I. Overview of Digestive System

Lecture: Physiology of Digestion

I. Overview of Digestive System

A. Structures of Digestive System

1. alimentary canal (gastrointestinal [GI] tract)

a. digestion - break down molecules

b. absorption - move into circulatory system

c. mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum, anus

2. accessory digestive organs

a. function - assist in breakdown and absorption of foodstuffs

b. teeth, tongue, gallbladder, salivary glands, liver, pancreas

B. Primary Functions of Digestive System

1. ingestion - getting food into the GI tract (eating)

2. propulsion - moving food along the tract

a. swallowing and peristalsis (wave-like motion)

3. mechanical digestion - the physical grinding and churning of foodstuffs to breakdown and expose to enzymes and the surface of the GI tract

4. chemical digestion - breakdown of larger molecules into absorbable parts by enzymatic action

5. absorption - transport of digested molecules, vitamins, minerals, water, into the blood

6. defecation - elimination of unused foodstuff (feces)

C. Control of Conditions in the GI Tract

1. mechanoreceptors and chemoreceptors respond to:

a. stretching of the lumen by foodstuffs

b. solute concentration and pH within the lumen

c. presence of digestible and digested molecules

d. initiate reflexes that: activate or inhibit digestive glands; stimulate smooth muscle to mix and move contents

2. actions initiated by these receptors:

a. activate/inhibit secretions into the lumen

b. activate/inhibit muscular "mixing" activity

c. activate/inhibit secretion of hormones

d. activate/inhibit local "nerve plexuses"

3. types of digestive reflex processes:

a. short reflex - controlled by "nerve plexus" within the GI tract (enteric plexus); respond to stimuli in GI tract.

b. long reflex–respond to stimuli inside and/or outside the GI tract; those involving the CNS and extrinsic autonomic nerves; hormones from cells in stomach and small intestine stimulate target cells in same or different organs to secrete and contract.

II. Digestive Processes Occurring in the Mouth, Pharynx, Esophagus

A. Composition of Saliva & Control of Salivation

1. major components of saliva:

a. water (97-99.5%)

b. electrolytes: Na+, K+, Cl-, PO4-

c. mucin - protein that forms thick, slimy mucus

d. IgA antibodies - immune defense

e. lysozyme - antibacterial enzyme

f. defensins – antibacterial compounds

g. salivary amylase - starts breakdown of carbo's

h. metabolic wastes – urea, ammonia, creatinine

i. 1,500 ml/day (1.5 L)

2. control of salivation:

intrinsic glands strive to keep mouth wet all day

ingestion of foodstuffs ----->

activate chemoreceptors and pressoreceptors ----->

salivatory nuclei (pons & medulla) ----->

PARASYMPATHETIC nerve activation ----->

Facial (VII) and Glassopharyngeal (IX) nerves ----->

secretion by salivary glands

SYMPATHETIC nerve activation ->

decreased salivation

results in dry mouth (xerostomia)

B. Mechanical Processes

mastication (chewing) - cheeks, tongue, and teeth involved in both voluntary and involuntary grinding, ripping, and tearing of foodstuffs

partly voluntary and partly reflexive
stretch reflexes – pressure receptors in cheeks, gums and tongue

2. deglutition (swallowing) - moving "bolus" on its way; involves tongue, soft palate, pharynx and esophagus

a. tongue compacts ground food into a "bolus"

b. buccal phase (voluntary)

tongue against hard palate ----->

tongue contraction ----->

bolus forced into oropharynx

c. pharyngeal-esophageal phase (involuntary) – primarily the vagus nerve; control center in the medulla and lower pons

- tongue blocks off mouth

- soft palate blocks off nasopharyx

- epiglottis blocks off trachea

------> peristaltic waves moves food to stomach

III. Esophagus

Flat muscular tube from laryngopharynx to stomach.

Pierces the diaphragm at esophageal hiatus
Joins stomach at cardial orifice
Gastroesophageal (cardiac) sphincter – surrounds cardial orifice

Heartburn – when acidic gastric juices reflux into the esophagus
Likely with excess food/drink, extreme obesity, pregnancy, running
Also with structural abnormality: part of stomach above diaphragm; esophagitis, esophageal ulcers, esophageal cancer

IV. Regulation of Gastric Secretion, Motility, and Emptying

A. Regulation of Gastric Secretion ("Gastric Juice")

1. cephalic (reflex) phase

sight, aroma, taste, thought ----->

hypothalamus gustatory centers ----->

vagal nuclei of medulla ----->

vagus nerve (parasympathetic) ----->

increased gastric secretion

2. gastric phase

a. food reaches the stomach ------>

neural mechanismhormonal mechanism

distention & low acidity --->digested proteins --->

vagal afferents to medulla --->increase in pH --->

vagal efferents to stomach --->gastrin released --->

parasympathetic ACh release --->enzymes & HCl released

increased gastric secretion

b. control of HCl secreting parietal cells

i. gastrin, histamine, & ACh increase the release of HCl from parietal cells

ii. H+ comes from carbonic acid release

3. intestinal phase

excitatory phaseinhibitory phase

chyme enters the duodenum ->inhibition of vagal nuclei

release of intestinal gastrin ->inhibition of local reflexes

continued gastric secretionactivation of sympathetics

release of inhibitory hormones:

(secretin, cholecystokinin CCK, gastric inhibitory peptide GIP)

4. if small intestine pushed to accept more chyme > nausea and vomiting

Gastric gland secretions

Parietal cells – hydrochloric acid (HCl) and intrinsic factor

pH 1.5 – 3.5; denatures proteins; activates the enzyme pepsin; breaks down plant cell walls; kills many bacteria
H+ comes from H+/K+ ATPase pumps – facilitated diffusion of Cl-
intrinsic factor – glycoprotein required for absorption of vitamin B12 in intestine

Chief cells – pepsinogen (inactive form of pepsin);

pepsinogen converted to active pepsin by HCl and pepsin itself (positive feed back)
lipases for the digestion of lipases (fats)

Enteroendocrine cells – secrete chemical messengers that act as paracrines.

serotonin and histamines
hormones: somatostatin and gastrin

Gastric Motility and Emptying

chyme enters the duodenum
receptors respond to stretch and chemical signals
carbohydrate rich chyme moves quickly through the duodenum
fatty chyme remains in duodenum 6 hours or more
enterogastric reflex and enterogastrones inhibit gastric secretion and duodenal filling

1. receptive relaxation - trilayer of muscles in wall of the stomach relax to allow filling to occur

2. plasticity - smooth muscle tension specially regulated to prevent regurgitation of food

3. basic electrical rhythm - pacemaker cells of longitudnal muscle allow rhythmic contractions

4. emptying to duodenum - regulated by amount and type of chyme entering into the duodenum; faster with high carbo, slower with higher fats

vomiting (emesis) - irritants activate neurons which stimulate the "emetic center" of medulla

extreme stretching, intestinal irritants e.g. bacterial toxins, excessive alcohol, fatty or spicy foods and certain drugs
chemicals/sensory impulses > emetic center of the medulla
excessive vomiting – dehydration and electrolyte and acid/base imbalance (alkalosis)
chemotherapy – targets rapidly dividing cells; nausea, vomiting, diarrhea

The efferent branches of cranial nerves V, VII and IX as well as vagus nerve (X) and sympathetic trunk produce the complex coordinated set of muscular contractions, cardiovascular responses and reverse peristalsis that characterizes vomiting.

E. mucosal barrier–epithelium lining the stomach provides protection

thick layer of bicarbonate rich mucus
tight junctions between epithelial cells
epithelial cells replaced every 3-5 days

Homeostatic imbalance

gastritis – anything that causes inflammation of the stomach lining
peptic or gastric ulcers – erosions of the stomach wall; can perforate the wall; peritonitis or hemorrhage; mostly caused by Helicobacter pylori; some by Non-steroidal anti-inflammatory drugs (NSAIDs)
excessive acid – can cause dyspepsia; use of antacids; H2 receptor antagonists (cimetidine or rantidine); proton-pump inhibitors (omeprazole or lansoprosole)

V. Content of Bile and Bile Release into Small Intestine

A. Content of Bile (made in Liver, released by Gall Bladder)

1. bile salts, bile pigments, cholesterol, neutral fats, phospholipids, electrolytes

2. bile salts - derivatives of cholesterol (cholic acid, chenodeoxycholic acid)

a. emulsify fats - separate fats into tiny droplets for digestion & absorption

b. enterohepatic circulation - conservation of bile salts by re-processing

i. reabsorbed at in distal small intestine

ii. to liver via hepatic portal blood

iii. resecreted as bile from gall bladder

3. bile pigment (bilirubin) - waste product of heme from broken-down erythrocytes

a. urobilinogen - breakdown product of bilirubin, causes darker coloration of feces

B. Enterohepatic circulation – recycles bile salts; bile > duodenum > reabsorbed in ileum > hepatic portal vein > liver

C. Regulation of Bile Release to Small Intestine

1. hepatocytes - cells of the liver that produce 0.5-1.0 liters of bile each day

2. parasympathetic - stimulates gall bladder release

3. cholecystokinin (CCK) - hormone released by cells of the mucosa of the duodenum

acidic, fatty chyme enters duodenum ----->

duodenal mucosa secretes CCK ----->

a. gall bladder contracts to release bile

b. pancreas secretes pancreatic juices

c. hepatopancreatic sphincter opens

gallstones - crystallized formation of cholesterol and salts, causing obstruction of bile release; may cause obstructive jaundice; gall bladder contracts against sharp crystals > pain; treated with drugs; ultrasound vibrations (lithotripsy), laser vaporization, surgery

D. Cirrhosis of the liver

progressive, chronic inflammation of the liver from chronic hepatitis or alcoholism
liver transplants are successful but liver donors are rare

Hepatitis

Usually viral infection; could be drug toxicity or mushroom poisoning

VI. Composition of Pancreatic Juice and Regulation of Secretion

A. Composition of Pancreatic Juice

1. 1.2 - 1.5 liters per day

2. water and electrolytes (mainly bicarbonate ions)

3. alkaline solution – to neutralize pH from the stomach

3. enzymes - precursors and active digestive forms

a. trypsinogen ------> trypsin

enterokinase

b. procarboxypeptidase ------> carboxypeptidase

chymotrypsinogen ------> chymotrypsin

trypsin

c. amylase (carbohydrates), lipases (fats), nucleases (nucleic acids)

B. Regulation of Pancreatic Secretion

1. parasympathetic - causes release during cephalic and gastric phases of gastric secretion

2. secretin - hormone that causes release of "bicarbonate-rich" pancreatic juices in response to the presence of HCl; causes liver to produce bile more rapidly

3. cholecystokinin - hormone that causes release of "enzyme-rich" pancreatic juice in response to the presence of proteins and fats; causes gall bladder to contract and hepatopancreatic sphincter to relax resulting in bile release.

VII. Digestive Processes of the Small Intestine

A. Optimal Conditions for Digestion & Absorption

1. pancreatic juice & bile - enzymes, emulsifying fats, and pH are essential for proper intestinal processes

2. small intestine is PRIMARY site for absorption of nutrients into the cardiovascular system

B. Movement in the Small Intestine

1. segmentation - longitudnal flow of chyme through the tube (duodenum -> ileum); most common movement through the small intestine

migrating mobility complex - activity that moves the chyme from the ileum to the cecum through the ileocecal valve

peristalsis – initiated by rise in hormone motilin in late intestinal phase; every 90 – 120 minutes; meal remnants, bacteria and debris moved to large intestine; from duodenum > ileum in two hours.

C. Requirements for Digestion and Absorption in Small Intestine

slow delivery of acidic and hypertonic chyme
delivery of bile, enzymes and bicarbonate ions from liver and pancreas

D. Increased surface area for absorption

circular folds > more nutrient absorption
villi – capillary beds and lacteals for absorption
microvilli – contain enzymes for carbohydrate and protein digestion

Mucosa of Small Intestine

Peyer’s patches – protect especially distal part against bacteria; my protrude into the submucosa
B lymphocytes – leave the intestine, enter blood, protect lamina propia with their IgA antibodies
Duodenal (Brunner’s) glands – secrete alkaline mucus to neutralize acidic chyme

Intestinal juice

1-2 Liters secreted each day in response to distention or irritation of mucosa
slightly alkaline; isotonic with blood plasma
largely water; enzyme poor (enzymes of small intestine only in brush border)
facilitates transport and absorption of nutrients

VIII. Digestive Processes of the Large Intestine

A. Bacterial Flora

1. digest remaining carbohydrates

2. responsible for producing gas (flatus)

3. synthesize complex B vitamins and vitamin K

B. Digestion and Absorption

1. reclaim most of the water – about 200 ml left to be excreted with feces

2. reclaim some of the electrolytes (Na+ and Cl-)

3. water is absorbed passively following an osmotic gradient set up by Na+/K+ pumps

C. Motility of the Large Intestine

1. haustral contractions - slow acting segmental motion; moves chyme from one segment to next

2. mass movements - peristaltic waves that move food to the rectum during/after eating

diverticula - herniation of the mucosa through the wall of the colon sigmoid colon

low fiber > narrowed colon > strong contractions > increased pressure on the walls > herniations of the colon

diverticulosis – common in the sigmoid colon; about 50% of people over 70 years
diverticulitis – inflamed diverticula; may rupture and leak into peritoneal cavity; may be life threatening

irritable bowel syndrome (IBS) – recurring abdominal pain; stool changes, bloating, flatulence, nausea; stress is a common precipitating factor

D. Defecation

1. defecation reflex - when feces (stool) enters rectum, spinal cord reflex is triggered

a. internal sphincter (involuntary)

b. external sphincter (voluntary)

2. Valsalva's maneuver - contraction of diaphragm and abdominal muscles to increase pressure for defecation

3. diarrhea - too much water in the stool

4. constipation - insufficient water or fiber

IX. Chemical Digestion

A. Enzymatic Hydrolysis ("water" "breaking")

1. hydrolysis - a water molecule is added between two "monomers" of a complex organic molecule in order break it down into its component parts

B. Carbohydrate Digestion

1. monosaccharides - "monomers" such as glucose, fructose, and galactose

2. disaccharides - sucrose (table sugar), lactose (milk sugar), and maltose (grain sugar)

3. polysaccharides - starch (grains), glycogen (muscle)

4. carbohydrate hydrolyzing enzymes

a. salivary amylase - produces "oligosaccharides"

b. pancreatic amylase - in small intestine

c. intestinal enzymes - dextranase & glucoamylase (> 3 sugars), maltase, sucrase, and lactase

lactose intolerance - decreased ability to digest lactose in the diet (use "lactase" supplements

C. Protein Digestion

1. amino acids - the "monomer" components of protein

2. stomach - pepsinogen -----> pepsin (low pH)

3. small intestine

a. enzymes that cleave throughout the protein

trypsinogen ------> trypsin

chymotrypsinogen ------> chymotrypsin

b. carboxypeptidase (carboxyl end of protein)

c. aminopeptidase, dipeptidase (amino end)

1. Proteins and protein fragments are digested to amino acids by pancreatic enzymes and brush border enzymes.

2. The amino acids are then absorbed by active transport into the absorptive cells and then move to the opposite side.

3. The amino acid then leaves the villus epithelial cell by facilitated diffusion and enter the capillary via intercellular clefts.

D. Lipid (Fat) Digestion

1. lipid structure - glycerol + 3 monoglycerides

2. lipases - enzymes that break down lipids

3. bile salts - "emulsify" fats in 1 micron "micelles"

E. Nucleic Acid Digestion

1. pancreatic nucleases - break down DNA and RNA

a. pancreatic ribonuclease and deoxyribonuclease > nucleotide monomers

b. brush border enzymes nucleosidases and phosphatases > free bases, sugars, phosphate ions.

X. Absorption of Nutrients

A. General Features

1. transepithelial transport - nutrients must pass across the epithelial lining of the small intestine

2. active transport - most nutrients must be transported across membrane using ATP of the cells

B. Carbohydrate Absorption

1. facilitated diffusion - glucose and galactose (coupled with active transport of Na+)

a. "carrier molecule" has binding sites for both sugar and Na+; relies on Na+ gradient

C. Protein (Amino Acid) Absorption

1. facilitated diffusion - amino acids and small peptides (coupled with Na+ active transport)

a. "carrier molecule" has binding sites for both amino acid and Na+; relies on Na+ gradient

2. food allergies - absorption of proteins in infant gut causes early immune reaction

D. Lipid Absorption

1. micelles - tiny balls of fats that result from bile salt emulsification and "lecithin"

a. contain cholesterol and fat-soluble vitamins

b. diffuse through lipid bilayer of membrane

c. chylomicrons - micelles combined with associated proteins within the cell; enter the lacteals of the lymphatic system

E. Nucleic Acid Absorption

1. pentoses, nitrogen bases, phosphates - absorbed by similar processes as sugars and amino acids

F. Vitamin Absorption

1. fat soluble - Vitamins A, D, E, K are absorbed by epithelial cells along with lipid micelles

2. water soluble - Vitamins B & C absorbed by diffusion or passive or active transporters

3. Vitamin B12 - large and electrically charged, must bind with "intrinsic factor" before being taken into the cell by endocytosis

G. Electrolyte Absorption

1. Fe and Ca - primarily absorbed in duodenum of small intestine

a. ferritin - sequesters Fe in intestinal cells

b. transferrin - transfers Fe into circulation when need is present (menstruation)

c. Vitamin D - facilitates Ca absorption along with parathyroid hormone

2. Na - exchanged for sugars and amino acids; coupled with active transport of these molecules

3. Cl–transported actively; absorbed into cells and exchanged for HCO3-

4. K - absorbed into cells due to osmotic gradients; lost if there is poor water reabsorption

H. Water Absorption

1. small intestine - 95% of water absorbed by small intestine following transport of solutes

2. large intestine - absorbs remaining water before moving the chyme on to the rectum

I. Malabsorption of Nutrients

1. impairment of bile or pancreatic juice release

2. infections of the intestinal mucosa

3. gluten sensitive enteropathy (Celiac disease)–

"gluten" protein in grains damages the mucosa of the intestines
immune reaction to gluten
gluten causes immune cell to damage intestinal villi and brush border
treated by eliminating gluten from the diet (all grains but rice and corn)

J. GI Tract in Old Age

GI tract activity declines
Less digestive juice
Absorption less efficient
Peristalsis slows > less frequent bowel movements
Taste/smell are less acute
Periodontal disease develops
Diverticulosis, fecal incontintence
Cancer can be present as well