Physiology Review Flashcards
Histological layers of GI tract
Epithelium Lamina propria Muscularis mucosae Submucosa Submucosal plexus Circular smooth muscle Myenteric plexus Longitudinal smooth muscle Serosa
What are the components of the ENS and where does it receive info from?
Comprises the myenteric and submucosal plexuses
Receives info from parasympathetic and sympathetic nervous systems and CNS, as well as mechanoreceptors and chemoreceptors in the mucosa
Roles of CNS in regulation of GI function
Vagovagal reflex (e.g., gastric receptive relaxation reflex)
Modulates ENS responses
Centers that control food intake are located in the brain (NTS communicates with gut via vagal innervation — sensory ganglion of vagal nerve is nodose ganglion)
Parasympathetic innervation of the GI tract is via the ____and ____ nerves.
Preganglionic cell bodies are located in the _____ or the _____
Postganglionic neurons lie in the wall of the organ (enteric neurons)
Synapse between pre and post ganglionic cells is ______
Vagus; pelvic
Brainstem; sacral SC
Nicotinic (nAChRs)
Sympathetic innervation of the GI tract is via nerves running between the SC and the prevertebral ganglia, and between these ganglia and GI organs.
Preganglionic efferent fibers arise within the SC and end in prevertebral ganglia
Postganglionic fibers from the prevertebral ganglia innervate the myenteric and submucosal plexuses
Mostly, preganglionic efferent fibers release ___, while postganglionic efferent fibers release ____
ACh; NE
Action of peptides like somatostatin or messenger molecules like histamine in the GI tract is via _____ signaling
Paracrine
______ cells in the gut contain secretory granules filled with hormones that are released upon stimulation
Hormones then enter the _____ circulation, passing through the liver then entering systemic circulation and traveling to the target cell
Enteroendocrine
Portal
Stimuli of secretion, site of secretion, and action of the following GI hormone:
Gastrin
Stimuli of secretion: small peptides and aa, distention of stomach, vagal stimulation (via GRP)
Site of secretion: G cells of stomach
Actions: increased gastric H+ secretion; stimulates growth of gastric mucosa
Stimuli of secretion, site of secretion, and action of the following GI hormone:
CCK
Stimuli of secretion: small peptides and aa, fatty acids
Site of secretion: I cells of duodenum and jejunum
Actions: increased pancreatic enzyme secretion; increased pancreatic bicarb section, stimulates contraction of gallbladder and relaxation of sphincter of oddi, stimulates growth of exocrine pancreas and gallbaldder, inhibits gastric emptying
Stimuli of secretion, site of secretion, and action of the following GI hormone:
Secretin
Stimuli of secretion: H+ in duodenum, fatty acids in duodenum
Site of secretion: S cells of the duodenum
Actions: increased pancreatic bicarb secretion, increased biliary HCO3 secretion, decreased gastric H+ secretion, inhibits trophic effect of gastrin on gastric mucosa
Stimuli of secretion, site of secretion, and action of the following GI hormone:
Glucose-dependent insulinotropic peptide (GIP)
Stimuli of secretion: fatty acids, aa, oral glucose
Site of secretion: duodenum and jejunum
Actions: increased insulin secretion from pancreatic beta cells (incretin effect), decreased gastric H+ secretion
What is the incretin effect?
The ability of a GI hormone to promote secretion of insulin (GIP is classified as an incretin)
____ and ____ mediate the incretin effect
GLP-1; GIP
Source and actions of the following on the GI tract:
ACh
Source: cholinergic neurons
Actions: contraction of smooth muscle, relaxation of sphincters, increased salivary secretion, increased gastric acid secretion, increased pancreatic secretion
Source and actions of the following on the GI tract:
NE
Source: adrenergic neurons
Actions: relaxation of smooth muscle wall, contraction of sphincters, increased salivary secretion
Source and actions of the following on the GI tract:
Vasoactive intestinal peptide (VIP)
Source: neurons of the ENS
Actions: relaxation of smooth muscle, increased intestinal secretion, increased pancreatic secretion
Source and actions of the following on the GI tract:
NO
Source: neurons of the ENS
Action: relaxation of smooth muscle
Source and actions of the following on the GI tract:
GRP
Source: vagal neurons of gastric mucosa
Actions: increased gastrin secretion
Source and actions of the following on the GI tract:
Enkephalins
Source: neurons of the ENS
Actions: contraction of smooth muscle, decreased intestinal secretion
Source and actions of the following on the GI tract:
Neuropeptide Y
Source: neurons of the ENS
Actions: relaxation of smooth muscle, decreased intestinal secretion
Source and actions of the following on the GI tract:
Substance P
Source: co-release with ACh by neurons of the ENS
Actions: contraction of smooth muscle, increased salivary secretion
Slow waves vs. APs
Slow waves are NOT APs - they consist of depolarization and repolarization of membrane potential
APs occur when the depolarization moves the membrane potential to or above threshold (to more positive membrane potentials) —> mechanical response
[modulated by neural and hormone activity]
Phasic vs. tonic contractions in GI tract
Phasic: periodic contractions followed by relaxation [esophagus, stomach (antrum), small intestine, and all tissues involved in mixing and propulsion]
Tonic: maintain a constant level of contraction without regular periods of relaxation [stomach (orad), lower esophageal, ileocecal, and internal anal sphincters]
What factors increase vs. decrease the amplitude of slow waves and # of APs?
Stretch, ACh, and parasympathetics increase
NE and sympathetics decrease
Pacemaker cells for GI smooth muscle
Interstitial cells of Cajal (ICC) in myenteric plexus
[ICCs generate and propagate slow waves, which occur spontaneously in the ICC and spread rapidly to smooth muscle via gap junctions, driving the frequency of contractions]
Phases of swallowing
Oral phase = voluntary
Pharyngeal phase = involuntary (soft palate pulled up, epiglottis moves, UES relaxes, contraction initiated in pharynx, food propelled through UES)
Esophageal phase = involuntary (control by swallowing reflex and ENS, consists of primary and secondary peristaltic waves)
What region of the brain controls the involuntary swallowing reflex?
Medulla
[food in the pharynx —> afferent sensory input via vagus/glossopharyngeal n.—>medulla—>brainstem nuclei—>efferent input to pharynx]
Differentiate primary from secondary peristaltic waves; which one can still occur after vagotomy?
Primary: continuation of pharyngeal peristalsis, controlled by medulla, CANNOT occur after vagotomy
Secondary: occurs if primary wave fails to empty esophagus or if gastric contents reflux into esophagus; medulla and ENS involved, can occur in absence of oral and pharyngeal phases - occurs even after vagotomy
Opening of the LES is mediated by peptidergic fibers in the ____ nerve and is accompanied by release of ______
Vagal; VIP
Receptive relaxation occurs in the __ region of the stomach, which is the process of decreasing pressure and increasing volume of this region — aka the ____ reflex
Orad; vagovagal
Large particles of undigested residue remaining in the stomach are emptied by ______ ____ ____, which are periodic, bursting peristaltic contractions that occur at 90 min intervals during fasting; ____ plays a significant role in mediating the complex and these contractions are inhibited during feeding
Migrating myoelectric complex (MMC); motilin
Does the rate of gastric emptying increase by increasing or decreasing the following?
_____ distensibility of the orad stomach
______ force of peristaltic contractions of the caudad stomach
_____ tone of the pylorus
____ the diameter and inhibition of segmenting contractions of the proximal duodenum
Decreased
Increased
Decreased
Increased
[gastric emptying takes ~3 hrs]
What is the enterogastric reflex
Negative feedback from the duodenum slows down the rate of gastric emptying
—Acid in duodenum —> stimulate secretin release —> inhibit stomach motility via gastrin inhibition
—Fats in duodenum —> stimulate CCK and GIP —> inhibit stomach motility
—Hypertonicity in duodenum —> (unknown hormone) —> inhibit gastric emptying
Describe electrical activity of ICCs and smooth muscle cells in intestine
Slow wave activity always present whether contractions occurring or not
Unlike the stomach, slow waves themselves do NOT initiate contractions in the SI; spike potentials (AP) are necessary for muscle contraction to occur and slow wave frequency sets max frequency of contractions
What hormones stimulate vs. inhibit contractions in the intestine?
Stimulate: serotonin, prostaglandins, gastrin, CCK, motilin, insulin
Inhibit: epinephrine, secretin, glucagon
What is the rectosphincteric reflex?
As the rectum fills with feces, SM wall of the rectum contracts and internal anal sphincter relaxes
It is under neural control, primarily by ENS and reinforced by activity of neurons in SC
The vomiting reflex is coordinated in the _____; nerve impulses are transmitted by vagus and _______ afferents to multiple brainstem nuclei
Medulla; sympathetic
Events in vomiting reflex
Reverse peristalsis in the small intestine
Stomach and pylorus relaxation
Forced inspiration to increase abdominal pressure
Movement of the larynx
LES relaxation
Glottis closes
Forceful expulsion of gastric contents
Short reflex that is generally inhibitory, involving only the ENS and completely independent of the extrinsic ANS (atropine has no effect on it); e.g., ileocecal sphincter
Intestino-intestinal reflex
Reflex in which gastric distention relaxes ileocecal sphincter
Gastroileal reflex (gastroenteric)
Function of gastro- and duodeno-colic reflexes
Distention of stomach/duodenum initiates mass movements (transmitted by way of ANS)
Structural change that occurs in GERD
LES relaxes or abnormally weakens
May be d/t motor abnormalities that result in abnormally low pressures in the LES or intragastric pressure increase (large meal, heavy lifting, pregnancy)
Physiological effect of achalasia on esophagus
Impaired peristalsis, incomplete LES relaxation during swallowing (LES stays closed so food backs up), elevation of LES resting pressure
D/t lack of VIP or ENS has been knocked out, or damage to nerves in esophagus
Common cause and symtpoms of gastroparesis
DM; also injury to vagus nerve
Symptoms: nausea, vomiting, early feeling of fullness when eating, weight loss, abdominal bloating, abdominal discomfort
Cause of hirschsprung disease
Ganglion cells absent for segment of colon — VIP levels low —> SM constriction/loss of coordinated movement —> colon contents accumulate
[in affected newborn it is characterized by inability to pass meconium]
Chemical components of saliva
H2O, electrolytes, alpha-amylase, lingual lipase, kallikrein, and mucus
Saliva is hypotonic compared to plasma [increased K and bicarb, decreased NaCl]
2 main steps in saliva formation
- Formation of isotonic, plasma-like soluction by acinar cells
- Modification of the isotonic solution by the ductal cells
There is overall net absorption of solute! — more NaCl is absorbed than KHCO3 secretion
Salivary secretion is exclusively under the control of the ANS. What is the effect of parasympathetic vs. sympathetic stimulation?
Both increase salivary secretion
Difference between oxyntic glands and pyloric glands in gastric mucosa
Oxyntic glands — located in proximal 80% of stomach (body and fundus), secrete acid
Pyloric glands — located in distal 20% of stomach (antrum), synthesizes and releases gastrin
What components of gastric juice are secreted by: parietal cells, chief cells, G cells, and mucous cells?
[closest to fundus]
Parietal cells = intrinsic factor, HCl
Chief cells = pepsinogen
G cells = gastrin (to circulation)
Mucus cells = mucus, HCO3, pepsinogen
[closest to antrum]
T/F: pepsinogen is secreted only when the gastric pH is acidic enough to convert it to pepsin
True
[pepsinogen is secreted by chief cells and mucus cells in oxyntic glands; it requires H+ secretion from parietal cells to lower pH of gastric contents. Vagus n. stimulation is most important stimulus for pepsinogen secretion. H+ triggers local cholinergic reflexes that stimulate chief cells to secrete pepsinogen]
With net secretion of HCl by gastric parietal cells, there is net absorption of _____
HCO3
A passive feedback mechanism regulates HCl secretion from parietal cells: as pH falls, ___ release is inhibited, thus decreasing HCl secretion
Gastrin
What effect does Omeprazole have on HCl secretion from parietal cells? What is its MOA?
Inhibits H/K-ATPase of parietal cells to reduce HCl secretion
Effect and MOA of cimetidine medication
H2 receptor antagonist that treats GERD, duodenal, and gastric ulcers by reducing H+ secretion
[H2 receptor is what histamine acts on to increase H+ secretion via cAMP]
Vagus n. stimulation resulting in ACh binding its muscarinic receptor on parietal cell would result in GPCR activation and ____ and _____ second messengers leading to ____ H+ secretion
IP3; Ca2+; increased
[gastrin acts at CCK-b receptor in same way with same result]
Effect of somatostatin and prostaglandins on H+ secretion
Both decrease H+ secretion via Gi GPCR which inhibits cAMP
Effect of atropine on HCl secretion
Atropine decreases H+ production by inhibiting communication between ACh and M3 receptor (PNS via vagus n.)
Potentiation involves the combed response of 2 stimulants that exceed their summed response; requires separate receptors for each stimulant
Examples include histamine and ACh, what do these signals potentiate?
Histamine potentiates ACh and gastrin responses
ACh potentiates actions of histamine and gastrin
Histamine potentiates ACh and gastrin responses
ACh potentiates actions of histamine and gastrin
What are the pharmacologic implications?
Antagonists of H2 receptors (e.g. cimetidine) block the direct action of histamine and also block potentiated effects of ACh and gastrin
Antagonist of mAChRs (e.g., atropine) block the direct effects of ACh and the ACh-potentiated effects of histamine and gastrin
Regulation of gastrin release by somatostatin, vagal activation, gastrin itself, and H+ in gastric lumen
Somatostatin acts on G cells to inhibit gastrin release
Vagal activation stimulates gastrin release by releasing GRP and inhibiting release of somatostatin
Negative feedback regulation by gastrin (gastrin itself increases somatostatin)
H+ in the gastric lumen stimulates release of somatostatin
3 phases of gastric HCl secretion
Cephalic (via vagus)
Gastric (local nervous secretory reflexes, vagal reflexes, gastrin-histamine stimulation)
Intestinal (nervous and hormonal mechanisms)
IF is important for ____ absorption in the _____; failure to secrete IF leads to _____ _____
Vit B12; ileum; pernicious anemia (aka megaloblastic anemia)
Direct vs indirect pathway of vagus n. on HCl secretion from parietal cells
Direct: directly synapses on parietal cells [ACh] —> HCl production
Indirect: synapse on G cells [GRP] —> gastrin release to circulation —> gastrin acts on parietal cells to increase HCl production
How does H.pylori damage the gastric mucosa?
Releases cytotoxins that break down the mucosal barrier and underlying cells
The enzyme urease allows the bacteria to colonize the gastric mucosa [urease converts urea to NH3 which alkalinizes local environment; diagnostic test is based on urease activity]
Duodenal ulcers are ____ common than gastric ulcers, do not usually become malignant, and involve higher than normal ___ secretion rates
More; H+
What is Zollinger-Ellison syndrome
Tumor, usually in the pancreas, secretes large quantities of gastrin —> increase H+ secretion by parietal cels and increased parietal cell mass (trophic effect)
Low duodenal pH inactivates pancreatic lipases —> steatorrhea
How is secretin used in the dx of gastrin-secreting tumors?
Under normal conditions, secretin admin inhibits gastrin release
In gastrinomas, injection of secretin causes a paradoxical increase in gastrin release
2 components of pancreatic secretions
Aqueous secretion by centroacinar and ductal cells (produce initial solution which is isotonic and contains Na, K, Cl, and HCO3 - then modified by transport processes in ductal epithelial cells)
Enzymatic secretion by acinar cells (pancreatic amylases and lipases secreted as active enzymes, pancreatic proteases are secreted in their inactive forms and converted to their active forms in the lumen of duodenum)
When net result is secretion of HCO3 from pancreatic ductal cells, there is net absorption of ___
H+
Phases of pancreatic secretion
Cephalic phase: initiated by smell/taste/conditioning, mediated by vagus n., produces mainly enzymatic secretion
Gastric phase: initiated by stomach distention, mediated by vagus n., produces mainly enzymatic secretion
Intestinal phase: accounts for 80%, enzymatic and aqueous secretions are stimulated
CF and the pancreas
Mutations in CFTR (regulated Cl channel in apical surface of pancreatic ductal cell)
In CF, pancreas is one of first organs to fail; may lead to acute and chronic pancreatitis
How does liver dysfunction lead to hepatic encephalopathy?
Decreased hepatic urea cycle metabolism in the context of liver cirrhosis or portosystemic shunting leads to accumulation of ammonia in systemic circulation —> ammonia readily crosses BBB and alters brain function
Mechanism of bile secretion and absorption of bile salts
- Synthesis and secretion of bile salts in liver
- Bile salts are stored and concentrated in gallbladder
- CCK-induced gallbladder contraction and sphincter of oddi relaxation
- Absorption of bile salts into portal circulation
- Delivery of bile salts to the liver
Bile salts are recirculated to the liver via the enterohepatic circulation
Uptake across the basolateral membrane of hepatocytes is mediated by what 2 systems?
NTCP and OATPs
Hemolytic anemia is associated with increased levels of _____ bilirubin
Indirect (unconjugated)
Physiological neonatal jaundice is associated with increased ____ bilirubin
What are the 2 main causes?
Indirect (unconjugated)
Caused by elevated bili d/t increased breakdown of fetal erythrocytes and/or low activity of UDP-glucuronyl transferase
Gilbert syndrome is associated with increased levels of ____ bilirubin d/t mutation in the gene that codes for _____
Indirect (unconjugated); UDP glucuronyl transferase (UGT)
Crigler-Najjar syndrome is associated with increased levels of _____ bilirubin d/t mutations in the gene that codes for _____.
Which type is more severe?
Unconjugated; UGT
Type 1 is very severe (no function of UGT, associated with kernicterus); type 2 is less severe
What condition is associated with increased levels of conjugated (Direct) bilirubin and a black pigmentation of the liver?
What is the mutation in?
Dubin-johnson syndrome
Mutation in multidrug resistance protein 2 (MRP2)
What condition is characterized by buildup of both unconjugated and conjugated bilirubin in the blood (but majority is conjugated), and involves gene mutations in OATP1B1 and OATP1B3
Rotor syndrome
Cell types in intestinal epithelium
Enterocytes (epithelial cells) - digestion, absorption, secretion, high turnover rate, susceptible to irradiation and chemo
Paneth cells - part of mucosal defenses, secrete agents that destroy bacteria or produce inflammation
Goblet cells - mucus-secreting
Only monosaccharides are absorbed by the enterocytes - what are the 3 monosaccharides that are end products of carbohydrate digestion?
Glucose
Galactose
Fructose
Disaccharides are lactose (glucose+galactose) and sucrose (glucose+fructose)
What type of diarrhea occurs in lactose intolerance?
Osmotic diarrhea — undigested lactose remains in the lumen and holds H2O, and causes osmotic diarrhea
What enzymes participate in protein digestion in the stomach, small intestine, and pancreas?
Stomach: pepsin
Pancreas: trypsin, chymotrypsin, elastase, carboxypeptidases (secreted in inactive form)
Small intestine: trypsin
Most lipid digestion occurs in the SI. What pancreatic enzymes are secreted to participate in lipid digestion?
Pancreatic lipase - secreted as active enzyme
Colipase - binds pancreatic lipase and displaces bile salts
Cholesterol ester hydrolase
Phospholipase A2
Mechanism for processing lipids in small intestine
- Solubilization by micelles
- Diffusion of micellar content across apical membrane
- Reesterification
- Chylomicron formation
- Exocytois of chylomicron
What condition is characterized by a deficiency of ApoB?
Abetalipoproteinemia —> no absorption of dietary lipids!
Factors that cause deficits in bile salts
Ileal resection (interrupts enterohepatic circulation of bile salts; total bile salt pool is reduced)
Small intestinal bacterial overgrowth (SIBO) - bacteria deconjugate bile salts, impairing micelle formation and fat malabsorption (2 main causes are decreased gastric acid secretion and small intestine dysmotility)
Tropical sprue
Likely d/t intestinal infection —> decreased # of intestinal epithelial cells; reduces microvillar surface area —> impaired lipid absorption —> steatorrhea
Characterized by nutritional deficiencies, especially of folate and B12, main symptom is diarrhea
Celiac sprue
Autoimmune disorder in which antibodies develop against gliadin —> destruction of small intestine villi and hyperplasia of intestinal crypts
Malabsorption related to deficiencies in folate, iron, calcium, and vitamines A, B12, and D
What surgical procedures might produce B12 deficiency?
Gastrectomy — loss of parietal cells (source of IF)
Gastric bypass — exclusion of stomach, duodenum, and proximal jejunum alters B12 absorption
Where are medium chain triglycerides absorbed?
Colon
What nutrients are absorbed in distal small intestine?
Bile acids
Vitamin B12
Water
Electrolytes
What type of diarrhea is seen in Cholera?
Secretory diarrhea
[Cholera toxin produced by Vibrio cholerae causes uncontrolled secretion of Cl- into intestinal lumen, resulting in copious secretory diarrhea]
