levels: Indicate liver injury.

Anatomy of the Liver

• Lobes: Two main lobes and two smaller lobes (caudate and quadrate).
• Ligaments: Falciform and round ligaments.
• Other Structures: Inferior vena cava, hepatic portal vein, hepatic artery proper, common bile duct, porta hepatis.

Functions of the Liver (Multifunctional)

• Metabolism of Nutrients:
  • Carbohydrates: Maintain blood glucose levels.
    • Stores glucose as glycogen (glycogenesis).
    • Forms glucose by glycogenolysis (glycogen breakdown) and gluconeogenesis (formation of glucose from some amino acids, lactate, glycerol, etc.).
  • Fats:
    • Storage of triglycerides.
    • Lipoprotein formation for transport of lipids and cholesterol.
    • Removal of lipids from circulation (e.g., LDL, VLDL).
  • Proteins:
    • Remove amino group NH2 from amino acids (deamination) to generate ammonia (toxic), which is converted to urea (less toxic) for removal in urine.
  • Drugs & Alcohol: Metabolism and excretion of toxic products.
• Bile Production:
  • Major digestive function (~0.6 – 1.0 liter green alkaline bile/day).
  • Two main bile acids: cholic acid and chenodeoxycholic acid.
• Hematological Regulation:
  • Plasma protein synthesis, e.g., albumin, clotting factors (prothrombin, fibrinogen), alpha and beta globulins, etc.
• Storage of Vitamins and Minerals:
  • Fat-soluble vitamins A, B12, D, E, & K; iron, copper, etc.
• Phagocytosis:
  • Kupffer cells destroy (phagocytose) aged blood cells and bacteria.
• Activation of Vitamin D:
  • Inactive forms of Vit D generated in skin or from dietary intake.

Absorption of Products of Digestion

• Process:
  • Movement of absorbed nutrients into the blood and lymph.
  • Chylomicrons, amino acids and monosaccharides are absorbed.
• Key Structures:
  • Villus.
  • Lacteal.
  • Blood capillary.

Blood Flow to the Liver from Intestines

• Hepatic Portal System:
  • All blood leaving the GI tract enters the hepatic portal system and flows into the liver (First Pass metabolism).
  • Liver cells extract nutrients, vitamins, minerals, drugs, and other chemicals/toxins from blood.
  • Blood then leaves the liver via the hepatic veins to enter the systemic circulation.
• Liver Stores Excess Nutrients:
  • Corrects nutrient deficiencies by mobilizing stored reserves (e.g., glycogen) or performing synthetic activities.

Hepatic Portal Circulation

• Overview:
  • Venous blood from the intestines flows into the liver via the hepatic portal vein.
  • The liver processes the blood, and then it drains into the inferior vena cava via the hepatic veins.
• Key Vessels:
  • Hepatic portal vein.
  • Superior mesenteric vein.
  • Splenic vein.

Hepatic Blood Supply

• Arterial Blood Supply:
  • 1/3 of blood supply from the hepatic artery
• Venous Blood Supply:
  • 2/3 venous blood from hepatic portal vein coming from GI tract
• Return to Systemic Circulation:
  • Via hepatic veins into the inferior vena cava

Liver Lobules

• Basic Functional Units: The basic functional units of the liver
• Structure: Each lobe is divided by connective tissue into about 100,000 liver lobules, each about 1 mm in diameter.

A Liver Lobule

• Shape: Hexagonal in cross-section.
• Portal Areas: Has 6 portal areas, one at each corner of the lobule.
• Portal Triad: Located in portal areas and includes:
  • Branch of hepatic portal vein.
  • Branch of hepatic artery.
  • Small branch of bile duct.

Hepatic Blood Flow

• Blood Enters Liver Sinusoids:
  • From small branches of the hepatic portal vein & hepatic artery.
• Kupffer Cells:
  • Many phagocytic Kupffer cells are located in the sinusoidal lining.
  • Destroy old RBCs, bacteria, etc.

Liver Structure - Microscopic

• Illustration
  • Bile Duct
  • Bile Canal
  • Kupffer cell
  • Branch of hepatic portal vein
  • Branch of Hepatic Artery
  • Hepatic Sinusoids
  • Central Canal

Hepatocytes

• Shape: Cube-shaped liver cells that form a series of irregular plates arranged like wheel spokes, radiating out from the central vein.
• Mass: 70-80% of liver mass.
• Function: Many functions.

Hepatocyte Function

• Absorption: As blood flows through sinusoids, hepatocytes absorb solutes from plasma (e.g., glucose, amino acids, drugs, etc.).
• Secretion: Secrete products into the blood (e.g., plasma proteins).

The Bile Duct System

• Bile Canaliculi:
  • Hepatocytes secrete bile into a network of narrow channels known as bile canaliculi.
  • Extend outward away from the central vein.
• Connection to Larger Bile Ducts: Bile canaliculi connect with larger bile ducts.
• Bile Composition: Water, ions, bilirubin, cholesterol, & bile salts.

Red Blood Cells, Bilirubin and Bile

• Red blood cells are broken down into heme, which is converted into biliverdin and then bilirubin.
• Excess RBC breakdown can lead to jaundice

Bilirubin and Bile

• Bilirubin enters the bloodstream, binds to albumin, and travels to the liver.
• In the hepatocyte, bilirubin undergoes conjugation with glucuronic acid, forming bilirubin diglucuronide.
• This is delivered into the duodenum and excreted in feces

The Right and Left Hepatic Ducts

• Function: Collect bile from all bile ducts of the liver lobes.
• Unite to Form: Common hepatic duct, which leaves the liver.

The Gallbladder

• Shape and Location: Pear-shaped, muscular sac located under the liver’s right lobe.
• Function: Stores and concentrates bile prior to excretion into the small intestine.
• Contraction: Forces bile into the cystic duct.

Functions of Bile

• Emulsification: Bile salts break fat droplets apart (emulsification).
  • Creates tiny emulsion droplets coated with bile salts.
  • Increases surface area exposed to enzymatic pancreatic lipase to maximize lipid digestion.
• Micelle Formation: For absorption of fatty acids into epithelial cells.
• Waste Removal: Removal of cholesterol and bi-products metabolism (bilirubin, drugs/drug metabolites, etc.).

Gallstones

• Composition: Crystals of insoluble cholesterol and minerals.
• Formation: Form if bile is too concentrated.
• Consequences:
  • Small stones may be flushed through the bile duct and excreted, but if trapped in a duct:
    • Cholecystitis: Inflammation of the gallbladder (intense pain, fever, jaundice).
    • Cholecystectomy: Removal of the gallbladder.
    • Cholestasis: ‘Bile stopped’ due to blockage or ↓ bile production in liver disease.

The Large Intestine

• Location: Extends from the ileocaecal sphincter (valve) to the anus.
• Dimensions: Approximately 1.5m (5ft) long and 6cm wide.
• Comparison: The small intestine is longer (6m or ~20ft) and narrower (~3cm wide).

3 Parts of the Large Intestine

• Caecum:
  • Pouch-like first portion.
  • Stores materials & starts compaction.
• Colon:
  • Ascending, transverse, descending & sigmoid sections.
  • The wall forms a series of pouches (Haustra).
• Rectum:
  • The last 15 cm of the digestive tract; ends in the anal canal (5 cm).
  • Expandable for temporary storage of faeces.

Anal Sphincters

• Internal Anal Sphincter:
  • Smooth muscle (not under voluntary control).
• External Anal Sphincter:
  • Ring of skeletal muscle (under voluntary control).
• Epithelium:
  • Stratified squamous epithelium in the lower 1/3 of the anal canal (protection).

Colon Muscles

• Circular Smooth Muscle Layer: Of the muscularis externa continues along the colon.
• Longitudinal Layer: Of the muscularis externa is reduced to 3 longitudinal bands of smooth muscle in the colon.
• Taeniae Coli: These bands of longitudinal muscle known as taeniae coli.
• Haustra: Muscle tone in taeniae coli creates the haustra.
• Appearance: Give the LI a puckered appearance.

Functions of the Large Intestine

• Reabsorption of Water and Bile Salts: Bile salts reabsorbed (main function).
• Compaction: Of intestinal contents into faeces.
• Absorption: Of important vitamins produced by bacteria in LI (e.g., Vit K) and some bacteria-derived metabolites (e.g., butyrate).
• Storage: Of faecal material prior to defaecation.

Water Absorption (Main Function)

• Watery Material Input: ~1500 ml of watery material enters the colon each day.
• Faeces Output: Only ~200ml of faeces is produced.
• Faeces Composition: 75% water, 5% bacteria, 20% indigestible material, epithelial cells, etc.

Intestinal Bacteria (Gut Microbiome or Gut Flora)

• Trillions of bacteria live in LI –’good/friendly’ & ‘bad’
• Balance Important for Health:
  • If disrupted (diet, diarrhoea, parasitic organisms, overuse of antibiotics, etc.) can be detrimental.
• Probiotics – food and supplements:
  • lactobacillus, bifidobacteria, etc.
  • Potential health benefits.
• Normal Bacteria Benefits: Normal (‘good’) bacteria in the colon make several vitamins (e.g., Vit K) that supplement diet (but not usually enough to meet total needs).

Vitamin K

• Type: A fat-soluble vitamin.
• Function: Required by the liver for synthesizing several clotting factors, including prothrombin.
• Deficiency: Leads to impaired blood clotting.
• Source: Intestinal bacteria produce ~50% of daily req.

Characteristics of the Colon

• Villi and Folds: No villi or permanent folds.
• Epithelium: Simple columnar epithelium with the presence of many goblet cells (lubrication).
• Glands: Presence of distinctive deep intestinal glands.
• Enzymes: No enzymes produced apart from bacterial enzymes.

Movements of the Large Intestine

• Peristaltic Waves: Move material along the length of the colon (slower than in SI).
• Segmentation Movements (Haustral Churning): Mix contents of adjacent haustra.
• Mass Peristalsis:
  • Very strong peristaltic wave from the middle of the transverse colon through the rest of the large intestine.
  • Drives contents into the rectum.
  • Occurs 3-4 times a day immediately after a meal à Defaecation Reflex.

Defaecation Reflex (Stimulus-Stretching of Rectal Wall)

• Sphincter Requirements: Requires relaxation of both internal and external anal sphincters.
• Reflex Actions:
  • The reflex opens the internal sphincter but closes the external sphincter.
• Voluntary Control:
  • Opening the external sphincter requires a conscious/voluntary response.
• Assistance: Aided by voluntary contractions of the diaphragm & abdominal muscles.