Gastrointestinal Flashcards
1
Q
What is the definition of an endocrine hormone?
A
Released into the bloodstream and travels to a distant site
2
Q
What is the definition of a paracrine hormone?
A
Diffuses only short distances through the extracellular space. Acts LOCALLY
3
Q
What is the definition of an autocrine hormone?
A
Subset of paracrine but acts on same cell that produces it
4
Q
What is the definition of a neurocrine hormone?
A
Released from nerve endings, diffuses short distances through extracellular space
5
Q
What are the enteroendocrine cells?
A
“Taste buds” of the gut
Scattered throughout the mucosal layer of the gut
LARGEST endocrine organ in the body
6
Q
Is the parasympathetic or sympathetic nervous system stimulatory to the GIT for digestion?
A
Parasympathetic stimulates digestion
“rest and digest”
7
Q
What nerves innervate the upper and lower GIT in the parasympathetic portion of the extrinsic nervous sytem?
A
Vagus nerve - upper GIT
Pelvic nerve - lower GIT
8
Q
What is the neurotransmitter of the parasympathetic system?
A
Acetylcholine
9
Q
What neuropeptides are released by the parasympathetic system in the GIT?
A
Substance P
Vasoactive intestinal peptide (VIP)
Neuropeptide Y (NPY)
10
Q
What percentage of the nerve fibers in the vagus nerve are afferent vs. efferent?
A
75% afferent
25% efferent
11
Q
Most of the sympathetic action of the GIT in the extrinsic nervous system comes from what nerves?
A
Spinal segments of T1 to L3
50/50 afferent to efferent
Norepinephrine is the neurotransmitter
12
Q
What are the two main components of the enteric nervous system of the GIT and what are their functions?
A
Myenteric plexus - movements
Submucosal plexus - secretion and local blood flow
13
Q
What glands are found in the body of the stomach? What cells are found in these glands and what do they secrete?
A
Oxyntic glands - secrete a number of hormones.
Parietal cells - secrete HCl
Enterochromaffin-like cells - secrete histamine
D cells - secrete somatostatin
Chief cells - secrete pepsinogen
14
Q
What glands are found in the antrum of the stomach? What cells are found in these glands and what do they secrete?
A
Pyloric glands - less hormone secretion than in the body
G cells - secrete gastrin
D cells - secrete somatostatin
15
Q
What three major stimuli cause release of gastrin?
A
Stretch - causes vagal stimulation which releases bombesin
Peptides
Amino acids
16
Q
Stretch in the stomach causes stimulation of what nerves and results in what effects?
A
Stretch signal received by nerves of the gastric mucosa which are part of the parasympathetic system –> release ACh which acts on G cells to release gastrin
Stretch signal also stimulates vagus nerve –> release of gastrin-releasing peptide (bombesin) from vagus nerve –> stimulates G cell to release gastrin
17
Q
What two amino acids are the major stimulators of gastrin release?
A
Phenylalanine
Tryptophan
18
Q
What cells does gastrin act on?
A
Parietal cells
Enterochromaffin like cells
19
Q
Does gastrin act in an endocrine, paracrine, or neurocrine manner?
A
endocrine - after release, enters the bloodstream, goes through portal vein, then goes through liver and are circulated back to the body of the stomach
20
Q
__ is secreted by enterochromaffin like cells (ECLs) and acts in what manner (endocrine, paracrine, or neurocrine manner) and in what cells?
A
Histamine
Paracrine - acts on parietal cells within the oxyntic glands where the ECLs are located
21
Q
Tubulo-vesicles within parietal cells have what receptors?
A
H/K/ATPases
22
Q
What three receptors are found on pareital cells and what are the three secretagogues that bind them to activate the parietal cells?
A
M3 receptor: muscarinic receptor that binds ACh (which comes from vagal input)
H2 receptor: binds histamine
CCK-B: gastrin
23
Q
M3 receptors on parietal cells bind __ which causes increases in __ inside the cell for activation.
A
Bind ACh
Causes increases in calcium
24
Q
What two secretagogues that bind parietal cell receptors cause increases intracellular calcium levels?
A
ACh
Gastrin
25
CCK-B receptors on parietal cells bind __ which causes increases in __ inside the cell for activation.
Gastrin
Causes increases in calcium
26
H2 receptors on parietal cells bind __.
Histamine
27
Which receptor is the most potent stimulator of parietal cells?
H2 receptor
28
By what mechanism does histamine binding to H2 receptors activate parietal cells?
Causes increases in cAMP
29
After activation, what happens to the parietal cells?
They undergo conformation change. The luminal membranes become highly folded to increase surface area for proton pumps to have more access to the outside of secretion of HCl
30
Describe the steps of acid production in the proton pumps of parietal cells
Water cleaved to OH- and H+
H+ is exchanged for K+ (H+ goes out, K+ comes in) via H/K/ATPase pumps. H+ is secreted into lumen of canaliculus.
On the opposite side (membrane by interstitial fluid), Na/K/ATPase pumps exchange Na+ for K+ (Na+ goes out, K+ goes into cell). This contributes to passive excretion b/c of high intracellular gradient of K+, which allows for exchange with hydrogen.
Na+ will leak into cell from lumen of canaliculus which drives the Na/K/ATPase pump
Carbon dioxide that diffuses into the cell combines with the OH- ion to form bicarb (HCO3-)
BIcarb is exchanged for Cl- from the interstitial fluid. Chloride passively diffuses all the way through the parietal cell to the lumen of canaliculus
Finally, water passes through parietal cell to canaliculus.
31
What hormones inhibit acid secretion by parietal cells?
Secretin
CCK
Prostaglandins
Dopamine
Somatostatin
GIP
Peptide YY
Enteroglucagon
32
What is pepsinogen and where does it come from?
Precursor for pepsin, which is a protein digestive enzyme
Comes from chief cells
33
What two main stimulus cause release of pepsinogen?
ACh binding chief cells (from vagus nerve)
HCl secretion from parietal cells
34
Pepsin results in how much of total protein digestion?
10-20%
35
What stimulus tells D cells to release somatostatin?
Decrease in gastric pH (happens when food starts to leave the stomach --> parietal cells are still secreting acid but food is no longer there to buffer it so it creates a very acidic environment)
36
What is the paracrine action of somatostatin?
Inhibit gastrin secretion by G cells (this leads to decreased activation of ECL cells which in turn decreases activation of parietal cells leading to decreased acid production)
37
What is the endocrine action of somatostatin?
Decrease parietal cell acid secretion
38
What is the neurocrine action of somatostatin?
Decreases gastric motility
39
What are the phases of gastric secretion?
Cephalic phase - 30%
Gastric phase - 60%
Intestinal phase - 10%
40
What stimulates the cephalic phase of gastric secretion and what happens in this phase?
Stimulated by sight/smell of food
ACh release from Vagus n.
Gastrin release from G cell
Histamine release from ECL cells
41
What stimulates the gastric phase of gastric secretion and what happens in this phase?
Stimulated by gastric digestion and release of peptides, as well as stretch of the stomach
Gastrin is released by G cells
42
What stimulates the intestinal phase of gastric secretion and what happens in this phase?
Stimulated by gastric emptying
Causes decrease in intestinal and gastric antral pH --> mediated by release of somatostatin from D cells, release of secretin from S cells, and release of CCK from I cells
43
What is Zollinger-Ellison Syndrome (ZES) and what tumor type is it associated with?
Triad of Non-B-islet cell tumor of pancreas, hypergastrinemia, and refractory peptic ulcer disease
Can be sporadic and a genetically linked form, sporadic more common
Gastrinomas
44
What is MEN-1?
Rare heritable disorder in people characterized by predisposition to tumors of the parathyroid gland, anterior pituitary gland, and pancreatic islet cells
45
What PANCREATIC cell types transform to form gastrinomas in dogs and cats?
Delta cells
46
Gastrinomas cause excessive release of __.
Gastrin
47
What changes to the GIT result from excessive release of gastrin in cases of gastrinomas?
Esophageal and gastroduodenal erosins and ulcerations
Enzymatic maldigestion
Gastric antral hypertrophy (b/c gastrin stimulates growth of these cells) --> results in delayed gastric emptying and possible gastric outflow obstruction
48
What are the two most common clinical signs associated with gastrinomas?
Vomiting
Weight loss
49
How do we diagnose a gastrinoma in veterinary medicine?
Measure fasting serum gastrin
If >3x reference range (often will be at least 10x reference range)
Remember gastrin levels may be transiently normal so you may need to retest
50
What drugs can be used to treat gastrinomas?
Somastostatin analogs
51
What is an example of a somatostatin analog?
Ocretotide
52
What does ocretoide do?
Inhibits gastric acid release form parietal cells
Inhibits gastrin release from G cells
Decreases tumor load in gastrinomas
Reduces ECL cell hyperplasia
53
What two hormones in the stomach are involved in control of hunger?
Grehlin
Leptin
54
__ increases hunger and __ stimulates satiety/decreases hunger
Grehlin increases hunger
Leptin stimulates satiety
55
Where is the majority of ghrelin produced? What are other minor sites that produce ghrelin?
Major source= stomach, specifically from the oxyntic glands
Also intestine, pancreas, hypothalamus
56
What stimulates ghrelin release?
FASTING
57
What are the actions of ghrelin?
Acts on pituitary to stimulate growth hormone secretion
Stimulates appetite, body growth, and fat deposition
Decreases production of pro-inflammatory cytokines (like NFkB) and increases production of anti-inflammatory cytokines (like IL-10)
Increases rate of gastric emptying (which may be helpful in post-op ileus)
58
What is an example of a ghrelin agonist?
Capromorelin (Entyce in dogs/Elura in cats)
59
Capromorelin is though to help with lean muscle mass due to effects on what two substances?
Growth hormone
IGF-1 concentrations
Transient increases in GH and sustained increase in IGF-1 concentrations has been documented in healthy adult beagles. Concern theoretically that it may lead to insulin resistance, so use caution in diabetics
60
What cells secrete leptin?
Adiopocytes
61
What is the stimulus for leptin scretion?
Increased adipose tissue
62
What are actions of leptin?
Decrease production of appetite stimulators in hypothalamus (neuropeptide Y, Agouti-related protein)
Activation of POMC neurons (alpha-melanocyte-stimulating hormone which increases activation of melanocortin receptors)
Increases sympatetic activity which leads to increased metabolic rate and increased energy expenditure
Decreased insulin secretion
Increased TNF-alpha productions and macrophage activation—> makes inflammatory conditions worse
63
What cells of the duodenum secrete secretin?
S cells
S cells are also found in the jejunum
64
What stimulates release of secretin?
Low duodenal pH
Intraduodenal lipid
Aka chyme entering duodenum
65
Secretin acts in an edocrine/paracrine/autocrine function
Endocrine - enters bloodstream and travels to stomach to act on parietal cells
66
What are the actions of secretion?
Inhibit acid secretion by inhibition of parietal cells
Slows gastric emptying
Secretion of HCO3- rich pancreatic fluid
67
Cholecystokinin (CCK) is released from what cells of the duodenum?
I cells
I cells are also found in the jejunal mucosa
68
What stimulates CCK release?
Intraduodenal FAs, amino acids, and H+ ions
Usually driven by amino acids
69
Does CCK act in an endocrine/paracrine/neurocrine manner?
Endocrine
70
What organs does CCK act on?
Pancreas
Gallbladder
71
What are the actions of CCK in the pancreas?
Potentiates secretin
Pancreatic enzyme secretion - acts on acinar cells
Stimulation of pancreatic growth
72
What are the actions of CCK in the gallbladder?
Gall bladder contraction
Relaxation of sphincter of Oddi
73
What two cell types are found in the exocrine pancreas?
Acinar cells
Ductal cells
74
Which pancreatic digestive enzymes are secreted by acinar cells?
Which are secreted in their active form?
Amylase
Lipase
Trypsinogen
Amylase and lipase secreted in active form
75
What enzyme converts trypsinogen to trypsin?
Enterokinase - this is a brush border enzyme
76
What stimulates acinar cells to secrete digestive enzymes?
CCK
ACh
77
Amylase digests what?
Starch
78
Lipase hydrolyzes what?
Triglycerides
79
What stimulates ductal cells to release bicarb and water?
Secretin
80
What are the three phases of pancreatic secretion?
Cephalic - 20%
Gastric - 5-10%
Intestinal - 70-75%
81
What do bile acids do?
Help emulsify large fat particles of food to smaller particles that can be digested by lipase enzymes
82
In the duodenum, bile acids are ionized to form __, which prevents their reabsorption from the small intestine.
Bile salts
83
In the ileum, bile acids are deconjugated into what?
Secondary bile acids
84
What are the two most common secondary bile acids?
Deoxycholic acid
Lithocholic acid
85
Can secondary bile acids be reabsorbed from the distal ileum?
Yes - this is enterohepatic recirculation
86
What percentage of bile acids are reabsorbed for enterohepatic recirculation and what percentage are excreted?
95% reabsorbed
5% secreted
87
In the liver, what amino acid are bile acids conjugated to?
Taurine (main in dogs, only one in cats)
Glycine to a lesser extent in dogs (not in cats)
88
What is an incretin?
A hormone that stimulates pancreatic insulin release
89
What cells in the duodenum produce GIP?
K cells
90
What stimulates release of GIP?
Intraduodenal FA and AAs, and to a lesser degree carbohydrates
91
Does GIP act in endocrine/paracrine/neurocrine function?
Endocrine - travels via blood to act on parietal cells and pancreatic Beta cells)
92
What are the actions of GIP?
Inhibition of gastric acid secretion (acts on parietal cells)
Stimulation of pancreatic insulin release during hyperglycemia
93
Other than GIP, what is the other main incretin?
Enteroglucagon/Glucagon-like peptide-1 (GLP-1)
94
Where is GLP-1 produced?
L cells of the ileum and colon (widely distributed throughout the gut in cats)
95
What is the stimulus for GLP-1 release?
Intraluminal glucose and lipids
96
What are the actions of GLP-1?
Inhibit gastric acid secretion
Acts on pancreatic islet (Beta) cells to stimulate insulin secretion
Acts as the "ileal brake" - when there are FAs in the ileum it will act on the stomach to inhibit gastric emptying
97
What effects on pancreatic Beta cells do GLP-1 and GIP have?
- Stimulation of insulin biosynthesis --> replenishment of stores
- Stimulation of Beta cell proliferation
- Promotion of Beta cell resistance to apoptosis
- Enhanced Beta cell survival
98
GLP-1 inhibits __ secretion by alpha cells in the pancreas
Glucagon
99
What enzyme inhibits GLP-1?
DPP-4
100
Cats lack what receptor that causes sweet compounds to taste bitter?
TiR2
101
Where is peptide YY produced?
distal ileum and colon
102
What stimulus causes peptide YY release?
Fatty acids
To a lesser degree carbohydrates
103
What are the actions of peptide YY?
Ileal brake
Inhibition of CCK and secretin
Proliferation of gut mucosa
Slows gastric emptying
Peptide YY is also known as GLP-2
104
What is the MOA of dirlotapide/Slentrol
A microsomal membrane transfer protein (MTP) inhibitor --> results in increased peptide YY secretion and GLP-1 secretion in rats
Utilized for weight loss in dogs
105
What is the gastrocolic reflex?
Distention of the stomach leads to activation of the colon resulting in defecation
106
What are the two general types of movement that are involved in GI motility?
Segmentation
Peristalsis
107
What is segmentation and what does it cause GI contents to do?
The random contraction of circular muscles
Mixes food with digestive enzymes and brings nutriends in contact with absorptive surfaces. Also slows transit time
108
What is peristalsis and what does it cause GI contents to do?
Short wave of constriction moving abnorally over a short segment of intestine
Moves contents aborally
109
Craniual contraction in peristalsis is regulated by what two things?
ACh
Substance P
110
Caudal relaxation in peristalsis is regulated by what two things?
Vasoactive intestinal peptide (VIP)
Nitric oxide
111
What are the two periods of motility?
Fasting motility (interdigestive period)
Fed motility (digestive period)
112
What part of the gastric nervous system regulates fasting motility?
Enteric nervous system
113
What part of the gastric nervous system regulates fed motility?
Vagus coordination with enteric nervous system
114
What is the migrating motility complex?
"housekeeper" that clears gut of undigested residue and prevents bacterial overgrwoth
Happens every 90 minuts
115
What species DO NOT have the MMC? (but have somthing sijmilar)
Cats
Rabbits
116
What do cats and rabbits have in place of MMC?
Migrating spike complex
117
Where does the MMC start?
Stomach
118
T/F: The MMC includes the gallbladder
True
119
What are the three phases of MMC?
Phase 1 - quiescence - slow waves that don't progress to threshold so no contraction
Phase 2 - Intermittent contractions that gradually increase in frequency and amplitude - similar to that with feeding
Phase 3 - intense propulsive motility - happens every 4-8mins - initiated by motilin
120
Where is motilin produced?
M cells in the stomach, small intestine, and colon
121
What stimulates motilin release?
H+ and lipid in the fed state
Episodically released into serum during fasting
122
In what state is motilin most important?
Fasting (interdigestive) state
123
What is the action of motilin?
Initiate phase 3 of the MMC
124
What drug mimics motilin?
Erythromycin and other macrolide-like antibiotics
125
5-hydroxytryptamine is also known as what?
Serotonin
126
Where is serotonin produced?
Enterochromaffin cells and enteric neurons throughout the GIT
127
What are the actions of serotonin in the GIT?
Stimulates gastrointestinal smooth muscle contraction
Intestinal electrolyte secretion
128
5-HT4 agonists include what?
Metoclopramide (also a dopaminergic D2 antagonist)
Cisapride
Tegaserod
129
What is the MOA of 5-HT4 receptor agonists?
Bind 5-HT4 receptors on enteric cholinergic neurons causing depolarization and contraction of GI smooth muscle
130
Cisapride stimulates distal esophageal peristalsis in what species and why?
Cat, human, Guinea pig
NOT DOG
b/c these species have a distal esophageal muscularis composed of smooth muscle
131
What are intestinal carcinoids?
Tumors of endocrine cells of the GIT. They contain secretory granules that contain serotonin, secretin, somatostatin, and gastrin
Can also present in tracheobronchial tree, pancreas, and genitourinary system
132
What is the most common form of gastritis in dogs?
Mild to moderate lymphoplasmacytic gastritis with lymphoid follicle hyperplasia
133
What parasites are associated with parasitic gastritis in dogs and cats?
Ollulanus tricuspis (cats)
Physaloptera
Gnathostoma (cats)
Spirocerca (dogs)
134
What fungal organism causes granulomatous gastritis?
Pythium
135
What is the treatment and prognosis for pythium?
Itraconazole and terbinafine
Poor prognosis
136
Gastric ulcers develop when __ and __ overcome the protective mechanisms of the mucosa
gastric acid and pepsin
137
What clin path abnormalities would you expect with gastric ulcers?
Microcytic hypochromic minimally regenerative anemia
Thrombocytosis
High BUN
138
What drug can be used to treat gastric ulcers?
Misoprostal
139
What is the MOA of misoprostal?
PGE2 analog
140
Pyloric perforation has been associated with what drugs?
NSAIDs
141
Helicobacter is a gram __, __ shaped bacteria
Gram negative
Spiral shaped
142
Helicobacter produce __ which results in production of ammonia and bicarbonate when in contact with __ in gastric juices
Urease
Urea
143
True/false: There is correlation between Helicobacter infections and gastritis/ulceration in cats and dogs.
FALSE
144
How is Helicobacter treated?
Triple therapy with amoxicillin, metronidazole, and omeprazole/famoitine
+/- bismuth subsalicylate
145
What is the most common gastric neoplasm in dogs and the most common in cats?
Dogs - gastric adenocarcinoma
Cats - lymphoma
146
Where does feline gastrointestinal eosinophilia sclerosing fibroblasia (FGESF) form lesions and in what breed and sex of cats is it most common?
Stomach, intestines, and regional LNs
Male rag doll cats
147
What is the treatment for FGESF?
Surgical excision
Immunosuppressive steroids, and antibiotics (to prevent translocation)
148
What might you see on histopath with FGESF?
Eosinophilic inflammation, large reactive fibroblasts, and dense collagen
+/- intralesional bacteria
149
Are adenomatous gastric polyps typically associated with malignant transformation?
No
150
What is the definition of the microbiome and metabolome?
Microbiome: collective genome of microorganisms inhabiting the body
Metabolome: complete set of metabolites produced by the body’s microbiota
151
What are the roles of the microbiota in the GIT?
Energy and nutrient production (synthesis of biotin, folate, vitK; metabolism of bile acids)
Intestinal wall health
Immune system regulation
Protection against pathogenic microbes
152
What happens to serum cobalamine and folate with dysbiosis?
Cobalamin decreases
Folate increases
153
What is the dysbiosis index?
QPCR based test that reflects the abundances of key bacterial taxa in a fecal sample; can be used to monitor dysbiosis over time and as fecal donor screening
154
What is SIBO?
Small intestinal bacterial overgrowth - describes the increased number of anaerobic bacteria in the proximal small intestine
155
What are the “good bacteria” in the GIT?
Lactobacillus
Bifidobacterium
Enterococcus
Faecalibacterium
156
What are the “bad bacteria” in the GIT?
Clostridium perfringens
Clostridium difficile
Salmonella
Campylobacter
157
Serum cobalamin is most useful to detect trouble where?
Distal small intestine
158
What are examples of dysbiosis-associated disease?
IBD
Acute gastroenteritis (AHDS)
Intestinal stasis
EPI
Motility disorders (mega colon)
Antibiotic therapy
159
What is a probiotic?
A living microorganism that upon ingestion in sufficient numbers impart health benefit beyond basic nutrition
160
What are the mechanisms by which probiotics work?
Displacement of pathogenic bacteria
Production of antimicrobial byproducts
Improvement in GIT barrier function
Improvement in micronutrient absorption
Modulation of the metric and innate immune responses
161
What is the definition of a prebiotic?
Non-digestible dietary carbohydrates that stimulate the growth and metabolism of endogenous enteric protective bacteria upon consumption
162
What are examples of prebiotics?
Psyllium
Insulin
Bran
163
What are the mechanisms by which prebiotics work?
Production of short-chain fatty acids (lactate, butyrate)
Reduced cytokine production by intestinal mucosa
164
What are some pathophysiologic mechanisms of intestinal disease?
Luminal disturbance
Brush border membrane disease
Micro villas membrane damage
Enterocyte dysfunction
Epithelial barrier disruption
Villus atrophy
Disordered motility
Mucosal inflammation
Hypersensitivity
Neoplasia
Nutrient delivery failure
Congenital abnormalities
165
What is the cardinal sign of SI dysfunction?
DIARRHEA - usually osmotic, malabsorptive
166
Borborygmi and flatulence are most commonly caused by
Swallowed air and bacterial fermentation
167
What are BIPS?
Barium-impregnated polyethylenes - radiopaque markers that provide info on gastric emptying, intestinal transit, and obstructive disorders (particularly partial obstruction)
168
What is AHDS/HGE and what causes it?
Acute hemorrhagic diarrhea syndrome/hemorrhagic gastroenteritis
Cause unknown, but thought to be due to Clostridium perfringens enterotoxin production (other considerations: dysbiosis, type I hypersensitivity)
169
What are some viral causes of small intestinal disease?
Parvovirus
Panleukopenia
FIP
FIV
FeLV
Distemper
170
What are some bacterial causes of small intestinal disease?
Enteroinvasive bacteria - campylobacter, salmonella, Ecoli
171
What GI parasites cause small intestinal disease?
Roundworm (Toxocara)
Strongyloides (also cause LI disease)
Hookworms (Ancylostoma)
Tapeworms (Dipylidium caninum)
172
What protozoa can cause small intestinal disease?
Isospora
Cryptosporidium
Giardia
173
What are the top 3 causes of a protein losing enteropathy?
Lymphangiectasia
IBD
Infiltrative lymphoma
174
What clin path abnormalities might you see with PLE?
Hypoproteinemia (usually albumin and globulin, but can see hyperglob in histo, severe IBD, LSA)
Hypocholesterolemia
Lymphopenia
Ionized hypocalcemia
Hypomagnesemia
Loss of fat soluble vitamins (ADEK)
175
Why are dogs with PLE are hypercoagulable?
They lose antithrombin
176
What breed is associated with immunoproliferative enteropathy?
Basenjis
177
What breed gets concurrent PLE and PLN?
Wheaten terriers
178
What are the goals of nutritional therapy in PLE?
High protein/aa (to replace what they are losing)
Low fat (they can’t absorb it)
Low fiber (b/c it impedes with nutritional digestion)
179
What are the different types of IBD and which is most common
In order of most common to least common:
Lymphoplasmacytic
Eosinophilic
Neutrophilia
Granulomatous
180
Neutrophilia IBD is associated with what bacteria?
Campylobacter
Salmonella
181
Eosinophilic IBD is most commonly associated with what two things?
Parasites
Food intolerance
182
IBD is classified clinically as
Food responsive
Antibiotic responsive
Steroid responsive
183
What is the pathophysiology of IBD?
Complex, but involves an overly aggressive cell-mediated response resulting from the loss of tolerance to antigens of the microbiome in susceptible hosts
184
Polymorphisms in what TLRs have been identified in IBD?
TLR 4 and TLR 5
185
Mutation in TLRs in IBD causes what effects?
The immune cells identify good commensal bacteria as pathogens and signal “danger” to the host, initiating an inflammatory response
186
What is fecal calprotectin?
Calcium binding protein that is highly abundant in neutrophils and has been shown to be increased in humans with IBD
187
What are negative prognostic indicators in IBD?
Hypoalbuminemia
Decreased cobalamin
Severe duodenal lesions
188
What is lymphangiectasia?
Loss of protein and lymphocytes via ruptured abnormal lacteals
Loss of lymphocytes leads to immunodeficiency, putting these patients at risk for inflammatory or neoplasticism disease
189
What is the difference between primary and secondary lymphangiectasia?
Primary - often congenital and limited to the intestines, but can be more widespread (ie chylothorax)
Secondary - caused by intestinal lymphatic obstruction (infiltration/obstruction of lymphatics by inflammation, fibrosis, neoplasia; obstruction of thoracic duct; right CHF)
190
What is sulfasalazine?
A pro-drug consisting of 5-amino salicylic acid
NSAID used for treatment of ulcerative colitis in people
191
What is the main adverse effect of sulfasalazine?
KCS
192
Granulomatous colitis is associated with what organism?
Intracellular E. coli most commonly
Can also be caused by strep, campylobacter, mycobacteria, histo, prototheca
193
What histopath findings might you see with granulomatous colitis?
Mucosal infiltration of macrophages with variable infiltrates of neutrophils, lymphocytes, and plasma cells
Used to be called histiocytic ulcerative colitis
194
What breeds of dog are associated with granulomatous colitis? What is the typical age of onset?
Boxers
Frenchies
<2y
195
How is granulomatous colitis treated?
Enrofloxacin for 12 weeks - although now there is developing resistance
196
What is tritricomonas?
A flagellate protozoan that causes persistent diarrhea in cats
Colonizes in the large intestine causing chronic colitis, anal irritation, and fecal incontinence
197
What are the three main types of mega colon in dogs?
Idiopathic
Neurologic
Orthopedic
198
What are the 2 pathologic methods through which megacolon can develop?
Dilation secondary to electrolyte abnormalities, neuromuscular disorders, or idiopathic
Hypertrophic - develops from obstructive lesions (pelvic fracture male ion, tumor, FB) - **this type is reversible**
199
What is the most common cause of megacolon in cats?
Obstipation
200
What is cricopharyngeal dyssynchrony?
A functional/pump problem (oropharyngeal dysphasia) where weak pharyngeal muscles are unable to propel a bonus through the upper esophageal sphincter
201
What is cricopharyngeal achalasia?
Structural problem (oropharyngeal dysphagia) where there is an inability of the cricopharyngeal muscle to open during the cricopharyngeal phase of swallowing
202
How is cricopharyngeal achalasia treated?
Surgery - myotomy/myectomy
OR
Injection of botulinum toxin into the muscle (weakens contraction of the muscle by blocking release of acetylcholine)
203
PPIs should be tapered over __ if used for __.
Tapered over 7-10d if used for >2 weeks
204
What GI condition is thought to maybe contribute to pulmonary fibrosis in Westies?
GERD - thought is chronic intermittent micro aspiration may cause pulmonary fibrosis
205
What is the most common cause of esophageal stricture in dogs?
Reflux during anesthesia
206
What drugs in cats can cause esophageal stricture?
Doxycycline
Clindamycin
207
Where to esophageal foreign bodies tend to lodge?
Points of minima distention like thoracic inlet, base of heart, diaphragmatic hiatus
208
What type of hiatal hernia is most common?
Sliding - esophagus, LES, and stomach all herniate through hiatus
209
What is a paraesophageal hiatal hernia?
When the esophagus and LES stay put while gastric fundus herniates through the hiatus alongside the esophagus
210
What is the most common cause of regurgitation in the dog?
Idiopathic megaesophagus
211
What causes primary megaesophagus?
A defect in affect vagaries signaling or of esophageal muscle
212
What are some causes for secondary (acquired) megaesophagus?
Neuromuscular - myasthenia gravis, dysautonomia, lar par, muscular dystrophy
Esophagitis
Toxicity - lead, organophosphate
Neoplasia - thyme a
Addison’s
Hypothyroidism
Obstruction
213
What are the two types of acquired esophageal diverticula and what causes each?
Traction diverticula - caused by periesophageal inflammation and fibrosis
Pulsion diverticula - caused by increased intraluminal pressure secondary to obstruction or altered motility
214
Esophageal fistulas usually communicate with what other structure?
Bronchus or trachea
215
What dog breed is predisposed to congenital esophageal strictures?
Cairn terries
216
What is Spirocerca lupi?
Esophageal worm
217
What does Spirocerca lupi cause
Granulomatous nodules in the caudal esophageal submucosa
These can undergo malignant transformation to osteosarcomas or fibrosarcomas
218
How is Spirocercosis treated
Macrocyclic lactones (ivermectin)
Non-neoplasticism nodules should regress with treatment
219
What is masticatory muscle myositis?
Autoimmune disease affecting temporal, masseter, and pterygoid muscles of the dog
220
Why are the temporal, masseter, and pterygoid muscles of the dog affected by MMM?
They possess 2M fibers (different from 2C fibers of other skeletal muscles)
221
How is MMM treated?
2M antibodies and/or muscle biopsies
222
What drugs can cause mild induction of ALT and ALP?
Phenobarbital
Corticosteroids
These don’t affect ALP in cats
223
Where are ALP and GGT found in the liver (cellular level)?
Hepatocyte canalicular membrane
ALP also on the luminal surface of biliary epithelial cells
224
Cells in which zone of hepatic blood supply are most susceptible to toxins?
Zone 1
225
Cells in which zone of hepatic blood supply are most susceptible to hypoxia injury?
Zone 3
226
Where does hepatic biotransformation occur in the liver? (Zone)
Zone 3 - closest to venules
227
The liver makes all coagulation factors except __
Factor VIII
228
What coagulation inhibitors does the liver produce?
Antithrombin
Antiplasmin
Plasminogen
Protein C
229
If you have a fasting hyperammonemia, what should your top ddx be?
PSS
230
What causes hepatic encephalopathy?
Hyperammonemia
231
Hepatic encephalopathy can occur in cats without shunting as a result of fasting. Why?
Cats can’t make arginine which is needed for the urea cycle. Deficiency of arginine causes inadequate detoxification of ammonia
232
What factors affect bile acids in normal animals?
Completeness of GB emptying
Rate of gastric emptying
GI transit rate
Efficiency of ideal bile acid reabsorption
Frequency of enterohepatic cycling
Inadequate fat/amino acid content of test meal (failed CCK release)
233
How much functional liver mass must be lost before seeing hypoglycemia?
>75%
234
How much functional liver mass must be lost before developing hypoalbuminemia?
70%
235
Bilirubinuria is always abnormal in what species?
Cats
Can be normal in dogs
236
What percent of liver FNAs agree diagnostically with biopsies?
30%
237
In cases of liver disease, what form of pred should be used?
PrednisOLONE (prednisone is metabolized to prednisolone in the liver)
238
What is the MOA of SAMe?
Precursor of glutathione (GSH; primary endogenous cellular antioxidant)
239
What is the MOA of silymarin
Strong free radical scavenger
240
What is the MOA of N-acetylcysteine
Stimulates GSH production, free radical scavenger, anti-inflammatory
241
What medications are used for copper hepatopathy treatment?
D-penicillamine (binds extracellular copper)
Zinc
Antioxidants
242
What is colchicine?
Antifibrotic agent that inhibits the microtubular apparatus (aka inhibits collagen deposition)
Also hepatoprotective and anti-inflammatory (inhibits WBC migration)
