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The Integrated Gut from mouth to anus

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... decides what gets swallowed. The decision making process ... Swallowing. Neural Feedback from the pharynx and esophagus initiate swallows to clear 'leftovers' ... – PowerPoint PPT presentation

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Title: The Integrated Gut from mouth to anus


1
The Integrated Gut(from mouth to anus)
  • Jim Pierce
  • Bi 145b
  • Lecture 10, 2008-9

2
Gut Function
  • Organisms gastrulate to make a gut
  • The gut exists
  • To take in nutrients
  • To excrete wastes
  • We understand the locoregional function
  • Lets talk about global function

3
Gut Function
  • The brain is nothing more than
  • An overgrown ganglion
  • Near the Mouth
  • That decides what gets swallowed
  • The decision making process for eatingis beyond
    the scope of this class
  • We will talk about nutrition and neurohormonal
    nutritional axes during integration lectures

4
Gut Function
  • Once food is available
  • The somatic nervous system allows us to
    consciously control the act of eating.
  • From the planning of eating on, the gut must
  • Feedforward (in the segments of gut ahead)
  • Feedback (in the segments of gut behind)

5
Gut Function
  • Mechanisms of Feedforward
  • Cell to Cell (Single Unit Smooth Muscle)
  • Enteric Nervous System
  • Parasympathetic input (Vagus Nerve)
  • Sympathetic input (Splanchnic Nerves)
  • GI and Neuro Hormones

6
Gut Function
  • Mechanisms of Feedforward
  • Locoregional
  • Cell to Cell (Single Unit Smooth Muscle)
  • Enteric Nervous System
  • Global
  • Parasympathetic input (Vagus Nerve)
  • Sympathetic input (Splanchnic Nerves)
  • GI and Neuro Hormones

7
Gut Function
  • Mechanisms of Feedback
  • Enteric Nervous System
  • Parasympathetic (Vagus Nerve)
  • 90 sensory / afferent fibers
  • 10 effector / efferent fibers
  • GI and Neuro Hormones

8
Gut Function
  • Mechanisms of Feedback
  • Locoregional
  • Enteric Nervous System
  • Global
  • Parasympathetic input (Vagus Nerve)
  • GI and Neuro Hormones

9
Enteric Nervous System
  • Parasympathetic Input
  • Primarily Cholinergic Neurons
  • Sympathetic Input
  • Primarily Adrenergic Neurons
  • Underlying ENS
  • Primarily NANC (non-adrenergic non cholinergic)
    neurons
  • Exitatory Substance P
  • Inhibitory Vasoactive Intestinal Peptide

10
Substance P
  • Substance P is an 11 amino acid polypeptide
  • CNS Effects include pain modulation
  • Gut Effects of administration include Nausea and
    Pain
  • Inhibitor Substance P antagonist (SPA) (aka
    aprepitant) is available in the market in the
    treatment of chemotherapy-induced nausea /
    emesis.

11
Substance P
12
Vasoactive Intestinal Polypeptide
  • Source Made by many different cells throughout
    gut, pancreas, and peripheral nerves
  • Main Role Rest and Digest
  • Effects
  • Vasodilation
  • Smooth muscle relaxation
  • Increase water and electrolyte secretion by gut
  • Stimulated by intragastric fat and vagus nerve

13
Vasoactive Intestinal Peptide
14
Gut Hormones
  • Gut Hormones
  • Provide autocrine, paracrine, endocrine signals
    for feedforward and feedback regulation and
    control.
  • Provide a level of computation to modulate gut
    function.
  • Allow integration with body neurohormonal state.

15
Hormones involved in Gut Function
16
Eating
  • Eating consists of
  • The Cephalic Phase(Brain prepares gutvia Vagus
    Nerve)
  • Transitioning gutfrom SOMATICto
    AUTONOMICcontrol

17
Feed Forward from the Mouth
18
Swallowing
  • Transitioning from somatic to autonomicinvolves
    the pharynx swallowing reflex.
  • Proximal Pharynx is Skeletal Muscle
  • Distal Pharynx is Smooth Muscle
  • Middle Pharynx is a transition from Skeletal to
    Smooth

19
Swallowing
  • A midlevel somatic signalstimulates tongue,
    mouth, and pharynx contraction to pushthe food
    bolus into the pharynx.
  • This signal also relaxesthe upper and
    loweresophageal sphincters
  • This signal also initiatespharyngeal and
    esophagealperistalsis

20
Swallowing
  • Neural Feedback from the pharynx and esophagus
    initiate swallows to clear leftovers
  • Neural Feedback from the Larynx and
    Tracheainitiate cough to clearthe airway
  • Locoregional Feedback (reflexes) in the
    esophagusensure esophageal stripping

21
Stomach Function
  • Stomach indicates to the CNSFullness via Vagus
    nerve
  • Gut indicates to the CNSFullness via GI
    Hormones
  • Body indicates to the CNSMetabolic State via
    Hormonal Axes
  • Well talk more about these decisionsduring
    endocrine system

22
Stomach Function
  • The whole purpose of the stomach reservoir is to
    convert BOLUS feedingsinto CONTINUOUS feedings.
  • To understand all the feedback that goes on,
    lets introduce the GI Hormones

23
Hormones involved in Gut Function
24
Proximal Stomach
  • Proximal Stomach Hormones
  • Several Neurotransmitters (especially Seritonin)
  • Ghrelin Hot New Hormone
  • Likely to be more

25
Ghrelin
  • Source produced in proximal stomach
  • Main Role initially identified as a Growth
    hormone releasing hormone
  • Integrates proximal stomach stateinto total body
    metabolic phenotype.
  • Not much is known its the new guy

26
Ghrelin
  • Green is Peptide Backbone

27
Leptin
  • Source produced by fat cells (not gut)
  • Main Role complete the neurohormonal fat axis
    give feedback about fat state to the rest of the
    body
  • It circulates at levels proportional to body fat.
  • It enters the central nervous system (CNS) in
    proportion to its plasma concentration.
  • Its receptors are found in brain neurons involved
    in regulating energy intake and expenditure.

28
Leptin
29
Proximal Stomach
  • Goal of Proximal Stomach Hormones
  • Integrate the stomach into the bodysmaster
    metabolic plan.

30
Distal Stomach
  • Distal Stomach (Antrum) is part of thesecond gut
    MVR
  • We will find several hormones produced both at
    the distal stomach as well as duodenum and
    pancreas

31
Distal Stomach
  • Main Distal Stomach GI Hormones
  • Gastrin
  • Somatostatin

32
Gastrin
  • Sources Distal Stomach G-cells and Pancreatic
    Islet D-Cells
  • Main Role Stimulates proximal stomach secretion
  • Growth Role Long term growth hormone for
    intenstinal mucosa
  • Functional Roles
  • Stimulates parietal cells to secrete acid
  • Stimulates chief cells to secrete pepsinogen
  • Augments gastric mucosal flow by vascular dilation

33
Gastrin
  • Gastrin Secretion from G-Cells
  • Stimulated by
  • Antral Amino Acids oligopeptides
  • Antral Calcium or Alchohols
  • Antral pH gt 3
  • Vagus Nerve
  • Inhibited by Antral pH lt 1.5

34
Gastrin
35
Somatostatin
  • Produced in small amounts by Stomach and in
    larger amounts by Pancreatic D cells
  • Main Role Globally inhibits GI function
  • Keeps the activation by Gut hormones under
    control

36
Somatostatin
  • Somatostatin Secretion
  • Stimulated by All kinds of food
  • Inhibited by nothing yet identified
  • Clinical Uses Turning down gut secretion and
    controlling gut bleeding (reduces blood flow)
  • Disease (too much) Inability to secrete
    wellleads to steatorrhea, gallstones, weight
    loss.

37
Somatostatin
38
Duodenum
  • Duodenal Hormone Secretion
  • Secretin
  • Cholecystokinin
  • Motilin
  • Gastric Inhibitory Peptide

39
Secretin
  • Source Argyrophil S-cells in duodenum
  • Major role Increases secretion from pancreas
    (particularly bicarbonate)
  • Minor roles
  • Increase bile flow
  • Decrease stomach acid by decreasing gastrin
    release
  • Inhibit gastric emptying

40
Secretin
  • Secretin Secretion
  • Stimulated by
  • Acid
  • Fats and Lipids in the Duo
  • Bile salts
  • Inhibited by high pH in the Duo


41
Secretin
42
Cholecystokinin
  • Source I-cells of the duodenum and proximal
    jejunum
  • Main Role Aids in fat processing by increasing
    bile secretion
  • Growth Role Trophic factor for Pancreas and
    Gallbladder
  • Targets Gallbladder, Pancreas, Sphincter of Oddi

43
Cholecystokinin
  • Functions
  • Squeeze Gallbladder
  • Relax Sphincter of Oddi
  • Increase pancreatic secretion
  • Increase intestine motility, decrease gastric
    emptying
  • Trophic factor on pancreas and gallbladder mucosa
  • Secretion stimulated by
  • Duodenal Fat (long chain FA and micelles)
  • Duodenal Amino Acids (tryptophan phenylalanine)
  • Secretion inhibited by trypsin, chymotrypsin

44
Cholecystokinin
45
CCK and Secretin
  • Compare and Contrast
  • Both cause bile and pancreatic juice secretion
  • CCK increases Liver gt Pancreas
  • Secretin increases Pancreas gt Liver

46
Motilin
  • Source Cells throughout gut, highest in duodenum
    and proximal jejunum
  • Main Role Initiates MMC and increases
    interdigestive gut motility
  • Transitions from postprandial to fasting

47
Motilin
  • Motilin secretion stimulated by
  • Duodenal acid and food
  • Vagus Nerve
  • Gastrin Releasing Peptide
  • Inhibited by
  • Somatostatin
  • Secretin / CCK
  • Pancreatic polypeptide
  • Duodenal fat

48
Motilin
49
Gastric Inhibitory Peptide
  • AKA Glucose-dependent insulinotropic polypeptide
  • Source K-cells of Duodenal glands
  • Targets Pancreatic islets, Proximal Stomach
  • Main Role Inhibits Gastric Secretion
  • Secondary Roles
  • Enhances insulin effects
  • Trophic Factor for Beta Cells

50
Gastric Inhibitory Peptide
  • Gastric Inhibitory Peptide secretion
    isstimulated by
  • Duodenal Presence of
  • Amino Acids
  • Glucose
  • Long chain Fatty Acids
  • Hyperglycemia

51
Endocrine Pancreas
  • The majority of the pancreasis a secretory
    exocrine gland
  • A minority of the pancreas isan secretory
    endocrine gland
  • These collections of endocrine cellsare called
    the Islets of Langerhans

52
Endocrine Pancreas
53
Endocrine Pancreas
  • Islets contain
  • Alpha Cells - Glucagon (15-20)
  • Beta Cells - Insulin (65-80)
  • Delta Cells - Somatostatin (3-10)
  • PP Cells - Pancreatic Polypeptide (lt 1)
  • Epsilon Cells Ghrelin? (lt0.5)

54
Alpha Cells - Glucagon
55
Beta Cells - Insulin
56
Delta Cells - Somatostatin
57
Glucagon
  • Sources
  • Stomach Gastric Glucagon
  • Intestines Enteroglucagon
  • Primarily from Alpha cells of islets Glucagon
  • Main Role Energy Utilization
  • Targets Liver and Adipose Tissue, Gut
  • (these effects will be covered in endocrine)
  • Starts as preprogluagon (180 AA)
  • Can become glicentin, glucagon, GLP1,2

58
Glucagon
  • Functional Liver and Adipose Roles
  • Increases hepatic glycogenolysis
  • Increases hepatic gluconeogenesis
  • Increases hepatic mobilization of glucose
  • Increases lipolysis
  • Increases ketogenesis
  • All produce energy for cellular use

59
Glucagon
  • Functional Roles in the Gut
  • Inhibits gastric acid, pancreatic secretion
  • Relaxes stomach and duodenum
  • Increases intestinal motility
  • Clinical use slows stomach / duodenum / ampulla
    emptying for GI radiology

60
Glucagon
  • Secretion of Glucagon is stimulated by
  • Hypoglycemia
  • Elevated serum AA
  • Acetyl-choline,
  • Gastrin inhibiting peptide
  • Gastrin releasing peptide
  • It is inhibited by
  • Hyperglycemia
  • Insulin
  • Somatostatin
  • Alpha adrenergic stimuli
  • GLP-1

61
Glucagon
62
Insulin
  • Well discuss insulin more duringendocrine
    physiology and nutrition
  • Source Beta Cells of the Pancreas
  • Role 70 Growth Hormone 30 Acute Metabolism

63
Pancreatic Polypeptide
  • Source PP Islet cells of pancreas
  • Main Role Indicates Switch from Gastricto
    Intestinal Phase of Gut Function
  • Functional Roles
  • Pancreas Decreases Bicarb and Water secretion
  • Gallbladder Inhibits contraction
  • Intestine Changes from Fasting to Postprandial
    pattern
  • Stimulated by Food, Vagus, GI hormones like
    CCK and Secretin

64
PP and Motilin
  • Compare and Contrast
  • Both work proximally to changethe motor pattern
    of intestinal function
  • Motilin changes from postprandial to fasting
    patterns
  • PP changes from fasting to postprandial patterns

65
Peptide YY
  • Source Cells in distal ileum, colon, rectum
  • Main Role Ileal Brake (For Gastric Emptying)
  • Effects
  • Inhibits gastric emptying
  • Inhibits gastrin stimulated acid secretion
  • Inhibits cck-stimulated pancreatic secretion
  • Stimulated by intraluminal fat

66
Neurotensin
  • Source N Cells in distal small intestine
  • Main Role Ileal Brake (for Absorption)
  • Effects
  • Inhibits gastrin mediated gastric acid secretion
  • Stimulates pancreatic secretion
  • Inhibits intestinal motility
  • Triggers mesenteric vasodilation
  • Stimulated by luminal fat

67
Bombesin
  • Source Bombina bombina a european tree frogs
    skin
  • Similar structure to gastrin releasing peptide
  • Function
  • Stimulates release of most GI hormones
  • Increases secretion in gut
  • Increases motility
  • Lick frog get diarrhea

68
Bombesin
69
Gut Neurohormone Pairs
  • ENS
  • Adrenergic Neurons, Cholinergic Neurons
  • Substance P Neurons, VIP Neurons
  • Proximal
  • Gastrin, Somatostatin
  • GIP, GRF
  • CCK, Secretin
  • Motilin, Pancreatic Polypeptide
  • Distal
  • Peptide YY, Neurotensin

70
Gut Function
  • Weve met the neurohormones.
  • Weve eaten some food.
  • What happens next?

71
Stomach
  • Have we secreted and mixed enough?

72
Duodenum
  • How much secretions do we need?

73
Small Intestine
  • Which motor pattern do we need?

74
Colon
  • Have we absorbed enough water?

75
Questions?
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