GI Ettinger Flashcards

1
Q

Which cell in the stomach makes intrinsic factor?

A

Parietal cells

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2
Q

What are the 3 major components of acid secretion?

A

Histamine, Gastrin, ACh

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3
Q

Which hormone is responsible for decreasing gastrin, histamine, and acid secretion when stomach pH

A

Somatostatin

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4
Q

What are the components of the gastric mucosal barrier?

A
§ Tightly opposed epithelial cells
				§ Bicarbonate rich mucous
				§ Abundant mucosal blood supply
				§ Prostaglandins (PGE2) are important in modulating
					· Blood flow
					· Bicarbonate secretion
					· Epithelial cell renewal
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5
Q

What factors slow emptying of stomach?

A

Carbs, AA, fats

Release of CCK in response to FA and AA

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6
Q

What are the 3 major digestive enzymes in the stomach?

A
Pepsin (releases as pepsinogen in response to ACh and histamine)
Gastric lipase (in response to pentagastrin, histamine, PGE2, and secretin, active in SI)
Intrinsic factor (dogs)
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7
Q

Which breeds get hypertrophic gastropathy?

A

Basenji, small breed dogs (shih Tzu)

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8
Q

Which breed gets atophic gastritis?

A

Lundehund

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9
Q

What can stoamtocytosis tell you on a CBC?

A

Stomatocytosis has been described in Drentse Patrijshond dogs with familial stomatocytosis-hypertrophic gastritis

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10
Q

What are causes of metabolic alkalosis?

A

· Metabolic alkalosis
o Associated with pyloric/duodenal outflow obstruction
o Associated with parvo and pancreatitis
o Gastrinomas
§ Also associated with aciduria
§ hypoCl/K due to gastric acid hypersecretion

Conservation of volume at expense of pH (renal reabsorb HCO3 and exchange Na for H+ = promotes acidic urine (paradoxical aciduria)

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11
Q

What breed when given IV secretin will have a high gastrin level w/o a gastrinoma?

A

Basenjis (with enteropathies)

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12
Q

What gastric tumors are found in these locations? Pyloric antrum, cardia, diffuse

A
§ Pyloric antrum
					· Adenocarcinoma (lesser curvature also)
				§ Cardia
					· Leiomyoma
				§ Diffuse
					· LSA
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13
Q

What is the most common site of an adenomatous polyp?

A

Pyloric antrum

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14
Q

Which breeds are predisposed to PLE?

A

SCWT, Yorkie, Basenji, Lundehund, Shar-Pei

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15
Q

What AA def can results in high ammonia in cats?

A

Arginine def

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16
Q

Which coag factor is NOT made by the liver?

A

Factor VIII

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17
Q

What defines DIC?

A
Prolonged PT/PTT
Decreases fibrinogen
thrombocytopenia
increased FDPs
(all of which can be seen with liver dz too)
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18
Q

What is the most toxic bile acid?

A

Lithocholic acid

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19
Q

How can diuretics exacerbate HE?

A

Alkalosis and HypoK!!!

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20
Q

What tropic factors are important for hepatic growth?

A

Insulin and Glucagon (from portal blood)

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21
Q

What is the toxin in cycad?

A

Cycasin (converted to MAM (methylazoxymethanol) by GI microbes) and unnamed neuro toxin

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22
Q

What is the MOA of cycad toxin?

A

Cycasin: MAM results in GI, hepatotoxin, neurotoxin

MAM alkylates DNA/RNA

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23
Q

What are the target organs of cycad toxin?

A

Cycasin: LIVER, GI, Neuro

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24
Q

What is the clinical presentation of cycad toxin?

A

Cycasin: within 24 hrs (GI signs and neuro signs)

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25
What are the main clin path signs of cycad toxin?
50-60% increased transaminases 30-50% increased bili 50% increased PT/PTT 30% decreased platelets
26
What are the histopath features of cycad toxin?
Cycasin: MIXED Acute: Centrilobular necrosis and neutrophilic inflammation Chronic: LP inflammation, fibrosis, biliary hyperplasia
27
What is the definitive test for cycad toxin?
None, hx of eating plant = Look for plant in vomit
28
What antidotes are recommended for cycad toxin?
Charcoal! Shown to be protective!!!!
29
What is the prognosis for cycad toxin?
Cycasin: Guarded - 30-50% mortality
30
What are the known prognostic indicators for cycad toxin?
Higher ALT, T bili, lower albumin (at presentation), prolonged coag = NONSURVIVORS Early charcoal admin was PROTECTIVE!!
31
What is the toxin in amanita?
Alpha-amanitin (1 cap can kill!)
32
What is the MOA of amanita?
Alpha-amanitin: Inhibits RNA polymerase II (no transcription or protein synthesis) Apoptosis of hepatocytes Insulin Release
33
What are the target tissues of amanita?
LIVER Intestines (crypts) Kidneys (prox tubules)
34
What is the onset of CS with amanita?
GI phase: 6-12 hrs - Severe gastroenteritis Recovery: 12-24 hrs HEPATIC FAILURE: 36-48 hrs Fulminate liver and kidney failure
35
What are the clin path changes with amanita?
Hypoglycemia (releases insulin) Coagulopathy Azotemia Increased AST, ALT, ALP, bili
36
What are the histopath findings with amanita?
Pan-lobular hepatocellular necrosis | Acute tubular necrosis
37
How do you make a definitive diagnosis of amanita?
LC/MS or ELISA for alpha-amanitin (toxin) Early in urine or in vomit (also see mushrooms) Later kidney or liver
38
What is the antidote for amanita?
Silibinin has helped!!! | Charcoal (if early)
39
What is the prognosis for amanita in dogs?
Poor | 50% mortality in dogs
40
What is the toxin in cyanobacteria?
Microcysts aeruginosa (blue green algae) = Microcystins
41
What is the MOA in cyanobacteria toxin?
Microcystins: Inhibit serine-threonine phosphatases = Build up of phosphorylated proteins = Necrosis = Apoptosis = Massive HEMORRHAGE
42
What are the target organs of cyanobacteria?
Microcystins: Liver, Kidney (prox tub) and Neuro (anabaena)
43
What is the presentations of cyanobacteria?
Microcystins: ACUTE (hours) - GI, respiratory, liver, tremors, seizures, comas
44
What are the clin path findings with cyanobacteria?
Increased ALP, GGT, bili | Marked increased in ALT (can be less if microcystoin inhibits tansminase synthesis??)
45
What is the histopath finding for cyanobacteria?
Hepatic necrosis - MASSIVE hemorrhage Acute renal tubular necrosis
46
How is a definitive diagnosis of cyanobacteria made?
ELISA (confirmed with LC/MS) or MMPB method to detect all forms of toxin) Best in vomit!!!, can check water source too Liver (toxin level)
47
What is the antidote for cyanobacteria?
NONE | Rifampin in mice/rats can inhibit uptake
48
What is the prognosis for cyanobacteria?
GRAVE
49
What is the toxin with aflatoxin?
Aspergillus = Aflatoxin B1 converted to AFB1 8,9 epoxide | esp dogs and poultry
50
What is the MOA of aflatoxin?
P450 converts to AFB1 8,9 epoxide Inhibits RNA polymerase Bind to mitochondrial DNA Depletes GSH
51
What are the target tissues of aflatoxin?
Liver | Kidney (prox tubules) - CASTS before azotemia
52
What is the CS onset of aflatoxin?
Highly variable, most are chronic (>1 month of eating food)
53
What are the clin path findings with aflatoxin?
Increased LEs, icterus, low cholesterol, decreased AT and protein C
54
What are the histopath findings with aflatoxin?
Acute: Centrilobular necrosis ****Diffuse hepatocyte lipid vacuolization**** Chronic: MIXED
55
How do you make a definitive diagnosis of aflatoxin?
ELISA, HPLC, LC/MS for toxin AFB1 in food source (>60 ppb) Serum, liver, urine = Alfatoxin M1
56
What is the antidote for aflatoxin?
``` Replenish GSH (N-acetylcysteine or SAMe) Sulfhydryl groups may bind AFB1 8,9 epoxide too ```
57
What is the prognosis for aflatoxin?
Guarded, 60% mortality
58
What are the prognostic indicators for aflatoxin?
100% predictive of death = CASTS Longer PT/PTT, decreased AT, decreased protein C, increased bili, decreased albumin and cholesterol = Risk factors for mortality
59
What is the MOA of xylitol?
Rapid, severe increased in insulin from Beta cells (6X more than glucose)!! Hepatic depletion of ALP (from metabolism via pentose phosphate pathway)
60
What are the target organs of xylitol?
``` LIVER (>0.5 g/kg) Beta cells (>0.1 g/kg) ```
61
What are the clinical presentation with xylitol?
30 min-1 hrs - Hypoglycemia | 9-72 hrs = Acute hepatic failure
62
What are the clin path findings with xylitol?
Marked increased ALT, bili Hypoglycemia Coagulopathy HypoK, HypoPhos
63
What is the histopath findings with xylitol?
Periacinar-mid zonal necrosis
64
What is the definitive diagnosis of xylitol?
HX, no tests for it
65
What is the antidote for xylitol?
Early emesis, SAMe, dextrose ****Charcoal DOES NOT bind it****
66
What is the prognosis for xylitol?
Good if early, guarded if prolonged hypoglycemia and LEs increased
67
What is a prognostic indicator for xylitol?
Hyperphosphatemia - Poor prognosis
68
What is the MOA of carprofen?
Idiosyncratic cytotoxic hepatocellular reaction (maybe IM) - Labs?
69
What are the target organs for carprofen?
LIVER, kidney, GIT
70
What breed is susceptible to carprofen tox?
Labs
71
What is the onset of carprofen tox?
VARIABLE - 5-30 days (longer onset in labs)
72
What are the clin findings in carprofen tox?
Increased ALT and bili | 2/3 = Proteinuria, glucouria, and granular casts!!!
73
What is the histopath of carprofen tox?
MIXED (necrosis and inflammation)
74
What is the antidote for carprofen tox?
STOP carprofen!!
75
What is the prognosis for carprofen tox?
Good, 100% labs recover | Only 50% in other breeds
76
Does the dose and duration of carprofen predict the prognosis?
NO!!
77
What is the toxin in diazepam?
Oral dosing in cats - converted to "reactive metabolite" of unknown structure = Idiosyncratic
78
What is the target tissue for oral diazepam in cats?
LIVER
79
What is the onset of CS in diazepam liver failure in cats?
Within first 7 days after oral dosing
80
What are the clin path findings with diazepam in cats?
Relative decrease in glucose, marked increase ALT>>>>>>ALP, prolonged PT/PTT Increased CK
81
What is the histopath with oral diazepam in cats?
Centrilobular necrosis (MASSIVE!)
82
What is the antidote for oral diazepam in cats?
STOP diazepam | Silymarin within 24 hrs, SAMe and N-Acetylcystein worked in one cat
83
What is the prognosis for oral diazepam liver failure in cats?
GRAVE - MOST died within 1-5 days of onset of CS!!!!
84
What are two complications of gastrinomas?
Acid hypersecretion = GI bleeding | Gastric mucosal hyperplasia - Outflow obstructions
85
What are the stimulation test for gastrinomas?
Secretin stimulation and Ca stimulation to increased gastrin
86
What are the tx for gastrinomas?
1. Sx 2. Octerotide 2. Antacids
87
What are risk factors for pancreatitis?
1. Dietary indiscretion (high fat) 2. Hyperlipidemia (Min Schnauzer) 3. Hereditary (SPINK1 Mini Schnauzer) 4. Drugs (azathioprine, KBR, vincristine) 5. HyperCa 6. Endocrine dz (HypoT4, HAC, DM - weak associations) 7. Sx manipulation and trauma 8. Infections (B. canis rossi) 9. Autoimmune 10. Neoplasia
88
Can steroids result in pancreatitis?
NO! Can increased lipase (some dogs) w/o pncreatitis
89
What are the 4 safegaurds within pancreas?
1. Zymogens (inactive) 2. Zymogens granules are separate from lysosomes (physically) 3. Pancreatic Secretory Trypsin Inhibitor (PSTI) - immediate inhibition of trypsin 4. Larger antiproteases in circulation (alpha 2 macroglobulin)
90
What is the process of acute pancreatitis?
1. Apical Block: Zymogens are not secreted 2. Colocalization of zymogens and proteases (overwhelm pancreatitic secretory trypsin inhibitor = Phospholipase A2, elastase, chymotryspin, lipase) 3. Recruitment of neutrophils and ROS production 4. Change in pancreatic circulation = vasconstriction 5. Activation of complement and change in permeability 6. Cytokine Storm!!! End result = Massive inflammation
91
What % of dogs with pancreatitis have amylase and lipase within RR?
About 50% | Can be increased in 50% dogs that do NOT have pancreatitis too
92
What is the most sensitive and specific test for pancreatitis?
cPLI Spec cPL SNAP cPL (good to exclude pancreatitis, so if normal NOT pancreatitis; abnormal SNAP may not be pancreatisi check Spec cPL)
93
What are potential complications with pancreatitis?
Pancreatitic cytokines = Systemic effects 1. AKI 2. DIC 3. Cardiac arrhythmias 4. ALI (neutrophilic inflammation) 5. EPI 6. Pseudocytes 7. Pancreatitic encephalopathy (dog) 8. MODS 9. SIRS 10. Chronic relapsing pancreatitis
94
What is the principle behind use of plasma in pancreatitis cases?
More alpha 2 macrolobulin (protease) BUT there is no proof in vet med that it is of benefit
95
What protease inhibitor has shown some benefit in pancreatitis?
Aprotinin
96
Which anti-emetic may be benefit in pancreatitis since inflammed pancreas can secrete substance P?
Maropitant
97
Is there a benefit of ABX with pancreatitis?
None seen with cochrane review
98
What are tx for chronic pancreatitis?
``` Seen in Mini Schanzuers Spec cPL >400 + waxing adn waning CS (every few days) Ultra low fat diet (RC GI low fat) Hypoallergenic diet Prednisone (14 days with taper) Cyclosporine ```
99
Why should you not used TLI to dx pancreasitis?
Lacks sens for pancreatitis | Can increased with renal failure!
100
What are not useful tests to dx pancreatitis?
``` Amylase/Lipase Trypsinogen Activation Peptide (TAP) Trypsin alpha1 proteinase inhibitor Alpha 2 macroglobulin CRP ```
101
How long can the PLI remain elevated after pancreatitis?
10-12 days
102
Can PLI predict severity on histopath of pancreatitis?
NO!
103
What are the ranges of PLI for pancreatitis?
DOGS >400 | CATS >5.4
104
Is the PLI affected by renal failure?
NO! | But TLI is affected by renal failure
105
What are the two main forms of EPI?
``` Acinar atropy (GSD, collies) - Endocrine functional Chronic pancreatits = Atrophy and fibrosis (all parts of endocrine lacking too) ```
106
Which single pancreatic enzyme def has been reported in dogs?
Lack of pancreatic lipase (will have normal TLI, but CS of EPI)
107
Are there markers of progression in EPI?
NO! Can be subclinical for years | Early immunosuppression is NOT recommended
108
What is the diagnostics of choice for EPI?
TLI Low
109
Can fecal pancreatitic elastase be used to dx EPI?
Yes, but need to verify with cTLI | Since false + 23% (low elastase and normal cTLI)
110
What % EPI dogs have Vit B 12 def?
About 82%
111
What is a potential complication of EPI?
Mesentric torsion!
112
What is associated with a shorter survival in EPI dogs?
Concurrent Vit B12 defs (need to check B12 in every patient with EPI)
113
What % EPI dogs have poor response?
About 20%
114
What are potential reasons for treatment failure in EPI dogs?
1. IBD, DM, SIBO - Need to tx | 2. Need PPI - To prevent pancreatic enzymes from being destroyed
115
What is a complication with pancreatitic extract in EPI dogs?
Oral bleeding (need to reduce dose and wet it)
116
Why can GI disease result in high false + fecal pancreatitic elastase-1?
Due to high neutrophil elastase
117
What are 3 reasons to have a normal TLI with EPI?
1. Pancreatic duct obstruction 2. Congenital def intestinal enteropeptidase 3. Selective pancreatic enzyme def (NOT trypsin)
118
Is EPI inherited in GSD?
Based on test mating - NO!
119
What are 6 options for pancreatic dz in cats?
1. Acute necrotizing panceratitis 2. Acute suupurative panc (Neutrophils = Younger cats) 3. Chronic panc (lymphocytic inflammation and fibrosis) 4. Panc Neoplasia (adenocarc - ductal) 5. Pancreatic Nodular Hyperplasia (unknown significance) 6. EPI?? (mainly from chronic panc, can occur with flukes too - Eurytrema procyonis)
120
What are risk factors for panc in cats?
1. Concurrent biliary dz (cholangitis) 2. Concurrent GI disease (IBD) - Direct communication from bile duct to pancreatic duct - Reflux 3. Ischemia 4. Infeciton (toxo, FHV-1, FIP, Eurytrema, Amphimerus, virulent calici) 5. Pancreatic Obstructions (neoplasia, fluke, stone) 6. Trauma (high rise) 7. Organophosphates 8. Lipodystrophy 9. HyperCa (exp) 10. Nutrition = UNDERWEIGHT cats
121
What is a common electrolyte abnormality in cats with AP?
HypoCa - 65% - Worse prognosis (more common than in dogs)
122
What are 4 complications of AP in cats?
1. Chronic panc 2. EPI 3. Hepatic Lipidosis ****even worse if together*** 4. DM
123
Why are H2 and H1 blockers recommended in feline panc?
Histamine and bradykinin induced vascular permeability can be blocked to prevent hemorrhage and necrosis
124
Which test has been validated in cats for AP?
fPLI
125
What are pulmonary manifestations of GERD?
From chronic microaspiration events 1. Aspiration pneumonia 2. Chronic Bronchitis 3. Interstitial Pulmonary Fibrosis
126
What is the tx for Spirocerca?
Doramectin
127
What are the 3 defensive lines to prevent epithelial damage?
1. Mucus and Bicarbonate Barrier 2. Epithelial cell mechanisms; barrier function of apical plasma membrane, intrinsic cell defenses 3. Blood flow mediated removal of back diffused H and energy supply If all FAIL = Epithelial Cell Injury!!
128
What are the effects of NSAIDs on mucosa?
1. Direct effect (uncoupling mitochondria) 2. COX 1 inhibition: Neutrophil activation and ROS 3. COX 2 inhibition: Neutrophil activation and ROS; Also inhibits GF production and impairs repair
129
What is the stomach worm in cats?
Ollulanus tricuspids Ingesting cat vomit Tx: Fenbendazole
130
What is a stomach worm in dogs/cats? Where is it from?
Physalloptera; Ingestion of cockroach/beetle (IH) or lizards | Tx: Pyrantel
131
What is the recommend tx for Helicobacter?
Amoxicillin, Clarithromycin, and omeprazole for 3 weeks
132
What is the tx for Campylobacter?
Fluoroquinolones
133
Which hookworm can result in pedal pruritus in greyhounds?
Uncinaria stenocephala
134
What is a treatment for round worms?
Fenbendazole
135
What is a tx for hookworms?
Pyrantel
136
What is a tx for tapeworms?
Praziquantel and flea control
137
An increase in which TRL is seen with IBD?
TLR2 | Also 4, 9
138
Does clinical improvement with IBD mean that there is histopath improvement?
NO!
139
What are the 5 steps of cobalamin absorption?
1. Cobalamin released from food in stomach 2. Binds to cobalamin binding protein (Haptocorrin - from salivary and gastric source) 3. In duodenum: Haptocorrin degraded (by pancreatic proteases) and Cobalamin binds to intrinsic factor (pancreas and stomach in dog and ONLY pancreas in cats) 4. Cobalamin-IF binds to receptors (cubilin) in microvillus 5. Cobalamin transcytose portal blood bound to tanscobalamin 2 - mediated absoprtion by target cells Can undergo enterohepatic recirculation with haptocorrin in bile
140
In which breed can you see Vit 12 def (cubilin defects)?
Border Collies Giant Schnauzer Beagles Aust Shap
141
Name several compounds that are associated with hepatic encephalopathy?
``` Ammonia Tryptophan Glutamine Aromatic AA/Branch Chained AA SCFA GABA Endogenous benzodiazepines Bile Acids Phenol Flase neutrotransmitters ```
142
What are the proposed mechanisms of how ursodeoxycholic acid works?
1. Replace more hydrophobic hepatotoxic bile acids in circulation 2. Induced choleresis 3. Stabilization of mitochondrial function (preventing apoptosis) 4. Immunomodulation (increased glutathione, decreased Ig from B cells, activate GC receptors)
143
Which breed gets lobular dissecting hepatitis?
Standard Poodles
144
Where is copper location in inherited copper storage dz?
Centrolobular
145
Where is copper located if you have secondary copper accumulation?
Periportal
146
What is the mutation seen in Bedlington terriers with copper hepatopathy?
COMMD1 or MURR1
147
What is the tx for copper hepatopathy?
Low copper diets 1. Penicillamine (which increased metallothionein that binds copper) - Trientine is another option 2. Zinc (increased metallothionein in enterocytes to prevent copper uptake, lost with enterocyte)
148
What is zone 3 necroinflammatory hepatitis?
Associated with IBD and see in Maltese ASCITES!!! Portal Hypertension Inflammation veno-occlusive dz (lymphs and eosins around hepatic v.)
149
What is noncirrhotic portal hypertension?
Portal v hypoplasia with portal hypertension Seen in Dobies, Rotties, and Cockers Have abdominal effusion with acquired shunts
150
What is portal v. hypoplasia?
MIcroscopic malformation in hepatic microvascular Thought to nonprogressive Can be asymptomatic increased bile acids with normal Protein C, CBC, chem, AUS, scinitgraphy Can be seen with macroscopic PSS too
151
Why do PSS get microcytosis?
iron transport defect
152
What % of shunty dogs can have normal bile acids?
21%
153
How can Protein C help with PSS vs Portal v hypoplasia?
Low with PSS | Normal (>70%) in MVD
154
Does hepatic bx allow for discrimination btwn PSS and protal v. hypoplasia?
NO!
155
How does portal hypertesion lead to ascites?
Progressive splanchnic dilation - Peripheral vasodilation Compensatory hyperdynamic changes (increased CO), compensatory failure, increased circulating volume RAAS activation and ADH release = Na and Water retenion = Ascites
156
What are precipitating factors of HE?
Increased production of ammonia in GIT (high protein meal, GI bleeding) Increased systemic generation of ammonia (blood transfusion, poor quality protein) Factors affecting uptake and metabolism of ammonia in CNS (metabolic alkalosis, hypoK, hypoglycemia, inflammation, infections, sedation/anesthesia)
157
What is a major complication of feline PSS correction?
75% neurologic complications = Central blindness
158
What is the lesion in neutrophilic cholangitis in cats? Signalment, tx
Neutrophils in bile ducts and epithelium Acute and chronic forms - Ill cats Associated with pancreatitis, IBD, triaditis Tx: ABX
159
What is the lesion in lymphcytic cholangitis in cats?
Small lymphocytes in portal area, portal fibrosis, biliary duct proliferation Not always ill but have jaundice, ASCITES, increased globulins TX: Steroids
160
What is the cat live fluck?
Platynosum | Tx: Praziquantel
161
What is lymphocytic portal hepatitis?
Nonspecific thought to be an aging change | Older cats
162
What has been identified as a mutation in Shelties with GB mucoceles?
ABCB4 transport mutation (phospholipid transporter)
163
Dog with what disease are 29X more likely to develop a GB mucocele?
HAC
164
Does biliary rupture and bile peritonitis have prognostic factor?
NO!!
165
What is the progression with complete occlusion of the CBD?
24 hrs = GB distension 48-72 hrs = Extrahepatic bile duct distension 5-7 days = Intrahepatic ductal dilation
166
What is hepatic lipidosis?
Enhanced mobilization of peripheral fat to lover and impaired dissemination of lipid from hepatocytes = Severe hepatic dysfunction
167
Do all cats with HE have increased ammonia?
NO!! Ptyalism could be from HE
168
What was associated with worse survival in Hepatic lipidosis?
HypoK Advanced age Decreased PCV
169
What are the mainstays in Tx of hepatic lipidosis?
1. Feeding!!! High quality protein!!! 2. B vitamins (B1 and B12) 3. Fat soluble vits (E and K1) 4. Amino Acids = L-carnitine and taurine 5. Antioxidants = SAME and ursodiol 6. electrolytes: HypoK and HypoMg
170
Which breed gets idiosyncratic hepatotoxicty to sulfas?
Dobies!!