Digestive System II - Comprehensive Notes

Liver Functions

• Bile Production & Secretion: The liver produces bile, which is essential for emulsifying fats during digestion.
• Detoxification of Blood:
  • Removes hormones, drugs, and toxic wastes via bile.
  • Phagocytosis by Kupffer cells: Kupffer cells are specialized macrophages in the liver that engulf and break down harmful substances.
  • Chemical alteration:
    • Ammonia \rightarrow Urea: Converts toxic ammonia into urea, which is excreted by the kidneys.
    • Hydrophobic molecules \rightarrow Hydrophilic: Modifies hydrophobic molecules to make them more water-soluble for excretion.
  • Cytochrome P450 enzymes: These enzymes metabolize lipophilic drugs, making them easier to eliminate from the body.
• Regeneration: The liver has a remarkable capacity to regenerate damaged tissue.

Hepatic Portal System

• Deoxygenated Blood Source: Deoxygenated blood from the capillaries of the intestine, gallbladder, pancreas, and spleen enters the liver via the hepatic portal vein.
• Blood Flow Contribution: Accounts for approximately 80% of the blood flow to the liver.

Hepatic Portal System Components

• Inferior Vena Cava
• Hepatic Vein
• Liver
• Stomach
• Cystic Duct
• Hepatic Portal Vein
• Superior Mesenteric Vein and Its Tributaries
  • Right Gastro-epiploic Vein
  • Pancreaticoduodenal Vein
  • Middle Colic Vein (from transverse colon)
  • Right Colic Vein
  • Ileocolic Vein
  • Intestinal Veins
  • Ascending Colon
  • Small Intestine
  • Pancreas
• Esophagus
• Aorta
• Left Gastric Vein
• Right Gastric Vein
• Splenic Vein and Its Tributaries
  • Spleen
  • Left Gastro-epiploic Vein
  • Pancreatic Veins
  • Descending Colon
• Inferior Mesenteric Vein and Its Tributaries
  • Left Colic Vein
  • Inferior Mesenteric Vein
  • Sigmoid Vein
  • Superior Rectal Vein

Liver Histology

• Liver Lobule:
  • Composed of hepatocytes, which perform detoxification and form bile.
• Sinusoids:
  • Mixing of blood from hepatic artery and portal vein occurs in sinusoids.
  • Stellate (Kupffer) macrophages are present within sinusoids.
• Bile:
  • Functions to emulsify fatty acids, aiding in their digestion and absorption.
  • Drains out the right and left hepatic ducts, which merge to form the common bile duct, emptying into the duodenal papilla.
• Countercurrent Flow: There is a countercurrent flow of blood within the liver lobules.

Liver Histology Components

• Interlobular Septum
• Interlobular Bile Duct
• Interlobular Vein
• Portal Triad
• Bile Ductules
• Central Vein
• Liver Lobules
• Interlobular Artery

Portal Triad

• Composition: Composed of three vessels:
  • Hepatic artery
  • Portal vein
  • Bile duct
• Blood Flow: Blood mixes in sinusoids, which then drain into a central vein.

Bile Flow

• Branch of Hepatic Artery
• Branch of Hepatic Portal Vein
• Branch of Bile Duct
• Sinusoid
• Liver Cells (Hepatocytes)
• Kupffer Cell
• Bile Canaliculus
• Branch of Hepatic Vein

Enterohepatic Circulation

• Definition: The recirculation of compounds between the liver and intestine.
• Exogenous Compounds: Exogenous compounds secreted in bile are primarily eliminated in feces.
• Reabsorption: Some substances in bile may be absorbed by the intestinal epithelium and re-enter the hepatic portal blood.
• Bile Salts Recycling: Bile salts undergo a "recycling" process, where they are reabsorbed in the intestine and returned to the liver.

Clinical: Liver Cirrhosis

• Definition: Chronic liver damage that leads to scarring and liver failure.
• Common Causes: Hepatitis and chronic alcohol abuse.
• Irreversible Damage: Liver cirrhosis cannot be undone, but further damage can be limited.
• Later Stage Symptoms: Jaundice, GI bleeding, abdominal swelling.
• Treatment: Liver transplant is often required in advanced cases.

Gallbladder

• Description: Hollow, pear-shaped organ.
• Function: Stores and concentrates bile; it does not produce bile.
• Anatomical Features:
  • Round ligament
  • Right hepatic duct
  • Cystic duct
  • Left hepatic duct and artery
  • Fundus, body, and neck of the gallbladder
  • Bile duct
• Location: Inferior surface of the liver.
• Relationship to Other Organs:
  • Duodenum
  • Pancreas
  • Stomach
• Other Structures:
  • Cut edge of lesser omentum
  • Hepatic portal vein
  • Common hepatic artery
  • Right gastric artery

Clinical: Cholecystitis

• Definition: Inflammation of the gallbladder, usually caused by the development of gallstones.
• Pain Referral Pattern: Pain is often referred to the right shoulder or right scapula.
• Predisposition (Five F’s):
  • Forty’s (age)
  • Female (gender)
  • Fertile (childbearing status)
  • Flatulent (gas)
  • "Overweight"

Clinical: Gallstones

• Gallstones are crystalline formations in the gallbladder or bile ducts.

Pancreas

• Location: Lies posterior to the stomach, between the duodenum and spleen.
• Activity: Has both endocrine and exocrine activity.
• Arterial Supply:
  • Abdominal aorta
  • Celiac trunk
  • Common hepatic artery
  • Splenic artery and great pancreatic artery
  • Caudal pancreatic artery
  • Gastroduodenal artery
  • Superior pancreatic artery
  • Superior pancreaticoduodenal artery
  • Transverse pancreatic artery
  • Superior mesenteric artery
  • Inferior pancreaticoduodenal artery
• Ducts:
  • Bile duct
  • Accessory pancreatic duct (to lesser duodenal papilla)
  • Pancreatic duct (to greater duodenal papilla) with bile duct
• Anatomical Parts:
  • Head, body, and tail of pancreas
• Lobules: Present in the pancreas

Pancreas Histology

• Exocrine Cells:
  • Group together to form pancreatic acini.
  • Drain contents into the pancreatic duct.
  • Include enzymes like lipases, proteases, nucleases, amylase, and bicarbonate (HCO3-).
• Endocrine Cells:
  • Group together to form Islets of Langerhans.
  • Alpha cells secrete glucagon.
  • Beta cells secrete insulin.
  • Drain contents into systemic blood flow.

Pancreas Histology Components

• Duct
• Pancreatic Acini (exocrine)
• Pancreatic Islet (endocrine)
• Pancreatic Acinar Cells

Islets of Langerhans

• Glucagon:
  • Secreted by α-cells when glucose levels are low.
  • Increases blood glucose during fasting.
  • Breaks down fats and glycogen.
• Insulin:
  • Secreted by β-cells when glucose levels are high.
  • Promotes the entry of glucose into cells.
  • Utilizes GLUT4 receptors.
  • Converts glucose into glycogen and fat.
  • Decreases blood glucose levels.

Clinical: Diabetes Mellitus

• Type 1 Diabetes:
  • Pancreas fails to produce insulin.
• Type 2 Diabetes:
  • Cells fail to respond to insulin properly (insulin resistance).
• Characteristics Depicted in Figure:
  • Healthy: Normal insulin and glucose function.
  • Type 1: Lack of insulin production.
  • Type 2: Insulin resistance.
• Statistics:
  • Graphs indicating percentage and number of people with diabetes over time.

Pancreatic Enzyme Activation

• Inactive Enzymes (Zymogens): Include trypsinogen and other inactive enzymes.
• Trypsinogen Activation: Trypsinogen is converted into active trypsin by a brush border enzyme in the duodenum.

Nutrients

• Macronutrients:
  • Carbohydrates
  • Lipids (fats)
  • Proteins
  • Nucleic acids
• Micronutrients:
  • Vitamins: Organic compounds with hormone-like functions and antioxidant properties.
  • Minerals: Inorganic electrolytes.

Carbohydrate Digestion

• Initial Digestion: Begins in the mouth with salivary amylase.
• Duodenum: Pancreatic amylase continues digestion in the duodenum.
• Completion: Brush border enzymes of the small intestine complete the digestion process.
• Absorption: Glucose is moved through the intestinal epithelium and secreted into blood capillaries.

Glucose Absorption

• Apical Surface: Glucose is transported with Na+ via secondary active transport (symporter).
• Basolateral Membrane: Glucose moves through GLUT transporters to enter the blood.

Carb Absorption & Digestion

• (a) Carbohydrates break down into monosaccharides:
  • Glucose polymers (starch, glycogen) are broken down by amylase into maltose.
  • Disaccharides (sucrose, lactose) are converted by sucrase and lactase into monosaccharides.
• (b) Carbohydrate absorption in the small intestine:
  • Glucose enters with Na+ on SGLT and exits on GLUT2.
  • Fructose enters on GLUT5 and exits on GLUT2.

Protein Absorption & Digestion

• Stomach: Begins in the stomach with pepsin.
• Duodenum: Pancreatic juice contains zymogens like trypsinogen, which are converted into active enzymes.
• Completion: Brush border enzymes complete digestion.
• Absorption: Amino acids are moved through the duodenal epithelium and secreted into the blood.

Lipid Digestion & Absorption

• Emulsification: In the duodenum, lipids are emulsified by bile salts.
• Digestion: Pancreatic lipase digests lipids.

Lipid Digestion

• Step 1: Emulsification:
  • Fat droplets (triglycerides) are emulsified by bile salts.
• Step 2: Hydrolysis:
  • Triglycerides in emulsified fat droplets are hydrolyzed into fatty acids and monoglycerides by lipase.
• Step 3: Micelle Formation:
  • Fatty acids and monoglycerides dissolve into micelles to produce "mixed micelles."

Lipid Absorption

• Micelle Transport: Fatty acids and monoglycerides are transported into the epithelium via micelles.
• Chylomicron Formation: Subunits are reorganized, and protein is added to form chylomicrons.
• Lymph Transport: Chylomicrons are transported by lymph to the blood via lacteals.

Lipids in Blood

• Lymph Re-entry: Lymph re-enters the blood via the thoracic duct into the left subclavian vein.
• ApoE Addition: A protein constituent, ApoE (apolipoprotein E), is added, enabling triglyceride digestion.
• Fatty Acid Release: This process releases fatty acids into the blood.
• Cholesterol Release: Cholesterol is also released into the blood.

Lipid Transports

• Lipoproteins: Carry lipids in the blood.
• Low-Density Lipoprotein (LDL): Carries cholesterol to the tissues for storage.
• High-Density Lipoprotein (HDL): Carries excess lipids to the liver for degradation.
• Question: LDL contributes to atherosclerosis, while HDL protects against it.

Hunger Regulation

• Ghrelin:
  • Produced mostly by the stomach.
  • Produced during fasting and signals hunger.
  • Leads to food intake.
• Leptin:
  • Produced by adipose cells.
  • Produced when full.
  • Signals that eating should stop.
• Obesity Development: Imbalance between ghrelin and leptin may contribute to the development of obesity.

GI Tract Regulation

• Extrinsic:
  • Autonomic Nervous System:
    • Parasympathetic NS increases motility and secretions via the vagus nerve.
    • Sympathetic NS has antagonistic effects.
  • Endocrine System: Hormones like gastrin, CCK, and secretin.
• Intrinsic:
  • Enteric Nervous System:
    • Myenteric plexus and submucosal plexus.
  • Interstitial Cells of Cajal: Control peristalsis and segmentation.

GI Tract Regulation (Hormones)

• GIP & GLP-1: Promote glucose uptake into tissues.
• CCK (Cholecystokinin):
  • Released with the presence of fat in the duodenum.
  • Stimulates gallbladder and pancreas function.
• Secretin:
  • Stimulated by gastric acid (low pH).
  • Stimulates pancreas release.
• Serotonin: Increases GI motility.

Pancreas & Bile Regulation

• Pancreatic Juices:
  • Acidic chyme in the duodenum stimulates Secretin to release HCO3- in pancreatic juice.
  • Fat in the duodenum stimulates Cholecystokinin (CCK) to secrete pancreatic juice enzymes.
• Bile:
  • Secretin: Causes secretion of bile.
  • CCK: Stimulates gallbladder contraction.

GI Hormones

• Gastrin (G cells):
  • Stimulus for Release: Peptides, amino acids, and neural reflexes.
  • Primary Target: ECL cells and parietal cells.
  • Primary Effect: Stimulates gastric acid secretion and mucosal growth.
  • Other Information: Somatostatin inhibits release.
• Cholecystokinin (CCK):
  • Stimulus for Release: Fatty acids and some amino acids.
  • Primary Target: Gallbladder, pancreas, and stomach.
  • Primary Effect: Stimulates gallbladder contraction and pancreatic enzyme secretion; Inhibits gastric emptying and acid secretion.
  • Other Information: Promotes satiety; Some effects may be due to CCK as a neurotransmitter.
• Secretin:
  • Stimulus for Release: Acid in the small intestine.
  • Primary Target: Pancreas, stomach.
  • Primary Effect: Stimulates HCO3- secretion; Inhibits gastric emptying and acid secretion.
• Motilin:
  • Stimulus for Release: Fasting: periodic release every 1.5-2 hours.
  • Primary Target: Gastric and intestinal smooth muscle.
  • Primary Effect: Stimulates migrating motor complex.
  • Other Information: Inhibited by eating a meal.
• Gastric Inhibitory Peptide (GIP):
  • Stimulus for Release: Glucose, fatty acids, and amino acids in the small intestine.
  • Primary Target: Beta cells of pancreas.
  • Primary Effect: Stimulates insulin release (feedforward mechanism); Inhibits gastric emptying and acid secretion.
• Glucagon-like Peptide-1 (GLP-1):
  • Stimulus for Release: Mixed meal that includes carbohydrates or fats in the lumen.
  • Primary Target: Endocrine pancreas.
  • Primary Effect: Stimulates insulin release; Inhibits glucagon release and gastric function.
  • Other Information: Promotes satiety.

Insulin as Dominant Hormone

• System Overview:
  • Stimulus: Eat a meal + Plasma glucose, amino acids
  • Sensor: Stretch receptors (Distension of GI tract wall), Endocrine cells of small intestine (Presence of carbohydrates in GI lumen)
  • Input signal: Sensory Neuron Input, GLP-1 and GIP
  • Integrating center: CNS, Beta cells of Pancreas
  • Output Signal: Parasympathetic Ouput, Insulin
  • Target: Liver, a cells of pancreas, Muscle, adipose, and other cells
  • Tissue response: Glycolysis, Glycogenesis, Lipogenesis, Protein synthesis, Glucose transport, Plasma Glucose is decreased
  • Systemic Response: Negative feedback

Semaglutide (Ozempic/Wegovy)

• Semaglutide is a GLP-1 agonist used to help manage diabetes and obesity.