Unit 6A: Gastrointestinal (GI) Function

58 slides

what is digestion in the GI system

breaking down macromolecules (nutrients) into forms that CAN be transported across epithelium

what are the 4 functions of the GI system

1. digestion

2. absorption

3. secretion

4. motility

what is absorption in the GI system

actually transporting nutrients, water, ions, vitamins across epithelium

what is needed to accomplish digestion and absorption

secretion and motility

what is secretion

releasing enzymes into the gut lumen

what is motility

keeping the gut contents moving

what happens if the protective barriers in the GI tract break down alongside macromolecules

peptic, duodenal ulcers

Peptic ulcers = open sores on the lining of the stomach

duodenal ulcers = ulcers specifically in the duodenum

what are some things that provide protection from pathogens in the GI tract? why is this important in the GI tract specifically

important bc GI lining is largest area of contact btwn internal and external environment

mediated by…

• epithelial barrier

• mucus

• digestive enzymes

• acid

• Gut Associated Lymphoid Tissue (GALT)

  • needs to react to pathogens but not to “foreign” proteins associated w food

what are some important considerations the GI tract specifically has to abide by

• needs to digest macromolecules but not itself

• needs to allow entry of digested nuts but not pathogens

• needs to maintain balance btwn water input/output (balance btwn secretion and absorption)

what is gut associated lymphoid tissue (GALT)

note: also called mucosa lymphoid tissue

part of immune system that works in the GI tract → acts as kinder, gentler immune system

• needs to react to pathogens but not foreign proteins associated w food

explain water balance in the GI tract

fluid input = fluid ingested + secretions from body

• (~9L / day = 2L ingested + all the rest are secretions)

fluid output = fluid absorbed + fluid excreted (in feces) (~9L)

fluid input = fluid output

when is food considered to be “in” your body

Food isnt really "in” your body until it crosses your gut epithelium

what are rugae

characteristic folds on the inner lining of the stomach

where does food go after exiting the stomach (explain all the following steps)

into the small intestine

• duodenum → jejunum → ileum

into large intestine

• colon → rectum

what are mucosal surfaces

the inner lining of certain passages and organs in the body that are exposed to the external environment (eg in the GI tract, back of eyes, vagina, etc)

what are the 4 main components of mucosal surfaces

1. mucosa

   • inner lining

2. submucosa

   • some deeper glands protrude from here

3. smooth muscle layers

4. serosa

   • like bag holding everything tg

what are the 3 things the mucosa comprised of? explain them

1. Epithelial layer: The top layer of cells that can absorb or secrete substances.

2. Lamina propria: layer of connective tissue underneath

   • supports epithelium.

   • where a lot of secretory glands are

3. Muscularis Mucosa: thin layer of smooth muscle found at the base of the mucosa → just below lamina propria.

   • Moves the mucosa gently to enhance contact with contents (like food or air).

   • Helps expel glandular secretions.

   • Maintains the tone of the mucosal layer

epithelial layer, then connective tissue, then thin smooth muscle layer

what is the submucosa comprised of

the submucosa itself is connective tissue but it contains

• Meissner’s (submucosal) plexus

  • provides outtermost innervation for GI tract

connective tissue containing nerves

what are the smooth muscle layers comprised of? explain them

• Circular muscle

  • Myenteric (Auerbach’s) plexus

    • runs btwn these 2 sets of muscles

• Longitudinal Muscle

2 types of muscle and nerves between

what is the serosa

epithelial tissue

• outlines intestines

• submucosa

• myenteric plexus

• muscularis

• serosa

• mucosa

what are the 3 main differences in the structure of the stomach compared to the intestines? why are those differences there

1. stomachs in addition to circular and longitudinal muscle in their smooth muscle layers, they also have oblique (diagonal) muscles

• bc the stomach is a bag not a tube → has to contract in more dimentions

2. stomachs have gastric glands → deep epithelial grooves → for exocrine secretions

3. rugae

   • allow stomach to expand / contract as needed w varying amounts of food → inc SA of the stomach → aids in digestion

     • smooth out as the stomach expands

what are some notable structures in the small intestine that are not within the stomach? what do they do

1. plica → permanent, crescent-shaped folds of the mucous membrane → increase SA for nutrient absorption

• do NOT smoothen out like rugae in stomach

2. Villi (and microvilli) → tiny, finger-like projections → further inc SA of intestine → facilitate absorption of nutrients into the bloodstream

3. Payer’s patches → only obvious evidence of immune system cells in small intestine

   • patches of immune cells → more numerous at far end of small intest (far away from stomach)

what are the 3 ways the intestines inc their SA

1. plica

2. villli

   • made of epithelial cells

3. microvilli

   • on epithelial cells that make up the villi

what is the brush border in the small intestines

the densely packed, microvilli-covered surface of absorptive epithelial cells (enterocytes)

what are peristalsis and segmental contractions? explain them

the 2 main patterns of contraction in gut motility

peristalsis → moving food from mouth to anus

segmental contractions → mixing / churning

• maximizes exposure to digestive enzymes and epithelium

explain single-unit smooth muscle. where are they commonly located

smooth muscle all connected by gap junctions → fxs as a single unit → easier for single waves of depolarization to travel

most common in walls of GI tract, urinary tracts, and blood vessels

which areas of the gut are tonically active

smooth muscle sphincters

• prevent food from moving backwards

  • eg btwn esophagus n stomach, anus and external environment, etc

stay contracted for minutes to hours

which ares of the gut undergo phasic contractions

posterior stomach, small intestine

stay contracted for a few seconds

explain gut motility in the small intestine between meals

migrating motor complexes sweep slowly down tract (~90 mins from stomach → large intest)

• electrical complexes that sweep and slowly move things down

explain gut motility in the small intestine during/after meals

peristaltic and segmental contractions

what determines the force and duration of muscle contraction

force = amplitude

duration = frequency

what are the amplitude and duration of contraction influenced by

• neurotransmitters (autonomic input)

• hormones

• paracrine factors

what are slow wave contractions in gut smooth muscle similar to

pacemaker potentials in cardiac tissue → BUT much less frequent and do not necessarily reach threshold

explain slow wave contractions in gut smooth muscle

below threshold → no contraction

above → V-gated Ca+ channels open, action pots, contraction

t/f: slow wave frequency varies in diff regions of tract? explain why or why not

true → set by pacemaker cells between smooth muscle layers

• eg more frequent in duodenum than stomach

what are the interstitial cells of cajal

specialized cells in the gastrointestinal (GI) tract → act as pacemakers → generate electrical slow waves that regulate gut motility

explain the secretion of water and ions in the GI tract

ions mostly are excreted via mem transporters

water follows via osmotic gradient

water and ions can also pass between cells (paracellular) in some regions

explain acid secretion by parietal cells

as H+ is secreted from the apical side, bicarb (from CO2 + OH-) is absorbed into blood

• H+ (acid) gets pumped into lumen of stomach in exchange for K+

• AT SAME TIME Bicarb gets pumped into blood in exchange for Cl- (which then diffuses into stomach lumen to make HCl with H+)

Overall:

• hydrogens and Cl pushed out into stomach lumen

• HCO3- goes into blood

note: this happens in gastric glands

explain the alkaline tide

temporary increase in blood pH (making it more alkaline)

• occurs after a meal, especially one that stimulates gastric acid secretion

  • bc bicarb goes into blood (inc pH)

  • and H+ and Cl- goes into stomach (dec pH)

explain how salt (NaCl) is secreted in the small intestine, colon, and salivary glands

Via Crypt Cells

Na, K, and Cl enter the epithelial cells via NKCC transporters

• Cl- enters lumen through CFTR channel

  • this is the driving force

• Na and K go back into interstitial fluid

  • Na+ is reabsorbed (pumped back into interstitial fluid)

  • K+ diffuses through ion channel back into interstitial fluid

• Negative Cl- in lumen attracts Na+ by paracellular pathway

  • Na+ goes through paracellular pathway and water gets dragged along with it

• Na, Cl, (making NaCl) and water are now in the intestinal lumen

Creates intestinal saline that mixes w mucus

which cells secrete mucus

goblet cells

explain why bicarb is secreted from the pancreas into duodenum

pancreatic ducts secrete bicarb into duodenum to neutralize acid from stomach

• Stomach makes acid -> dumps extremely acidic contents into top of small intestine -> enzymes in small intest cannot work in high acidic conditions -> needs to b quickly neutralized -> duct cells dumb bicarb on them to minimize acidity

what are acinar cells

cells in the pancreas that secrete digestive enzymes

explain pancreatic bicarb secretion on the cellular level? what is the driving force

bicarb is secreted via apical Cl-/HCO3 antiporter

1. Cl enters pancreatic duct cell / duodenal cell via basolateral NKCC transporter and leaves via apical CFTR channel

2. Luminal Cl then reenters the cell via Cl/HCO3 antiporter

bc chloride is the driving force, this is referred to as a chloride shift mechanism

what is needed in excess for pancreatic bicarb secretion

requires a lot of carbonic anhydrase so a lot of bicarb is produced

explain what cystic fibrosis is

• mutation in the gene that encodes for CFTR channel in pancreatic cells that secrete bicarb

• leads to deficits in Cl (and water) transport

• named for changes in the pancreas

  • creates fluid-filled cysts and fibrosis (scarring)

• without it, the luminal Cl levels will stay low and it can’t be antiported back into the pancreatic duct cells and push bicarb back

would taking a pill that replaced enzymes in the pancreas/small intestine help with cystic fibrosis

yes → would include bicarb and help neutralize HCl from stomach

explain how and what secretes enzymes

secreted by either exocrine glands (eg pancreas, salivary) or epithelial cells lining stomach and small intestine

• synthesized by rough ER, packaged by golgi into vesicles, stored in cell under signal for release by exocytosis

wht are “brush border” enzymes

enzymes that remain linked to apical mems by protein or lipid “stalks”

what are zymogens

inactive precursors for enzymes → enzymes are often released as these inactive precursors to prevent auto-digestion (enzymes digesting/breaking down things on their way to their targets)

what types of stimulation typically regulates secretion → sympathetic or parasympathetic

parasympathetic stimulation (through vagus nerve)

what is mucus primarily made of

“mucins” → mixture of glycoproteins

what types of cells produce mucus

exocrine cells

• serous cells in salivary glands

• mucous cells in stomach

• goblet cells in intestine

what is the hepatic lobule? what shape are they

the functional unit of the liver

• hexagonal in shape

• blood and bile flow through it

explain how bile flows from the liver to the digestive tract (how it is secreted)

note:

• bile ductules

• gall bladder

• sphincter of Oddi

• duodenum

• common bile duct

• bile canaliculi

• hepatocytes

in hepatic lobule

1. Hepatocytes (liver cells arranged around central vein) → secrete bile into →

2. Bile canaliculi (tiny channels btwn hepatocytes where bile is secreted - collect bile and carry it in opposite direction of blood flow (away from central vein) → drain into →

3. Bile ductules (receive bile from canaliculi and lead to larger ducts outside of lobule)→ merge into →

4. Common hepatic duct

5. From here, bile can take two paths:

   • Stored in gall bladder

   • Or go directly through common bile duct to small intestine

6. Common bile duct passes through the sphincter of Oddi and empties bile into the duodenum (the first part of the small intestine)

what are xenobiotics

foreign substances

what does the hepatic portal system do

ensures most nutrients and xenobiotics (foreign substances) absorbed in the GI tract are processed by liver before they enter general circulation

• xenobiotics (eg drugs and toxins) are detoxified by the liver BEFORE reaching systemic circulation

where does blood flow through the hepatic portal system

1. Absorption in the GI Tract:

• Nutrients from digested food are absorbed through the capillaries in the intestinal villi.

  • nuts enter hepatic portal vein → carries de oxy blood from GI tract and spleen to liver (high in nuts, low in O2)

    • Note: Fats are exception—they enter the lymphatic system instead of the blood.

2. Hepatic Portal Vein (~75% of Liver Blood Flow):

• Carries nutrient-rich, deoxygenated blood from the GI tract and spleen to the liver.

2. Hepatic Artery (~25% of Liver Blood Flow) (another place blood comes into liver from) :

• Carries oxygen-rich blood from the aorta to the liver.

3. Sinusoids of Liver:

• Blood from the hepatic artery and portal vein mix here.

• Sinusoids are leaky capillaries that allow for the exchange of substances between the blood and hepatocytes (liver cells).

• The liver can filter toxins, process nutrients, and add plasma proteins here.

4. Central Vein → Hepatic Vein → Inferior Vena Cava:

• After processing, blood drains into central veins, then into the hepatic veins, and finally enters the inferior vena cava to return to the heart.

what are the 3 key components of bile

• bile salts (facilitate fat digestion)

• bile pigments (eg bilirubin from hemoglobin breakdown)

• cholesterol

how do we still feel the effects of drugs if they are filtered at the liver

Drugs come into liver and detox can happen, liver can completely break it down and dump it into duodenum to end up in feces BUT then body wouldn’t feel many effects -> usually some of it exits via hepatic portal vein and into circulation so there are systemic effects

what is bilirubin and where does it go

Bilirubin -> breakdown of RBCs goes into speeel, makes Hb, makes bilirubin -> goes into liver and is sent out with bile into feces

 

Colour of bilirubin is most of the reason why feces are the colour they are

t/f: the liver builds proteins or contributes to circulating AA pool that rest of body can use

true

what are some of the main substances that go into the liver from the GI tract (through hepatic portal vein)

• bilirubin

• nutrients

• drugs / foreign substances

what are some of the main substances that go into the liver from the peripheral tissues (hepatic artery)

• bilirubin

• nuts

• hormone and drug metabolites

what gets secreted by the bile duct of the liver and into the duodenum

• bile salts

• bilirubin

what gets secreted into the hepatic vein by the liver and into the peripheral tissues

• glucose

• plasma proteins

t/f: the liver makes glucose

true → oscillates between creating glucose and glycogen

what is bilirubin responsible for

the normal colour of feces

normal colour of urine

what are some indicators of injury / pathology related to bilirubin

• yellow phase of bruises (blood pools and cant get bilirubin filtered out)

• yellow pigmentation in jaundice (hyperbilirubinemia)

what is digestion a combination of? why and where does that occur

combination of mechanical and enzymatic processes

• occurs in mouth, stomach, small intestine

• chewing and churning exposes more SA to enzymes

  • emulsification (combination) via bile exposes more SA for lipid digestion

where does most absorption occur

in the small intestine

t/f: digestion and absorption are directly regulated (explain why or why not)

false → influenced by motility and secretion, which are regulated by hormones, NS, and. local mechanisms

explain absorption in the small intestine

goes from the gut lumen → the apical mem → into epithelial cell (called enterocyte) → through basolateral mem → into lamina propria → into either the capillaries or lymph

where are enterocytes located

on microvilli

where are crypt cells located

in the lamina propria

how much of our caloric intake consists of carbs

around half

• mostly starch and sucrose

how do artificial sweeteners work

trick body into activating their “sweet” receptors but don’t get broken down into monosaccharides to enter enteroctes on microvilli -> just excreted

what are some examples of glucose polymers

starch and glycogen

what are some examples of dissacharides

maltose, sucrose, lactose

which monosaccharides do maltose, glucose, and lactose digest into? which enzyme(s) are used?

Maltose

Maltase

Glucose + Glucose

Sucrose

Sucrase

Glucose + Fructose

Lactose

Lactase

Glucose + Galactose

explain how carbohydrates are digested and absorbed

starches and disaccharides are broken down and how the resulting monosaccharides are absorbed by intestinal epithelial cells

Digestion:

• glucose polymers (eg. starch, glycogen) broken down by amylase (from pancreas and saliva

• amylase converts them into disaccharides (maltose, sucrose, lactose)

• disaccharides are broken down by its specific brush border enzyme (ie lactase, maltase, sucrase) into monosaccharides

Absorption:

• Glucose and Galactose

  • work like in kidneys

    • enter apical mem of epithelial cells in small intest via SGLT (sodium glucose transporter) using Na+ cotransport

    • exit basalateral mem into bloodstream via GLUT2 (facilitated diffusion)

• Fructose

  • enters apical mem via GLUT5 (facilitated diffusion)

  • exits via GLUT2 just like (glucose and galactose)

what are endopeptidases

proteases (break down proteins) in the middle (make them smaller chunks)

what are some exs of endopeptidases

pepsin (from stomach)

trypsin and chymotrypsin (from pancreas)

what are exopeptidases

cleaves peptide bonds at the end of a protein or peptide chain, releasing single amino acids, dipeptides, or tripeptides

what does it mean when an enzyme has “ogen” at the end of it

it means the enzyme is a zymogen (in its inactive form)

explain protein digestion and what its products are

stomach:

• HCl in stomach denatures proteins

  • stomach endopeptidases can then break them down (eg pepsin in stomach)

Small Intestine:

• pancreatic endopeptidases (trypsin, chymotrypsin) break them down further

• exopeptidases from brush border and pancreas digest terminal peptide bonds to release individual AAs

produces free AAs, di and tri peptides

explain protein absorption

di and tri peptides are cotransported w H+ into enterocytes

• di and tripeptides → enter through H+ cotransport

  • broken down into individual AAs by intracellular peptidases

• AA → enter through Na+ cotransport

• all intracellular AAs now enter blood through antiport with Na+

when are proteins carried in tact across the cell (transcytosis)

only for first few hours/days of human life

where are most of our fat calories from

triglycerides

explain what makes digestion of fats in the stomach unique

HCl in stomach is polar → can’t dissolve fats (like-dissolves-like)

• leave stomach as large droplers mixed with aqueous chyme (other stuff digested in stomach that stuck to it)

  • low SA available to interact w enzymes

what helps break down fats

broken down into smaller particles through action of bile salts

what are bile salts all derivates of

cholesterol → just all have diff side chains

t/f: bile salts are amphipathic

true

explain what happens to fats when they enter the duodenum

• small intestine senses fats enter it → release hormone called cholecystokinin (CKK)

  • causes the gallbladder to secrete bile produced by the liver → contains bile salts

• hydrophobic parts → conduct emulsification → coat the large lipids and break them down

  • higher surface area to volume ratio, meaning → more SA for digestive enzymes to work on

• Pancreatic lipases (digestive enzymes originating from the pancreas) break down triglycerides into free fatty acids and monoglycerides

  • bile salts can actually inhibit lipase (make it harder to bind) → co-enzyme called colipase is secreted by pancreas w lipase → binds to lipase and fat droplets, anchoring them together even when bile salts are present

• all fats (except for cholesterol) are digested into smaller components

  • broken-down fats, now monoglycerides free fatty acids, and phospholipids, alongside bile salts form micelles

explain how micelles are arranged

cholesterol molecules and free fatty acids, along with hydrophobic pieces of the other molecules (like the phospholipids) located inwards, and the hydrophilic pieces pointing outwards

what are micelles used for

used to transport the digested fats through the watery environment of the small intestine until they reach enterocyte