1

195........................ 199..................................................IBD 201.................................Liver tumors- clinics 205...........................Liver tumors- pathology 208.... 211... -

2................................. 10....................... 14..........................Gastrointestinal histology 18............................................... 23..........................Gastrointestinal radiology 27................................... 34................................... 38...............................................GI bleeding 46............ 53............................... GI bacterial infections 61...........................................................IBS 66................................................Bile stones , * 71................................ Inflammatory conditions of the bowel74.................................................pathology 77........ 83.................................................. 90.......................................Intestinal tumors 96........................................................ 99.......................................... '

213.................................Peptic ulcer disease 217.................................Cirrhosis- pathology 219..................... 224.....................................

226.............................................Pancreatitis 234.................... ...

102...................Management of rectal cancer 107.................Introduction to liver pathology 110........................................ 117.......................... '

135......Pancreas, gallbladder & liver histology 139.....Neuroendocrine tumors of the GI tract 146.......... -

154......................................... 156........ 166..................................

170........................................IBD- pathology 173.........................................IBD- radiology 175..............................................IBD- clinics 182............. 188....................................... -

( '

Esophagus
" 25 . , . : :Sliding hernia , . . 90% -Hernia

, . . . .

:Paraesophageal hernia 10% (cardia ) . junction

.(traction)

-Diverticula (Zenker's)

(squamocolumnar junction) gastroesophageal junction . .( ) ,GE junction . ) , , , .

, ,

squamous epithel .( , :

. ,

' .

, .

-Varices

.( .

) . , ,( ) reflux . , .

ulceration "

, ,( )

-Esophagitis

, . , ) uremia , ,( . ( " . . GE junction , GE , .Barrett's esophagus , . . ,junction " ' . Erosive esophagitis ) ( )

-Barrett's esophagitis/esophagus " 3 .

, , . . squamous epithelium . .(colloid iron -

: ) , ' .

, -Mild (low grade) dysplasia .( o

, .

' ,

. , -

. , )

-Moderate (high grade) dysplasia , , .( -Severe (high grade) dysplasia , severe . . , . Barrett's esophagus ' . , -

moderate

. .low & high grade

Stomach
.chief cells , .( G cells .(chief/ parietal cells ) . : (' ,e.coli) -Acute gastritis pepsin body ,parietal cells cardia ) antrum

uremia .( : ) , Acute superficial gastritis .1 Acute hemorrhagic gastritis .2 ,( ) :Acute hemorrhagic erosive gastritis .3 . " . -Phlegmanous .4 .H.pylori ,

, .( ' )

ulcer stress gastiritis .( :

-Chronic gastritis ( ) peptic ulcers

(B12

) pernicious anemia :

Non atrophic diffused antral gastritis (type B) Atrophic autoimmune gastritis (type A)

o o

(type B

) Atrophic multiphocal Chemical gastritis (NSAIDS/ bile)

o o o o

.H.pylori ,( Wegener's

-Lymphocytic gastritis

) Crohn's disease -Noninfectious granulomatous gastritis ,( , ) .granulomatosis . ' -Eosinophilic gastritis

Helicobacter Pylori and it's gastritis . . , . EM .( , . , . :intestinal metaplasia .brush border : . ' . . , .intestinal metaplasia , )

-Complete type-type 1 -Incomplete type

" ) brush border

, .(

,type 2 -

-(colonic type

) . .sulphomucins type 3 , ,

,type 3 -incomplete

sialomucins

type 2

) , ."active gastritis" ) ,

.(mild, moderate & severe *.

-lymphoid follicle formation .( Autoimmune chronic atrophic gastritis .Type A gastritis

.IF )

. ( .gastric atrophy, inestinal metaplasia & carcinoma .pernicious anemia

body ) high pH .(G cells type 1 ,

10%

, . Chemical gastropathies .( NSAIDS . ) . . Lymphocytic gastritis . . . , ,

.'

,CMV ,

: Hyperplastic gastropathy : ' -Menetrier's disease .

, , , . " .

. .

"

-Zollinger allison syndrome

Chronic peptic ulcer , pH . , . ,(Barrett's esophagus) (zollinger allison ) ,( 4 3 ) , ,marginal ulcer .Meckel's diverticulum

.body . . . ,

,lesser curvature

. .

' : (1) . (2) ) ' ) .( (3) (4)

.( .

: . ) .( .(coffee grounds . ) . , . . .pyloric stenosis ) , , ( o o o o o

10

( '

Esophagus
: . . . . . spindle cells ' . : squamous cell : ' . . , -Squamous papilloma -Fibroma -Lipoma -Leiomyoma

-Squamous cell carcinoma

:Superficial :Polypoid :Ulcerated o o o o o

( .( . , , ' )

:Fungating :Diffusely infiltrating

. . )

SCC ' ,

.(

-Adenocarcinoma
. . , . .(back to back) . 50% ,SCC 90% Barrett's

11

Stomach
: Leiomyoma . -Shwannoma Lipoma : : , 1 . . .( ) Menetrier disease . , . , . . . 50% . 5-10% ] !( ( . ) [ : ( , ) -intestinal metaplasia colonic type metaplasia .90-95% . . . ) " 1 . Adenoma o ' Fundic gland o . " Hyperplastic polyps o

post ,gastric polyps ,chronic gastritis ) chronic peptic ulcer (

) ) Menterier's disease ,gastrectomy state .( 4%-

12

leiomyosarcoma, malignan shwannoma, GIST- ) 1-2% (gastrontestinal stromal tumor Early gastric cancer . ' , . ) : . . . . early , .gastric cancer . [ 5 99% ] .93% .(70% ) Gastric cancer .(47%) 23% -body ) 21% cardia ( 2% -fundus ( ) , .7% -linitis plastica . Vs :(linitis plastica) intestinal type diffuse type ,2:1 o o o o o , -Excavated .( -Exophytic -Superficial

.(55)

13

-Signet ring cells .mucicarmin . intestinal type well differentiated .

. ,

, .( . ) , ' , )

papillary type ,

poorly differentiated .(diffuse type )

.(

, , .Krukenberg tumor .

, Krukenberg tumor .signet ring cell Gastrointestinal stromal cell -GIST

. . CD117 /c KIT .( .GIST . . , " 5-10 , 50 . 5 5 ) , , ' ,

, , ,

" ,c KIT ,

.Cajal cells

" 5 " 10 .uncertain/ low malignant potential

. .( ) (spindle cells) ,

14

Gastrointestinal hystology
( : 3 alimenteary canal -Mucosa -Submucosa ' ' -Muscularis .serosa enteric ' , ' . . ( ) ,muscularis ' , ' . ' ' ' nervous system . , )

.muscularis mucosa lamina propria , . . '

Meissner's submucosal plexus Aurbach's myenteric plexus . " , -Hirschsprung disease

. . . ' 24-48

Esophagus muscularis lamina propria ,stratified squamous nonkeratinized epithelium . . ,( . NO ( ) .Achalasia " , ) , (LES) lower esophageal sphincter .( ) Stomach .chyme , . rugae , Harbors glands -Mucosa mucosa -Submucosa -Muscularis externa

15

' ' pH

(simple columnar epithelium) .autodigestion

-Mucosa .

5-7

-foveolae (pits) .lamina propria -Mucus neck cells .( -Parietal cells , .canaliculi

chyme .

.(B12 . "

) gastric intrinsic factor

B12 B12

Gastric IF ,

pernicious anemia ' . HCl -Cephalic phase .1 . -Gastric phase .2

: " , . , . . , .gastric lipase ,( pH " .( . . . , , . " ) rennin ,pepsinogen . G

-Intestinal phase .3 -Chief cells

pepsinogen )

diffuse neuroendocrine cells -DNES cells . ' . Regenerative cells Small intestine . " 25 : . 7

-Plicae circularis

16

. , . . ,surface absorptive cells paneth cells .( paneth cells . .( 7-10 ) plasmalemma

-Villi -Microvilli .villi -Crypts of lieberkuhn

1%

,enteroendocrine cells -) DNES lysozyme

, chyme

. Large intestine

, .

' . DNES

,chyme . (' . 6-7 . , , )

17

Recto anal junction pectinate line/ dentate line/ anocutaneous line .nonkeratinized stratified epithelium simple epithelium . ectinate line . low fiber diet , " , . -Hemorrhoids

18

( , . 10 .' 2-3 . ) US .( . , . , , . cancer 5 . . . 2-3% 28,000 (10-15%) : . 15-19 . 6-10 . . . . : ,( ) : chronic pancreatitis BRCA2 . . CEA CA 19-9 ,Losec , , ,61 : ,peptic ulcerative disease

.related death

-Resectable disease -Locally advanced disease -Metastatic disease

Familial adenopolyposis (FAP) HNPCC (2 . , ) ,

19

. . :

: . , ]. -Palpable liver [ -Palpable gallbladder . . ( ) .migratory thrombophlebitis -Trousseau's syndrome .( ) .upper GI track .DVT : . . .US .( . ) urinalysis ,CBC , , . . .( ) . , , , , CT US

20

.( .common bile duct .

) CT : . " 2.5 . .common bile duct : -ERCP

staging in situ -Tis " 2 " 2 , SMA -T1 -T2 -T3

.celiac trunk . "

-T4 .resectable disease . T1-3 -Nx -N0

. . . . . -Stage 4a& 4b . : pancreactectomy . ]. [. 15-20% ,(' laparotomy .Whipple's procedure . ERCP . .stage 2 ) . , CT T3, N0, M0 5-20% .(.. : . , ,SMA ! . .( ) -

-N1 -M0 -M1 Stage 1-3

21

. . ' . , . ' .local control ,

" . . . , . ) , . celiac , . bypass ERCP , . .local advanced disease , . CT . , . . . . , . ,5 Fu Gemcitabine . : ) Karnofsky status . 20 50% ( 20 , .7% , . . 50-40 , . 5 Gemcitabine 5-Fu , , " 8 , , .plexus , -ESPAC trial ,

100

22

. . , ,Xeloda

Gemcitabine Gemcitabine Gemcitabine .( :( ) ) ' Gemcitabine

. . . .( . ) Gemcitabine 5-Fu locally advanced disease

23

Gastrointestinal radiology
( . . , . , . . ) ,( , . . / . . , plain film . soft tissue mass . . ' )

,(

.( , . .' ]. , , , , [ , , . , -Stuck horn* . .calyces , . . chronic ) . -

.(pancreatitis , . AP . . " -

24

' ' single/ double ) . . . . ). . ' .

. , , . . , .(contrast * -small bowel enema* , (C5 : Superior pharyngeal constrictor muscle (1) Left bronchus (2) . .cardia * (3) (4)

Diverticulum . . . , .( . .rugae , . . , . : ) , , ,

. cardia ,sliding hernia . , ] paraesophageal hernia [

, cardia duodenal bulb

. . bulb , ,

25

, . . . , . . .crohn's disease . " .( . . , ) , , ,small bowl enema , . .( . . ileocecal valve . . . ) , , , , , bulb ,

bulb .

'

20

double contrast

) .

. . .rectal tubes .( . . .familial polyposis , ' .( ) .CBD . . " , , / double contrast )

26

, . .( . .

. ,

CBD "

) oral cholangiography . " . . " ' -Angioma

. . . ' , ) .( ' , ,

MRI . , , , , . (

MRI CT ) CT

. ) CT .( Meckel ) .( . .( .' , ) US . ( diverticulum US )

27

'
( . . ' , . .( submucosal plexus . . ( , , A . ,ENS) enteric nervous system . A , , , . ' . ' CNS , " ) ' ' , .(' " ' .(ANS , ' ,pH) ) , , , myenteric plexus , , , ' )

ENS .

" . . " ) -intrinsic primary afferent neurons -IPAN ' .( ,

28

' .IPAN " . , , ,ACH IPAN ,

,IPAN ' . , , . .VIP NO . ' ' ' NE ,NO ,GABA ,ATP

) . . ' ' ' ,

-interstitial cells of Cajal -ICC . .(

-Extrinsic primary afferent neurons (EPAN) ' . . ' , " ' (IBS) . * A

. . . ' . , '

'

' " , . ' -Basic electrical rhythm , A '

, . ICC . . . : ' ' ' (

(slow waves) " -

electrical response activity ' , ) ENS ' , ' .gastrocolic, enterogastric & colonileal ' . ' , "

. . -

Mixed

29

.Mixing movements , . , " . .CNS , -Peristaltic reflex

,body)

cardia ) .( ,

. . receptive relaxation ,

. ,

. ENS 3 ) greater curvature , , .( . . : .(! . , . . ) , .( : . . , ' . , .( ' 20 ) ( ) , " . " 7 ) , pacemaker zone

"

***

30

: :

: -( . . ) , "

" . , . . . GIP , VIP ,CCK o o

31

, .

.'

. , : )

pyloric stenosis ,

, .(

, . .

.dumping syndrome vagotomy flushing , , .gastroperesis . ,

.gastroperesis

. , ,

, , . , retching

. . .(' . , , ' , , , , , )

medulla oblongata (ipecac

chemoreceptor trigger zone ' ' , . , ,

, , LES . !! . " "

. . ICC .10 10-12 ' , ' 12

'

basic electrical rhythm .

32

'

"

" .(

, . ' .ECG '

-Intestinal segmentation , , . .

) . ' , ) ( )

.( interdigestive motor , . .' 75-90 -1 -2 ( "

'

) .complex- IDMC

-3 ' pacemaker zone 3 . migrating motor complex (MMC) ) . .( . " 2 ) " 2 , . . ** (

33

) "

, * .( .

-Gastrocolic reflex

) IBS : , . FMF , . -Intestino-intestinal reflex . ) . . , Ileus . .intestino-intestinal reflex . . , .( . .ileal break , . . . . -Colono-colonic reflex . ) -Ileocecal valve ' " -Ileus . ' ,( , Colchicine

34

( .( . . " 50-200 , . , ,(teniae coli) 3 . . ,teniae . . . , , . . . . . : Electrical response activity . , ' -Mass movements . o basic electrical rhythm . . . . . CT . ) . , 0.5-1.5 ' .

-Colonic manometry

-Short & long spike bursts . -massLSB . . ,

3-4

35

" .

. mass movements . Transit time

, , .' . . ' 72 , 12

.(

) ' 9

'

4 , ' 6

. . ( , )

, 70%

:transit time .

" .( )

. . .

"

o . o . . levator ani

" .

. (defecation reflex)

"

. , . .

. , , , , . . :

36

-fecal sampling , CNS . ,

.( .

, . , .( ) E

: . , , , , ,( ) . , . , , , ." " " .( . . " ) -Hirschprung's disease . -Fecal retention o o o o o o

. .chagas disease ,

( . , : . 60-70

37

crohn's

, .

o o o

. . -

o o

: lower motor neuron , . -upper motor neuron .

38

GI bleeding
( )

Upper GI bleeding
: coffee grounds . . " .hematemesis ' , . , .( , ' ) . ,bismuth ' . . -Hematochezia ' ) -Melena

' .

.(

50% . 25% .( 10% . , , . , -Mallory Weiss tear 7-10% ( ) . : , : . . ' -Hemobilia Aorto-enteric fistula )

39

20% 8-10% . ) .'

80% ,

.(

'

Management

. . , ) , .( ,

. , .

) .(K .nasogastric tube , . [ . . 80% , , ]. .

].

60% [.6-14% 65

" " , '

40

:(NGT) , . ,coffee grounds . , . . , . 6% 10% 18%

, . . 5% , -EGD- upper endoscopy ' ) upper GI . . . . ' , . -' 6 . : Spurting arterial bleeding ." " , 6-12 ' 24 (UES)

. ,(

41

. . . .

-Nonbleeding visible vessel -Adherent/ non-washable clot 40%

total Erosive gastritis] .NSAIDS [. " . . . " 2 gastrectomy -Mallory Weiss tear

80%

. . .

) -Antacids -H2 receptor antagonists "

PPI
(Omeprazole) proton pump inihibitor -PPI PPI (1) :' 2 . ,PPI . . PPI [ ( ) ]. , IV PPI " ' : . , PPI PPI (2)

-Endoscopic therapies
.(bipolar probe ) , . .(

, )

, . .

, , .

bipolar probe

42

, ( . , ) . , , , " . .PPI .( ). :

-Stress induced lesions , ) . H2 blockers (antacids) . , -Arteriovenous malformations . ( , .' . ,

43

, .watermelon stomach

, . .

-Antral vascular ectasia , -Mallory weiss tear ) -Hemobilia , Vater (1) : (2) .' " .

, .

. .(DD . , . (3) .

) .(

. . .

-Esophageal varices

. . : . ,overexpension . (C)

(A)

, 8.5-9

44

. ,

IV somatostatin analog (Octerotide) band ligation . suction . . . . , . ,band ligation . , . ) ' . , 80-90% .( , , *** . jugular vein - transjugular intrahepatic protosystemic shunt-TIPS .portosystemic shunt ,hepatic vein portal vein . , . sclerotherapy , -Sclerotherapy . endoscopic band ligation

-Sengstaken Blakemore tube- Balloon tamponade

.band ligation

Lower GI bleeding
, . ' . : .UGI .(5-8%) .UGI . .diverticular disease . ' ' , , 15% 10% . ( -Hematochezia ) -Melena

45

: -Internal hemorrhoids , ! -Diverticulosis (40%) Arteriovenous -malformations (AVM) (40%) Ischemic colitis Colon cancer .radiation colitis ,anal fissure , , ,IBD , -Other

Management

, " .( . ( )

. )

.(

46

Esophageal cancer
. 10% . .3 . squamous cell carcinoma 50% " SCC 7 , Barrett's esophagus . . , SCC SCC . . , . . :SCC SCC . .SCC 30 . esophageal webs , -Lye ingestion -Thermal injury -Plummer vinson syndrome . .( EBV ,HPV . .65 , SCC . SCC 95% SCC -Tylosis . LES -Achalasia , ' SCC , ,

) angular stomatitis

47

. . . . . Barrett's .[ ] GE reflux : . 80% . . . . . . . .reccurent laryngeal nerve : . ' -Virchow's node -Sister mary josef sign Axillary nodes -Acanthosis nigricans imaging Imaging . esophageal hiatus ) .( , . . . . -Odynophagia . , H.pylori .esophagus Barrett's esophagus ,intestinal metaplasia Barrett's

48

' ,

cardia

double contrast . .

. . . , , ,(

. , ) . .(fungating) , .( )

, .

. ,

, staging . , . CT

. : , . . . (1) : . , , . , .staging resection , " US (2) ,

.(in situ)

-Tis

49

.(

-T1 -T2 ' -T3 -T4 -N0 -N1 -M0 -M1 :

.5-10% . .T2 T1 . .( )

. . ' , . . ' . . . . . , :Prevention . .Barrett's ' . , 1-3 , SCC ,Barrett's Barrett's ,endoscopic resection photodynamic therapy . "

50

Stomach tumors
. 5% . -1930 , .( ) : " . . -H.Pylori Chronic atrophic gastriris Pernicious anemia . -Gastric ulcers . Gasterectomy -Adenomatous polyps , . cardia ' , 90-95%

Obesity

,H.Pylori " : .

receptive relaxation )

, -

51

.cardia . GI . -

-Migratory thrombophlebitis . , -Acanthosis nigricans ) ,Virchows node )

. ,( , , ) ,

.( .

, ('

:Imaging . . . , .( . , . . .staging . . body , . , . . : . stage overestimation . :Staging . -T&M , US body , CT AFP) , , , -GIST

52

" 3 . .CT :

-N1 -N2 *

. . , 1/3

"

. . . . . ' . . . , , . , . . " 2 8 .30% " " 10

Gastric lymphoma
. 2-5 . . 2-4% -B . " ,H.pylori .( .H.pylori 50% . ) primary gastric lymphoma -MALT lymphoma** . ,

53

Bacterial gastrointestinal pathogens

( , ' . , . . , , , . .' ( . , 10^5-10^8) pH e.coli ]. [campylobacter 5 . , , . :Risk factors immune deficiencies : salmonella, campylobacter, shigella enterohemorrhagic e.coli (0157:H7) Bacillus cereus S.aureus, salmonella salmonella vibrio species, salmonella , ) .H.pylori , ' , ' ) ( " GI , GI )

54

(e.coli .

: pH . ' . , . . . , . , .(' " lactoferrin , , ,lysozyme ,IgA ' . , "

GI Bacillus cereus & S.aureus . ) "

(CMV /

" . H.pylori . Helicobater Pylori . ,

55

. .( , . . 1% ,

, )

, -

80-90% 10% , .MALT lymphoma ,

, . .(BabA, SabA ,(GagA . ) , ** .NF-kB .GagA )

. Lewis blood group antigens

, " , :H.Pylori

, ' . . , . pH , CD47 MHC class II ' . , .T CO2

'

-Cytotoxin VacA ,

-Urease ' .IL-8

. . [

CO2

urease

"

LPS ,Hsp60 ,(neutrophil activating factor) NAP ]. , ,carbon urea breath test . , . ( ) omeprazole : :

,rapid urease test

Metronidazole/Amoxicillin/ ) .(Clarithromycin Food poisoning

56

.cAMP : .( ' + ) secretory mechanisms S.aureus & B.cereus " . S.aureus . -Enterotoxins

-Cytotoxins ' -Neurotoxins C.botulinum . .

.'

12 . ' .

'

1-6 , ,

:S.aureus

.Staph .( . , ,

)'

30

. . fried rice ) enterotoxin type 1 ,

:Bacillus cereus

.(syndrome ' .cAMP type 2 enterotoxin .' 8-14 ) . . . .' 24 . , ' . . brush border .( , 1-16

.'

:Clostridium perfingens

:Clostridium botulinum
, .antitoxin .(infant botulism) . 1-6 ) .botulism . , .' 12-24 . .

' .(

57

Non inflammatory diarrhea " . . ETEC . . .Vibrio cholera . : .Gi- proteins . -ADP V.cholera Cholera toxin E.coli cAMP . E.coli LT toxin , 60-80% ,(enterotoxigenic E.coli) ! ,

E.coli ,

cGMP

guanylate cyclase

ST toxin .

. .indol + ,(McConkey agar .LT & ST (heat labile/ stable) : enteroaggregative E. . .PCR , .ETEC ) lactose + ,

. , " ,E.coli diffusely adherent E.coli (DAEC) coli (EAEC) .McConkey . . "

:E. coli

ELISA LT toxin ,

. . , , .( . . ,mucinase ,(E.coli LT ) cholera enterotoxin , " ' .( ,O1

:Vibrio cholera
2-3 , ) ' ,

.siderophores endotoxin GM1 B' . A' B ' . 5 cholera toxin ADP A'

58

rice water " ,thiosulfate citrate bile salts sucrose TCBS .adrenal cell assay " . .

."stool Vibrio cholers

Vibrio parahaemolyticus " . , .V. parahaemolyticus ETEC " . , , , 1-5 ( ) . . 4-6 .

**** .

:Travellers' diarrhea

Inflammatory diarrhea . ' . ,( ) tenesmus . .lactoferrin

, :"

Campylobacter :jejuni
. . . pH , '' . ... , , , .' 3 3 reservoir . 2-11 ' , , . ,(S shaped) , 13 , ,

.( . lactase ) McConkey . ,

B ,

Skirrow's medium) .

:Shigellosis- Bacillary dysentery

. ,(-

59

.food, feces, fingers & flies :4 F's . shiga , . Gb3 , .rRNA hemolytic ) HUS , ' .(uremic syndrome SLT1 & SLT2 (verotoxins) . . , o157:H7 .rRNA ,EHEC :E. coli shiga toxins , toxin

3-5 .(hemorrhagic colitis) . ,HUS . :Laboratory tests . , ,McConkey " ) SS agar C. jejuni

ARF ,

. . .( , . " ,

lactose negative ( 42) Skirrow's " " .

:Clostridium difficile
, . ' , .B A , ,

) cytotoxin assay " .(

30% . . . .

pseudomembraneous colitis , .

ELISA

.Metroniazide :

'

60

SS agar

McConkey C. Difficile

McCon key

E.coli !

) EHEC

shiga toxin

Invasive gastroenteritis (enteric fever) .enteric fever . , , . .(S.typhi) typhi salmonella enterica " . , .( , , ,malaise , , , , , , ) , . .( , , , ) ) Widal test . . .oxidase negative , , ,50-80% , .( , ) , .(O-somatic & H- flagella

:Enteric fever (typhoid fever)

,

:Yersinia enterocolitica
4) -yersiniosis .( , . , .( 22-25

, . ) .( . ,

61

Irritable Bowel Syndrome

( . , , . [ : . . . 28% ' . 3 12% IBS (23% ) ( , ]. ) )

, . " ' .( . . , : , post ( , ) CNS ENS .(PI-IBS) infectious IBS Pre disposing factors . , ( ) , ) "

Precipitating factors

62

GI . . .

Psychological comorbidity , . , , ' . ENS .Brain- Gut axis .IBS ,

strech receptors -Visceral hypersensitivity . ' ,IBS , ) .( CNS . , . ) .( . IBS

SSRIs (selective serotonin reuptake inhibitors) , .( ) . ballon rectal . ' IBS MRI .

.CNS

hypersensitivity Post infectious IBS .IBS . 7-33% 6 : . , ...' : " .PI 50% IBS 10-15%

vicious cycle

63

-Rome criteria (Rome 3) : 2 , (1) (2) (3) 3 6 . :IBS -IBS-C . -IBS-D . -IBS-M (mixed) undetermined -IBS-U ,

, ,(50 .

' ) , , ,

Rome 3 .' US ,barium enema . Alarm features (CRC ) 50 GI

IBS

3-6

. Rome criteria "

.IBS

Rome 3 ,alarm features

'

64

97% .( :Treatment " , .

. . : . 2-3 . , . ,( ) . , . , ,polyethilen glycol , , . ,lactase , , . .IBS ' . , . 2-3 . . . moderate IBS ( . .(soiling) . ,34 -' . , , ,27 , . -'

brain-gut axis .SSRIs

. . . . "

65

. , .

. . . ' . . .( . . 2 ) severe IBS 4

,45

-'

' .

66

Bile stones
( ' .( . 15-20% 60 ' . ) )

, . ' , .( , ) nucleation

. . , ' . .( ) ,

, ,

80-90%

. , . , . .

Pigment stones

67

. . . cholangitis " ) .( . Risk factors ) ( . -terminal ileum ,Crohn's disease) .( . , -Primary biliary cirrhosis .

70-75%

. Cholelithiasis .(Gallstone ileus) -(biliary colic) cystic duct (Cysticus) .(acute cholecystitis) , . ampulla of Vater

10 1% .12-14

) , ]. [ . sickle cell anemia , .(

68

. laparoscopic ) ]. . [ UDCA- ursodeoxycholic ) .( " 5 ) ' . , , , ' 24

(cholecystectomy

.(acid . " (lithotripsy) US " . UDCA

Biliary colic .(epigastrium/ right hypochondrium) , . . .US " cystic duct . ,

Acute cholecystitis . .( cystic duct ) . , , , .Amylase .CT " ( .( ) HIDA ,US " )

Choledocholithiasis .common bile duct , . . , ERCP .ERCP " ERCP ERCP EUS " . . .( ,percutaneous transhepatic cholangiograpy ) " . ERCP . PTC ,( , , US) EUS "

PTC

69

ERCP

ERCP .open choledochotomy .(! ) Cholangitis

CBD .[Gram sepsis . . .

15% ]

-Charcot "

. , , , .E.coli

.GGT

MRCP

EUS

.ERCP

cholangitis .(magnetic resonance cholangiopancreatograpy) ERCP

. pappilotomy

.gallbladder in situ . , ERCP

Emphysematous cholecystitis . .cholecystitis , . . Cholecystenteric fistula . . ileocecal valve CT .ERCP . . " 2 Mirizzi syndrome CBD ) CBD cystic duct .(Charcot " US , CT .

" MRI

70

cystic duct .ERCP

.ERCP , . Porcelain gallbladder . . . US Imaging

"

,gold standard US , .(95% .

). , 80-90% . CT

US '

. . .CBD . , .

MRCP

CT

EUS- endoscopic US gold standard ERCP

71

( . 5% , (70% 25% , ) . . ,brush borders . " , . ' . .( : ( ) H2 blockers . ]. [ , , . : ,Na-Cl pump .( , ) gastrectomy ) ' 4 " . . '

')

70% '

brush border deficiency lactase

.shigella, enterotoxigenic e. coli, cholera -Secretory . brush border . . , , ' . . ' , rotavirus -Osmotic .

'

,(4

. malabsorption

giardia lamblia, enteroaggregative e.coli -Adherent , .

salmonwlla, shigella, enteroinvasive e.coli, campylobacter, enterohemorrhagic -Invasive , " .e.coli, entamoeba histolytica . ,RBC , .colitis

72

, , .(metabolic acidosis , . .immunodeficiency ,HIV , ) , -

GI

, malnutrition

(100-150ml/kg) , . : . 5% .

-Mild

.5-10% -Moderate . . . . . . . , , . , . secretory diarrhea . : , . . , , . , , ) .( . , 130 ,150 130 ,150 10% -Severe

-Mild water depletion

-Moderate water depletion

73

. ) .( 5% . , ' , . ( ) , . , . .CNS Taurine ' . . . . , , . . , ,

-Severe water depletion .

brain shrinkage

. idiogenic osmoles

brain shrinkage . .

, .( . . , . , . . , .(Traveler's diarrhea) , . , ' , . . , .autotransfusion -" ) "

74

Inflammatory conditions of the bowel- pathology

( celiac disease, Whipple's disease, pseudomembranous colitis & Celiac & Whipple's . pseudomembranous colitis & amebiasis , " . " )

.amebiasis UGI LGI

Celiac disease
. . " Crohn's ,(malabsorption)

,Gluten sensitivity enteropathy , .

.1%

" 70%)

, .(

, .

.( . .

) FTT

gliadin

.HLA-D2,D8

anti- TTG (tissue , .

,anti- gliadin & anti endomesial , . : . .(villi villous atrophy ) . .CD 8 . , 3 -

.transglutaminase)

, villi (1) (2) (3) '

villi . ,

. .enteropathy associated T cell lymphoma .

75

'

Whipple's disease
, ' .malabsorption . . .( ' ) foamy histiocytes PAS . .Tropheryma whippeli . ' . " . . ' CNS villi PAS

Pseudomembranous colitis
. " .( 3% ' , . . " " . . ) . . , .clostridium difficile "

-volcano/mushroom lesions , ,

Amoebiasis
" .entamoeba histolytica , , . . (10%~) . , . , .

76

.flask shaped ulcer . . . PAS , ' " ,

77

Gastric cancer
, 13 . " 8 .

, cardia & GE ) . . , , , . .40-50%

(junctions

/ .C A

/ /

.10% , , , -

-EBV

A .pernicious anemia , ,

,BRCA2 ,HNPCC ,H.Pylori -Predisposing factors

UGI bleeding

78

. . : . . 3% ,

stage 90-95%

,(A . . ,

-Diffuse type

-Intestinal type

. . . .

) UGI endoscopy EUS

CT .stage . PET scan

, .

) local extension , ,(

Sister Mary Joseph's nodule -Periumbilical nodule Lt supreclavicular adenopathy- Virchow's nodule Ovarian mass - Krukenbergs tumor Rectal mass - Blumers shelf Ascites and palpable liver mass Paraneoplastic manifestations (rare) Treatment " 6 . . staging 16 total gastrectomy ,distal gastrectomy .(carida

) esophagogastrectomy

79

Staging -T1 . -T2 -T3 -T4

-N0 1-6 -N1 7-15-N2 15 -N3

,10% 90% . , . , .(44-45Gy : ) . . . 5 , ( 1.8-2 Gy) , , , , . . , '

dyspepsia, gastritis, gastric ulcer , , .

. ' , .standard of care ' ( stage IIIb) .

80

) . , .( 20 staging '

, , .(

epirubicin, cisplatin & fluorouracil -ECF 24) . ECF , ,ECF ,

.(N positive/ T3) high risk

0% , .

10% 6-10% ,

, 35-40% , .(FAMTX ' , ToGA trial , HER2

14%

) ECF

5%

HER2 20-25%

Herceptin (Trastuzumab) . overall survival .

Esophageal cancer
. ,

Barrett's esophagus

81

Achalasia . . , (85%) 60% SCC

SCC SCC 1980 . , .Barrett's esophagus

UGI EUS .staging . .( ) . CT -PET scan

Staging T3 , . cervical esophagus, intra thoracic esophagus & gastro-esophageal junction .lymph nodes , .M1 upper celiac .M1a .M1a lower thoracic esophagus . thoracic esophagus lymph nodes M1b N1 N0 . T

82

5 . . . IIA .30-50% .5-15% IIB 5

, ,stage 1 15-30%

transthoracic esophagectomy (TTE) & transhiaal esophagectomy . THE , THE . . . , . . .standard of care . . , . " . '

TTE .(THE) ,TTE

-Neoadjuvat therapy . , -Adjuvant therapy

83

( malabsorption . " , . , , , . lipase . , . . , pancreatic proteases .mucosal peptidases mucosal " , pancreatic amylase , -

maldigestion

FFA 2

.disacharidases post , malabsorption .absorptive (processing) phase -Luminal phase Zollinger Ellison synd -Post Bilroth II procedure , " . , . / .( , )

. . . pH "

pernicious ) IF

pH

B12 .

"

' /(anemia -Mucosal phase , '

.( .

) brush border ) .

" (lactase def

Hartnup disease .

'

-Postabsorptive phase .( :

84

Bile acid deficiency : Disaccharidase deficiency brush border : -Protein losing enteropathy

85

, .

. ,

' ' ,

Connective tissue disease

) -

) .(

, ,' 3

B12 .'

,CBC

: . , . . ' 7 .' 72 . : -' 4 )' 5 20mg/dl ) D-xylose ' 25 ' 3 .( " , , , .false positive -Lactose tolerance test ' 18% . ' 50 . -Breath test -' 3 -D-xylose test .( 18.5mg/dl -Fecal fat determination . -Sudan III stain

86

: .protein losing enteropathy . . . .' 72 trypsin & chymotrypsin , " alpha 1 trypsin protein losing enteropathy DD . . -malnutrition :bacterial overgrowth ' ' . . small intestine bacteial overgrowth -SIBO gold standard .(10^5cfu/ml ) , :B12 . " . ) B12 . , pernicious anemia .(' , terminal ileum resection ,SIBO , : gold standard lipase, amylase, ,780 . .(Lundh) 80-90 CCK , ) .trypsin .( , bicarbonate .B12 ) , B12 1mg B12 ,IF . ,( B12 , .R binder . -Schilling test IF .

muscle atrophy ,

,pancreolauryl & bentiromide tests .

" Imaging

, .

87

. .

MRI

CT

-VCE-video capsule endoscopy -Enteroscopy . -ERCP . . . : , -MRCP -EUS

3 Small bowel mucosal disease Small bowel bacterial overgrowth Pancreatic insufficiency :

underlying disease Celiac disease , .zonulin ' , . . ' HLA-DQ2/DQ8 . HLA-DQ2 ,10-40 .B12 , . .villi , villi -CXCR3 gliadin .

.T cell lymphoma . .

88

drum like distension) meteorism -dermatitis herpetiformis . .( )D

10-20% .( , B12

.total villous atrophy .( . .

) asymptomatic villous atrophy , . . : ' Sjogren syndrome , , " Autoimmune hepatitis Down syndrome Premature onset of osteoporosis Primary biliary cirrhosis Unexplained elevations in liver transaminase levels Unexplained iron deficiency anemia : DD

FP

.(

IgG .

) anti tTG , ,

89

,villi . . . 4 . -

gold standard .

FN

12 .(

. )

) .( : . (.. , , ) ,B12 , .

90

Intestinal tumors- pathology

( . . )

squamous epithelium glandular epithelium

-Anal zone carcinome -Malignant carcinoid -

o o

. .

Non neoplastic

-Hyperplastic polyp ( ' ) -Hamartomatous polyp .Juvenile polyp/ Peutz Jeghers polyp : ' -Inflammatory polyp Lymphoid polyp . .

o o

.(IBD

o o

-Neoplastic o o

tubular/villous/tubulo-villous adenoma -Adenomatous polyp Carcinoid

-GIST Gastro-Intestinal Stromal Tumor - benign or malignant -Lymphoma Lipoma Liposarcoma Leiomyoma Leiomyosarcoma Angioma Angiosarcoma

91

Kaposi sarcoma

ampulla of Vater . FAP . . -exophytic tumor** FAP "

.UGI

, :

.vater " , ( Peutz Jeghers HNPCC ,FAP )

. .non neoplastic . ( 90%) 60 " .( , .( ) . .(serrated epithelium) ) .(pedunculated polyp)

-Non neoplastic polyps

. .Peutz-Jeghers polyps juvenile polyp . . . 2-3 , . .14-15 -Hamartoma :Juvenile polyp

-juvenile polyposis syndrome . .BMPR1A SMAD4 . ,

92

, .( )

:Peutz-Jeghers polyps . .

-(PJ syndrome) .LKB1 . , . . -intussusception

. , , , ,

) ,

' .

PJ syndrome .(

, .

'

) ,( , ,

-Neoplastic polyps ' .60 ' 50% ,40 . . , . . . . . ! , , . . 1 . " 2 . " . . , . , ( ) " , . ( ) ( 40% , , ( . 5-10 ,tubular " 4 villous) sessile villous polyp -Tubular adenoma ) , ' 20-30%

93

"

. . .(

-Villous adenoma )

' .50 ( ) . , , , . . . .

FAP .5q21 tumor suppressor gene . ,APC , , . .16-18 . 500-2500 , 100 .100% ' (30-40) , : Classical FAP 100 . Gardner syndrome * attenuated FAP *

. . .(50%) '

-Multiple osteomas (particularly of mandible, skull, and long bones)

Epidermal cysts -Fibromatosis Less frequent: abnormalities of dentition thyroid cancer classic . 2/3 . HNPCC

Tucrot syndrome 1/3 .

* FAP

94

HNPCC-Lynch syndrome . . . . .

80% ,HNPCC ,

. 10-15% .APC/ catenin pathway .microsatellite instability pathway . . .caretaker genes , ' genes

gatekeeper ,

. . . 10% .IBD . , ,

first hit ,P53

80% APC K-RAS ,

98% 1-3% .60-80 . . , , , (fungating) . , .

. ,

95

: .( !!! . , ) 60 (

96

( .obesity . , . obese (2) . , , (4) , , , . , . : ' , , ' , . (1) : (3) ( ,

Malnutrition

BMI 3-6 . , , ) . 2 .

.(' nutritional risk screening -NSRBMI 3 , . : . . . , ,6 score . , -Caliber

97

. . " . .18-25 BMI .(' . , , " . . . . . , . . , .(overhydration ) .BMI , , intake . / / " , , pre-albumin , . . , ' 3 ' . , ) ,18 3 * -BMI ,BMI

. ' 24 25-

, . . .30kcal/kg/day . .( ) .( .antigen presenting medium ) " . . (glycemic control) 200 . , . , . -Post pyloric feeding , , , , .(chain fatty acids -Parenteral nutrition )

98

. .

-Nasogastric feeding/ nasal feeding tube -PEG0 percutaneous endoscopic gastrostomy .

. " , . , , , . . .(post pyloric feeding) surgical .jejunostomy PEG . PEG

, . , . . . . , . .(Jevity ) 3 .

99

( )

. : , ,NSAIDS , . . . : . .

,58

. ,(? , ) MCV ,( ) CBC CA .screening -Stool guaiac test UGI .[FN , ' -Heme porphyrin test .(high FP rate) -Fecal Immunochemical Test .FP . FP :UGI ( ) NSAIDS** DD

. C ]

,heme .LGI

100

" Esophagitis

Mallory weiss tear -Cameron ulcer , :LGI IIBD DD

, .

, '

-Diverticulitis

. " 1.5 ,

-Fissure

. . villous adenoma .( .high risk .high risk . .tubulovillous tubular ,( " 1 ( ) ) villous : 3: : : ) 30%

101

. . 10

, ,50 . 3 Screening 50 .50 10 . (1) (2) (3) ,

. .(CT) . . , , . . .video capsule , 10 , 2 5 , 40 DNA 5

10 5 . (4) (5)

60 .(5 )

.42 , (pan colitis) . 3 . UC 15 UC . colitis UC . " 5 1-2 ,12 . 1-2 8-10 FAP . HNPCC UC

.21

102

Management of rectal cancer

( )

. :

,pectinate/dentate line ,

(1) .left lower houston valve right left lower (2) .houston valve " 15 (3)

right houston valve ,rectosigmoid junction .(anal verge ) . ampulla

. .CBC . . . . . ,GIST , : . -transrectal ultrasound -TRUS . . . . .( , , 15%) " .' MRI TRUS CT -MRI CT CBC

digital rectal examination -DRE 95%

.total body PET-CT "

103

Staging -Tis

-T1

-T2

-T3 ' -T4 ) ( , , N0 1-3 -N1 4 -N2 M0 M1

' (CRT) ' CRT

total proctectomy . , permanent

, " 2 anterior resection

anterior resection (APR-abdominoperineal resection) .( ,

) colostomy

total mesorectal excision -TME .

104

, pouch

total protectomy .incontinence

CRT 2 .CRT , ' . , ). , , . ' . ,CRT . . 5 ,1.8-2Gy/day ' 6-8 , 3-4 , , . .44-45Gy .50.4Gy . . .( , ' ' 5 , .

'

, 3

.5-FU 5

IV bolus . : IV 5-FU '

.PO -(tegafur-uracil) UFT . .PO -(Xeloda) Capcetabine .

5-FU . .

105

5-FdUMP DNA . . ,( ) DPD

5-FUDP ,

RNA 5-FUTP ,thymidylate synthase 5-FU leucovorin 5-FU 80% .dihydro5-FU -tegafur DPD " , . UFT ,UFT Xeloda 5-DFUR ,

"

, , .

5-FU .

. 5-FU

4 DPD

.5-DFCR .cytidine deaminase '

5-DFUR ) .(

, " 5-FU

' :

1/3

. ,

, ,

, -

-GI

Hand and foot syndrome -Cardiovascular , . 4 , 5-FU '

Trans anal excision , trans anal excision ,stage I . : " 3 (1) (2) grade . . , , Endocavitary radiotherapy (3)

106

. : ( " 10 )

'

stage I . (1) " 5*3 (2) (3)

30Gy

4-

. .

. . ' + '

, +

stage 1 : stage 2 & 3

107

Introduction to liver pathology

( . , ' . portal ) portal track : central vein .' , , , )

,(vein, hepatic artery & bile duct .( ) '

' , 1 . , . 3

. , .3 ' Bridging necrosis

3 acinus .acini

, , .

/ bile ' ,(biliary canaliculi-BC) . Space of Disse . . , " . ' "

EM duct

Lipocytes

Acute viral hepatitis : . (ballooning) " . .(disarray) , .( ) : ' . -Inflammation ,(T ) (injury)

108

.( , .focal necrosis

. ) acidophilic bodies

-Focal necrosis

. " . " .( , , . ) confluent necrosis ' -Confluent necrosis , ,portal vein

. -Bridging necrosis terminal portal tracks , .hepatic venule ) fulminant hepatitis .( reticulum stain , .bridging necrosis confluent . ) , .( -Panacinar necrosis ,necrosis

,(

,HCV

) .interphase hepatitis .(limiting plate limiting plate .

.( "

-Piece-Meal necrosis ,HBV ) portal track -active chronic hepatitis

limiting

portal tract

inactive chronic hepatitis .(Piece Meal necrosis ) plate : . , ) -Disarray Ballooning .( Focal necrosis Acidophilic bodies " .

"

109

) portal duct

-Portal inflammation .( ' Focal Kupffer cell proliferation :acute viral hepatitis DD

, ,acute onset

.' , .

.Mallory bodies , .

110

( : (' , ) . " . , . ,elevated lesion . , .

, ,( ) -

) 2'

, .( . , ) 3' ' . . 5 60%

" (

, ,

,2007 . .1300 ' . 90 .( '

, ' .

' 2004-2007 . 90 ' ) ' ]. [

3400

steady state

, "

" . . 65-85% ) 10-30%

111

1% .Lynch syndrome -HNPCC . .

5% .( 0.1% FAP -screening .cost effective , . .100%

, ,

. Polyp carcinoma sequence

10 ' 40 55 .25% .

.50

. :

" 2-3 .biopsy forceps

" , ( .(SNARE) )

*** . , .' .(SNARE " ) . " , ,

112

" , . ,

' , . .

" 2 . ,

***

Major genetic syndromes familial adenomatous polyposis -FAP . 1% .( " 1-2) 10 . .(adenomatous polyposis coli) APC . . .papilla of vater . .18 . ,(extra colonic neoplasia) 50% total colectomy Attenuated FAP .40 , .( ) HNPCC- hereditary non polyposis colon cancer- Lynch syndrome , .( ) .endometrial cancer . . .mismatch repair . :Amsterdam criteria HNPCC +3 . . .50 / 2 / o o o 5% .FAP -MYH FAP tumor supressor gene 100%

.20-25

113

. .(50 .' , 1, 2, 3) 3,2,1 " screening : 50 Lynch syndrome ) ( microsattelite instability hystology ,Lynch syndrome tumor 50 ,Lynch syndrome tumors 2 CRC 60

FAP

Test line guidlines CRC associated tumor CRC CRC

CRC

" -A -B

114

-C

-D

T,N,M "

, .

. Prevention Risk factors . . o 2-5% . .6% 45 .50% o o

HNPCC -Chronic colitis o

Crohn's, ulcerative ) , . . ) .(total colectomy o Previous colorectal neoplasia . Primary prevention o 8-10 , .(colitis

115

: . risk . ) factor ( . , , , . . , , . .bioactive IGF-1 . NSAIDS , . . Secondary prevention , o ,NSAIDS o o o o

. , , , , . ' . , , , 90 . , . . 2000-2008 . 35,000 ) 25,000 Screening .( :screening (FOBT) o

116

Flexible sigmoidoscopy . FOBT 10 )

. .

o o o o :FOBT

.(55-60 . . . ) . , . 3. , 95% , . , 90% .50% . , 5 6

Double contrast barium enema

90 .( , 5

, : .100%

. CT

:virtual colonscopy . . .( ) " 1 , . . . . . . , . . . ' , 50 10 40 :Video capsule ,

.(CT)

. ,

117

'
( ) Neurohormonal regulation ' .' . . . CCK . , ' , . ) ' .( ' " aurbach plexus . ' Meisner's plexus . ' , . ' ,splenic flexure

, , , '

.( ,

) " , . " . . '

, : ' , . o

, , " .

" CCK

. .

. . , ' .( "

-Juxtacrines )

118

VIP CCK , , . " . , 34 ,17 . . ' ) .( " ' .

" .

CCK FFA " . . (

CCK 12 .

CCK , .

Motilin . , . G cell . , . .CCK-B receptor I- " CCK .CCK-A & CCK-B receptors ,cell CCK-B receptor , " CCK-BR . , CCK . '

119

, . CCK , . . ,secretin family , . .CCK-BR CCK

.I & G cells ' I cells , ,gastrin family .GIP VIP , CCK . candidate

' .G cells ,

, . CCK-A receptor

-hormones , , . ,

Pancreatic polypeptide Peptyde YY . ' . Enteroglucagon . Saliva : . . . . ] ' .[ .ducts . ACh) ' .(NE) ( . , , . ducts , -parotid glands

-submaxillary (submandibular) glands -sublinguinal glands

120

,( .( ! ' . ,

) betanechol .( ) !

) Atropine

'

lipase . "

amilase

.( pH , ATP

) 6.8

pH ,' . ,

" (7.8)

, .flow rate .

.OH

pH

betanechol

:Case study .atropine Esophageal secretion

' . . " , . Gastric secretion

"

pH

cardia

121

. . , " . . ,( , ) chief , .(surface & neck mucous cells) . ]. oxyntic gland pH , [ ,chief . , .( ) , . . chief cells . . . .( " 30%) " ] , .[ ,Omeprazole proton pump . NaHCO3 , .( ) pCO2 , , . , " , . , .( . D cells G) pyloric glands .

. .

. Trefoil peptides growth factors . .

GF

122

, .( . ,

. ) pH " . .0.8 . pH , . .6.8 pH " pepsin ,

"

canaliculi . canaliculi , , . .H-K ATPase

.proton pump ,CA " .( ) pH . . [omeprazole, lansoprazole & pantoprazole] . , ' , H-K ATPase

123

omeprazole

,omeprazole . plavix ,

,plavix .P450

plavix

H2

3 .receptor

.ECL

. cAMP . CCK " CCK-B

ECL cell CCK-B receptor , .M3 . ,Pirenzepine M3 receptor , , H-K ATPase ECL proglumide . D . " ECL ACh , . antagonists PPIs ,

H2 receptor

. .cimetedine

.(omeprazole, pantoprazole) , .

.ACh "

124

" .

The magic number- pH 3 3 pH , pH .3 pH , . . . .3 . pH , : .(' , . ) , , . . , . .pH . . . .PYY , CCK " . , " .( . ( ' . . , . , . Non parietal gastric secretion , .7.4 surface neck cells pH , ) . -Circulatory , , ) -Intestinal . . . 40% cephalic phase -Gastric . , " -Cephalic .3 pH

125

30 . NSAIDS ,(PGE1,2 " . ,

chief cells

"

leptin PYY . Ghrelin . . Cholecystokinin .

L cells

Duodenal secretion . . . , villi goblet & columnar cells , . , . . -proximal to distal gradient of secretion , pernicious anemia PGE1,PGE2,cAMP, VIP, HCl " . 5-hydroxytryptamine, carbachol , ,NSAIDS PCO2 [! ]. 1600 . pH , . pernicious anemia

. .calcium channel blockers ,

126

Pancreatic secretion

.papilla of Vater ,CCK " ,ACh " ' . , . , . . "

, I cells

. , " .

CCK .CCK ' . " . , I cells CCK pancreatic duct . CFTR ,cAMP . .

, H2O CO2 CA . . , CFTR " .CA "

127

, . . . .(CCK ) , . , pH

,protein malnutrition -Kwashiorkor , , , .CCK pancreatic duct pH , . , I & S cells . FFA , S cells ,FFA .I cells . : 90% . 7% -Amylase .2% -Lipase , . .1% -Nuclease '

. .

, .lipase ) , (

128

.lipase

amylase ,

) proelastase .

, " , . . ,

,colipase . .

-Procolipase

-Trypsin inhibitor ,

.pH=7 . "

, trypsin inhibitor , .

'

"

enterokinase (enteropeptidase) microvilli . congenital enterokinase deficiency . deficiency ) .( . CCK carboxypeptidases .

. ,

-Monitor peptide ** Liver and bile

.bile duct . . , bile duct . )

, , portal vein sphincter of Oddi , .

, , 3-4 .( ,

.duct . .(pancreatic duct ) ' hepatic duct primary & secondary bile acids " 400 . , .( ) . .(Crohn , . . bile acid pool .bile salt )

. .conjugated or unconjugated 7-hydroxylase , . terminal ileum , ,10 . .

. .

129

, ] .[10% 4% : 50% 18% 8% 2%mucin 1% 17% . , , . . , . . , ,( lithocholate ) . , . . . 5%) . cholate & chenodeoxycholate . . deoxycholate & lithocholate " .( . " . . . , . , .( (75%) Glycine .(25%) Taurine Lithocholate acid . , .( . , ) ) , .

130

, . cAMP . . ,

. . . ' . , . , . . . . -Ursodeoxycholic acid ,primary biliary cirrhosis .bile acid pool 40% 15mg/kg/day . .(bile salt binding resin) -Cholestyramine .ursodeoxycholic acid . " 200 " 800 intake . : . , ,lecithin , . . ' .

. " 1000 .

Small and large intestines Digestion & absorption of protein- small intestine . . . " . , . . . " . . .Na-K ATPase . Digestion & absorption of lipids- small intestine " pH .( acid lipase ) . brush border peptidases . "

131

.[ pH

pH=4

,pH=3-4 , .

pancreatic lipase . .pH=7 , pH pH ,

. , .7

acini

colipase pH 7

.long chain fatty acids . , .

. .

. 3 " . , . . acid lipase

pancreatic lipase ,

, , 5

. . " .

. , . . . ( . , , , ,left subclavian vein . medium ) MCT . ,thoracic duct ) . thoracic duct . , " , ,

MCT .(chain triglycerides Digestion & absorption of carbohydrates- small intestine

132

pH .(

.(! -

) maltase

"

"

amylase sucrase ) lactose ,maltase ,

brush border .( .

Congenital maltase deficiency . lactase . . lactose . ' maltose Fructose intolerance , ( ) ' . , -Amylase

.amylose

. -( . . lactase deficiency lactase , , , ) sucrose

. . ,

, ' 2-3

, lactase ,

'

, ,lactase def ,

Lactase def . .' . fructose def

133

, lactose ,

. . -

lactose intolerance .SCFA (short chain fatty acid) . cAMP Methane (CH4) . . [ ' " 1:50 *] lactose ,lactate

. . lactase

SCFA CO2

Water flux- small & large intestines , . tight junctions leaking , . , , . . . , '' . junctions

: " 8500 . " 8300 . . , '' .( '' . , . < < ' ' : , , .

'

134

, ,

4.6 " . . ,

. , , " . ' !( , ) .

''

. Colon

'

24

' !

36

" .

short chain fatty acids

. " . candidate hormone , . PYY " . . ' . SCFA . . , . , , , PYY . . ,' 20-30 , . ' ,

. , . PYY '

135

Pancreas, gallbladder & liver histology

( ) Pancreas . .centroacinar cells 3-4 interlobular ducts intralobular ducts duct system .papilla of Vater .centoacinar cells " 1200 .acinar cells 40-50 acinus

common bile duct

intercalated ducts main pancreatic duct

amylase, lipase, DNase, trypsinogen, trypsin inhibitor , DNES cells " CCK " ACh ,

acinar cells . . .

chyme ACh " DNES cells " secretin " duct system .(... "

Centroacinar cells . . ) , , ' 50% .70% Gallbladder

.acinar cells . .

DNES , .

CCK " CCK . .

. ' ,

,villus

.simple columnar epithelium . 8% common hepatic ducts 20% . .(pigment stones 20% cystic duct Gall stones

. .

80% ) Liver :

136

. . ( , )

" . " ,urea ,

-Detoxification of ammonia .

cognitive ,ataxia ,tremor

.impairments & coma , . . . . , 15-20 . :Endocrine like function . , . . IGF-1 ( . D ) T3 T4 25-vitamin D , , , , protein malnutrition -Protein synthesis

:Liver and vitamins . . 2,7,9,10 ). " IF uptake -Vitamin A -Vitamin D -Vitamin K -Vitamin B12 .(

137

75% hepatic artery hepatic ( )

25% .portal vein .portal vein model 1 -Hepatic lobule

portal hepatic artery , . ' .

central vein .tracts central vein portal canal hepatic artery ' model 2 -Hepatic acinus

, . zone 2 . ,zone 1 .zone 3 , zone 3 . . zone 1 zone 3 ,

hepatic

hepatic artery .intralobular bile ductules

-Portal triad ,portal vein

central .vein . . . space , space of Disse microvilli hepatic stellate cells (Ito cells)

138

pericyte )

.of Disse .(like : Ito cells Ito cells

. stem cells & progenitor cells . .vascular resistance . . " duct .bile canaliculus .tight junctions " " ' , Ito

Ito cells -

-Portal hypertension Kupffer cells

139

Neuroendocrine tumors of the GI tract

( )

Pathology
Carcinoid tumors
, . ,low grade malignancy .( . , , . . . " 2 . .keratin .S-100 chromogranin, synaptophysin, neurofilaments mesocolon , . .( ) EM .( ) , .

, ) neuroendocrine bodies : -Foregut papilla . -Midgut . -Hindgut . -Midgut .

80-100%

" 2

]. [

140

. .

, , . . , , . . . -surgical margin . .(

. 99%) -mucinous carcinoid *** . , " ' " ,

Pancreatic islet cell tumor

insulinoma, gastrinoma, .(30%) (70%) . . , . 10% ,multiple adenomata 10% , 10% .( , . . . ACTH , 5 , " 1-2 .islet cell tumor 2-3 . . ' . . . . . , islet cell adenoma " Poorly differentiated islet cell tumor , , 1,300,000 stem cels ) , , 70% - cell tumors .' somatostatinoma

141

. .(

VIP ,

, .

.paragolgi )

'

EM

, , .(

Clinics
NET- neuroendocrine tumors PET- pancreatic endocrine tumors (amine precursor uptake decarboxylation) Apudomas . , , 84 post mortum , . .PPIs . , , ' : ' . 10 7-13 , , GI-NETs NET .

Multiple endocrine neoplasia, type 1 and type 2/medullary thyroid carcinoma Carcinoid tumors Islet cell tumors Pheochromocytoma/paraganglioma Poorly differentiated/small cell/atypical lung carcinoid Small cell carcinoma of the lung : . MEN-1 Parathyroid hyperplasia (>95%) PET (80-100%) Pituitary adenomas (54-65%) Adrenal adenomas (27-36%)

142

. .

:NETs . 4% , 28% , 28% ' 64% 28% 8% , , . uptake . . , .pellagra , . 12 ) . ! 20 . ( 6 flushing ' , . .

, 5-HIAA

Carcinoid tumors
Small intestinal carcinoid , . 60% ' . . , , . . " .(IBS ) Rectal carcinoid . 50% . . . , 5% 50% . Carcinoid of the appendix " 2 , " 2

143

35%

, " 1

95% . .

200-300

. " 2 . , . " 2 , Gastric carcinoid . , .atrophic gastritis IF .10% . ( ) .Zollinger Ellison syndrome . . pernicious anemia . -Type 1 B12 -Type 2

. ,

-Type 3 . 15% . 50-70% . , , . . ' . Carcinoid syndrome . , : 94% -. , . -Flushing (1) 78% . . " paroxysmal hypotension , , , ,( ) telangiectases .( . 53% (2) (3) .

"

144

.( " . '

) , . 5-HIAA

.( " ) ,

, , .(0% ) .(

, , ] 5-HIAA .[FP

, . , , . , , ,

somatostatin receptor . . EUS] .

-scintigraphy OctreoScan EUS MRI ,CT capsule endoscopy .[CT

. . , .

, .

5-7

. , .

. , . . . . . Zollinger Ellison syndrome . . " . , Octreotide

145

. , .H.pylori

MEN-1

ZES ZES 95% .ZES

.ZES .pernicious anemia .

, , ,ZES Insulinoma

, .

. c-peptide .' ,EUS .

146

( ) , . 3,000 . , , . . . , ' , . . . , , . 90% . , ' . " . ' , , " 1:20 , 50 , 2000 .screening ' ' . ,

20-30% . .HNPCC FAP FAP

, .

.APC 20 .total colectomy . 90-100%

total colectomy

, )3 . " , . . CT

.( . " colon carcinoma

desmoid tumor

147

.( .(FAP

) ureters ) HNPCC/ Lynch syndrome

,(

) .

"

type 2 ,lynch syndrome .

mismatch repair .

'

HNPCC ,

.genes Family history

) , 75 !

,' .(3-4 .40 Other Predisposing Factors polyposis syndromes . ,(crohn/ulcerative colitis) IBD (Peutz-Jeghers ,Turcot ,Gardner's) Colon carcinogenesis

, ) carcinoma in situ .

. . .(

10-15 .

148

, Primary prevention

5 ,'

45

Screening

. 10 ' . .

+50

' , ,50 +50

. , , . . . . . , .' . , , ,( , , , ) , . , .( ' , ) tenesmus . , , , ,

Virtual colonoscopy CT Barium enema CBC & blood chemistry

149

25% . 75% ,

-CEA (carcinoembyonic antigen) , . screening PET scan

.(90-95%) . .undifferentiated

' ,mucinous adenosquamous signet ring SCC Carcinoid tumors Nonepithelial Tumors Leiomyosarcoma Others " T,N,M " , . , seminal .T4 , ) . ' . .4 -M1 , . , T , vesicles N grade staging N T

Hematopoietic and Lymphoid neoplasms .

150

.(A-D=1-4) , . 85-95% ,1 .5% 5 -

stages

dukes' stage

. ,

4 .

5 2-4

Prognostic factors . CEA Stage ! signet ring & mucinous , , -

, . . ' , -

-Neoadjuvant therapy

151

-Adjuvant -Palliative , . .right hemicolectomy .sigmoidectomy .Anterior or Low anterior resection of rectum -abdomino perineal resection and colostomy lower rectum .

. ,

, -

'

. .( ) ' ' . . . . , ' ' ,3 , . 2 . CRC .5-FU .Leucovorin , .thymidilate synthase . .hand foot syndrome .(Xeloda) PO . , , . , FU-5 , , , ,

-Stage 1 -Stage 2 -Stage 3 , -Stage 4

5-FU

Hand foot syndrome

152

.tumor specific : TOPO 1 , . , .

Xeloda

-Irinotecan (CPT II) .DNA . ' 60 days mortality .

. . , . , dose limiting toxicity , , .(atropine PO 5-FU .hand foot syndrome . .DNA ,( .(' -laryngopharyngeal dysesthesia .(' , , . ' ) ) .

-Capecitabine (Xeloda), UFT ,Xeloda UFT

-Oxaliplatinum , , )

" .

) . :

. . , ,VEGF

-Bevacizumab (Avastin)

Avastin .

, . .' , .

) (

) '

EGFR .

-Cetuximab (Erbitux)

EGFR

KRAS .KRAS-WT

, .

153

, . .

, dose limiting toxicity Panitumab

) 5

5 10% ,

20% , .( .

154

( ' ." , ) .strech ' " .( . .( , . , .' . , . , . . ) LES . . . ," ( ) : Barrett's esophagus , cachexia .(' , ) , , .( . .' . -intestinal metaplasia . Barrett's esophagus ,(achalasia) reflux disease . (' ) . ,72 DD , , , .( Achalasia . . , , . , ' , , . , , . . )

) . -

155

. . . . . 1%) Barrett's 10% .reflux . , , ,

, , ,

, 10% Barrett's esophagus ,(reflux Barrett's .

' .LES . LES ,' LES ,

. , , .

156

( ) , , . . , . : , [ " . ] .850 400-850 ' , .400 , "

,(

. . , IgA . 2 , . 13% . . ' tight junctions . canaliculus . . , . .ductules of Hering , . terminal ileum ,Crohn's , ,papilla of vater .( .termianl ileum , " ' , (central vein , ) .

.1m

157

. . , . , ' .17 . cholic acid & chenodeoxycholic acid taurine & glycine . . " . . .(lithocolic acid & deoxycholic acid) . , , .( " , ,ursodeoxycholic acid ) . . . , . . ,

'

BSDF & BSIF bile salt dependent/ independent . BSIF " 250 , . " 250 . ( Na K ) ) ,

.bile flow

80% .(ATPase -Na/H exchange .

CA "

]. [ ' ,

-Na/HCO3 symport

. '

-NTCP-Na taurocholate cotransporting polypeptide NTCP . . taurine . cAMP NTCP . ,

(organic anion transporting polypeptides) OATPs .(organic cation transporters) OCT ,

, . , ' ,'

158

. .multidrug resistance proteins (MRPs) , . . , . . , ) , . . . : ' , fine tuning .( " . , , , , . , , .

. , .

, , , .

CCK .

, .

CCK

. .Na-K ATPase . .10 " , . " 600 6-10 . .

.' 3-5 ,(T tube )

Cholestasis
. .(GGT ALP) . ALP : .

GGT*

159

. . ,

. . , . . . . . . . . ,( .( )D ) . . " , . . .( ( iris 80%) ) Kayser-Fleischer ring .RTA . . , , K . A E , " . 3 . , 450dl/mg ( )

. , . 5 n nucleotidase GGT ]. [

160

. .

2-3

, ,

. , .K , . RBC . : . . Ursolid- ursodeoxycholic " , .acid : .MCTs , , , " -

1'25-vitamin D .

A,K,D . :

. , . . . . . . . . , , . .

-Cholestyramine 4-5

-Naloxon -Rifampin -Phenobarbitol . -

o o o o

161

. .

-Ursolid

: ) CBD .( papilla of Vater .( ( ) ) PSC : . " ,RUQ

AIDS cholangiopathy

US .' . , ,

. , .

, ,

-US (EUS) -ERCP

.PSC . . MRI -MRCP

162

.(percutanous

. : . , .( , ) TPN . : , -

" : .PSC PBC ,

"

,CF Primary biliary cirrhosis

. . , 0.5-2% .40-60 , .PBC HLA-II ' , [ . . . , : . PSC ( , ) Drug induced cholestasis . , DD graft vs host PBC ]. CTLs .

163

( ) C : * * * Mixed connective tissue disease * CREST * * * * * * Sjorgen : anti ) AMA-M2 .IgM .pyruvate dehydrogenase

(mitochondrial antibody .rheumatoid factor ANA : staging -1 -2

. .

. -3 . . 2-7 2mg/dl . . . . , , ,6mg/dl . -4

164

, HLA ' . .

. . . , .

UDCA

. . ,colchicin . Primary sclerosing cholangitis . . . . ,

.( [PSC ,

) 25-45 2-7% ,UC ,

(2:1) ] .UC

2-7:100,000 70% , .

.Graves disease

,SLE .HLA-B8, DR3

T . 1

IgM .cd4:cd8 , .

( .

15% ) RUQ

, . . 12 :

.PMN . .piece meal necrosis . -

-1

-2 , -3 -4

.MRCP

ERCP

.AMA

165

, . AIDS

secondary sclerosing cholangitis , . .

CBD

, .

. . . .UC PSC !

Ursodeoxycholic acid

166

( , . , : hepatocellular injury ALP .bile duct ,cholestatic injury .GGT . , . . : . . ,' 8 ' 25 , ' . . ) -Idiosyncratic response of the individual (2) , " ' . .( ' ' 4" " (1) " 10% .

. ) Microvesicular cholestasis ,steatosis -( , . ( ' .isoniazid )

167

,( . , ,

) bile cholestasis , (cholopromazine)

.Valporic acis .allopurinol , . . , mixed ) MFO , " , . .cytP450 (function oxidases .epoxide hydrolases .P450 , , , , ,macro/ micro stetosis , , Granulomatous hepatitis

' ,P450 . , . "

: ! . . veno-occlusive disease , 5 ALT AST

, Isoniazid . Halothane Azathioprine .

168

, .' (HIV

3-4

ALT AST 60 .drug induced liver disease , .

3 3

. . . . ,

) , -biliary obstruction .

.(

.anti smooth muscle antibodies, Wilson's disease , . ) , .( . : , ' , ,

' **

-Very likely .drug hepatitis -Compatible -Doubtful

. :

-Incompatible

paracetamol, isoniazid, pyrazinamide, ketoconazole, valproic acid .NSAIDs, sulfaonamides, antidepressants, halothane :acute cholestasis

169

.azathioprine ,tamoxifen ,erythromycin ,

-Pure cholectasis

phenothiazines, NSAIDs, macrolides, sulfonamides, beta- -Acute cholectasis hepatitis .lactames, tricyclics, carbamazepine . amiodarone . . induced liver disease Amiodarone***

'

8 .

100%

. ' .( ) 12 -

-N acetylcysteine .

.Phase 2&3 . .

170

IBD- pathology
( ) , 2 IBD ulcerative -UC crohn's disease -CD : . , .colitis , . . (CD IBD . . ' terminal ,( .terminal ileitis . ,( 40% ) , ) , ,

-CD
) .ileum 30% .colitis

crohn's

.skip lesions ,

CD . , .(inflammation , , ,

trans mural ) .

' , -fissure ulcer . . . ,

.creeping fat , , . Cobble- . .CD CD .

cross section

-stone apperance

171

aphtoid ( ) .

, -ulcers

' fissure

aphtoid ulcer , . .ulcers ,CD UC ) CD '

40-

, .(50% .30-40% .

pan ) .

-UC

continuous colonic involvement . (colitis terminal ileum pan colitis .back wash ileitis 10% . UC ,pseudo-polyps .( . , .mucosal bridges UC .crypt distortion , .

.(

) .( ) shallow ulcers ) non neoplastic polyp ,

UC -cryptitis [inter-epithelial neutrophils] . ** . .UC ,

,CD

172

.carcinoma . , . , '

, , , '

CD

10

UC

. ,high grade dysplasia low grade dysplasia . .

173

IBD- radiology
( )

CD
: ' ,

aphthous ulcers . . : .(UC . . . . ) ' , , -Skip lesions -Cobblestone appearance

. CD .

( . , .

.(string sign) .prestenotic dilattion -sinus tract , .

174

, . . , .CD . ,creeping fat ,skip lesions , CT , , . . , , , , . , . . CT , .CT , . DD ' CT Crohn's colitis

UC
. ( , ) thumb printing .plain field splenic flexure

" :

' : -Pipe stem Back wash ileitis

. , ) sacroileal joint . ,CD UC , .( **

175

IBD- clinics
( )

.indeterminate colitis/IBD . . , , . . . ,' ) , UC , , .( , . , , CD ' IBD

'

"

. .

. . incidence UC ' .

,60 . ' .60-70 20 peak

UC CD

.~20

,(

) .

IBD

. . , .IBD : UC .UC . . nicotine patches CD .UC , ,

176

.UC

.(crohns colitis) .UC -

CD ,20 ,

UC

-Appendix 20

( . , , , , , , ) NSAIDS .UC ,16 (crohn's 20% ) CD NOD2/CARD15 CD . .ASCA ASCA -CD , ASCA UC ,CD . ) . CD .8% 20% , ,CD . CD .60-70% pANCA 15-20% pANCA , . " UC , " -50% . ' .( 5% ASCA

UC
. ' , .(' ) UC -(relapsing) 10 , UC ) UC , .( ,UC , . CD UC

bacterial colitis

177

.( .(CD

) )

, UC ALB:UC

IBD

.UC

, .

CD -Age

-Location .

,Proctitis :E1

Left sided, up to splenic flexure :E2 Extensive proximal to splenic flexure :E3 .E2 " ,E2 -Behaviour -S0 mild . 6 -S1 .moderate -S2 Severe . (4) (3) (2) , . : , -toxic megacolon) .( " 6 . . , . ' 20% CD ] . [40% : " , . 10 30 , UC (1) " 20 -S3

Mayo score

-Refractory disease

178

.20% . ' , :CRC . . .(E1 , . , E3 , )

, :

, CRC .5-ASA NSAIDS .

-Extra-testinal manifestations

CD
, . (PSC ) . ' , . . . , , . . : . CD ( ) ANCA positive NOD2 mutant ) .( : 3 ) penetrating stricturing ,( , , ' , , . , bile duct ,

179

,video capsule ,MRCP ,MRI ,EUS ,CT ,

" .

. . :

-Deep enteroscopy

-Crohn's disease activity index (CDAI) Number of liquid or very soft stools during the previous week Severity of abdominal pain / cramping General well-being Extra-intestinal manifestations Presence of abdominal mass Use of antidiarrheal drug therapy Hematocrit (compared with normal) Body weight (compared with normal) 450 . 150 . .CD .(0 . .UC CD . ,UC ) 70 -c reactive protein -CRP CRP CD . CRP ' " ALB Age ( ) 16 17-40 40 -A1 -A2 -A3 -TNF

Location -L1 -L2 -L3

180

-upper gastrointestinal system -L4

Behavior nonstricturing nonpenetrating -B1 -stricturing -B2 .' , -penetrating -B3 IBD . . , ,

. ,CD

UC . .

5-ASA

prednisone . . , . .

. .budesonide . ,budesonide

(Imuran) azothioprine .Methotrexate

181

CD

(humanized

" ) Adalimumab Infliximab (anti TNF) . Certolizumab Natalizumab .UC [IBD T

.CD

T cell depletion

Visilizumab ]

182

. , . ' 20% , . 40% . , ,16 : ,

.isolated indirect hyperbylirobinemia , . Gilbert . .( . , Gilbert syndrome ) -

, . .

, . , ,16 :2 . . 57.5 . . -ALT ,AST . .' ( , , . , , . " . 3 PT ) 3.5ALKP

, , .

3 PT . . , ,ALKP .( . . . " , ) ' . "

.ALKP -

183

: . . , :16 HAV,HBV,HCV (herbal medicine) 100% , . . , , .(coombs negative hemolysis ' , , . , . .' : 3 IgM . . HBsAg IgM anti HBc Anti HCV , , .HCV . anti HCV , ) , , HBV . . HAV . IgM anti HBc ,HBV . anti HBc HBsAg IgM anti HAV .HBV anti HBs . , HCV , HAV -IgM anti HAV ,CMV , 100% -"all or none" . (5-45) , -Wilson's disease PT

.(

184

. . " .

, , .anti HBs HBV ,A : , .

anti HBc , anti HBs

anti HBs anti HBc

, occult hepatitis b infection , ,

CMV

) [

, ]

,(

. ? . . . ( , AVH ) . ' 3 . " . ,50 , .( .ischemic hepatitis . DD . . . ( ,50 )1 AST ALT . :4 , :3 ) -PT

185

. . . isolated "transaminasitis" . , : (1) (2) (3) . , .50 . " , . , ,( . ! : , HBs Ag [. ,HBV -Anti HBs] Anti HCV ) US , (4)

HCV
20% -PCR " . . .( . , ) . , PEG-interferon .( , , )1 , PCR PCR ,HCV

186

, .

, HCV 4 . 80%) 1-3 , . 6 5

. .50%

, 1 .(1

, , PCR

.sustained virologicl response . : "

12 ,early virological response PCR .' 48 , .24 ' PCR

, . , -

(2log) 24 ' .' 72

100 PCR

. . . , 4' , PCR

100 "

PCR

. . . .1 , , , . . 15-30 . . , 2 HCV , ' 48 ' 24 3 2

HBV
.( ) . . 30% , PCR ,HBV '

187

,(HBV

DNA ,

RNA .

) HIV Reverse Trancriptase . 20% , lamivudin .

. . ,

, , B . 2 " ' 2000 -

. , . ,

. . , ,

188

( ,25mmHg . . . .(gastroesophageal reflux disease) GERD . , . : ' , 1/3 sliding hernia , paraesophageal hernia LES 5mmHg

.LES , .LES , .(25mmHg) UES ,(60mHg) . . : , . . . . . . . -Heartburn -Chest pain . .

189

, pulmonary ) , , .

. (aspiration .

) osteophytes Zenker's diverticulum, neoplasms, cervical web . ( , ) . . .( , . . , . , .( ,achalasia) , ) -( ) .( ,

190

. . . .Chagas disease ) . , achalasia achalasia

-Achalasia . dorsal motor nucleus ** .( )

.(20 : .

,60mmHg

. . . ) . ] . .[ , , ,

achalasia , .(

, ,

.[

achalasia -

. ,(" ") . ,

191

) .( .LES achalasia . , 80-85% .anti reflux procedure , , ' -Myotomy , . -Pneumatic dilation . , . . . ' . achalasia calcium channel blockers ,botulinum toxin -Hypertensive LES ,

3 .

. 10%

" , ,

LES calcium

. .

-Diffuse esophageal spasm achalasia , . . .channel blockers

Gastroesophageal reflux disease- GERD

, .[GERD , . ] 60% . " .esophagitis .( 20% . .GERD , " ) .( : . 1-1.5 . , , " , , GERD 40% 5%) ' 60%

-non esophagitis reflux disease -NERD

'

192

. : -(weak LES) ] .0 [ , ]. [ ) . . , . transient LES relaxation , . transient LES relaxation . . : . LES . , . , reflux .(NERD , ) . ' .esophagitis . .( . " . .guide wire . . , Barrett's . . , -Schatzki ring -Barrett's esophagus ) Barrett's esophagus " , . , , , . , , , , , . esophagitis . LES LES , -Transient relaxation of LES ( , , , . LES "

weak LES

193

Barrett's confocal endoscopy . :Barrett's . 3 . . , low grade dysplasia high grade dysplasia :

75% . . , : -ambulatory pH monitoring -Dyspepsia

.(4

pH ) .

4%

.' ,GERD .

24

. . .Barrett's .

PPI

-proton pump inhibitors . . .(antacids)

, , ,

, .

194

, . , . , .

.(fundoplication) . ,

195

( ,portal vein , . . . . . . . , ,ER , . , : , , , ' , , , , , -first pass effect , .hepatic vein ' .

-Phase 1 , , ( , , ) .p450 -Phase 2 ' ,

, .('

2 . .2 2 .( . . ,prodrug 1 )

196

.( .(50%

) ) -

PO IV

-First pass metabolism .

Age Diet Genetic Variation -State of Health " ' -Gender -Degree of Protein Binding Species Variation Substrate Competition , . .' . IM ,IV Route of Drug Administration Phase 1 , ' . CytP450 .cytochrome P450 ' , . . , ER , ' -Enzyme Induction

60% .

' ' .CYP ' ' CYP 10 NADPH . ' [reductase , , 5 ' ' ]. heme flavoproteins 450nm . heme '

. .

197

. . 60% . . CYP CYP ' .

CYP

CYP

CYP3A4

cimetidine

, .( . CYP 28% . 60% . first .

CYP ) -CYP3A4

pass effect .PO

CYP3A4 . ) Ketoconazole ( .CYP3A4 HIV protease inhibitors . imiparamine ,theophyline ,nitrosamines , -CYP 1A2 . . , .CYP2D6 . : -Poor metabolizers Intermediate metabolizers pro drugs . ' ' . -Fast metabolizers , -CYP2E1 , -CYP2C -CYP2D6

.(diclofenac) . ,

198

. . CYP2C9 "

-Ultra rapid metabolizers Warfarin .

.CYP ' . 100% , 8 . . ,

-Nonmicrosomal oxidations , , ,

. Phase 2 .UDP- glucoronosyltransferase , . ( . BBB ) . 3 6 .6 3 . . .quinones epoxides ( DNA , , . . ) , heme , . '

199

IBD
( ' , . . 30 . . . UC , . . . . , CD ' , . . . . . . .mild/moderate/severe (-carcinoma in situ) . . .( ) .total colectomy . ) ,( ) UC ,( " 10 , 10 . ,B12 , CRP , ) ,( . ' ' folate conjugase . .(UC ,( . ) . . ( ) . ) sulfapyridine pipe like , , , 0.5 , , UC* " : . ileostomy , .60 20 .(CD ) UC : emergency , 20 total colitis )

200

. . . . .

, .total colectomy

sulfapyridine . 5-ASA , ' .distal colitis/ left side colitis , . .' , , . ,folate def , ,

5-ASA ,

5-ASA sulfapyridine , , . .male infertility

" .cyclosporine .(

. , ) toxic mega colon . . asothioprime (purinethol) . " 1.5 . -budenozide* .PO

6 mercaptopurine

) IV

-anti TNF infliximab.adalimumab (humira) SC 100% asothioprime cyclosporine .(

.(

sulfapyridine + 5-ASA ) infliximab/adalimumab ( ) : " -toxic mega colon .

, metabolic , ( total

, " 1.5-2) ' 72

. " 6 IV . .(50%) (

alkalosis colectomy

) :Extra intestinal presentations pyoderma gangrenosum -

.UC

201

Liver tumors- clinics

( " 2 . US MRI . . , scan , , CT ,HBV . ,55 : feto protein (AFP) . ,55 :2 US . feto protein CT . AFP . . , . . .hepatocellular carcinoma AFP )

feto protein , :

)' .

1-20%

.vascular malformation , .(5 . " 4-5 " 5

,giant hemangioma .(Kasabach Merritt syndrome) DIC , .

202

" ) -

, ,

CT . . .( " 5 .

US

. , . .US ) SPECT .( 10 . ( " 10-15) . . " 2 ,US 25 . , .MRI CT , , .

,MRI (SPECT)

" :3

MRI

CT . . ,55 . :4

. . . ,

Hepatocellular adenoma
, CT , . ) rupture .( . ) , .rapid wash out (hepatocellular carcinoma) HCC CT wash out .HCC , . , . " 5 ) . ( , CT ( DD , ) .( hepatocellular carcinoma ' -portal tracts .' portal vein

, .

203

Focal nodular hyperplasia

.(30-50 ) . .FNH , . .central scar CT . : , , CT

. HCC . 80-90% .

4 . , .

HCC
.( ) HBV : HBV 50 ,40 . US . US ,US HCC ,AFP . . . . , , HCC 20%

204

. . , .rapid washout .( ) 80% 200ng/ml ( ) .10ng/ml . , CT HCC CT .HCC . FNA . , " 2 AFP HCC HCC . 20-30%

, AFP

,CT *** HCC US

. AFP

US .

, " 1 MRI . . MRI

200 " 2 1

HCC .

205

Liver tumors-pathology
( . . .( .(stellate star) . . needle biopsy DD , . (feeding artery) . , , , focal nodular hyperplasia , ' , " ) )

. Hepatocellular adenoma

. . , .adenomatosis , , , ) , .( .portal tracts

Rupture . Cavernous hemangioma

. . 20%

. " . . HCC . "

206

. " -

,( , )

) , ,

.( . .

-tumor thrombus . vena cava . tumor emboli ) , HCC .( intra hepatic HCC ,

.HCC portal vein

.spread well . . DD . ) . well .differentiated , , ( ' HCC , differentiated

.(pseudoglandular/ acinar pattern)

. , bile " .plug

DD , . . HCC ,bile , poorly differentiated

HCC

207

.(vascular invasion) . .( ' , ) FNH . " , HCC HCC

tumor thrombi

HCC )

Fibrolamellar variant of HCC HCC .(

, . , . , ' . ( . ) " HCC

208

( .( 15 ) ALT AST : , ,42 : DD / . " hepatic -Wilson disease ,Budd-Chiari syndrome .artery ligation -Acute bile duct obstruction . ! (ALD) Alcoholic liver disease .ALD .( " .(' HCC ) , ) . alcoholic , 80-90% , . : ? ? ? ? : -portal hypertension ' 8-20% ,steatohepatitis CAGE criteria 30% 4% 5000 60% )

209

" Palmar erythema Testicular atrophy Malnutrition Dupuytrene's contractures, parotid enlargement : . . 50% -AST/ALT AST GGT . , ) .(' . . .RUQ , , US 300 MCV

vascular spider

(non alcoholic fatty liver disease) NASH .

' 20

.K . "

B12

, 1.2-1.5

. , '

, 35-40

210

,18

MELD

32

MDF

anti TNF -Pentoxifylline NAFLD- non alcoholic fatty liver disease . . .( NASH . . ,PMNs ) ,NAFLD , . 50% , 80-90% , 80-90% . NASH , , NASH , , NASH NAFLD 5% ( )

. US .US .US , ' 800

5-10% NAFLD , (

5% ) . morbid obesity . ,

, .

211

( . : ' -Steatosis (fatty liver) . . , . . -Alcoholic hepatitis . )

. -Mallory bodies . .( Wilson ,HCC , ) ,

(ballooning)

.( .

'

, ,(perivenular) chicken wire/ pericellular -" " .(Masson) " .fibrosis central vein .portal tract . ridges -Cirrhosis

212

, . , . , ) .( ( . , ) -Hepatocellular carcinoma NASH NAFLD , "

213

Peptic ulcer disease

. .5%

Chronic gastritis
:(ABC) ,pernicious anemia . ,(HCl ) H.Pylori -Bacterial . . bile reflux ,NSAIDS -Chemical 3 -Autoimmune

intestinal metaplasia .

. . . NO , NSAIDS , , . , , , . : Ach (M3) Gastrin (CCK-B) Histamin (H2) PG .H/K ATPase .H2 receptor antagonist ,Cimetidine .H/K ATPase . , . , ' . . : , PPIs , , , ,PMNs ,H.pylori , , -

214

. NSAIDS coated aspirin . , . . ,PG COX . COX2 . NSAIDS , . , . . . .GI .( Zollinger ) ) , COX2 inhibitor ,

-H.pylori (1) -NSAIDS (2)

COX1

Vioxx , (3) , .(Ellison syndrome

duodenal ulcer 25-75 , hypersecretion malaena

gastric ulcer 40< ,

hematemesis
.(! )

, , .

. crohns, eosinophilic gastritis, ZES . :

' .

.(malaena) 10%

(1)

. . . '

'

(2)

(3)

. . . ,

215

Antrectomy .

" .

, selective . .

vagotomy pyloroplasty vagostomy

Helicobacter pylori
. CO2 urea -urease . ' ,

, ) Meckels diverticulum

. gastric metaplasia ,Barretts esophagus .(gastric metaplasia . H.pylori

' . .

. ' , . .

, urease .

. .

3-4

' :

"

Gastiris .Hp .Hp DU GU 90% -Duodenal ulcer 70% -Gastric ulcer

50%

-Mucosal associated tissue lymphoma (MALToma) ?

.(

) D cells , gastric metaplasia "duodenal gastritis" , , ,

, . ! ) , DU .' " , ,

Hp

.('

216

. . '

" 40%

,hypochloridria , .fecal-oral .MALToma , oral- oral ,

: , . , . . . . . CO2 urea .urease , -Urea breath test (2) -(IgG ) (1)

-Stool detection test (3) : :

7-14

Amoxicillin, Clarithromycin, PPI -Triple therapy

.Metronidazole amoxicillin :sequential therapy Amoxicilin PPI Clarithromycin ,PPI , 5 .Metronidazole : Active peptic disease Gastritis Gastric MALToma , . -Univestigated dyspepsia , 5 (1) (2)

217

Cirrhosis- pathology
( , . . ' portal triad , central vein : .( .( - " 3 ) ) ( ( " 3 ) ) ) .( .(piece meal necrosis ) : , , , , , -Established causes .. : , . prussian blue . " ] -Hemochromatosis . o . )

[ ,

-Wilson's disease -1 antitrypsin def

o o

]. .1 anti trypsin .( , ) NASH . PAS+ Diastase ) . [

-Cryptogenic cirrhosis (' Primary biliary cirrhosis

.cholangitis

" Florid duct lesion Stage I -Ductular proliferation Stage II Scarring Stage III

218

Cirrhosis Stage IV .GGT ALP .anti mitochondrial antibodies -AMA Ito cells .lipocyte/ hepatic stellate cell (HSC) .space of Disse '

, ,Ito .

. .(piece meal necrosis) .

central vein

, , ,

.portal HTN .

-Portal hypertension (1) ,caput mrdusae Portal-systemic shunting of blood (2) Dysfunction of liver cells (3)

219

. : . . -Gastrin antagonists (CCK-B) -H2 receptor antagonists o o o . . : . o o o . . Intragastric pH-3 -Intragastric pH<1.5 o o o ' , -PPIs o

220

. .COX2 inhibitors . COX1

-PGE2

Proton pump inhibitors . . ,

-Rapeprazole , Lansoprazole (Prevacid),Omeprazole (Losec) . . . . .GI tumors

Omeprazole

'

' . !

pH

H2 recepto antagonists , , H2 . ECL cells . .

.Nizatidine (Axid) ,Famotidine (Pepcid) ,Ranitidine (Zantac) ,Cimetidine (Tagamet)

calcium TCAS

cimetidine ,

CYP450 . ' .(channel blockers

221

-Cimetidine , . . . ' . -Rinatidine -Nizatidine & Famotidine

, .(blood dyscrasia) , .PPI .( " )

*** pH Anticholinergic drugs .ACh

Atropine (all muscarinic receptors) Telenzepine (M1) Pirenzepine (M1) ,CNS .H2 antaginists . ' 1-2 , ,urinary retention , . 40-50% , 1-3% . .( )

.constipation

: "

H.pylori
. :active ulcer H2 receptor antagonists (1) -PPI (2) -Maintenance therapy . . : ' , , 2 -H2 receptor antagonists (1) -PPIs (2)

222

Amoxicillin Clarithromycin Metronidazole Tetracyclin (2) PGE2 ,20% . .95% Antacids .moderate long acting -Magnesium hydroxide . -Aluminium hydroxide . . . *** (1) : ' -Bismuth .(cytoprotective)

o o o o o

. .

.slow acting -

,fast acting -Calcium carbonate -Sodiume bicarbonate Coating agents .

H.pylori , . ,

,Bismuth , " ' .Bismuth . . "

-Colloidal bismuth . . -Sucralfat (Carafate)

Prostaglandins .PGE2 PG PGE1 .PGE1

20-30 .

'

PGE2 ,

. . .

Misoprostol (Cytotec)

NSAIDS

223

.( .( )

224

( 67 ' . .portal HTN ' , , ' . . , .1.1 Budd Chiari , :13-16 , 1.1 . , . 1.2 1.9 . ,SBP -1.3 -0.8 :17 )

, . . , free wedge

SBP

wedge

Post sinusoidal HTN . .(5 ) Sinusoidal HTN free . 12mmHg Pre sinusoidal HTN

. .

wedge .

free

. . wedge -

69 ' .SBP , .10,000 :32-33

225

" . " 40 . . . .(HRS 1) , . , , . SBP urine output 8-9

,90 -33 ,

, .

. . 160 CT .

,0.6 -

:36

:37 . 70 '

. .flapping tremor , . ) .' , , ! . . . , ' , .( :

:42

Hepatorenal syndrome . . " , . HRS1 MELD

226

Pancreatitis
( . 20% , , )

Pathology
, . . " , Acute pancreatitis , .autodigeation . .phosphorilase lipase interstitial inflammation fat necrosis , .elastase : . , " . ) , . . ) " ) ' , fat necrosis saponification .( . . , .dystrophic calcification , ARF ,ARDS .pseudocysts . . ' ' . pancreatic pseudocyst , . 80% ,phosphorilase lipase . . , . ,( Cholelithiasis . -Acinar cell injury (2) ) ,( CBD -Duct obstruction (1) ,

227

. . Chronic pancreatitis , .

fusion santorini's . . , '

-pancreas divisum , .minor papilla 3-10% "

,duct

.(pancreatic ductal concretions) . SCC .( , ) squamous metaplasia . .pancreatic ductal adenocarcinoma . ,desmoplastic reaction . ,

Clinics & Radiology

Acute pancreatitis . 10% . . ' (2) . , , . .microbilliary stones , , . . ' CCK .autodigestion . ( , ,imuran, 6-MP) . -Drug induces (1) : 88% 2 ,

10%

228

' . . acinarization ,ERCP , .sphincterotomy ,minor papilla . .pancreatic duct .'

. ( 5-15% , ERCP . .IgE IgG4 ,Bile reflux ) -Pancreas divisum

. . , .

Catapepsin B . . , , , . : . ( DIC .( turner syndrome . . . ARDS . , , ) . .

Intracellular digestion

third space losses

, Kellikrein depletion ) Elastase

Phospholipase A lipase :

. . . . 80%

229

.(

) lipase ,amylase , .

: lipase

amylase : DD

Choledocholithiasis Perforated ulcer Mesenteric ischemia Intestinal obstruction Salpingitis Ectopic pregnancy , amylase amylase salivary amilase .3

) .

, " . . . amylase .( ' 1000

biliary colic

lipase ARF -Macroamylasemia

.CT

US .

. .( . )

, ,

, .US

62-78%

US , .

, . , . . , . , ( , ) . .CT 98% , CT ,ERCP

230

.paracolic gutter . . . . , . ' -necrotizing pancreatitis 80% . : , 1% , 10% interstitial pancreatitis . ) 30% .( Tachycardia, hypotension, tachypnea, hypoxemia, hemoconcentration, oliguria, (2) encephalopathy ' 48 . -Ranson's criteria : (1) . ' Focal pancreatitis

: -3

'

10-30% -3-5 . ] .CT CT 80% 9

-Balthazar's CT severity index MRI

231

.[ : ) splenic . , , , . multiorgan failure , , ,ARF ,ARDS : , ,PPIs ,IV .' .ERCP . , , . . , . severe pancreatic ' ' , 24-72 ERCP , ERCP pancreatitis .divisum Chronic pancreatitis .pancreas divisum ,CF , , .protein plugs , . . . . . , CBD US Malabsorption .( ) . , ' " , NGT PPIs ,( vein -

severe cholangitis ERCP .'

232

85% . 10-20 .

. . , , , , EUS .MRCP EUS . . . .( ( . . , [ Bentromide . . . ] -Bentiromide test PABA) ) . ) -Secretin test CCK , gold standard ERCP CT US

( ,

. . :

, .(

. ) . . . , . . : Malnutrition ERCP -

-CBD

233

Splenic vein thrombosis : . , " . CP ' . CCK CCK ,CCK releasing proteins , , . . . , . 50% . cyst structure dilation , sphincterectomy .drainage ' . . US , " 1 . ' " 2 ,lateral pancreaticojejunostomy " , , 3-4 . , . 15 , , ERCP . CCK

.pancreatic duct *** CP

234

. : A . '

(foregut, midgut,hindgut) . , . , , . " . ' . , , , , ) , , .' , .( . . . , . . .(paralytic ileus) . , . . . , . ) . . ( , , , , 6

235

: , . . . . . . , [! . paralytic ileus , . , . -Rovsing's sign , -Guarding -Rebound tenderness

]. : ,

, ,

'

12-24

. , . , , . . . . . , , -explorative laparotomy , , , IBD , .

-Referred pain . ,