GI Lecture 1: Control/Regulations, Blood Circulation, Motility, Secretion

the control mechanisms of the GI system regulates:

conditions of the lumen

versus internal control

the control mechanisms of the GI system are NOT governed by the nutritional status of the body but rather

by the volume and composition of luminal content

Luminal stimuli:

• Distension of the wall by the volume of the luminal contents

• Chyme osmolarity (total solute concentration)

• Chyme acidity

• Chyme concentrations of specific digestive products (aa, glucose,FA, peptides)

GI receptors are located where and are what type of receptors?

• located on the wall of the tract

• mechanoreceptors, osmoreceptors, chemoreceptors

what are the effectors of the GI tract?

• muscle layer in the wall of the tract

• Exocrine glands that secrete substances into the lumen

Neural control of the GI system

1) enteric system
-myenteric plexus
-submucosal plexus
2) ANS
3) sensory nerves

Describe the enteric system components and its functions

• Lies entirely in the GI wall

• Extends from esophagus to anus

• Controls movement and secretion

• May be excitatory OR inhibitory

• Can function on its own or under ANS

Describe Myenteric plexus (Auerbach's plexus) location and control

• Between longitudinal and circular muscle

• Controls movement; excitatory and inhibitory

• Extends all the way

Primarily controls:

1. Local and inter-regional motility activity through regulation of Circular and Longitudinal Muscle Layers

2. Blood Flow. However, overlapping and integrated control exists between the plexuses

Describe Submucosal plexus (Meissner's plexus) location and control

• Submucosa

• Controls local secretion and blood flow

• Local

Primarily Controls:

1. Smooth muscle activity of the Muscularis Mucosae, affecting mucosal surface area

2. Secretion from mucosal endocrine and other secretory cells

What are the Neurotransmitters of the enteric system

• ACh: excitatory

• NE: inhibitory

What are the Effectors of the enteric system

• Muscle cells

• Exocrine glands

  • all have ducts, secrete into Lumen

Sensory Neurons of the Enteric system

-respond to various stimuli (stretch, food composition)
-mainly via receptors (mechano-, chemo-)
-located w/in mucosal epithelium of SM layers
-afferent fibers may RELAY SENSORY info to either enteric or extrinsic neurons which relay the appropriated efferent response

Secretory Neurons of the Enteric System

-innervate mucosal secretory cells
-regulate endocrine & exocrine functions of the mucosa

Motor Neurons of the Enteric System

-innervate smooth muscle layers
-control gut motility & mucosa surface area
-Blood vessel vasoconstriction & vasodilation are also affected

Interneurons of the Enteric System

-synapse with other neurons to relay information between
neurons within the same or adjacent plexus or between enteric
and extrinsic neurons
-This allows communication and integration of functions up and
down as well as outside the GI tract.
-Allows communications between enteric system and CNS

P-ANS connection with enteric system
-cranial through?
-sacral through?

cranial through the VAGUS nerve (CNX)
sacral through the PELVIC NERVE (PN)

P-ANS stimulation has an ______influence on the functions of the GI tract?

Excitatory

motor innervation of the vagus nerve

-tongue
-pharynx
-upper esophagus (swallowing)

Vagus nerve innervates what parts of the GI tract?

from tongue to transverse colon

Pelvic nerves innervates what parts of the GI tract?

Descending colon to rectum

motor innervation of the pelvic nerves

external anal sphincter (defecation)

S-ANS connection with Enteric System
-originates at?
-through what?

-Originates in T5 and L2
-Through the sympathetic chain

S-ANS stimulation generally has an ______influence on the functions of the GI tract?

Inhibitory

Sensory nerve endings in the GI epithelium and wall send AFFERENT fibers to

-Enteric plexus
-Sympathetic system
-Parasympathetic system

There is some motor VOLUNTARY innervations in the GI. For example

-Swallowing
-Defecation

Non neural control involves what molecules

hormones and GI peptides

GI regulatory peptides carry the non-neural control of GI functions and are classified according to

mechanism of delivery to target cell
-endocrine peptide: hormone
-paracrine peptides
-neruocrine peptides

GI regulatory peptides

-detected in lumen
-reach their target cells via circulation
-Exist in CNS and in GI plexus neurons where they function as neurotransmitters

Endocrine Peptide Hormones

Released (Secretion) from specialized mucosal Endocrine Cells (APUD = Amine Precursor Uptake Decarboxylation) into the blood

Endocrine Peptide Hormones act via what on target cells?

Act via hormone-specific Receptors on Target Cells--all acting on smooth muscle of a gland
ex. of peptide hormones
o Cholecystokinin
o Gastrin
o Gastric inhibitory peptide
o Motilin
o Secretin

Paracrine peptides

-Released from APUD Cells
-Do NOT enter the circulation
-Delivered by DIFFUSION to closely neighboring Target Cells
ex. histamine

Neurocrines

-produced in neurons
-released from axon endings in response to an action potential
-act on target cells via synapses
ex.
-Vasoactive Intestinal Peptide (VIP)
-Gastrin Releasing Peptide (GRP)
-Enkephalins

Most GI endocrine hormones are secreted by?

Duodenum & Jejunum

Only hormone secreted by stomach

Gastrin

Hormones released from colon

None

Basic principles of GI regulatory peptides

-each hormone participates in a feedback control mechanism that regulates some aspect of the GI luminal environment
-each hormone affects more than 1 type of target cell

FA and AA trigger what?

Trigger CCK secretion from cells in small intestine into blood

CCK stimulates what?

Stimulates the pancreas and gall bladder

When FA and AAs are absorbed what happens to the stimuli for CCK

The stimuli for CCK is removed (feedback)

A single GI effector cell contains

-Receptors for more than one hormone
-Receptors for more than one neurotransmitter
-Receptors for more than one paracrine agent

Potentiation

Occurs when one hormone effects amplifies the response of another, e.g., secretin and CCK

Arterial blood is carried to the GI tract through

1. Superior mesenteric artery
2. Inferior mesenteric artery
3. Celiac trunk

From the GI tract, spleen and pancreas blood is carried to the liver through ________

The portal vein

In the liver blood flow through large ______ along which specialized cells remove bacteria and particulate matter

Sinusoids

The liver cells also detoxify the blood from the GI tract. From the liver, blood returns to circulation through _______

Hepatic Vein

Hepatic Portal System: 4 basic steps

1) small intestine absorbs products of digestion
2) Nutrient molecules travel in hepatic portal vein to liver
3) liver monitor blood content
4) blood enters general circulation by way of hepatic vein

The Splanchnic circulation is blood flow through GI tract, the spleen, pancreas, and liver

What 3 arteries are involved?

1. Superior mesenteric artery

2. Inferior mesenteric artery

3. Celiac artery

   Main takeaway: bring blood from the AORTA to the wall of the gut

Splanchnic circulation: The circling arteries penetrate the wall and branch into smaller arteries within __________

the muscle, mucosa and submucosa

Mechanics of the special arrangement of smaller arteries within the villi of the small intestine

-the arterial and venous blood flow in the villi are in OPPOSITE DIRECTION
-Blood oxygen diffuses directly from the capillaries into the venules WITHOUT the NEED TO REACH THE TIP OF THE VILLI

Liver cells _____ the blood and use nutrients absorbed from the GI

Detoxify

Blood then enters the _______ (2) which empties into the _______

Central Vein, Hepatic Vein

The types of GI motility

1) propulsive movement
2) mixing movement

What is propulsive movement: peristalsis

A series of alternating contractions and relaxations of smooth muscle that lines the walls of the digestive organs and that forces food to move forward

An inherent property of smooth muscle

stimulation of propulsive movement (peristalsis)

Distension, Chemical, physical

Effectual peristalsis requires an active what?

Active Myenteric Plexus

Contractile ring in circular muscle behind the point of distension

Absence of myenteric plexus

-Congenital megacolon
-Atropine

Congenital megacolon

Congenital disorder of peristalsis of distal bowel caused by absence of parasympathetic ganglion cells in the myenteric plexuses

Atropine

Paralyzed cholinergic nerves

Peristalsis results from the initiation of

• A unidirectional Spreading Contraction of the Circular Muscle

• This typically forms behind a food bolus and serves to move the bolus in the aborad (away from the mouth) direction

• Physiologically, peristalsis mainly results in a Propulsive Action on GI contents which causes net movement. Some mixing of content also occurs

Mixing movement: segmentation results from:

• A Focal Contraction of the primarily Circular Muscle layer that constricts the lumen and compresses GI contents at the site

• This action is coordinated with Longitudinal Muscle layer contraction and circular muscle layer relaxation on either side of the constricted site

• Physiologically, segmentations primarily results in a mixing action that reduces food particle size, homogenize particles with digestive enzymes and other secretions, and exposes contents to the mucosal surface

• Segmentations does NOT typically results in significant net movement (propulsion) of material along the tract

Peristalsis is PRIMARILY PROPULSION + Mixing, while segmentation is

Mixing only

transit time through segments of GI tract:
-esophagus
-stomach
-small intestine
-large intestine and colon
-total

esophagus: 5-15 sec
stomach: last: 3-5 hrs, first= 1-5 min
small intestine: 2-4 hrs
large intestine and colon: 36-48 hrs
total: 48 hrs

relaxation of SM sphincters = _________ GI propulsion
constriction of SM sphincters =_________GI propulsion

relaxation of SM sphincters = increase GI propulsion

constriction of SM sphincters = decreased GI propulsion

Extrinsic Autonomic Control

Increased Parasympathetic = Increased propulsion and mixing

Increased Sympathetic = Decreased propulsion and mixing

Enteric Autonomic Control

• Primarily Myenteric Plexus (Muscularis Externa)

• integrates with Extrinsic Controls

• Allows fine local control

• Coordinates interregional propulsive/mixing movements

Voluntary and GI Peptide Control:

Overall minor roll

• Voluntary - Swallowing reflex and defecation control

• GI Hormones - Motilin: stomach motility action

Intrinsic Basal Tone

Some Smooth Muscle regions of the GI tract (e.g. Lower Esophageal Sphincter) are under almost constant Tonic Contraction

The “natural” state of the muscle without any extrinsic influences is the contracted state

This basal contractile tone is distinguished because it is initiated without apparent extrinsic input from nerves or hormonal factors

Tone is generated intrinsically by the smooth muscle cells themselves

→ Regions displaying basal muscle tone are said to be under Intrinsic Myogenic Control

Tonic Contractions can be __________ physiologically by certain extrinsic factors such as

• autonomic neural input or

• hormones

• other regulatory peptides.

Transiently Modulated

GI secretion refers to the ______ and ______ of fluids and substances into the lumen of the GI tract by mucosal cells and/or accessory GI organs

Production; Release

__ L of fluid is secreted into the GI tract each day, not including approximately 2 L of daily fluid intake in the diet .

>7 L

Secretions along the GI tract are _______ in Composition, depending on

Highly Variable

-Mucosal Cell Type (APUD, Parietal, Chief, Goblet, etc.) within the segment
-Accessory Organs (e.g. Salivary Gland, Pancreas, Liver).

Compostion of GI secretions

-water
-mucus
-ions
-enzymes
-hormones

Goblet cells

-single-celled glands lining the GI mucosa (most in large intestine/colon)
-secretes MUCUS onto the the mucosa to lubricate and protect the surface from abrasion and chemical digestion

Brunner's Glands

-compound glands near the proximal duodenum
-secrete alkaline mucus that neutralizes gastric acid

Tubular Glands

-stomach and duodenum
-parietal cells (secretes acids)
-chief cells (secretes pepsinogen)

Crypts of Lieberkuhn

-deep pits formed by mucosal folds
-mainly small intestine
-contain several types of secretory cells including: goblet cells and enterocytes that secrete:

• digestive enzymes

• H2O

• ions that facilitate digestion and absorption

APUD cells

-single-cell mucosal endocrine glands
-mainly small intestine
-secrete various GI hormones involved in endocrine regulation of GI functions

Accessory Glands

-salivary glands
-pancreas
-liver
-secrete saliva, HCO3-, enzymes, & bile) for Lubrication, Acid Neutralization, Digestion & Absorption.

Basic Mechanics of Stimulation of Secretion

1. Contact of food

   1. direct stimulation of glandular epithelium

   2. activation of enteric nervous system

2. Autonomic stimulation

   1. Parasympathetic

3. Hormonal Regulation