Lecture 31-34 (gastrointestinal system)

What is the major function of the digestive system?

to transfer nutrients from the food we eat into our body to be used as fuel and building blocks

Overview of the Digestive Organs:

1. mouth and salivary glands

2. pharynx and esophagus

3. stomach

4. small intestine

5. large intestine

What is the general structure of the digestive tract wall?

made up of four major tissue layer

• serosa

• muscularis externa

• submucosa

• mucosa

Serosa:

provide a protective outer layer and to secrete serous fluid (lubricates), which reduces friction between digestive organs and surrounding structures

• allows freedom for mixing and propulsive movements

• continuous with mesentery throughout much of the tract

Muscularis Externa:

major smooth muscle coat of digestive tube where contractile activity produces propulsive and mixing movements

• Usually two layers

  • Inner circular layer → Contraction decreases diameter of lumen

  • Outer longitudinal layer → Contraction shortens the tube

• myenteric plexus

Myenteric plexus:

is part of the enteric nervous system that controls and coordinates muscle contractions (peristalsis) to propel food through the digestive tract

• increases overall gut tone and the strength/speed of contractions

• provides motor innervation to the muscular layers of the digestive tract

  • in-between muscle layers

Submucosa:

providing support, elasticity, and nourishment via its blood vessels, lymphatics, and nerves, facilitating nutrient absorption, glandular secretion (mucus, enzymes, electrolytes), and regulating muscle activity (peristalsis) through its nerve network

• acts as a structural scaffold, joining the mucosa to the muscle, and plays a key role in sensing stretch and initiating pain signals

• contains submucosal plexus nerve network part of the enteric nervous system

Mucosa:

inner lining responsible for protection, secretion, and absorption, acting as a critical barrier against pathogens and toxins while secreting mucus, enzymes, and hormones, and facilitating nutrient uptake through its folded structure that vastly increases surface area

1. epithelial layer

2. lamina propia

3. muscularis mucosa

Epithelial layer:

cells modified for secretion and absorption

• contains exocrine gland cells → secrete digestive juices, mucus, enzymes into lumen

• contains endocrine gland cells → secrete gastrointestinal hormones into capillaries

Lamina propia:

loose connective tissue

• small blood vessels, lymphatics, and enteric neurons

• contains gut-associated lymphoid tissue (GALT)

True or False: The lumen of the gastrointestinal tract is continuous with the external environment.

True

Why is the lumen being continuous with the external environment important?

• pH in the stomach can fall as low as 2 where inside the body the range of pH that is compatible with life = 6.8 - 8.0 (homeostatic range is 7.35 - 7.45)

• Harsh Enzymes that hydrolyze food could destroy the body’s own tissues

  • therefore enzymes are synthesized in an inactive form and are activated when they reach the lumen

• Millions of microorganisms inhabit the GI-tract, and these could be lethal if they entered the body proper

What is the process of the digestive system?

1. ingestion, chewing, swallowing, defecation

2. secretion

3. digestion

4. absorption

What is the purpose of ingestion, chewing, swallowing, defecation?

transfers food into the digestive tract via the mouth

• skeletal muscle → voluntary

Digestive motility:

muscular contractions that mix and move forward the contents within the tract, facilitating later steps in the digestive process

• smooth muscle → involuntary

• propulsive movements

• mixing movements

Propulsive movements (peristalsis):

move the contents forward through the digestive tract

• happens in the esophagus and when you defecate (large intestine)

Mixing movements (segmentation):

happens mainly in the stomach + small intestine and serves 3 purposes

• aid digestion by mixing food with digestive juices

• facilitate absorption by exposing food to absorbing surfaces

• forward movement (slow and non-linear)

Exocrine secretion:

digestive juices are secreted into the lumen by exocrine glands upon appropriate neuronal or hormonal stimulation

• secretions contain enzymes, acids, buffers, electrolytes, and water that

  • promote digestion

  • adjust tonicity

  • provide lubrication for better movement throughout the tract

Endocrine secretion:

gut hormones are secreted into the blood by endocrine glands upon appropriate neuronal or nutritional stimulation

• gut hormones are chemical messengers released into circulation and act on receptors in distal locations to regulate motility, pancreatic secretions, and other digestive tract (and non-digestive tract) functions

Digestion:

accomplishes the breakdown of structurally complex foodstuffs into smaller, and eventually absorbable units

• chemical

Chemical digestion:

enzymatic hydrolysis of carbohydrates, proteins, and fats into absorbable units

Chemical digestion of carbohydrates:

complex carbohydrates broken down by 1) amylase into disaccharides and then 2) set of enzymes into monosaccharides

• only absorb glucose

Chemical digestion of proteins:

each enzymes chops bonds between proteins to make smaller fragments of amino acids

Chemical digestion of fats:

chopping fatty acid tails to form three free fatty acids

Absorption:

the transfer of small absorbable units along with water, vitamins, and electrolytes from the lumen into the blood or lymph

• why our blood sugar goes up after a meal

Basic electrical rhythm (BER):

creates a fluctuating potential that allows stronger "spike potentials" to trigger actual muscle spasms, coordinating movements like peristalsis and segmentation, with frequencies varying along the gut

• sets the rhythm and frequency for gut contractions, but usually doesn't cause them directly

• membrane potential of pacemaker cells in the stomach → interstitial cells of Cajal

What happens when no food is in the lumen of digestive tract?

1. the membrane potential of pacemaker cells (ICC) oscillate at 3-5 times per sec (3-5 Hz)

2. ICCs in the small intestine depolarize more frequently (8-11 Hz) → the BER in the small intestine

3. these depolarizations spread thru gap junctions to smooth muscle cells, then signal propagated through the tract by the enteric nervous system

4. however, these depolarizations exceed spike threshold only 10-15 times per day → the migrating motility complex

Migrating motility complex:

triggers contractions that are frequent enough to “sweep” residual contents from the stomach & small intestine to the large intestine

• triggered by hormone motilin → extrinsic regulation

What happens with food in the lumen?

1. stretch and gastrin (hormone induced by protein in the stomach) activate neural circuits that increase the amplitude & frequency of the basic electrical rhythm (BER) depolarizations

2. when these depolarizations exceed spike threshold (approx -35 mV), the smooth muscles spike & therefore contract

3. stretch & gastrin thereby increase digestive tract motility

What else can move the ICCs below threshold, inhibit motility signal, or act directly on muscle cells?

certain hormones, intrinsic nerve reflexes, or sympathetic output move ICCs below threshold and inhibit motility signal, or act directly on muscle cells themselves

What are intrinsic factors controlling digestive system functions?

• autonomous smooth muscle cells

• interstitial cells of Cajal (ICC)

• enteric nervous system

Autonomous smooth muscle cells:

connected by gap junctions, thereby forming a functional syncytium

• single-unit smooth muscle

Interstitial cells of Cajal (ICC):

act as pacesetter cells and generate slow-wave potentials (Basic Electrical Rhythm; BER)

• If threshold is reached and action potentials are triggered, then the whole muscle sheet contracts as a unit

Enteric nervous system:

vast network of neurons in the gut wall controlling digestion (motility, secretion, blood flow) autonomously, yet communicating bidirectionally with the central nervous system (CNS) via the gut-brain axis

• coordinates local activity within the digestive tract

• myenteric + submucosal nerve plexuses

What are the functions of intrinsic factors controlling digestive system?

refers to extrinsic nerves and gastrointestinal hormones

Extrinsic nerves:

originate from outside the digestive system from both the sympathetic and parasympathetic branch where they influence motility and secretion by:

• Modifying activity of the enteric nervous system

• altering gastric hormone secretion

• acting directly on smooth muscle and glands

Gastrointestinal hormones:

long-range chemical messengers secreted into blood and act on receptors in distal locations to regulate digestive tract (and non-digestive tract) functions

Lips and Tongue:

contain food in mouth and guide food during chewing and swallowing

Teeth:

begin mechanical breakdown by chewing of food

Palate:

roof of oral cavity from nasal passage

• allows chewing and breathing to occur simultaneously

Uvula:

soft tissue that hangs from the rear of the mouth and seals off nasal passage during swallowing

Salivary glands:

made up of 3 gland and secrete saliva in response to autonomic stimulation 

• sublingual

• submandibular

• parotid

What does saliva contain?

• mucus to moisten food and lubricate

• lysozyme to lyse bacteria

• Bicarbonate buffers which neutralize acids

• amylase, which begins chemical digestion of carbohydrates by cleaving polysaccharides into maltose

Mouth and Salivary Glands:

describes how salivation works

• simple or conditioned reflexes

Where does the digestion of carbohydrates (polysaccharides) start?

starts in the mouth

Swallowing:

refers to the entire process of moving food from the mouth, through pharynx
and esophagus, to the stomach in two stages

• is a sequentially programmed all-or-none reflex, initiated when bolus is voluntarily forced by tongue to rear of mouth into pharynx

  • can be initiated voluntarily but cannot be stopped once it has begun

What are the two stages of swallowing?

• oropharyngial stage → when the food is still in your mouth entering the pharynx

• esophageal stage → when food is in the esophagus

True or False: In the esophageal stage, peristaltic (propulsive) waves move bolus (food) into the stomach.

True, at the end of the oropharyngeal stage, the pharyngoesophageal sphincter closes & breathing resumes

Stomach:

J-shaped chamber located between the esophagus and the small intestine

• thick layer of smooth muscle connected to small intestine by pyloric sphincter and is a key regulator of gastric emptying

  • fundus → located above the gastroesophageal sphincter

  • body → middle

  • antrum → bottom

Main functions of the stomach:

• store ingested food until it can be emptied into small intestine

  • occurs in the body of the stomach

• create gastric secretions → including HCl and enzymes that begin chemical digestion of protein

• gastric motility converts pulverized food to chyme → a thick liquid mixture of pulverized food and gastric secretions

Gastric filling:

gastric volume can expand ~20-fold during a meal, by expansion/ flattening of deep folds

• expansion of gastric volume is a vagally-mediated process called receptive relaxation

What are the two distinct areas of secretory gastric mucosa?

oxyntic mucosa (body and fundus) and pyloric gland area (antrum)

In oxyntic mucosa, what are the 3 types of gastric EXOCRINE secretory cells, associated with gastric pits?

1. Mucous cells → secrete thin, watery mucus

2. Chief cells → secrete enzyme precursor, pepsinogen

3. Parietal (oxyntic) cells secrete HCl and intrinsic factor (essential for normal function of red blood cells)

HCl activates what in the stomach?

activates pepsinogen in the lumen, protecting stomach from itself

Functions of HCl in the stomach?

activates pepsinogen to active enzyme pepsin and provides acid medium for optimal pepsin activity

• denatures protein

• along with salivary lysozyme, kills most of the microorganisms ingested with food

Enterochromaffin- like (ECL) cells:

secrete histamine (activates parietal cells) and is usually a local intermediate in a signaling loop

• in this case, activates parietal cells which are the HCl- producing cells

• purple spots

How do stomach cells survive despite the acid?

in between gastric pits, the actual lining of the stomach has mucus producing cells that make a very thick layer of mucus that release bicarbonate

• prevents outside of stomach from directly damaging mucosal cells

• cells are not meant to last long

Endocrine secretory cells in the pyloric gland area secrete what?

• secrete hormone gastrin into bloodstream which stimulates parietal, chief, and ECL cells

  • G cells

• secretes hormone somatostatin into the bloodstream which inhibits parietal and ECL cells

  • D cells

Gastrin increases what?

increases gastric motility and promotes movement of leftover, undigested/unabsorbed material out of ileum into large intestine

Gastric mixing and emptying:

strong peristaltic contractions occur in the antrum that

• mix food with gastric secretions to produce chyme

• propel chyme towards pyloric sphincter, where a small amount is pushed into the duodenum

• in response to chyme, sphincter closes and remaining chyme is tumbled back into the antrum.

How does the volume of the chyme control gastric mixing and emptying (pyloric function)?

distention directly stimulates stretch receptors on the smooth muscle, stimulates enteric and parasympathetic nervous system as well as the stomach hormone gastrin to increase motility

• more volume, more contractions (to an extent)

How does the fluidity of the chyme control gastric mixing and emptying (pyloric function)?

liquids do not require extensive mixing and churning; contents must be rendered fluid before they are evacuated

How does fat control gastric emptying (via neural and hormonal factors)?

fat is only digested and absorbed within the small intestine, so when fat is present in the small intestine further emptying is inhibited

• more fat, less movement for absorption

How does acid control gastric emptying (via neural and hormonal factors)?

highly acidic chyme from the stomach is neutralized by sodium bicarbonate (secreted from pancreas) in the duodenum

• Un-neutralized acid in the duodenum inhibits gastric emptying

• acidic = less emptying

How does hypertonicity control gastric emptying (via neural and hormonal factors)?

increased osmolarity in the duodenum indicates a back-up of nutrients and delays gastric emptying

• lots of nutrients = preventing gastric emptying for more absorption

How does distension control gastric emptying (via neural and hormonal factors)?

stomach initiates gastric emptying promoting motility while simultaneous duodenal distension triggers inhibitory hormones

• Stomach → has brakes to prevent overfilling of duodenum

• Small intestine → too much chyme in the duodenum inhibits gastric emptying

  • if stretched too much = can’t process efficiently

Factors that regulate gastric motility by triggering neural responses:

neural responses are mediated through both intrinsic nerves (short reflex) and autonomic nerves (long reflex)

• collectively this is called the enterogastric reflex

Factors that regulate gastric motility by triggering hormonal responses:

hormonal response involves release of hormones from duodenal mucosa collectively known as “enterogastrones”

• cholecystokinin (CCK) → stimulated by fat in the duodenum

  • inhibits antral contractions and induces contraction of the pyloric sphincter

• secretin → stimulated by unneutralized acid in the duodenum

  • released by S cells and slows gastric emptying

What are the 3 phases in gastric secretion?

• cephalic

• gastric

• intestinal

Cephalic phase:

pre-activation of your stomach by signals that have not yet reached the stomach, that are entirely in the head → seeing, smelling, tasting, chewing, swallowing of food

• excitatory → activates the stomach

• nervous and endocrine response involved

  • ACh → Parasympathetic + enteric NS neurotransmitter

  • intrinsic nerves + G cells activating gastric secretion and motility

Gastric phase:

once food hits the stomach, gastric emptying will become activated

• same as cephalic phase but more potent due to direct signals from within the stomach

• excitatory

Intestinal phase:

will activate both nerves and hormones (CCK + secretin) that collectively inhibit H⁺ secretion, pepsinogen, smooth muscle contraction, and overall reduce gastric secretion and motility

• inhibitory → slow down stomach

  • not a lot of acid content

• removing protein and extension as stomach empties gradually removes signal that activated stomach

Pancreas:

located dorsal and caudal to the stomach and is a mixed gland that contains both endocrine and exocrine tissue

Exocrine pancreas includes what?

• duct cells → release sodium bicarbonate (NaHCO3) into duodenum to neutralize acidic chyme

• acinar cells

Pancreatic acinar cells:

release digestive enzymes into duodenum and work better at a neutral or alkaline pH

• pancreatic amylase → carbohydrate digestion

• pancreatic lipase → only enzyme secreted throughout human digestive system that can significantly digest fat

• proteolytic enzymes

Proteolytic enzymes:

secreted as inactive forms and cleave bonds between amino acids

• Trypsinogen → converted to the active form trypsin by enteropeptidase in the luminal (brush border) membrane of small intestine

• Chymotrypsinogen → converted to active form chymotrypsin by trypsin

• Procarboxypeptidase → converted to active form carboxypeptidase by trypsin

Why are protein-degrading (proteolytic) enzymes (pepsin, trypsin, chymotrypsin and carboxypeptidase) secreted as inactive precursors, while lipid- and carbohydrate-degrading enzymes (amylase, lipase) are secreted as active precursors?

proteins are part of your own body’s structure, so proteases must be tightly controlled; fats and carbs aren’t, so their enzymes can be active right away

• ensures they are only activated in the right place and at the right time

How does the pancreas know when to secrete (CCK)?

same CCK that told pancreas to slow down in response to fat is telling to release more lipase and other enzymes (3 proteolytic and amylase) from acinous cells

• chyme in the duodenum stimulates pancreatic secretions via intestinal hormones, aka enterogastrones

• vagovagal reflex in response to increased volume in duodenum secretin and CCK

  • weak direct stimulation of duct and acinar cells by vagus (cephalic phase)

• CCK feedback loop

How does the pancreas know when to secrete (secretin)?

secretin released in response to acid in duodenum separates endocrine cells called S cells which trigger the release of secretin

• goes around in the duct cells which release bicarbonate and neutralize acid → a feedback loop

Both the secretin and CCK loops work in parallel as they stimulate and inhibit what?

stimulate the pancreas and inhibit the stomach so as to carefully dose the pace with which we empty our stomach

The liver receives its blood from what two sources?

the hepatic artery which provides oxygenated blood and the hepatic portal vein that ensures venous blood from digestive tract is first carried to the liver

• blood leaves liver through hepatic vein

Liver functions:

allows for detoxification of absorbed foreign compounds by the liver first, before they access the general circulation

• ensures that all absorbed monosaccharides and amino acids are routed to the liver first for processing

The major contribution of the liver to the digestive system is what?

the secretion of bile that is stored in the gall bladder due to CCK

• during, between, and after meals

During meals, what happens to bile?

it is secreted from the liver (and/or released from gall bladder) and enters the duodenum

• help digest fats by breaking large globules into smaller droplets

Between meals, what happens to bile?

the sphincter of Oddi closes and bile flows to the gallbladder for storage and concentration, becoming 5-10 times stronger as water is removed

• ready to help digest fats when you eat again

After meals, what happens to bile?

used bile salts get reabsorbed and recycled back to the liver with some ending up in the large intestine and being excreted

• ~95% of bile salts are reabsorbed in the distal small intestine and carried to the liver

Bile consists of what?

• Bile acids/salts

• Cholesterol

• Phospholipid (Lecithin)

• Bilirubin (RBC breakdown product)

• Aqueous mixture or bicarbonate, ions, water

Bile plays a role in what?

aids in fat digestion by emulsification → increases surface area for lipase

• helps neutralize stomach acid

• cholesterol balance

*CCK causes bile to be secreted!

Which of these is NOT a role for cholecystokinin (CCK)?

A) CCK promotes the release of pancreatic digestive enzymes from acinar cells

B) CCK slows down gastric emptying and gastric motility

C) CCK stimulates the release of bile by promoting smooth muscle contractions of the gall bladder and relaxing the sphincter of Oddi

D) CCK promotes the release of gastrin from G cells in the mucosae of the pyloric gland area

D) CCK promotes the release of gastrin from G cells in the mucosae of the pyloric gland area

Small intestine:

primary site of digestion and absorption

• duodenum → 5%

• jejunum → 35-40%

• ileum → 55-60%

Motility in the small intestine occurs via what?

occurs via segmentation which both mixes and propels chyme

• propulsion occurs because the frequency of local contractions gradually decreases along length of small intestine

• mixing food with digestive juices

• facilitate absorption

• forward movement

How does the small intestine facilitate absorption?

facilitates absorption by having a large surface area to allow nutrients to be absorbed by diffusion over the mucosal lining

• contributes to increase of surface area

  • circular folds → visible

  • villi → inside circular folds

  • microvilli → inside villi

Small intestine digestion:

carbohydrate and protein digestion accomplished by pancreatic enzymes, with fat digestion enhanced by bile secretions all occurring in the intestinal lumen

• small intestine produces digestive enzymes but act on surface if cells lining brush border

Brush border:

vastly increases surface area for absorption and secretion packed with digestive enzymes for final nutrient breakdown and plays a crucial role in nutrient transport and forming a protective barrier

• enteropeptidase

• disaccharidases →which complete the digestion of carbohydrates

  • maltase, sucrase, and lactase

• aminopeptidases →which complete the digestion of proteins

Carbohydrate digestion:

1. polysaccharides starch and glycogen are converted to the disaccharide maltose by amylase in the mouth and digestive tract lumen

2. maltose, lactose, and sucrose are converted to monosaccharides (glucose, galactose, and fructose) on the brush border of intestinal epithelial cells by the enzymes lactase, maltase, and sucrase

3. glucose and galactose are absorbed into the epithelial cells by active transport

4. fructose enters the epithelial cells by passive facilitated diffusion

5. glucose, galactose and fructose exit the cell into the blood by passive facilitated diffusion

Protein digestion:

1. proteins hydrolyzed into small peptide fragments and individual amino acids by pepsin and pancreatic proteolytic enzymes

2. small peptides are broken down into amino acids on the brush
   border by peptidases and aminopeptidases

3. amino acids absorbed into cell via Na⁺ and energy-dependent active transport and enter blood down their concentration gradients (6/7)

Fat digestion:

1. fat is emulsified by the detergent action of bile salts

2. lipases hydrolyze triglycerides into monoglycerides and free fatty acids

3. water insoluble products move within the interior of micelles to the epithelial cell surface

4. monoglycerides and free fatty acids diffuse into cell

5. monoglycerides and free fatty acids resynthesize into triglycerides

6. triglycerides coated with lipo- protein and form chylomicrons that are exocytosed from cell

7. chylomicrons enter lymphatic vessels

Small and Large intestine:

separated by the ileocecal valve and sphincter which is a one-way flow 

• contents from the ileum into cecum (first part of the large intestine)

• necessary to keep colonic bacteria from entering the ileum

Large intestine:

primarily for drying and storage, includes

• Cecum → blind-ended pouch below ileocecal valve

• Appendix → finger-like projection of lymphoid tissue

• Colon → ascending, transverse, descending, & sigmoid

• Rectum → “straight”, connected to anal canal

Large intestine motility is influenced through what?

through Haustral contractions, mass movement, and defecation reflex