Physiology/Pathophysiology of the Digestive System

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Physiology/Pathophysiology

for Nurses

Agenda

• Overview of Processes– Secretion, digestion, absorption, motility

• A Functional Anatomy Primer– Histophysiology of gut and accessory organs

• Regulation of GI Processes• Selected Disorders

– Secretion, digestion, absorption and motility– Inflammation in the gut

Overview ofGI Processes

Food

Secretion

Digestion

Absorption

Blood Vessels

Motility

Microanatomy of the GutThe Basic Plan

• Mucosa• Submucosa• Muscularis• Serosa

• Regional variations ?

Regional Variations in the Gut

• Mucosal layer – form reflects function:

Regional Variations in the Gut

• Submucosa can contain lymphoid tissue:– Eg: “Peyer’s Patches” in

the Ileum

– Function?

Specialized Secretory Structures

Small Intestine Large Intestine

Specialized Secretory Structures

Small Intestine

Nerve Plexes in the Gut

Histology of Accessory Organs

pancreas

Liver

• Review liver functions

• Digestive secretions?

Secretion

Primary Types of Secretions

• Digestive Enzymes

• Mucous

• Fluid and Electrolytes

Digestive Enzymes

Location Enzyme TargetsSalivary Glands Amylase

LipaseStarchTriglycerides

Stomach PepsinLipase

ProteinsTriglycerides

Pancreas AmylaseLipase and ColipasePhospholipaseTrypsinChymotrypsin

StarchTriglyceridesPhospholipidsPeptidesPeptides

Intestine EnterokinaseDisaccharidasesPeptidases

Activates trypsinComplex sugarspeptides

Mucous

• Glycoproteins called mucins

• Produced by …– Salivary, Mucous and Goblet cells

• Functions?

• Release factors– Ach, neuropeptides, cytokines

So how does secretion occur?

Secretion of Proteins

Secretion of Water and Electrolytes

Na+

K+

Cl-

Na+

K+Cl-

Na+

H2OLUMEN

Enterocyte

Enterocyte Tight Junction

K+

H+ Secretion by Parietal Cells

K+

H+

Enterocyte

Enterocyte

LUMEN

CO2 + H2O

HCO3- + H+

Cl-

HCO3-

CA

CO2

HCO3- Secretion by Pancreatic Cells

Enterocyte

Enterocyte

K+Na+

LUMEN

Cl-

HCO3-

CA

CO2 + H2O

H+ + HCO3-

CO2

Digestion

Three Phases

• Cephalic Phase

• Gastric Phase

• Intestinal Phase

Cephalic Phase

• Anticipatory/Sensory

• Mediated via vagus/Ach– Chief cells secrete acid– Parietal cells secrete pepsinogen– G cells secrete gastrin

• Vagus also mediates via pancreas

Gastric Phase

• Begins with arrival of food in stomach

• Two stimuli:– stretch receptors in stomach– digested protein

• G cells in antrum stimulated by vagus and by protein

An Integrated Example …

ACh

STIMULUSSTIMULUS

Long Reflex

Short Reflex

STIMULUSSTIMULUS Vagus

EffectorEffector

Absorption

Primary Substances Absorbed

• Carbohydrates

• Peptides

• Fats

CarbohydratesThe GLUT Family of Transporters

Enterocyte

Enterocyte

K+Na+

Na+

Glucose

Fructose

LUMEN

Peptide Absorption

Enterocyte

K+Na+

Na+

H+Na+

H+

LUMEN

Fat Absorption

• Please review role of bile salts in micelle formation

• What types of molecules can cross the gut barrier without specialized transporters?

Motility

Two Types of Movement

• Peristaltic– moves food forward

• Segmental– mixing

Motility - How is it controlled?

• Single unit smooth muscle

• Certain cells generate slow wave pacemaker potentials

• Change in potential not required for contraction

TIME

mV

Force

Integration:Endocrine Reflexes

STIMULUSSTIMULUS Feedforward, Distension, Acid, Food

Receptor/Receptor/IntegratorIntegrator

Endocrine cells (stomach, intestine)

EffectorEffectorSmooth muscle Exocrine cells

Endocrine and Nervous Systems

EfferentEfferentPathwayPathway

Gastrointestinal hormones

ResponseResponse Contraction, secretion, synthesis, hunger

Some Selected GI Disorders

• Disorders of the GI Tract– malabsorption (lactase deficiency)– motility (GERD)– constipation/diarrhea– bleeding and pain

• Disorders of Accessory Organs– Ascites

Lactase Deficiency

• Deficiency of lactase at brush border

• Increased lactose provides carbon for bacteria

• Presents as bloating, crampy pain, osmotic diarrhea Microvillus

Enzymes

GERD

• Lower esophageal sphincter relaxes spontaneously

• Acid, bile, enzymes erode esophagus

• worsened by delayed emptying

• Presentation: post-prandial heart burn, regurgitation at 1 hour

• Tmt: ?

Constipation

• Many Causes– Neurogenic

• eg: Hirschsprung’s

– Muscle weakness• eg: post-surgery

– Low-residue diets

• Tmt?

Laxatives We Know and Love

• A. Irritants and Stimulants– Castor oil, aloe, phenophthalein

• B. Bulking Agents– Psyllium, bran, magnesium

• Stool softeners– Ducosate, mineral oil, glycerin

Diarrhea - Three Mechanisms• Osmotic

– osmoticant in intestine

• Secretory– excessive mucosal secretion– toxins, some tumours

• Motility– surgical

H2O

Antidiarrheals

• Antimotility Agents– Diphenoxylate, loperamide

• Adsorbents– Kaolin, pectin

• Agents that modify fluid/electrolyte transport– NSAIDS

Bleeding and Pain

• Bleeding– causes: varices, peptic ulcers, Mallory-Weiss tear– hematemesis, hematochezia, melena, occult– causes?

• Pain– parietal, visceral, reffered– mediators: histamine, bradykinin, serotonin– causes?

Ascites - Third-Spacing in the Abdomen

Cirrhosis

IncreasedLymph Portal

Hypertension

HepatocyteFailure

Inc. CapillaryHydrostatic Press.

Decr. Albumin

Decr. OncoticPressure

Ascites

And now, a few words about free radicals and GI pathophysiology...

The Gut Lining has cells in different states

• Differentiated cells– columnar epithelial cells– secretory cells

• Mitotically-active basal cells

• Apoptotic cells

Redox status affects enterocytes...

Redox Status

Gro

wth

Reduced Oxidized

Quiescence Proliferation Apoptosis Necrosis

Differentiated

MitoticallyCompetent

Transformed

Initiation of Inflammatory Processes

I-BB

TRAF

IRAK

TIR

LPS

NF-κB

InflammatoryMediators

Redox Control of NF-B?

I-I-BB

TRAF

IRAK

TIR

LPS HydroperoxidesLipid Peroxides

NF-B

Balancing Redox Statein the Gut

Oxidants Reductants

IschemiaLipid Peroxides

Vitamin EOther Antioxidants

NEC: An Inflammatory Process in the Neonatal Intestine

• Stage 1:– Abdominal distension,

vomiting, increased gastric residual, lethargy, apnea, bradycardia

• Stage 2: – Pneumatosis intestinalis

• Stage 3:– Shock, DIC, acidosis,

thrombocytopenia, intestinal perforation

Loren Yamamoto, MD University of Hawaii

Histologic Presentation of NEC(Hsueh et al, 1998. Pediatr. Dev. Pathol. 1:2-16)

So What?

• What factors affect redox state of the gut?