Physiology & anatomy Flashcards
Describe the innervation of the GI tract
- Extrinsic innervation
- Parasympathetic (excitatory): vagus nerve for proximal parts, pelvic nerve starting at lower large intestine)
Uses ACh or peptides (eg. vasoactive intestinal peptide = VIP, serotonin) as neurotransmitters
- Sympathetic (inhibitor)
Uses norepinephrine as neurotransmitter - Intrinsic innervation = Enteric nervous system
- Myenteric plexus = Auerbach plexus (motility)
- Submucosal plexus = Meissner plexus (secretion and blood flow)
Receive information from extrinsic afferents and sensory afferents
What are the different layers of the GI tract
- Mucosa: epithelium, basement membrane, lamina propria, muscularis mucosae
- Submucosa (contains the submucosal plexus)
- Muscular propria: circular muscle, myenteric plexus, longitudinal muscle
- Serosa
What are the 5 GI hormones and their actions
- Gastrin:
- Increases gastric H+ secretion
- Stimulates growth of gastric mucosa - Cholecystokinin (CCK):
- Stimulates contraction of gallbladder and opening of sphincter of Oddi
- Stimulates pancreatic enzymes and HCO3- secretion
- Stimulates growth of pancreas / gallbladder
- Inhibits gastric emptying - Secretin:
- Stimulates pepsin secretion
- Increases pancreatic HCO3- secretion
- Increases biliary HCO3- secretion
- Decreases gastric H+ secretion - Glucose-dependent insulinotropic peptide = gastric inhibitory peptide (GIP):
- Increases insulin secretion
- Decreases gastric H+ secretion - Motilin:
- Stimulates gastric and intestinal motility
What cells secrete gastrin? Under what stimulus?
G cells of the stomach (antrum)
Stimulated by meal:
- Small peptides / amino-acids (phenylalanine & tryptophan)
- Distension of stomach
- Vagal stimulation via gastrin-releasing peptide (GRP)
Inhibited by H+ in stomach and somatostatin
What cells secrete CCK? Under what stimulus?
I cells of the duodenal and jejunal mucosa
Stimulated by:
- Fatty acids, monoglycerides
- Small peptides and amino acids
** fatty meals stimulate secretion to slow gastric emptying –> more time for digestion
What cells secrete secretin? Under what stimulus?
S cells of the duodenum (mucosa)
Stimulated by:
- H+ in duodenum
- Fatty acids in duodenum
What cells secrete GIP? Under what stimulus?
Cells of the duodenal and jejunal mucosa
Stimulated by:
- Oral glucose
- Fatty acids
- Amino-acids
What cells secrete motilin? Under what stimulus?
M cells of the duodenum and jejunum
Stimulated by:
- Fatty acids
- H+
What are the 2 major paracrines of the GI tract? What cells secrete them and what are their actions?
- Histamine
- Secreted by mast cells of the gastric mucosa + enterochromaffin-like cells
- Increases gastric H+ secretion and intestinal Cl secretion - Somatostatin
- Secreted by D cells throughout GI tract (in response to H+ in lumen)
- Inhibits release of GI hormones and H+ secretion
What are the actions of the vasoactive intestinal peptide (VIP)
- Relaxation of GI smooth muscle (including lower esophageal sphincter)
- Stimulation of pancreatic HCO3- secretion
- Inhibition of gastric H+ secretion
Name 2 endogenous substances that stimulate appetite and 2 that inhibit appetite
Stimulate:
- Ghrelin
- Neuropeptide Y
Inhibit:
- Insulin
- Leptin
- CCK
Explain what are the “slow waves” of the GI tract
Oscillating membrane potentials that occur spontaneously due to cycling opening of Ca2+ channels followed by opening of K+ channels. They don’t trigger contraction by themselves but the probability of action potentials occurring is higher during depolarization phase. They set the max frequency of contractions (3/min in stomach, 12/min in duodenum)
Where are the “slow waves” of the GI tract initiated
Interstitial cells of Cajal (= pacemakers of the gut)
What types of muscles are found in the esophagus of cats / dogs
Cats: upper 2/3 = striated muscle / lower 1/3 = smooth muscle
Dogs: only striated muscle
What is the migrating myoelectric complex = migrating motor complex? What are its phases?
Contractions of the stomach occurring every 90 min during fasting.
Phase I = quiescence (~1h)
Phase II = intermittent contractions (~15-40 min)
Phase III = intense propulsive motility (~4-8 min). Under the influence of motilin.
What mediates relaxation of the stomach during meal
Vagovagal reflex also increased by CCK (“receptive relaxation”)
The orad region of the stomach relaxes
What are the 2 types of small intestinal contractions? What are their equivalents called in the colon?
- Segmentation contractions = mixing movements -> stimulated by local stretch and vagus
- Peristaltic contractions = propulsive movements
In colon:
- Mixing movements = haustrations
- Propulsive movements = mass movements
What are the 2 types of electric activity in the GI smooth muscle cells
- Slow waves (fixed rhythm, do not initiate contraction)
- Action potentials (initiate contraction)
What is in charge of coordinating peristaltic contractions
Enteric nervous system, initiated by serotonin (=5-hydroxytryptamine = 5-HT) and stimulated by CCK, gastrin, insulin, and motilin
What is the most important control of gastric emptying
Duodenal feedback: volume of chyme, presence of unprocessed fat or protein, excessive H+, hypertonicity or hypotonicity of chyme, and any irritants in chyme decrease gastric emptying
What mediators cause contraction / relaxation of the lower esophageal sphincter
Contraction: ACh, gastrin
Relaxation: NO, VIP
As a general rule, what neurotransmitters cause contraction / relaxation of GI smooth muscles
Contraction: ACh, 5-HT (= serotonin)
Relaxation: NO, VIP
What is the composition of saliva (in terms of electrolytes, tonicity, enzymes). Where does it get its final composition?
- High K+ and high HCO3-
- Low Na+ and low Cl-
- Hypotonic
- Contains alpha-amylase (not in cats and dogs?) and lingual lipase
- Anti-microbials (IgA)
At the lowest flow rates, saliva has the lowest osmolarity and lowest Na+, Cl−, and HCO3− concentrations but has the highest K+ concentration
Composition acquired in salivary ducts by re-absorption / secretion mechanisms
3 functions of salive
- Initial starch (Alph-amylase) and triglyceride (Lingual lipase) digestion
- Lubrication of ingested food
- protection by dilution and buffering
What nervous systems stimulate saliva production? Via what receptors?
- Parasympathetic nervous system via muscarinic receptors (most important)
- Sympathetic nervous system via beta-adrenergic receptors
What are the different gastric cells, their location and their secretions
- Body -> oxyntic glands = gastric glands:
- Parietal cells: secrete HCl and intrinsic factor
- Chief cells: pepsinogen
- ECL cells: histamine
- D cells: somatostatin
- Mucus cells: mucus - Antrum -> pyloric glands:
- G cells: gastrin
- Mucus cells (= goblet cells): mucus
What transporters are involved in gastric acid secretion
- H+ - K+ ATPase (“proton pump”) on the apical membrane of parietal cells
- Cl channel (CFTR) on apical membrane of parietal cells
- Cl- - HCO3- exchanger on the basal membrane of parietal cells
What stimulates / inhibits gastric acid secretion (indicate receptors and second messenger)
- Stimulates:
- Gastrin (CCKb receptor, Gq receptor -> increased IP3 + stimulates histamine release)
- ACh (muscarinic receptor (M3), Gq receptor -> increased IP3) / vagus stimulation
- Histamine (H2 receptor, Gs receptor -> increased cAMP) - Inhibits:
- Somatostatin (Gi receptor -> decreased cAMP + indirect by inhibition of gastrin and histamine) - released in response to pH<3.0
- Prostaglandins (Gi receptor -> decreased cAMP)
What is the composition of pancreatic secretions (in terms of electrolytes, tonicity, enzymes). Where does it get its final composition?
- Same Na+ and K+ as plasma
- High HCO3-
- Low Cl-
- Isotonic
- Enzymes: lipase, amylase, trypsin, chymotrypsin (secreted in inactive forms: zymogen)
- Trypsin inhibitor to prevent auto-digestion
Final HCO3- and Cl- composition gotten in ducts, but enzymes are secreted by acinar cells
What transporters are involved in pancreatic HCO3- secretion
- HCO3- - Cl- exchanger on apical membrane
- Cl channel (CFTR) on apical membrane
- H+ - Na+ exchanger and Na+ - HCO3- cotransporter on basal membrane with Na+ - K+ ATPase keeping Na gradient
What stimulates pancreatic secretion
- Secretin: stimulates HCO3- secretion (action on ductular cells)
- CCK: stimulates enzyme secretion (action on acinar cells) + potentiates secretin
- ACh: stimulates enzyme secretion + potentiates secretin
What is the composition of bile
Bile salts, phospholipids, cholesterol and bilirubin
What stimulates secretion of bile
- CCK (contraction of gallbladder + relaxation of sphincter of Oddi)
- ACh (contraction of gallbladder)
- Secretin (stimulation of bile secretion from hepatocytes)
What is the difference between primary bile acids and secondary bile acids?
Primary bile acids are formed by synthesis in the liver and consist of chenodeoxycholic acid and cholic acid (which can be conjugated or unconjugated)
Secondary bile acids are those made by bacteria in the gut, specifically by dehydroxylating primary bile acids. As a result, lithocholic acid (dehydroxylated chenodeoxycholic acid) and deoxycholic acid (dehydroxylated cholic acid) are secondary bile acids. These bile acids are poorly water soluble and toxic to cells.
What part of the GI is required for recycling of bile acids
Ileum
Where are pancreatic secretions released in cats and dogs
Cats: in the common bile duct (20% of cats have a separate duct that enters the duodenum)
Dogs: directly in the duodenum via the accessory collecting duct
What are the main salivary glands
- Parotid
- Sublingual
- Mandibular
- Zygomatic
What is the role of the intrinsic factor? Where is it secreted?
Required for absorption of vitamin B12
Secreted by parietal cells
What are the 3 phases of gastric and pancreatic secretion
- Cephalic phase (before food enters the stomach)
- Gastric phase (when food is in the stomach ; most of gastric secretions)
- Intestinal phase (when food has reached duodenum ; most of pancreatic secretions)
What is required for activation of pancreatic enzymes
Enterokinase (secreted by intestinal mucosa when in contact with chyme) -> cleaves trypsinogen into trypsin which can then activate other enzymes
What is the precursor of bile salts? What are their functions?
- Precursor = cholesterol
- Functions = emulsification of fat in the intestinal lumen to allow their digestion + absorption of lipids by formation of micelles
What is mostly secreted by intestinal epithelial cells
- Mucus (++ in Brunner’s glands in proximal duodenum, stimulated by ACh and secretin)
- Water
- Electrolytes
What is the name of the major lymphoid tissue of the GI tract? What cells are mostly found in it?
Peyer’s patches
Contain:
- B lymphocytes
- T lymphocytes
- Antigen presenting cells = dendritic cells, macrophages, epithelial M cells
Name enzymes responsible for hydrolysis of carbohydrates / proteins / lipids. Where does hydrolysis happen?
- Carbohydrates: amylase (stomach) / lactase, sucrase, maltase (intestine)
- Proteins: pepsin (stomach) / trypsin, chymotrypsin, carboxypolypeptidase (intestine)
- Lipids: lingual liaise (stomach) / pancreatic lipase (intestine) ; emulsification by bile acids
Hydrolysis happens in the lumen and at the level of the brush border (enzymes anchored to microvilli)
What are the 3 levels of increase of the absorptive surface area in the intestine
- Valvular conniventes = folds of Kercking (->3-fold increase of surface)
- Villi (-> 10-fold)
- Microvilli = brush border (-> 20-fold)
=> 1000-fold increase
How is water absorbed through the intestinal membrane
By diffusion / osmosis
What hormone increases sodium absorption in the intestine? Where is its action most important?
Aldosterone ; main action in colon
Where is bicarbonate absorbed / secreted in the GI tract
- Absorbed in duodenum and jejunum (same mechanism as renal proximal tubule with Na+ - H+ exchanger)
- Secreted in ileum and large intestine against Cl-
(- A large amount is secreted via pancreatic secretions and bile +/- saliva)
How are carbohydrates and proteins absorbed in the intestine
- They are first hydrolyzed to monosaccharides and small peptides or amino acids
- Then they are absorbed at the apical pole of the epithelial cells by co-transport with sodium (with Na-K ATPase at the basal membrane)
*Fructose is transported by facilitated diffusion (GLUT-5), not coupled with sodium
Describe absorption of fats from the gut
- Lipids undergo emulsification by bile acids and hydrolysis by lipase
- Monoglycerides and free fatty acids are dissolved in bile micelles
- Monoglycerides and fatty acids dissolve out of micelles into epithelial cells
- They enter the smooth endoplasmic reticulum where they form new triglycerides
- Triglycerides are released at the basal pole as chylomicrons and end up in the lymphatic circulation
(Some fatty acids are directly absorbed into the portal blood)
What are the names of glucose transporters in the intestinal epithelial cell
- SGLT-1 at apical pole
- GLUT-2 at basal pole
*Fructose is transported by facilitated diffusion (GLUT-5), not coupled with sodium
How can vitamins be absorbed in the intestine
- Water-soluble vitamins have a co-transport with Na+
- Vitamin B12 is absorbed with intrinsic factor in ileum
- Fat-soluble vitamins (A,D,K,E) are absorbed as fatty acids
What are mechanisms to prevent activation of pancreatic enzymes within the pancreas
- Secretion of enzymes as zymogens, which need to be activated in the duodenum (by enterokinase and then trypsin itself)
- Secretion of trypsin inhibitor by acinar cells
What hormones are in charge of GI motility
- Motilin
- Serotonin = 5-hydroxytryptamine
What are the main arteries irrigating the stomach? Where do they originate from?
Originate from the celiac artery
- Left gastric artery
- Splenic artery -> left gastroepiploic artery + short gastric arteries
- Hepatic artery -> right gastric artery and gastroduodenal artery
Where do the bile and pancreatic ducts open in the duodenum
- Major duodenal papilla: bile duct and pancreatic duct (2 adjacent openings in dogs, same opening in cats)
- Minor duodenal papilla: accessory pancreatic duct (in all dogs ; only 20% of cats)
Where does the vasculature of the small intestine originate from
Cranial mesenteric artery
True or false: aldosterone can increase K+ secretion in the colon
True (same action as distal tubule)
Where are the satiety center and feeding center located?
Hypothalamus
- Satiety –> ventromedial nucelus
- Feeding –> lateral hypothalamic area
Which layers of the GI tract are responsible for decrease in diameter and decrease in length of the GI tract when they contract?
Circular muscle –> decrease in diameter
Longtitudinal muscle –> decrease in length
Where is the swallowing reflex coordinated?
Medulla
What is the intra esophageal pressure equal to?
Thoracic pressure
Where does water absorption mostly occur in the colon?
Proximal colon
3 things that stimulate the vomiting center in the medulla? The chemoreceptor trigger zone in the 4th ventricle?
Tickling back of throat
Gastric distention
Vestibular stimulation
Emetics
Radiation
Vestibular stimulation
Explain the mechanism of metabolic alkalosis in upper GI obstruction
- In the parietal cell, CO2 + H2O –> H+ and HCO3-
- H+ secreted into the lumen by H+, K+-ATPase pump
- HCO3- is absorbed via Cl- HCO3 - exchange
- This HCo3- is eventually secreted in pancreatic secretions to neutralize H+ in intestine
- If H+ never makes it to intestine –> no stimulus for pancreatic HCO3− secretion –> alkalosis
Why are H2 blocker drugs effective for treatment of ulcers?
They block the direct effect of histamine on parietal cells (activation of H2 receptors and stimulation of H+ secretion) AND potentiating effects of histamine on ACh and gastrin
What are roles of prostaglandins in the GI tract?
- Inhibition of gastric H+ secretion by activating a Gi protein, inhibiting
adenylyl cyclase and decreasing cAMP levels - Maintain the mucosal barrier and stimulate HCO3− secretion,
protecting the gastric mucosa from the damaging effects of H+
True or false: In the face of a gastric ulcer, H+ secretion is decreased and gastrin secretion is decreased
True
H+ secretion is decreased because secreted H+ leaks back through the damaged gastric mucosa.
Gastrin levels are increased because decreased H+ secretion stimulates gastrin secretion.
What are protective factors and damaging factors to the gastric mucosa?
Protective factors:
- Mucus
- HCO3−
- Prostaglandins
- Mucosal blood flow
- Growth factors
Damaging factors
- H+
- Pepsin
- Helicobacter pylori (H. pylori)
- NSAIDS
- Stress
3 drugs that block H secretion
- Atropine - inhibition of ACh
- Cimetidine - blocks H2 receptor
- Omperazole - inhibition of H+, K+-ATPase
Name the 7 enzymes involved in digestion of carbohydrates
α-Amylases, maltase, α-dextrinase, sucrase. lactase, trehalase, sucrase
At what pH is pepsin denatured?
> 5
Optimal pH: between 1-3
Name 6 causes of lipid malabsorption
- Pancreatic disease
- Hypersécrétion of gastrin (low pH inactivates pancreatic lipase)
- Ileal resection (depletion of bile acid pool)
- Bacterial overgrowth
- Decreased number of intestinal cells
- Failure to sythesize apoprotein B
What are the 4 mechanisms by which Na+ moves into the intestinal cells?
- Passive diffusion (through Na+ channels) –> colon, stimulated by aldosterone
- Na+–glucose or Na+–amino acid cotransport –> small intestine
- Na+–Cl− cotransport.
- Na+–H+ exchange –> small intestine
What happens to K+ with diarrhea?
K+ secretion by the colon is increased because of a flow rate–dependent mechanism similar to that in the renal distal tubule –> hypokalemia.
True or false: the secretory mechanisms are located in the crypts. The absorptive mechanisms are located in the villi.
True
What is required for calcium absorption in the small intestine?
The presence of adequate amounts of the active form of vitamin D, 1,25- dihydroxycholecalciferol, which is produced in the kidney and induces the synthesis of an intestinal Ca2+- binding protein, calbindin D-28K.
In what form is iron absorbed in the intestine?
As heme iron or free Fe2+
Free Fe2+ binds to apoferritin and is transported into the blood
In the blood, free Fe2+ circulates bound to transferrin
What are the main nerve groups innervating the esophagus?
Nerve fibers arising from various branches of the vagus:
- Pharyngoesophageal nerves
- Recurrent laryngeal and paralaryngeal nerves
- Dorsal and ventral vagal trunks
What 2 veins of the stomach drain into the portal vein?
Gastrosplenic vein on the left Gastroduodenal vein on the right
By what 3 mechanisms is sodium absorbed in the small intestin?
- Passive diffusion along with Cl- down an electrochemical gradient
- Coupled with Na+-K+-ATPase–mediated active transport of monosaccharides or amino acids, such as glucose or alanine
- Cotransport with other electrolytes
True or false: pancreatic lipase participates in lipid degradation and pancreatic amylase participates in carbohydrate degradation
True
What is a micelle?
Aggregates of bile salt that forms a hydrophilic outer shell and a hydrophobic inner core –> facilitate normal fat digestion through breakdown of large aggregates or droplets into smaller and smaller droplets + aids access of pancreatic lipase
What is the normal intestinal length in cats and dogs?
1-1.5m in cats
2-5m in dogs
What are the main physiological functions of the colon?
Reabsorption of water, Na+, Cl−, and short-chain fatty acids
Secretion of K+, HCO3−, and mucus
