Digestive system

Gastrointenstinal (GI) tract or alimentary canal organs

Mouth, most of pharynx, esophagus, stomach, small intestine, and large intestine

Accessory digestive organs

Teeth, tongue, salivary glands, liver, gallbladder, and pancreas

Ingestion

Taking in foods and liquids

Secretion

Of water, acid, buffers, and enzymes into lumen

Digestion

Mechanical digestion churns food
Chemical digestion - hydrolysis

Absorption

Entrance of ingested and secreted liquids, ions, and digestive products into blood or lymph

Defecation

Elimination of feces

Digestive tract description

- Long muscular tube
- Lined with permanent ridges and temporary folds
• Both features increase surface area for absorbing nutrients

Mesentery

- Double sheets of peritoneal membrane
• Areolar tissue lies between mesothelial layers
- Provides access route for blood vessels, nerves, and lymphatics
• Stabilizes attached organs
• Prevents entanglement of intestines

Mucosa

(inner lining)
Mucous membrane of epithelium, moistened by glandular secretions, and lamina propria of areolar tissue

Submucosa

• Layer of dense irregular connective tissue
• Contains blood vessels and lymphatic vessels
• Also contains exocrine glands in some regions
- Secrete buffers and enzymes into the digestive tract

Muscular layer

• Smooth muscle in two layers (inner circular layer; outer longitudinal layer)
• Involved in mechanical processing and movement along tract

Serosa

• Layer of visceral peritoneum along the digestive tract in the abdominal cavity
• No serosa in oral cavity, pharynx, esophagus, and rectum
- Covered instead by adventitia (sheath formed from a dense network of collagen fibers)
- Firmly attaches tract to adjacent structures

Mucosal epithelium

• Tract begins and ends with stratified squamous epithelium
• Stomach, small and large intestines are simple columnar with goblet cells

Villi

Small mucosal projections that increase surface area for absorption
- Fingerlike projections of mucosa
- Contains arteriole, venule, blood capillary, and lacteal

Lamina propria

Areolar tissue containing blood vessels, sensory nerve endings, lymphatic vessels, smooth muscle cells, lymphoid tissue, and some mucous glands

Muscularis mucosae

• Thin layer of smooth muscle cells at the bottom of the mucosal layer
• Alter shape of lumen and move the circular folds and villi

Circular folds (plicae circulares)

Permanent transverse folds in the intestinal lining
- Permanent ridges of mucosa and submucosa
- Cause chyme to spiral

Nerve plexuses

- Involved in local control of digestive activities
• Parasympathetic stimulation increases digestive muscle tone and activity
• Sympathetic stimulation decreases muscle tone and activity

Submucosal neural plexus

• Located in the submucosal layer
• Innervates the mucosa and submucosa
• Contains sensory neurons, autonomic nerve fibers

Myenteric plexus

• Network of sensory neurons and autonomic nerve fibers
• Located in the muscularis externa between the circular and longitudinal layers
• Works with the submucosal plexus to coordinate local control of digestive activity

Peritoneum

Largest serous membrane of the body

Parietal peritoneum

lines wall of cavity

Visceral peritoneum

covers some organs
• Also called serosa

peritonial cavity

opening between the two membranes in the abdomen

Major peritoneal folds

• Greater omentum, falciform ligament, lesser omentum, mesentery, and mesocolon
• Weave between viscera binding organs together

Mouth

• Oral or buccal cavity
• Formed by cheeks, hard and soft palates, and tongue
• Oral cavity proper is a space that extends from gums and teeth to fauces (opening between oral cavity and oropharynx)
• Salivary glands release saliva- Ordinarily, just enough is secreted to keep mouth and pharynx moist and clean
- When food enters mouth, secretion increases to lubricate, dissolve and begin chemical digestion
• 3 pairs of major salivary glands secrete most of the saliva
- Parotid, submandibular,- and sublingual

Saliva

- Mostly water 99.5%- 0.5% solutes
- ions, dissolved gases, urea, uric acid, mucus, immunoglobulin A, lysozyme, and salivary amylase (acts on starch)
- Not all salivary glands produce the same saliva

Salivation

- Controlled by autonomic nervous system
- Parasympathetic stimulation promotes secretion of moderate amounts of saliva
- Sympathetic stimulation decreases salivation

Mechanical digestion in the mouth

- Chewing or mastication
- Food manipulated by tongue, ground by teeth, and mixed with saliva
- Forms bolus

Chemical digestion in the mouth

- Salivary amylase secreted by salivary glands acts on starches
• Only monosaccharides can be absorbed
• Continues to act until inactivated by stomach acid- Lingual Lipase secreted by lingual glands of tongue acts on triglycerides
• Becomes activated in acidic environment of stomach

Pharynx

passes from nasal cavity to esophagus

Esophagus

- Function:
• Actively moves food and liquids to the stomach
- Structure:
• Hollow, muscular tube ~25 cm (10 in.) long and 2 cm (0.8 in.) wide
• Narrowest point at the beginning(posterior to cricoid cartilage)- Descends posterior to the trachea- Enters the abdominopelvic cavity through the esophageal hiatus (opening in the diaphragm)
• Lower esophageal sphincter (cardiac) at inferior end and normally contracted

Deglutition

• Act of swallowing
• Facilitated by secretions of saliva and mucus
• Involves mouth, pharynx, and esophagus
• Stages:
- Voluntary - bolus passed to oropharynx
- Pharyngeal - involuntary passage through pharynx into esophagus
- Esophageal - involuntary passage through esophagus to stomach
• Peristalsis pushes bolus forward

Stomach

• Serves as mixing chamber and holding reservoir
• Regions- Cardia, fundus, body, pylorus

Exocrine gland cells

- Mucous neck cells (mucus)
- Parietal cells (intrinsic factor and HCl)
- Chief cells (pepsinogen and gastric lipase)

G cell

- Endocrine cell
- Secretes gastrin

Mechanical digestion in the stomach

- Mixing waves
• Gentle, rippling peristaltic movements
• Creates chyme
• Waves of muscle contraction that propel bolus (moist compact mass of food) through digestive tract
- Circular muscle contracts behind bolus

Chemical digestion of the stomach

- Salivary amylase
• Digestion continues until inactivated by acidic gastric juice
- Lingual lipase
• Acidic gastric juice activates lingual lipase
• Digest triglycerides into fatty acids and diglycerides
- HCl• Parietal cells secrete H+ and Cl- separately but net effect is HCl
• Kills many microbes, denatures proteins
- Pepsin• Secreted by chief cells
• Secreted as inactive pepsinogen
• Digests proteins
- Gastric lipase• Splits triglycerides into fatty acids and monoglycerides
• Absorption- Small amount of nutrient absorption- Some water, ions, short chain fatty acids, certaindrugs (aspirin) and alcohol

Pancreas

• Lies posterior to greater curvature of stomach
• Pancreatic juice secreted into pancreatic duct and accessory duct to small intestine
- Pancreatic duct joins common bile duct and enters duodenum at hepatopancreatic ampulla
• Histology- 99% of cells are acini
• Exocrine
• Secrete pancreatic juice - mixture of fluid and digestive enzymes- 1% of cells are pancreatic islets (islets of Langerhans)
• Endocrine
• Secrete hormones glucagon, insulin, somatostatin, and pancreatic polypeptide

Pancreatic Juice

- 1200-1500ml daily
- Mostly water
• Sodium bicarbonate - buffers acidic stomach chyme
• Enzymes- Pancreatic amylase- Proteolytic enzymes» Trypsin (secreted as trypsinogen)» Chymotrypsin (chymotrypsinogen)» Carboxypeptidase (procarboxypeptidase)» Elastase (proelastase)- Pancreatic lipase- Ribonuclease and deoxyribonuclease

Liver

Liver is the heaviest gland of the body

Hepatocytes

- major functional cells of liver
• Wide variety of metabolic, secretory, and endocrine functions
• Secrete bile (excretory product and digestive secretion)

Bile canaliculi

- ducts between hepatocytes that collect bile
• Exit liver as common hepatic duct
• Join cystic duct from gallbladder to form common bile duct

Hepatic sinusoids

Highly permeable blood capillaries receiving oxygenated blood from hepatic artery and deoxygenated nutrient-rich blood from hepatic portal vein

Gallbladder

• Contraction of smooth muscle fibers eject contents of gall bladder into cystic duct
• Functions to store and concentrate bile produced by the liver until it is needed in the small intestine
• Absorbs water and ions to concentrate bile up to ten-fold

Role and Composition of Bile

• Hepatocytes secrete 800-1000mL of bile daily
• Bile- Mostly water, bile salts, cholesterol, lecithin, bile pigments and several ions
- Partially excretory product/ partially digestive secretion
• Bile salts play role in emulsification

Bilirubin

- principal bile pigment
- Derived from heme of recycled RBCs
- Breakdown product stercobilin gives feces brown color

Small Intestine

• Regions - duodenum 10 in., jejunum 8 ft., and ileum(11 ft.)
• Histology- Mucosa
• Absorptive cells (digest and absorb), goblet cells (mucus), intestinal glands (intestinal juice), Paneth cells (lysozyme), and enteroendocrine cells
• Abundance of MALT
- Submucosa
• Duodenal glands secrete alkaline mucus
• Peyer's patches - lymphatic tissue to help fight bacterial entry \-- Muscularis
• Circular and longitudinal muscles
- Serosa
• Completely surrounds organ except for major portion of duodenum

Microvilli

- Fingerlike projections of apical membrane of absorptive cells
- Brush border with brush border enzymes

Intestinal juice

- 1-2L daily
- Contains water and mucus, slightly alkaline
- Provides liquid medium aiding absorption

Brush border enzymes

- Inserted into plasma membrane of absorptive cells
- Some enzymatic digestion occurs at surface rather than just in lumen
- α-dextrinase, maltase, sucrase, lactase, aminopetidase, dipeptidase, nucleosidases and phosphatases

Carbohydrates

- Pancreatic amylase- α-dextrinase, sucrase, lactase, maltase in brush border
- Ends with monosaccharides which can be absorbed

Proteins

- Trypsin, chymotrypsin, carboxypeptidase, and elastase from pancreas
- Aminopeptidase and dipeptidase in brush border

Lipids

- Pancreatic lipase most important in triglyceride digestion
- Emulsification by bile salts increases surface area
• Amphipathic - hydrophobic and hydrophilic regions

Nucleic acids

- Ribonuclease and deoxyribonuclease in pancreatic juice
- Nucleosidases and phosphatases in brush border

Monosaccharides

- All dietary carbohydrates digested are absorbed
- Only indigestible cellulose and fibers left in feces
- Absorbed by facilitated diffusion or active transport into blood

Amino acids, dipetides and tripeptides

- Most absorbed as amino acid via active transport into blood
- ½ of absorbed amino acids come from proteins indigestive juice and dead mucosal cells

Lipid processing in the liver

- From absorbed chylomicrons, the liver removes the triglycerides, adds cholesterol, and alters the surface proteins
- Creates low density lipoproteins (LDLs) and very low density lipoproteins (VLDLs)
• VLDLs transport triglycerides to muscle and adipose tissue
• LDLs deliver cholesterol to peripheral tissues
• Cells extract and use the cholesterol to build membranes, hormones, and other materials
- Excess cholesterol diffuses back into the bloodstream
- High density lipoproteins (HDLs)
• Proteins released by the liver
• Absorb excess cholesterol in the bloodstream and return it to the liver
• Cholesterol used to synthesize more LDLs or VLDLs
- Also used to synthesize bile salts
Applications to health
- Indicators of potential cardiovascular problems
• Total cholesterol above 200 mg/dL• High LDL:HDL ratio- These values show:
1. High levels of cholesterol in circulation
2. Most of the cholesterol is going into the tissues and staying instead of returning to the liver-
Consequences• Excess cholesterol can accumulate as plaques in blood vessels, causing heart attacks and strokes

Absorption in the Small Intestine of Lipids

- All dietary lipids absorbed by simple diffusion
- Short-chain fatty acids go into blood for transport
- Long-chain fatty acids and monoglycerides
• Large and hydrophobic
• Bile salts form micelles to ferry them to absorptive cell surface
• Reform into triglycerides forming chylomicrons
• Leave cell by exocytosis
• Enter lacteals to eventually enter blood with protein coat of chylomicron keeping them suspended and separate

Electrolytes

- From GI secretions or food- Sodium ions (Na+) reclaimed by active transport
- Other ions also absorbed by active transport

Vitamins

- Fat-soluble vitamins A, D, E, and K absorbed by simple diffusion and transported with lipids in micelles
- Most water-soluble vitamins also absorbed by simple diffusion

Water

- 9.3L comes from ingestion (2.3L) and GI secretions (7.0L)
- Most has been absorbed (80%) by the time solids leave small intestine, remainder taken up in large intestine
- Only 100ml excreted in feces
- All water absorption by osmosis

Five major hormones regulate digestive activities

gastrin, secretin, gastric inhibitory peptide (GIP), cholecystokinin (CCK), and vasoactive intestinal peptide (VIP)
- Four of them produced by duodenum
• Duodenum coordinates gastric activity and digestive secretion according to arriving chyme characteristics

Gastrin

• Secreted by G cells in pyloric antrium and enteroendocrine cells of duodenum
• Stimulated by food presence in stomach and duodenum- Particularly for high protein content
• Increases stomach mobility and production of gastric acids and enzymes

Secretin

• Released by duodenum upon arrival of chyme
• Increases secretion of bile from liver and buffers from pancreas
• Also decreases gastric motility and secretory rates

Gastric inhibitory peptide (GIP)

• Released by duodenum when fats and carbohydrates (especially glucose) enter small intestine
• Inhibits gastric activity while increasing insulin release
• Secondary effects include stimulating duodenal glands, stimulating lipid synthesis in adipose, increased skeletal muscle glucose use

Cholecystokinin (CCK)

• Secreted by duodenum when chyme arrives- Especially high in lipids and partially digested proteins
• Increases enzyme production and secretion from pancreas
• Increases release of bile from gallbladder
• Also inhibits gastric activity and may reduce hunger sensation in CNS

Vasoactive intestinal peptide (VIP)

• Released by duodenum
• Stimulates secretion of intestinal glands, dilates regional capillaries (to absorb more nutrients), and inhibits gastric acid production

Large Intestine

• Overall function- To complete absorption, produce certain vitamins, and form and expel feces
• Regions- Cecum, colon, rectum, and anal canal
• Ileocecal sphincter between small and large intestine
• Colon divisions- Ascending, transverse, descending and sigmoid
• Opening of anal canal (anus) guarded by internal anal sphincter of smooth muscle and external anal sphincter of skeletal muscle
Histology- Mucosa - mostly absorptive and goblet cells
• Microvilli present• No circular folds or villi
- Submucosa
- Muscularis• Forms haustra - pouches
- Serosa

Mechanical digestion in large intestine

- Haustral churning
- Peristalsis
- Mass peristalsis - drives contents of colon toward rectum

Chemical digestion in the large intestine

- Final stage of digestion through bacterial action
• Ferment carbohydrates, produce some B vitamins and vitamin K- Mucus but no enzymes secreted
• Remaining water absorbed along with ions and some vitamins

Esophagitis

(esophageal inflammation)
• Usually from escaping stomach acids (gastroesophageal reflux)

Hepatitis

(liver inflammation)
• Can be caused by drugs, alcohol, or infection

Cirrhosis

replacement of hepatocytes with scar tissue

Viral hepatitis A, B, and C

virus destroys liver cells

Jaundice

skin and eyes appear yellow due to accumulation of bilirubin

Gallstones

• Crystals of insoluble minerals and salts forming when bile becomes too concentrated
• If they block cystic duct, can cause cholecystitis (chole, bile +kystis, bladder + itis, inflammation)
- Removal of gallbladder may be necessary but bile production occurs normally

Gastritis

lining inflammation

Ulcers

Peptic ulcer- (gastric enzymes and acids erode wall)
• Gastric ulcer (stomach wall)
• Duodenal ulcer (duodenum wall)
• Over 80% of ulcers caused by infection by Helicobacter pyloribacterium
• Treatment includes acid reducers (cimetidine or Tagamet) and antibiotics for H. pylori if present

Colitis

(inflammation of colon)
• Often with diarrhea or constipation
- Diarrhea from too much fluid or absorption capabilities compromised
- Constipation from excess water reabsorption due to slow-moving feces

Colorectal cancer

• Most common in those over age 50
• Diets usually include high animal fat and low fiber
• Begin as small, localized tumors (polyps)

Metabolism

All chemical reactions that occur in an organism

Catabolism

Breakdown of organic substrates in the body
- Catabolism in the cell required for:
• Converting substrates to a two-carbon molecule- Utilized by mitochondria to produce ATP

Anabolism

Synthesis of new organic molecules
- Anabolism in the cell required for:
• Replacing membranes, organelles, enzymes, and structural proteins

Cellular metabolism

Chemical reactions within cells

Metabolic turnover

• Process of continual breakdown and replacement of all cellular organic components except DNA
• Cells obtain building blocks from:- Catabolic reactions- Absorption of organic molecules from the surrounding interstitial fluids
• Both processes create an accessible source of organic substrates called a nutrient pool

Cellular catabolism (aerobic metabolism)

• Occurs in the mitochondria
• 40 percent of energy is captured- Used to convert ADP to ATP- ATP is used for anabolism and other cellular functions
• 60 percent of energy escapes as heat- Warms the interior of the cell and the surrounding tissue

Nutrient pool

Source for organic substrates (molecules)for both catabolism and anabolism

Mobilization of metabolic reserves

- Reserves are mobilized when absorption across the digestive tract is insufficient to maintain normal nutrient levels
• Liver cells break down triglycerides and glycogen- Fatty acids and glucose can be released
• Adipocytes break down triglycerides- Fatty acids can be released
• Skeletal muscle cells break down contractile proteins- Amino acids can be released

Restoration of metabolic reserves

- Reserves are stocked when absorption by the digestive tract is greater than immediate nutrient needs
• Liver cells store triglycerides and glycogen
• Adipocytes convert excess fatty acids to triglycerides
• Skeletal muscles build glycogen reserves and use amino acids to increase numbers of myofibrils

Utilization of resources

- Cells in most tissues continuously absorb and catabolize glucose
- Neural tissue must have a continuous supply of glucose
• During starvation, other tissues can shift to fatty acid or amino acid catabolism- Conserves body's glucose for neural tissue

Catabolic and anabolic pathways

- Cells must synthesize some organic molecules
• Insufficient nutrients from nutrient pool and diet
• Nutrients are often used to create 2-carbon chains for mitochondrial ATP production- Oxygen required must be continuously provided by diffusion from ECF- CO2 produced must diffuse out of cell to ECF
- Glucose dynamics
• Can be stored as glycogen through glycogenesis
• Can be created from:- Glycogen digestion (glycogenolysis)- Smaller carbon chains (gluconeogenesis)
• Can be broken down into two 3-carbon chains(glycolysis) for use in ATP production
- Fatty acid dynamics
• Can be stored as triglycerides
• Can be created from:- Breakdown of triglycerides
• Can be broken down, releasing acetyl-CoA- Part of ATP production starting in the citric acid cycle
- Amino acid dynamics
• Can be stored as proteins
• Can be created from:- 3-carbon chains- Protein catabolism (only during starvation)
• In starvation, can be converted to 2-carbon chains for ATP production

Citric acid cycle

- Overall function is to remove hydrogen atoms from specific organic molecules and transfer them to coenzymes- Process of cellular ATP production begins in the cytoplasm
• Organic nutrients from the nutrient pool are broken into smaller 3-carbon and 2-carbon molecules
- In the mitochondrial matrix, pyruvate (3-carbon molecule) is converted into a 2-carbon acetate
• In the process, 1 NADH and 1 CO2 are produced- Common substrate for mitochondria is acetate
• Attaches to coenzyme A to form acetyl-CoA
• This acetyl-CoA then enters the citric acid cycle
-The acetyl group (CH3CO) from acetyl CoA attaches to a 4-carbon molecule
• Releases coenzyme A• Produces citric acid (a 6-carbon molecule)
- In a series of reactions, hydrogen atoms are removed from organic molecules•
Hydrogen atoms (and their electrons) are transferred to coenzymes
• Two carbon atoms are lost as CO2- Remaining 4-carbon molecule is then ready to receive another2-carbon acetyl group from acetyl-CoA
• Each cycle turn results in production of 1 ATP
-Coenzymes
• Deliver hydrogen atoms to the electron transport system (ETS)
• NAD (nicotinamide adenine dinucleotide)- Each NAD can carry 1 hydrogen atom asNADH
• FAD (flavin adenine dinucleotide)- Each FAD can carry 2 hydrogen atoms asFADH2

Aerobic respiration Overview

Stage One:• Glycolysis (cytoplasm)
Stage Two:• Preparation for Krebs (mitochondria)• Krebs Cycle (mitochondria)
Stage Three:• Electron Transfer Chain (mitochondria)

In glycolysis

- a single molecule of glucose (6 carbon sugar) is enzymatically cut in half through a series of steps,
- two molecules of pyruvate (3 carbon compound) are produced,
- two molecules of NAD+ are reduced to two molecules of NADH, and- a net of two molecules of ATP is produced

If oxygen is around

Aerobic respiration, proceed to Krebs cycle

If no oxygen

Anaerobic respiration, Proceed to Fermentation

Preparatory reactions

Oxidation of pyruvate
Pyruvate is oxidized into two-carbon acetyl units and carbon dioxide
NAD+ is reduced

The Second Stage

• The acetyl units are oxidized to carbon dioxide
• NAD+ and FAD are reduced - they pick up electrons and hydrogen (3 NADH and 1 FADH2)
• All of the carbon atoms in pyruvate end up in carbon dioxide
• One molecule of ATP forms
• Four-carbon oxaloacetate regenerates
• This happens for each pyruvate generated in glycolysis \-- so double the above totals for each original molecule of glucose