Unit 9 - Digestive System Flashcards
Digestive system role
The digestive system plays a critical role in breaking down and absorbing the nutrients, electrolytes, and water the body needs in order to maintain homeostasis.
Basic Functions of the Digestive Tract
- Motility
- Digestion
- Secretion
- Absorption
- Storage & Elimination of Wastes
- Immune Functions
Motility
food is ingested and moved through the tube of the GI tract using the following processes:
a. Ingestion
b. Deglutition
c. Peristalsis
d. Mass movements
Ingestion
taking food into the mouth
Deglutition
swallowing of food.
Peristalsis
rhythmic wavelike contractions of smooth muscle that move food through GI tract (like squeezing toothpaste out of a tube starting from the closed end and squeezing toward the open end).
Mass movements
a strong wave of smooth muscle contraction over a long segment of the tract (usually intestines). Usually involved in defecation reflex.
Digestion
a. Mechanical
i. Mastication
ii. Churning
iii. Segmentation
b. Chemical
i. Acidic pH
ii. Digestive enzymes
Mechanical Digestion
the physical breakdown of large pieces of food into smaller pieces. Involves:
i. Mastication
ii. Churning
iii. Segmentation
Mastication
chewing of food and mixing it with secretions from the salivary glands.
Churning
mixing of food in stomach due to contraction of 3 layers of smooth muscle.
Segmentation
alternating contractions of smooth muscle between adjacent areas of the stomach / intestines – mixes material being digested/absorbed.
Chemical Digestion
the chemical breakdown of large nutrient molecules (macromolecules/macronutrients) in small molecules (micronutrients) that are capable of being absorbed. Involves:
i. Acidic pH
ii. Digestive enzymes
Acidic pH
important for the chemical digestion of proteins and fats.
Digestive enzymes
act on macromolecules to break them down into smaller ones. For example, PANCREATIC AMYLASE digests complex carbohydrates like starch and glycogen into disaccharides and oligosaccharides in the small intestine.
Secretion
various substances are secreted either by cells lining the tract or cells of accessory organs.
a. Exocrine secretions
b. Endocrine secretions
Exocrine secretions
into lumen of GI tract. Includes:
i. Water (note: water is also reabsorbed)
ii. Hydrochloric acid (HCl)
iii. Bicarbonate (HCO3-)
iv. Enzymes
v. Bile
vi. Mucus
Endocrine secretions
into blood. Includes hormones such as gastrin, cholecystokinin, secretin, etc. that help to regulate digestion.
Absorption
transport of digested molecules from the lumen of (primarily) the small intestine into enterocytes (cells of the intestinal epithelium) followed by transport into the interstitial fluid and then into the blood or lymph.
Storage and Elimination of Wastes
- The large intestine (colon) stores waste and any undigested material until they can be eliminated.
- Excretion of waste by the digestive tract = DEFECATION
Excretion of waste by the digestive tract =
DEFECATION
Immune Functions
- Acts as a PHYSICAL BARRIER to foreign pathogens. TIGHT JUNCTIONS between columnar cells of the gastrointestinal epithelium stop pathogens and their toxins from entering into the body.
- Gut microbiome outcompetes harmful microbes and promotes production of antimicrobial peptides on the surface of intestinal cells (recall Unit 4: the Immune System).
- M cells (microfold cells) in small intestine sample gut contents and endocytose any antigens. Antigens are transported to Peyer’s patches (in contact with basolateral membrane of M cells) and are presented to dendritic cells, macrophages and B and T lymphocytes that will initiate the immune response.
M cells (microfold cells) in small intestine
sample gut contents and endocytose any antigens. Antigens are transported to Peyer’s patches (in contact with basolateral membrane of M cells) and are presented to dendritic cells, macrophages and B and T lymphocytes that will initiate the immune response.
The gastrointestinal tract is essentially a
long tube, divided into various regions that are specialized to carry out the basic functions related to digestion. Accessory organs including the salivary glands, pancreas, liver, and gall bladder, produce and/or release secretions into the tube (or blood) that assist the processes of digestion and absorption.
Accessory organs including the…
salivary glands, pancreas, liver, and gall bladder, produce and/or release secretions into the tube (or blood) that assist the processes of digestion and absorption.
GI Tract structures, listed in order, include:
- Mouth/Oral Cavity
- Pharynx
- Esophagus
- Upper Esophageal Sphincter
- Lower Esophageal Sphincter - Stomach (passage time ~2.5-5 hours)
- Small Intestine – digestion and absorption of nutrients. (passage time ~2.5-6 hours)
a. Duodenum – main site of chemical digestion b. Jejunum
c. Ileum
- Ileocecal valve - Caecum
- Large intestine (colon)
- Rectum
- Anus
- Internal Anal Sphincter
- External Anal Sphincter
Upper Esophageal Sphincter
skeletal muscle – opens so that food bolus can enter esophagus; closes to prevent backflow from esophagus into pharynx.
Lower Esophageal Sphincter
closes to prevent backflow (reflux) of food and gastric juices into the esophagus (i.e. heartburn).
Stomach
(passage time ~2.5-5 hours)
- Connected to duodenum via pyloric sphincter/valve. This valve controls the release of chyme (mix of partially digested food material and gastric juices) into the duodenum.
Small Intestine
digestion and absorption of nutrients. (passage time ~2.5-6 hours)
a. Duodenum – main site of chemical digestion b. Jejunum
c. Ileum
- Ileocecal valve
Duodenum
main site of chemical digestion
Ileocecal valve
controls release of chyme from ileum into caecum. Prevents entry of bacteria from colon into small intestine
Caecum
blind pouch that includes appendix, leads into ascending colon. Contains bacteria (probiotics).
Large intestine (colon)
absorbs water, vitamins (passage time ~30-40 hours).
- Parts: Ascending, Transverse, Descending, Sigmoid colon.
Anus
two sphincters involved in the defecation reflex.
- Internal Anal Sphincter – smooth muscle, involuntary control.
- External Anal Sphincter – skeletal muscle, voluntary control.
Internal Anal Sphincter
smooth muscle, involuntary control.
External Anal Sphincter
skeletal muscle, voluntary control.
Accessory structures to the GI tract include:
- Teeth
- Tongue
- Salivary glands
a. Parotid
b. Sublingual
c. Submandibular - Liver
- Gall Bladder
- Pancreas
Teeth
chop and tear food into smaller pieces.
Tongue
manipulates food and plays a role in taste and swallowing.
Salivary glands
secrete saliva which helps to moisten food and contains digestive enzymes to begin chemical digestion.
a. Parotid (just anterior to the ears)
b. Sublingual (under the tongue)
c. Submandibular (under the lower jaw bone)
Parotid Salivary Glands
just anterior to the ears
Sublingual Salivary Glands
under the tongue
Submandibular Salivary Glands
under the lower jaw bone
Liver
produces bile and filters and detoxifies absorbed nutrients.
Gall Bladder
stores, concentrates and releases bile, which acts to emulsify fats and increase the surface area for the action of pancreatic lipase.
Pancreas
secretes digestive enzymes and alkaline fluid into duodenum.
Tissue Layers of the GI tract wall:
- Mucosa
- Submucosa
- Muscularis externa
- Serosa
Mucosa Includes
a. Mucosal Epithelium
b. Lamina propria
c. Muscularis mucosae
Mucosal Epithelium
lines inside surface of the tract
- Apical surface is in contact with lumen of tract, basolateral surface in contact with basement membrane.
- Esophagus and rectum – have stratified squamous epithelium (provides protection from abrasiveness of swallowed foods and solid wastes respectively).
- Stomach and Intestines – have simple columnar epithelium (involved in absorption and secretion)
Lamina propria
holds the epithelium in place
- Loose connective tissue layer
- Contains small blood vessels, lymph LACTEALS (i.e. lymphatic capillaries, which will play an important role in fat absorption).
Muscularis mucosae
Thin layer of smooth muscle separating mucosa and submucosa. Contraction can help to dislodge food from the folds/crypts of the intestine.
Submucosa
- Thick layer of connective tissue containing glands, nerves and blood vessels.
- Contains the SUBMUCOSAL PLEXUS, the first nerve network of the enteric nervous system.
Muscularis externa
Two layers of smooth muscle:
a. Inner layer = circular muscle; allows for constriction/dilation of the tract.
b. Outer layer = longitudinal muscle that shortens and lengthens tract.
- Stomach has a third layer that helps to churn stomach contents.
a. oblique layer = muscle located between the submucosal plexus and the
the circular layer. - Contains the MYENTERIC PLEXUS (between the inner circular and outer longitudinal), the second nerve network of the enteric nervous system.
- While most of the tract consists of these 2-3 layers, of smooth muscle, the middle 1/3 of the esophagus contains both skeletal muscle and smooth muscle to allow for some voluntary control of swallowing.
Serosa
- Part of peritoneal membrane (peritoneum) lining the abdominal cavity.
- Composed of connective tissue and simple squamous epithelium.
- Forms sheets of connective tissue that help to hold organs in place.
- Also provides support for blood vessels and nerves going to/from abdominal organs.
Motility of the gastrointestinal tract is
critical not only for moving material along the tube, but also for controlling the conditions and amount of time available for adequate digestion and absorption of nutrients.
Contraction of smooth muscle in the GI Tract is of 3 types:
- Peristalsis
- Segmental contractions
- Migrating Motor Complexes
Peristalsis
- small, weak waves of contraction in which circular smooth muscle contracts upstream from the bolus of food, while muscle downstream (in front of bolus) relaxes. Result is bolus is pushed further along the tube.
- In small intestine. – occurs as part of a reflex response triggered by distension of intestinal wall
- The frequency of waves is efficient enough to move the contents of the lumen.
- Transit time along the small intestine is ~3-9 hours
- Primarily controlled by MYENTERIC PLEXUS
Segmental contractions
mixes
- Alternating contraction and relaxation of circular muscle in adjacent sections of the intestine.
- Mixes up and churns the ingested material, which ensures that it all gets exposed to the absorptive surface (material from the middle of the lumen gets moved to be in direct contact with the mucosa). And also ensures exposure to digestive enzymes (mixing distributes enzymes amongst the food particles for digestion).
- Contributes very little to propulsion of the material through the tube, since material is being moved both backward and forward along the tube.
Migrating Motor Complexes
(mass movements)–
- Similar to peristalsis but involves a larger/stronger wave of
contraction that propels the substance over a longer distance (up to the entire length of the small and large intestines).
- These movements are a cleansing contraction that propel undigested material as well as pathogens and bacteria out of the small intestine and into the large intestine.
- Typically occur during or right after a meal (cleans out the tube to get it ready to process the incoming food).
- Part of the gastrocolic reflex (a long reflex arc, also known as the defecation reflex) which is initiated by distension of the stomach or duodenum when consuming a meal. And is the reason that people may feel the urge to defecate right after (or even during) a meal, particularly breakfast. Any physiological response after eating a meal is known as a POSTPRANDIAL RESPONSE.
Accelerated motility of the gut results in
diarrhea, which is associated with increased frequency and strength of migrating motor complexes.
Decreased motility results in
constipation.
Constipation may lead to perforation of the large intestine (a hole in the bowel). This causes the release of bacteria and feces into the abdominal cavity, and the resulting infection (sepsis) is often life threatening (similar to a burst appendix)
Regulation of GI Tract Motility & Secretion
Involves
Involves both intrinsic control by the enteric nervous system and local signaling molecules (paracrines) and extrinsic control by the parasympathetic and sympathetic branches of the nervous system and hormones of the endocrine system.
Involves reflex responses that are integrated in both the enteric nervous system (short reflexes) and the central nervous system (long reflexes). This includes any reflex involving the brain (cephalic reflexes).
Regulation of GI Tract Motility & Secretion
- Neural Control
a. Enteric NS
b. The Autonomic Nervous System
c. Cognitive and Emotional Control - Chemical Signaling
Neural Control
a. Enteric NS – “brain” of the gut; contains as many neurons as the spinal cord and provides local intrinsic control of motility and secretion. Involved in short reflexes.
i. Submucosal plexus
ii. Myenteric plexus
b. The Autonomic Nervous System
i. Parasympathetic Nervous System (PSNS)
ii. Sympathetic
c. Cognitive and Emotional Control
Enteric NS
“brain” of the gut; contains as many neurons as the spinal cord and provides local intrinsic control of motility and secretion. Involved in short reflexes.
Submucosal plexus
- Located within the submucosal layer of the GI tract wall
- Controls functions associated with the mucosa including: sensing the environment of the GI tract lumen; regulating local blood flow; and controlling epithelial cells (including secretions from glands).
Myenteric plexus
- Located in the muscularis externa between the circular and longitudinal layers.
- Controls GI motility by:
- Increasing smooth muscle tone
- Increasing the intensity of rhythmic contractions
- Increasing the rate of rhythmic contractions
- Increasing the velocity of peristaltic waves
- Decreasing sphincter muscle tone
The Autonomic Nervous System
i. Parasympathetic Nervous System (PSNS)
- Involved in long reflexes.
- Activity of the PSNS increases most GI functions.
- The proximal gut is innervated by the vagus nerve (controls the esophagus, stomach, pancreas, and upper large intestine)
- As a result this nerve plays an important role in deglutition (swallowing), vomiting gastric emptying, and pancreatic secretion).
- The distal gut is innervated by the pelvic nerves which control the remainder of the large intestine and rectum and so help to control defecation.
- There is very little innervation of the small intestine, as the activities carried out there are primarily regulated by the enteric nervous system as well as hormones.
The Autonomic Nervous System
ii. Sympathetic
- Involved in long reflexes.
- Activity generally decreases most GI functions.
- Involves spinal nerves from T5 to L2 that carry preganglionic neurons to the autonomic sympathetic ganglia. Postganglionic neurons then carry signals from the ganglia to all parts of the GI tract
- The release of norepinephrine (noradrenaline) inhibits the neurons of both the myenteric plexus and submucosal plexus.
Cognitive and Emotional Control
- There are neurological pathways connecting the senses and brain with the stomach – cephalic reflexes (long reflexes).
- Feedforward reflexes in response to the sight, smell, thought of food, increases acid production, motility and blood flow in the gut.
Intrinsic control GI Motility:
- The smooth muscle cells of the digestive tract have a resting membrane potential of -50 mV.
- Interstitial Cells of Cajal (ICC), act like pacemakers for the contraction of gastrointestinal smooth muscle.
Intrinsic control GI Motility:
Interstitial Cells of Cajal (ICC), act like pacemakers for the contraction of gastrointestinal smooth muscle.
- They spontaneously produce slow waves of depolarization that spread to adjacent smooth muscle cells through gap junctions.
- The cells slowly depolarize toward threshold (-40mV), and if threshold is reached, action potentials (sometimes referred to as spike potentials) and contraction will occur. The frequency of the spikes determines the strength of the muscle contraction. Frequency depends on the amount of depolarization. (Unlike cardiac pacemaker potentials, each slow wave depolarization does not always reach threshold, so the number of contractions produced through these pacemaker cells is variable.
- Depolarization of the Cajal cells can be stimulated by intrinsic factors such as stretch in the smooth muscle cells (which allows for greater entry of Ca++ during depolarization or extrinsic factors including, parasympathetic stimulation via acetylcholine (which opens ligand-gated Ca++ channels in the smooth muscle cell membrane). .
- Recall from BIOL2410 – Depolarization of smooth muscle cells triggers calcium induced calcium release from the sarcoplasmic reticulum. Ca++ then binds to calmodulin, which activates myosin light chain kinase and initiates contraction.
- Hyperpolarization of the cells of Cajal (which can occur as a result of stimulation by norepinephrine) results in no muscle contraction.
Chemical Signaling
more important in regulating the control of secretion than motility.
- Signaling molecules involved in digestion can act as hormones, or paracrine signaling molecules. Most are peptides that bind to cell surface receptors on targets. They include:
a. Gastrin
b. Cholecystokinin (CCK)
c. Secretin
d. Gastric Inhibitory Peptide
e. Glucagon-like Peptide GLP-1)
f. Motilin
g. Histamine
h. Somatostatin
Gastrin
released by G-cells of stomach in response to distension, the presence of peptides and amino acids, and neuronal stimuli of G-cells..
Action= stimulate gastric (stomach) acid secretion
Cholecystokinin (CCK)
released by I- cells (a type of enteroendocrine cell) in the small intestine in response to the presence of peptides and amino acids in chyme.
Stimulates gall bladder contraction and emptying, pancreatic enzyme secretion, and motility of the small intestine between meals.
Inhibits gastric emptying and acid secretion.
Promotes satiety (feeling full after meal).
Secretin
released by S-cells (enteroendocrine) in the intestinal crypts (glands) of duodenum in response to the presence of H+ in the chyme entering the duodenum from the stomach.
Stimulates HCO3- secretion from duct cells of pancreas and bile production in liver.
Inhibits gastric (stomach) emptying and acid secretion.
Gastric Inhibitory Peptide
released by K-cells (enteroendocrine) in the duodenum and jejunum in response to the presence of peptides, amino acids, glucose, and fatty acids in the chyme coming from the stomach. .
Stimulates insulin release from beta cells of pancreas (before there is a change in blood glucose levels).
Inhibits acid secretion, motility and emptying in the stomach.
Glucagon-like Peptide GLP-1)
released by L-cells (enteroendocrine) of the small intestine in response to high levels of glucose and fatty acids in the chyme passing through the small intestine.
Stimulates insulin release from pancreas and also acts on brain to promote satiety.
Inhibits gastric acid secretion, gastric motility and gastric emptying.
Motilin
released by M-cells in small intestine in response to neuronal stimuli.
Stimulates migrating motor complexes (motility) in the intestines and gastric emptying..
Histamine
released by enterochromaffin-like cells in stomach in response to the presence of amino acids and peptides in the ingested food, and in response to neural stimulation..
Stimulates acid secretion.
Somatostatin
released by D-cells in stomach in response to high H+.
Inhibits gastric stomach) acid secretion and motility.
Each part of the digestive tract plays a role in
each of the four main digestive processes (secretion, digestion, absorption and motility).
The activity in one section of the tract can influence the activity in other parts of the tract via neuronal or hormonal signaling.
The overall process of digestion is separated into 3 phases:
- The Cephalic Phase
- The Gastric Phase
- The Intestinal Phase (which can be further subdivided into events occurring in the small intestine and the large intestine).
Events of the Cephalic Phase
Begins with feedforward reflexes (long reflexes) that prepare the stomach and intestines for digestion.
- Sight, smell and thought of food stimulates the long vagal reflex:
Sensory neuron –> medulla –> preganglionic parasympathetic neuron in vagus nerve –> integration in enteric plexus (submucosal for secretion, myenteric for motility) –> postganglionic parasympathetic and intrinsic enteric neurons –> target cells (secretion and motility)
Target cells innervated by the submucosal plexus include
- Mucous cells
- Chief cells
- Parietal cells
- G-cells
Mucous cells
secrete mucus that protects stomach epithelium from hydrochloric acid (HCl).
Chief cells
secrete pepsinogen and gastric lipase, which will digest protein and lipids respectively.
Parietal cells
secrete HCl
G-cells
secrete gastrin.
Digestion begins in the mouth. Digestive processes include:
- Secretion
- Digestion
a. Mechanical
b. Chemical - Absorption
- Motility
a. Chewing
b. Swallowing (deglutition)
Secretion: (Cephalic Phase)
a. Saliva – mostly water with dissolved solutes.
Digestion: (Cephalic Phase)
a. Mechanical digestion – mastication (chewing) of food breaks it up into smaller pieces and mixes the food with saliva.
b. Chemical digestion – Salivary amylase begins the breakdown of complex carbohydrates (starch from plants and glycogen from animals). The presence of lingual lipase to initiate the breakdown of fat in the mouth is controversial, but it appears to occur at least in some individuals. The exact source (whether produced by the salivary glands, or other secretory glands or even microbes in the mouth is disputed.).
Absorption: (Cephalic Phase)
a. No nutrients can be absorbed.
b. Some drugs (e.g. nitroglycerin spray for the treatment of angina – chest pain due to reduced blood flow to heart).
Motility (digestion begins in the mouth)
Cephalic Phase
a. Chewing
b. Swallowing (deglutition)
Deglutition - The Swallowing Reflex
- Tongue pushes bolus against soft palate & back of mouth, triggering swallowing reflex
- Breathing is inhibited as the bolus passes the closed airway
- Food moves downward into the esophagus, propelled by peristaltic waves & aided by gravity
Events of the Gastric Phase
Initiated by presence of food stomach – distension/ stretch (stimulates baroreceptors) and presence of amino acids in food (stimulates chemoreceptors)
- Secretion
- Digestion
- Absorption
- Motility
Secretion: (Gastric Phase)
- gastric secretions are involved with digestion of ingested material and protection of the stomach lining.
- The simple columnar epithelial lining of the stomach has deep invaginations called gastric pits that contain the gastric glands. These glands are formed from multiple cells types, all of which produce secretions involved in the gastric phase. They include:
a. Mucous cells
b. Parietal cells
c. Chief cells
d. Endocrine cells
Mucous cells
secrete mucus and/or bicarbonate to produce a protective barrier against HCl.
Mucus acts as a physical barrier and bicarbonate acts as a chemical barrier (neutralizes the acid that is in close proximity to the wall of the stomach. .
Parietal cells
secrete gastric acid (HCl) which plays a role in protein digestion (denaturation and hydrolysis of peptide bonds) and intrinsic factor which is required for vitamin B absorption.
Acid production involves:
i. A H+/K+ -ATPase pump in parietal cell apical (luminal) membranes that pumps H+ out of the cell and K+ into the cell.
ii. This establishes an electrical gradient (more positive charge outside of the cell), and Cl- follows H+ down the electrical gradient out of the cell through open chloride channels.
iii. The same process that produces the H+ in parietal cells also results in production of HCO3-. Unlike mucous cells however, the HCO3- is released across the basolateral membrane of the parietal cell in exchange for chloride, It is then absorbed into the blood. This increases the pH of blood leaving the stomach after a meal – known as the ALKALINE TIDE.
Chief cells
produce pepsinogen (a proenzyme or zymogen) involved in protein digestion and gastric lipase.
Endocrine cells:
i. Enterochromaffin-like cells (ECL cells)
ii. G-cells
iii. D cells
Enterochromaffin-like cells (ECL cells)
secrete histamine – acts on parietal cells to stimulate acid secretion.
G-cells
gastrin (acts on parietal cells to and chief cells to stimulate HCl and pepsinogen secretion respectively)
D cells
somatostatin
Regulation of gastric secretion involves:
a. Presence of amino acids and neural signals from vagus nerve stimulate G cells.
b. G-cells release Gastrin.
c. Gastrin (and signals from vagus nerve) stimulates secretion of histamine from ECL cells, and directly
stimulates parietal cells to release HCl.
d. Histamine stimulates HCl secretion by parietal cells (reinforces action of gastrin and PSNS signaling through vagus nerve).
e. As pH of stomach drips, low pH inhibits release of gastrin (likely mediated by somatostatin from D-cells_
Digestion: (Gastric Phase)
a. Mechanical digestion – churning of stomach b. Chemical digestion – of fats and proteins.
- Protein – pepsinogen secreted by chief cells is activated by HCl, which converts it to pepsin. Pepsin (an endopeptidase) enzymatically breaks peptide bonds. It digests 10-20% of ingested proteins while in the stomach. Products of pepsin digestion are shorter polypeptides.
- Fats (Lipids) – minimal digestion by gastric lipase (<10%). Enzymatically breaks down triglycerides into monoglycerides and fatty acids.
Absorption: (Gastric Phase)
a. Lipid soluble substances like alcohol and aspirin, but no absorption of carbohydrates/amino acids, etc.
Motility: (Gastric Phase)
a. Peristaltic mixing and propulsion..
Events of the Intestinal Phase
Chyme (mixture of gastric juice and partially digested food from stomach) enters small intestine.
Gastric emptying into intestine is regulated so that
1) acid can be neutralized in the small intestine;
2) tonicity does not overwhelm small intestine,
3) so that there is adequate time for digestion and. absorption of nutrients.
Chyme
(mixture of gastric juice and partially digested food from stomach) enters small intestine.
Gastric emptying into intestine is regulated so that
1) acid can be neutralized in the small intestine;
2) tonicity does not overwhelm small intestine,
3) so that there is adequate time for digestion and. absorption of nutrients.
The structure of the of the small intestine, includes many
villi (projections of the submucosa into the lumen that contain blood capillaries and lymph lacteals for absorption) is specialized to maximize its absorptive surface area.
Each villus is lined with a simple columnar epithelium, whose cells all have microvilli (which form the brush border, as they resemble the tines on a brush)/comb).
The Crypts (of Liberkühn) are pits between villi that contain secretory cells.
Each villus is lined with a
simple columnar epithelium, whose cells all have microvilli (which form the brush border, as they resemble the tines on a brush)/comb).
The Crypts (of Liberkühn) are
pits between villi that contain secretory cells.
Events of the Intestinal Phase
Events of the intestinal phase are initiated in response to duodenal stretch and the presence of H+, amino acids and lipids in the chyme. The latter are detected by chemoreceptors that extend into the lumen from the submucosal plexus.
Events of the Intestinal Phase
Overall Process:
- Partially digested food enters the duodenum from the stomach.
- Actions of hormones:
a. Secretin
b. CCK
c. GIP and GLP-1 - Inactive digestive enzymes (zymogens) are activated in the intestinal lumen.
- Mechanical and Chemical digestion of carbohydrates, fats, polypeptides and nucleic acids takes place in the intestinal lumen. Molecules are also further digested by brush border enzymes (found on the surface of the microvilli of of intestinal cells). (See notes in section J for digestion and absorption details).
- Absorption of the products of digestion.
Partially digested food enters the duodenum from the stomach…
(Intestinal Phase)
a. The presence of H+ in chyme as it enters the duodenum stimulates the S-cells in the intestinal crypts to release secretin.
b. At the same time the presence of fatty acids and amino acids in the chyme (as result of digestion that was carried out in the stomach) stimulate I-cells in the intestinal crypts to release cholecystokinin (CCK).
c. The presence of carbohydrates in chyme stimulates the release of GIP and GLP-1
Actions of hormones:
a. Secretin
b. CCK
c. GIP and GLP-1
Secretin
i. Stimulates duct cells of pancreas to secrete a watery, bicarbonate (HCO3-) rich fluid that will act to buffer H+ in the chyme and raise the pH to a value that is suitable for pancreatic enzyme action (~7.4)
ii. Acts on smooth muscle of stomach to inhibit motility and on cells in gastric glands to inhibit secretion of pepsinogen, gastric lipase and HCl. As a result, gastric emptying is slowed.
CCK
i. Stimulates exocrine pancreas to secrete digestive enzymes (these are really precursors to digestive enzymes called zymogens, that will be activated in the duodenum).
ii. Stimulates gall bladder to contract and release bile into the bile duct.
iii. Also slows gastric emptying.
GIP and GLP-1
both involved in feedforward reflexes that stimulate release of insulin from pancreas. Both feedback to stomach to inhibit events of the gastric phase.
Events of the Intestinal Phase
- Secretion:
- During the intestinal phase, secretions are released by the pancreas, liver, and gall bladder, in addition to the intestine itself. Mechanisms:
a. Secretion from CRYPT CELLS IN THE SMALL INTESTINE
i. ISOTONIC NaCl SECRETION
ii. S-cells
iii. I-cells
iv. K-cells
v. L-cells
vi. M-cells
- Secretion:
- During the intestinal phase, secretions are released by the pancreas, liver, and gall bladder, in addition to the intestine itself. Mechanisms:
a. Secretion from crypt cells in the small intestine
i. Isotonic NaCl secretion
- Mixes with mucus sections from goblet cells to form a protective, lubricating barrier on the apical surface of intestinal cells (enterocytes).
- Chloride from ISF enters enterocytes via secondary active transport through NKCC channels (similar to those we saw in the nephron).
- Chloride then diffuses into lumen of intestine through CFTR channels (cystic fibrosis transmembrane conductance regulator proteins – so called because mutations in the gene for this protein cause cystic fibrosis)
- The electrical gradient established by Cl- leaving the cell causes Na+ ions to diffuse out though the paracellular pathway. Water is obligated to follow (osmosis), creating an isotonic saline solution on the surface of cell.
S-cells
acid in chyme stimulates secretion of SECRETIN
I-cells
fats and protein in chyme stimulates secretion of CHOLECYSTOKININ (CCK)
K-cells
carbohydrates in chyme stimulates secretion of GASTRIC INHIBITORY PEPTIDE (GIP)
L-cells
carbohydrates in chyme stimulates secretion of GLUCAGON-LIKE INHIBITORY PEPTIDE (GLP-1)
M-cells
secrete MOTILIN (stimulates mass movements in between meals)
Secretion from crypt cells in the small intestine
Involved in either:
- Regulating exocrine or endocrine secretions
from pancreas and/or gall bladder. - Inhibiting gastric motility and secretions.
Pancreas
consists of both endocrine and exocrine tissue - Endocrine pancreas controls blood sugar levels
- Insulin (𝛽-cells)
- Glucagon (𝛼-cells)
Insulin (𝛽-cells)
promotes uptake of glucose by cells
Glucagon (𝛼-cells)
causes breakdown of glycogen in skeletal muscle cells and liver to mobilize more glucose
Exocrine pancreas produces enzymes (________) and alkaline fluid (_____) that are secreted via the pancreatic duct into the lumen of the duodenum. Fluid plus enzymes are collectively referred to as _______
in acinar cells
in duct cells
pancreatic juices.
Alkaline fluid component, consists of
K+, Na+, bicarbonate ions and water. Neutralizes acidic chyme from stomach. Increases luminal pH from ~3 to ~7. Bicarbonate is produced by carbonic anhydrase (via the same process we observed in red blood cells for respiration and transport of CO2 and in tubule cells of the nephron for reabsorption and secretion of bicarbonate ions.
- Secretion: (Intestinal Phase)
Mechanisms of secretion in the intestinal phase:
a. Secretion from crypt cells in the small intestine
b. Pancreas
c. LIVER – produces bile salts
d. GALL BLADDER – stores and concentrates bile between meals, and
releases bile in response to signaling from CCK.
Liver
produces bile salts
Gall Bladder
stores and concentrates bile between meals, and releases bile in response to signaling from CCK.
Digestion: (Intestinal Phase)
a. Mechanical – segmentation.
b. Chemical – digestion of carbohydrates, polypeptides, fats and
nucleic acids (details for each process in notes section J).
Absorption: (Intestinal Phase)
a. The small intestine is the site of most absorption of nutrients (see notes section J for mechanisms of absorption for the different nutrients).
Motility: (Intestinal Phase)
a. Segmental contractions for mixing.
b. Some peristalsis, but movement is slowed here to allow for digestion and absorption of nutrients.
Digestion and Absorption of Nutrients
- Once nutrients are mechanically and chemically digested, the products must be absorbed and transported from the lumen of the GI tract into the blood.
- Most absorption occurs in the small intestine.
- Not all nutrients require digestion, some can be absorbed as is (ingested glucose, fructose, vitamins, minerals, etc.).
- Digestive enzymes are produced and released by glands in the superior portions of the GI tract – including salivary glands, gastric pits, exocrine pancreas.
- Enzymatic digestion starts in the mouth and continues through to the small intestine, however different enzymes may work optimally in different parts of the tract. For example, pepsin has a pH optimum that allows it to function best in the low pH of the stomach to function properly, trypsin requires the higher neutral pH of the duodenum.
- In addition to enzymes found in the pancreatic secretions, the small intestine also has enzymes attached to the epithelial brush border (for example enteropeptidase, which is responsible for activation of trypsinogen into trypsin for protein digestion). These enzymes play a critical role in getting nutrients into a small enough form that can be absorbed.
Digestion and Absorption of Nutrients
What is?
- Carbohydrates
- Proteins
- Lipids
Carbohydrates
Carbohydrates make up 50% of the average human diet and include foods like bread, potatoes, pasta and rice as well as all fruits and vegetables.
Carbohydrates can be categorized based on the number of monomers in their structure: polysaccharides
a. Polysaccharides (polymers of glucose) include:
i. Starch
ii. Glycogen
iii. Cellulose
b. Disaccharides
i. Sucrose
ii. Lactose
iii. Maltose
c. Monosaccharides
i. Glucose
ii. Fructose
iii. Galactose
Polysaccharides (polymers of glucose) include:
i. Starch - is a polysaccharide used to store glucose in plants.
ii. Glycogen – is the storage form in animals (found in liver and muscle tissue)
iii. Cellulose – is an indigestible plant structural material (also a polysaccharide).
Disaccharides (composed of two carbohydrate monomers)
i. Sucrose (glucose-fructose)
ii. Lactose, the sugar found in milk (glucose-galactose)
iii. Maltose (glucose-glucose) - maltose is also the breakdown product of starch digestion.
Monosaccharides (carbohydrate monomers) are the only sugars that can be absorbed by the intestine, meaning that all polysaccharides and disaccharides must be enzymatically digested down to monosaccharides before they can be absorbed. The most common monosaccharides ((C6H12O6) are:
i. Glucose
ii. Fructose
iii. Galactose
Carb Digestion:
a. Oral cavity
b. Stomach
c. Duodenum
Carb Digestion:
a. Oral cavity
- SALIVARY AMYLASE hydrolyzes polysaccharides like starch (amylose) into disaccharides like maltose (dimer), and oligosaccharides like maltotriose (trimer) and 𝛼-dextrin.
- Only 5% of starch digestion occurs in mouth
Carb Digestion:
Stomach
GASTRIC AMYLASE - has a very minor contribution to carbohydrate digestion. .
Carb Digestion
Duodenum
PANCREATIC AMYLASE – powerful amylase that can completely hydrolyze polysaccharides like starch into disaccharides and oligosaccharides within 30 minutes. However not able to breakdown ingested disaccharides like sucrose and lactose.
Brush border enzymes – enzymes (disaccharidases) bound to the microvilli of the intestinal cells (enterocytes) complete the digestion of disaccharides into monosaccharides: Includes:
- Sucrase
- Isomaltase
- Lactase
Brush border enzymes
enzymes (disaccharidases) bound to the microvilli of the intestinal cells (enterocytes) complete the digestion of disaccharides into monosaccharides: Includes:
- Sucrase
- Isomaltase
- Lactase
Carb Absorption:
- Only monosaccharides can be absorbed by the epithelium.
- Must cross the apical (luminal) and basolateral membranes of the enterocytes before they can enter the blood.
Carb Absorption:
At apical membrane :
i. Glucose and galactose are taken up by SGLT1 (sodium glucose linked transporter-1).
- Na+ and glucose or galactose are COTRANSPORTED into the cell together (symport).
ii. Fructose is transported via facilitated diffusion using the carrier protein GLUT5 (glucose transporter 5) .
Carb Absorption:
At basolateral membrane:
i. Glucose, galactose, and fructose use facilitated diffusion to enter the ISF through a GLUT2 transport
protein (glucose transporter 2).
ii. Na+.K+ ATPase pumps in basolateral membrane establish concentration gradient needed for SGLT 1 cotransport in apical membrane (keeps concentrations of Na+ in the cell low, so that it can keep moving into cell through SGLT1, down its concentration gradient carrying glucose/galactose with it).
Fate of absorbed glucose/galactose/fructose::
- Galactose and fructose are converted to glucose
- Glucose is stored as glycogen in muscle and liver cells.
- Any any excess beyond the capacity of the muscles and and liver are converted into lipids
Lactase deficiency results in
lactose intolerance. In most humans and other mammals, expression of the lactase gene is downregulated once an infant is weaned (i.e. lactose intolerance is a normal result of switching to an adult diet). In the absence of lactase, lactose passes through the gut undigested and is fermented in the colon by bacteria. This results in abdominal bloating, flatulence, diarrhea, nausea, etc after consuming dairy products.
Proteins
- Protein digestion:.
a. Oral cavity
b. Stomach
c. Duodenum
Oral cavity
Mechanical digestion only.. Mastication physically tears meat and plant protein apart.
Stomach
- HYDROLYSIS BY HCl – low pH denatures (unfolds) proteins and acid
hydrolysis breaks down the protein into peptides.. - PEPSINOGEN (a proenzyme) from chief cells is activated by HCl, converting it into pepsin.
Pepsin enzymatically breaks peptide bonds. It is only
active in low pH environments (pH = 2 – 3). - Pepsin digests 10-20% of ingested proteins while they are in the stomach.
- Products of pepsin digestion are shorter polypeptides.
i. Pancreatic proteolytic enzymes are secreted into lumen – all are proenzymes (zymogens) released from pancreas that need to be activated in the lumen of the small intestine in order to function. Includes:
- Trypsinogen
- Chymotrypsinogen
- Procarboxypeptidase
ii.A brush border enzyme, enteropeptidase, activates
trypsinogen to form trypsin.
trypsinogen enteropeptidase trypsin on intestinal wall
iii. TRYPSIN ACTIVATES THE PANCREATIC PROENZYMES, including trypsinogen (which results in a positive feedback mechanism in which trypsinogen promotes its own formation). The resulting active forms are referred to collectively as proteases.
iv. TRYPSIN and CHYMOTRYPSIN act to cleave (cut) polypeptides in the middle of the peptide chain (endopeptidases), while CARBOXYPEPTIDASE removes amino acids from the carboxyl end of the polypeptide (and is therefore considered an exopeptidase). Unlike carbohydrate digestion, the proteases are non -pecific and act on a wide range of proteins.
v. Products of digestion by proteases are dipeptides, tripeptides and oligopeptides and a few amino acids.
vi. BRUSH BORDER PEPTIDASES – enzymes embedded in apical membrane of enterocytes including AMINOPEPTIDASES and DIPEPTIDASES digest the remaining oligopeptides into tripeptides, dipeptides and amino acids.
vii. Once they are absorbed into the cytosol of the intestinal cells, tripeptides and dipeptides are broken down into amino acids by CYTOSOLIC PEPTIDASES.
Protein Absorption:
Amino acids, dipeptides, and tripeptides can be absorbed, intact proteins cannot. One exception is the absorption of immunoglobulins (IgA) from breast milk in neonatal infants (recall from Unit 4).
Protein Absorption:
- Amino acids, dipeptides, and tripeptides can be absorbed, intact proteins cannot. One exception is the absorption of immunoglobulins (IgA) from breast milk in neonatal infants (recall from Unit 4).
- Must cross the enterocyte membrane:
a. At apical membrane :
i. Amino acids are cotransported into the cell with Na+ (secondary active transport)
ii. Di-andtripeptidesarecotransportedintothecell,withwithH+. Ø Once inside the cytosol, di- and tri-peptides are broken down
into amino acids by cytosolic peptidases.
iii. Some small peptides are transported across the intestinal cells via transcytosis (endocytosis into the cell, and release via exocytosis into the ISF/blood).
b. Atbasolateralmembrane:
i. Amino acids are transported out of the cell by facilitated diffusion using carrier proteins.
Fate of Absorbed proteins:
Used for protein synthesis.
Lipids
- The vast majority of dietary lipids are triglycerides (which consist of three fatty acids attached to a glycerol backbone).
- Fats in the diet can be saturated or unsaturated.
Saturated fats
have fatty acids with single bonds between each carbon atom and are saturated with hydrogen. These are solid fats at room temperature, like butter, coconut oil., animal fats
Monounsaturated fats
have a single double bond between carbon atoms. They include fats that are oils at room temperature, such as olive oil as well as the oils in tree nuts like almonds..
Polyunsaturated fats
have more than one double bond between carbon atoms. They include fats that are oils at room temperature, such as the omega 3 and omega-6 fatty acids found in fish, eggs, some tree nuts, etc.
Lipid digestion:.
a. Oral cavity
b. Stomach
c. Duodenum
Lipids
Lipid digestion:.
a. Oral cavity
Salivary lipase – short lived activity contributing very little to lipid digestion. Lipase breaks down triglycerides into monoglycerides and free fatty acids.
Lipids
Lipid digestion:.
b. Stomach
- Churning helps to physically break up insoluble fats into large fat droplets.
- Gastric Lipase – limited action, since without bile salts, can only act on the surface of the large droplets.
Lipids
Lipid digestion:.
c. Duodenum
- ACTIVATION OF PANCREATIC PROENZYMES (ZYMOGENS)
- EMULSIFICATION
- PANCREATIC LIPASE
- COLIPASE
- PHOSPHOLIPASE
- MICELLE FORMATION
Lipids
Lipid digestion:.
c. Duodenum
- Activation of pancreatic proenzymes (zymogens): pancreatic juice contains procolipae and prophospholipase which are activated into colipase and phospholipase by trypsin. Pancreatic lipase is released in its active form.
- Emulsification – by bile salts breaks larger lipid droplets into smaller ones and provides a larger surface area (50X greater) for enzymatic digestion by pancreatic lipase.
- Pancreatic lipase – breaks down triglycerides into monoglycerides and fatty acids.
- Colipase – bile salts block access of pancreatic lipase to fats contained in emulsified lipid droplets. Colipase displaces the bile salts to allow pancreatic lipase access to the lipids. As such it is a cofactor that does not actually do any of the enzymatic digestion itself.
- Phospholipase – breaks down phospholipids.
- Micelle formation – Bile salts combine with phospholipids, mono- and diglycerides, cholesterol and fatty acids to form a “bubble” in which the insoluble products of digestion are stored and transported called a MICELLE. Micelles have a hydrophobic interior and hydrophilic exterior (due to amphipathic bile salts and phospholipids) ) which helps to keep the products of fat digestion in solution so that they can be transported in close proximity to the enterocyte cell membrane for absorption.
Lipids
Lipid Absorption:
In order to be absorbed and transported in the body fluids, lipids must be repackaged inside of the enterocyte.
Lipids
Lipid Absorption
Steps:
a. At apical membrane :
i. Micelles carry products of fat digestion to apical membrane
ii. Most fatty acids, monoglycerides, cholesterol, enter the enterocyte via simple diffusion.
- Long chain fatty acid diffusion (>12 carbons long) is mediated by fatty acid transporter
proteins (FATP4) located in jejunum and ileum. *i.e. facilitated diffusion).
b. Inside of enterocyte::
i. Some fatty acids are combined with monoglycerides in the smooth endoplasmic reticulum to reform triglycerides.
ii. Triglycerides are then combined with cholesterol and apolipoproteins to form a chylomicron (a soluble package of lipids) in the Golgi apparatus..
c. At basolateral membrane:
i. Chylomicrons (as well as fat soluble vitamins) exit enterocyte
via exocytosis.
ii. Chylomicrons are absorbed into lymph lacteals (package is too large to diffuse into blood capillary). Transported in lymph to the blood circulation (lymphatic thoracic duct empties into left subclavian vein which drains into vena cava).
Lipids
Fate of Absorbed lipids:
Most lipids are stored in the adipose tissue cells::
a. At the membrane of the adipose cell triglycerides in chylomicron are broken down by an enzyme called lipoprotein lipase (LPL) into monoglycerides and fatty acids.
b. Monoglycerides and fatty acids move into the cells via simple diffusion.
c. Once in the adipose cells, they are reassembled into triglycerides for storage.
d. Empty chylomicron packages are recycled in the liver.
Absorption of Water
- Water enters the GI tract through ingested fluids and foods, as well as through secretions from the GI tract itself.
- ~ 2.0 L/day ingested
- ~6.5-7.0 L/day from secretions (saliva, bile, gastric secretion, pancreatic
secretions, intestinal secretions). ØTotal = 8.5 – 9.0 L/day - Most (~90%) of water reabsorption occurs in the small intestine via osmosis (~7.5 L/day).
- Only 9-10% (~ 1-1.4 L) is reabsorbed by the large intestine, but this reabsorption is important for feces formation.
• Poor uptake = wet stool (diarrhea) - can lead to severe dehydration and death
• Too much uptake (slow movement of feces) can lead to constipation. - Less than ~1% (~100 mL) of ingested/secreted water is excreted with the feces per day.
Elimination of Wastes (Defecation)
Defecation Reflex (rectal reflex)
- Stimulus is presence of feces in rectum (activates stretch receptors in rectal wall)
- Signals are integrated in the sacral segment of spinal cord (PSNS)
- Effector is smooth muscle of the rectum which contracts, and pressure from the feces causes the internal anal sphincter to relax and open.
- External anal sphincter is skeletal muscles that is under voluntary control (i.e. not part of reflex) so that you can decide when and where is an appropriate time to defecate.
