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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.