What are the storage sites for proton/potassium pumps in the parietal cells?
tubulovesicular membranes - fuse to the apical membrane for proton secretion **this is caused by gastrin, histamine, and acetylcholine binding to respective receptors **there are 2 types of second messengers involved in this process (calcium and cAMP), which allows for potentiation
What stimulates the secretion of somatostatin from D cells?
likely acetylcholine actually inhibits somatostatin secretion acid
Which drug blocks the M3 receptors?
Describe the local control mechanisms for the GI system
- the GI system is controlled locally by the enteric nervous system (ENS) - comprised of the submucosal plexus and the myenteric plexus - it is located close to the effector systems (which makes sense because it is local control)
What are the primary characteristics of Absorption?
- nutrients, electrolytes, and water are absorbed - active transport, diffusion, and osmosis
What is the role of colipase?
- lipase absorbs to the surface of fat droplets 2. lipase is displaced by the binding of amphipathic bile acids 3. colipase binds to bile acids and lipase, which brings lipase in proximity to its substrates
What are the regulatory factors of CCK, and how do they regulate?
- Increased by proteins/aa 2. increased by fatty acids 3. increased by neural stimulation 4. increased by peptide releasing factors
What are the layers of neural control of the GI system?
- Local - ENS - Systemic - CNS - Global - CNS
Interstitial Cells of Cajal
- mediate between efferent neurons and smooth muscle cells - responsible for slow waves - “pacemaker cells” - amplify neuronal input - they are central to GI motility regulation - keep pacemaker function by randomly depolarizing at specific intervals - loss of ICC causes motility disorders
What are the relative frequencies of the BERS in the different sections of the GI tract?
Rate small intestine>colon>stomach
What is primarily responsible for gastric motility in the stomach?
smooth muscle - pacemaker region in the antrum
Functions of the myenteric plexus
- muscle control (between the 2 muscle layers of the GI tract) - increases intensity of rhythm of contraction, tone, rhythm rate, and velocity of conduction - ICC - interstitial cells of cajal are located here
What types of motility occur in the mouth and esophagus?
chewing swallowing peristalsis
What types of motility happen in the large intestine?
haustral shuttling mass movements defecation
Which systems exert control over salivary secretions?
parasympathetic is the dominant system of control. it is possible that the sympathetic nervous system affects the sublingual gland (cotton mouth feeling)
What do chief cells secrete?
pepsinogen and gastric lipase
What is the response to the smell/sight/thought/taste of food?
- preganglionic vagus nerves stimulate postganglionic nerves that are part of the enteric system of the stomach - postganglionic nerves stimulate secretion from parietal and chief cells - gastrin secretion by endocrine cells is also stimulated - the gastrin moves through circulation and returns to the stomach where it continues to stimulate secretion from parietal and chief cells (feed forward!)
How are short peptides absorbed in the intestine?
coupled with proton transport using protons that are transported in through sodium/hydrogen exchangers… the H+ gradient created drives the transport of the short peptide sequences *they are then digested by intracellular/cytosolic peptidases and the resulting amino acids are transported out of the basolateral side of the cell through basolateral aa transporters
Describe the 2-stage model of salivary secretions
- The acinar cells secrete the primary secretion, which includes amylase and isotonic ion solution 2. While traveling through the duct, the ductal cells engage in ion exchange, primarily reabsorbing sodium in exchange for potassium and chloride in exchange for bicarbonate
What are the primary characteristics of Secretion?
- water, electrolytes, acid, and enzyme movement - aids in digestion and absorption
Which part of the brain responds to special signals during the cephalic phase of digestion?
medulla oblongata, which causes parasympathetic action potentials to travel via the vagus nerves to the stomach
What are the key requirements for acid generation/release by parietal cells?
Carbonic anhydrase catalyzes the reaction between carbon dioxide and water to form carbonic acid - bicarbonate is exchanged with chloride and moves into circulation and the dissociated proton can be released through primary active transport mechanism
What do D cells secrete?
What are the four processes in the GI system?
- Motility 2. Secretion 3. Digestion 4. Absorption
What are the regulatory factors of Gastrin, and how do they regulate?
- increased by proteins/amino acids 2. decreased by acid 3. increased by neural stimulation and stretch ** the inhibition of SST is most likely a primary driving force for the release of Gastrin
Where and how does the water ABSORPTION in the small intestine occur?
at the villi of epithelial and following sodium being cotransported into the cell along with nutrients
What are the primary characteristics of Digestion?
- enzyme secretion and activation - food is broken down into absorbable molecules
Functions of the submucosal plexus
- regulates GI blood flow - controls epithelial function
What is the function of the gallbladder?
- Absorptive: sodium, chloride, and water - concentrates bile 2. Secretory: H+, Mucin - acidification of bile and protection of epithelial layer 3. Motor: Relaxation, Contraction - storage of bile and delivery of bile
Which ion is involved in the movement of water into the intestinal lumen and how is it transported out?
chloride - through CFTR proteins
What do G cells (enteroendocrine) secrete?
in which parts of the intestine is protein absorbed
throughout the entire small intestine
name the 3 primary pairs of glands responsible for salivary secretions and what quality of fluid they secrete
- Parotid glands - serous (watery) fluid 2. sublingual glands - mucous 3. submaxillary glands (aka submandibular) - mixture of the 2 **90% of salivary secretions
Describe the neural pathways of the GI system
- they are activated by special senses (smell, taste, sight, etc) and by sensory nerve endings - regulated primarily through feedback loops (both positive and negative)
Which contractile parameters do pacemaker potentials in the stomach determine?
- Maximum frequency 2. Propagation velocity 3. Propagation direction **note: the pacemaker region in the mid corpus is the first place where you start to see ICC cells
How does slow wave frequency change as you move from the duodenum to the ileum?
decreases in a step-wise motion
which transporter transports glucose?
SGLT-1 co-transported with sodium (also galactose)
Which hormone is released from the duodenum, travels to the DVC, and ultimately causes relaxation?
CCK - this is a big way that the timing of gastric emptying is controlled
What are the regulatory factors of GIP, and how do they regulate?
- increased by fatty acids 2. increased by glucose
which transporter transports fructose?
What queue from the duodenum also triggers relaxation in the fundus?
distension in the duodenum
What can stimulate the secretion of chief and parietal cells?
- direct stimulation by gastrin 2. acetylcholine from vagal/ENS nerves 3. histamine from ECL cells, which are stimulated by gastrin
Name the H2 blocker examples
zantac, pepcid, axid
Name the additional salivary glands (not primary)
Von ebner’s gland (provides most of the lingual lipase in the mouth) and the glands in the mucous membrane of the lips, palate, and cheeks also secrete mucous **remaining 10% of salivary secretions
Describe primary peristalsis
distension in the esophagus triggers peristalsis locally and through vago-vagal reflex the action of swallowing causes the upper esophageal sphincter to relax and then to have increased pressure (to prevent backflow. the lower esophageal sphincter relaxes and primes receptive relaxation in the stomach. Peristaltic waves in the esophagus immediately following a food bolus are primary
Name the proton pump inhibitors
Prilosec, prevacid, nexium
What types of motility happen in the small intestine?
segmental contractions peristalsis
What are the primary characteristics of Motility?
- neural regulation of smooth muscle - works to propel food from the mouth to the rectum - mixes and grinds food to increase its surface area (to allow for better digestion by digestive enzymes)
What is another name for “slow waves” and what are their characteristics?
BER - basal electric rhythm - controlled by ICC cells, and set the rate of contraction - only produce a contraction when a threshold is reached - contractile stimulus is needed - determine maximal rhythm of phasic contraction - parasympathetic input (ach) increases the force of contractions - sympathetic inputs (epi) stops contractions
What is secreted in the antrum?
- mucus, pepsinogen, gastrin
What do mucous cells secrete?
mucous bicarbonate trefoil peptides
What does peptide YY do?
inhibits meal-stimulated GI functions
What do parietal cells secrete?
HCl intrinsic factor
What are MMCs and how are they controlled?
MMC - migrating motor complex - controlled by an increase in motilin concentration during fasting - concentration of motilin decreases immediately after eating
How are triglycerides treated in the stomach?
Gastric lipase and acid break ONE fatty acid from the triglyceride. The rest travels to the duodenum where they trigger CCK release
What is secreted in the body/fundus?
- HCl, mucus, pepsinogen
Name the 5 true GI hormones
- CCK 2. Gastrin 3. Secretin 4. GIP 5. Motilin
What are the basic steps in swallowing?
- Receptors in the pharynx are stimulated by food/drink and brought to the rear of the mouth (primarily mechanoreceptors) 2. Impulses are sent via afferent parasympathetic to medulla oblongata in the brain stem (swallowing center) 3. Efferent impulses are sent back to the muscles of the pharynx and esophagus to coordinate the swallowing reflex
Describe secondary peristalsis
the primary wave immediately after swallowing may be followed by a secondary wave, but only in the smooth muscle. the secondary wave serves the function of continuing to clear the bolus as well as preventing gastric reflux acid can trigger secondary peristalsis
What are the functions of the fundus
- primary role is reservoir function. - relaxes to accommodate additional food
What are the primary biliary solutes?
secretory: bile acid (micelle-forming), phospholipids, and sIgA excretory: cholesterol is the most important
What are the 3 phases of the MMC cycle?
- Quiescence - basically nothing going on 2. intermittent, non-propulsive contractions - enough said 3. intense, propulsive contractions - these start to look more like the contractions seen during peristalsis after feeding
Describe the musculature of the esophagus and which neural circuits control them
The upper 1/3 of the esophagus is made of striated squamous skeletal muscle, which is under somatic control There is a middle 1/3 section of mixed muscle (autonomic control) The bottom 1/3 is made of columnar smooth muscle cells that are under autonomic control **regulation comes from the swallowing center of the brain
What are the phases of digestion?
- cephalic - Sugar and fat digestion begins, primarily to enhance the taste sense. - Salivary secretions begin - Acid secretion starts - Peristalsis Starts 2. gastric - Protein digestion begins - Acid secretion - Pancreatic and biliary secretions begin - Mixing and churning - Some drug absorption (acidic drugs) 3. early intestinal and late intestinal - Digestion - Pancreatic and biliary secretions - Mixing and peristalsis - Nutrient and drug absorption
What stimulates the secretion of Gastrin from G cells?
- Vagus/ENS release GRP which stimulates gastrin release 2. presence of peptides/aa in stomach
What stimulates GIP release and what are its effects?
Glucose in the duodenum stimulates release from GIP cells; it stimulates the islets of lagerhans in the pancreas to secrete insulin
What do ECL cells secrete?
What happens to salivary amylase while food is digested?
While it is most active in the higher pH of the mouth, amylase continues to have activity throughout digestion
Describe the regulation of pepsinogen release
after the initial release of pepsinogen in the stomach from chief cells (caused by vagal response) - gastrin, histamine, acetylcholine and inhibition of somatostatin S cells in duodenum detect H+, which stimulates them to release secretin, which further stimulates chief cells and inhibits parietal cells - this occurs so that more pepsinogen is released to digest the food - once the food is almost completely digested, it can no longer buffer the acid in the stomach and the pH drops, stimulating the release of somatostatin from the D cells (this inhibits gastrin release and stops the rest of the cycle)
What are the 3 phases of the 3 sub-phases of intestinal digestion?
- luminal - proteins, CHO, and fat - chyme is mixed with enzymes 2. brush border - proteins and CHO - enzymes on the luminal surface of enterocytes 3. cytosolic/intracellular - only proteins - intracellular digestion in enterocytes (only di and tai-peptides)
where does digestion of carbohydrates occur?
in the intestinal lumen and at the brush border - only monosaccharide are absorbed - glucose is completely absorbed along the small intestine
What are the regulatory factors of Secretin, and how do they regulate?
- increased by fatty acids 2. increased by acid
Why is iron the only ion that is absorbed in the duodenum?
it requires an acidic environment to be absorbed
What types of motility happen in the stomach?
filling churning peristalsis emptying
What neurotransmitters trigger relaxation?
NO and VIP (vasoactive intestinal polypeptide)
What are the regulatory factors of Motilin, and how do they regulate?
- reduced by feeding (so decreased by all of the macromolecules 2. increased by neural stimulation
What regulates movement through sections of the GI tract?
Where and how does water SECRETION in the small intestine occur?
in the crypt epithelial cells and following chloride and bicarbonate being secreted
What are the 2 phases of receptive relaxation?
- true receptive relaxation (caused by swallowing) 2. accommodation (mechanoreceptors)
What are the characteristics of the cardia?
- includes the esophagus and the area where the esophagus comes in contact with the lower esophageal sphincter - squamous epithelial cells transition into columnar epithelial cells (now a single layer)
What are the 2 divisions of the autonomic nerves?
1. Sympathetic - cell bodies originate in the thoracolumbar region
2. Parasympathetic - cell bodies originate in the craniosacral region
What are the primary neurotransmitters of the autonomic nervous system?
Ach - acetylcholine
NE - norepinephrine
Name the cholinergic receptors
ion channel/depolarization mechanism
can be both excitatory and inhibitory
*Both receptors respond to acetylcholine, but the specific response is dictated by which receptor is present in target organ/cell type
Name the adrenergic receptors
alpha1, alpha2, beta
*beta2 also exists, but only has affinity for epinephrine
Summarize the characteristics of autonomic nerves
- innervates all organs except skeletal muscle
- synapses are located in ganglions outside cerebrospinal axis
- extensive peripheral plexuses
- postganglionic nerves are not axonated
- some level of spontaneous activity without intact innervation
Summarize the characteristics of somatic nerves
- innervates only skeletal muscle
- synapses within CNS
- deenervation results in paralysis and atrophy
List the functions of the parasympathetic nervous system
- conservation of energy
- vasodilator predominance
- blood pressure reduced
- renal blood flow increased
- urine output increased
- salivation increased
- respiration reduced
- GI motility and secretions increased
List the functions of the sympathetic nervous system
- expenditure of energy
- vasoconstrictor predominance
- blood pressure increased
- renal blood flow decreased
- urine output decreased
- salivation reduced
- respiration increased
- GI motility and secretions reduced
How does the sympathetic nervous system act on the eye?
mydriasis by innervating the iris dilator muscle
How does the sympathetic nervous system act on the eye?
Miosis by innervating the iris sphincter muscle
What are the 5 key steps in neurotransmission?
List the effects of activating muscarinic receptors
increased GI motility
List the effects of activating the beta1 receptor
increased contractile force
increased heart rate
increased renin release
List the effects of activating the beta2 receptor
List the effects of activating the alpha receptors
List the effects of activating adrenergic receptors
vasodilation (beta1) vasoconstriction (alpha1 or 2)
decreased urination (beta2)
decreased GI motility (beta2)
relaxation of the uterus (beta2)
What are the exceptions to dual innervation?
blood vessels (only sympathetic)
bronchiolar smooth muscle (only parasympathetic)
What are the exceptions to the fact that the predominant tone of the autonomic nervous system is parasympathetic?
sweat glands (sympathetic cholinergic)
blood vessels (sympathetic adrenergic)
What are the potential adverse effects of overstimulating muscarinic receptors
How does botox work?
acts by inhibiting the release of ACh from cholinergic nerve terminals
treatment for ailments involvement overactive skeletal muscle
helps form scaffold for other bacterial species in oral biofilm
What are the key roles for gut microbiota?
- Metabolism/fermentation of unused energy substrates
- Training of the immune system
- Production of Vitamins, like vitamin K
- Competitive inhibition of harmful species
What are the protective functions of good gut flora?
- Pathogen displacement
- Nutrient competition
- Receptor competition
- Production of anti-microbial factors
Structural functions of of good gut flora
- Barrier fortification
- Induction of IgA
- Apical tightening of tight junctions
- Immune system development
Metabolic functions of good gut flora
- control of IEC differentiation and proliferation
- metabolize dietary carcinogens
- synthesize vitamins
- ferment non-digestible dietary residue and endogenous epithelial-derived mucus
- ion absorption
- salvage of energy
What are the different types of organisms existing in the bicrobiota?
bacteriophage, archaea, protozoa, ameboa, flagellates, algae, fungi
What is a major role for colonic flora?
major source of short-chain fatty acids, which are primary source of fuel for the epithelium of the colonic epithelial cells
Which species of bacteria alters placental blood vessels?
What are the metabolic effects of enteric bacteria?
- endogenous substrates produced by the body are modified by microbiota
- SCFA are produced and are actively reabsorbed by epithelial cells
Name some of the primary diseases associated with dysbiosis of the microbial communities
Adipose Tissue: Obesity/insulin resistance
Liver: NAFDL/NASH (cause of liver disease)
Pancreas: Type 2 Diabetes
Cardiovascular System: Stroke, atherosclerosis, thrombosis
Brain: autism spectrum disorder, stress response, metabolic disease
Lung: allergic response
What are M cells?
specialized epithelial cells that sample the environment of the lumen and travel through the lamina propria into area with immune cells
What are the beneficial functions of bacterial metabolites in the GI system?
- metabolites are an energy source for colonocytes
- stimulate naive T cells to differentiate into Treg, which prevents autoimmunity
- increase barrier integrity for neutrophil function
What is the name of the voluntary defecation reflex?