The Digestive System

• The digestive system consists of the digestive tract and associated glands
• The digestive tract is also referred to as the gastrointestinal (GI) tract or alimentary canal

Digestive Tract

• Oral cavity
• Esophagus
• Stomach
• Small intestine
• Large intestine
• Anal canal

Associated Glands

• Salivary glands
• Liver
• Pancreas

Gastrointestinal Tract Structures

• Structures within the digestive tract facilitate various processes
• These include ingestion, mastication, motility, secretion, hormone release, chemical digestion, absorption, and elimination

General Structure of the Digestive Tract

• The GI tract has four main layers: mucosa, submucosa, muscularis, and serosa

Mucosa

• Innermost layer
• Consists of the Lamina propria with loose connective tissue
• Has the Muscularis mucosae, a thin layer of smooth muscle separating it from the submucosa

Submucosa

• Contains dense connective tissue
• Contains submucosal (Meissner's) plexus of autonomic nerves

Muscularis

• Consists of smooth muscle cells
• Contains myenteric (Auerbach) nerve plexus
• Coordinates contractions for mixing and propelling luminal contents
• The Auerbach plexus is named after Leopold Auerbach

Serosa

• Outermost layer
• In the GI tract, the muscularis propria contains smooth muscle cells organized into a tightly coiled, inner circular layer and outer longitudinal layer
• It is continuous with portions of the mesentery in the small and large intestines
• The stomach, small intestine, and large intestine are suspended by mesenteries

Oral Cavity

• The oral cavity has stratified squamous epithelium, keratinized depending on the location
• Keratinized cell layers resist damage from abrasion
• There is increased amount of keratinized cells in the masticatory mucosa on the gingiva and hard palate

Lips or Labia

• Contains well-developed striated muscle, making it highly mobile for ingestion, speech, and other forms of communication

Tongue

• Manipulates ingested material during mastication and swallowing

Lingual Papillae

• Four types exist
• Filiform papillae: heavily keratinized, covering most of the tongue's top surface
• Fungiform papillae
• Foliate papillae: ridge-like on the sides and best developed in young children
• Vallate (or circumvallate) papillae: largest papillae, with 8 to 12 aligned in front of the terminal sulcus

Taste Buds

• Taste buds sample the general chemical composition of ingested food
• Ovoid structures mostly found on the sides of fungiform and circumvallate papillae

Teeth

• Adults have 32 permanent teeth
• Each quadrant contains eight teeth: two incisors, one canine, two premolars, and three permanent molars
• The crown is covered by hard, acellular enamel called cementum
• The bulk of a tooth is composed of calcified material called dentin
• The dental pulp is highly vascular and well-innervated

Clinical Applications - Oral Cavity, Esophagus

• Pharyngitis and Tonsillitis are caused by Streptococcus pyogenes
• Oral thrush is caused by a yeast (Candida albicans) infection
• Oral thrush usually affects neonates or immunocompromised patients

Esophagus

• A muscular tube approximately 25 cm long
• Transports swallowed material from the pharynx to the stomach
• Mucosa: nonkeratinized stratified squamous epithelium
• Submucosa: Small mucus-secreting glands (esophageal glands) which lubricate and protect mucosa

Esophagus Muscle Fibers

• Unlike other parts of the GI tract, it contains two types of muscle fibers: striated and smooth
• It lacks a serosa, instead has a thick adventitia and is bound directly to adjacent structures

Clinical Applications - Esophagus

• Heartburn or reflux esophagitis: results from the movement of acid from the stomach to the esophagus
• Gastroesophageal reflux disease (GERD): erosion of the esophageal mucosa secondary to prolonged untreated reflux esophagitis

Stomach

• Continues the digestion of carbohydrates initiated by salivary amylase
• Adds an acidic fluid to ingested food, mixing it into a viscous mass called chyme
• Begins digestion of triglycerides by a secreted lipase
• Promotes the initial digestion of proteins with the enzyme pepsin

Major regions of the Stomach

• Cardia and Pylorus are primarily involved with mucus production
• Fundus and Body are the sites of gastric glands releasing acidic gastric juice
• The mucosa and submucosa of the empty stomach have large, longitudinally directed folds called rugae, which flatten when the stomach fills with food

Stomach Mucosa

• The cardiac and pyloric mucosa contains mucous glands (cardiac and pyloric glands) that secrete mucus
• This coats the stomach and protects it from self-digestion by helping to dilute acids and enzymes

Fundus and Body of the Stomach

• The mucosal epithelial surface is penetrated by numerous microscopic indentations: gastric pits
• The gastric pits contain gastric glands with parietal cells, chief cells, mucous neck cells, and G cells

Stomach Cells

• Mucous neck cells produce less alkaline mucus
• Parietal (oxyntic) cells produce hydrochloric acid (HCl) and secrete intrinsic factor for uptake of vitamin B12
• Chief (zymogenic) cells secrete pepsinogen (activated by low pH to form pepsin) and gastric lipase
• G (Enteroendocrine) cells release peptide hormones to regulate activities of neighboring tissues during food digestion

Clinical Application: Stomach

• Damaged parietal cells lead to insufficient intrinsic factor, causing non-absorption of vitamin B12, resulting in pernicious anemia
• Gastric and duodenal ulcers are caused by bacterial infections with Helicobacter pylori and effects of nonsteroidal anti-inflammatory drugs

Small Intestine

• Main site where digestive processes are completed and nutrients are absorbed
• Approximately 5 meters in length and consists of the duodenum, jejunum, and ileum

Duodenum

• The first portion of the small intestine
• Extends approximately 25 to 30 cm from the pyloric sphincter

Jejunum and Ileum

• Located between the duodenum and ileocecal sphincter
• 1/3 being the jejunum and the rest being the ileum
• The mucosa is lined by circular or semilunar folds (plicae circulares)
• Short outgrowths called villi extend densely into the lumen

Microvillus

• 1.5-2 µm in length and 100 nm in diameter

Intestinal Glands

• The openings of short tubular intestinal glands (crypts of Lieberkühn) are found between the villi
• Secrete ions, water, IgA, antimicrobial peptides into the lumen

Intestinal Gland Cells

• Enterocytes: absorptive cells
• Goblet cells: Protect and lubricate the lining of the intestine; secrete mucus, ions, and water; most numerous in the lower ileum

Paneth Cells

• Release defensins for innate immunity of the intestine and secrete antimicrobial agents

Submucosa - Small Intestine

• Submucosal (Meissner) nerve plexus controls secretion and blood flow
• Duodenal (or Brunner) glands secrete alkaline mucus, neutralizing chyme from the pylorus

Peyer Patches

• Large lymphoid nodule aggregates
• Contained in a well-developed Mucosa-Associated Lymphoid Tissue (MALT) in the ileum

Mucosa Associated Lymphoid Tissue (MALT)

• Large aggregates of lymphoid tissue (containing lymph nodules) in mucous membranes of digestive, respiratory, and genitourinary tracts

Muscularis Small Intestine

• Myenteric (Auerbach) nerve plexus controls motility

Clinical Applications: Small Intestine

• Leiomyoma: benign tumors of smooth muscle cells in the stomach and small intestine
• Celiac disease (celiac sprue): Inflammation of the small intestine mucosa that causes malabsorption and can lead to damage or destruction of the villi, affecting the enterocytes

Large Intestine

• Approximately 1.5 m in length with three major regions: cecum, colon and rectum
• The Colon contains the ascending, transverse, descending and sigmoid segments

Cecum

• Is a major region of the large intestine
• Contains the appendix

Wall structure of the Colon

• The wall of the colon is puckered into a series of large sacs called haustra

Mucosa of the large intestine

• Has millions of tubular intestinal glands, lined by lubricant goblet cells and absorptive cells (colonocytes) for the uptake of water and electrolytes

Longitudinal Layer Contractions

• This is subdivided into three bands of smooth muscle called teniae coli
• Teniae Coli act in the peristaltic movement of feces to the rectum

Muscularis

• Inner Circular Layer - smooth muscle
• Auerbach's Plexus - provides motor innervation of the muscularis externa
• Outer Longitudinal Layer - smooth muscle with Teniae coli

Anal Canal

• The simple columnar epithelium lining the rectum shifts to stratified squamous epithelium of the anal canal

Clinical Application: Large Intestine

• Crohn disease: chronic inflammatory bowel disease of the colon causing: pain, localized bleeding, malabsorption, and diarrhea
• Hemorrhoid: swollen blood vessels in the mucosa or submucosa of the anal canal, due to: constipation, prolonged sitting, or straining at defecation
• Colorectal cancer: is an adenocarcinoma that develops from adenomatous polyps in the mucosal epithelium, and occurs in individuals with low-fiber diets

Liver

• All nutrients absorbed in the intestines enter through the hepatic portal vein
• Complex lipid products are transported by lymph vessels, not blood
• Hepatic artery supplies liver cells with oxygenated blood, forming a dual blood supply

Liver Structure

• Exhibits repeating hexagonal units called the Hepatic Lobules
• Has 3-6 portal areas per lobule in humans
• Each unit has a central vein, from which radiate plates of liver cells called hepatocytes, and sinusoids toward the periphery

Blood Flow

• Venous and arterial blood from peripheral portal areas first mix in the liver sinusoids as it flows toward the central vein
• From here, blood enters the general circulation through the hepatic veins that leave the liver and enter the inferior vena cava

Hepatic Sinusoids

• Tortuous, dilated blood channels lined by a discontinuous layer of fenestrated endothelial cells with fenestrations and discontinuous basal lamina
• Separated from underlying hepatocytes by a subendothelial perisinusoidal space of Disse

Sinusoid Structure

• The tortuous structure allows for efficient exchange of materials between hepatocytes and blood

Hepatic Sinusoid Cells

• Contain macrophages called Kupffer cells on the luminal side of endothelial cells

Hepatocytes

• Secrete bile into tiny channels called bile canaliculi between individual hepatocytes

Hepatic Lobule Microvasculature

• The lobule's central vein is a venule consisting of little more than an endothelial tube with smaller sinusoids coming in from all directions

Hepatic lobule arterial inflow

• Peripheral portal areas are a portal venule, an arteriole branching off the hepatic artery, and one or two branches of the bile duct

Hepatic lobule connective tissue

• Reticulin (collagen type III) fibers running along the plates of hepatocytes are the major support for the sinusoids and central venules

Liver Regeneration

• Loss of hepatic tissue triggers a mechanism where remaining healthy hepatocytes divide in a process of compensatory hyperplasia
• Surgical removal of a liver portion produces a similar response in remaining hepatocytes

Liver regeneration success

• The regenerated liver tissue is usually well organized, replaces functions of destroyed tissue and the human liver can be donated by living donors

Liver Stem Cells

• Stem cells in the initial epithelium of bile ductules near the portal areas
• These can give rise to both hepatocytes and cholangiocytes

Alcohol and Liver Damage

• Alcohol alters hepatic regeneration, favoring the development of cirrhosis
• This is because ethanol is metabolized primarily in the liver

Gallbladder

• Stores and concentrates bile that flows from the liver's hepatocytes via the cystic duct

Duodenal Bile transport

• Bile enters via the common bile duct through the major duodenal papilla
• It absorbs water, stores, then concentrates bile

Clinical Application: Gallbladder and Bile

• Malignant liver tumors derive from hepatocytes or cholangiocytes of the hepatic ducts and their pathogenesis are associated with chronic viral hepatitis
• The exocrine pancreas results in tumors from duct epithelial cells

Pancreas

• A mixed exocrine-endocrine gland, the pancreas produces both digestive enzymes and hormones

Thin Capsule

• A thin capsule of connective tissue covers the pancreas and sends septa into it, separating pancreatic lobules
• The secretory acini are surrounded by a basal lamina supported by a delicate sheath of reticular fibers and a rich capillary network

Exocrine Pancreas

• Most of the pancreas is this

Acini

• Exocrine secretory units in pyramid-shaped acinar cells

Granules

• Granules contain precursors of pancreatic digestive enzymes secreted into excretory ducts

Centroacinar Cells

• Excretory ducts start with pale-staining centroacinar cells, becoming intercalated ducts and then intralobular ducts

Endocrine Pancreas

• Units are scattered among the exocrine acini as isolated, pale-staining vascularized units called pancreatic islets of Langerhans

Pancreatic Islet Tissues

• alpha, beta, delta and pancreatic polypeptide fine fibers of reticular connective tissue that surround each islet

Endocrine Pancreas Cell Types

• Alpha: constitute about 20% of the islets and are around the islet periphery
• Beta: comprise 70% of the cells, concentrated in the islet center

Acinar Cell influence

• Each exocrine acinus of the pancreas is composed of several serous cells surrounding a very small lumen
• The acinar cells are highly polarized, with a spherical nucleus, and are typical protein-secreting cells

Pancreatic Excretion Composition

• Pancreatic secretion is controlled mainly through secretin, cholecystokinin (CCK), and the vagus nerve

CCK Influence

• CCK promotes the exocytosis of zymogens and enzymes from the pancreatic acinar cells Acid and partially digested food in the gastric chyme enters the duodenum and stimulates local release of CCK and secretin

Clinical Application: Pancreas

• In acute necrotizing pancreatitis, the proenzymes are activated and digest tissues, leading to complications
• Also, in extreme malnutrition such as kwashiorkor, pancreatic acinar cells and other active protein-secreting cells atrophy and lose much of their rough ER