GI - part 1
Terms
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- Mitochondrial damage
- cytochrome C release and caspase activation
- sinusaoidal endothelial cell apoptosis
- initial event in the ischemic reperfusion of liver - relevant in transplantation - cold storage and reperfusion - and graft survival
- stellate cells
- produce growth factors such as HGF and other cytokines
- NAFL seen in
- kwashiorkor, total parenteral nutrition, jejunal bypass
- ALT
- cytosol, liver, def of pyridoxine 5 phosphate results in reduces ALT in alcoholic liver disease
- AST
- cytosolic, mitochondrial, many organs
- alkaline phosphatase
- present in apical poles of hepatocytes and choliangoles and secreted in bile in large amounts, ATPase, marker of cholestasis
- liver synth clotting factors
-
I II V VII XI X
F P - causes of chirrosis
- wilson's, alpha-1 antitrypsin def, liver fluke (schistosoma), PBC, PSC, autoimmune
- features of chirrosis
- peptic ulcers, anemia, palmarerythema
- HCC development
- increasing ascites, change in color-bloody, alphafetoprotein levels increase, alkaline phosphatase increase, hypoglycemia
- acute viral hepatitis
-
lobulat dissaray, smudging of cell outline
balooning and acidiphillic hyaline bodies (councilman bodies)
areas of focal hepatic necrosis
lymphocytic parenchymal and portal inflammation
cholestasis
kupfercell and macrophage hypertrophy, hyperplasia
then, regeneration, binucleation of hepatocytes - acute viral hepatitis with submassive or massive necrosis
-
entire central and/or midzones necrotic (all involved in massive and marked collapse occurs)
bridging necrosis-to hepatic failure or chirrosis
when all lobules involved death is inevitable
inflamation with mononuclear cells, few neutrophils - HBV extrahepatic
- polyarteritis nodosum, membrano-proliferative glomerulonephritis
- HCV
-
itty bitty fat, germinal centers
(not with HBV) - PBC
-
AMA (against 2-oxo acid dehydrogenase complex, 2-oxo glutaric acid dehydrogenase complex, and pyruvate dehydrogenase complex)
gradual destruction of small bile ducts (ductopenia)
the retension of components of bile st sites proximal to the bile cannaliculous and associated lack of bile in the intestine are responsible for most of the symptoms
pruritis, fatiguability,jaundice,xanthomas, osteoperosis, osteomalacia, night blindness
increased alkaline phosphatase - PBC pathology
-
chronic non-supporative destructive cholangitis involving septal and iterlobular bile ducts
epithelioid granulomas containing cytotoxic T cells and inflammation in portal tracts realted to bile ducts
loss of ducts(ductopenia)
progression to billiary chirrosis 5-20yrs
increased risk of liver cancer - PSC
-
elevated serum alkaline phosphatase
inflammation,cholangitis, fibrosis, obliteration of intralobular and septal bile ducts,ductopenia, billiary chirrosis,cholestasis
risk of HCC and cholangiocarcinoma (free radical or inflammation) - Angiosarcoma
- (hemangiosarcoma) following vinyl chloride, thorotrast. Arsenic
- cytosolic ALDH
- ALDH1 - same in a races
- lipogranuloma
-
livercell breaks, realeses fat, histyocytes accumulate around fat
common in alcoholic liver - alcoholic hepatitis
- necrosis of liver cells in the pericentral lobule, mallory bodies, neutrophils, perivenular fibrosis
- complications of acute pancreatitis
-
hypotension, renal failure, respiratory failure
pancreatic necrosis, pancreatic abscess, pseudocyst, chronic pancreatitis, bacterial infections - chronic calicified pancreatitis
-
alcohol realted
characterized by intraductal stones and ductal injury, parenchymal fibrosis, protein plugs - chronic pancreatitis
- shrunken, hard, fibrotic, whitish, ducts have irregular calibers and may contain calliculi
- chronic pancreatitis complications
- pseudocyst, common bile duct obstruction, DM, steatorrhea, pancreatic cancer (slight)
- acute pancreatitis
-
swollen, edmatous, whitish yellow plaques on surface and in septa (fat necrosis), congestion , hemorrhage, inflammatory infiltrate
symptoms: abdominal pain, nausea, low grade fever, hypotension - acute pancreatitis diagnosis
- serum amylas x 3, trypsinogen-2, trypsynogen-2-alpha-1 antitrypsin complex
- benign pancreatic ductal tumors
-
serous cytadenoma
mucinous cystadenoma
intraductal papillary mucinous tumor - borderline pancreatic ductal tumors
-
solid pseudopapillary tumor
mucinous tumor with dysplasia
intraductal papillary mucinous tumor with dysplasia - malignant ductal tumors of the pancreas
- ductal adenocarcinoma and its variants
- molecular alterations in oancreatic cancer
-
oncogenes: ***K-ras, c-erbB-2
tumor supressor genes: p53, p16
growth factors:epidermal growth factor-r, TGF-alpha - pancreatic adenocarcinoma diagnostics
- carcinoembryonic antigen, CA19-9, imaging, ERCP
- intercalatedduct
- centroacinar cells
- intralobular duct
- low cuboidal cells
- interlobular duct
- cuboidal of low columnar
- main duct
- columnar with goblet
- reflux esophagitis findings
- erythema, edema , friability, erosions, leukoplakia, hyperemia, ulcers, basal cell hyperplasia, vascular congestion andextension of CT papilae almost to surface, esinophils, neutrophils
- autoimmune chronic gastritis
-
body and fundus
lymphocytes and plasma cells in the deep mucosaand pseudopyloric and intestinal metaplasia
Complications: 1)hyper plasia of gastrin producing cells and enterochromaffin like cells
2)development of carcinoid tumors
3)development of epithelial dysplasia followed by adenocarcinoma - diffuse antral chronic gastritis
-
antrum, H pyplori, lymphoid follicles
complications: 1)prepyloric and duodenal ulcers
2)gastric lymphoma
3)risk of gastric carcinoma is low - multifocal chronic atrophic gastritis
-
dietary and environmental risk factors, finland and japan, begins at incisura
complications:1)gastric ulcer
2)intestinal type of adenocarcinoma
3)lymphoma - noninflammatory pathogens
- vibrio cholerae, clostridium perfringens, s aureus, giardia, cryptosporidium
- inflammatory pathogens
- shigella, salmonella, campylobacter jejuni, yersinia entericolitica, clostridium difficile, entameba hystolitica
- most common bacterial cause of food born ilness in US
- campyplobacter
- most common viral cause of food born illness in US
- norwalk
- vibrios - general
- live in salt water, gram neg comma shaped rod, facultative anarobe, cholera, O1, O139
- vibrio determinants of pathogenicity
-
toxin co-regulated pilli TCP- binding to intestinal epi
cholera toxin CTX - A-B txin, encoded by a phage, A1 is an ATP ribosylating enzyme to increase cyclic AMP which increases chloride secretion and decreses sodium absorbtion - vibrio symptoms
- rice water stools
- vibrio labs
-
thiosulfate-citrate- bile salt-sucrose TCBS selective agar
oxidase pos (to diff from enterobacteriacaea) - ETEC
- heat labile (simmial to cholera A-B toxin) and stable toxin
- clostridium perfringens
-
anaerobic, gram pos, bacillus
from meat, poultry, legumes - bacillus cereus
-
gram pos rod
2 toxins:1)like LT 2)like staph causing vomiting from rice (heating issues) - staph
-
enterotoxins ABCDE
lasts 10 hrs
vomiting diarrhea - rotavirus
-
fever
immunoassay for anitgen in stool - norwalk
-
fecal oral
vomiting, diarrhea
incubation 18-72
low grade fever 50%
enzyme linked immunosorbent assays
lasts 24-48hrs - giardia
-
adheres to epi of SI and causes maladsorbtion
diahrrhea, flatulence, bloating, cramping
1-4 wks
repeat stool examination, enzyme immunoassay of parasite Ag - cryptospridium
-
fecal-oral
domestic animals
chronic malabsorbtion in immunocomp
acid-fast,direct imunoflourescence antibody staining - EHEC
-
bloody, crampy, no/low fever
HUS-no antibiotics
undercooked meat, unpasturized milk.juice - Shigella
-
enterobacteriacaea
fingers food flies feces fomites
only 200 needed
invade colonic mucosa
transcytose through M cells
type III secretion / Ipa
cell to cell
some sectrete shiga toxin - HUS
fever
stool culture
community acquired
water chlorination - campylobacter jejuni
-
curved gram neg rod (sea gull)
self limited
guillian barre - yersinia enterocolitica
-
gram neg rod, enterobacteriaceae
enlargement of mesenteric lymph nodes, possible bacteremia
survives well at 4 deg C
CIN agar cefsulodin irgasan novobiacin - clostridium difficile
-
toxin A - enterotoxin - diarrhea
toxin B - cytotoxin - kills cells
can lead to seriousPMC pseudomembranous colitis
tissue culture assay detects toxin B, now immunoassays detect both - entamoeba histolytica
-
trophozoites and cysts
releases pore-forming toxin that lyses cells and leads to flask-shaped ulcers
visualize in stool, Ag in stool, Ab in serum - histamine on heart
-
H1 slows conduction in AV node
H2 increases rate and force of cardiac contraction - urticaria pigmentosa
- disease - huge number of mast cells in skin
- chlorpheniramine
-
otc anti-allergy,cold tablets
(anticholinergic effect of drying up secretions-block muscarinic receptors) - diphenhydramine
-
for sleep
for insect bites, poison ivy, and othermild allergic rxns
anticholinergic/muscarinic - dimenhydrinate
-
dramamine
central anti-ACh - hydroxyzine
-
opioid plus antihistamine
with morphine as pre-op
reduces anxiety and emesis from opiates
atropine-like actions - astemizole
- 2nd generation,minimal sedative effects but arrythmias
- terfenadine
- 2nd generation,minimal sedative effects but arrythmias
- loratadine
-
2nd gen
rapid onset
no arrythmias
recemic mixture
nives, itching, and allergic rhinitis - desloratadine
-
single isomer of loratadine
(2nd gen
rapid onset
no arrythmias
recemic mixture
nives, itching, and allergic rhinitis) - fexofenadine
-
2nd generation
terfenadine derivative
w/o cardiac effects - cetirizine
- 2nd generation
- cimetidine
-
cns effects w/ renal or hepatic disturbance
anti-androgenic
hyperprolactinemic - ranitidine
-
5-10 time more potent than cimetidine
lower affinity for p450
infrequent CNS effects
reverses anti-androgenic effects - famotidine
-
4-5 times more potent than
no side effects
less expensive
one a day - H1 works through
- phospholipase C
- H2 works through
- adenylyl cyclase
- doxepin
-
tricyclic anti depressant
acts as combined H1 H2 blocker - esophageal spasm
-
usually retains primary parastaltic waves
non-parastaltic high amplitude prolonged contractions with chest pain
corkscrew eophagus
dysphagia for solids and liquids - olgive's syndrome
-
acute colinic pseudoobstruction
marked colonic dilation in absence of obstruction
post operative
parasympathetic underactivity, sympathetic over activity, metabolic disturbances and opiate effects - granulaoma
- collection of epitheliod cells
- crypt abscess
- collection of neutrophils in lumen of gland
- what is absorbed in the proximal SI
- iron, calcium, vitamins, and fat
- what is absorbed in the midinterstin
- carbs and AA
- what is absorbed in the terminal illeum
- bile acid and B12
- normal height of SI villous
- 3 x that of crypt
- hahartomas
-
tumor-like malformations
abnormal mixture and overgrowth of tissues
eg. peutz-jegher - peutz-jegher
-
dominant
intestinal polyposis and mucocutaneous melanin pigmentation
lobulated,pedunculated polyps in GI,esp small bowel
branching smooth muscle covered by epi w/ a lamina propria
paneth cells and endocrine cells at base of crypts
diorganized, hyperplastic mucosal glands, containging absorbtive, mucous and paneth cells
possible hmmorhage, intussusception or malignancy - whipples
-
migratory polyarthragia, steattorhea, wasting, diarrhea
immune def. host allows bacteria to enter body through SI
mitral and aortic valve, CNS, mesenteric lymph nodes, lungs, kidney
intestine:dialated, thick ,rigid
mesentary: thickened
villous atrophy
macrophages in lamina propria containing acid-schiff staining bacilli - celiacs 100% soecificity
- antiendomysial antibodies
- complications of celiacs
-
lymphomas and adenocarcinomas
ulcerative jejunoileitis - carcinoids
-
appendix and rectum-usually singular
small bowel-multiple
insulartrabecular and microacinar patterna
tumor cells are small and uniform w/ round nuclei and granular esinophillic cytoplasm
prognosis: size, depth, location - cacinoid syndroms
- carcinoid syndrome ,gastrinoma syndrome (zollinger ellison), somatostatinoma syndrome, cushings sydrome
- carcinoid syndrome
-
carcinoid cells take up large amounts of dietary tryptophan and convert it to seritonin
flushing, athsma attackish, diarrhea, R sided hear failure due to stenosis of tricuspid and pulmonary valves
occasionally peptic ulcers and malabsorbtion
classically midgut - chron's
-
sarcoid type granulaomas
transmural inflammation
apthous ulcers
thickened bowel wall
amyloidosis
ankylosing spondylitis
polyarthritis
adenocarcinoma - appendicitis
-
leukocytosis
left shoft of neutrophils in blood
complications: thrombophlebitis, fistula to intestine or bladder