Digestive Physiology

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Digestive Physiology
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Overview

• Inside gastrointestinal (GI) tract, food is
  broken down by hydrolysis reactions into
  molecular monomers
• Most digestion of nutrients and absorption of
  monomers occurs in small intestine (90)

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Functions of the Digestive System

• Ingestion--taking food into mouth
• Mastication--chewing food and mixing it with
  saliva
• Deglutition--swallowing food
• Peristalsis--rhythmic wave-like contractions that
  move food through GI tract
• Absorption--Is passage of digested end products
  into blood or lymph
• Storage and Elimination--Includes temporary
  storage and subsequent elimination of
  indigestible components of food

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Functions of Digestive System

• Secretion
• Includes release of exocrine and endocrine
  products into GI tract
• Exocrine secretions include HCl, H2O, HCO3-,
  bile, lipase, pepsin, amylase, trypsin, elastase,
  and histamine
• Endocrine includes hormones secreted into stomach
  and small intestine to help regulate GI system
• e.g. gastrin, secretin, cholescytokinin, gastric
  inhibitory peptide, and somatostatin

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Digestive System

• Is composed of GI tract (alimentary canal) and
  accessory digestive organs
• Organs include oral cavity, pharynx, esophagus,
  stomach, and small and large intestine
• Accessory organs include teeth, tongue, salivary
  glands, liver, gallbladder, and pancreas

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Layers of GI Tract

• Termed tunics
• The 4 tunics are mucosa, submucosa, muscularis,
  and serosa

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Mucosa

• Is the absorptive and secretory layer lining
  lumen of GI tract
• In places is highly folded with villi to increase
  absorptive area

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Submucosa

• Is a thick, highly vascular layer of connective
  tissue where absorbed molecules enter blood and
  lymphatic vessels
• Contains glands and nerve plexuses (submucosal
  plexus) that carry ANS activity to muscularis
  mucosae

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Muscularis

• Is responsible for segmental contractions and
  peristaltic movement through GI tract
• Has an inner circular and outer longitudinal
  layer of smooth muscle
• Activity of these layers moves food through tract
  while pulverizing and mixing it
• Myenteric plexus between these layers is major
  nerve supply to GI tract
• Includes fibers and ganglia from both Symp and
  Parasymp systems

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Serosa

• Is outermost layer serves to bind and protect

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Regulation of GI Tract

• Parasympathetic effects, arising from vagus and
  spinal nerves, stimulate motility and secretions
  of GI tract
• Sympathetic activity reduces peristalsis and
  secretory activity
• GI tract contains an intrinsic system that
  controls its movements--the enteric nervous
  system
• GI motility is influenced by paracrine and
  hormonal signals

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From Mouth to Stomach

• Esophagus connects pharynx to stomach
• Upper third contains skeletal muscle for
  voluntary swallowing control
• Peristalsis moves food from pharynx to stomach

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From Mouth to Stomach continued

• Peristalsis propels food thru GI tract
• wave-like muscular contractions
• After food passes into stomach, the
  gastroesophageal sphincter constricts, preventing
  reflux

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Stomach

• Is most distensible part of GI tract
• Empties into the duodenum
• Functions in
• storage of food
• initial chemical digestion of proteins
• some mechanical digestion of all nutrients
• kills bacteria with high acidity (HCl)
• moves soupy food mixture (chyme) into intestine

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Stomach continued

• Is enclosed by lower esophageal sphincter on top
  and pyloric sphincter on bottom
• Is divided into 3 regions
• Fundus
• Body
• Antrum

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Stomach continued

• Gastric mucosa has gastric pits in its folds
• Cells that line folds deeper in the mucosa, are
  exocrine gastric glands

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Stomach continued

• Gastric glands contain cells that secrete
  different products that form gastric juice
• Goblet cells secrete mucus
• Parietal cells secrete HCl and intrinsic factor
  (necessary for B12 absorption in intestine)
• Chief cells secrete pepsinogen (precursor to
  pepsin)

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Stomach continued

• Enterochromaffin-like cells secrete histamine and
  serotonin
• G cells secrete gastrin
• D cells secrete somatostatin

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HCl in Stomach

• Is secreted into stomach lumen by proton pumps of
  epithelial parietal cells in response to the
  histamine secreted by ECL cells and ACh from
  vagus (parasympathetic stimulation)
• These are indirect effects since release of
  histamine is due to gastrin release from G cells
• Proton pump inhibitors (medicines) are common and
  work to reduce stomach acids (treat ulcers)

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HCl in Stomach continued

• Makes gastric juice very acidic which denatures
  proteins to make them more digestible
• Converts pepsinogen into pepsin
• Pepsin is more active at low pHs

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Digestion and Absorption in Stomach

• Proteins are partially digested by pepsin
• Carbohydrate digestion by salivary amylase is
  soon inactivated by acidity
• Alcohol and aspirin are the only commonly
  ingested substances that are absorbed

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Small Intestine (SI)

• Is longest part of GI tract approximately 3m
  long
• Duodenum is 1st section after pyloric sphincter
• Jejunum is next region
• Ileum empties into large intestine

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Small Intestine (SI) continued

• Surface area increased by foldings and
  projections
• Large folds are plicae circulares
• Microscopic finger-like projections are villi
• Cell apical hair-like projections are microvilli

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Intestinal Enzymes

• Attached to microvilli are brush border enzymes
  that are not secreted into lumen
• Enzyme active sites are exposed to chyme

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Large Intestine (LI) or Colon

• Has no digestive function but absorbs H2O,
  electrolytes, B and K vitamins, and folic acid
• Internal surface has no villi and is not very
  elaborate
• Intestinal Flora Contains large population of
  microflora
• 400 different species of commensal bacteria
• Which produce folic acid and vitamin K and
  ferment indigestible foods to produce fatty acids
• And reduce ability of pathogenic bacteria to
  infect colon
• Antibiotics can kill commensals

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Fluid and Electrolyte Absorption in Colon

• SI absorbs most water but LI absorbs 90 of water
  it receives
• Begins with osmotic gradient set up by Na/K
  pumps
• Water follows by osmosis
• Salt and water reabsorption stimulated by
  aldosterone
• LI can also excrete H2O via active transport of
  NaCl into intestinal lumen

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The Liver
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Hepatic Portal System

• Food absorbed in SI is delivered 1st to liver
• Capillaries in digestive tract drain into the
  hepatic portal vein which carries oxygen poor/
  nutrient rich blood to liver
• Liver also receives blood from the hepatic artery
  (oxygen rich, nutrient rich)

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Enterohepatic Circulation

• Is recirculation of compounds between liver and
  intestine
• Many compounds are released in bile, reabsorbed
  in SI, and returned to liver to be recycled
• Liver excretes drug metabolites into bile to pass
  out in feces

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Liver Lobules

• Are functional units formed by hepatic plates
• In middle of each is central vein
• At edge of each lobule are branches of hepatic
  portal vein and artery which open into sinusoids

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Liver Lobules

• Bile is secreted by hepatocytes in bile
  canaliculi
• Empty into bile ducts which flow into hepatic
  ducts that carry bile away from liver

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Functions of the Liver

• Lipid metabolism lipolysis, lipogenesis,
  synthesis of cholesterol
• Protein metabolism synthesizes the plasma
  proteins
• (albumin, fibrinogen, alpha and beta globulins,
  and prothrombin) breaks down proteins and
  converts the to carbohydrates or lipid for
  storage.
• Carbohydrate metabolism helps to maintain normal
  blood glucose levels by
• breaking down glycogen into glucose and then
  secreting it into the blood
• converting serum glucose into glycogen and
  triglycerides for storage

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Functions of the Liver

• Detoxification processes drugs and hormones
  detoxifies substances such as alcohol or excretes
  drugs such as the antibiotics into bile.
• Synthesis of bile salts bile salts are used in
  the small intestine for the emulsification and
  absorption of lipids, cholesterol, phospholipids,
  and lipoproteins.
• Storage stores glycogen, vitamins and minerals.
• Phagocytosis Kupffer cells phagocytize RBCs,
  WBCs, bacteria, and toxins.

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Detoxification of Blood

• Liver can remove hormones, drugs, and other
  biologically active molecules from blood by
• Excretion into bile
• Phagocytosis by Kupffer cells
• Chemical alteration of molecules
• e.g. ammonia is produced by deamination of amino
  acids in liver
• Liver then converts it to urea which is excreted
  in urine

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The Gallbladder

• Stores and concentrates bile continuously
  produced by liver
• When SI is empty, sphincterof Oddi in common
  bile duct closes and bile is forced up into
  gallbladder
• Expands as it fills with bile
• When food is in SI, sphincter of Oddi opens, gall
  bladder contracts, and bile is ejected thru ducts
  into duodenum

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The Pancreas

• Has both endocrine and exocrine functions
• Endocrine function performed by Islets of
  Langerhans cells
• Secrete insulin and glucagon
• Exocrine secretions include bicarbonate (HCO3-)
  solution and digestive enzymes
• These pass in pancreatic duct to small intestine
• Exocrine secretory units are acini

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The Physiology of DigestionRegulation of Gastric
Function

• Gastric motility and secretion occur
  automatically
• Waves of contraction are initiated spontaneously
  by pacesetter cells and secretion occurs in
  absence of hormonal and neural input
• ANS and hormonal effects are superimposed on
  automatic activity
• Extrinsic control of gastric function is divided
  into cephalic, gastric, and intestinal phases

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Cephalic Phase

• Refers to control by brain via vagus nerve
• Stimulated by sight, smell, thought, and taste of
  food
• Activation of vagus nerve stimulates
• Chief cells to secrete pepsinogen
• G cells to secrete gastrin
• ECL cells to secrete histamine
• Parietal cells to secrete HCl

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Gastric Phase

• The presence of short polypeptides and amino
  acids in the stomach raises the pH. This change
  in chemical nature, along with stomach
  distension, activates the gastric (stomach) phase.

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Gastric Phase

• Short polypeptides and amino acids present in the
  stomach stimulate G cells to secrete gastrin and
  chief cells to secrete pepsinogen
• Gastrin then stimulates ECL cells to secrete
  histamine which stimulates parietal cell
  secretion of HCl
• This is a positive feedback mechanism as more
  HCl and pepsinogen are secreted, more
  polypeptides and amino acids are liberated, and
  more digestive processes occur.

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Gastric Phase

• As polypeptides leave the stomach and move into
  the duodenum, the pH begins to drop again and the
  gastric phase slows.

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Intestinal Phase

• Begins when chyme enters the small intestine
• Arrival of chyme in duodenum causes a neural
  reflex that inhibits gastric motility and
  secretion
• Fat in chyme stimulates SI to secrete
  enterogasterones--hormones that inhibit gastric
  motility and secretion
• Include Somatostatin, Cholecystokinin, Secretin,
  and Gastric Inhibitory Peptide

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Intestinal Phase

• Enterogasterones
• Somatostatin inhibits acid secretion.
• Cholecystokinin stimulates secretion of
  pancreatic enzymes regulates release of bile
  from the gall bladder brings about a feeling of
  fullness after eating slows gastric motility and
  acid secretion. Its secretion is stimulated by
  presence of fats in duodenum.
• Secretin stimulates secretion of pancreatic
  HCO3- inhibits acid production and gastric
  motility.
• Gastric Inhibitory Peptide Inhibits gastric
  motility and secretion stimulates secretion of
  insulin from pancreas.

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Digestion and Absorption of Carbohydrates

• Most carbohydrates are ingested as
  starch--structured of glucose
• Salivary amylase begins starch digestion in the
  mouth and continues for a short time in the
  stomach (until it is denatured by the low pH)
• Pancreatic amylase secreted into duodenum
  converts starch to oligosaccharides
• Oligosaccharides are hydrolyzed by small
  intestine brush border enzymes into
  monosaccharides
• Monosaccharides are absorbed directly into the
  bloodstream

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Digestion and Absorption of Carbohydrates

• Lactose Intolerance Milk sugar (lactose) is
  digested
• by lactase (a brush border enzyme) usually only
• found in juvenile mammals. Some humans maintain
• this enzyme into adulthood, most do not. Without
• lactase, milk sugars delivered to intestines are
• digested by bacteria which proliferate (thrive)
  and
• excrete gas and organic acids leading to bloating
  and
• flatulance, termed lactose intolerance.

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Digestion and Absorption of Proteins

• Chemical digestion begins in stomach when pepsin
  digests proteins to form polypeptides
• In small intestine, endopeptidases (trypsin,
  chymotrypsin, elastase) from pancreas cleave
  peptide bonds from interior of polypeptides
• In small intestine exopeptidases
  (carboxypeptidase, aminopeptidase) cleave peptide
  bonds from ends of polypeptides. Carboxypeptidase
  is a pancreatic enzyme while aminopeptidase is a
  brush border enzyme.

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Digestion and Absorption of Protein

• Protein digestion in small intestine results in
  free amino acids, dipeptides, and tripeptides
• Which are absorbed into small intestine cells
  where they are broken down into amino acids
• Which are then secreted directly into the
  bloodstream

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Digestion and Absorption of Lipids

• Small amount of lipid chemical digestion begins
  in mouth via lingual lipase
• No chemical digestion in stomach (except in
  infants who can digest milk fats)
• Arrival of lipids in duodenum causes secretion of
  bile from gall bladder
• Fat is emulsified by bile salt micelles
• Form tiny droplets of fat
• Greatly increases surface area for digestion by
  pancreatic lipase

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Digestion and Absorption of Lipids continued

• Products of fat digestion are dissolved in
  micelles which move to the brush border

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Digestion and Absorption of Lipids continued

• Pancreatic lipase then hydrolyzes exposed
  triglycerides to free fatty acids and
  monoglycerides which are then absorbed into
  epithelial cells

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Digestion and Absorption of Lipids continued

• Products of fat digestion dissolved in micelles
  move to the brush border for absorption

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Digestion and Absorption of Lipids continued

• Free fatty acids and monoglycerides leave
  micelles and enter epithelial cells
• Inside epithelial cells, they are resynthesized
  into triglycerides and phospholipids, and then
  packaged into protein transport structures termed
  chylomicrons.

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Transport of Lipids

• Chylomicrons are then secreted into lacteals of
  the lymphatic system.
• After traveling through lymphatic system
  chylomicrons enter the bloodstream via the
  subclavian veins
• In blood, chylomicrons bind to receptors on
  capillaries of muscle and fat
• There endothelial lipoprotein lipase hydrolyzes
  the triglycerides to free fatty acids and
  glycerol for energy use by muscle, and storage in
  fat
• Cholesterol-containing remnants are taken up by
  liver

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Lipids in chylomicrons are transported from
epithelial cells of villi into central lacteals
of lymphatic system before entering bloodstream
at subclavian veins
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Transport of Lipids continued

• Cholesterol and triglycerides from liver are
  packaged into VLDLs (Very low density
  lipoporteins) which are secreted into the blood.
  VLDLs take triglycerides, cholesterol, and
  phospholipids to body cells
• Once triglycerides are removed, VLDLs are termed
  LDLs (Low density lipoproteins)
• LDLs transport remaining cholesterol to blood
  vessels and organs
• An excess of LDLs over time is associated with
  cardiovascular disease (heart attack, stroke)
• HDLs, also made by liver, transport excess
  cholesterol from tissues back to liver for
  metabolism
• High ratio of HDL-cholesterol to total
  cholesterol is believed to confer protection
  against cardiovascular disease (atherosclerosis)
• LDLs and HDLs are water soluble protein capsules
  able to transport insoluble lipids in a
  water-based plasma

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