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medsurg3
10/27/98

washabau

a few things....
remember the 
handout manual you got yesterday? he has some extras. if you need one, 
let dr washabau know.

regarding exam 2 for this class...and the 
scheduling thereof...omar is goign to discuss it with us later.


yesterday we discussed esophageal disease which we will now wrap up 


Gastroesophageal intussusception:

intussusception is  telescoping of 
distal segment into a more proximal segment. this is unlike hiatal 
hernia.  here, we have stomach going into the lumen of the esophagus. 
rare, but occurs in dogs and cats and is a life threatening emergency.


slide: older dog with regurgitation, salivation, acute loss of condition, 
and frank red blood regurgitation. he has acute gastroesophageal 
intussusception. we see on this VD rad, something in the caudal thorax 
that doesn't belong there. barium stops midthorax. we can't see normal 
gastric silhouette on this xray either. rugal folds of stomach are seen 
within esophagus.

this is urgent - you need emergency surgery.


endoscopic image: looking down toward LES, we see stomach lining poking  
up into esophageal lumen. this mild case might be reducible with 
endoscopic tip, just pushing it back down into abdomen as done in this 
case. more severe cases, this is not possible, esp if mucosa is 
devitalized and friable.

usually - laparotomy, reduction, stabilization 
by gastropexy.
it's clear, from retrospective studies,t hat dogs with 
megaesophagus have increased risk for this. most reports of this in fact 
are in dogs with megaesophagus. it's rare, but seems to occur more in 
these animals, perhaps b/c of increased compliance of dilated esophagus.


idiopathic megaesophagus: this is a common disorder. in most cases we do 
not know etiology/pathogenesis - some causes are known, though. this is a 
dilation, enlargement of esophagus; usually these animals also have 
hypomotility or dysmotility of esophagus. other names: achalasia 
(inability of LES to relax, causing dilation and loss of function 
proximal to that -  human condition, not documented in dogs and unlikely 
to occur in dogs)

signs usually: progressive regurgitation, some 
dysphagia, some salivation, good appetite. we think this is a 
degenerative neural condition,  not inflammatory, so no signs of 
esophagitis, usually - no odynophagia or anorexia. 

survey rads: ventral 
depression of major airway, dilation of esophagus.
VD view: more obvious 
- very wide esophagus - hugely dilated. in some animals, you see food or 
liquid in the esophagus on the radiograph. you could do some contrast 
studies but often do not have to.

quick discussion of cause: 
there are 
afferent and efferent pathways...
achalasia in humans - LES abnormality - 
hypertension of LES, failure to relax, causing obstruction, and 
dilation/loss of function proximally. not in dog/cat!
other things we see 
in dogs: 
one: motor end plate disease - myasthenia gravis - 
junctionopathy, if you will. dz of nicotinic, cholinergic receptors on 
skeletal  muscle. recall in dogs, esophagus is entirely skeletal muscle! 
dogs can have full expression of MG and classically will present with 
profound muscle weakness of all limbs. however, dogs can also express the 
disease differently - not like in people - but rather can manifest MG as 
a pure esophageal entity and present with megaesophagus, regurgitation, 
wt loss. up til about 8 yrs ago we didn't know that. now,, we know that 
about 25-35% of adult onset k9 megaesophagus are due to this form of MG. 


Diane Shelton did a study published in J.Vet.Intern.Med - on aquired MG 
with selective involvement of esophageal, pharyngeal and facial muscles. 
they assay for Ab and if dog has titer >0.6nM, it probably has disease. 
28% of dogs with megaesophagus they looked at had this focal MG. other 
places repeated the study. it is clear if you survey dogs presenting to 
you with adult onset MG, 25-35% of them have MG. you should always test 
megaesophagus dog cases for MG b/c you can treat it.

pathogenesis in 
brief: there is an Ab directed against certain epitopes of the nicotinic 
cholinergic receptor, so there is less receptor available for Ach 
binding, so muscle will fatigue early. animals can go into myasthenic 
crisis, with acute muscle failure.

we can dx and treat that - Dr 
Steinberg will discuss it later.

OK, fine. what about the other 65-75% 
of the dogs? well, possibly the rest of them havae some abnormality of 
sensory information processing, or transmission to brainstem, or some 
efferent transmission problem. 

suffice it to say - retrospective 
studies show that if you look at dogs with acquired MG and perform 
risk-factor analysis - MG increases risk tremendously (for 
megaesophagus). there is also increased risk for laryngeal paralysis ad 
other peripheral neuropathies. so perhaps another subset of animals do 
not have motor end plate disease, but some abnonrmality in innervation - 
sensing, transmission, whatever. that's what this suggests. 

if you go 
on to read about this...it has been stated that hypothyroidism is a known 
cause of k9 megaesophagus. this study was unable to show hypothyroidism 
conferring risk. Dr Washabau says hypothyroidism may be a caause, but it 
can't be an important one. It can't be a major cause. 

summary:
1. 
myasthenia gravis is a major cause - 25-35% - can treat medically with 
cholinesterase inhibitors like pyridostigmine to increase available ACH. 

2. >70% have other causes
3. risk factors include breed, laryngeal 
paralysis, esophagitis, GDV, other neuropathies. we think it is a problem 
with the afferent pathway
4. medical therapy not feasible for those dogs


we try then to convert them to vertical esophagus. make them stand up to 
eat, feed from elevated counter. use gravity to get food to stomach. that 
often helps but these animals have repeated aspiration pneumonias, and 
have nutritional problems.so we still say the prognosis is guarded. there 
is a great need to further characterize the pathogenesis of this.


megaesophagus in the cat: remember cats have proximal esophageal body of 
striated  muscle, and distal esophgus is smooth muscle. cats can get 
esophageal MG, but only proximal segment is affected. there are a few 
case reports of cats with proximal megaesophagus due to MG in cats. we 
also do see esophagitis in cats, and if severe, distal part of esophagus 
may dilate. 
even more rarely cats may have complete esophageal dilation, 
pathogenesis unknown. much bigger problem in dogs.

moving on into the 
stomach...

gastric/small intestinal disease:
read the notes in the 
handout 

when you are in practice, owner will come in and say "my dog is 
vomiting" not "my dog might have histoplasmic gastroenteritis..." so you 
have to assimilate these notes in the handout and use them to address 
problems.

Vomiting: we talked about neuroanatomic pathways annd 
pharmacology of this last year - please revisit it. now, we will consider 
how to tackle the chronic vomiting patient.

what do you do? well, take a 
good history, and do a detailed PE.
those two things are always first. 


after that, consider some diagnostic tests. CBC/chem/UA, perhaps 
amylase/lipase/trypsinogen assays and fecal exam (even if no diarrhea, 
b/c some gastric parasitic infections do  occur. read about them in the 
handout! dr. littman's notes..)

so initial workup includes some labwork. 
fecal can be parasitologic exam, might aso include bacterial culture for 
salmonella, campy, etc. more important in animal with diarrhea (culture)


might consider some imaging studies: survey rads still have a place in 
dx. these rads may show a foreign body, a mass, a displaced organ - or 
they may appear normal, requiring further imaging studies with contrast. 
barium study may reveal other things like gastric outlet obstruction. 


we might use endoscopy if we suspect upper GI problems. contrast studies 
are best for obstructive diseases. upper GI endoscopy is not entirely 
routine, because we can't really do it on light sedation like they do in 
people - you hve to anesthetise the animal for endoscopy. this exam may 
reveal esophagitis, gastritis, gastric neoplasia - you can take biopsies 
and wait for histologic diagnosis. or study may be unrevealinng, and 
maybe you will do exploratory surgery.

exploratory surgery will be 
discussed by holt/brockman

hopefully you end up with definitive dx and 
specific therapy can be prescribed.  
some differences b/w dog/cat: 
dog 
can get addison's disease - and present with GI signs - v/d, etc. we may 
or may not see abnormalities on bloodwork. so we maay consider adrenal 
function test like ACTH stimulation test as well. 
tickborne diseases can 
cause vomiting - mostly in dogs - rocky mountain spotted fever, for 
example - hard to dx and vomiting may be the main  sign. 

there are a 
lot of reasons for vomiting in animals. we could go through a list but it 
is not worth it. 

another thing: if this is a cat - aged cat with 
vomiting might have hyperthyroidism, so check T4. heartworm in cats may 
cause vomiting. Dr Washabau doesn't think most cats with vomiting should 
be checked for HW though. be aware of this, though.

vomiting in cats 
(chronic) - etiologies:

Inflammatory Bowel Disease: 45%
heptobiliary dz: 
21%
chronic recurrent pncreatitis: 18%
GI malignancy: 8%
GI obstruction: 
5%
other: 3%

this is pretty important stuff to realize. 
it will help 
you to shape your workup.

what tests do you do? well, half the cats have 
IBD - so what tests will you want to do? CSF tap? no. Urinary contrast 
study? no. 

endoscopy: 95% specificity, 85% sensitivity
radiography: 77% 
specificity, 32% sensitivity
u/s: 85% specificity, crappy sensitivity

so 
endoscopy is good!
slide: survey rad of cat with IBD - looks normal

slide: endoscopy - proximal small intestine of the cat showing loss of 
normal, velvety appearannce - looks nodular.

pancreatitis:
rads: 100% 
specificity, 5% sensitivity
u/s: 91% specificity, 79% sensitivity

so if 
you suspect pancreatitis, you'd choose u/s

radiographic changes in dogs 
with pancreatitis - 3 or 4 major findings - pncreas is in upper right 
quadrant. when inflamed, we  see right duodenal displacement to llateral 
wall, mass effect in right upper quadrant, left gastric displacement, and 
the inflammation by direct extension can produce colitis - we may see 
gas/fluid in ascending/transverse colon. these findings are consistent 
with acute pancreatitis in dog, but not  pathognomonic or definitive. if 
history/PE /lab data fit and you find these findings, you can feel pretty 
confident with your dx, in dog. 

these findings do not hold up well in 
the cat.

u/s in cat - we put the probe on abdomen, and we see spleen, 
pancreas, kidney, etc. if there is art to radiology....you start to see 
these changes over time. this scan is normal - if pancreas in health 
llooks like this - of similar echodensity to spleen - then with necrosis, 
inflammation, edema, we see there are hypoechoic changes to pancreas. 
pancreas looks blacker than spleen.

hepatobiliary disease:
rads: 83% 
specifcty, 47% sensitivity
u/s 85% specificity, 81% sensitivity

cauases 
of hepatobilliary dz in cats:
cholangitis/cholangiohepatitis
hepatic 
lipidosis (starvation and mobilization of fat)
hepatobiliary neoplasia

--those are major ones
pyogranulomatous hepatitis
portosystemic shunts

--those are sometimes seen

u/s is better imaging study than radiography 
for this.
liver will have been infiltrated by lipid in cases of hepatic 
lipidosis, conferring hyperechoic changes to it as compared to falciform 
fat. if there are hyperechoic changes like this it is likely due to lipid 
infiltration.

GI malignancy/obstruction:
rads and u/s both pretty good 
for this.
can detect masses

summary for cats with vomiting:
half have 
IBD (about half) - best test  = endoscopy
HBD/pancreatitis - best test is 
u/s
85% of cases due to IBD/HBD or pancreatitis so those tests are best

malignancy/obstructionn - rads or u/s
exploratory sx - < 10% IBD, >50% 
HBD

vomiting in dogs: etiologies:

IBD 32%
pancreatitis 30%
GI 
malignancy: 18%
HBD (hepatobiliary dz): 10%
GI obstruction 7%
other 3%


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so...

garden variety gastritis/gastric erosion

see dr 
littman's notes!!! read them!!!

quickly - here is a dog who has been 
given ibuprofen by the owner for a few days. came in to ES with gastric 
hemorrhage, cardiac arrest. had some big gastric ulcers. both dogs and 
cats are at risk for this following NSAID use. this is important. you see 
this hopefully less and less often these days with the development of 
some newer drugs that are COX2 inhibitors instead of COX1 inhibitors. 
COX1 allows production of cytoprotective prostaglandins; COX2 is the 
inducible inflammatory mediator.

some COX2 inhibitors are on the mrket 
now but they are not that specific yet.

NSAID induced ulcers are caused 
by inhibition of production of prostaglndins needed for epithelial 
renewal, blood flow, bicarb secretion, mucus production and secretion. 


other causes of gastric ulcer - do occur - many causes are outlined in 
the notes, be aware of them. some infectious diseases, metabolic diseases 
(addisons), hypergastrinemic states, mast cell tumors with 
hyperhistaminemia stimulating increased acid production.

dx/tx 
straightforward
1. dietary management - CHO rich diet
2. antacids
3. 
diffusion barrier
4. anticholinergics
5. histamine receptor antagonists

6. gastrin receptor antagonists
7. H+, K+ ATPase antagonists
8. 
prostaglandins (misoprostol)

all of these have a place in tx of 
gastritis, erosions, ulcers in companion animals. 

other causes - 
bacterial infection, mast cell dz, hypergastrinemic states are main 
causes of gastric ulcers in addition to NSAIDS

Other gastric dzs:

cat 
with vomiting - on survey rads we see something in the stomach - it is a 
hairball. we pulled this out endoscopically. this is an  example of 
obstructive disease. 

slide: older cat with chronic vomiting/wt loss/not 
feeling so well. VD rad - stomach is full of air and a soft tissue 
density structure at the lesser curvature. on endoscopy, fairly prominent 
gastritis was evident - polypoid type. FIP was the culprit. 
polypoid/granulomatous changes in stomach were present. tx: 
antiinflammatory doses of glucocorticoids are the best we can do. this 
animal transiently improved but then relapsed.

another cat with chronic 
progressive vomiting - similar radiograph - something is mostly in the 
distal stomach, involving lesser and greater curvature. this was a large 
tumor, a bit pedunculated, on bx was carcinoma. surgical resection was 
attempted but failed. tumor recurred. 

slide: radiograph with a lot of 
bones in a stomach! this is another example of obstructive gastric 
disease. 

with obstructive gastric diseases, you should not be reaching 
for prokinetic drugs! you could cause perforation. 

slide: hugely 
dilated stomach - no volvulus. severe gastric distension in young chinese 
shar pei. some shar peis have hiatal hernias, others have functional 
gastric emptying disorders. some functional motility disorders are seen 
in vet med - not associated with obstruction. here you could use a 
prokinetic drug. 

some emptying disorders may be associated with chronic 
bacterial infection, or be see post-GDV recovery. so there are mechanical 
disorders impeding gastric emptying - those you have to treat 
specifically; and there are functional disorders of perhaps smooth muscle 
or neural function...and this is when you reach for a prokinetic agent to 
facilitate emptying.

key things - 
when you see gastric motility 
disorders, try to figure out is it mechanical or functional? if 
mechanical - polyp, tumor, foreign body - dx and treat specifically with 
surgery or chemo or whatever. if functional problem, may be due to 
infection, inflammation, or idiopathic. abx treat infxn, antiinflammatory 
drugs for inflammation...then if it turns out to be idiopathic, you can 
try the dietary management option - low fat/low protein diet with neutral 
pH, low osmolality, liquid consistency will promote gastric emptying - 
so, boil some rice, mix with water, blend it up. if there is no 
improvement then you can go on to prokinetic therapy - cisapride, 
erythromycin, ranitidinne or nizatidine. cisapride is a 5HT4 agonist 
(serotinergic agonist). if animal fails cisapride therapy, could try 
erythromycin. this is an antibiotic of the macrolide type. it has the 
side effect of nausea and vomiting at therapeutic doses. this is because 
of the effect on gastric emptying it has via the motilin receptor. 
erythromycin at therapeutic doses stimulates motility and retrograde 
peristalsis, nausea and vomiting. at microbially ineffective doses - 
0.5-1 mg/kg, this drug is an effective prokinetic agent, useful to tx 
vomiting disorders in the dog. not so much in the cat, though.
third 
choice - ranitidine or nizatidine - we talked about these as drugs that 
inhibit the histamine H2 receptor - inhibit gastric acid secretion - they 
also have been shown to have a side effect of inhibition of ACHesterase. 
this allows accumulation of ACH in vicinity of smooth muscle cells. they 
are also concentrated in GI tissue. so they stimulate gastric/colonic 
smooth muscle action. so these would be a third choice.

take home 
points:
we do see animals with emptying disorders. rule out mechanical 
obstruction first. if it is functional, tx any inflammation or infection, 
then try dietary therapy, then prokinetic therapy

a few words on 
helicobacter gastritis in dogs/cats - fact or fiction? 
quick summary: 
probably occurs, but probably not as significant as in people. 


helicobacter organisms:
humans: h.pylori, h.felis, h.heilmannii
macaques: 
h.pylori
ferrets: h.mustelae (known serious pathogen in ferret)
cheetahs: 
h.felis, heilmannii, acinonyx (acinonyx important cheetah pathogen)

cats/dogs: h.heilmani, felis
cats: h.pylori
dogs: h.bizzozeronii

so cats 
and dogs can be experimentally infected with these organisms. in fact, 
four years ago, a lab animal medicine resident showed that cats with no 
GI disease purchased from a commercial vendor were in fact colonized with 
H. pylori. the MD gastroenterologists all jumped up and down and claimed 
that cats were the problem. 

note: prior to isolation of HIV, several 
veterinarians from Penn publicly stated that FeLV could possibly be the 
cause of AIDS. hmmm. 

however, four years down the road, there are good 
studies that show that veterinarians have no increased risk for H.pylori 
infection - indicating, then, that people are probably not getting 
h.pylori from cats. 

h. mustelae is a cause of gastritis in ferrets - 
significant gastric pathology is associated with this infection. 


h.pylori in cats - no signs, but they did have lymphoplasmacytic 
gastritis on histological exam. 

more recent studies - there is no good 
evidence for a relationship b/w infection, clinical signs, and 
histopathology in dogs with helicobacter. in cats, there is. more studies 
are ongoing, but it seems some cases of gastritis in cats are associated 
with some types of helicobacter infection. on EM, these look like big 
dill pickles with flagellae on the end, by the way :)
histopath: lymphoid 
proliferation, infiltration of lymphs and plasma cells. 

dx of 
helicobacter gastritis:
history and PE consistent - vomiting is major 
sign
endoscopic exam - characterize changes, get biopsy
serology

histopath - H&E, warthin-starry staainn

slide: endoscopic view of marked 
gastritis in cat, associated w/helicobacter. resolved with abx therapy. 
do not think this is a major or common cause of gastritis in the cat! 
some studies suggest it is an entity but it probably isn't that 
important. 

incidence of helicobacter in cats: many studies have been 
done to look at this -  cats from vendors, cats at shelters, etc.  up to 
80-90% of cats have some colonization by helicobacter organisms. that 
doesn't mean infection, though. 
most of these cats have no signs or 
histopathological changes. 

intestinal disease:
case:
boring workup

culminated in endoscopy which revealed inflammation and loss of villus 
integrity. 
biopsy revealed replacement of normal architecture with 
lymphosarcomatous lymphocytes. 

LSA is a cause of diarrhea in the cat


read Dr Littman's notes on causes of diarrhea.

specific therapies for 
diarrhea:
1. dietary manipulation: tx food allergy, etc
2. abx: tx campy, 
salmonella enteritis
3. antivirals: not used much - viral enteritis 
usually self limiting
4. parasiticides: anthelmintics, antiprotozoals
5. 
antifungals: tx histoplasma enterocolitis (MO river valley)
6. pancreatic 
enzymes: tx exocrine pancreatic insufficiency
7. chemotherapy - tx 
intestinal LSA, etc
8. anti-thyroid - tx hyperthyroidism

point here is, 
dx disease and then treat that disease.

now do not panic but...
we are 
going to skip the slide that is supposed to show some nonspecific 
antidiarrheal meds to use for an animal with small intestinal diarrhea. 
we'll do that in clinical pharm in the spring if you take that.

small 
intestine motility disorders:

mechanical obstruction
pseudo obstruction 
(functional problem)
inflammatory bowel disease

examples of SI motility 
disorders:
slide: aged cat with severe  progressive vomiting. gassy 
distension of small bowel visible on lat abd rad; also C-shapes 
indicating some plication of bowel, as if there were obstruction - 
suggests linear foreign body like string. contrast study shows 
gassy/liquid distension and plication. linear fb removed via enterotomy


another mechanical obstructionn - middle aged cat has something 
obstructing midjejunum - loss of detail, sense of mass effect in 
midabdomen.  u/s of same animal - midjejunal intussusception. prokinetic 
therapy = bad idea. needs surgery.

slide: severe obstruction - not 
mechanical. this is severe functional obstruction in puppy with 
parvovirus. parvoviral enteritis causes a purely functional obstruction 
due to infection/inflammation affecting the muscle function. can be hard 
to sort out - sometimes causes us to take animal to surgery and this is 
not  a good idea in a debilitated animal esp if you can't help! this is 
functional obstruction.


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