GI/Exocrine Pancreas Flashcards
How are protons pumped out of parietal cells?
Carbonic anhydrase converts H2O & CO2 to HCO3 & H. H secreted through apical H/K ATPase pump. HCO3 exchanges with Cl- in the basolateral membrane
Name the three stimulants for gastric acid production and the associated receptor
- Histamine - H2 receptor 2. Acetylcholine - M3 receptor 3. Gastrin - CCK2 receptor
Where are stress related mucosal disease (SRMD) lesions found?
Stomach with oxyntic glands: fundus & body Contrast: peptic ulcer @ antrum and pylorus
What pH is required for platelet aggregation and fibrin clot formation?
>6
What is the function of the extracellular mucus barrier?
- maintain surface pH 7 2. prevent pepsin infiltration & proteolytic degradation 3. Hydrophobic properties of surfactant repel water soluble agents
What are the most common causes of hemorrhage in dogs with acute abdomen?
Splenic rupture (secondary to neoplasia) Hemorrhage from GI ulceration
What is the most common range for glucose in a dog with sepsis?
40-60 mg/dL although it can be lower
Where is the most common place to detect free gas in the abdomen on radiographs?
Between the stomach or liver and the diaphragm on a lateral projection
Large volumes of free gas in the abdomen are associated with which conditions?
Pneumocystography with a ruptured bladder Vaginal rupture Recent surgery Ruptured GDV Pneumoperitoneography Extension of pneumomediastinum
Small volumes of free gas in the abdomen are associated with which conditions?
Rupture of the GI tract Infection with a gas-forming organism
What is the normal diameter of the small intestine in the dog? and in the cat?
Dog: 2-3x the width of a rib or less than the width of an intercostal space Cat: Should not exceed twice the height of the central portion of the L4 vertebral body, or 12 mm
What difference between blood glucose levels between the periphery and abdominal effusion would you expect in a septic abdomen?
BG of periphery should be > 20 mg/dL higher than the abdominal effusion. This has a 100% specificity in dogs and cats, and is 100% sensitive in dogs, 86% sensitive in cats
What difference between lactate levels between the periphery and abdominal effusion would you expect in a septic abdomen?
Peritoneal fluid lactate should be > 2.0 mmol/L higher than blood lactate 100% specificity and sensitivity in dogs, not reported in cats
What ratio between potassium levels in abdominal fluid vs blood would you expect in a uroabdomen?
Dog 1.4 : 1 Cat 1.9 : 1 100% sensitive in the dog, considered diagnostic for uroabdomen, not reported in the cat
What ratio between creatinine levels in abdominal fluid vs blood would you expect in a uroabdomen?
Dog 2 : 1 Cat 2 : 1 86% sensitive, 100% specific in the dog Not reported in the cat
What ratio between bilirubin levels in abdominal fluid vs blood would you expect in a bile peritonitis?
> 2 : 1 100% sensitive in dogs
What is the sensitivity and specificity of cPLI?
Sensitivity: 82% with severe pancreatitis, 63.6% with less severe pancreatitis Specificity: 96.8%
What is the sensitivity and specificity of fPLI?
Sensitivity: 67% in all cats with pancreatitis, 100% in cats with moderate to severe pancreatitis Specificity: 100%
What is the sensitivity and specificity of SNAP cPLI?
Sensitivity: 92-94% Specificity: 71-78%
What is the sensitivity and specificity of SNAP fPLI?
Sensitivity: 79% Specificity: 80%
What is the ratio of maximal small intestinal diameter to the narrowest width of L5 on the lateral radiograph in dogs?
Ratio > 1.6
What is the ratio of maximal small intestinal diameter to the height of the cranial endplate of L2 in the cat?
Ratio > 2.0
On abdominal ultrasound in dogs, the jejunum should have a luminal diameter of less than what value?
Less than 1.5 cm If greater than 1.5cm with normal wall layering, intestinal obstruction should be investigated
List some breeds predisposed to congenital megaesophagus?
wire haired fox terriers, mini schnauzers, g shepherds, great danes, shar peis, irish setters, labs, newfies
Most adult-onset cases of acquired megaesophagus are?
idiopathic
Name 4 causes of a small intestinal transit disorder?
Enteritis Post-surgical ileus Nematode impaction Intestinal sclerosis Radiation enteritis
True or false: The enteric nervous system can function independently of the central nervous system
TRUE The enteric nervous system uses enteroendocrine cells (such as the enterochromaffin cells) as sensory transducers because no nerve fibers actually penetrate the intestinal epithelium
What is the neurotransmitter in the enteric nervous system?
5-HT or serotonin
What receptor in the enteric nervous system is responsible for initiating peristaltic and secretory reflexes?
5-HT 1p
What receptor in the enteric nervous system is responsible for the sensation of nausea and induction of vomiting?
5-HT3
What does stimulation of the 5-HT4 receptor in the enteric nervous system do?
It increases the presynaptic release of acetylcholine and calcitonin gene-related peptide, which results in enhanced neurotransmission. This results in enhanced propulsive peristaltic and secretory reflexes
What is the mechanism of action of cisapride?
5-HT4 agonist This results in enhanced neurotransmission. however, it depends on natural stimuli to evoke peristaltic and secretory reflexes.
How is cisapride different from metoclopramide?
It does not cross the blood-brain barrier or have antidopaminergic effects. It does not have antiemetic effects and it does not cause the extrapyramidal effects seen with metoclopramide It is a more potent prokinetic than metoclopramide and has a wider activity as it increased colonic motility
What is the mechanism of action of metoclopramide?
It is a central dopaminergic antagonist and peripheral 5-HT3 receptor agonists. It stimulates and coordinates esophageal, gastric, pyloric, and duodenal motor activity. It also increases lower esophageal sphincter tone and stimulates gastric contractions while relaxing the pylorus and duodenum
What can be done to reverse the extrapyramidal signs (involuntary muscle spasms, motor restlessness, inappropriate aggression) associated with metoclopramide administration?
Need to restore an appropriate dopamine to acetylcholine balance with the anticholinergic action of diphenhydramine
What is the mechanism of action of erythromycin as a prokinetic?
At microbially ineffective doses, it stimulates migrating motility complexes and antegrade peristalsis in the proximal GI tract. It also stimulates cholinergic and noncholinergic neuronal pathways that increase motility. It also increase gastroesophageal sphincter pressure in dogs and cats
What is the mechanism of action of ranitidine and nizatidine as prokinetics?
They are both histamine H2 receptor antagonists. The prokinetic activity is due to acetylcholinesterase inhibition.
What is the postulated mechanism of primary peritonitis?
Hematogenous dissemination
What is the most common form of primary peritonitis?
Feline infectious peritonitis (FIP)
What percentage of patients that have had an enterotomy or intestinal resection and anastomosis will develop septic peritonitis secondary to surgical site dehiscence?
6-16%
What percentage of feline peritonitis patients will exhibit abdominal pain?
38-62%
What are the pros and cons of using a Jackson-Pratt drain in a septic abdomen as opposed to the open abdomen technique?
Pros: Decreased risk of nosocomial infections Less intensive nursing and bandaging Decreased risk for evisceration Only one surgical procedure Quantitative and qualitative assessment of fluid Cons: Drain may induce fluid production Drain can become occluded
What is the survival rate for canine patients with peritonitis? Feline patients?
Canine: 44-71% Feline: Depends on the study, up to 70%
What is the reported mortality rate for patients with septic peritonitis secondary to GI leakage?
30-85%
Why should metoclopramide not be used in patients with a pheochromocytoma?
Metoclopramide causes release of catecholamines from the tumor. It is better to use cisapride or erythromycin if a prokinetic is needed.
Describe the differences between osmotic diarrhea, secretory diarrhea, diarrhea from altered permeability, and deranged motility
Osmotic- excess luminal osmoles drawing fluid into the intestinal lumen; this is common in diarrhea Secretory- net increase in intestinal fluid secretion; can be caused by an absolute increase in secretion vs decreased intestinal absorption Altered permeability- microscopic and macroscopic damage to epithelial cells and/or junctions can lead to abnormal permeability; vital substances can be lost into the intestinal lumen Deranged motility- least understood cause; increased peristaltic contractions vs decreased segmental contractions
Describe the characteristics of large vs small bowel diarrhea
Large: mucus common, +/- hematochezia, normal to decreased stool volume, absent melena, increased frequency, increased urgency/tenesmus Small: stool volume increased to normal, melena may be present, frequency increased to normal, no urgency/tenesmus
When is it indicated to start symptomatic tx for diarrhea?
Pt quality of life is decreased, possibility IVC/u cath infection, fecal scald
Name some medications commonly associated with diarrhea
PPI, H2 antagonists, chemotherapeutic drugs, digoxin, procainamide, ACE inhibitors, azathioprine, cyclophosphamide, cyclosporine, NSAIDs, mitotane, methimazole, parasiticides, amitriptyline
How does R sided CHF potentially cause diarrhea?
Congestion of the splanchnic vasculature can cause alterations in the absorptive capacities of the SI
How does hypoadrenocorticism potentially cause diarrhea?
cortisol is vital for maintenance of normal GI fxn, motility and integrity and vascular tone/perfusion
Name some common bacterial causes of diarrhea
Salmonella, Campylobacter, E coli, Clostridium difficile, Clostridium perfringens
Viral infections commonly causing diarrhea?
parvo, feline panleukopenia
What is one of the most common causes of chronic diarrhea in cats and dogs?
IBD
What are the different types of IBD?
Lymphocytic-plasmacytic Eosinophilic Granulomatous
What test is useful for testing for exocrine pancreatic insufficiency? For small intestinal bacterial overgrowth?
Trypsin-like immunoreactivity; cobalamin and folate
What other medications besides steroids can be used for IBD?
locally actie steroid budesonide, azathioprine, chlorambucil, metronidazole for abx and anti-inflammatory effects
T/F: a recent study in HGE (aseptic) in dogs showed an improvement in clinical signs and outcome with administration of clavamox?
False- no change in outcome
T/F: one one veterinary report, probiotics have been shown to shorten the duration of clinical signs in dogs with acute gastroenteritis?
true
How does hyperthyroidism lead to diarrhea?
increased food intake, increased intestinal hypermotility
which type of IBD is the most common?
Lymphocytic-plasmacytic
List vasoconstrictors of the GI mucosa
Leukotriene C4, thromboxane A2, endothelin-1
How does H2S modulate inflammation of the GI mucosa?
Inhibition of leukocyte adherence to the vascular endothelium and diminishes tissue injury induced by neutrophils
List 4 bacterial causes of gastroenteritis
Campylobacter, clostridium, escherichia coli, Salmonella, Helicobacter
List 5 out of 7 viral causes of gastroenteritis
Parvovirus (CVP2), rotavirus, enteric coronavirus, FIP, distemper, FeLV, FIV, Feline panleukopenia
What are 3 fungal/algal causes of gastroenteritis?
Histoplasmosis, pythiosis, protothecosis
List 5 parasitic causes of gastroenteritis
Ascarids, hookworms, strongyloides stercoralis, whipworms, isospora canis/felis, toxoplasma, cryptosporidium parvum, giardia, tritrichomonas, balantidium coli
What rickettsial disease is a possible cause of gastroenteritis?
Neorickettsia helminthoeca (salmon poisoning)
List the three cell types of the glandular portion of the stomach and their chief secretion
Parietal cell - HClChief cell - pepsinogenMucous producing cells - mucous and bicarbonate
What is the approximate life span of an enterocyte?
2-5 days
E.coli is thought to be the causative organism for what disease process?
Histiocytic ulcerative colitis (in boxer dogs)
How is HUS treated and the diagnosis of organisms confirmed?
Fluoroquinolones; FISH (fluorescent in situ hybridization) to confirm
What is the suggested pathogenesis of HGE?
Abnormal immune responses to bacteria, bacterial endotoxins, or dietary indiscretion/ingredients. C. Perfringens have been isolated from HGE dogs but exact role is not known.
Why is the PCV elevated in HGE?
Splenic contraction and/or hemoconcentration
Why are the total solids normal to decreased in HGE?
GI loss of proteins or redistribution of body water into the vascular space
What are 4 causes of PLE?
Severe lymphoplasmacytic IBD, eosinophilic IBD, granulomatous IBD, lymphangectasia, diffuse GI fungal disease, diffuse neoplasia (ie lymphoma)
List 4 extra GI causes of gastroenteritis
Addison’s, liver disease, kidney disease, acute pancreatitis, peritonitis, DKA, vestibular disease, pyometra, prostatitis
What are 3 possible drugs to treat Camphylobacter
Erythromycin, enrofloxacin, cefoxitin
What are the 3 proposed mechanisms through which probiotics may provide benefits in GI disease in vet med?
May compete with pathogenic organisms for nutrition, may produce anti microbial substances, and may stimulate the immune system
Congenital megaesophagus is found in what breeds?
Wire-haired fox terriers, mini schnauzers, GSD, GD, Irish Setters, Labs, Newfies, and Chinese Shar-Peis
What are 4 causes of secondary megaesophagus?
Myasthenia gravis, generalized neuromuscular disease, Addison’s, lead toxicity, hypothyroidism, dysautonomia
List 4 mechanical obstruction causes of regurgitation
Esophageal stricture, foreign body, neoplasia, vascular ring anomalies, extra luminal compression (ie mediastinal mass), hiatal hernia, gastroesophageal intussussception
Most cases of drug induced esophagitis are related to the administration of what?
Doxycycline
Why are metoclopramide and cisapride potentially not useful in regurgitating canine patients?
The canine esophagus is almost exclusively striated muscle, those drugs work on smooth muscle; these drugs may also decrease transit of food to the stomach by increasing lower esophageal tone
What is the parasympathomimetic that may be a useful prokinetic in dogs with megaesophagus?
Bethanechol
T/F: regarding animals with congenital idiopathic megaesophagus, with appropriate care many animals develop improved esophageal motility over several months
T
What are the 3 CNS sites that provide input to the vomiting center?
Vestibular system, cerebrum, CRTZ
What is the most common acid/base finding in patients with GI foreign bodies?
Hypochloremic metabolic alkalosis
What is the most common electrolyte abnormality in vomiting patients?
Hypokalemia
List 5 risk factors for developing GDV
First degree relatives that have had GDV, higher thoracic depth to width ratio, lean body condition, advancing age, stressful events, fearful, nervous, or aggressive temperament, raised food bowl, eating only dry food, single meal/day
What cause of GDV in children has been proposed as a cause of GDV in dogs?
Laxity or agenesis of the peri gastric ligaments
T/F: Stretching or transection of peri gastric ligaments (as with splenic torsion or splenectomy) were suggested in early studies to increase the risk for GDV
T
T/F Gastric dilitation always occurs before volvulus
F - it is unknown - isolated cases of both gastric dilatation and gastric volvulus have been reported
Decreased venous return and increased venous pressure result in what 2 abnormalities that can contribute to interstitial edema and loss of intravascular volume?
Splanchnic pooling and portal hypertension
List 2 physiological side effects of compression of intra abdominal veins secondary to significant gastric distention
Decreased caudal vena cava flow rate, decreased venous return, subsequently decreased cardiac output and MAP
Describe 2 respiratory complications secondary to gastric distention and increased abdominal pressure associated with GDV.
decrease total thoracic volume, prevent normal caudal diaphragmatic excursion, may result in partial lung lobe collapse resulting in decreased tidal volume and V/Q mismatch. RR and RE increase to compensate though efforts may not be enough
What might be a mechanism for aspiration pneumonia specifically suggested for GDV patients?
Aspiration of pharyngeal contents preoperatively resulting in sub clinical pneumonia preoperatively but contributing to post op morbidity and mortality
List 3 reasons for decreased gastric blood flow in a patient with GDV
Compression, thrombosis, avulsion of the splenic and/or short gastric arteries, elevated intragastric pressures, and reduced cardiac output
What is the expected pattern of gastric necrosis in GDV?
Fundus most commonly affected followed by progression to the body of the stomach.
How is necrosis of the cardia potentially different from other gastric necrosis in GDV?
Cardia necrosis is likely related to direct vascular occlusion
Why is intestinal blood flow compromised in dogs with GDV?
Direct compression of the portal vein and decreased cardiac output
T/F splenic compromise is not uncommon in dogs with GDV and is associated with a worse outcome
T
List 3 splenic complications reported in dogs with GDV
Splenic vascular avulsion, intravascular thrombosis, splenic torsion, and splenic infarction.
List 3 possible causes of ventricular arrhythmias associated with GDV
Decreased coronary blood flow, myocardial ischemia which may lead to ectopic foci of electrical activity, circulating epinephrine and proinflammatory cytokines
Describe 2 possible acid/base disorders associated with GDV and their causes
High anion gap (lactate), metabolic acidosis (decreased DO2), hypochloremic metabolic alkalosis (from sequestration of gastric HCL), respiratory acidosis (from Hypoventilation and hypercapnia)
List 4 possible causes of hypokalemia in a patient with GDV
Administration of low K fluids, sequestration of K in the stomach or lost through vomiting or lavage, hyperchloremic metabolic alkalosis with transcellular shifting, activation of the RAAS, and catecholamine induced intracellular shifting of K.
In a dog with GDV, where is the pylorus located on the DV view?
To the left of midline
Why is VD positioning potentially contraindicated in GDV?
May lead to further cardiovascular compromise, and may predispose to aspiration if the dog regurgitates/vomits
T/F the presence of 2 or more abnormal hemostatic parameters consistent with DIC has been shown to correlate with gastric necrosis
F…3 or more
What are 2 possible complications associated with attempted trocharization?
Splenic laceration, gastric perforation
T/F - dogs with GD and no V do not require surgical intervention
False- recommend explore if are unresponsive to medical treatment; also pexy is recommended In the future to prevent GDV
What is the most common degree of pyloric rotation in a GDV?
180-270 degrees
What are the 3 markers to assess gastric wall viability?
Serosal color, palpation of gastric wall thickness, and evidence of arterial bleeding if incised
List 3 possible consequences associated with gastric wall necrosis
Peritonitis, DIC, sepsis, and arrhythmias
Why is tube gastropexy associated with higher morbidity?
Due to premature tube removal and peristomal cellulitis
List 4 gastropexy techniques
Tube, incisional, muscular flap, circumcostal, belt loop
List 4 risk factors associated with death before suture removal
Hypotension during hospitalization, combined splenectomy and partial gastropexy, peritonitis, sepsis, and DIC
What are the two plexuses of the enteric nervous system and where are they located?
Myenteric (or Auerbachs) which is between the longitudinal and circular muscular layers, and the submucosal (or Meissners) which is in the submucosa
What does the myenteric plexus control? and the submucosal plexus?
myenteric controls gastrointestinal movements, the submucosal controls gastrointestinal secretion and local blood flow
When the myenteric plexus is stimulated, what are its effects?
1 - increased tonic contraction of tone of the gut wall 2- increased intensity of rhythmic contractions 3- slightly increased rate of the rhythm of contraction 4- increased velocity of conduction of excitatory waves along the gut wall
Name 6 neurotransmitters secreted by enteric neurons
acetylcholine norepinephrine adenosine triphosphate serotonin dopamine cholecystokinin substance P vasoactive intestinal polypeptide somatostatin leu-enkephalin met-enkephalin bombesin
In the enteric nervous system which is the main excitatory and which is the main inhibitory neurotransmitter?
excitatory is acetylcholine inhibitory is norepinephrine
What is the gastrocolic reflex?
Signal from the stomach to cause evacuation of the colon (reflex from the gut to the prevertebral sympathetic ganglia and then back to the GI tract)
what are the two types of electrical waves that cause excitation of the GI tract?
slow waves, spike potentials
What is the colonoileal reflex?
reflex from the colon to inhibit emptying of the ileal contents into the colon (reflex from the gut to the prevertebral sympathetic ganglia and then back to the GI tract)
What gastrointestinal reflexes travel from the gut to the spinal cord or brain stem and then back to the GI tract?
1- reflexes to control gastric motor and secretory activity 2- pain reflexes that cause general inhibition of the GI tract 3- defecation reflexes that travel from the colon and rectum to the spinal cord and back to produce contractions required for defecation
List the layers of the intestinal wall from outer surface inwards
serosa, longitudinal smooth muscle, circular smooth muscle, submucosa, mucosa
how are spike potentials involved in smooth muscle contraction of GIT?
occur automatically when resting membrane potential of GI smooth muscle is more positive than -40 mV; appear on peaks of slow waves
compare the types of channels used for action potentials in GI smooth muscle vs nerve fibers
nerve fibers- action potential caused by rapid entry of Na through sodium channel to interior (Na channels); more rapid open/close GI smooth muscle- large numbers of Ca enter alone with smaller # of Na ions (Ca-Na channels); slower to open/close; results in longer duration of action potential
What cells secrete cholecystokinin (CCK)?
I cells in the mucosa of the duodenum and jejunum
what are the two types of electrical waves that cause excitation of the GI tract?
slow waves, spike potentials
list factors that may cause hyperpolarization (more negative) of membrane potential
effect of epi or norepi on fiber membrane, stimulation of sympathetic nerves that secrete norepi at their endings
What cells secrete secretin?
S cells of the duodenum, jejunum, and ileum
Name stimuli for secretin secretion
Acid Fat
What are the actions of secretin?
Stimulates pepsin secretion, pancreatic bicarbonate secretion, biliary bicarbonate secretion, growth of exocrine pancreas Inhibits gastric acid secretion
what are the two plexuses that compose the enteric nervous system
myenterix/Auerbach’s; submucosal/Meissner’s
What are the actions of cholecystokinin?
Stimulates pancreatic enzyme secretion, pancreatic bicarbonate secretion, gallbladder contraction, growth of the exocrine pancreas Inhibits gastric emptying
What cells secrete secretin?
S cells of the duodenum, jejunum, and ileum
Name stimuli for secretin secretion
acid fat
What are the actions of secretin?
Stimulates pepsin secretion, pancreatic bicarbonate secretion, biliary bicarbonate secretion
describe slow waves and how they cause electrical excitation in the GIT
slow, undulating changes in the resting membrane potential that may be caused by interactions between smooth muscle cells and specialized cells such as interstitial cells of cajal
what is the proposed role of interstitial cells of cajal?
act as an electrical pacemaker for smooth muscle cells
in what part of the GIT can slow waves cause muscle contraction by themselves (i.e. not along with intermittent spikes)
stomach
compare the types of channels used for action potentials in GI smooth muscle vs nerve fibers
nerve fibers- action potential caused by rapid entry of Na through sodium channel to interior (Na channels); more rapid open/close GI smooth muscle- large numbers of Ca enter alone with smaller # of Na ions (Ca-Na channels); slower to open/close; results in longer duration of action potential
what is the average resting member potential in the GI?
-56 mV
list factors that may cause depolarization (less negative) of membrane potential
stretching of muscle, stimulation by Ach released from parasympathetic nerves, stimulation by GI hormones
list factors that may cause hyperpolarization (more negative) of membrane potential
effect of epi or norepi on fiber membrane, stimulation of sympathetic nerves that secrete norepi at their endings
t/f- slow waves cause calcium ions to enter the smooth muscle fiber
false- only Na ions enter
t/f- spike waves cause significant amts of Ca ions to enter smooth muscle fiber
true; this is why they more often cause action potential and muscle contraction
where is the enteric nervous system located
wall of gut from esophagus to anus
what are the two plexuses that compose the enteric nervous system
myenterix/Auerbach’s & submucosal/Meissner’s
what does the myenteric plexus mainly control?
GI movements
what does the submucosal plexus mainly control?
GI secretion and local blood flow
What cells secrete gastric inhibitory peptide?
K cells of the duodenum and jejunum
Name stimuli for gastric inhibitory peptide secretion
Protein Fat Carbohydrate
What are the actions of gastric inhibitory peptide?
Stimulates insulin release Inhibits gastric acid secretion decreases motor activity of stomach
What cells secrete motilin?
M cells of the duodenum and jejunum
Name stimuli for motilin secretion
Fat Acid Nerve
What are the actions of motilin?
Stimulates gastric motility and intestinal motility
Give the 3 motor functions of the stomach: (Guyton)
- Storage of food - Mixing of food with gastric secretions (formation of chyme) - Emptying of the chime at a rate suitable for proper digestion
How is the reflex triggered by a bolus of food and allowing the stomach to distend called? (Guyton)
Vagovagal reflex (from the stomach (stretching) to the brain stem to the stomach)
Are the gastric glands present in the entire wall of the body of the stomach? (Guyton)
No, almost except along a narrow strip on the lesser curvature of the stomach
What are the 2 types of gastric contractions (presence of food or not)? (Guyton)
- Peristaltic contractions (when food is present) - Hunger contractions (when the stomach has been empty for several hours)
What is the ratio between weak peristaltic contractions (mixing) and strong ringlike peristaltic contractions? What is the pressure generated by strong peristaltism? (Guyton)
20% of ringlike contractions, 50-70 cmH2O
T or F: Peristaltic constrictor waves increase in intensity as they progress from the body of the stomach to the antrum (Guyton)
True
What is the frequency of the gastric peristaltic constrictor waves when food is present in the stomach? (Guyton)
One every 15-20 seconds
What are the 2 roles of the gastric peristaltic constrictor waves? (Guyton)
- Propulsion of food - Mixing (by retropulsion: peristaltic wave while the pylorus is contracted, squeezing the antral content)
How is called the mixture of food with gastric acid? (Guyton)
Chyme
What parts of the GI tract regulate the stomach emptying? (Guyton)
Duodenum >> Stomach
What are the main gastric factors promoting stomach emptying and name the reflexes elicited when needed? (Guyton)
- Increased gastric food volume resulting in gastric wall stretching (and not increased storage pressure) -> local myenteric reflexes -> accentuate the activity of the pyloric pump, inhibit the pylorus - Gastrin
What are the main duodenal factors inhibiting stomach emptying? Name the reflexes elicited and their pathways, or hormones released. (Guyton)
- Distention of the duodenum / Irritation of the duodenal mucosa / Osmolality of the chyme (hypertonic > hypotonic) / Presence of certain breakdown products in the chyme (breakdown of proteins > fat) -> Enterogastric nervous reflexes - From the duodenum to the stomach through the enteric nervous system in the gut wall - Through extrinsic nerves that go to the prevertebral sympathetic ganglia and then back through inhibitory sympathetic nerve fibers to the stomach - Through the vagus nerves all the way to the brain stem, where they inhibit the normal excitatory signals transmitted to the stomach through the vagi - Fatty substances in the chyme -> Hormones from the duodenal and jejunal epithelium (cholecystokinin, +/- secretin +/- gastric inhibitory peptide)
most of the chewing muscles are innervated by which cranial nerve?
the motor branch of the 5th CN (trigeminal)
the nuclei in control of the chewing process are located in which area of the CNS?
brain stem
what is the chewing reflex?
presence of a bolus of food in the mouth at first initiates reflex inhibition of the muscles of mastication, which causes the lower jaw to drop
what is rebound contraction in regards to chewing?
raising of the jaw to cause closure of the teeth to allow chewing
why is chewing especially important for fruits and raw veggies?
they have indigestible cellulose membranes around the nutrient portions that must be broken down before digestion can occur
the rate of digestion is absolutely dependent on what?
the total surface area of the food exposed to the digestive secretions
what are two benefits of the GI tract that occur when food is ground into a very fine particulate consistency in the mouth?
prevents excoriation of GI tract and increases the ease with which food is emptied from stomach to SI
what are the 3 general stages of swallowing
voluntary stage, pharyngeal stage, esophageal stage
describe the voluntary stage of swallowing
the tongue voluntarily moves food to the pharynx and backward against the palate
briefly describe the pharyngeal stage of swallowing
the food in the posterior mouth/pharynx stimulates epithelial swallowing receptor areas, then brain stem initiates automatic pharyngeal muscle contractions
There are 5 steps to the pharyngeal stage of swallowing. Describe.
- Soft palate is pulled upward to closer posterior nares 2. palatopharyngeal folds on each side of pharynx are pulled medially to form a slit for masticated food to pass 3. vocal cords are approximated and larynx is pulled upward and rostrally, causing epiglottis to cover opening of larynx 4. upward mvmt of larynx pulls up and enlarges the opening to the esophagus; upper esophageal sphincter relaxes 5. entire muscular wall of the pharynx contracts, which propels food into esophagus
where is the swallowing center located in the brain?
medulla and lower pons
which cranial nerves control motor impulses from swallowing center to to pharynx/upper esophagus?
V, IX, X, XII trigeminal, glassopharyngeal, vagus, hypoglossal
how does swallowing center affect the respiratory center?
it inhibits respiratory center of medulla during pharyngeal stage of swallowing, which only takes about 6 sec
list and describe the 2 types of esophageal peristaltic movements
- Primary peristalsis- continuation of the peristaltic wave that begins in the pharynx and spreads into the esophagus 2. secondary peristalsis- results from distension of esophagus itself by retained food when primary peristalsis fails to move food into stomach; they continue until all food has reached stomach
how long does it take for food to pass from pharynx into stomach in normal adults?
8-10 seconds; 5-8 seconds if person is upright
what type of muscle makes up the pharyngeal wall and upper 1/3 of esophagus? what controls the muscle?
striated muscle- controlled by skeletal nerve impulses from glossopharyngeal and vagus nerves
what type of muscle makes up the distal 2/3 of the esophagus? what nerves control the muscle?
smooth muscle; controlled by vagus nerves or myenteric nerve plexus
t/f: the stomach and duodenum become relaxed as the esophageal peristaltic wave approaches the stomach?
true
where is the LES located in esophagus?
about 3 cm above esophageal juncture with stomach
what ist he normal intraluminal pressure at the LES?
30 mm Hg
t/f: the esophageal mucosa is capable of resisting the digestive actions of gastric secretions for long periods of time?
false- only the distal 1/8 can resist for long
what are two mechanisms that help prevent reflux of stomach contents into esophagus?
Lower esophageal sphincter being contracted Valvelike mechanism of esophagus that extends into the stomach- caves the esophagus inward with increased intra-abdominal pressure
What cells mostly contain the pyloric glands? What is mainly secreted by the pyloric glands on top of gastrin and pepsinogen?
- Mucous cells (+ few peptic cells and almost no parietal cells) - Thin mucus to help lubricating food movement
How are called the type of mucous cells covering the entire surface of the stomach mucosa? What do they secrete? Give 3 roles for this secretion?
- Surface mucous cells - Large quantity of viscid mucus - Shell of protection for the stomach wall / Lubrification of food transport / Alkaline protection (wall not directly exposed to the highly acidic, proteolytic stomach secretion)
What are the only cells secreting hydrochloric acid?
Parietal cells of the oxyntic glands of the main body of the stomach
What type of cells operate in close association with the parietal cells of the oxyntic glands?
- Enterochromaffin-like cells (ECL)
Describe the association between gastrin, histamine and hydrochloric acid
- Gastrin secreted by the G cells in the pyloric glands in response to proteins being digested - Stimulation of histamine secretion by the ECL - Stimulation of hydrochloric acid release by the parietal cells of the oxyntic glands
What are the 2 stimuli for pepsinogen secretion by the peptic cells in the oxyntic glands?
- Stimulation by acetylcholine released from the vagus nerves or from the gastric enteric nervous plexus - Stimulation in response to acid in the stomach (which acts indirectly by eliciting additional enteric nervous reflexes)
T-F: Intestinal chyme always inhibits gastric secretion
F: Intestinal chyme can stimulate gastric secretion during the early intestinal phase
How is called the reflex responsible for stomach secretion inhibition? Give 5 triggers for this reflex.
Reverse enterogastric reflex, initiated by: - Presence of food in the small intestines, transmitted through the myenteric nervous system and extrinsic sympathetic and vagus nerves - Distension of the small bowel - Presence of acid in the upper intestine - Presence of protein breakdown products - Irritation of the mucosa
T-F: Secretin stimulates gastric and pancreatic secretion.
F: Secretin opposes gastric secretion and stimulates pancreatic secretion
What is the composition of the gastric secretion during the ‘interdigestive phase’?
(nonoxyntic type) Composed mainly of mucus with little pepsin and almost no acid
Give 2 causes for increased peptic and acidic phases of the interdigestive gastric secretion.
- Emotional stimuli - Cephalic phase (idea/visualization of a meal)
What are the 2 (3) main compounds of the pancreatic juice and where are they secreted from?
- Pancreatic digestive enzymes secreted by pancreatic acini - Large volumes of sodium bicarbonate solution secreted by the epithelial cells of small ductules and larger ducts from the acini (- Water secreted by the epithelial cells of small ductules and larger ducts from the acini)
What is the main stimulus for pancreatic juice secretion?
Presence of chyme in the upper portions of the small intestine
T-F: The pancreatic juice also contains insulin secreted by the islets of Langerhans
F: insulin is secreted directly into the blood
What are the 3 most important pancreatic enzymes for digesting proteins? Which one of those splits some peptids into individual amino acids?
- Trypsin > chymotrypsin, carboxypolypeptidase (secreted in their inactivated form -> activated by enterokinase and trypsin) - Carboxypolypeptidase
What are the pancreatic enzymes responsible for digesting carbohydrate? fat?
- Pancreatic amylase - Pancreatic lipase, cholesterol esterase, phospholipase
What is the mechanism to prevent pancreatic autodigestion by the pancreatic enzymes?
Concurrent secretion of trypsin inhibitor by the cells into the acini (overwhelmed if large quantities of pancreatic secretion are pooled in damaged area of the pancreas)
What are the basic steps in the cellular mechanism for secreting sodium bicarbonate solution and water into the pancreatic ducts?
- CO2 diffuses into the cell -> carbonic anhydrase -> carbonic acid (H2CO3) -> dissociation into bicarbonate ions and hydrogen ions (HCO3- and H+) - Active symport transport with sodium through the luminal border of the cell - Formed hydrogen ion exchanged for sodium ion through the blood border of the cell - Overall movement of bicarbonate and sodium creates an osmotic pressure gradient -> osmosis of water into the pancreatic duct
What are the 3 basic stimuli for pancreatic secretion?
- Acetylcholine released from the parasympathetic vagus nerve (mainly pancreatic enzymes) - Cholecystokinin in response to food entering the small intestine (mainly pancreatic enzymes) - Secretin in response to acidic food entering the small intestine (mainly water and sodium bicarbonate solution to ‘flush’ the accumulated pancreatic enzymes)
What are the 3 phases of pancreatic secretion?
- Cephalic phase (acetylcholine release by the vagal nerve endings in the pancreas -> 20% of total secretion of pancreatic enzymes) - Gastric phase (same nervous stimulation -> 10%) - Intestinal phase (After chyme leaves the stomach and enters the small intestine, pancreatic secretion becomes copious, mainly in response to the CCK (70-80% of total pancreatic enzymes) and secretin (mainly H2O and NaHCO3))
What is the pH below which secretin begins to be released from the mucosa of the small intestines? What is the optimal pH for the pancreatic enzymes to be effective?
- 4.5 / 5 (increases greatly as the pH falls to 3) - 7.0-8.0
What are the 2 most important functions of the bile?
- Fat digestion and absorption - Excretion of waste products
What is the most abundant fat in a diet?
Neutral fat = triglycerides
Which one of those is considered a fat (similar characteristics and metabolites) but does not contain fatty acids? Phospholipids, cholesterol, cholesterol ester
Cholesterol
Which enzyme is responsible for 10% of triglycerides digestion in the stomach?
Lingual lipase
what is hydrolysis?
return of hydrogen and hydroxyl ions from water to the polysaccharides, which separates the monosaccharides from each other; it occurs when carbs are digested
t/f: almost all of the carbs in the diet are either large polysaccharides or disaccharides?
true
What is emulsification? Under which influence?
Breaking down of the fat globules into small sizes so that water-soluble lipase enzymes can act on the globule surfaces under the influence of bile salts, lecithin (decreasing interfacial tension of the globules) and agitation
What is the most important enzyme for digestion of triglycerides? What are the products?
- Pancreatic lipase - Free fatty acid and 2-monoglyceride
How are called the small intestinal mucosa folds? Where are they
Valvulae conniventes or folds of Kerckring
What are the 2 enzymes to hydrolyze cholesterol esters and phospholipids? Where are they produce?
- Cholesterol ester hydrolase and phospholipase A2 - Pancreas
How are caled the small intestinal mucosa folds? Where are they
Valvulae conniventes or folds of Kerckring
Why is the stomach a poor absorptive area? (2 reasons)
- Lack of villus type of absorptive membrane - Tight epithelial cells junction
By how many folds the presence of villi on the mucosal surface enhance the total absorptive area? By how many folds the presence of a brush border (microvilli) on each villus enhance the total absorptive area? By how many folds the presence of the folds of Kerckring, villi and microvilli enhance the total absorptive area?
- 10-fold - 20-fold - 1000-fold
How does the distribution of the villi on the mucosal surface differ between the upper and distal small intestine?
The villi lie very close to each other and touch in most areas of the upper small intestine.Their distribution is less profuse on the distal small intestine
What is the motive power for sodium absorption by the epithelial intestinal cells (necessay to create a gradient) between the sodium concentration inside the cell and the chyme)?
Active Na-K-ATPase pump on the basolateral membrane (+ passive absorption along with a negatively charged chloride on the basolateral membrane)
Which portion of all the sodium present in the body is absorbed everyday to prevent net loss of sodium into the feces?
About one seventh
What is the motive power for sodium absorption by the epithelial intestinal cells?
Active Na-K-ATPase pump on the basolateral membrane (+ passive absorption along with a negatively charged chloride on the basolateral membrane)
Give 3 transporters for sodium present on the intestinal brush border membrane?
- Na-amino acid cotransporter - Na-glucose cotransporter - Na-H exchanger
t/f- the chemistry of digestion with all 3 major types of food (proteins, fats, and carbs) is due to hydrolysis?
true
what is ptyalin?
a digestive enzyme that is secreted by the parotid glands to mix up the food with saliva; it hydrolyzes starch into maltose and other small glucose polymers
the carbs are almost totally converted into maltose and/or other small glucose polymers before passing what part of the SI?
duodenum or upper jejunum
at what stomach pH is pepsin most active?
2-3
above what stomach pH is pepsin inactive?
>5
list the four major proteolytic pancreatic enzymes
trypsin, chymotrypsin, carboxypolypeptidase, proelastase
Green, JVECC, 2011, Eval initial lactate and gastric necrosis and subsequent lactate survival. What were main findings?
- NO * sig relationship b/t survival and presence of macroscopic gastric necrosis with initial lacate > 62. * sig relationship b/t initial lactate > 2.9 mmol/L for predicting necrosis and 50% reduction in lactate 12h after tx (of the 40 that had repeat lactate)4. The other 3/40 that had repeat lactates that were not more than 50% lower, all died
Beal, JVECC, 2011. Regarding fluoroscopically placed NJT, which of the following is true?a) Most common primary diagnosis was adenocarcinomab) Ability to achieve transpyloric passage was 92.3%c) Ability to achieve jejunal access was 58.2%d) Median duration of feeding was 6.5 days
bpanc most common primary dz, jejunal access in 78.2%, medial duration feeding 3.3 d
What is stress related injury?
Diffuse, superficial mucosal erosions that are unlikely to result in GI bleeding associated with hemodynamic compromise.
What is stress related mucosal disease?
Stress ulcers extend deeper into submucosa and are more focal. Increased risk for bleeding necessitating pRBC transfusion and intervention to control bleeding
Difference in mortality in humans with SRMD?
48.5% with bleeding vs. 9.1% w/o bleeding
Alaskan sled dogs SRMD incidence?
48.5%
Pathogenesis for SRMD involves…
Splanchnic ischemiaLoss of host defensesAssault by gastric acid
What is the GMDS?
gastric mucosal defense system that protects against gastric acid, pepsin, and bile acids
What makes up the GMDS?
- Extracellular mucus barrier2. Cellular membrane properties3. Rapid epithelial cell restitution4. Mucosal HCO3 secretion5. High mucosal blood flow rate6. Neurohormonal factors7. Prostaglandins
What is the extracellular mucus barrier?
unstirred layer of mucus gel, bicarb, and surfactant phospholipids
What is fxn of extracellular mucus barrier?
- maintain surface pH 72. prevent pepsin infiltration and proteolytic degredation3. hydrophopic properties of surfactant phospholipids to repel water soluble agents
Mucus gel is…
95% water, 5% mucin glycoproteins
What are trefoil factor family proteins?
peptides co-secreted with mucus gel - fxn in intracellular assembly and packing of mucins and increase mucus viscosity
What influences gastric mucus secretion?
ACTH, corticosteroids, NSAIDS
What prevents back diffusion of acid and pepsin in stomach?
cellular tight jxns and correct functioning of membrane pumps and exchanges
What do gastric epithelial cells secrete?
prostaglandins, TFFs, heat shock proteins, cathelicidins, defensins
What do cathelicidin and defensins do?
participate in innate immunity, preventing bacterial colonization
What is epithelial restitution?
rapidly sealing epithelial compromise
pH requirement for epithelial restitution?
>3.0
What is survivin?
protein expressed by progenitor cells that prevents apoptosis and promotes mitosis. Takes 3-7 days for epithelial restitution.
What do parietal cells do?
secrete acid from apical membrane and bicarb from basolateral membrane (alkaline tide). The interstitial bicarb transported paracellularly to GI epithelial surface to be trapped in mucus.
What vasodilators do endothelial cells produce?
NO, prostacyclin (PGI2)protects from vasoconstrictors
What are vasoconstrictors?
leukotriene C4, thromboxane A2, endothelin-1
How does H2S help maintain mucosal blood flow?
mucosal protectant, modulates inflammation via inhibiting leukocyte adherence to vascular endotheliam
Vagal stimulation does what in GMDS?
increases mucus secretion and intracellular bicarb concentration
When vagal afferents detect noxious stimulus or acid at gastric epitheliam, nerve endings release..
calcitonin gene-related peptidesubstance PResult: NO mediated vasodilation
What other peptides enhance mucosal blood flow?
gastrincholecystokininthyrotropin-releasing hormonecorticotropin releasing factorepidermal growth factor
What does ghrelin do?
stimulates appetite and increases acid secretionMaybe: enhance mucosal blood flow thru NO and CGRP, and inhibit IL-1B, IL-6, TNF-alpha
What prostaglandins are cytoprotective in the gastric mucosa?
PGE2 and PGI2Fxn: stimulation of mucus, bicarb, and phospholipid secretion AND inhibit acid secretion, tissue mast cell degranulation, leukocyte and plt adhesion
ROS
superoxide anion, hydrogen peroxide, hydroxyl radical
Where are parietal cells found?
oxyntic glands
What happens in parietal cells?
carbonic anhydrase converts water and CO2 to H and HCO3. H secreted thru apical H-K-ATPase pump and HCO3 secreted thru basolateral membrane in exchange for Cl-
Secretion of gastric acid is mediated by…
gastrin (paracrine) acetylcholine (neurocrine)histamine (endocrine)
What is the most potent secretogogue?
histamine
How do gastrin, ACh, and histamine increase acid secretion?
Bind their receptors, activates second messenger that increases intracellular calcium (gastrin, ACh) of increases cAMP (histamine). The second messengers then activate protein kinase, increasing cytosolic phosphoproteins, which ultimately activate proton pump
Risk factors for SRMD
PPV and coagulopathy (HIGHEST)sepsisshock/hypotensionrenal failurehepatic failureneuro trauma and sxMOFtraumaaspiration pneumoniaileusmajor sxburns >35% BSAorgan transplanthigh dose corticosteroidprolonged ICU stay
Where are SRMD lesions found?
stomach with oxyntic glands - fundus, bodycontrast peptic ulcer dz is antrum and pylorus
Pepsin inhibited and fibrinogen halted at pH over…
>4
pH over ___ required for plt aggregation and fibrin clot formation
>6
Histamine released from…
tissue mast cells and enterochromaffin cells
Where is the H2 receptor?
basolateral membrane of parietal cells
List H2 receptor antagonists
cimetidinenizatidineranitidinefamotidinemetabolized in liversecreted in kidneys
Which H2 receptor antagonists have prokinetic actions?
ranitidinenizatidine
Which H2 receptor antagonist impairs P450 liver?
cimetidine
Adverse effects of H2RAs
diarrhea, headache, drowsiness, fatigue, muscle pain, constipation, leukopenia, thrombocytopenia, anemia
What reaction has IV famotidine caused in cats? Speculated reason?
hemolysis, maybe due to benzyl alcohol preservative
How do PPIs work?
Substituted benzimidazoles that bind to the proton pump, inhibiting the final step in gastric acid secretion in a dose dependent mannerweak base, accumulates in canaliculi where converted to sulfenamide form which irreversibly binds to proton pump
List PPIs
omeprazole
lansoprazole
pantoprazole
esomeprazole
rabeprazole
Bases behind why PPIs provide more potent acid suppression than H2RAs?
Irreversible proton pump inhibition, progressive intracellular acidification, drug accumulation
What drug has decreased bioactivation via CYP 450 when administered with omeprazole?
clopidogrel
What drugs have prolonged eliminates when administered with PPIs?
cyclosporinediazepamphenytoinwarfarintheophyllinepropanololP450 pathway
Reported adverse effects of PPIs in people?
Abd pain, nausea, vomiting, diarrhea, pancreatitis, hepatic necrosis/failure, pancytopenia, agranulocytosis, hypergastrinemia with chronic use
What is sucralfate?
Complex salt of sucrose sulfate and aluminum hydroxideAluminum negative and will bind everything
What are benefits of sucralfate?
- Coat mucosa2. Inhibit pepsin molecules3. Stimulate prostaglandin release4. Increase mucosal blood flow5. Increase HCO3 and mucus secretion6. Stimulates epidermal growth factor for cell renewal
What are potential benefits of EN?
- Acid buffering2. Mucosal energy source3. Enhance mucosal immunity4. Induction of prostaglandin secretion5. Improve mucosal blood flow
Gastric layers.
Serosa, longitudinal SM, circular SM, submucosa, mucosa
When myenteric plexus is stimulated, what happens?
- Increased tonic contraction2. Increase intensity of rhythmical contractions3. Increase rate of rhythm of contraction4. Increase velocity of conduction of excitatory waves along the gut wall
Some of the neurons of the myenteric plexus secrete what inhibitory NT?
vasoactive intestinal polypeptide
Where is gastrin released from?
G cells of antrum, duodenum, and jejenum
What stimulates release of gastrin?
protein, distension, vagal stimulation (ACh)
What inhibits release of gastrin?
acid
What does gastrin do?
stimulates gastric acid secretion and mucosal growth
Where is cholecystokinin released from?
I cells of dudenum, jejunum, and ileum
What stimulates release of CCK?
protein, fat, acid
What does CCK do?
Stimulates pancreatic enzyme and bicarb secretion, stimulate GB contraction and growth of exocrine pancInhibits gastric emptying
Where is secretin released from?
S cells of duodenum, jejunum, ileum
What stimulates release of secretin?
acid!!!!!! and fat
What are the actions of secretin?
Stimulates: pepsin secretion, pancreatic bicarb secretion!!!!, biliary bicarb secretion, growth of exocrine pancInhibits: gastric acid secretion
Where is gastric inhibitory peptide (GIP) released from?
K cells of duodenum and jejunum
What stimulates release of GIP?
protein, fat, carbs
Fxns of GIP
Stimulates insulin release and inhibits gastric acid secretion
GIP also known as
glucose-dependent insulinotropic peptide
Where is motilin secreted from
M cells of duodenum and jejunum
Motilin secretion stimulated by?
fat, acid, nerve
What does motilin do?
Stimulates gastric and intestinal motility
Oxyntic glands (acid forming) secrete…
hydrochloric acid and intrinsic factor (from parietal cells), pepsinogen (from chief or peptic cells)mucus (from mucous neck cells)
Pyloric glands secrete…
mucus and gastrin
Ach stimulates what in the stomach
pepsinogen by peptic/chief cells, HCl by oxyntic/parietal cells, and mucus by mucous cells
Gastrin and histamine stimulate what…
strongly stimulate acid by parietal/oxyntic cells
Pyloric glands secrete…
mucus and gastrin
What activates pepsinogen to pepsin?
hydrochloric acid
Fxn of pepsin.
proteolytic enzyme, optimal pH 1.8-3.5
What are the 3 phases of gastric secretion?
cephalic, gastric, intestinal
Basic stimuli that cause pancreatic secretion.
ACh, CCK, secretin
Young GSDs with EPI predisposed to what severe cause of acute abdominal pain?
mesenteric torsion
Severe vomiting and GI FBs have what typically on blood gas?
hypochloremia metabolic alkalosis with hypokalemia and hyponatremia
Where is free peritoneal gas usually seen on radiographs?
B/t stomach or liver and diaphragm on lateral viewOr, can increase sensitivity with pet in LEFT lateral recumbency and horizontal beam focused on least dependent area
Most common causes of pure transudate in abdomen?
hypoalbuminemiaportal vein obstruction
Most common causes of modified transudate in abdomen?
R-CHF, HWD, cancer, liver dz
What is a poor prognostic indicator in cats with acute panc?
ionized hypocalcemia
Radiographic signs of acute panc?
increased density and loss of detail right cranial abdomenwidening of angle b/t prox duodenum and pylorusdisplacement of descending duodenum to rightcaudal displacement of transverse colon
What is the rational for using FFP for pancreatitis?
provide a source of alpha-2 macroglobulins (protease inhibitors to help clear activated circulating proteases)
In experiimental feline panc, what pressor has shown ability to reduce panc inflammation by decreasing microvascular permeability?
dopamine
What is feline triaditis?
pancreatitis, cholangitis, IBD
Obstructive biliary dz in dogs most commonly…
pancreatitis
What makes up bile?
water, conjugated bile acids, bile pigments, cholesterol, inorganic salts
Obstructive biliary dz in cats most commonly d/t…
cancer
Sensitivity of US to detect GB rupture with mucocele?
86%
What percent of dogs with GB mucocele had rupture intraop?
50%
Liver fluke in cats?
Platynosomum fastosum
What is Caroli’s syndrome?
congenital malformation of the bile ducts
What are the most common causes of bile peritonitis?
necrotizing cholecytitis, trauma, cholelithiasis
MOA of ursodeoxycholic acid
Hydrophilic bile acid that increases water content of biliary secretions, encourages choleresis, decreases inflammation and immune-mediated reactions, and lessens hepatotoxic nature of bile acis
Mortality with biliary surgery if…
septic bile peritonitis, prolonged PTT, post op hypotension
MOA chlorpromazine
alpha-2 adrenergic antagonistD2 dopaminergic antagonistH1 histaminergic antagonistM1 muscarinic cholinergic antagonist
MOA cisapride
5-HT4 serotinergic agonist
MOA dimenhydrinate
H1 histaminergic antagonist
MOA diphenhydramine
H1 histaminergic antagonist
MOA dolasetron
5-HT3 serotonergic antagonist
MOA domperidone
D2 dopaminergic antagoistincreased gastroesophageal sphincter tone and antiemetic
MOA erythromycin
motilin agonist
MOA famotidine
H2R antagonist
MOA maropitant
NK1 receptor antagonist
MOA metoclopramide
D2 dopaminergic antagonist5HT3 serotinergic antagonist5HT4 serotonergic agonist
MOA nizatidine
cholinesterase inhibitorH2RA antagonist
MOA omeprazole
PPI
MOA ondansetron
5HT3 serotonergic antagonist
MOA pantoprazole
PPI
MOA prochlorperazine
alpha2 adrenergic antagonistD2 dopaminergic antagonistH1 histaminergic antagonistM1 muscarinic cholinergic antagonist
MOA ranitidine
H2R antagonist
MOA scopolamine
M1 muscarinic cholinergic antagonist
MOA sucralfate
sucrose sulfate aluminum complex cytoprotective
MOA yohimine
alpha-2 adrenergic antagonist
Enterocyte life span
2-5 days
Rotavirus and coronovirus affect the intestinal crypts. T/F
F - affect the tips of villi (parvo affects crypts)
Bacterial causes of gastrointeritis.
Clostridium (perfringens and difficle), Campylobacter, Escherichia, Salmonella, Heliocobacter
Where does serotonin come from in GI tract?
Enterochromaffin cells (95% of body’s serotonin in GI tract) - released and secreted into lamina propria in high concentrations which overflows into portal circulation and intestinal lumen
5HT^1P
Initiates perstaltic and secretory reflexes (no drugs for this receptor)
5HT3
activates extrinsic sensory nerves and is responsible for the feeling of nausea and induction of vomiting from visceral hypersensitivity5HT3 antagonist = ondansetron, dolasetron, granisetron, metoclopramide
5HT4
Increases presynaptic release of AcH and calcitonin gene-related peptide, enhancing neurotransmission5HT4 agonist = cisapride, tegaserod, metoclopramide
Why does metoclopramide cause extrapyramidal signs?
It crosses the BBB to antagonize D2 receptors in CRTZ
Extrapyramidal signs: involuntary muscle spasms, motor restlessness, inappropriate aggression (can reverse with diphenhydramine)
How do ranitidine and nizatidine increase GI motility?
Acetylcholinesterase inhibition - so increase amt of acetylcholine available to bind smooth muscle muscarinic cholinergic receptors
If severe GI bleed and underlying cause not found on diagnostics, not responding to medical mgmt, options are:
- Exploratory sx2. Scintigraphy with technetium-labeled red blood cells3. arteriography
Causes of secondary megaesophagus.
MG, NM dz, hypoadrenocorticism, lead toxicity, hypothyroidism
What is odynophagia?
pain on swallowing
What drug may stimulate esophageal contractions in some dogs?
bethanechol - parasympathomimetc that stimulates muscarinic receptors, not nicotinic
Where is the chemoreceptor trigger zone?
floor of 4th ventricle, lacks complete BBB
What receptors make up the CRTZ?
D2, H1, alpha2, 5HT3, M1, NK1, ENKudelta
What receptors make up the vestibular system?
H1, M1, NMDA
What receptors are in teh vomiting center?
alpha2, 5HT^1a
What receptor does apomorphine work on?
D2 - CRTZ
What increases risk of post op peritonitis?
preop peritonitis, intestinal FB, alb < 2.5 g/dL
Single paracentesis (blind) successful in ….
20% patients with low volume (10 ml/kg)
DPL technique
Clip, scrub, use peritoneal dialysis catheter or 14/16 g cath, insert caudal to umbilicus, influse 22 ml/kg warm isotonic crystalloid and remove
Uroperitoneum if fluid:serum creatinine and K>
>2:1 (creat) or >1.4.1 (K)
Presence of bicavitary effusion increases mortaliy by…
3.3 fold
What are gastropexy options?
tube incisional, muscular flap, circumcostal belt loop
Post op GDV arrhythmia source?
poor myocardial perfusionelectrolyte disturbanceacidosisDICpainmyocardial depressant factor
Perioperative risk factors significantly associated with death before suture removal GDV.
hypotension at any point during hospitalizationcombined splenectomy and partial gastrectomyperitonitissepsisDIC
In the cat, mean serum:abd fluid creatinine and K for diagnosis of uroabd.
creat 1:2K 1:1.9
In the dog, serum:abd fluid creatinine and K for diagnosis of uroabd.
creat 1:2 (86% sensitive, 100% specific)K 1:1.4 (100% sensitive and specific)
Bilirubin serum:abd fluid for diagnosis of bile peritonitis?
> 1:2
What is hypotensive resuscitaiton?
Mean 60, SBP 80 are goals to prevent excessive bleeding or diruption of clot fxn or formation
Most common cause of uroperitoneum in cat?
blunt trauma (60%) due to ruptured bladder (85%)
What is most common cause of bile peritonitis after blunt trauma?
Ductal rupture just distal to the last hepatic duct
Blind needle paracentesis may yield peritoneal fluid when _____ fluid present.
5.2-6.6 ml/kg
A peritoneal dialysis catheter used for abdominocentesis may detect presence of _____ abd fluid.
1-4.4 ml/kg
Indications for abdominocentesis.
- loss of serosal detail on rads2. abd injury w/o obvious peritoneal entry wound3. shock, multiple injuries, signs of abd injury blunt trauma4. head or spinal injury precluding abd exam5. persistent abd pain or fluid distension of unknown cause6. postop complications
What is a Cullen sign?
periumbilical ecchymosis (abd or retroperit bleeding)
Significant hemorrhage is present if the PCV of peritoneal fluid exceeds _____ from a DPL.
5%
Indications for peritoneal drainage.
Septic peritonitisBile peritonitisUroperitoneumPancreatitis-associated peritonitisPeritoneal dialysisIncreased IAHAbdominal pressure compromising ventilation or causing pain
What two H2RAs have gastric prokinetic effects?
ranitidine and nizatidineMOA: anticholinesterase activity
What’s special about cimetidine?
Inhibits hepatic P450 so can be used therapeutically (acetaminophen tox) or can delay metabolism of drugs
H2RA MOA
block H1 receptor on parietal cellscompetitive inhibitors
Rank potentcy of nizatidine, famotidine, ranitidine, cimetidine
famotidine > nizatidine > cimetidine = ranitidine
Which H2RA absorption is delayed by food?
cimetidine
Which H2RA has longest duration of action?
famotidine
Which H2RA does NOT undergo substantial first pass metabolism in liver?
nizatidine
Which H2RA is most bioavailable? least bioavailable?
MOST - nizatidineLEAST - famotidine
Which two H2RAs undergo extensive liver metabolism? Which two excreted unchanged in urine?
extensive metabolism: cimetidine, ranitidineexcreted unchanged in pee: famotidine, nizatidine
In what toxicity should cimetidine be considered for?
acetominophen - b/c cimetidine inhibits P450 markedly can lessen severity of acetominophen toxicityAlso decreases metabolism of other drugs (theophylline, lidocaine, metronidazole) - potentiating toxic effects of these meds
Cimetidine decreases hepatic blood flow by 40%. T/F
F - 20%
Side effects of H2RAs
CNS and cytopenias (only reported in humans)hemolytic anemia with famotidine (CATS)
PPI MOA
irreversibly inhibit H-K-ATPase on luminal side of parietal cell, thus stopping secretion of hydrogen ions into the gastric lumen
Why should omeprazole be given 1 h before feeding?
undergoes 1st pass metabolism and remainder sequestered in acidic environment of parietal cells, so if give after feeding, maximize acidity of parietal cell and therefore increasing amt omeprazole sequestered in cell
Side effects of PPIs
diarrhea (dogs), inhibits P450, elevations in liver enzymes, increased gastric pH can affect absorption of other meds (ketozonazole and digoxin)
Sulcralfate MOA
octasulfate of sucrose combined with Al-OH; in acidic environment binds to epithelial cells for 6 h, stimulates local production of prostaglandins and pinding to epidermal growth factor
Misoprostal MOA
PGE1 analog; antacid and mucosal protective properties (stimulates bicarb and mucus and increases gastric mucosal blood flow)Acts directly on parietal cells to inhibit both nocturnal acid secretion and secretions in response to food, histamine, pentagastrinfood delays absorption, short half life
Misoprostal side effects
diarrhea, uterine contractions
What are 3 promazine derivatives used for antiemetics?
chlorpromazine, prochlorpromazine, acepromazinemay cause hypotension d/t alpha1 adrenergic antagonism
Maropitant MOA
NK1 antagonist that blocks action of substance P in CNS and peripheral NK1 receptors in GI tract
What is aminopentamide? Who should not take this?
anticholinergic antiemetic, not very good, maybe acts on muscarinic receptorsContraindications with glaucoma, cardiomyopathy, tachycardia, hypertenion, MG, gastroesophageal reflux
Consequences of IAH
increased CVP, PAP, RAP, PCWP, MAP, SVRDecreased CO and urine outputIncreased lactateDecreased pulmonary complianceIncreased ICPDecreased hepatic, portal, intestinal and gastric blood flowIncreased ADH, renin, aldosterone (reverse when reduce pressure)
Renal effects of IAH
10-20 cm H20 decreases GFRoliguria and anuria at > 25 cm H20
Bacterial translocation to mesenteric LN reported with ACS pressures at…
34 cm H20
IAH assessment
0-10 = normal10-20 = mild increase, ensure p normovolemic and press on20-30 = moderate to severe IAH, volume resuscitation, diagnostics, consider decompression>35 = severe IAH, decompression necessary to reverse organ damage and prevent further deterioration, explore or tap
Enteropeptidase synthesized by…
duodenal enterocytes
Where do salmonella organisms colonize?
ileum, invade M cells w/i Peyer’s patches
What was always associated with failure to tolerate complete surgical attentuation of a CPSS, JAVMA, 2011, Lamb?
Ductular reaction w/o identifiable intrahepatic portal veins
Breeds with benign familiarl hyperphosphatemia
Siberian huskyScottish terrier
McCord, JVIM, 2012. Spec cPLI vs. SNAP cPL in dogs suspected of having acute panc. Findings?
SNAP: SN 90%, SP 70%Spec (>200): SN 90%, SP 75%Spec (>400): SN 75%, SP 85%Amylase: SN 55%, SP 75%Lipase: SN 50%, SP: 90%Negative result very likely to be accurate. Used to rule out panc.
Israeli, JVIM, 2012. Serum pepsinogen-A, canine PLI, CRP as prognostic markers in dogs with GDV. Findings:
cPG-A * higher in GDV dogs compared to controls. Median cPB-A higher in nonsurvivors, compared to survivors. cPG-A increased with gastric wall damage. cPG-A as predictor of death: AUC 0.75 (lactate AUC 0.66), SN 53%, SP 88%CRP increased 75%, cPLI 40%, but no assc’n with outcome
