Pancreas and Bile Function

Pancreas

• Located retroperitoneally, deep to the stomach's greater curvature, with its head encircled by the duodenum and tail near the spleen.
• Exocrine function: secretes pancreatic juice via ducts. Acini are clusters of secretory cells producing zymogen granules containing proenzymes (inactive digestive enzymes).
• Endocrine function: secretes insulin and glucagon via pancreatic islet cells.
• Pancreatic juice composition: watery, alkaline solution (pH 8) to neutralize acidic chyme. Contains electrolytes (primarily bicarbonate) and digestive enzymes (proteases [for proteins], amylase [for carbohydrates], lipases [for lipids], nucleases [for nucleic acids]). Proteases are secreted in inactive form to prevent self-digestion.

Bile & Pancreatic Secretion

• Bile and pancreatic ducts unite in the hepatopancreatic ampulla in the duodenum.
• The ampulla opens into the duodenum via a major duodenal papilla.
• Hepatopancreatic sphincter controls the entry of bile and pancreatic juice into the duodenum.
• Regulation: Neural and hormonal controls stimulate bile and pancreatic juice secretion. Hormonal controls include cholecystokinin (CCK) and secretin. Bile secretion increases with: enterohepatic circulation returning large amounts of bile salts; duodenal mucosa secreting secretin in response to acidic chyme; and duodenal mucosa secreting CCK in response to fatty chyme. The hepatopancreatic sphincter is closed unless active digestion occurs. Bile is stored in the gallbladder and released to the small intestine only with contraction.

Relationship: Liver, Gallbladder, & Pancreas

• The liver's right and left hepatic ducts combine into a common hepatic duct.
• The common hepatic duct joins the bile duct and the Pancreatic duct in the hepatopancreatic ampulla, which is in the duodenum.
• A major duodenal papilla is the opening to the duodenum.

Small Intestine

• Major organ of digestion and absorption, extending 7-13 ft from the pyloric sphincter to the ileocecal valve.
• Subdivisions:
  • Duodenum (~10 inches): mostly retroperitoneal, curves around pancreas.
  • Jejunum (~8 feet): attached posteriorly by mesentery.
  • Ileum (~12 feet): attached posteriorly by mesentery, joins large intestine at ileocecal valve.
• Structural modifications for absorption: greatly increased surface area (approximately 200 m2) via circular folds, villi, and microvilli. Circular folds are permanent folds that slow chyme. Villi are fingerlike projections with a capillary bed and lacteal. Microvilli form the brush border containing brush border enzymes for final digestion.

Microscopic Anatomy Small Intestine

• Intestinal crypts: tubular glands between villi.
• Cell types:
  • Enterocytes: absorb nutrients and electrolytes; contain brush border enzymes.
  • Goblet cells: secrete mucus.
  • Enteroendocrine cells: source of enterogastrones.
  • Paneth cells: secrete antimicrobial agents.
• MALT (mucosa-associated lymphoid tissue) protects against microorganisms. Peyer's patches in ileum extend into submucosa.
• Submucosa contains areolar tissue and duodenal glands in the duodenum, secreting alkaline mucus to neutralize acidic chyme.

Clinical View - Cancer Treatments

• Cancer treatments targeting rapidly dividing cells (e.g., radiation and chemotherapy) can cause nausea, vomiting, and diarrhea as a side effect due to targeting the GI tract epithelium.

Intestinal Juice

• 1-2 L secreted daily in response to distension or irritation of the mucosa. Hypertonic or acidic chyme is the major stimulus. Slightly alkaline and isotonic with blood plasma. Consists largely of water and mucus, secreted by duodenal glands and goblet cells.

Digestive Processes in Small Intestine

• Chyme contains partly digested carbohydrates, proteins, and undigested fats. Takes 3-6 hours to absorb nutrients and water.
• Enzymes from liver and pancreas aid in digestion, and brush border enzymes complete the process.
• Chyme is hypertonic, so slow delivery prevents water loss. Chyme's pH is adjusted, and it's mixed with bile and pancreatic juice. Enterogastric reflex and hormones control chyme entry.
• Motility: Segmentation (mechanical breakdown) is common after a meal, mixing chyme with enzymes and bile. Between meals, peristaltic waves (propulsion) move remnants every 90-120 minutes towards the large intestine. Ileum and ileocecal valve control passage into the large intestine.

Large Intestine

• Unique features include taenia coli (3 bands of longitudinal smooth muscle) and haustra (pocketlike sacs).
• Subdivisions: cecum, appendix (lymphoid tissue), colon (ascending, transverse, descending, sigmoid), rectum, and anal canal. The anal canal has an internal and external anal sphincter. Superficial venous plexuses can form hemorrhoids if inflamed. Rectal valves prevent feces from being passed with gas.

Appendix

• Contains masses of lymphoid tissue (part of MALT).
• A bacterial storehouse.
• Twisted shape can be susceptible to blockages.

Clinical View - Appendicitis

• Acute inflammation of the appendix often caused by blockage and trapped bacteria.
• Most common in adolescence.
• Venous drainage impairment can lead to ischemia and necrosis.
• Ruptured appendix can cause peritonitis.
• Symptoms include pain, loss of appetite, nausea, and vomiting.
• Treatment is usually surgical removal (appendectomy) or antibiotics in some cases.

Large Intestine Microscopic Anatomy

• Thicker mucosa of simple columnar epithelium, except in the anal canal (where stratified squamous epithelium is present to withstand abrasion).
• Lacks circular folds, villi, and digestive secretions. Contains abundant deep crypts with mucus-producing goblet cells.

Bacterial Flora

• Contains 1000+ types of bacteria, vastly outnumbering our own cells.
• Colonizes the colon from the small intestine or anus.
• Metabolic functions: ferment indigestible carbohydrates and mucin, producing short-chain fatty acids and gases (flatus); synthesize B complex vitamins and some vitamin K.
• Beneficial bacteria suppress pathogenic bacteria. Mounting evidence suggests gut bacteria influence body weight, mood, and susceptibility to various diseases (e.g., diabetes, atherosclerosis, fatty liver disease). Irritable bowel disease (IBD) might be due to the immune system attacking harmless bacteria. Interventions manipulating gut bacteria may become more routine.

Digestive Processes in Large Intestine

• Chyme resides 12-24 hours. No digestion occurs, except by enteric bacteria.
• Absorbs vitamins made by bacterial flora, water, and electrolytes (largely NaCl).
• Major functions are propulsion of feces to anus and defecation.
• Motility: Mass movements (slow, powerful peristalsis) 3-4 times daily. Initiated by the gastrocolic reflex and fiber intake. Descending and sigmoid colon act as storage.
• Defecation reflex initiates with mass movement: parasympathetic signals initiate actions. Relaxation of internal sphincter and voluntary relaxation of external sphincter follow. Valsalva's maneuver aids. Infants have involuntary defecation.

Clinical View – Stool Imbalances

• Diarrhea: watery stools due to insufficient water absorption in the large intestine (occurs due to colon irritation or physical forces). Prolonged diarrhea can lead to dehydration and electrolyte imbalances.
• Constipation: hardened stools due to extended colon residence and excessive water absorption (caused by insufficient fiber/fluid, improper habits, lack of exercise, or anesthesia).

Mechanisms of Digestion & Absorption

• Digestion breaks ingested foods into absorbable building blocks.
• Enzymes carry out hydrolysis to break chemical bonds. Absorption moves substances into the body. Tight junctions force molecules through epithelial cells (not between). Lipid molecules can passively absorb; other substances need transport proteins. Nutrients are mainly absorbed via active transport.

Digestion of Carbohydrates

• Only monosaccharides are absorbed.
• Starch and disaccharides are broken down to oligosaccharides and disaccharides (begins with salivary amylase). Further broken down (lactose, maltose, sucrose) to monosaccharides (glucose, fructose, galactose).
• In the intestine: pancreatic amylase breaks down starch or glycogen; brush border enzymes further break resulting molecules into monosaccharides.

Digestion of Proteins

• Proteins are broken down into large polypeptides, then smaller peptides into amino acids (some dipeptides and tripeptides).
• Digestion begins in the stomach with pepsinogen converting to pepsin (active at pH 1.5–2.5, inactive at higher pH in the duodenum).
• Pancreatic proteases and brush border enzymes further break down proteins and peptides to amino acids.

Digestion of Lipids

• Emulsification: bile salts break large fat globules into smaller ones.
• Digestion: pancreatic lipases break triglycerides into fatty acids and monoglycerides.
• Micelle formation: digested lipid products coat with bile salts, making them absorbable. Micelles are essential to access lipid surfaces and absorb them.
• Diffusion: Lipid products move from micelles to the epithelial membrane via diffusion. Lipids are converted back to triglycerides and enter lymphatic lacteals. Short-chain fatty acids directly enter the blood.

Digestion of Nucleic Acids

• Pancreatic nucleases hydrolyze DNA and RNA to nucleotides.
• Brush border enzymes further break nucleotides into free nitrogenous bases, pentose sugars, and phosphate ions.

Clinical View - Absorption Inbalances

• Lactose intolerance: deficient lactase enzyme causes undigested lactose, an osmotic gradient, diarrhea, gas, bloating, and cramps. Treatment involves lactase supplements.
• Malabsorption: impaired nutrient absorption due to damage to the intestinal mucosa (infection, antibiotics, celiac disease). Celiac disease is an immune reaction to gluten harming intestinal villi. Treatment involves a gluten-free diet.

Absorption of Vitamins, Electrolytes, & Water

• Fat-soluble vitamins (A, D, E, K) are absorbed by diffusion with micelles. Water-soluble vitamins (C, B) are absorbed via passive or active transport. Vitamin B12 requires intrinsic factor for absorption by endocytosis.
• Electrolyte absorption: most ions are actively transported along the small intestine (with exceptions of iron and calcium absorption related to need). Iron stores in mucosal cells (ferritin). Calcium absorption regulated by vitamin D and PTH -- PTH stimulates vitamin D activation for calcium absorption.
• Water absorption: 9 L water enters small intestine. 95% absorbed in the small intestine and rest in large intestine by osmosis coupled with solute uptake.

Developmental Aspects of Digestive System

• Alimentary canal forms by week 5.
• Fetal nutrition is via placenta, but amniotic fluid stimulates GI tract maturation.
• Infants progress to solid foods and an adult diet by 2 years.
• GI activity declines in aging with reduced digestive juice, decreased absorption, slowed peristalsis, less frequent bowel movements. Taste/smell becomes less acute, and periodontal diseases develop. Fecal incontinence and GI cancers are more common. Most GI cancers are treatable early. Screenings (e.g., for colorectal cancer) and prevention through regular examinations are important.