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Flashcards in GIT Deck (373):
1

Major risk factor for squamous cell carcinoma of the mouth

Smoking 

2

– “White plaque on the oral mucosa that can not be removed with scraping”

– Involves the buccal mucosa, tongue or floor of mouth

Leukoplakia 

3

Predisposing factors of leukoplakia 

Tobaccouse

– Ill-fittingdentures/persistent irritants

– HPVinfection

4

 Poorly circumscribed red, velvety eroded area

– AKA-“Erythroplasia” in mouth

Erythroplakia 

5

Erythroplakia vis leukoplakia 

Malignant transformation in >50% in erythoplakia, lower in leukoplakia 

6

White confluent fluffy/hairy hyperkeratotic thickenings

Oral hairy leukoplakia 

7

Oral hairy leukoplakia sene in

HIV

– Epstein Barr Virus (EBV) related in majority of cases

8

Histo of hairy leukoplakia 

marked hyperkeratosis with acanthosis

9

Is there malignant risk for hairy leukoplaki

No

10

Oral cavity bx needed for 

Benign squamous process

• Inflammatory or reactive

– Benign squamous papilloma

– Squamous dysplasia (pre-cancerous)

• Low-grade dysplasia

• High-grade dysplasia

– Invasive squamous cell carcinoma

11

Esophageal lesion path overview 

A image thumb
12

Esophageal atresia 

disruption of elongation and separation of esophagus and trachea during embryogenesis

13

Reasons for esophageal atresia

Maternal polyhydramnios, single umbilical artery

14

Sx of esophageal atresia 

Choking, cyanosis and excessive drooling

15

Stomach protrudes through an enlarged esophageal hiatus in the diaphragm (Sliding vs Paraesophageal types)

Hiatal hernia

16

Sx of hiatal hernia 

Reflux of gastric contents due to incompetence of the lower esophageal sphincter (LES)

– Epigastricpain,heartburn(sliding-type)

– Volvulus, strangulation and perforation (paraesophageal-type)

17

Incomplete relaxation of LES in response to swallowing – Functionalesophagealobstruction

Achalasia/cardiospasm 

18

Three main features of achlasia 

 

– Aperistalsis

– Partial or incomplete relaxation of LES

– Increased resting tone of LES

19

Main form of achalisa 

 Loss of intrinsic inhibitory innervation of LES and smooth muscle

– Loss or absence of ganglion cells in myenteric plexus

20

Secondary form of achlasia 

Impaired function from a variety of causes e.g. Chagas due to Trypanosoma cruzi, polio, paraneoplastic syndrome, sarcoidosis

21

Clinical features of achalisa 

– Dysphagia

– Odynophagia

– Refluxofcontents

– Vomiting

– Aspirationpneumonia

• Progressive dilatation of esophagus above the LES

22

Dx of achlasia 

Manometry

23

Longitudinal mucosal tears at esophagogastric junction

• Inadequaterelaxation  of LES during vomiting

– Common in alcoholics after bout of severe retching

• Tear may be only mucosal or transmural, leading to hematemesis

– Usually heal, but can be fatal

 Mallory Weis Tear 

24

 Dilated tortuous veins (collaterals) in the lower esophagus

– Associated withportal  hypertension(30-60%cirrhoticpts)

• Overlying mucosa may be normal, inflamed or ulcerated

• Usually no symptoms until they rupture

– Responsible for 50% deaths in pts with advanced cirrhosis

Esophageal varices 

25

Causes of esophagitis 

• IRRITANTS

– Alcohol, acids, alkalis etc.

– Gastroesophageal reflux esophagitis/disease (GERD)

• INFECTIONS

– Herpes simplex virus, Cytomegalovirus, Candida, etc.

• ALLERGIC

– Eosinophilic esophagitis

• UREMIA

• ANTICANCER THERAPY

26

Reflux esophagitis 

CNS depressants, hypo- thyroidism, pregnancy, alcohol, tobacco, nasogastric intubation.

27

Endoscopy of reflux esophagitis see

Irregularareaof hyperemia (vascular congestion) at the EGJ

28

• Inflammation–eosinophils,lymphocytes+/-neutrophils

• Elongation of lamina propria papillae

• Basal zone hyperplasia

Reflux esophagitis 

29

– Dyspepsia

– Burning sensation

– Waterbrash “sour

brash”

– Symptoms increase after lying down or after a large meal

– Nocturnal cough

Reflux esophagitis 

30

Complications of reflux esophigitis 

– Bleeding

– Stricture formation

– Aspiration pneumonia

– Barrett’s esophagus & Adenocarcinoma

31

 Endoscopy-

• Esophageal rings, linear furrows, white plaques

• Pathology (can be patchy)-

• ≥ 15 eosinophils/HPF with microabscess and superficial layering, basal zone hyperplasia

Eosinaphilic esophagitis 

32

Clinicopathologic of eosinaphilic esophagitis 

Normal pH and fail to respond to medication

33

normal esophageal squamous mucosa is replaced by metaplastic columnar epithelium because of prolonged injury

Barrets esophagitis 

34

#1 risk factor for esophageal adenocarcinoma

Barrets 

30-40 fold increased risk of adenocarcinoma

– Monitor by repeat endoscopy and biopsy looking for dysplasia/carcinoma

35

Endoscopy

• Thenormalpearly- white esophageal squamous mucosa is replaced by velvety pink columnar mucosa.

– “Serpiginous salmon colored patch”

Barretts

36

Histology

• AGA guidelines require the presence of columnar mucosa AND goblet cells

Barretts 

37

Benign esophageal neoplasms 

– Squamous Papilloma

– Leiomyoma

• Benigntumorof smooth muscle

38

Malignant esophageal neoplasms 

More common)

– Squamous cell carcinoma

– Adenocarcinoma

39

Which Esophageal neoplasm is most common in the US

Adenocarcinoma is more common

40

Which esophageal neoplasm is most common globally

SCC is more

common

41

Which cancer 

• Adults over the age of 50

• Morecommoninmales

• Highest incidence in central Asia and Northern China

• In the US, incidence is 2-8 per 100,000 yearly

• Blacks are at higher risk than whites

Squamous cell carcinoma 

42

Etiopahtology of squamous cell carcinoma of the GI

A image thumb
43

Location of squamous cell carcinoma of the esophagus 

Location

– 20% upper 1/3

– 50%  middle 1/3

– 30% lower 1/3

 

44

Growth patterns of esopageal squamous cell carcinoma 

– Exophytic

– Excavated

– Infiltrative

45

Local spread of squamous cell carcinoma 

What kind of invasion

transmural invasion with extension to adjacent mediastinal structures

46

Lymphatic spread squamous cell carcinoma 

– Cervical

– Mediastinal

– Paratracheal

– Tracheobronchial

– Gastric and celiac nodes

47

Accounts for 5-10% of ALL esophageal carcinomas

Adenocarcinoma....not the case in US! 

48

Location of adenocarcinoma 

Lower 1/3 esophagus 

49

Epi of adenocarcinoma of GI

Median age 50 years

• More common in whites

• Poorprognosis

50

NON-NEOPLASTIC stomach lesions 

• Pyloricstenosis

• Gastritis – Acute

– Chronic

• Pepticulcerdisease

51

NEOPLASTIC - BENIGN stomach lessions 

– Gastric polyps

– Adenomas

– Leiomyomas

52

NEOPLASTIC - MALIGNANT stomach lesions 

– Carcinomas

– Endocrine tumors

(Carcinoids)

– Lymphomas

– Leiomyosarcomas

– GIST

53

Acquired Pyloric stenosis 

Chronicantral gastritis

• Pepticulcers

• Malignancy

54

•More common in first male child

• M:F=3:1

•Concentric hypertrophy of circular muscle layer

Congenital hypertrophic pyloric stenosis 

55

•Clinically:

• Regurgitation

• Projectile vomiting

• Palpable epigastric mass

• Visible peristalsis

Congenital pyloric stenosis 

56

Tx of congenital pyloric stenosis 

Treated by surgery

• Myotomy

57

Acute, often transient, inflammation and injury of the mucosa of stomach

acute gastritis 

58

Etiology of acute gastritis 

– NSAIDs

– Excessive alcohol consumption

– Heavy smoking

– Ischemia and shock

– Severe stress (burns, surgery)

– Cancer chemotherapy

– Systemic infections – Uremia

59

 Epigastric pain, nausea and vomiting

– Hematemesis and melena

• Bleeding can rarely be fatal

Acute gastritis 

60

Acute gastritis pathology

– Mucosal erosion- loss of surface epithelium

– Erosions with hemorrhage = acute erosive gastritis

– Edema and congestion of lamina propria

– Neutrophils in the surface epithelium and glands

61

Chronic mucosal inflammatory changes leading eventually to mucosal atrophy and/or epithelial metaplasia

Chronic gastritis 

62

Etiology of chronic gastritis 

– Chronic infection with H. pylori

– Immunologic causes (autoimmune)

– Alcohol and smoking

– Post surgical e.g. after antrectomy

– Radiation

– Granulomatous conditions (Crohn’s disease, sarcoidosis)

 

Fisrt 3 most common causes 

63

Two patterns of gastritis in h. pylori 

– Predominantly antral inflammation

– Multifocal leading to gastric atrophy

64

Dz associated with H pylori 

-Peptic ulcers

-Gastric carcinoma

-Gastric lymphoma

65

H pylori characteristics 

Gram (-), curvilinear, motile (flagella), non- invasive and urease positive bacillus

66

Endoscopy(Gross):

• Varies form normal to patchy/diffuse erythema ± hemorrhage to boggy appearing mucosa with thick mucosal folds

in stomach

Chronic gastritis 

67

 Histology:

• Chronic inflammatory infiltrate (lymphocytes,

plasma cells) in the lamina propria

• Addition of neutrophils in the surface epithelium and glands = “Activity” 

• Lymphoid aggregates (fairly specific for H. pylori)

• Intestinal metaplasia and glandular atrophy may develop

Chronic gastritis 

68

Dx of h pylori

A image thumb
69

• Corpus (body/fundus) restricted mononuclear cell

infiltrate within the submucosa

• Autoantibodies:

o Blocking or binding Intrinsic Factor or B12

o Destroy parietal cell/chief cells (proton pump-ATPase)

• Manifests as pernicious anemia

o Vitamin B12 deficiency anemia, neurologic deficits, iron deficiency, loss of pepsin/pepsinogen, achlorhydria, hypergastrinemia and gastric neoplasms

Autoimmune gastritis 

70

Immuno path of autoimmune gastritis 

A image thumb
71

Injury that causes a loss of mucosa that extends to the muscularis mucosa or deeper

– Healing time is greater than with erosions

• Common (gastric and duodenal)

Gastric ulcers 

72

– Due to exposure to aggressive acidic peptic juices

– Chronic, often solitary lesions

Peptic gastritis 

73

Etiology acute gastric ulcers 

– Severe trauma, major surgeries

– Extensive burns (“Curling ulcers”)

– Head injuries and other intracranial lesions (“Cushing Ulcers”)

74

Pathogenesis of acute gastric ulcers 

– Systemic acidosis and hypoxia (severe trauma and burns)

– Vagal stimulation (intracranial lesions)

75

– Multiple small and circular ulcers with non-indurated bases

– Gastric rugae are normal (adjacent mucosa appears normal)

Acute gastric ulcers 

76

Peptic ulcer dz 

chronic, often solitary lesions that occur in any part of the GIT exposed to aggressive gastric acid peptic juices

77

Sites of involvement in peptic ulcer 

– Duodenum

– Stomach

– Gastro-esophageal junction

– Margins of gastrojejunostomy

– Meckel’s diverticulum

– Stomach, duodenum and jejunum in Zollinger Ellison syndrome

78

Pathogenesis of peptic ulcers 

A image thumb
79

Peptic ulcer etiopathogenesis 

1) H.PYLORI- 70% of gastric and 90% of duodenal ulcers 2) NSAIDS- inhibit prostaglandin synthesis

3) SMOKING- impairs mucosal blood flow

4) ALCOHOL

5) PSYCHOLOGICALSTRESS

6) ZOLLINGER ELLISON SYNDROME- multiple ulcers

80

Clinical features of peptic ulcers 

• Burning epigastric pain 1- 3 hours after meals

• Relieved by food and alkali

• Worse at night

• Associated weight loss

• Gastric outlet obstruction

81

COmplications of peptic ulcers 

• Bleeding

• Perforation

Gastric outlet obstruction

Malignant transformation ?

– Unknown in duodenal ulcer and exceedingly rare in gastric ulcer

• Possiblymalignantinitially rather than transformation

82

• Round to oval, punched out ulcer

– 50% < 2cms

– Sharp and raised margins with

smooth and clean base

– Depth varies but may penetrate entire wall

– Radiating surrounding mucosal folds

Peptic ulcer dz 

83

Epi of gastric adenocarcinoma 

 Highest incidence in Japan, Chile, Costa Rica and E. Europe

– Rate of gastric cancer is decreasing in most other places

84

Clinical-

• Non-specific sx: Weight loss, anorexia, abdominal pain – Mostlyasymptomaticinearlystages

• Pyloric obstruction

Gastric adenocarcinoma 

85

Prognosis of gastric adenocarcinoma 

depends upon depth of invasion and nodal status

86

Intestional type- gastric adenocarcinoma 

• Associated with chronic gastritis and H. pylori

• Intestinal metaplasia is precursor lesion

• Neoplastic glands resemble intestinal epithelium

87

Diffuse/signet cell type gastric adenocarcinoma 

• Signet ring cells

– Single cells, sheets, clusters

• No intestinal metaplasia

• Familial types with female predominance

– E-cadherinimplicated • Linitis plastica

88

Location of gastric adenocarcinoma 

– Pylorus/Antrum - 50-60%

– Cardia 25%

– Body and Fundus

89

Growth patterns of gastric adenocarcinoma 

– Exophytic

– Exacavated/Ulcerative

– Flat/Infiltrative

90

Routes of spread in gastric adenocarcinoma 

– Regional

– Transceolomic

– Lymphatic

– Hematogenous

91

#1 mesenchymal tumor of GI tract

– Occur any where along the GI tract, but 60% occur in the stomach

Gastrointestinal Stromal tumor 

92

Gastrointestional Stromal tumor derived from 

Derived from interstitial cells of Cajal (pacemaker cells) – ExpressCD117(c-Kit)

• Majorityhavec-Kitmutations(exon11)

• Rx: Tyrosine kinase inhibitor (Imatinib; Gleevec©)

93

Due to incomplete involution of vitelline duct

MEkels diverticulum 

94

Rules of 2's in meckels diverticulum 

– – –

Affects 2% of the normal population Occurs within 2 feet of the ileocecal valve Averages 2 inches (5 cm) in length

95

Out pouching on the anti-mesenteric side that includes all layers of GIT (true diverticulum)

Meckels diverticulum 

96

COmplications associated with Meckels diverticulum 

Complications occurs in 4% of pts (usually by 2 yrs old) – Hemorrhage,ulceration+/-perforation

– Intestinalobstruction – Diverticulitis

– Fistula

97

 Changes more marked in 2nd part of duodenum and proximal jejunum

– Marked atrophy and loss of villi (reduced area for absorption)

– Increased intraepithelial lymphocytes

– Elongated and hyperplastic crypts

– Increased number of lymphocytes, macrophages and plasma cells in lamina propria

Celiac dz 

98

Glutensensitiveenteropathy

Celiac dz 

99

Epi of Celiac dz 

Common in European ancestry (0.5 to 1%)

Adults and children

100

Pathogenesis of celiac dz 

A image thumb
101

Dx of celiac dz 

Documentation of malabsorption, other symptoms

– Classic findings on small intestinal biopsy

– Serologic tests

• Anti-gliadinandanti-endomysialantibodies(oldertests)

• Anti-tissueTransglutaminase(tTG)antibodies

– Is directed against a more specific antigen.

– Sensitivity of 95% and specificity of 94% in untreated celiac patients

– Reversal of histologic changes and signs and symptoms after gluten free diet

102

Long term risks associated with celiac dz 

intestinal lymphomas (T-cell type)

103

Affects people living in or visiting the tropics who contract diarrheal illness

• Symptoms of malabsorption can appear months or even years after the visit/illness

– Pathogenesis is likely related to infection but the specific pathogen is unknown

Tropical sprue 

104

Celiac vs tropical sprue 

Similar sx 

Antibioltics tx for tropical sprue 

Celiac tx by cutting out celiac 

105

Krukenberg tumor

Ovarian metastasis

106

Virchow’s lymph node

Supraclavicular lymph node metastasis

107

Sister Mary Joseph nodule

Periumbilical metastasis

108

Systemic infectious disease

– Mainly involves the intestines,

joints and CNS

– More common in males (10:1)

– Causesmalabsorptionmechanically through lymphatic obstruction.

– Caused by a gram + bacilli- Tropheryma whippelii

Whipple dz 

109

Lamina propria is laden with distended macrophages that contain PAS + granules/bacilli

– Bacilli seen by Electron Microscopy

• Treated with antibiotics

Whipples dz 

110

Proximal duodenal inflammation

– Due to hyperacidity of gastric contents

Peptic duodenitis 

111

– Acute and chronic

inflammation

– +/-villousatrophy

– “Gastricfoveolarmetaplasia”

– Must be distinguished from sprue

Peptic duodenitis 

112

Peptic dueodenitis can also appear with 

H pylori infection

113

 Protozoan gut pathogen with flagellum

– Trophozoites and cysts are shed

• Usually acquired from drinking water contaminated with cysts

Giardia 

114

Anti-tissue transglutaminase antibodies for celiac disease will give a false negative when

IgA deficiency pts 

115

• Self-limited infection in a normal host

• Chronic diarrhea in AIDS pts – Butnowprophylaxisgiven

• Intracellular but appears at top of cell microscopically

Cryptosporidium

116

Infectious Enterocolitis causes 

– Toxin-mediated bacterial diseases

• Salmonella, Cholera, Shigella, Campylobacter, Yersinia, etc.

– Invasive infections

– Viral enteritis

• CMV,adenovirus,rotovirus,etc

117

GI tract obstruction most commone here

Small intestine 

118

Pseudo obstruction in small intestine seen with 

– Functional obstruction

– Failure of propulsion

• Disorder of smooth muscle, disorder of innervation or both

– Paralyticileusfollowingperitonealirritation(surgery)

119

General causes of intestinal onstruction

– Extramural/Mechanical  causes (most common)

– Luminal (with in lumen)

– Within the bowel wall (Intramural)

120

Extramural intestinal obstructions 

• Peritoneal disease

– Congenitalmesenteric/omentalbands

– Peritonealtumors(primaryormetastatic)

– Peritonealadhesionsfromsurgeryorothercauses(infection,endometriosis)

• Intussuscception

– Telescoping of proximal bowel segment into distal

• In adults often due to tumor

• Volvulus

– Twistingofbowelloop

• Hernia allowing incarceration/strangulation of bowel

121

Luminal intestinal obstructions 

• Food Bolus (e.g. fruit or vegetable) or Bezoars (ingested hair)

• Mass of Round worms (Ascaris lumbricoides)

• Tumors

• Meconium ileus in infants with cystic fibrosis

• Gallstone ileus

– Stone lodges in the TI, often from a cholecystoduodenal fistula

122

Intramural intestional obstructions

• Congenital atresias

• Inflammatory conditions

– Crohn’sDisease

– Tuberculosis

– Drug induced, ischemic related or radiation associated stricture

– Polypoidorinfiltrativeneoplasms

123

Small bowel tumors 

(benign more common than malignant)

A image thumb
124

Overview pathological overview of LI lessions 

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125

Most common cause of congenital intestinal obstruction

Hirschsprung's Dz 

126

Hirshsprung Disease epi 

Incidence- 1 in 5000 live births

– M:Fis4:1

– 10%ofDownSyndromepatients

127

Hirshsprung pathogenesis 

Defect in migration and survival of neuroblasts

Congenital absence of ganglion cells

Functional obstruction

Dilatation proximal to affected segment

128

Defect in what for hirshsprung dz

– Absenceofganglioncellsin Meissner and Auerbach’s plexus

– Dilatation and hypertrophy proximal to aganglionic segment (congenital megacolon)

129

Q image thumb

Hirshsprung disease 

130

Hirschsprung complications 

• Enterocolitis

• Perforation and peritonitis

131

Clinical Features:

• Diarrhea

– Mucoid – Bloody

• Abdominal pain (Usually below umbilicus)

• Abdominal cramps

• Tenesmus (painful defecation)

Colitis 

132

Colitis etiologies 

• Infections

Bacterial, Viral, Protozoal Immunosuppressed pts Antibiotic-associated colitis

Pseudomembranous colitis (C. difficile)

• Necrotizing enterocolitis

• Ischemic colitis

• Idiopathic-Inflammatory bowel disease (IBD)

• Medication related (NSAIDs)

• Radiation associated

133

Epidemiology of diverticular disease 

Common in western world

– Presentin50%ofindividuals>60yearsold

134

Pathogenesis of diverticular disease 

– Lack of dietary fiber leads to sustained bowel contractions and increased intraluminal pressure

– Herniation of colonic wall at sites of focal defects

135

Clinical picture diverticulosis and diverticulitis 

Diverticulosis is usually asymptomatic

– Sometimes causes painless bleeding

• Diverticulitis

– Lower abdominal pain

– Constipation, diarrhea, flatulence – Fever

– Can lead to perforation

136

• Flask-like structures (95% sigmoid colon) extending from lumen through the muscular layer

• Not a true diverticulum

Diverticulosis 

137

Pseudomembranous colitis caused by 

• Associated with broad spectrum antibiotic use

• Caused by Clostridium difficile

– Toxin-mediateddamage

138

• Colon, particularly rectosigmoid, exhibits raised yellow plaques

– Fibrinopurulent-necrotic debris (pseudomembranes)

– Surface epithelium becomes denuded

– Superficially damaged crypts distended by mucopurulent exudate which erupts to form a mushrooming cloud

– Coalescence of these lesions leads to pseudomembrane formation

– Candeveloptoxicmegacolon

Pseudomembrane colitis 

139

Amebic colitis cause 

• Entamoeba histolytica

• Parasitic infection (protozoan)

• Acquired by Fecal-oral route • Gradual dysentery

140

• Identified in aspirates or biopsy samples

• May resemble IBD on biopsy

• Chronic destructive colitis with

flask shaped ulcers

• Organisms engulf red cells

Amebic colitis 

141

Amebic colitis txx

antiparasitic agents

142

Causes for infectious colitis 

• Infectious “enterocolitis” as previously mentioned (diagnosed best by stool cultures)

• Bacterial (E. coli, Shigella, Salmonella, Yersinia, etc)

• Typhoid

– Fever, headache, abdominal pain, rash and diarrhea – Longitudinalulcers,typicallyoverPeyerpatches

• Tuberculosis

– Chronic abdominal pain

– Multifocal involvement, jejunum to ileum, TI most common

– Annular circular or oval ulcers, lying transversely

– Granulomatousinflammation,oftennecrotizing

143

Inflammatory bowel dz etiology pic 

A image thumb
144

• Includes Crohn’s disease and Ulcerative colitis

– Chronic  relapsing, inflammatory disorders of obscure origin

– Attacksofbloodymucoid diarrhea

– Lowe rabdominal pain, abdominal cramps; tenesmus

– Flare ups with physical and mental stress

– Fever and weight loss in severe cases

– Features of malabsorption

Inflamatory bowel dz 

145

Extraintestional associatons with inflammatory bowel dz 

• Can be seen in both Crohns Dz and Ulcertive Colitis (more common with UC)

• Can develop even before the onset of GI sign symptoms

– Migratory polyarthritis

– Sacroileitis

– Ankylosing spondylitis

– Erythema nodosum

– Clubbing of finger tips

– Sclerosing cholangitis

A image thumb
146

Which inflamatory bowel dz has an increase of malignancies 

Ulcerative colitis 

147

EPi of ulcerative colitis 

• More common in Caucasians

• Peak between 20 and 25 years

• Associated with Primary Sclerosing Cholangitis (PSC)

• HLA-DRB1 association

148

Location of ulcerative colitis 

• Ulcers and inflammatory disease limited to colon and affecting mucosa and sub mucosa

• Extends in continuous fashion

– Starts in rectum and extends proximally (variable involvement)

149

Ulcerative colitis histo

• Inflammatory injury is usually limited to the mucosa

– Mucosa grossly appears red, granular, and friable

– Acute (“active”) cryptitis, basal lymphoplasmacytosis, lymphoid hyperplasia

– Broadbasedulcers

• Isolated islands of regenerating mucosa bulge in between to

create classic “pseudopolyps”

• Serosa is usually normal

• 10% cases demonstrate “backwash ileitis”

– Superficial acute inflammation of the terminal ileum

150

Epi of Crohn's dz 

• Common disease in the U.S. (3 per 100,000)

• Adolescents and young adults; F>M (1.6:1)

– Also small spike in incidence within the elderly

– More common in the Jewish population

151

– Sharply delineated patches (skip lesions) & transmural

involvement by an inflammatory process

– Presence of non-caseating granulomas

– Mucosal fissuring with formation of fistulas and/or strictures

– “Creeping fat”

– Thickened/fibroticmesentery

Crohn's dz 

152

Crohn's location

• Involves anywhere along GI tract

– Small intestine alone 30%

– Small intestine and colon 40%

– Colon alone 30%

• Long narrow thickened segments of small intestine (unlike tubercular strictures which are short in length): radiographically - String sign

153

Crohn's vs ulcerative colitis pic 

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154

Table summary Crohn's dz vs ulcerative colitis 

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155

Occlusive ischemic bowel dz 

– Arterial thrombosis- systemic atherosclerosis, systemic vasculitis, hypercoagulable states, angiographic procedures

– Arterial embolism- cardiac vegetations, athero- thromboembolism and angiographic procedures

– Venous thrombosis- hypercoagulable states, Oral contraceptives, intraperitoneal, sepsis, post operative etc.

156

Non-occlusive ischemia bowel 

cardiac failure, shock, dehydration

157

Epi of ischemic bowel dz 

Elderly 

158

Involvment in ischemic bowel dz 

• Mucosal only involvement (mild features)

– Nausea, vomiting and bloody stools

• TransmuralInvolvement

– Severe abdominal pain and tenderness

– Gangrene, perforation, peritonitis – Shock and vascular collapse

– Mortality is very high (50-75%)

159

Pathology of ischemic bowel dz 

– Acute colitis with epithelial atrophy +/- erosion/ulcer

– Stromal hyalinization

160

• Insidious

• Chronic inflammation and fibrosis

• Can lead to stricture formation or perforation

• Common at water-shed areas

   – Splenic flexure (most common)

• Intermittent attacks of pain – Intestinal angina

• Can mimic inflammatory bowel disease

Chronic ischemic colitis 

161

Tumors of colon and rectum overview pic 

A image thumb
162

Colon polyps overview pic 

A image thumb
163

Juvenile polyp epi

Typically children < 5 yrs of age, but also seen in adults

– Rarely,juvenile polyposis syndrome

(AD)-leads to increased risk of malignancy.

164

Malignent potential for juvenile polyps

No, bc single sporadic polyp formation 

165

– Rectumismostcommonsite

– Usually 1-3 cms, lobulated with stalk

– Lamina propria forms the bulk and encloses abundant cystically dilated glands (“swiss cheese”)

– +/-Inflammatorycells

Juvenile polyp 

166

– Autosomaldominant

– Multiple polyps in entire GIT

– Melanotic pigmentation in mucocutaneous areas, lips, perioral areas, face, genitalia and palms

– Increased risk of developing carcinomas of pancreas, breast, lung, ovary and uterus

Peutz Jegher syndrome

167

Peutz Jegher polyp/ Hamartomatous polyp

pathology  

– Arborizing network of smooth

muscle extending into the polyp and surrounds glands

– Glands are lined by non-dysplastic epithelium rich in goblet cells

– No malignant potential per se

168

All are a result of epithelial proliferative dysplasia

– Considered precursor lesions of carcinoma and

potentially harbor malignancy in colon 

Colon Adenomas 

169

3 types of adenomas 

Tubular, Villous and Tubulovillous

170

Adenomas increase risk of malignancy with 

– Polyp size (>2 cm; most important criteria)

– Histologic architecture (tubular versus villous) – Severity of dysplasia (low versus high grade)

171

Pathology of adenomas 

– Sessileor Pedunculated (stalk)

– Adenomatousepitheliumlines

the glands- tall, hyperchromatic

and disordered epithelium

– Invasion of the submucosa(stalk)

constitutes invasive carcinoma

172

Clinical feature of colon adenomas 

 Most adenomas are usually asymptomatic

– May present with anemia because of occult blood loss – Rarely present with intussusception

• Usually solitary lesions, with the majority occurring within the colon (90%)

– Lifetime risk ~ 50%

173

• Fourth most common cancer overall

– ~5% of individuals diagnosed in their lifetime (1 in 19)

• Most commonly occurs in elderly individuals

– When in young individuals typically in the setting of

ulcerative colitis or polyposis syndromes

Colorectal cancer 

174

Risk factors for colorectal cancer 

– Family History

– Obesity, physical inactivity

– Diet low in indigestible fiber and rich in animal fat – Smoking and alcohol intake

– Antioxidants protective

175

Clinical features of colon rectal cancer 

• Often asymptomatic until there’s advanced disease

• RIGHT SIDED-

– Fatigue, weakness & iron deficiency anemia

– Bulky & bleed easily

• LEFTSIDED-

– Altered bowel habits

• Tumormarker-CEA

• Iron deficiency anemia in an elderly man is due to GI malignancy unless proved otherwise

176

Colon cancer major pathways 

• Chromosomal Instability Pathway (85-90% cases)

– Arise from adenoma-carcinoma sequence

– APC gene mutations

• Familial Adenomatous Polyposis Syndrome (FAP)

• Microsatellite Instability Pathway (10-15% cases)

– May arise from adenomas or other polyps (SSA)

– Defect in DNA mismatch repair genes

• MLH1, MSH2, MSH6, or PMS2 – 85% Sporadic

– 15% Familial

• Hereditary non-polypos is colon cancer (HNPCC) / Lynch syndrome

177

Familial adenomatous polyposis- genetic defects 

• Autosomal dominant

   • Germline APC gene (5q21) mutation  

    • ~1 in 10,000 affected; M=F

• Somatic mutation of the remaining allele leads to the development of multiple adenomas (>100 by definition)

    • 100% chance of progressing to colorectal cancer

     • 3-5% risk of upper GI cancer (small intesine and/or stomach)

178

Prophylactic colectomy typically done when

FAP cancer genetic defect detected 

179

FAP can be associated with

Gardner’s syndrome- multiple osteomas, desmoid tumors and epidermal cysts

Turcot’s syndrome- CNS gliomas

180

Hereditary Non-polyposis colorectal cancer is also known as 

Lynch syndrome 

181

Genetic defect related to HNPCC 

– MLH1, MSH2, MSH6 or PMS2

• Leads to microsatellite instability and increased mutation

accumulation (MSI-H)

 

(mismatch repair genes)

182

Compared to FAP HNPCC has 

• Fewer number of polyps as compared to FAP

• Tumors;

– May be multiple

– More common on right side (proximal colon)

– Mucinous histology

– Increased number of tumor infiltrating lymphocytes

• Associated with carcinomas of other sites

– Endometrium, ovaries, stomach, small intestine, biliary tract

183

Spread of adenocarcinoma seen in 

• Spread to regional lymph nodes is frequent

• Systemic spread to liver, lung and bones

184

Most important prognositc factor for adenocarcinoma of the colon 

Most important prognostic factor is extent of tumor at the time of diagnosis (i.e. tumor stage)

– 5 year survival is approximately 97% for stage 1 (pT1) but decreases to about 4% for stage IV (M1)

185

• Acute inflammatory injury of the appendix

– Underlyingobstructionofthe lumen in 50-80% cases

– Pathogenesisunclearinnon obstructive cases

Acute appendicitis 

186

Epi of acute appendicitis 

Adolescents and young adults most commonly affected

187

Clinical pic of acute appendicitis pts 

– Most common symptomis Pain- initially periumblical then localizes to RLQ

• Tenderness (McBurney’s point)

– Nausea,vomiting

– Mild fever and leucocytosis (Neutrophilia )

188

Possible pathogenesis of acute appendicitis 

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189

Complications for acute appendicitis 

• Perforation

• Peritonitis

• Peri appendiceal abscess

• Liver  abscess

• Bacteremia

190

Appendiceal mucocele is what 

• Dilation of lumen due to mucinous secretions

– Lining epithelium may be adenomatous (appendiceal mucinous neoplasm) or frankly invasive (adenocarcinoma)

191

Rupture of appendiceal mucocele can lead to 

 Rupture may lead to diffuse peritoneal mucin

– Pseudomyxoma peritonei (“jelly belly”)

• Range of peritoneal studding by mucinous implants:

– Entirely mucinous (No epithelium)

– Abundant mucin (Scant low grade neoplastic epithelium)

– Abundant malignant epithelial cells (Signet ring cells and/or infiltrating columnar epithelium)

192

Epithelium GI neoplasms 

adenomas, carcinomas

193

Enterochromaffin cells GI neoplams 

neuroendocrine tumors

194

Lymphocyte GI neoplasms 

lymphomas

195

Mesenchymal cells GI neoplasms 

smooth muscle tumors, GI Stromal Tumors

196

Lymphoma presenting with the main bulk of disease in the gastrointestinal tract +/- contiguous lymph nodes

Primary Gastrointestional lymphomas 

197

Incidence and location of primary gastrointestional lympohomas 

• Incidence:

– 40% are extranodal lymphomas

• 4-18% are GI Lymphomas (Western world) • 25% are GI Lymphomas (MiddleEast)

– Incidence has been increasing • Sites

– Stomach (50%)> small intestine (37%)> colon and rectum

198

B cell lymphoma types of primary GI lymphoma

– Mucosa associated lymphoid tissue (MALT)-type (including immunoproliferative small intestinal disease [IPSID])

• Lowgrade

• Highgrade(DLBCL)

– Mantle cell (lymphomatous polyposis)

– Burkitt and Burkitt-like lymphoma

– Follicular lymphomas and other nodal types of lymphoma

199

T Cell typs of GI lymphomas 

– Enteropathy associated (EATL) including ulcerative

jejunitis

– Other types not associated with enteropathy

– Gamma delta hepatosplenic T-cell lymphoma

– Angioimmunoblastic-type T cell lymphoma

– Extranasal NK-cell and NK-cell like T-cell lymphoma

200

Other types of GI lymphomas 

 OtherSubtypes:

– Anaplastic large cell (Ki-1) lymphoma

– True histiocytic lymphoma (sarcoma)

– Hodgkin’s disease

– Leukemic infiltration of GI tract

201

MALT is associated with

H. Pylori infections 

202

H pylori connection to MALToma 

– In-vitro MALToma cell line mixed with heat killed H. Pylori

• Cells die in absence of H. Pylori

• Cells die when only chemical mitogens are used

• Supernatantfromotherculturedoesn’trestoregrowth

• The proliferative response is strain specific and varies amongst tumors from different patients

– B-cells themselves are not H. Pylori specific

203

Epi of MALToma

Age: 27-84 (Mean 60); M:F=1.5:1

204

Maltoma sx 

• Symptoms(non-specific):

– Dyspepsia: 80%

– Abdomenal pain, vausea/vomiting, or weight loss: 45%

• Physical and Clinical Examination

– Abdominal mass: 25%

– Blood loss: acute 20%, chronic 10%

205

Endoscopy of MALToma pts 

– Ulcers: large 31%, small 20%

– Mass: 25%

– Infiltrate: 18%

206

Treatment and prognosis of MALToma

• Eradication of H. pylori with antibiotics – 67-90% remission, 10% relapse

• Typically slow growing and remain localized

• Survival at 5 years -90% and 10 years -65-75%

• Unresponsive case treated with chemotherapy/ Rituximab

207

Neuroendocrine carcinoid stomach

 Stomach- Occurs in three settings:

– Type-I: Chronic atrophic gastritis and achlorhydria

• Hypergastrinemia leads to ECL cell hyperplasia

• May be multiple, usually follows benign course

– Type II: Gastrinoma (Zollinger-Ellison syndrome)

• Usually in MEN 1 syndrome, hypergastrinemia

– Type III: Sporadic

• Usuallyaggressivetumorwithmetastasis

208

Small intestine and appendix carcinoid tumor 

– Most common site in GI tract

– Often small, occult primary tumors

– Can metastasize widely leading to carcinoid syndrome when liver involved

• Carcinoidsyndrome:Wheezing,Diarrhea,Flushing

209

Rectum carcinoid tumors 

Often small and benign

210

 Ballooning degeneration

swollen hepatocyte with irregularly clumped cytoplasm

211

Feathery degeneration of liver

fine foamy cytoplasm because of detergent action of bile salts (usually seen with CHOLESTASIS (bile accumulation in liver)

212

Macrovesicular fat in liver seen due to 

Large fat vacuole displaces the nucleus to periphery

• Alcohol

• NASH/NAFLD

• Malnutrition (PEM)

213

MICROVESICULAR small fat vacuoles due to 

Numerous tiny vacuoles, nucleus is central

• Acute fatty liver of pregnancy

• Reye’s syndrome

• Drugs

214

Apoptosis in liver

Councilman bodies / Acidophil bodies

215

Acute signs of liver disease 

Acute and chronic

• Jaundice and/or Icterus

• Hepatomegaly

• Tenderness in right hypochondrium

• Peripheral edema

216

Chronic liver disease signs 

• Splenomegaly

• Palmar erythema

• Spider angiomas

• Gynecomastia

• Hypogonadism (testicular atrophy)

• Muscle wasting

217

Hepatocyte Integrity serum markers 

Serum aspartate aminotransferase (AST)

Serum alanine aminotransferase (ALT)

218

Biliary Plasma membrane enzymes markers 

Serum alkaline phosphatase

Serum γ-glutamyl transpeptidase (GGT)

219

Hepatocyte “Synthetic Function”

Secreted proteins (blood)

Serum markers 

Serum albumin

Prothrombin time

(factors V, VII, X, prothrombin, fibrinogen)

220

Hepatocyte metabolism marker

Serum ammonia

221

Jaundice is clinically seen at which levels 

total bilirubin levels > 2.0 mg/dl (normal is <1.2 mg/dl)

 

222

Pre-Hepatic Jaundice

Excess production* (unconjucated) 

• Hemolytic anemia

• Increased blood resorption from

    hemorrhage 

• Ineffective erythropoiesis

223

Post-Hepatic Jaundice 

– Impairedbileflow♮ (conjugated) 

• Gallstones, Ca head of pancreas

and extra hepatic bile ducts

• Biliary atresia common in neonates (partial or complete destruction or absence of extrahepatic bile ducts)

 

224

Hepatic jaundice 

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225

Fulminant Hepatitis

Denotes clinical hepatic insufficiency that progresses rapidly to hepatic encephalopathy with in 2-3 weeks

226

Causes of Fulminant Hepatitis

Viral hepatitis is the most important cause (60-70% cases)

• Remaining cases - drug and chemical toxicity and autoimmune related

• Rare causes include ischemic necrosis, acute fatty liver of pregnancy, Wilson’s disease

227

Causes of Chronic Hepatitis

• AlcoholUse

• Viral

• Metabolic and Genetic Liver Disease

– Wilson disease

– Alpha 1 antitrypsin deficiency

– Hemochromatosis

• Drugs

• Autoimmune • Sarcoidosis

228

Cirrhosis

• Defined by three characteristics

– Bridging fibrous septa

– Parenchymal nodules created by regeneration

– Architectural disruption

229

Cirrhosis based on 

nodule sized, often classified as:

– Micronodular < 3mm nodules

– Macronodular ≥ 3 mm nodules

230

Pathogenesis of Cirrhosis pic 

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231

Cirrhosis etiology

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232

Clinical picture of cirrohis 

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233

COmplications to cirrohis 

•Portal HTN

•Shunts

•Coagulopathy

•Hepatorenal syndrome

•Hepatopulomary syndrome

•Marked risk of hepatocellular carcinoma

234

Consequences of Portal hypertension 

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235

What is portal hypertension

Increased resistance against portal blood flow 

236

Causes of portal hypertension

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237

Most common cause is chronic right heart failure

Venous Outflow Obstruction

238

Effects of venous outflow obstruction

• Causes damage to zone 3

(perivenular) hepatocytes

• Initially “nutmeg liver” of passive congestion

• Eventually can lead to cirrhosis (prominent perivenular scarring)

239

Most common infective disease of the liver

Viral Hepatitis

240

systemic viral infections thant can involve the liver

– EBV, CMV, HSV, adenovirus, yellow fever etc.

– Hepatotropicvirus

241

Hepatotropic Viruses table 

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242

Acute hepatitis- asymptomatic with recovery seen with

– HAV and HBV infection during childhood

243

Acute hepatitis- symptomatic with recovery seen with

– Uncommon for HCV

244

Chronic hepatitis seen with

– Continued or relapsing disease for > 6 months

– Hallmark of HCV

245

Fulminant hepatitis seen with which hepatitis 

– Progression to hepatic failure within 2 – 3 weeks

– In the US, most commonly HAV and HBV (adults)

246

• Does not cause chronic hepatitis

• No carrier state

• Diagnosis-

– IgM appears at the onset of signs and symptoms

– After few months IgG

 Hep A 

247

Hep A in children

• Common in children

– Spread is by feco-oral route

– Incubation period is 2-6 weeks

– Typically a benign, self-limited

disease

248

Transmission of hep B 

• Transmission occurs by

 Transfusion of blood and blood products

 Sexual intercourse

 I/V drug abuse

 Needle stick injuries

249

Hep B prognosis pic 

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250

Most important cause of transfusion associated hepatitis and chronic liver disease

• Incubation period is 1-3 weeks

• Much higher propensity for chronicity and cirrhosis

– PERSISTENT INFECTION and CHRONICITY ARE HALL MARK

• Inherently unstable virus so no vaccine yet

Hep C 

251

Hep C prognosis 

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252

Hepatitis D

• It’s a replication defective RNA virus (“delta virus”) – Infective only when encapsulated by HBsAg (REQUIRES Hepatitis B to be present)

• Either co-infection or established HBV infection before (super infection)

– Super infection is more dangerous

• In the US, it’s relatively uncommon

• IVdrugabusers

• Hemophiliacs

253

Hepatitis E

• Entericallytransmitted

• Usually a self limited illness

– But high mortality in pregnant females (~20%)

• NOCHRONICITY

254

Autoimmune hepatitis seen in

Young to middle aged women primarily effected

• Chronic and progressive hepatitis of unknown etiology

– Most develop chronic hepatitis that can progress to cirrhosis

– But acute fulminant hepatitis can occur (40%)

255

Autoimmune mediated injury in liver

• Several potential “triggers” – infection, drugs, herbal products

• HLA DR3 and DR4

– ANA and Anti-smooth muscle Ab (ASMA) (Type 1)

• +/- anti-actin or anti-soluble liver/ liver-pancreas antigen (Type 3)

– Anti-liver kidney microsome-1 (ALKM-1) (Type 2 ) – HightitersofIgG

256

Autoimmune Hepatitis

Associations

Celiac disease, SLE, RA, Sjogren syndrome, UC, etc...

257

Autoimmune Hepatitis morphology

– Interface and lobular hepatitis with a predominant

population of plasma cells and lymphocytes.

– May present with zone 3 (perivenular) injury

– Can have overlap with PSC or PBC.

258

Autoimmune Hepatitis Tx 

– Immunosuppression (i.e. prednisone/ azothioprine)

– Transplantation if liver failure

259

Mallory bodies

• Tangled skeins of intermediate filaments

• Seen as eosinophilic cytoplasmic inclusions, usually WITHIN ballooned hepatocytes!

Alcohol related liver dz 

260

Alcohol related liver dz pic 

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261

Non-Alcoholic Fatty Liver Disease

• Strong association with

metabolic syndrome:

– Obesity, hyperlipidemia, hypertension and insulin resistance – Little to no alcohol consumption

262

Morphology of Non-Alcoholic Fatty Liver Disease

 Morphologic findings range from:

– Macrovesicular steatosis to steatohepatitis (NASH) – Minimal pericellular fibrosis to cirrhosis

263

Non-Alcoholic Fatty Liver Disease course 

 ~10-30% eventually develop cirrhosis

264

Fatty Liver Disease / Steatohepatitis

Features

• Steatosis

• Balloon cells with Mallory Bodies

• Inflammation

• Fibrosis

265

Hemochromatosis is characterized by

266

Two types of hemochromatosis

1. Hereditary/Primary Hemochromatosis

– Autosomal recessive

– HFE gene (6p) mutation most common cause- dysregulates

iron uptake in intestine, leading to too much iron

• Carrier rate of C282Y mutation in HFE in Caucasians is 1 in 70

2. Secondary Hemochromatosis (hemosiderosis) Treatment: phlebotomy or transplant

267

Hemochromatosis: Involvement of other organs

• PANCREAS

– Intensely pigmented

– Diffuse interstitial fibrosis

– Hemosiderin in both acinar and Islet cells

– Diabetes mellitus (“bronze diabetes”)

• HEART

– Hemosiderin in myocardial fibres (Cardiomyopathy)

– Delicate interstitial fibrosis

• SKIN

– Slate gray coloration

– Iron in dermal melanophages

– Increased melanin production

268

Causes of Secondary Iron Overload

• Parenteral iron overload

– Repeated blood transfusions

– Iron dextran injections

• Ineffective erythropoiesis

– β thalassemias

– Other chronic hemolytic anemias

• Increased oral intake – Bantu disease

• Chronic liver disease – Esp. alcoholic

269

Complications to hemochromatosis 

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270

 

Wilson Disease

an autosomal recessive disorder which creates a defective hepatocyte canalicular transporter

– ATP7Blocatedonchromosome13

– Cuaccumulatesinhepatocytes(hepatotoxic)

– Cu spills out into the circulation causing

hemolysis and pathologic changes in the brain (deposits in basal ganglia) and eyes (corneal deposits, “Kayser-Fleischer rings”)

271

Wilson dz Clinical course

– Acute hepatic failure: childhood to young adulthood

– Cirrhosis: adolescence to young adulthood (same for psychosis)

272

Investigations of wilsons

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273

Morphology of wilsons 

– Ranges from mild to severe :

• Cu accumulation

• Fatty change, hepatic necrosis

• With progression, cirrhosis

274

Tx of wilson's disease 

Treatment: Chelation therapy

275

Alpha-1-Antitrypsin Deficiency

 

• Autosomal recessive disorder

– Leads to low serum levels of a protease inhibitor- A1AT

• A1AT is a small glycoprotein synthesized in hepatocytes’ endoplasmic reticulum (ER)

• Mutations result in an abnormally folded A1AT protein  inhibits it from exiting the ER, produces cytoplasmic accumulation and systemic deficiency

• Low serum levels permits uninhibited tissue destruction (e.g., pulmonary emphysema)

– Gene located on chromosome 14 (carrier rate 10%)

276

Alpha 1 antitrypsin genetics 

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277

Alpha-1-Antitrypsin Deficiency Disease Associations

• Emphysema (75%-85%) • Hepatitis/Cirrhosis

• Panniculitis

• Anticytoplasmic neutrophilic antibody (C-ANCA)

-positive vasculitis (Wegener's granulomatosis)

278

Alpha-1-Antitrypsin Deficiency tx

– Transplant (curative)

279

Alpha-1-Antitrypsin Deficiency morphology

• Round/oval cytoplasmic globular inclusions in hepatocytes

– PAS-diastase (PASD) histochemical stain highlights the inclusions

• Can lead to advanced fibrosis and/or non-specific changes

• Neonatal (giant cell) hepatitis

280

Primary Biliary Cirrhosis

 

• Chronic, progressive cholestatic liver disease caused by the inflammatory destruction of intrahepatic bile ducts

– Autoimmune disorder- Anti-mitochondrial Ab (AMA), +/- ANA • IgMAbtopyruvatedehydrogenasecomplex-E2subunit(PDC-E2)found

on the inner mitochondrial membrane

– Elevated Alkaline Phosphatase and γ-glutamyl transpeptidase

281

Primary Biliary Cirrhosis epi

 Middleagedwomenprimarilyeffected

– M:F 6-9:1 with a mean age 50-55

282

Primary Biliary Cirrhosis associations 

Sjögren’s syndrome, arthropathy, sicca

283

Primary Biliary Cirrhosis

• Clinical features

– Insidious, can present with pruritis, fatigue, and/or abdominal discomfort

– Progresses over 10-20 years, ultimately developing cirrhosis

284

Primary Biliary Cirrhosis morphology

– Portal inflammation with non-suppurative, granulomatous destruction of medium-sized bile ducts (“Florid duct lesion”)

– Minimal to mild lobular hepatitis

– May have no cholestasis until late stages of the disease

– Cirrhosis develops in the final stage (biliary cirrhosis)

– Can overlap with autoimmune hepatitis

285

Primary Biliary Cirrhosis tx 

– Symptomatic (i.e. Ursodial)

– Liver transplantation

286

Primary Sclerosing Cholangitis

Fibrotic and inflammatory destruction of intra and

extra-hepatic bile ducts – Radiology- characteristic

“beading” and stricturing of the biliary tree

– Elevated Alk Phos and GGT – P-ANCA in about 80% cases

287

Primary Sclerosing Cholangitis epi

Slight male predominance

288

Primary Sclerosing Cholangitis associations 

Inflammatory bowel disease (~70%)

– May occur before, during, or after IBD onset (UC)

289

Primary Sclerosing Cholangitis

• Etiology and pathogenesis

are largely unknown

– Autoantibodies present in <10% of pts, possible overlap with AIH

290

– Symptoms include fatigue, pruritis

– Progressive clinical course which can lead to biliary cirrhosis

• Marked increased risk for cholangiocarcinoma

Primary Sclerosing Cholangitis

291

– Concentric periductal “onion skin” fibrosis- leads to fibrous obliteration of the liver duct

– Modest lymphocytic portal infiltrate +/- copper accumulation

– Biliarycirrhosis

Primary Sclerosing Cholangitis

292

Primary Sclerosing Cholangitis tx 

Symptomatic (Ursodiol) or Liver Transplantation

293

Benign liver tumors 

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294

Malignant liver tumors 

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295

Most common liver tumor

Hemangioma

296

Hemangioma epi

– Range from tiny to huge; one or several – F:M 5:1

297

Hemangioma tx 

• Typically an incidental finding on CT scan or at laparoscopy / laparotomy

• Vast majority require no treatment

• Indications for Treatment/Intervention:

– Pain (thrombosis, capsular stretch) or bleeding

– Location- large tumor below costal margin

– Size- increasing or > 10 cm (Bleeding very rare at < 10 cm)

– Platelet consumption

– Hemodynamic shunt

– Uncertain diagnosis

298

Hepatic Adenoma patholgy 

• Usually solitary and ill-defined (no capsule) – >10 lesions = “adenomatosis”

• Proliferation of bland hepatocytes, plates ≤3-cells thick.

• Isolated (‘naked’) arteries

• No bile duct differentiation

299

Benign neoplasm of hepatocytes AFP levels 

Normal 

300

Liver Cell Adenoma (Hepatic Adenoma) epi

Most commonly occurs in young women

301

Risk factors for Liver Cell Adenoma (Hepatic Adenoma)

MajorRiskfactors:

• Oral Contraceptive/anabolic steroids

• Glycogen Storage Diseases (i.e. Von Gierke’s, type Ia)

302

Clinical pic of Liver Cell Adenoma (Hepatic Adenoma)

– Acute (about 50%, Mortality 20%) – Abdomenal pain

– Shock and hemorrhage

» Hemorrhage into tumor or peritoneal cavity, which can be fatal in pregnancy – Incidental

303

Hepatic Adenoma tx

• Stop causative medication

• Resect tumor for

    – Symptoms

     – Large or increasing size because increased risk of       bleeding and/or risk of malignant transformation

    – Uncertaindiagnosis

304

Focal Nodular Hyperplasia epi

– F:M 4:1

– Usually asymptomatic.

– NorelationtoOCP

305

Focal Nodular Hyperplasia pathology 

– Ill-defined area with a cirrhosis–like appearance and typically has a characteristic central stellate scar.

– Proliferation of all 3 elements- benign hepatocytes (< 3 cells thick plates) and fibrous septa with inflammatory cells, bile ductules, and prominent (thick walled) arteries

306

#1 liver tumor in children (90% <5 y/o and 70% <2 y/o) – Slight male predominance

Hepatoblastoma

307

Hepatoblastoma associated with

Associated with Beckwith-Wiedemann syndrome, Down syndrome, familial polyposis coli, hemihypertrophy, renal malformation and various cytogenetic abnormalities

308

Hepatoblastoma tx 

• Surgical excision with adjuvant chemotherapy is the treatment of choice

– Neoadjuvant chemo may allow for surgical resection of previously ‘unresectable’ tumor

• Liver transplantation is another option

309

Hepatoblastoma growth

• Single/multiple heterogeneous mass(es)

– Rapid growth (poor prognosis)

– Spreads to lungs, LN and peritoneum

310

Hepatoblastoma morphology types 

 

– EpithelialType

• Fetal(bestprognosis)

• MixedEmbryonalandfetal • Macrotrabecular

– Mixed Epithelial and Mesenchymal Type

• Osteoid or cartilaginous differentiation

311

Hepatocellular Carcinoma epi US vs world 

• Globally

– ~600,000 cases per year

– Fifth most common cancer and third leading cause of cancer-related death worldwide .

– M:F is as high as 8:1

• United States

– Liver cancer is one of most rapidly increasing cancers – ~24,000 new cases in 2010

– 80%-90% occurring in cirrhotic livers.

312

Hepatocellular Carcinoma Risk Factors

• Cirrhosis

• Viral Hepatitis (HCV, HBV)

• Alcoholic steatohepatitis

• Non-alcoholic steatohepatitis

• Autoimmune hepatitis

• Hemochromatosis, Alpha-1-Antitrypsin deficiency

• Thorotrast, aflatoxins and anabolic steroid exposure. Surveillance should be with ultrasound or CT/MRI at 6 to 12 month intervals (AFP is not adequate).

313

Risk of HCC in different disorders 

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314

– Solitary/ multiple nodules that typically arise in a background of cirrhosis

• Bile stained or paler than surrounding liver

• Can have well-circumscribed or irregular borders, but tend to have a capsule

– Satellite nodules and venous invasion (portal or hepatic veins) is common.

• Worse prognostic features

HCC

315

Histo:

• Hepatocyteswithincreasednuclear:cytoplasmic, atypia, and thickened liver cell plates (>3)

– Well differentiated to poorly differentiated type

– Bile production by tumor cells

• VariablePatterns/Subtypes: – Trabecular

– Pseudoacinar/Pseudoglandular – Solid

– Scirrhous

– Fibrolamellar (better prognosis)

• Cirrhosisinadjacentliverparenchyma

HCC

316

Hepatocellular Carcinoma

Clinical Features

• Not characteristic or uniform, usually masked by underlying liver disease

– Illdefinedupperabdominalpain,fatigue,cachexia – Raised AFP levels in 60-75% (markedly increased)

• Characteristic radiographic finings, otherwise diagnosis-FNA/ biopsy

317

Serum Alpha Fetoprotein (AFP)

Serum Elevation associated with:

• HCC (especially with highelevation [>1000ng/mL])

• Other tumors such as:

– Hepatoblastoma

– Yolk Sac tumors/Other germ cell tumors

• Pregnancy with fetal neural tube defects

• Fetal distress or death

• Cirrhosis (mild elevation)

• Massive liver necrosis

318

Fibrolamellar Variant epi

Youngadults(20–40y/o) – M:F

319

Fibrolamellar Variant associations?

None 

320

Cholangiocarcinoma associations 

– Sclerosing cholangitis

– Cystic dilatations/ malformation of biliary system (Caroli’s disease)

– Gallstones

– Chemicals: thorotrast, benzidene, nitrosamines

Parasitic infections (Clonorchissinensis; Opisthorchisviverini)

321

Cholangiocarcinoma (CC) epi

– Older adults; M:F

– Normal serum AFP

322

Cholangiocarcinoma (CC)

Carcinoma of bile duct origin

323

Extrahapatic Cholangiocarcinoma

– Upper third (60%)

• Hilum = Klatskin tumor

– Middle third (20%)

– Lower third (15%)

– Diffuse (5%)

324

Pathology of Cholangiocarcinoma

– Firm, sclerotic mass with various

growth patterns

– Proliferation of malignant glands with dense fibrosis

325

tx of 

Cholangiocarcinoma

 

Surgical excision and/or chemotherapy

326

Intra hepative cholangiocarcinoma types 

Mass forming 

 

327

• Patients typically have non-cirrhotic livers and present with obstructive symptoms or pain

– Jaundice

– Cholangitis

• Charcot’striad:Jaundice,fever,chills – Malaise

– Weight loss

– Clinically silent for long periods

• More likely to spread beyond liver than HCC

Cholangiocarcinoma

328

Prognosis of Cholangiocarcinoma

death within 6-12 months

329

Cholelithiasis (Gallstones) epi

Afflicts 10-20% of adults in N. hemisphere

– 1,000,000 new patients/year; 50% undergo surgery

– More common in Latin American countries (20-40%)

330

Cholelithiasis (Gallstones) pain seen 

70-80% asymptomatic, buy may present with constant or colicky pain (after a fatty meal)

331

2 types of Cholelithiasis (Gallstones)

– Cholesterol stones- Cholestrol monohydrate (80%) – Pigmentstones-Bilirubincalciumsalts(20%)

332

Complications for gallstones 

 Empyema of gallbladder

 Perforation/Fistulas

 Extrahepatic bile duct obstruction leading to cholangitis/pancreatitis  Gallstone ileus

 Increased risk of carcinoma

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CHOLESTEROL STONE risk factors 

 

• Advancing age – <6%in<40Y

• Female gender

– OCPuse/Pregnancy

• Obesity

– Orrapidweightreduction

• Gallbladder stasis

• Inborn error of bile salt

metabolism

• Hyperlipidemia syndromes

The Four F’s: female, fat, forties, fertile, (+ family hx)

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PIGMENT STONES risk factors 

Common in Asians

Rural > urban

Chronic hemolytic syndromes

– SickleCell Anemia

Biliary infections

GI disorders

• Ileal disease (e.g. Crohn’s disease, ileal resection or bypass)

• Cystic fibrosis

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Pathogenesis of Cholesterol Gallstones

• Bile is supersaturated with cholesterol

• GB hypomotility promotes nucleation (precipitation of cholesterol from bile into vesicles)

• Cholesterol nucleation in bile is accelerated

• Mucus hypersecretion traps the crystals, permitting aggregation into stones (acts like a glue)

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Cholelithiasis may or may not lead to Cholecystitis means /

Stones may or may not lead to inflammation

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Acute “Calculous” or “Acalculous” Cholecystitis (Pathogenesis)

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• Sudden onset of pain- right hypochondrium or epigastrium

• May appear like surgical emergency

• Associated fever, nausea and vomiting

• Rarely jaundice if obstruction of CBD

• Most patients recover

• Morphology: Inflammation (PMNs), edema, and hemorrhage of the gallbladder wall

Acute Cholecystitis

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Morphology: Inflammation, thickening, and fibrosis of the gallbladder wall with Rokitansky-Aschoff Sinuses

– Rarely extensive dystrophic calcification (aka: Porcelain Gallbladder)

• Association with cancer

Chronic Cholecystitis

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Gallbladder Tumors common type 

Most are adenocarcinoma

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Gallbladder Tumors epi 

 

– Rarely discovered at a resectable stage

• Poor prognosis

– Slightly more common in women

– Most common in the elderly (60 – 70 years of age)

– Gallstones are present in 60 – 90% of the cases • Carcinogenic derivatives of bile may play a role

– Other risk factors-pyogenic and parasitic infections

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Acute Pancreatitis associated with 

GALLSTONES and ALCOHOLISM

• Other important CAUSES include

 Infections –Mumps, Coxsackie and Mycoplasma

 Acute ischemia – Shock, trauma, vascular thrombosis, embolism, vasculitis etc.

 Hyperlipoproteinemias (uncommon)

 Drugs –Diuretics, Azothioprine, Estrogens, sulfonamides etc

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Acute Pancreatitis-Clinical Features

 Leukocytosis

• DIC

• Hemolysis

• Peripheral vascular collapse

• Shock with ATN, ARDS

• Hypocalcemia (due to saponification)- tetany

• Raised amylase levels in first 24 hours

• Followed by lipase with in 72-96 hours

• Complications- – ARDS

– ATN

– Pancreaticabscess

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Acute Pancreatitis-Morphology

• Focal areas of fat necrosis in pancreas and peripancreatic tissues and abdominal cavity

• Chalky white areas of Ca++ deposition (saponification)- Appear radiopaque on radiographs

• Severe cases–necrosis of pancreatic tissue (acini, ducts and islets) with hemorrhage (Hemorrhagic pancreatitis)

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• Repeated bouts of mild to moderate pancreatic inflammation with loss of pancreatic parenchyma and its replacement by fibrous tissue

Chronic Pancreatitis

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Chronic Pancreatitis epi

Common in middle aged alcoholics

• Pancreatic divisum in about 12%

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Causes of Chronic Pancreatitis

– Autoimmune pancreatitis, tropical pancreatitis,

Hereditary pancreatitis, CFTR mutation associated

• ~40% no obvious cause

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Repeated attacks or persistent moderate-severe abdominal and back pain

• Pancreatic insufficiency and diabetes may develop

– Features of malabsorption, corrected by pancreatic

enzyme supplements

Chronic Pancreatitis

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Complications of chronic pancreatitis 

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Autoimmune Pancreatitis types 

Accounts for 2-7% of chronic pancreatitis.

• Type 1- Male predominance; 6th decade * IgG4 related disease*

• Type 2- Affects genders equally; 4th decade

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Autoimmune Pancreatitis assciated diseases 

•Sjogren’s, IBD, SLE, DM, and retroperitoneal fibrosis

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Lab findings in autoimmune pancreatitis 

• ↑ pancreatic enzymes

•Hypergammaglobulinemia •>40% have increased IgG4

(Sen 50%;Spec 100%) •Autoantibodies

•ANA (75%) •Antilactoferrin (ALF) (75%)

•Anticarbonic anhydrase II (ACA-II) (50%)

•Rheumatoid factor (Rh)

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Radiographic findings of Autoimmune Pancreatitis

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Type 1 Autoimmune Pancreatitis- Morphology

• Lymphoplasmacytic infiltrate centered around large and medium sized interlobular ducts

• Periductal and perivenular fibrosis

• Obliterative phlebitis (arteries typically spared)

• Increased IgG4 plasma cells

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Type 2 Autoimmune Pancreatitis

 

• Lymphoplasmacytic infiltrate centered around ducts

• Granulocytic epithelial lesions with partial/complete duct obstruction/obliteration

• IgG4 plasma cells usually absent

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Pancreatic Tumors

• Epithelial – Ductal Epithelium

– Ductal Adenocarcinoma

• Most common, very poor prognosis

– Cystic Neoplasms (can be benign or harbor Carcinoma)

• Serous cysts usually benign

• Mucinous lesions can be benign, dysplastic, malignant – Intraductal papillary mucinous neoplasm (IPMN)

– Mucinous cystic neoplasm (MCN)

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Pancreatic Tumors

Epithelial–Exocrinecells

– Acinar cell carcinoma (relatively uncommon)

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Pancreatic Tumors

Endocrine

– Islet cell tumors/ neuroendocrine “carcinoid” tumors

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Carcinoma of The Pancreas epi

• Fifth most common cause of death in U.S.

• Only convincing association is with smoking

– Other risk factors like alcohol or diet rich in fats are not consistent

• Familial relapsing pancreatitis (very rare) is strongly associated

with pancreatic carcinoma

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location of pancreas ca

– Head 60-70%

Carcinoma in this location causes obstruction to bile flow and jaundice

– Body5-10%

– Tail10-15% 

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Carcinoma of The Pancreas majority are this type 

 Majority are ductal-type adenocarcinomas – Dense stromal fibrosis (desmoplasia)

– Propensityforperineuralinvasion

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Often remain silent until late stage

• Pain is usually first symptom (because of invasion

posterior abdominal wall and nerves)

*• Obstructive jaundice (“Painless jaundice”)

– usually CBD obstruction -- HOP mass or CBD stone

• Trousseau’s sign (migratory thrombophlebitis)

– Platelet activating factors and procoagulants are released from the tumor (10% )

• No single specific marker – RaisedlevelsofCA19-9

• Very bad prognosis

Carcinoma of The Pancreas

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Pancreatic Endocrine Tumors

Islet cell tumors, make islet cell type hormones

– Functional (Insulinomas, Gastrinoma, Glucagonoma, etc.)

– Non-functional

• Behavior difficult to predict

reliably

– Benign (Islet cell adenoma) – Malignant

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Neuroendocrine tumors: Benign vs. Malignant

• In general, NE tumors ≤2 cm behave in a benign fashion

• However, the current histologic criteria is based on proliferative activity

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Insulinomas

• Usually benign, solitary

• Arise from ß cells

• ClinicallymanifestasWhipple’striad

– Signs and symptoms because of hypoglycemia

– Hypoglycemia relieved with intake of glucose (and accentuated by fasting)

– Low blood glucose levels

• Insulin levels are increased

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Gastrinomas (Zollinger- Ellison Syndrome)

Ulcer from hypergastrinemia from a gastrin-producing tumor in the pancreas, peripancreas or duodenum

– Do not use term ZE-syndrome for compensatory hypergastrinemia (ie. in autoimmune gastritis)

• Multiple ulcers- esophagus, stomach, duodenum and jejunum

• Refractory to conventional treatment – must remove tumor!

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Syndromes associated with functional islet cell tumors 

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Acinar cell carcinoma epi

• 1-2% of all exocrine neoplasms

• M:F = 2:1; 40-81Y (62Y)

• Rare cases in children

• Whites > Blacks

• Subcutaneous fat necrosis and panniculitis (16%) due to lipase

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• Arise within the ductal system (main/branched ducts) – Majority in the head of pancreas

• The duct often dilated and filled with mucin

• Cysts can be multiloculated

• Tall columnar mucin secreting cells often with papillary/pseudopapillary architecture

• Cytology-Benign-Borderline (low grade)-Malignant (high grade) +/- invasive adenocarcinoma

Lacks ovarian type stroma

Intra-ductal Papillary Mucinous Neoplasm (IPMN) pancreas 

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Tall columnar mucin secreting cells with the characteristic feature being the surrounding ovarian type stroma

• Cytology-Benign-Borderline (low grade)-Malignant (high grade) +/- invasive adenocarcinoma

Mucinous Cystic Neoplasms pancreas 

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Mucinous Cystic Neoplasms epi

• 2-5% of all exocrine neoplasms

• Exclusively in women; 20-82Y (49Y)

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Location of Mucinous Cystic Neoplasms

• Occur mostly in the tail

• Not connected to the ductal system

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Pathogenesis of acute pancreatitis 

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