Gastrointestinal Tract Physiology Flashcards
4 Main Functions of the GIT
Digestion
Absorption
Excretion
Host Defense
What is Digestion?
Chemical alteration of food into absorbable molecules
Affected by GI motility, pH changes, biological detergents, enzymes
What is Absorption?
Movement of digested food from the intestine into the blood or lymphatic system
What is Excretion?
Non-absorbable components of food, bacteria, intestinal cells, and hydrophobic molecules exit the body
What is Host Defense?
The GIT is continuous with the exterior of the body
-if the GIT is injured we can get sick because bacteria can enter the body
Highly developed immune system
Mouth
Chopper
Stomach
Blender, acid sterilizer, reservoir
Duodenum
Reaction vessel
Jejunum and Ileum
Catalytic and absorptive surfaces
Large Intestine
Residue combuster, desiccator, pelleter
Pancreas
Enzyme supplier
Neutralizer
Liver
Detergent supplier
Structure of the GIT
Long muscular tube stretching from mouth to anus
Layers of the GIT
Mucosa
Submucosa
Muscularis externa
Serosa
Layers of the Mucosa
Epithelium
Lamina propria
Muscularis mucosa
Epithelial Layer
Basolateral and apical arrangement
Different transport proteins at the apical surface compared to the basolateral
-tight junctions confine transport proteins to specific membrane regions
Provides selective uptake of nutrients, electrolytes, and water
-prevents the passage of harmful substances
Epithelial cells are born in crypts and daughter cells migrate up towards the villous
Nutrient Transport Across the Epithelium
Paracellular pathway
Transcellular pathway
Paracellular Pathway
Limited by tight junction seal
Water and small ions can diffuse through tight junctions
Transcellular Pathway
Two-step process which requires a transport protein on the apical and basolateral surface of the cell
Lamina Propria
Connective tissue Small blood vessels Nerve fibres Lymphatic vessels Immune and inflammatory cells
Muscularis Mucosa
A thin layer of smooth muscle
- not involved in contraction of the GIT
- might be important in the villi movement
Submucosa
Plexus (intricate network) of nerve cell bodies
-relay information to and way from the mucosa
Also composed of connective tissue, blood, and lymphatic vessels
Muscularis Externa
A thin layer of circular muscle
-fibers orientated to cause narrowing of the lumen
Myenteric nerve plexus
-regulates muscle function
Thinner outer layer of longitudinal muscle
-fibers oriented to shorten tube
Serosa
Thin layer of connective tissue
Forms connection between the intestines and the abdominal wall
Blood supply to the GIT
Blood perfuses the intestine and then flows to the liver via the portal vein
What is Portal Circulation?
The portal vein drains blood from the digestive tract and empties directly into the liver
Portal circulation = the circulation of nutrient-rich blood between the gut and the liver
What is the Purpose of Portal Circulation?
Allows the liver to:
- remove harmful substances
- process nutrients
Why is Portal Circulation Unusual?
The liver receives blood from both venous and arterial circulation
The venous supply is “in series” while most circulation to organs is “in parallel”
Regulation of GI Processes - Reflexes initiated by:
Distension of wall by volume of luminal contents
Osmolarity of contents
pH of contents
Concentrations of specific digestive contents
Regulation of GI Processes - Propagated by:
Mechanoreceptors
Osmoreceptors
Chemoreceptors
Enteric Nervous System (Intrinsic Neural Regulation)
Controls the activity of the secretomotor neurons -motility and secretory functions Contained completely within the walls of the GIT Dense and complex network of neurons Can function independently of the CNS Two nerve networks -myenteric plexus -submucosal plexus
Myenteric Plexus
Influences smooth muscle
Submucosal Plexus
Influences secretion
Extrinsic Neural Regulation
Regulation is through the ANS Influences the motility and secretion of the GIT -hunger -sight/smell of food -emotional state
Parasympathetic Response
Stimulates flow of saliva
Stimulates peristalsis and secretion
Stimulates release of bile
Sympathetic Response
Stimulates flow of saliva
Inhibits peristalsis and secretion
Short Reflexes
Intrinsic
Long Reflexes
Extrinsic
Endocrine Chemical Messenger
Chemical messenger passes from cell which produced it into the blood and is carried by the blood to its target
Neurocrine Chemical Messenger
Chemical messenger is released from a nerve cell, travels across a synapse and acts on a post-synaptic target cell
Paracrine Chemical Messenger
Chemical messenger diffuses through the interstitial fluid to nearby cells
Autocrine Chemical Messenger
Chemical messenger acts on the cell that produced it
Hormonal Control of GI Activity
One surface of each endocrine cell is exposed to the GI lumen
- chemical substances in lumen stimulate cell to release hormones across opposite surface of the cell into blood vessels in the lamina propria
- hormones travel though blood to target cells
Best Understood GI Hormones
Secretin Cholecystokinin (CCK) Gastrin Glucose-dependent insulinotropic peptide (GIP) All peptides
Generalized Facts about GI Hormones
Each participates in a feedback control system that regulates some aspect of the GI lumen
Most GI hormones affect more than one type of target cell
Types of Intestinal Motility
Peristalsis
Segmentation
Peristalsis
Circular muscle contracts on the oral side of a bolus of food (longitudinal layer relaxes)
Circular muscle contracted moves towards the anus, propelling the contents of the lumen in that direction
-as the ring moves, the circular muscle on the other side of the distended area relaxes (longitudinal muscle contracts) which facilitates smooth passage of the bolus
Segmentation
Contraction and relaxation of intestinal segments with little net movement of contents towards the large intestine
Mostly occurs in the small intestine
Allows mixing of contents with digestive enzymes
Slow transit time for absorption
Basic Electrical Rhythm
GIT had pacemaker cells throughout smooth muscle cells
-constantly undergoing spontaneous depolarization-repolarization cycles (slow waves)
In the absence of neural/hormonal input, spontaneous slow waves do not result in significant contraction
Phases of GI Control
Cephalic
Gastric
Intestinal
Cephalic Phase
Receptors in the had stimulated by:
-sight, smell, taste
-emotional state
Parasympathetic fibres activate neurons in the GI nerve plexuses
Gastric Phase
Receptors in the stomach stimulated by:
-distension, acidity, amino acids, peptides
Short and long neural reflexes mediate the response
Intestinal
Receptors in the intestine stimulated by:
-distension, acidity, osmolarity, digestive products
Mediated by short and long neural reflexes and by hormones secretin, CCK, and GIP
Parts of the brain involved in food intake
Hypothalamus
Ventromedial region
The hypothalamus and food intake
Feeding center in the lateral region
Activation increases hunger
-animals with damage to this area become anorectic and lose weight
The Ventromedial Region
Satiety centre
Activation makes you feel full
-animals with damage to this area overeat and become obese
Factors that Influence Food Intake
Orexigenic factors = increase intake
Anorexigenic factors = decrease intake
Orexigenic Factors
Neuropeptide Y
-neurotransmitter in the hypothalamus that stimulates hunger
Ghrelin
-synthesized and released from endocrine cells in the stomach during fasting
-stimulates the release of NPY and others in the hypothalamus feeding center
Anorexigenic Factors
Leptin (adipose)
Insulin (pancreas)
Peptide YY (intestines)
Melanocortin (hypothalamus)
4 Ways that Water Intake is Regulated
Increased plasma osmolarity
Decreased plasma volume
Dry mouth and throat stimulates thirst
Prevention of over-hydration
Water Intake - Increased Plasma Osmolarity
Osmoreceptors in thirst centre within the hypothalamus
When salt concentration increases, vasopressin is released and conserves water at the kidney
Water Intake - Decreased Plasma Volume
When we lose plasma due to vomiting or diarrhea stimulation of baroreceptors in the cardiovascular system
Baroreceptors in the kidney afferent arteries lead to activation of the renin-angiotensin system
-increases thirst
Water Intake - Prevention of over-hydration
A person stops drinking well before water is absorbed by the GIT
Probably mediated by stimulus from mouth, throat, and GIT
Main Salivary Glands
Parotid - watery (serous) secretion
Submandibular - serous/mucous secretion
Sublingual - mucous secretion
How much saliva does an adult produce per day?
1500 mL
Composition of Saliva
Water -hypotonic, slightly alkaline Electrolytes -rich in potassium and bicarbonate -poor in sodium and chloride Digestive enzymes -amylase, lipase Glycoproteins -mucin Other components -anti-microbial factors
Functions of Saliva
Moistens and lubricates food Initiates digestion Dissolves a small amount of food -allows diffusion to taste buds Antibacterial actions Aids in speech Buffering action -bicarbonate helps neutralize acid
Components of the salivary gland
Acinar cells
Ductal cells
Myoepithelial cells
Made up of many microscopic ducts that branch out from grossly visible ducts
Acinar Cells
Secrete the initial saliva
Ductal Cells
Create the alkaline and hypotonic nature of saliva
Myoepithelial Cells
Characteristics of both smooth muscle and epithelial cells
Formation of Saliva
Acinar cells secrete the initial saliva
-proteins are released by exocytosis
-chloride, bicarbonate, and potassium are actively secreted
-sodium and water follow paracellularly via leaky tight junctions
-initial secretion is isotonic
-myoepithelial cells contract and expel formed saliva from acinus into the duct
Ductal cells modify the initial saliva to a hypotonic, alkaline state
-net loss of sodium and chloride
-addition of potassium and bicarbonate
-duct cells are tightly joined and impermeable to water
Regulation of Salivary Gland Function
Both the parasympathetic and sympathetic systems stimulate salivary secretion
No hormonal regulation
Major influence is the parasympathetic system
-increases blood flow to glands which results in increased secretion
-also important for increase protein secretion from acinar cells and stimulate myoepithelial cells
Parasympathetic Salivary Gland Function
Stimulated by: -smell and taste -pressure receptors in the mouth -nausea (protective) Inhibited by: -fatigue, sleep, fear, dehydration, some drugs
Sympathetic Salivary Gland Function
Modestly increases saliva flow
Increased protein secretion from acinar cells
Stimulates myoepithelial cells
What is the role of saliva in digestion?
Amylase
- starch digestion is initiated
- inhibited by the acidic stomach pH
Lingual Lipase
-acid-stable and therefore active in the stomach
When would saliva play a bigger role in digestion?
When there are pathological conditions (pancreatic insufficiency) For neonates (immature digestive system)
What are some conditions that cause xerostomia?
Congenital conditions
Autoimmune conditions
Side effect of drugs
Radiation treatment
Consequences of Xerostomia
Dry mouth Decreased oral pH -tooth decay -esophageal erosions Difficulty in lubricating and swallowing food -poor nutrition
Treatment of Xerostomia
Frequent sips of water and fluoride
How is swallowing initiated?
This reflex is initiated by pressure receptors in the walls of the pharynx
-stimulated by food/liquid entering the pharynx
Receptors send signals to the swallowing centre in the brainstem which in turn signals muscles in the:
-pharynx
-esophagus
-respiratory muscles
Larynx
The air passage between the pharynx and trachea
Glottis
The area around vocal cords - where air travels through
Epiglottis
A tissue flap that covers the trachea during swallowing
The Steps of Swallowing
- Tongue pushes food bolus to the back of the pharynx
- Soft palate elevates to prevent food from entering the nasal passages
- Epiglottis covers the glottis to prevent food or liquid from entering the trachea
- Food descends into the esophagus
What is the function of the esophagus?
Transfers food from mouth to stomach
Food passes very rapidly
Structure of the Esophagus
Skeletal muscle surrounds the upper third, smooth muscle surrounds the lower two-thirds
What type of epithelium does the esophagus have?
Stratified squamous epithelium (20-30 cells thick) because the esophagus is exposed to rough and abrasive food contents
Upper Esophageal Sphincter
Ring of skeletal muscle just below the pharynx
Lower Esophageal Sphincter
Ring of smooth muscle at the stomach
When are the only times these sphincters are open?
Swallowing
Vomiting
Burping
The Esophageal Phase of Swallowing
- Relaxation of the upper esophageal sphincter
- Peristaltic waves move food bolus down the esophagus
- Lower sphincter opens and allows food to pass into the stomach
What is the main driving force of swallowing?
Peristalsis
Gravity assists but is not necessary
What is heartburn?
When stomach acid comes back up into the esophagus
What happens when small amounts of acid are in the esophagus?
Stimulates peristalsis
Increases salivary secretion
Results in neutralization and clearance
When does heartburn occur?
Due to an inefficient sphincter
After a big meal
During pregnancy
Where is the stomach located?
Between the esophagus and the small intestine
Functions of the Stomach
Storage of food
Mechanical breakdown of food
Chemical breakdown of food
-secretes pepsinogen and HCl
Controls the rate at which food enters the small intestine
Secretes intrinsic factor for absorption of vitamin B12
Very little absorption occurs across the stomach
what does pepsinogen digest?
Protein
What does HCl in the stomach do?
Dissolves food
Partially digests macromolecules in food
Sterilizes food
The Fundus and Body of the Stomach
A thin layer of smooth muscle Secretes: -mucus -pepsinogen -HCl
The antrum of the Stomach
The thicker smooth muscle layer Secretes: -mucus -pepsinogen -gastrin
Exocrine
Chemical messengers secreted into ducts then on to an epithelial surface without passing into the blood
Major Exocrine Secretions of the Stomach
Mucus = protective coating over the stomach epithelium to avoid self-digestion
HCl = hydrolysis of proteins
Pepsinogen = digestion of proteins
Minor Secretions of the Stomach
Intrinsic Factor = for B12 absorption
Gastrin (endocrine) = stimulates HCl production and stomach motility
Histamine (paracrine) = stimulates HCl production
Somatostatin (paracrine) = inhibits HCl production
Where is Chief Cells Found?
Gastric glands in all regions
What do chief cells secrete?
Secrete pepsinogen
- an inactive precursor to pepsin
- pepsinogen cleaved by acid to pepsin
- pepsin accelerates protein digestion
Where are enteroendocrine cells found?
Gastric glands in the antrum
What do enteroendocrine cells secrete?
Secretes gastrin (hormone)
- stimulates HCl production by parietal cell
- stimulates GI motility
Where are ECL cells found?
Gastric glands in all regions but more so in the antrum
What do ECL cells secrete?
Secrete histamine
-stimulate HCl release
Where are D-cells found?
Gastric glands in all regions but more so in the antrum
What do D-cells secrete?
Secrete somatostatin
-negative regulator of HCl secretion
Where are parietal cells found?
Found in gastric glands contained in the fundus/body regions
What do parietal cells secrete?
Secretes HCl and intrinsic factor
What are Canaliculi?
They increase the surface area of the parietal cells and maximize secretion into the stomach lumen
Actively secreting cell has better defined canaliculus
What pH does the stomach secrete?
2 L of 0.1 M HCl per day
Steps of Acidification of the Stomach Lumen?
- H+/K+ ATPase
- active transport - Carbonic anhydrase
- forms bicarbonate
- bicarbonate dissociates into H+ and HCO3- - Cl-/HCO3 exchanger
- excess HO- is effluxed from the cell as HCO3- isn exchange for Cl-
- critical step for the maintenance of neutral cellular pH - K+ channels
- K+ recycled back into stomach lumen
- diffusion through channel
- loss of positive charge - Cl- channels
- Cl- leaks back into stomach lumen
- diffusion through channel
Which 4 chemical messengers regulate the insertion of the H+/K+ ATPase into the plasma membrane of the parietal cell
Gastrin Acetylcholine Histamine Somatostatin -inhibits the release of HCl, gastrin, and histamine
Phases of Gastric Secretion
Cephalic Phase
Gastric Phase
Intestinal Phase
Cephalic Phase
Anticipatory, excitatory, mainly via the vagus
Gastric Phase
Major phase, excitatory, mainly via gastrin
Intestinal Phase
Mainly inhibitory, due to the presence of acid, fat, digestion products and hypertonic solutions in duodenum
Regulation of Gastric Secretion
Acetylcholine, gastrin, and histamine all directly increase acid secretion by the parietal cell
Somatostatin inhibits acid secretion by the parietal cell
Acetylcholine also stimulates the release of gastrin from G cells and histamine from ECL cells and inhibits somatostatin release from D cells
What happens when acid secretion is at a high rate?
Parasympathetic input reduces
Negative feedback occurs for gastrin production (acid inhibits release)
Somatostatin release increases
Stomach Size
50 mL
When we eat a meal, there is smooth muscle relaxation and the stomach can increase to 1.5 L without increased pressure
Food arriving in the stomach causes:
Peristaltic waves
- weaker contractions in the body of the stomach
- powerful contraction in the antrum
- mixes luminal contents, closes pyloric sphincter
Closure of the pyloric sphincter results in:
Small amount of stomach contents released to the duodenum
Most antral contents forced backward towards the body of the stomach
-mixing of contents with enzymes and acid
Electrical Basis of Stomach Motility
The stomach has pacemaker cells in the smooth muscle layer
-spontaneous slow waves of depolarization and repolarization = do not cause significant contractions
Excitatory hormones and neurotransmitters further depolarize and determine the strength of the contraction
Causes of vomiting
GIT disturbances Psychogenic Motion sickness Inner ear infection Alcohol Pressure on CNS
What happens when we vomit?
Nausea, salivation, breath held in mid-inspiration
Glottis closes off trachea
Lower esophageal sphincter and esophagus relaz
Diaphragm and abdominal muscles contract
Reverse peristalsis moves upper intestinal contents into stomach
Stomach contents move up through esophagus and out through the mouth
Benefits of Vomiting
Removal of harmful substances prior to absorption
Nausea and feeling bad should prevent individual from consuming noxious substance again
Negatives of Vomiting
Dehydration
Loss of salts
Metabolic alkalosis due to loss of H+
Acid erosion of tooth enamel
What is a Peptic Ulcer
A damaged/eroded area of the GIT mucosa, usually in regions that are acidic
What causes an Ulcer?
An imbalance between aggressive factors (acid) and protective factors (bicarbonate)
Bacterial infection is a major cause
Treatment for Ulcers
Antibiotics
H+/K+ ATPase inhibitor
Histamine (H2) antagonist
Prostaglandin-type drugs
Gastric Bypass Surgery
Used in treatment of morbid obesity
Stomach is smaller
The Pancreas
an exocrine and endocrine gland
Exocrine Pancreas
Produces secretions that go into the gut
Source for the majority of enzymes required for meal digestion
Enzymes are produced in excess
Critical for secreting bicarbonate into the duodenum for the neutralization of stomach acid = critical for enzyme function
Endocrine Pancreas
Non-digestive
Produces hormones that regulate the entire body (insulin)
Exocrine Pancreas Structure
Secretion of substances into ducts that drain onto an epithelial surface
Endocrine Pancreas Structure
Ductless gland, secretion occurs across the epithelial basolateral surface for diffusion into the blood
Where do the pancreatic duct and common bile duct join?
Just before entering the duodenum
Pancreatic Ducts
Similar to salivary glands
Acinar cells produce and secrete digestive enzymes
Duct cells secrete water and bicarbonate
Pancreatic Juices
Isotonic and alkaline
Contains electrolytes
-high bicarbonate, low chloride
-sodium and potassium the same as in plasma
Contains digestive enzymes
-secreted by acinar cells
proteolytic enzymes are stored and secreted in inactive forms, activated in the duodenum
Ductular Cell Secretion of Bicarbonate
- Chloride channel opens
-allows diffusion of chloride into duct lumen - Cl- in lumen is exchanged for bicarbonate in the cell
- Water and sodium follow paracellularly in response to electrochemical gradient across the epithelium
- Neutral pH of cytosol is maintained by exchange of H+ for Na+
-secondary active transport
Resulting in watery alkaline secretion neutralizes gastric acid and washes digestive enzymes through
Alkaline Tide
After a big meal:
Parietal cells in the stomach are producing lots of acid so large amounts of bicarbonate are pumped across the basolateral surface into the blood stream
Acid Tide
After a big meal:
Duct cells in the pancreas are producing and secreting bicarbonate so large amounts of protons are pumped across the basolateral surface into the blood stream
Alkaline and Acid Tide
Bicarbonate and protons from the pancreas eventually meet up in the portal vein
Two processes compensate for each other and maintain acid-base balance
Digestive Function of the Pancreas
Source for the majority of enzymes required for meal digestion
Starvation would occur without the pancreas
Proteases
Digests proteins in peptides and amino acids
Amylolytic Enzymes
Digest starch into sugars
Lipases
Digest triglycerides into free fatty acids and monoglycerides
Nucleases
Digest nucleic acids into free nucleotides
Acinar Cells and Enzymes
Acinar cells synthesize and package pro-enzymes into zymogen granules that are stored at the apical pole of the cell
Why are enzymes in the pancreas stored as inactive forms?
The enzymes can digest the pancreas
They are activated in the duodenum
Enterokinase
Enzyme embedded in the luminal membrane of the duodenum and cleaves trypsinogen to trypsin
Trypsin
Inactive trypsinogen is activated by enterokinase
Endopeptidase that results in mixture of peptides and amino acids
Chymotrypsin
Inactive chymotrypsinogen is activated by trypsin
Endopeptidase that results in a mixture of peptides and amino acids
Elastase
Inactive pro-elastase is activated by trypsin
Endopeptidase that results in a mixture of peptides and amino acids
Carboxypeptidase A and B
Inactive pro-carboxy peptidase A and B is activated by trypsin
Exopeptidase that results in a mixture of peptides and amino acids
Amylase
Cleaves starches to sugars
Lipase
Hydrolyzes triglycerides into free fatty acids
Phospholipase A2
Inactive prephospholipase A2 is activated by trypsin
Hydrolyzes phospholipids into free fatty acids
Cholesterolesterase
Hydrolyzes cholesterol-esters into free fatty acids and cholesterol
CCK and Secretion of Pancreatic Juice
Fatty acids and amino acids in the small intestine trigger CCK secretion from cells in the small intestine into the blood
Circulating CCK stimulates
-the pancreas to increase digestive enzyme secretion
-gall bladder contraction
-relaxation of the sphincter of Oddi
Fat and amino acids are absorbed and stimulation of CCK release is stopped due to their removal
Secretin Regulation of Pancreatic HCO3-
Acid enters the duodenum
Reduced pH triggers secretion from cells in the small intestine into the blood
Circulating secretion stimulates
-pancreas duct cells to increase HCO3- secretion
-liver duct cells to increase HCO3- secretion
Stomach acid is neutralized and stimulation of secretin release stopped
Secretin and CCK Influence on the Stomach
Secretin and CCK inhibit gastrin secretion
Results in reduced stomach motility and reduced acid secretion
Phases of Pancreatic Secretion
Cephalic phase = minor phase but sight, taste, smell will stimulate pancreatic secretion vis parasympathetic nerves
Gastric phase = minor phase but distension of the stomach will stimulate pancreatic secretion via the parasympathetic nerves
Intestinal phase = major phase of regulation. acid from the stomach in the duodenum results in secretin release. digested fat and protein in duodenum results in CCK release
Cystic Fibrosis
Still produce digestive enzymes but HCO3- and water secretion is low and enzymes do not get flushed from the ducts
Retained proteolytic enzymes can result in pancreatic autodigestion
Need supplements of digestive enzymes
Hepatic and Lobule Structure
Hexagonal structure with a central vein running through the centre and portal triads at each corner
What is the portal triad composed of?
Hepatic artery
Portal vein
Bile duct
Microanatomy of the liver
Bile components produced by the hepatocytes are put into the canalicular networks
Bile components flow towards the bile ducts
Blood flow occurs on the other surface of the hepatocyte
Major Functions of the Liver
Exocrine gland = formation and secretion of bile
Metabolism and storage of nutrients = liver matches supply demand
Deactivation and detoxification = drugs, hormones, waste products, toxins
Production of circulating proteins = blood coagulation factors, lipoproteins
Constituents of Bile
Bile acids = synthesizes within the hepatocyte from cholesterol and amphipathic Cholesterol = slightly amphipathic Salts and water Phospholipids Bile pigments = bilirubin Trace metals
Role of Bile in Fat Digestion
Pancreatic lipase is water-soluble enzymes and can only work on the surface of liquid droplets
Large lipid droplets need to be made smaller for efficient access by lipase in a process called emulsification
Emulsification
Mechanical disruption to make lipid droplets smaller (GI motility)
Emulsifying agent to prevent droplets from re-aggregating = bile acids
Bile Acid and Micelles
Bile acids also form mixed micelles with phospholipids and products of lipase digestion
Micelle is a soluble cluster of amphipathic molecules with nonpolar groups in the middle and polar groups on the outer layer
Micelle Function
Fatty acids are really insoluble in water
Micelles keep fatty acids in small soluble aggregates
Equilibrium between the micelle and free fatty acids (free forms diffuse across the SI epithelium
Micelles are like holding station for small nonsoluble lipids
Formation of Bile
Hepatocytes = produce and secret bile acids
-also secrete phospholipids, cholesterol, and bile pigments
-all components secreted through primary active transport pathways
Bile ducts add HCO3- and water to bile
Gallbladder = stores and concentrates the bile between meals then expels it into the duodenum after a meal
The Enterohepatic Circulation of Bile Acids
Bile acids are conserved
Recycling of bile acid occurs through the enterohepatic circulation
Allows the secretion rate to greatly exceed the synthesis rate
Steps for Bile Acid Recycling
- Bile acids are released by the liver/gallbladder into the duodenum for fat digestion
- Bile acids are reabsorbed across the Ileum into the portal circulation
- Bile acids are transported back into hepatocytes
How do Dietary Fibers Lower Cholesterol?
Bile acids are made out of cholesterol
High fibre foods bind with bile acids which prevent it’s reabsorption and the acids are lost in feces
Regulation of Hepatobiliary Secretion During Intestinal Phase - Bile Salts
As more bile salts are absorbed from the ileum and return to the liver, more will be secreted back into the bile
Bile salt synthesis is reduced when the enterohepatic circulation is working well
Regulation of Hepatobiliary Secretion During Intestinal Phase - Secretin
Secretin is produced and released by S-cells in the duodenum when acid stimulates the duodenum
Secretin increases HCO3- secretion by the bile duct cells and the pancreas
Regulation of Hepatobiliary Secretion During Intestinal Phase - CCK
Produced by the I-cells in the duodenum and jejunum
CCK increases contraction of the gallbladder and releases the sphincter of Oddi
-bile is released into the duodenum
Causes of Gallstones
Cholesterol stones
-when [cholesterol] gets too high then cholesterol will start to precipitate out
Pigment stones
- less common
- caused by excessive hemolysis which increases [pigment] which will precipitate with calcium ions
Consequences of Gallstones
May cause obstruction/infection of the gallbladder, liver, pancreas
Pain, nausea, jaundice
Treatment of Gallstones
Cholecystectomy
Removal of stones
Drugs to dissolve gallstones
The 3 Sections of the Small Intestine
Duodenum
Jejunum
Ileum
Major Functions of the Small Intestine
Digestion and absorption of protein, fat, carbohydrate, electrolytes, water, minerals, vitamins
Function of the Duodenum
Mixing of pancreatic digestive enzymes and bile with food
Absorption of nutrients, iron, calcium
Release of endocrine hormones secretin and CCK
Function of the Jejunum
Digestion and absorption
Ileum
Digestion and absorption
- bile acids
- vitamin B12
How is the Surface Area Increased in the SI?
In the lumen of the SI are folds of Kerckring (circular folds)
On these folds on villi with microvilli on the epithelium of the villi
Crypts are projections in the opposite direction
Villus
Protrusion of the epithelium into the lumen of the GIT
Crypts
Invaginations of the epithelium
Absorptive Cell (Enterocyte)
Absorption
Brush border enzymes
Goblet Cell
Secretion of mucus
Enteroendocrine Cell
Release of hormones
Paneth Cell
Secrete antibacterial proteins
What is a Brush Border?
Microvilli of epithelial cells covering the villi of the small intestine, major absorptive surface of the small intestine
What is a Brush Border Enzyme?
An enzyme anchored to the brush border with catalytic activity in the lumen
Important for breaking down carbs and peptides into sugars and amino acids prior to transport across the enterocyte
Digestion of Carbohydrates in the SI
Maltose and alpha-limit dextrins are broken down into glucose by brush border enzymes
Sucrose and lactose are also broken down by brush border enzymes
How are glucose and galactose absorbed?
Move from the intestinal lumen into the enterocyte through the Na+-dependent glucose transporter SGLT on the apical membrane
Glucose and galactose are transported across the basolateral surface through a facilitated glucose transporter, GLUT
How is fructose absorbed?
Moves into the enterocyte across the apical membrane through a facilitated carrier, GLUT5
Fructose is transported across the basolateral surface of the enterocyte through a facilitated glucose transporter, GLUT2
Digestion of Proteins in the SI
Proteins are further broken down into free amino acids by carboxypeptidase, aminopeptidase, other brush border enzymes
How are amino acids absorbed?
Free amino acids are absorbed by secondary active transport coupled to Na+
Small peptides can also be absorbed by different secondary active transport proteins coupled to H+
Amino acids then undergo facilitated diffusion across the basolateral surface of the enterocyte
Fat Digestion in the SI
Lipid droplets are emulsified by mechanical disruptions and pancreatic lipase
Products of lipase are incorporated into micelles
As micelles breakdown they release fatty acids and monoglycerides that can diffuse across the SI epithelium
How are fatty acids absorbed?
As soon as fatty acids are absorbed, they are converted into extracellular fat droplets called chylomicrons by the ER and Golgi
Chylomicrons enter the lymphatic system because lacteals are leakier and eventually enter systemic circulation via the thoracic duct
Lipoprotein lipase releases triglycerides from chylomicrons to be absorbed by tissues
Absorption of Iron in the SI
Iron is actively transported into the enterocyte and incorporated into the protein ferritin (stores iron)
Iron that is not stored is released on the blood side and transported by transferrin
Accumulation of Iron in Tissues
We do not expel iron
This can result in toxicity including skin pigmentation and heart failure
Why Would Someone Accumulate Iron?
Genetic defects in absorption control pathways
Adult males/post-menopausal women excessively supplementing
Poisoning
Iron-deficiency Anemia
Reduced number of red blood cells
Why is the Control of Fluid in the Intestine Critical for GI Function?
Permits contact between food and digestive enzymes
Diffusion of digested nutrients to absorption site
Fluidity provides for transit without damage to the epithelium
Generalizations about Water Absorption and Secretion
Water absorption at the villi, secretion from the crypts
Intestinal epithelium establishes an osmotic gradient and water follows through tight junctions
Absorption of Water in the SI
Predominantly depends on Na+ gradients generated during secondary active nutrient uptake
Secretion of Water in the SI
Predominantly depends on Cl- gradients generated by secondary active Na+/K+/2Cl- transporter
What is Segmentation During Digestion?
Continuous division and subdivision of intestinal contents
-mechanical breakdown of food
-mixing of food with digestive enzymes
Frequency is set by basic electrical rhythm
Contraction force determined by neurohormonal input
Slow net migration towards the LI
-allows digestion and absorption of food
What happens to Motility in the SI After Absorption?
Segmentation contractions stop
Replaced by a peristaltic activity called the migrating myoelectric complex
What is the purpose of the MMC?
Pushes any undigested material from the small to the large intestine
Prevents bacteria from remaining in the small intestine
Lactose Intolerance
Cannot completely digest lactose which causes
Results in decreased water absorption
Lactose goes to the LI and bacteria eats it
Causes diarrhea and gas
Cholera
Occurs after eating or drinking something that is contaminated with the bacteria
Vomiting and diarrhea
The treatment is fluid replacement and intravenous fluids
The Large Intestine
A tube approximately 6.5 cm in diameter and 1.5 m in length
Ileocecal Valve
Sphincter between the cecum and ileum
Open when ileum contracts post meal
Closed when large intestine distended
Retains large intestine contents
Function of the Cecum/Appendix
No apparent function
Function of the Ascending/Transverse/Descending/Sigmoidal Colon
Reabsorption of water
Reservoir for the storage of wastes and indigestible materials prior to elimination by defecation
Absorption of products of bacterial metabolism
Function of the Rectum
Reservior for feces
Function of the Anus
Two sphincters that control defecation
Lining in the Colon
Only contains crypts - no villi
Surface area is much lower than SI
Large Intestine Cell Types
Absorptive cells -no brush border enzymes Goblet cells -abundant Very few paneth and endocrine cells Ecosystem of bacteria (10^12 bacteria/g of large intestine) -produce vitamins -produce gas
Absorption of Water in the Large Intestine
Predominantly depends on Na+ gradients generated by Na+/K+ ATPase
Secretion of Water in the Large Intestine
Predominantly depends on Cl- gradients generated by secondary active Na+/K+/2Cl- transporter
The Purpose of Motility in the Large Intestine
Mixing the contents and retaining them for optimal salvage of fluid and bacterial products
Mixing in the Large Intestine
Segmentation but slower
Allows colon retention for 18-24 hours
Propulsion in the Large Intestine
Three to four times a day a wave of intense contraction known as a mass movement spreads rapidly over the large intestine, pushing contents towards the anus
Occurs after eating and prior to defecation
Defection
Rectum contracts, internal anal sphincter relaxes and the outer anal sphincter contracts
Increased peristaltic activity in the sigmoid colon, increasing pressure results in reflex relaxation of the external anal sphincter
Feces voided
What is feces made of?
Water, undigested food, bacteria, sloughed epithelial cells
