# Lecture 15: Digestion and Absorption — Lower GI and Accessory Organs
## Anatomy and Physiology II
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## Learning Objectives
By the end of this lecture, students will be able to:
1. Describe the anatomy and function of the liver and gallbladder
2. Explain bile production, composition, and the enterohepatic circulation
3. Describe the anatomy and function of the pancreas (exocrine)
4. Describe the anatomy, histology, and functions of the large intestine
5. Explain the processes of defecation and the defecation reflex
6. Discuss common clinical disorders of the digestive system
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## Lecture Content
### I. The Liver
The liver is the largest internal organ, weighing approximately 1.5 kg and located in the right upper quadrant beneath the diaphragm. It has four lobes: the right (largest), left, caudate, and quadrate. The liver receives a dual blood supply. The **hepatic artery** delivers oxygenated blood from the aorta, accounting for about 25% of the liver's blood supply. The **hepatic portal vein** delivers nutrient-rich, deoxygenated blood from the GI tract, spleen, and pancreas, accounting for the remaining 75%. Blood exits the liver via the hepatic veins, which drain into the inferior vena cava.
#### Liver Lobule — Structural and Functional Unit
The liver lobule is a hexagonal unit centered around a **central vein**. At each corner sits a **portal triad** (hepatic triad) containing a branch of the hepatic artery, a branch of the hepatic portal vein, and a bile duct. **Hepatocytes** (liver cells) are arranged in radiating plates that extend from the central vein like spokes of a wheel. Between the hepatocyte plates lie **sinusoids**, modified capillaries through which blood flows from the portal triads toward the central vein. These sinusoids are lined with fenestrated endothelium and **Kupffer cells**, the liver's resident macrophages. **Bile canaliculi** are tiny channels between adjacent hepatocytes that collect bile and carry it in the opposite direction from blood flow: from the hepatocytes outward toward bile ductules, then to bile ducts, then to the right and left hepatic ducts, and finally to the common hepatic duct.
#### Functions of the Liver
The liver performs an extraordinary range of functions. It produces 500 to 1,000 mL of bile per day. It metabolically processes nutrients, carrying out glucose metabolism (glycogenesis, glycogenolysis, and gluconeogenesis), lipid metabolism, and amino acid metabolism (deamination, transamination, and urea synthesis). It synthesizes plasma proteins including albumin, fibrinogen, clotting factors, and transport proteins. It detoxifies drugs, alcohol, and ammonia (converting the latter to urea) and conjugates bilirubin for excretion. It stores glycogen, fat-soluble vitamins (A, D, E, and K), vitamin B12, and iron (as ferritin). Its Kupffer cells provide immune defense by phagocytizing pathogens in portal blood. It also performs the 25-hydroxylation step in vitamin D activation, with the kidney completing the final 1-hydroxylation.
### II. Bile and the Gallbladder
#### Bile Composition
Bile is a yellow-green alkaline solution whose primary digestive component is **bile salts** (bile acids), derived from cholesterol. Bile salts are amphipathic molecules that emulsify fats, breaking large globules into smaller droplets to increase the surface area available for lipase action. They also form micelles with lipid digestion products to facilitate absorption. Bile additionally contains **bilirubin**, the waste product of hemoglobin breakdown that gives bile its characteristic color, along with cholesterol, phospholipids, electrolytes, and water. Importantly, bile contains no digestive enzymes.
#### Gallbladder
The gallbladder is a small, pear-shaped sac on the inferior surface of the liver that stores and concentrates bile up to 10-fold by absorbing water and ions. The **cystic duct** connects the gallbladder to the common hepatic duct, forming the **common bile duct**. The common bile duct joins the main pancreatic duct at the **hepatopancreatic ampulla (ampulla of Vater)**, controlled by the **sphincter of Oddi**. Between meals, the sphincter of Oddi is closed, causing bile to back up into the gallbladder for storage. After a fatty meal, CCK causes the gallbladder to contract and the sphincter of Oddi to relax, releasing bile into the duodenum.
#### Enterohepatic Circulation of Bile Salts
After bile salts are secreted into the duodenum and aid in fat digestion and absorption, approximately 95% are reabsorbed in the ileum by active transport. They return to the liver via the hepatic portal vein and are recycled back into bile, a pathway known as the enterohepatic circulation. Each bile salt molecule is recycled 6 to 8 times per day, and only about 5% is lost in feces and replaced by new synthesis from cholesterol in the liver.
A diagram of liver microanatomy and bile flow. Panel A: A liver lobule viewed from above showing the hexagonal arrangement — the central vein in the middle, hepatocyte plates radiating outward like spokes, sinusoids between the plates with blood flow arrows pointing from the portal triads at the corners toward the central vein, Kupffer cells lining the sinusoids, and bile canaliculi between adjacent hepatocytes with bile flow arrows pointing outward from the central vein toward the portal triads (opposite to blood flow). A portal triad is enlarged showing the hepatic artery branch, portal vein branch, and bile duct. Panel B: The biliary system — right and left hepatic ducts joining to form the common hepatic duct, the cystic duct connecting to the gallbladder, the common bile duct descending to join the main pancreatic duct at the ampulla of Vater, entering the duodenum at the major duodenal papilla, with the sphincter of Oddi labeled. Panel C: A circular diagram of the enterohepatic circulation of bile salts — liver produces bile → bile stored in gallbladder → released into duodenum → bile salts emulsify fats → reabsorbed in ileum → returned via hepatic portal vein to liver → recycled.
### III. The Pancreas (Exocrine Function)
The pancreas is a retroperitoneal organ extending from the duodenal C-loop to the spleen, divided into head, body, and tail regions. It serves both exocrine (approximately 99% of tissue) and endocrine (approximately 1%, the islets of Langerhans) functions.
#### Exocrine Pancreas
**Acinar cells**, arranged in clusters called acini, produce pancreatic digestive enzymes. Most proteolytic enzymes are secreted as inactive zymogens to prevent self-digestion. **Trypsinogen** is activated to trypsin by enterokinase in the duodenum, and trypsin then activates chymotrypsinogen to **chymotrypsin**, procarboxypeptidase to **carboxypeptidase**, and proelastase to **elastase**. Active enzymes secreted directly include **pancreatic amylase** for starch digestion, **pancreatic lipase** (with colipase) for triglyceride digestion, and **nucleases** (DNase and RNase) for nucleic acid digestion. **Duct cells** line the pancreatic ducts and secrete a bicarbonate-rich fluid that neutralizes acidic chyme from the stomach, raising duodenal pH to the 6 to 8 range optimal for pancreatic enzyme activity. Altogether, the pancreas produces 1.2 to 1.5 liters of pancreatic juice per day.
#### Regulation of Pancreatic Secretion
**Secretin**, released by duodenal S cells in response to acid, stimulates duct cells to secrete bicarbonate-rich fluid. **CCK**, released by duodenal I cells in response to fats and proteins, stimulates acinar cells to secrete enzyme-rich juice and also triggers gallbladder contraction. The **vagus nerve** (parasympathetic) stimulates both enzyme and bicarbonate secretion. A **trypsin inhibitor** in pancreatic juice prevents premature trypsin activation within the pancreatic ducts. **Pancreatitis**, inflammation of the pancreas, often results from premature activation of pancreatic enzymes within the organ, leading to autodigestion.
### IV. The Large Intestine
#### Anatomy
The large intestine is approximately 1.5 meters long and 6.5 cm in diameter, extending from the ileocecal valve to the anus. It begins with the **cecum**, a blind-ended pouch below the ileocecal valve, from which the **vermiform appendix** extends. The **colon** has four segments: the ascending colon (right side, retroperitoneal), transverse colon (crossing the abdomen, intraperitoneal), descending colon (left side, retroperitoneal), and sigmoid colon (S-shaped, in the left lower quadrant, intraperitoneal). The **rectum**, the last 15 cm, stores feces. The **anal canal**, the final 2 to 3 cm, contains the internal anal sphincter (smooth muscle, involuntary) and external anal sphincter (skeletal muscle, voluntary).
#### Unique Structural Features
The large intestine has several distinctive features. **Teniae coli** are three bands of longitudinal muscle running along the colon. **Haustra** are pouch-like sacculations formed by the tone of the teniae coli. **Epiploic (omental) appendages** are fat-filled pouches of visceral peritoneum on the colon surface. Unlike the small intestine, the large intestine has no villi. Its mucosa is flat with abundant goblet cells and deep crypts (intestinal glands) that secrete mucus to lubricate the passage of feces.
#### Functions of the Large Intestine
The large intestine absorbs about 0.9 liters of water per day, solidifying the feces, along with electrolytes (sodium via active transport, chloride, and bicarbonate) and some vitamins produced by gut bacteria (vitamin K, biotin, and B vitamins). Trillions of bacteria comprising the gut microbiota ferment indigestible carbohydrates (fiber) into short-chain fatty acids (SCFAs) that nourish colonocytes, produce vitamins K and B, generate gases (CO2, H2, and methane), and synthesize beneficial metabolites that maintain immune homeostasis. The large intestine also stores and compacts feces and secretes mucus for lubrication.
#### Motility of the Large Intestine
**Haustral contractions** are slow segmental movements that mix contents and promote water absorption. **Mass movements** (mass peristalsis), occurring 3 to 4 times per day, are strong peristaltic waves that move fecal material long distances toward the rectum, often stimulated by eating via the gastrocolic and gastroileal reflexes. Regular peristalsis is slower and less frequent than in the small intestine. Transit time through the large intestine is 12 to 36 hours.
### V. Defecation
The **defecation reflex** is initiated when feces enter the rectum and distend the rectal wall, stimulating stretch receptors. Signals travel to the sacral spinal cord (segments S2 to S4), and parasympathetic signals increase rectal contractions and relax the internal anal sphincter (involuntary). If conditions are appropriate, voluntary relaxation of the external anal sphincter allows feces to pass. The process is assisted by the Valsalva maneuver, in which contraction of the abdominal muscles increases intra-abdominal pressure. If defecation is delayed, the reflex subsides until the next mass movement delivers more feces to the rectum.
### VI. Feces Composition
Feces are approximately 75% water and 25% solid matter, which consists of bacteria (both dead and living), indigestible fiber (cellulose), fat, inorganic matter, sloughed epithelial cells, and bilirubin metabolites (stercobilin gives feces their brown color).
### VII. Clinical Correlations
**Gallstones (cholelithiasis)** are crystallized deposits of cholesterol or bilirubin in the gallbladder that can obstruct the cystic duct or common bile duct, causing biliary colic, jaundice, or pancreatitis. **Peptic ulcer disease** involves erosion of the mucosal lining of the stomach or duodenum, most commonly caused by Helicobacter pylori infection or chronic NSAID use, and is treated with proton pump inhibitors (PPIs) and antibiotics for H. pylori. **GERD** (gastroesophageal reflux disease) is chronic reflux of gastric acid into the esophagus due to LES incompetence, which can lead to Barrett's esophagus (metaplasia). **Inflammatory bowel disease (IBD)** includes Crohn's disease, which causes transmural inflammation that can affect any part of the GI tract (often the terminal ileum), and ulcerative colitis, which causes mucosal inflammation limited to the colon and rectum. **Celiac disease** is an autoimmune reaction to gluten (gliadin protein) that causes villous atrophy in the small intestine and malabsorption. **Colorectal cancer**, the third most common cancer, often arises from adenomatous polyps. **Constipation** involves infrequent or difficult defecation with excessively hard feces, while **diarrhea** involves frequent, watery stools from impaired water absorption or excessive secretion. **Hepatitis** is inflammation of the liver (viral, alcoholic, or autoimmune), and **cirrhosis** is chronic liver damage leading to fibrosis and impaired liver function.
An overview diagram of the large intestine and accessory organ connections. Panel A: The complete large intestine in anterior view showing the cecum with appendix, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, rectum, and anal canal with internal and external sphincters. The teniae coli, haustra, and epiploic appendages are labeled. The ileocecal valve at the junction with the ileum is shown. Panel B: A magnified cross-section of the colon wall showing the lack of villi, flat mucosal surface with deep crypts packed with goblet cells, the submucosa, muscularis externa (with the teniae coli as concentrations of the longitudinal layer), and serosa. Panel C: A histological comparison between small intestine mucosa (with tall villi and scattered goblet cells) and large intestine mucosa (flat surface with deep crypts densely lined with goblet cells) side by side.
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