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Gastrointestinal Physiology I

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Gastrointestinal Physiology I Dean Arnaoutakis Case 15: Treatment Her physician prescribed cholestyramine to control her diarrhea Cholestyramine binds bile acids in ... – PowerPoint PPT presentation

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Title: Gastrointestinal Physiology I


1
Gastrointestinal Physiology I
  • Dean Arnaoutakis

2
Functions
  • 4 major activities of GI tract
  • Motility
  • Propel ingested food from mouth toward rectum
  • Secretion
  • Aid in digestion and absorption
  • Digestion
  • Food broken down into absorbable molecules
  • Absorption
  • Nutrients, electrolytes, and water are absorbed

3
Structure of GI Tract
  • Arranged linearly in following sequence
  • Mouth, esophagus, stomach, small intestine, large
    intestine, and anus
  • Other structures of GI tract
  • Salivary glands, pancreas, liver, and gallbladder

4
Structure of GI Tract
  • Layers of GI Wall
  • Mucosa
  • Innermost layer (faces lumen)
  • Layer of epithelial cells specialized for
    absorption and secretion
  • Submucosa
  • Consists of collagen, elastin, glands, and blood
    vessels
  • Circular and Longitudinal Smooth Muscle
  • Provides motility for GI tract
  • Serosa
  • Faces the blood

5
Layers of GI Wall
6
Innervation of GI Tract
  • Autonomic Nervous System has an extrinsic and an
    intrinsic component
  • Extrinsic
  • Sympathetic and Parasympathetic innervation of GI
    tract
  • Intrinsic
  • Called Enteric Nervous System
  • Contained within wall of GI tract
  • Communicates with Extrinsic component

7
Intrinsic Innervation
  • Can direct all functions of GI in absence of
    extrinsic innervation
  • Controls contractile, secretory, and endocrine
    functions of GI tract
  • Receives input from
  • Parasympathetic and sympathetic nervous systems
  • Mechanoreceptors and chemoreceptors in mucosa
  • Sends information directly to smooth muscle,
    secretory, and endocrine cells

8
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9
Esophagus
  • Muscular tube that conveys food from pharynx to
    stomach
  • Inner circular muscle
  • Outer longitudinal muscle
  • Food passes through quickly because of
    peristalsis

10
Esophagus
11
Esophagus
  • Pyrosis (heartburn)common esophageal discomfort
  • Result of regurgitation of food and gastric fluid
    into lower esophagus
  • Acid reflux can cause esophagitis

12
Stomach
  • Specialized for accumulation of food
  • Capable of considerable expansion (can hold 2-3L)
  • Gastric juice converts food into semiliquid
    called chyme
  • 4 Parts
  • Cardia
  • Fundus
  • Body
  • Pylorus

13
Stomach
14
Stomach
  • Gastric mucosa has numerous openings called
    gastric pits
  • Gastric glands empty into bottom of pits
  • 4 functionally different cell types compose
    glands
  • Mucous cells
  • Chief cells
  • Parietal cells
  • Enteroendocrine cells

15
Stomach
16
Small Intestine
  • 3 Parts
  • Duodenum
  • Jejunum
  • Ileum
  • Primary site for digestion and absorption of
    nutrients
  • Bile duct and pancreatic duct empty into duodenum

17
Small Intestine
18
Small Intestine
19
Small Intestine
  • Intestinal lining increases absorptive surface
    area
  • Villi
  • Finger-like projections of the mucosa
  • Microvilli
  • Tiny projections on luminal membrane of each
    intestinal cell
  • Give the apical region striated appearance called
    brush border

20
Villi
21
Microvilli
22
Large Intestine
  • Cecum, ascending colon, transverse colon,
    descending colon, sigmoid colon, rectum, anal
    canal
  • Reabsorbs water and electrolytes
  • Eliminates waste
  • NO Villi
  • Mucosa contains numerous tubular glands called
    crypts
  • Responsible for mucus secretion

23
Large Intestine
24
Large Intestine
25
Liver
  • Largest internal organ
  • Receives major blood supply from hepatic portal
    vein
  • Brings venous blood rich in nutrients from
    digestive tract
  • Hepatocytes
  • Livers cells
  • Capable of regeneration

26
Liver
27
Liver
  • Functions
  • Protein synthesis (albumin, prothrombin)
  • Bile formation and secretion
  • Detoxification of drugs and steroids
  • Lipoprotein synthesis
  • Carbohydrate metabolism
  • Urea formation from ammonium

28
Gallbladder
  • Attached to surface of the liver
  • Blind pouch that stores bile
  • Ducts
  • Hepatic Duct
  • Cystic Duct
  • Common Bile Duct

29
Gallbladder
30
Pancreas
  • Exocrine and Endocrine Gland
  • ExocrineAcinar Cells
  • Secretes essential digestive enzymes through
    pancreatic duct into duodenum
  • EndocrineIslets of Langerhans
  • Secretes insulin and glucagon into blood stream

31
Pancreas
32
Pancreas
33
GI Peptides
  • Includes hormones, neurocrines, and paracrines
  • Regulate functions of GI tract
  • Contraction and relaxation of smooth muscle wall
    and sphincters
  • Secretion of enzymes for digestion
  • Secretion of fluid and electrolytes
  • Trophic (growth) effects
  • Some regulate secretion of other GI peptides

34
GI Peptides
  • Hormones
  • Peptides released from endocrine cells of GI
    tract
  • Secreted into portal circulation and enter
    systemic circulation
  • Target cells may be in GI tract or may be located
    elsewhere in body
  • Gastrin, Cholecystokinin, Secretin, and Gastric
    Inhibitory Peptide
  • Paracrines
  • Secreted by endocrine cells of GI tract
  • Act locally within same tissue that secretes them
  • Somatostatin (inhibitory actions)
  • Neurocrines
  • Released by neurons of GI tract following an AP
  • ACh, norepinephrine, Vasoactive Intestinal
    Peptide (VIP), Gastrin-Releasing Peptide (GRP),
    Neuropeptide Y, and Substance P

35
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36
GI Hormones
  • Gastrin
  • Secreted by G cells in stomach in response to
    eating
  • Stimuli include proteins, distention of stomach,
    and vagal stimulation
  • Gastrin-releasing peptide (GRP) is released from
    vagal nerve endings onto G cells
  • Secretion is inhibited by low pH in stomach
  • Promotes H secretion by gastric parietal cells
  • Stimulates growth of gastric mucosa

37
GI Hormones
  • Cholecystokinin
  • Secreted by I cells of small intestine in
    response to fatty acids and small peptides
  • 5 Actions
  • Contraction of gallbladder
  • Eject bile from gallbladder into small intestine
    necessary for emulsification lipids
  • Secretion of pancreatic enzymes
  • Digest lipids, carbohydrates, and proteins
  • Secretion of bicarbonate (HCO3-) from pancreas
  • Growth of exocrine pancreas and gallbladder
  • Inhibition of gastric emptying
  • Ensures adequate time for digestive and absorptive

38
GI Hormones
  • Secretin
  • Secreted by S cells of duodenum in response to H
    and fatty acids
  • Promotes secretion of pancreatic HCO3-
  • Neutralizing H allows for pancreatic enzymes to
    digest fats
  • Inhibits effects of gastrin on parietal cells (H
    secretion and growth)
  • Gastric Inhibitory Peptide (GIP)
  • Secreted by small intestine in response to all 3
    types of nutrients
  • Stimulates insulin secretion by pancreas
  • Inhibits gastric H secretion

39
GI Paracrines
  • Somatostatin
  • Secreted by endocrine cells in response to
    decreased luminal pH
  • Inhibits secretion of other GI hormones
  • Inhibits gastric H secretion
  • Histamine
  • Secreted in H-secreting region of stomach
  • Stimulates H secretion by gastric parietal cells
    (along with gastrin and ACh)

40
GI Neurocrines
  • Synthesized in cell bodies of GI neurons
  • AP causes release of neurocrine which interacts
    with receptors on postsynaptic cell
  • ACh (released from cholinergic neurons)
  • Norepinephrine (released from adrenergic neurons)

41
Motility
  • Contraction and relaxation of walls and
    sphincters of GI tract
  • Mixes ingested food to prepare it for digestion
    and absorption
  • Propels food along GI tract
  • Contractile tissue of GI tract is Smooth Muscle
  • Except pharynx, upper 1/3 esophagus, and external
    anal sphincter are striated muscle
  • Smooth muscle cells coupled via gap junctions
  • Permits rapid spread of APs for coordinated,
    smooth contraction

42
Motility
  • Segmentation Contraction
  • Circular muscle contracts sending chyme in both
    orad and caudad directions
  • Intestine then relaxes allowing chyme to merge
    back together
  • Peristaltic Contractions
  • Longitudinal muscle contracts orad to bolus
    propeling chyme along small intestine
  • Simultaneously, portion of intestine caudad to
    bolus relaxes

43
Motility
44
Secretion
  • Addition of fluids, enzymes, and mucus to lumen
    of GI tract
  • Secretions produced by
  • Salivary glands (saliva)
  • Gastric mucosal cells (gastric secretion)
  • Pancreatic exocrine cells (pancreatic secretion)
  • Liver (bile)

45
Salivary Secretion
  • Salivary glands produce 1 L/day of saliva
  • Functions of saliva
  • Initial digestion of starches and lipids by
    salivary enzymes
  • Dilution and buffering of ingested foods
  • Lubrication of ingested food to aid its movement
  • Structure of Salivary Glands
  • Parotid glands, submandibular glands, and
    sublingual glands
  • Each gland delivers saliva to mouth through a duct

46
Salivary Glands
47
Gastric Secretion
  • Gastric mucosal cells secrete gastric juice
  • HCl and pepsinogen initiate protein digestion
  • Intrinsic factor required for absorption of
    vitamin B12
  • Mucus protects gastric mucosa from HCl
  • Cell Types of Gastric Mucosa
  • Body of stomach contains oxyntic glands
  • Parietal cells ? HCl and Intrinsic Factor
  • Chief cells ? Pepsinogen
  • Antrum of stomach contains pyloric glands
  • G cells ? Gastrin into the circulation
  • Mucous neck cells ? Mucus, HCO3-, and Pepsinogen

48
Gastric Secretion
49
Gastric Gland
50
HCl Secretion
  • Parietal cells secrete HCl which converts
    inactive pepsinogen to pepsin
  • Within cell, CO2 combines with H2O to form H and
    HCO3-
  • At apical membrane, H secreted into lumen of
    stomach via H-K ATPase
  • Cl- follows H into the lumen by diffusing
    through Cl- channels
  • At basolateral membrane, HCO3- absorbed into
    blood via a Cl--HCO3- exchanger
  • Eventually HCO3- secreted back into GI tract by
    pancreas

51
HCl Secretion
52
Regulation of HCl Secretion
  • ACh
  • Released from vagus nerve
  • Binds to receptors on parietal cells
  • Produces H secretion by parietal cells
  • Atropine blocks muscarinic receptors on parietal
    cells
  • Histamine
  • Released from mastlike cells in gastric mucosa
  • Binds to H2 receptors on parietal cells
  • Produces H secretion by parietal cells
  • Cimetidine blocks H2 receptors
  • Gastrin
  • Released into circulation by G cells of stomach
    antrum
  • Binds to receptors on parietal cells
  • Stimulates H secretion

53
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54
Ulcers
  • Gastric Ulcers
  • Mucosal barrier is defective allowing H and
    pepsin to digest portion of mucosa
  • Helicobacter pylori produces NH4 from urea
  • NH4 breaks down mucosal barrier to H
  • Duodenal Ulcers
  • More common
  • H secretory rates are higher than normal
  • Excess H damages duodenal mucosa

55
Pancreatic Secretion
  • Exocrine pancreas secretes 1 L/day into duodenum
  • Fluid consists of HCO3- and enzymes
  • HCO3- neutralizes H delivered to duodenum from
    stomach
  • Enzymatic portion digests carbohydrates,
    proteins, and lipids into absorbable molecules
  • Structure of Pancreatic Exocrine Glands
  • Comprises 90 of pancreas
  • Rest of pancreatic tissue is endocrine pancreas
    and blood vessels
  • Acinar Cells
  • Line blind end of branching duct system
  • Secrete enzymatic portion
  • Ductal Cells
  • Line the ducts
  • Secrete aqueous HCO3- component

56
HCO3- Secretion
  • Apical membrane of ductal cells contains a
    Cl--HCO3- exchanger
  • Basolateral membrane contains Na-K ATPase and a
    Na-H exchanger
  • CO2 and H2O combine in cells to form H and HCO3-
  • HCO3- is secreted into pancreatic juice by
    Cl--HCO3- exchanger
  • H is transported into blood by Na-H exchanger
  • Absorption of H causes acidification of
    pancreatic venous blood

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58
Regulation of Pancreatic Secretion
  • Acinar cells (enzymatic secretion)
  • Receptors for CCK and muscarinic receptors for
    ACh
  • CCK is most important stimulant
  • I cells secrete CCK in presence of amino acids
    and fatty acids in intestinal lumen
  • ACh also stimulates enzyme secretion
  • Ductal cells (aqueous secretion of HCO3-)
  • Receptors for CCK, ACh, and secretin
  • Secretin (from S cells of duodenum) is major
    stimulant
  • Secreted in response to H in intestine
  • Effects of secretin are potentiated by both CCK
    and ACh

59
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60
Bile Secretion
  • Necessary for digestion and absorption of lipids
    in small intestine
  • Mixture of bile salts, bile pigments, and
    cholesterol
  • Bile salts emulsify lipids to prepare them for
    digestion
  • Solubilize products of lipid digestion in packets
    called micelles

61
Bile Secretion and Recycling
  • Produced and secreted by liver
  • Stored in gallbladder
  • Ejected into small intestine when gallbladder
    contracts
  • After lipids absorbed, bile salts are
    recirculated to liver via enterohepatic
    circulation
  • Absorption of bile salts from ileum into portal
    circulation
  • Delivery back to liver
  • Extraction of bile salts from the portal blood by
    hepatocytes

62
Bile Secretion and Recycling
63
Case 15 Chief Complaint
  • 36-year-old woman had 75 of her ileum resected
    following a perforation caused by severe Crohn's
    disease (chronic inflammatory disease of the
    intestine)
  • Postsurgical management included monthly
    injections of vitamin B12
  • After surgery, she experienced diarrhea and noted
    oil droplets in her stool

64
Case 15 Diagnosis
  • Crohn's disease caused intestinal perforation
    which necessitated subtotal ileectomy (remove
    terminal portion of small intestine)
  • Consequences of removing ileum
  • Decreased recirculation of bile acids to liver
  • Normally, 95 of secreted bile acids returned to
    liver
  • In patient with ileectomy, most secreted bile
    acids lost in feces increasing demand for
    synthesis of new bile acids
  • Liver unable to keep pace with demand ? ? total
    bile acid pool
  • Emulsification of dietary lipids for digestion
    and micelle formation for absorption of lipids
    are compromised
  • Dietary lipids are excreted in feces as oil
    droplets (steatorrhea)

65
Case 15 Diagnosis
  • Decreased absorption of intrinsic factor-vitamin
    B12 complex
  • Normally, ileum is site of intrinsic
    factor-vitamin B12 complex absorption
  • Intrinsic factor secreted by gastric parietal
    cells
  • Patient must receive monthly injections of Vit
    B12
  • Diarrhea caused by high concentrations of bile
    acids in lumen of colon (because not
    recirculated)
  • Bile acids stimulate Cl- secretion by colonic
    epithelial cells
  • Na and water follow Cl- into lumen producing a
    secretory diarrhea (sometimes called bile acid
    diarrhea)

66
Case 15 Treatment
  • Her physician prescribed cholestyramine to
    control her diarrhea
  • Cholestyramine binds bile acids in colon
  • In bound form, bile acids do not stimulate Cl-
    secretion (prevent secretory diarrhea)
  • She continues to have steatorrhea
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