Physiology Flashcards
(121 cards)
1
Q
What are the 6 major functions of the digestive system?
A
1 Motility
2. Secretion
3. Digestion
4. Absorption
5. Blood flow (splanchnic circulation stores large amounts of blood)
6. Metabolism (liver)
2
Q
How is the GIT innverated?
A
Autonomic Nervous System:
Extrinsic: Parasympathicus (vagus-upper GI + pelvic nerv-lower GI) + Sympathicus (Th1-L3)
Intrinsic: Enteric nervous sytem (submucosal + Myenteric plexus)
3
Q
What kind of neurons are enteric neurons?
A
- cholinergic
- adrenergic
- peptidergic
4
Q
What is the difference between skeletal muscle + smooth muscle contraction?
A
Skeletal = thin-filament regulated process:
Ca2+ binds to Troponin C –> conformational changes in troponin-tropomyosin complex –> permints binding of actin to myosin head, activation of myosin ATPase + crossbridge cycling
Smooth muscle = Thick-filament regulated process
Ca2+ binds to calmodulin (Ca2+-binding protein) –> activates myosin light-chain kinase –> phosphorylation of myosin light chains –> activation of myosin ATPase –> cross-bridge cycling
5
Q
Discuss the structural differences between skeletal and smooth muscle cells
A
6
Q
What does contraction of the smooth muscle cell rely on?
A
influx of Ca2+ via:
* voltage-gated Ca2+ channels
* ligand-gated Ca2ü channels
* inositol-triphosphate (IP3)-gated Ca2+ channels
7
Q
What are the two types of GI smooth muscle contractions?
A
- Phasic contractions: periodic contractions followed by relaxation (oesophageal body, gastric antrum, small intestine, colon)
- Tonic contractions: constant level of contraction with intermittent periods of relaxation (geatric fundus, gastroesophageal sphinctes, pyloric sphincter, ileocolic sphincter, internal anal sphincter)
8
Q
What are the two types of electrical waves of the smooth muscle cells?
A
Slow waves = oscillating depolarization and repolarization waves that originate in the intestinal cells of Cajal in the Myenteric plexus and spread to adjacent smooth muscle cells via gap junctions = Pacemaker
–> smooth muslce membrane potential fluctuates 20-30x/min –> these are insufficient to exceed threshold potential, but help coordinate depolarizations and contractions of the GIT
Spike potential: When something (e.g. distension through food bolus) stimulated GIT this can trigger release of neutrotransmitters –> depolarization of the membrane that eliciates an actions potential on top of slow wave –> threshold potential is reached –> spike potention –> smooth muscle contraction
9
Q
What influences des small intestinal motility?
A
- Enteric nervous system: Myenteric plexus + submucosal plexus –> operate semi-automatically, with inputs from:
–> parasympathetic NS: vagus nerce –> increases intestinal motility + stimulates GI secretions
–> sympathetic NS: prevertebral ganglia –> inhibition of enteric nervous system –> reduced motility + GI secretions + splanchnic vasoconstriction - Endocrine system:
–> Motilin: released from duodenal mucosa evere 90min during fasting –> stimulates MMC (Migrating Motility Complex)
–> Vasoactive intestinal peptide (VIP) –> inceases sectration of water + electrolytes + stimluates insteintal motility
10
Q
What is the difference in oesophageal anatomy between dogs and cats?
A
Dogs: whole oesophagus is striated muscle
Cats: distale 1/3 is smooth musccle
11
Q
What innervates the striated muscle of the oesophagus?
A
Vagus: somatic branches (glosssopharyngeal, pharyngeal, recurrent laryngeal) arising from the brainstem N. ambiguus
12
Q
What innervates the smooth muscle of the oesophagus?
A
Vagus: autonomic branches (oesophageal) arising from dorsal motor nucleus
13
Q
Who controls the swallowing reflex?
A
Swallowing center in the medulla oblongata
14
Q
What are the 5 anatomic and the 2 physiologic compartments of the stomach?
A
Anatomic: Cardia, Corpus, Fundus, Antrum, Pylorus
Physiologic:
* proximal stomach (cardia, fundus, first 1/3 of corpus) –> slow tonic contractions
* distal stomach (distal w/3 of the corpus + antrum) –> phasic propagating contractions
15
Q
What is responsible for the tonic contractinos of the proximal stomach?
A
Slow waves
16
Q
What is receptive relaxation?
A
Decrease of gastroesophageal and intragastric pressure during swallowing to accomodate emptying of solids and liquids –> large volumes can be accommodated without large increases in intragastric pressure
17
Q
What is responsible for the phasic contractinos of the distal stomach?
A
Pacermarker site in the proximal fundus of the greater curvature generates action potentials and phasic contractions –> propatgate from the site of origin circumferentially and distally to the pylorus –> repetitive cycle of propulsion, trituration and retropulsion –> reduces size of ingestsa
18
Q
What are the functions of the stomach?
A
- Temporary storage of large meals
- Secretion of digestive enzymes + initiation of protein digestion
- Mixing of gastric content
- Secretion of gastric acid
- Secretion of IF
- Endorine (secretion of hormones to contral gastric emptying + regulate gastric and pancreatic secretions)
- protection of the gastric mucosa from caustic effects of H+ and pepsins
- inactivation of ingested bacteria, viruses and parasites
19
Q
What regulates gastric emptying?
A
Rate of empyting is primarily controlled by duodenum:
1. duodenal distenion: reflex inhibition of the enteric nervous system –> reduces gastric empyting
2. Low duodenual pH (acid): –> release of secretin from duodenal mucosa –> pancreatic HCO3- secretion + inhibition of gastrin secretion –> reduced gastric emptying
3. Fatty duodenual content: –> secretion of cholecystokinin by duodenal mucosa –> increases pyloric sphincter tone –> reduced gastric emptying
4. Hyperosmaler chyme within duodenum: –> reflex inhibition of enteric nervous system
+
Chyme:
- Consistentcy of chyme: liquid passed through much faster –> pyloric sphincter constricts when solids come close
- Volume of chyme: increased volume promotes emptying
- Content of chyme: carbohydrates empty more rapidly > proteins > fat
+ Hot or cold temperatures
+ SNS activity
+ drugs (e.g. opioids)
+ diseases (e.g. Diabetic autonomic neuropathy, acute abdomen, ileus)
20
Q
What affects the time needed for gastric emptying?
A
Solid: intially 20-30min without gastric emptying –> allows mixing of food with gastric secretion + pepsin starts breaking down proteins –> after that gastric empyting is linear
Liquid: Exponential decline without lag phase - unless liquid contents are hyperosmolar, acidic or contain fat –> slower + more linear
21
Q
Where is vomiting controlled?
A
Vomiting centre in the medulla oblongata –> in close contact with 3 important structures:
1. repsiratory centre
2. Nucleus tractus solitarius (receives afferent information from cranial nerves)
3. Chemoreceptor trigger zone (on the floor of the 4th ventricle of the medulla) –> lacks BBB –> receives blood flow from the systemic circulation –> senstivie to drugs and toxins
–> coordiinates vomiting via parasympathetic NS, sympatheric NS and motor neurons
22
Q
What triggers vomiting?
A
Stimulatory receptors within CTZ:
* Dopamin 2 (D2)
* Serotonin (5-HT3)
* Acetylcholine (M1)
* Opioid
* Substance P (NK-1)
* a2 receptor
* H1 receptor
* ENKµ
CN VIII (vestibular system - motion):
* Muscarinic receptors
* H1 receptors
* NMDA
CN IX (afferent info from pharynx - gag reflex)
Enteric nervous system + CN X (activation of serotonin 5-HT3 receptor in response to distension, infection, chemotherapy, radiotherapy)
Higher centers (e.g. limbic system) –> in response to anxiety or emotional stress: ENKµ, W2
23
Q
What are the 3 phases of vomiting?
A
- Pre-ejection phase:
* Nausea
* Decreased gastric motility
* Reverse peristalsis of the SI (pushes proximal small bowel contents back into the stomach)
* Secretion of HCO3- rich saliva (parasympathetic nervous system)
* Sweating and tachycardia (sympathetic nervous system) - Retching phase:
* Deep inspiration followed by closure of the glottis (protects trachea from aspiration)
* Rhythmic contractions of the intercostal muscles, diaphragm and abdominal muscles against a closed glottis; the alkaline contents of the proximal small intestine are vigorously mixed with stomach contents, thereby increasing pH of gastric fluid
* The increased intrathoracic pressure compresses the oesophagus, preventing reflux of stomach contents - Ejection phase:
* Continuation of glottic closure
* Contraction of pylorus, which pushes gastric contents into the body and fundus of the stomach
* Relaxation of LOS and oesophagus
* Sudden, dramatic increase in intra-abdominal pressure, resulting from contraction of abdominal muscles and descent of the diaphragm (this pushes gastric contents completely * Soft palate occludes the nasopharynx, and reverse peristalsis rapidly expels oesophageal content out of the mouth
24
Q
What are the accessory organs involved in digestion?
A
- Teeth + tongue
- Salivary glands
- Liver + gallbladder
- Pancreas
25
What increases the absorptive surface of the SI?
1. Valvulae connivents (mucosal folds that porject into the luman of the SI)
2. Villi (finger-like projections of the intestinal wall)
3. Microvilli (brushborder)
26
What are the 2 types of epithelial cells in the villi and what are their functions?
1. Crypt epithelial cells: secretory
2. Villus epithelial cells: adsorptive
27
What are the 3 functions of intestinal contractions?
* mixing ingesta with digestive enzymes + other secretions
* facilitate contact of intestinal contents with mucosa
* caudal propulsion of contents
28
What are the 4 motility patterns of intestinal contractions?
1. segmentation
= circular smooth muscle contraction (contents are placed proximally + caudally)
2. peristalsis
food causes distension of SI --> contraction of cranial segment (Ach, Substance P) + relaxation of caudal segment (VIP, NO) --> short-segment peristalsis
3. intestinointestinal inhibition
gross distension of a SI area --> inhibition of the contractile activity of the rest of the SI (extrinsic nervous system - PS/S)
4. migrating-motility-complex (MMC)
moves indigestible material, mucus and secretions from stomach to colon (Motilin)
29
What are the 2 functions of the colon?
1. extraction of water + electrolytes (ascending + transverse)
2. storage of faeces and control of defacation (descending)
30
What are the 2 types of GI movements in the colon?
1. Segementation
--> proximal colon: mixing + exposing contents to mucosa
--> distal colon: resistance + retard the flow of contents from prox regions into rectum
2. Mass movement
--> inhibition of segmental activity + contraction sweeps contents caudally
31
How does defacation work?
faecal accumulation in anorectal canal stimulates smooth muscle contraction of the rectal wall + reflex inhibition of internal anal sphincter (rectosphincteric reflex) + transient relaxation of internal sphincter -->regains tone if defacation not possible
BUT external anal sphincter is striated muscle and under voluntary control (tonically contracted)
32
What is the gastrocolic reflex?
distension of stomach increases motility of colon + increases frequency of mass movements (increased motility via efferent limb: Cholecystokinen, gastrin)
33
What stimulates gallbladder contraction and relaxation of the spihincter of Oddi?
* Cholecytokinin
* Acetylcholin
* Secretin
34
Where are the following hormones produced, what is their target and what is their ultimate function?
35
What is saliva composed of?
98% water
2%: electrolytes (hypotonic - lower Na+/Cl- and higher K+), HCO3-, proteins + enzymes (mucin, haptocorrin, lingual lipase) + bactericidal substances (IgA, lactoferrin, lysozyme, thocyanate)
36
What are the functions of saliva?
* lubrication of food
* digestion (lingual lipase : triglycerides, haptocorrin --> binds VitB12, protecting it from low pH)
* buffering/neutroalization of acid via HCO3- (when reflux or vomiting occurs!)
* antibacterial effects (minor)
* Secretion of IgA
* Evaporative cooling
* Release of R factor binding proteins for VitB12 transport
37
How is saliva produced? What affects its composition? What effect does aldosterone have? How is are the salivary glands innvervated? Which gland produces which kind of saliva?
Acinar cells: produce primary secretion by active transport of electrolytes + water: isotonic
Duct cells: modify secretion to secondary secretions: NA+ and Cl- are reabsorved, K+ and HCO3- are secreted --> reabsorption faster than secretion --> becomes more hypotonic as it moves down the duct
Higher rate: rich in Na+ and HCO3-
Lower rate: rich in K+ and CL-
Aldosterone: increases Na+ reabsorptinon and K+ secretion
Parotid, mandibularis, sublingualis:
* parasympathetic: stimulation --> serous, electrolye-rich saliva
* sympathicus: vasoconstriction --> short increase in production (mucus + amylase), then decrease
Nerval supply:
parotid: glossopharyngeal nerve (CN XI)
submandibular, sublingual: facial nerve (CN VII)
Parotid + submandibular: serous saliva
sublingual: mucous saliva
38
What is the gastric pit?
= structural unit of the gastric mucosa
--> branched invaginations bearing multiple cell types with multiple secretory functions:
1. parietal (oxyntic) cells: H+ ,IF
2. chief (peptic) cells: pepsinogen
3. surface epithelial cells: HCO3-, prostanoids
4. neck and surface mucous cells: mucus (sulfated glycoproteins)
5. endocrine cells: gastrin, ghrelin
7. enterochromaffin-like cells: histamine
39
Where and how is gastric acid secreted?
Parietal (oxyntic) cells - stimulated by:
1. Histamine (from enterochromaffin-like cells via gastrin or parasympathetic stimulation) --> stimulates H2 receptors on parietal cell --> increased cAMP production within the cell
2. Parasympathetic stimulation (vagus) --> Ach on muscarinic M3 receptors
3. Gastrin:
--> direct: stimulation of parietal cells
--> indirect: stimulation of histamine release from enterochromaffin-like cells
Mechanism for HCL production:
1. CO2 diffuses into cell --> CA --> H2CO3 --> H+ and HCO3- --> H+ enters secretory canaliculi via H+/K+ ATPase (exchange = "proton pump") + K+ diffuses back into secretory canaliculi via its electrochemical gradient
2. HCO3- leaves cell again on basolateral side in exchange for Cl- --> Cl- diffuses down its concentration gradient through Cl- channel into the secretory canaliculi
--> rise in HCO3- in blood causes alkalizing effect = "alkaline tide"
40
What are the 3 stimulatory and the 1 inhibitory receptor of parietal (oxyntic) cells?
stimluatory; Acetylcholin, histamine, Gastrin
inhibitory: somatostatin
41
What are the 3 phases of HCl secretion?
Stimulation of HCl production:
1. cephalic phase: 30% --> anticipation --> vagus nerve stimulation
2. Gastric phase: 60% --> gastric distension -->gastrin release from G cells --> stimluates pepsinogen release from chief cells + histamin release from ECL cells --> stimulation of HCl secretion via parietal (oxyntic) cell
Inhibition of HCl production:
3. Intesitnal phase --> acidic chyme enters duodenum --> secretion relase from duodenual mucosa --> stimulates HCO3- secretion from pancreatic duct cells + inhibits gastrin release from G cells --> reduced HCl production
42
What triggers pepsiongen release, what cell is involved and what is its function?
Gastrin (from G cells) + parasympathetic stimulation (vagus) --> trigger pepsinogen release from chief cells --> acidic pH of stomach converts pepsinogen to pepsin --> protein breakdown in stomach
43
What triggers gastrin release, what cell is involved and what is its function? What inhibits gastrin release?
1. Parasympatehetic acitvity (vagus)
2. distension of stomach
3. presence of partially digested proteins in stomach
--> triggers release of gastrin from G cells:
1. stimulation of parietal cells --> HCl
2. stimulation of ECL cells --> histamine --> stimulation of pariental cells --> HCl
3. stimulation of cheif cells --> pepsinogen --> pepsin --> protein breakdown
4. stimulation of gastric motility
Inhibition of gastrin release:
1. high acid concentration --> release of somatostatin from gastric D-cells --> inhibition of gastrin release from G cells
44
What triggers IF release, what cell is involved and what is its function?
Same stimuli as HCl release - parietal cell:
1. Histamine (from enterochromaffin-like cells via gastrin or parasympathetic stimulation) --> stimulates H2 receptors on parietal cell --> increased cAMP production within the cell
2. Parasympathetic stimulation (vagus) --> Ach on muscarinic M3 receptors
3. Gastrin:
--> direct: stimulation of parietal cells
--> indirect: stimulation of histamine release from ELC
--> in Stomach VitB12 is initially bound to haptocorrin, because IF cannot bind VitB12 in acidic environment (due to low affinity) --> higher pH in duodenum: VitB12 is released from haptocorrin -->
1. Haptocorrin is digested by trypsin
2. IF has now higher affinity to bind VitB12 --> GI transport to iluem --> absoprtion of IF-VitB12 complex
45
What is the function of gastric mucus production?
1. Lubrication (protection against frictional damage from peristalsis)
2. protection of gastric mucosa from acidic pH in stomach
46
What are the submucosal Brunner's glands?
only in submucosa of duodenum --> produce mucus-rich, alkaline secretion:
* protect duodenum from acidic content
* provide alkaline environment for optimal activation of lipase + colipase
* lubricate chyme
* trap, inactivate and regulate intestinal bacteria
47
What regulates fluid and electrolyte secertion (Cl-) by the crypt cells?
1. Stimulation of fliud secretion (+ Cl-) via Parasympathicus (Ach, VIP)
--> Ach: Ca2+ second messanger signaling
--> VIP: stimulation of adenylate cyclase --> cAMP --> protein kinase A activation
2. Inhibition of fluid secretion via Sympathicus (NE) + Opioid neurons of enteric nervous system
48
What causes hypersecretion of the crypt cells in inflammation?
Bacerial infection --> stimulation of epithelial cells to express proinflammatory cytokines like:
* TNF-a
* IL-1b
* IL-8
* prostanoids
* leukotriens
49
What causes hypergastrinemia with resection of the ileocolic juction?
reduced GLP, neurotensin + peptide YY --> GLP usually inhibits gastrin secretion --> removal of inhibitory influence causes hypergastrinemia
50
What are the main cell types of the pancreas and their function?
98% exokrine tissue:
--> acniar cells: trypsinogen, chymotrypsinogen, pancreatic alpha amylase, pancreatic lipase, IF (esp. cat!), antibacterial proteins
--> ductal cells: HCO3-, water
2% endocrine: islet of Langerhans:
--> alpha cells: glucagon
--> beta cells: insulin
--> D cells: somatostatin
--> PP cells: pancreatic polypeptide)
51
What is the fate and function of trypsinogen, secreted by pancreatic acinar cells?
Trypsinogen enters duodenum -> enterokinase cleaves trypsinogen in trypsin ->
1. cleaves chymotrypsinogen + trypsinogen --> more trypsin (aotcatalysis)
2. activates phospholipase A2 + elastase (other pancreatic proenzymes)
52
What is autocatalysis?
Trypsinogen enters duodenum -> enterokinase cleaves trypsinogen in trypsin -> cleaves chymotrypsinogen + trypsinogen --> more trypsin = aotcatalysis
53
What is the function of pancreatic alpha amylase?
catalysis the hydrolysis of large polysaccharides to smaleller carboanhydrate polymers
54
What is the function of pancreatic lipase?
catalyses the hydrolysis of triglycerides to free fatty acid and 2-monoglycerides
55
What is the function of HCO3- produced by the pancreatic duct cells? How is HCO3- produced?
* neutralizes gastric acid etnering the duodenum --> increases pH so that pancreatic enzymes can work
similar to H+ production in parietal cells (stomach):
CO2 diffuses into cell --> CA --> H2CO3 --> H+ and HCO3- --> HCO3- diffuses down its concentration gradient into the pancreatic duct in exchange for Cl- --> water follows HCO3-
-->Cl- returns to pancreatic duct via Cl- channeld (CFTR)
--> H+ is expelled across the basolateral membrane into the capillary by exchange to Na+ --> this exchange is driven by the NA/K ATPase
56
What stimulates secretion of pancreatic fluid?
1. Vagus nerve (cephalic phase of digestion)
2. Gastrin (secreted by G cells in response to gastric distension) --> preparation fo arrival of carbohydrates, proteins + fat = feed-forward control system
3. Cholecystokinin (secreted by duodenal mucosa cells in response to fat- or protein-rich chyme) -->negative-feedback mechanism
4. Secretin (secreted by dodenual mucosa cells in response to presence of acidic chyme) --> stimulatino of pancreatid duct cells to secrete HCO3- + water
57
How do pancreaetic acinar cells protect themselves from intraacinar activation of zymogens and acinar cell necrosis?
1. Synthesis of digestives enzymes in inactive precursor form (zymogens) in ER
2. Selective glycosylation + phosphorylation of zymogens in Golgi complex --> lysosomal hydrolases are packed in lysosomes and therefore seperated from zymogens
3. Zymogens are packaged into maturing zymogen granules --> sequestration from contact with other subcellular fractions
4. Pancreatic secretory trypsin inhibitor (PSTI) is incorporated into zymogen granules --> inactivates trypsin in case of intraacinar activation of trypsinogen
5. Release of zymogen granules + their contents via exocytosis + membrane fusion
6. Activation of zymogens only after entering the duodenum at brush-border membrane via enterokinase
58
What is the benefit of bile?
1. source of bile acids for fat digestion + absorption
2. excretion of metabolites + xenobiotics
3. addition HCO3- for buffering of H+ in the duodenum
59
What are the contens of bile?
1. bile acids (50-66%)
2. water, electrolytes, cholesterol, protein, phospholipids, hormones, bilirubin
60
Where are the bile components synthesized, stored and secreted from?
Hepatocytes --> into the biliary ductal system
61
What stimualtes bile flow?
1. Secretin --> bile-salt independent flow
2. bile salts -->bile-salt dependent flow
62
How are bile acids synthesized?
5 to 8 carbon side changes with a temrinal carboxylic acid are attatched to cholesterol + hydroxyl groups are position at C3, C7 and C12 carbon atoms
63
What are the 2 major primary bile salts and what is their fate in the intestine?
1. cholic acid --> dehydroxylation by intestinal bacteria --> lithocholic acid
2. chenodeoxycholic acid --> dehydroxylation by intestinal bacteria --> deoxycholic acid
64
What are bile salts conjugated with and what is the benefit of this? How does this differ between dogs and cats?
conjugated with taurin and/or glycine (cat taurin only) --> lowers pKA --> bile acids become ionized anions (= bile salts) --> less likely to be absorbed from the SI --> emulsification, digestion and absorption of lipids
65
What are the main functions of bile salts? Where are bile salts absorbed?
1. Emulsification: detergent effect on fat particles --> break them up in smaller sizes --> facilitates intraluminal hydrolytic digestion
2. Formation of mixes micells --> transfer digested liipds across mucosa
--> following this, bile salts are transported to the ileum --> absorbed by ileal enterocytes --> transport into portal vein via Na+-bile salt cotransporter --> enterohepatic circulation
66
Explain the meabolism of bilirubin
67
What is the net effect of colonic electrolyte handling?
1. Absorption of water, Na+ and Cl-
2. Secretion of K+ and HCO3-
--> HCO3- neutralized acids produced by colonic bacteria (Cl-/HCO3- exchange)
68
What is aldosterone's effect on colonic electrolyte handling?
Stimulates syntehsis of Na+ channels --> Na+ retention and K+ secretion
69
What does mucin secretion in the colon depend on?
1. cystic fibrosis transmembrane regulator
2. Cl- secretion
3. granule exocytosis
70
What is the main biochemical mechanism of digestion and where does it take place within the GIT?
Hydrolysis
--> lumen (stomach: pepsin, lipase), duodenum (pancreatic enzymes: amylase, protease, lipase)
--> brush-border membrane of intestinal villi (reduction in size of dextrins and disaccharides to monosacchardies + small- and intermediate-sized peptides to AA)
71
Explain the digestion and absorption of carbohydrates
Digestion:
- lumen: gastric acid hydrolysis + pancreatic amylase hydrolysis --> dextrins, maltotriose, maltose
- brush-border enzymes: maltase, iso-maltase, lactase- sucrase --> hydrolyze dietary sugars to monosaccharides
Absorption:
- glucose + galactose: secondary active transport via Na+ co-transport (SGLT1) due to low intracellular Na+ conc generated via NA/K-ATPase
- fructose: faciliated diffusion (GLUT-5)
- pentose: simple diffusion
--> leave enterocytes on basolatreal membrane via faciliated diffusion (GLUT-2) with water (osmotically active)
72
Explain the digestion and absorption of protein
Digestion:
- lumen: gastric pepsin + pancreatic proteasis (trypsin, chymotripsin, elastase, carboxypeptidase A, carboxypeptidase B)
- brush-border enzymes: peptidases --> cleave di-peptides and tri-peptides to AA
Absorption:
- AA:similar to glucose via Na+-linked co-transport (different transporters for neutral, acidic and basic AA)
- Di- and tri-peptides: H+-linked co-transport (Pept-1) --> broken down within enterocyte to AA; H+ recirculates back into lumen via Na/H+ exchanger
--> leave enterocytes on basolateral membrane via faciliated diffusion with water (osmotically active)
73
Explain the digestion and absorption of lipids
main dietary lipid = triglyceride (+ small amounts of phospholipids, cholesterol, fat-soluble vitamins)
1. Emulsification in the duodenum – lipids are insoluble in water --> triglyceride aggregate in large droplets when exposed to aqueous environment --> bile acids coat the lipid droplets --> divide them into smaller droplets --> increases surface area --> important for pancreatic lipase -->enzymatic breakdown of triglyceride --> 2 free fatty acids + 2 monoglycerides
--> free fatty acids + monoglycerides combine with bile salts --> micelle formation --> micelle makes contact with enterocytes --> FFA + monoglycerides enter enterocyte via simple diffusion --> travel back to ER --> recombined to form triglyceride --> Golgi complex --> packed with cholesterol, phospholipid + apolipoprotein to chylomicrons --> lympahtic system --> thoracic duct
bile salts remain in the SI --> absorbed in the terminal ileum --> portal vein --> liver
74
How is Na+ absorbed within the intestine?
Jejunum: Major site for Na+ absorption (NaHCO3) via
1. Na+ monosacchardie cotransported (SGLT-1)
2. Na+- AA cotransported
3. Na+/H+ exchange (CA source of H+ for this)
Ileum: Cl-/HCO3- exchange --> NaCl absorption (smaller amounts)
75
How is Ca2+ absorbed within the intestine?
Vitamin D (1,25 dihydroxycholecalciferol) induced synthesis of vitamin-D-dependent C2+ binding protein (= calbindin D-28K) --> promotes Ca2+ absorption
76
How is iron absorbed within the intestine?
absorption as free iron or heme iron across apical membrane of enterocytes -->binds to apoferritin within enterocytes --> tranport across basolateral membrane --> portal circulation --> binding of iron to transferrin --> storage in liver and bone marrow
77
What are the water-soluble vitamins and how are they absorbed?
B1, B2, B12, VitC, folic acid, pantothenate
--> Na+ dependent cotransporter
Exception: Vitamin B12 --> depends on intraluminal binding to R proteins + IF --> absorption at ileal brush-border
78
What are the fat-soluble vitamins and how are they absorbed?
Vatmin K, A, D, E
Emulsification + Micelle formation (like lipids) by bile salts in SI --> absorption into enterocytes --> incorporation into chylomikrones at Golgi complex -> lymphatic circulation
79
Where are most of the short-chain fatty acids absorbed?
Colon:
- un-ionized form: diffusion
- ionized: binding with H+ first --> diffusion (H+ is generated insite the enterocyte via CA)
80
What are the 7 functions of gastrin?
1. stimulation of parietal cells to secrete HCl
2. stimulation of ECL cells to secrete Histamine --> parietal cells --> HCl
3. stimulation of gastric (antral) motility
4. stimulation of chief cells --> pepsinogen
5. stimulation of gastric mucosal blood flow
6. stinulation of pancreatic enzyme secretion
7. stimulation of gastric, duodenal and pancreatic growth
81
Where is cholecytokinin secreted and what are its 5 main functions?
Endocrine I cells in duodenum + jejunum --> in respones to intraduodenual fatty acids, AA and H+ ions
1. contraction of gallbladder
2- stimulation of pancreatic enzyme release
3. augmantation of pancreatic fluid secretion (in presence of secretin)
4. relaxation of the sphincter of Oddi
5. inhibition of gastric emptying
6. stimulation of pancreatic growth
82
Where is secretin secreted and what is its main function?
endorcine S cells of the SI --> in response to acidification of the duodenum and jejunum by gastric H+
--> stimulation of pancreatic duct cells to secrete HCO3- rich pancreatic fluid
83
Where is enteroglucagon secreted and what is its main function?
Endorine L cells in the terminal ileum + colon --> in response to intraluminal glucose + lipids
--> inhibition of HCl secretion
84
Where is gastric inhibitory polypeptide (GIP) secreted and what are its main functions?
Endorine cells of SI --> in response to intraduodenal glucose, FA and AA
1. stimulation of pancreatic insulin release
2. inhibition of HCl secretion
3. stimulation of intestinal fluid secretion
85
Where is somatostatin secreted and what are its 7 main functions?
Endocrine D cells throughout GIT --> in response to protein, lipid and bile
= MAIN inhibitor!
1. Inhibition of HCl secretion
2. inhibition of pepsin secretion
3. inhibition of pancreatic enzyme and fluid secretion
4. inhibition of gallbladder contraction
5. inhibition of intestinal AA and glucose absorption
6. inhibition of intestinal motility (as an enteric neuropeptide)
7. inhibition of gastrin secretion (paracrine effect)
86
Where is motilin secreted and what are its 2 main functions?
endocrine cells of the proximal SI --> in response to H+ and lipid content during the fed state
--> but most important function is during fasting state:
1. initiates phase III of the MMC
2. coordinates gastric, pancreatic, and biliary secretions with phase III of MMC
87
Where is neutrotensin secreted and what are its 3 main functions?
endocrine SI cells --> in response to intraluminal lipid
1. inhibition of gastric empyting
2. stimulation of pancreatic and biliary secretion
3. inhbition of acid secretion after fat ingestion
88
Where is pancreatic polypeptide (PP) secreted and what is its main functions?
F cells (pancreatic islet cells) --> in response to protein meals + by cholinergic reflexes
--> inhibition of pancreatic enzyme and fluid secretion
89
Where is 5-Hydroxytryptamine secreted and what are its 2 main functions?
endocrine cells (e.g. ECL) + enteric neurons
1. stimulation of GI smooth muscle contraction
2. intestinal electrolyte secertion
90
Name 12 gastric peptides?
1. Gastrin
2. Cholecystokinin
3. Secretin
4. Enteroglucagon
5. Gastric inhibitory polypeptide
6. Somatostatin
7. Motilin
8. Neurotensin
9. Pancreatic polypeptide
10. Peptide YY
11. 5-Hydroxytryptamine
12. Ghrelin
91
Name 7 enteric neuropeptides
1. Substance P
2. VIP
3. Peptide Histidine-Isoleucine
4. Opioids
5. Bombesins
6. Pacreatic polypeptides
7. 5-Hydroxytryptamine
92
What triggers Substance P release and what are its 3 main effects?
in response to luminal distension or depolarization
1. contraction of GI smooth muscle
2. pain input to CNS
3. stimulates pancreatic enzyme secretion
93
What triggers VIP and Peptide Histidine-Isoleucine release and what are its 3 main effects?
vagal stimulation
1. stimulation of pancreatic fluid and HCO3- secretion
2. stimulation of salivary and intestinal fluid secretion
3. increases intestinal blood flow
4. relaxation of GI smooth muscle
94
What are the main Opioid peptides, what are the binding sites and what are the main effects of opioid binidng?
Methionine-enkephalin, leucine-enkephalin and dynorphin
µ, D and K receptors on neurons/smooth muscle cells/epithelial cells
1. inhibition Ach release from myenteric plexus --> inhibition of contratction of longitudinal smooth muscle
2. stimulation of circular smooth muscle contraction
3. inhibition of submucosal plexus neurons --> inhibition of intestinal watera and electrolyte secretion
95
What triggers Bombesin (GRP) release and what are its 2 main effects?
GRP: vagal stimulation
1. stimulates gastrin release
2. stimulates pancreatic acniar cell enzyme secretion
96
What is the main function of NYP (pancreatic polypeptide)?
decrease Ach release from myenteric plexus --> inhibition of intestinal smooth muscle contraction
97
What are the main functions of N5-Hydroxytryptamine?
regulation of MMC and intestinal peristaltic reflex
98
Where is histamine released from in the dogs GIT?
Produced in ELC but released from mast cells
99
What are the effects of prostaglandins as paracrine substances in the GIT?
1. bind to inhibitory prostanoid receptors on parietal cells --> Gi proteins --> inhibition of AC --> inhibition of H+ secretion (HCl)
2. stimulation of mucosal HCO3- and glycoprotein (mucus) secretion
3. stimulation of epithelial cell renewal
4. stimulation of mucosal blood flow
100
How is the oesophagus innervated?
Striated muscle: efferent visceral neurong from bilateral nucleus ambiguus in MO
cervical region: paired pararecurrent laryngeal nerve
cranial thoracic: left pararecurrent laryngeal nerve
caudal thoracic + abdominal: vagus
101
What are the 4 phases of swallong? How does swallowing work?
1. Oral preparatory (voluntary)
2. Oral (voluntary)
3. Pharyngeal
4. Oesophageal
1. Oral phase
- Food bolus is pushed against the hard palate by the tongue
- Sensory information from the hard palate is fed back to the medulla via the glossopharyngeal nerve, which triggers the initiation of involuntary phases
2. Pharyngeal phase – MO coordinates
- Closure of nasopharynx by soft palate
- Protection of the laryngeal inlet (lateral cricoarytenoid, oblique and transverse arytenoid muscles) followed by abduction of the aryepiglottic folds (all these laryngeal muscles are supplied by the recurrent laryngeal nerve)
- Elevation of the hyoid (by the digastric and stylohyoid muscles), which moves the larynx superiorly and anteriorly; in addition, the epiglottis moves downwards to direct the food bolus towards the posterior pharynx and away from the larynx
- Food bolus is propelled towards the oesophagus by successive contractions of the superior and middle pharyngeal constrictor muscles; the inferior pharyngeal constrictor muscle (cricopharyngeus), which is normally closed, relaxes to allow the food bolus to pass (also known as upper oesophageal sphincter).
- During the pharyngeal phase, the larynx is involuntarily closed by the true and false vocal cords and covered by the epiglottis, only reopening once the food bolus has passed (it is therefore impossible to breathe during the pharyngeal phase and the medulla coordinated 1-2s period of apnoea).
3. Oesophageal phase – MO
- Once the food has entered the oesophagus, the upper oesophageal sphincter closes and the lower oesophageal sphincter (LOS) partially relaxes
- The food bolus is propelled along the oesophagus by peristalsis.
2 types of peristaltic waves propagated by the enteric nervous system:
1. Primary peristaltic waves: initiated by the medullary swallowing centre during swallowing, and continues from beginning of the oesophagus to LOS, regardless of the location of food bolus
2. Secondary peristaltic waves: initiated by the food bolus stretching the oesophagus wall
- By the time peristaltic waves reach the LOS, it has fully relaxed to allow the food bolus to pass
- Smooth muscles of the LOS then contract to prevent gastric contents refluxing into the oesophagus
- The speed at which the food bolus moves along the oesophagus is much slowed (3 cm/s) than along the pharynx (30 cm/s)
102
Where are the motor neurons for the oesophageal stage of swallowing loacated?
left and right nucleus ambiguus in MO --> vagus nerve
--> direct innveration of striated muscle or
--> ganglia near the oesophagus --> postganglionic excitatory cells -> smooth muscle
103
What controls the timing of swallowing?
Central pattern generator (group of interneurons in reticular formation and around nucleus ambiguus) --> get sensory input
104
What is the % absorption of fluid volume present within the differnet GI locations?
Jejunum: 50%
Ileum: 75%
Colon: 90% of fluid present
105
What are the 3 mechanisms for water absorption?
1. passive absorption
2. active absorption
3. Solvent drag
106
What immobilizes the proximal duodenum?
hepatoduodenal ligament
107
What immobilizes the distal duodenum?
duodenocolic ligament
108
Where in the GI can Peyer patches be found? What is this?
Duodenum --> mucosal immune system
109
What immobilizes the ileum?
ileocolic ligament
110
What is being absorbed in the ileum?
* bile saltes
* VitB12
111
What is the blood supply of the SI?
Arterial:
* celiac artery
* cranial mesenteric artery
Venous:
* hepatic portal vein
112
What is the main source of ATP production in the enterocyte? How does this differ from other cells?
Main source: oxidative phosphorylation in mitochondria (electron transport chain)
Other major source: glutamine (surge in enterocyte glutamine metabolism during digestion is probably partly responsible for postprandial rise in blood ammonia!)
--> CAVE: glycolysis and gluconeogenesis are suppressed because their primary role is to absorb glucose from the lumen, not to produce or store it.
113
What prevents diffusion of lipids back into the lumen of the GI?
reesterification of FFA within the enterocytes
114
What is facilitated acrrier-mediated transport?
carriage of substrates by a tranport protein across the "brush border" (microvillar membrane) down a concentration gradient without energy expenditure
115
What is active carrier-mediated transport?
against a concentration gradient with consumption of ATP
--> often linked to Na+ down its electrochemical gradient into the cell (this is maintained via the NA/K ATPase)
116
How much volume of blood must be lost within the faeces before it become grossly visible?
1ml/kg/d
117
How much of the fluid in the intestines is usually absorbed?
98%
118
How many pancreatic ducts exist in the dog and the cat? What part of the pancrease do they drain?
Dogs: accessory (right lobe) and dorsal (left lobe) pancreatic duct
cats: dorsal pancreatic duct (20% of cats have ≥ 1)
119
What is the blood supply of the pancreas?
Arterial:
1. Celiac artery via the cranial + caudal pancreaticoduodenal arteries
2. Splenic artery pancreatic brunch --> left side of pancreas
--> exokrine pancreas have no direct arerial blood supply (perfused by venous blood arising from islet vasa efferentia = islet-acinar portal blood system)
Venous:
1. caudal pancreaticoduodenal vein: right lobe
2. splenic vein: left lobe
120
what nerves supply the pancreas?
Parasympathetic postganglionic fibers: vagus --> stimulate pancreatic exocrine secretion
Sympathic postganglionic fibers: celiac + cranial mesenteric plexus --> inhibit pancreatic exocrine secretion
121
What are the 4 main functions of the pancreas?
1. initiate protein, carbohydrate and lipid digestion through secretion of digestive enzymes
2. neutralize the chyme in the duodenum (HCO3-, Cl-, water)
3. Facilitate VitB12 absorption in the distal ileus vis secretion of IF
4. regulate SI bacterial flora thorugh secretion of antibacterial proteins
