diseases of the gastrointestinal tract yun ma, m.d. professor dept. of pathology guangxi medical...
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Diseases of The Gastrointestinal Tract
Yun MA, M.D.
Professor
Dept. of Pathology
Guangxi Medical University
Tel: 5356534(O)
E-mail:[email protected]
April,2008
1. Chronic Gastritis 慢性胃炎2. Peptic Ulcer Disease 消
化性溃疡3. Acute Appendicitis 急性阑尾炎4. Idiopathic inflammatory Bow
el Diseases 非特异性肠炎5. Carcinoma of GI 消化道肿瘤
contentscontents
April,2008
Stomach:normal structure and function
April,2008
Stomach:
mucosa
submucosa
muscularis
serosa
April,2008 Fundic mucosa Antral/pyloric mucosa
Gastric pit
Gastric glands
Antral mucosa
April,2008
normal structure and function
Parietal cells
Chief cells
Mucous cells
Gastrin G cells
Mucus 粘液
hydrochloric acid, intrinsic factor. 胃酸 / 内因子Pepsinogen 胃蛋白酶原Gastrin胃泌素
why stomach doesn’t digest itself during the food processing?
April,2008
• Gastric mucus• The anatomic integrity of th
e mucosa-- regeneration 再生 of epithelium
• Mucosal blood flow • Prostaglandins(PG1) 前列腺
素 1
pH gradientMucin
HCO3-
Gastric Resistance to Acid
Any reason that can induce excess gastric juice secretion or damage the function of the mucus barrier will cause the injury of stomach.
normal structure and function
Mucus Mucus BarriersBarriers
Acid
neutral↑
April,2008
Inflammatory lesions of the stomach--Gastritis
Definition:
Classification acute gastritis chronic gastritis
Inflammation of the gastric mucosa
April,2008 www.barrettsinfo.com/content
The Endoscope 内窥镜
April,2008
Chronic Gastritis 慢性胃炎 Definition: Chronic mucosal inflammat
ory changes eventually leading to mucosal atrophy and epithelial metaplasia.
COMMON DISORDER, ESPECIALLY IN THE ELDERLY
Chronic superficial gastritisChronic atrophic gastritis
April,2008
morphology
Chronic superficial gastritis
1. the mildest form
2. superficial layer of mucosa,
3. lymphocytes and plasma cell.
4. without glands atrophy.
慢性浅表性胃炎
April,2008 morphology
Chronic superficial gastritis
April,2008
mucosal gland atrophy intestinal metaplasia.
Chronic atrophic gastritis
Decrease of the Decrease of the size & number size & number
of gastric of gastric glandsglands
morphology
慢性萎缩性胃炎
April,2008 morphology
Chronic atrophic gastritis
April,2008
Chronic atrophic gastritis
Adaptive response. Premalignant condition:
Intestinal metaplasia
Parietal cells
Chief cellsGoblet cells
Absorptive cells
Paneth cells
morphology
April,2008
Chronic atrophic gastritis
morphology
April,2008
Causes & pathogenesis
Helicobacter.pylori 幽门螺杆菌 Chronic irritants 慢性刺激 Autoimmune damage 自身免疫
April,2008
•Causes & pathogenesis
1. Helicobacter.pylori
Non-invasive, gram negative bacillus.
Present on the surface mucous layer.
Bettered demonstrated by special stain.
幽门螺杆菌
April,2008
Production of locally toxic products –
Recruit inflammatory cells Generation of an antibody response, Alteration of gastrin secretion-- elev
ated acid secretion
Urease, proteases, and lipases; vacuolating cytotoxin,
•Causes & pathogenesis
1. Helicobacter.pylori
April,2008
2. Chronic irritants Tobacco, Drugs(NSAID):pain relievers 去痛片 ,arth
ritis medicines,etc—regular use may cause trouble
Bile reflux 胆汁返流 Irritant foods or drinks Alcohol,
•Causes & pathogenesis
April,2008
3. Autoimmune Damage
T-cell mediated autoimmune damage Autoantibodies
•Causes & pathogenesis
1. Antiparietal cell antibody 抗壁细胞抗体2. Intrinsic factor blocking antibody 内因子
封闭抗体3. Intrinsic factor binding antibody 内因子
结合抗体
减少内因子分泌减少内因子分泌 // 干扰其功干扰其功能能
April,2008
April,2008
Vit B12 deficiency and pernicious anemia 恶性贫血恶性贫血
Parital cells↓ －→ Intrinsic factor ↓
Autoantibodies
VitB12 absorption↓
DNA synthesis → defective nuclear maturation
Pernicious Anemia 恶性贫血
April,2008
Differences between typeA & TypeB gastritis –Table 8-1
Rare Autoimmune Body and fundus Hypochlorhydria or
achlorhydria Low serum Vit B12 Megaloblastic ane
mia No ulcer Cancer
Common Helicobacter pylori Pyloric antrum Variable acid secreti
on Normal serum Vit B12 No anemia Predisposed to ulcer Cancer
April,2008
Clinical Features
Usually causes few or no symptoms Upper abdominal discomfort and dyspep
sia 消化不良 Hypochlorhydria 胃酸低 or achlorhydria
无胃酸 and pernicious anemia 恶性贫血 Increased risk to peptic ulcer 溃疡病 and
gastric cancer 胃癌 .
April,2008
Peptic Ulcer DiseaseDefinitions: Tissue defect 缺损 of
gastrointestinal tract caused by the digestion of gastric juice.
溃疡病
April,2008
Erosion 糜烂 -- superficial defect confined to mucosa.
Ulcer 溃疡 -- defect with penetration to deeper layers of gastric wall.
Muscularis mucosae 黏膜肌
April,2008
OCCUR MAINLY IN THE FOLLOWING LOCATIONS:
DUODENUM,
• GASTRIC ANTRUM, LESSER CURVATURE
• ESOPHAGUS• JEJUNUM
Barretts esophagus
DU/GU=4/1CONCURRENT=10~20%
98%
1st portion, anterior wall
Zollinger-Ellison syndrome
April,2008
Hypersecretion of Acid
Pathogenesis:
1. No acid,No ulcer2. Higher acid secretion in DU pati
ents3. Multiple ulcers in Zollinger-Elliso
n syndrome 4. Efficiency of anti-acid treatment
strategy
D U
Strong Attacker :
April,2008
Decreased Mucosal Resistance to Acid
Pathogenesis:
1. Normal or low acid production in GU
2. Decreased PG E2 levels in gastric juice
3. Pathological roles of Risk factors(smoking,drugs,etc)
G U
Weak Protector
April,2008
Helicobacter pylori Infection
Pathogenesis:
1. Pathological &Epidemiology evidences
2. Research results
3. Antibiotics treatment
4. Nobel Prize
Injury FactorsInjury FactorsWeaken mucosaWeaken mucosa
April,2008
The Nobel Prize in Physiology or Medicine 2005The Nobel Prize in Physiology or Medicine 2005
April,2008
Protector :
1. Mucus barrier
2. Integrated epithelia & its ability of regeneration
3. Normal circulation
Attacker :
1. H.P infection;
2. NSAIDs; 3. smoking;4. drunk; 5. duodenal-
gastric reflux.
Imbalance between mucosal resistant and acid-peptic digestion.
April,2008
1. Small-- 50% <2cm and 75% <3cm， 10% >4cm--giant gastric ulcers.
2. Round-oval , sharply punched-out perpendicular walls margins level with adj. mucosa
3. Smooth and Clean Base usually in submucosa, scarring in base may pucker surrounding mucosa with radiant mucosal folds.
pathology
Peptic Ulcers
April,2008
Clean base
Clear edge
April,2008
Microscopic: Peptic Ulcers
April,2008
What is the role of granulation tissue肉芽组织 present in the base of an peptic ulcer?
endarteritis
What are the effects of endarteritis within the base of the ulcer
April,2008
Complications
Hemorrhage出血 Perforation/penetration 穿孔 Obstruction 幽门梗阻 malignant transformation 恶变
Peptic Ulcers
April,2008
View under endoscope Complications 1. Hemorrhage
occur in 25-35% cases accounts for 10% of ulcer deaths-due to erosion into submucosal artery,
April,2008
•Occult blood in stool 潜血反应阳性•Melena (black stool) 黑便 •Hematemesis 呕血 : coffee-ground appearance vomitus 咖啡渣样
1. HemorrhageComplications
April,2008
2. Perforation 穿孔
Complications
April,2008
2. Perforation 穿孔
With 5% frequency and accounts for over 70% of ulcer deaths. Most common with anterior duo.ulcers 前壁 . Lead to spillage of gastric contents into the peritoneal cavity and peritonitis腹膜炎 .
Complications
April,2008
Contraction due to fibrosis(scar) and/or edema resulting in obstruction
3. Obstruction
Complications
April,2008
3. Obstruction
Hourglass stomach
•Constriction of pyloric canal or 1st part of Duo.•Severe vomiting with hypochloremic alkalosis 碱中毒
Complications
April,2008
• Uncommon event in gastric ulcer(1%).• Never become malignant in Duo. Ulcer?
4. Malignant transformation
Complications
April,2008
Quickly Review of Peptic Ulcer
ONE pathogenesisTWO main locationsTHREE common complicationsFOUR layers of basal structure und
er microscopeFIVE outcomes
April,2008
Appendicitis, p232
Most common acute abdominal condition
Most common among young adult（ 10 ～ 30yrs ）
Acute inflammation resulting from obstruction of the lumen
Characteristic with acute purulent inflammation
Profile
April,2008
Obstruction of appendiceal lumen
Appendicitis
•Fecalith 粪石•Kinking of the appendix 扭转•Lymphoid hyperplasia due to viral infection•Parasites&eggs
Pathogenesis
April,2008
Multiplication of luminal bacteria
Appendicitis
----Pathogenesis
Escherichia Coli 大肠杆菌Streptococcus faecalis 粪链球菌
•Invasion of mucosa and wall.
•Inflammation.
大肠杆菌
April,2008
Early acute appendicitis: Acute suppurative appendicitis 急性化脓
性阑尾炎 : Acute gangrenous appendicitis 急性坏疽
性阑尾炎 :
Neutrophilic infiltration of the muscularis propria
- an acute suppurative inflammation 急性化脓性炎
Appendicitis----Pathology
3 stages
炎症的进展
April,2008
Appendicitis
Pus in lumen
hyperemia
Early stage
----Pathology
April,2008
epithelia
pus
Erosion of mucous
Appendicitis----Pathology
April,2008
Appendicitis
Purulent inflammation involves whole intestinal wall.
April,2008
Appendicitis ----PathologyAppendicitis
红
肿
热
痛
April,2008
Try to indicate the complications of appendicitis
Perforation:
Distant abscesses
Sepsis 败血症
--1.acute peritonitis 腹膜炎--2.peri-appendiceal abscess （阑尾周围脓肿）
---Liver abscess
---critical state of the infection,may cause death 炎症的扩散
April,2008
Recall Basic lesion of inflammation Structrue feature of the gastroint
estinal tract Different presentation between a
cute and chronic inflammatory processes.
April,2008
1. Gastritis2. Peptic Ulcer Disease3. Acute Appendicitis4. Idiopathic inflammatory
Bowel Diseases5. Carcinoma of GI
Diseases of the Digestive SystemDiseases of the Digestive System
April,2008
Idiopathic Inflammatory Bowel Diseases— 特发性炎症性肠病，非特异性肠炎
Distinct immuno-related entities,include 2 different diseases.
Involve mainly intestines. Inflammatory diseases,lasting a long
period of time. Abdominal pain,diarrhea 腹泻— acute
phase;
April,2008
Crohn‘s Disease (Regional Enteritis )
Recurrent inflammatory bowel disease predominantly of the small intestine.
Characterized by intermittent attacks 间歇性发作 of mild diarrhea( 腹泻 ), abdominal pain, and fever--spaced by asymptomatic periods of weeks-months.
Unknown etiology( 病因学 ) － immunologic-related?-genetic predisposition?-psychologica mechanisms-age, sex,race ， etc.
April,2008
PATHOLOGY:
Locations
Other parts of GI:rare 75 ％ also with Skin lesions:perianal( 肛周） a
bscesses （脓肿） ,fistulas( 瘘管）
Systemic inflammation
局限性肠炎
• 80% at terminal ileum, and 50% of these cases also involve colon.
• About 20% involve colon only, especially cecum and right colon, isolated involvement of rectum is unusual.
April,2008
PATHOLOGY: Segmental distributio
n （节段性分布） is typical with sharply defined involved segments separated by "skip areas".
Thickened, inflexible, and resembles a rubber hose （橡皮管） . Lumen is narrow(stenosis)－ chronic phase.
Characteristics On Gross
IDIOPATHIC BOWEL DISEASES
normal
lesion
April,2008
cobblestone 鹅卵石状 appearance （ -inflamed thicken mucosa ）
linear narrow deep ulcers-fissures(裂隙状溃疡 ).
Adjacent mesentery is thickened and regional Ln‘s are enlarged.
Characteristics On Gross
April,2008
transmural chronic inflammation
lymphoid hyperplasia granulomas (noncasea
ting granulomas),seen in 40% to 60% cases.
（非干酪性肉芽肿性炎 , 病变可累及肠壁全层）
IDIOPATHIC BOWEL DISEASES
Transmural inflammation
Base of ulcer
?
Microscopic Features
PATHOLOGY:
April,2008
Chronic granulomatous inflammation 慢性肉芽肿性炎
IDIOPATHIC BOWEL DISEASES
Microscopic Features
April,2008
Diagnostic features of Crohn‘s Disease
Key points
April,2008
Chronic Ulcerative Colitis (UC) is an inflammatory disease which affects only large bowel .
Chronic, relapsing disease which is characterized by attacks of bloody diarrhea containing stringy mucous, cramps( 腹部绞痛 ), lower abdominal pain, and fever 。
Similar to CD on epidemiology.
Ulcerative Colitis 溃疡性结肠炎Ulcerative Colitis 溃疡性结肠炎
IDIOPATHIC BOWEL DISEASES
April,2008
Begins in rectum ， may involve the entire colon.
Continuous pattern of distribution
PATHOLOGY:
溃疡性结肠炎
April,2008
Intense hyperaemia and haemorrhage.
Pseudopolyps 假性息肉
PATHOLOGY:
IDIOPATHIC BOWEL DISEASES
溃疡性结肠炎
April,2008
Diffuse mucosal inflammation
Crypt abscesses extend into lamina propria/submucosa to produce ulcers.
The ulcers may coalesce 融合 and denude large areas of colonic mucosa.
PATHOLOGY:
IDIOPATHIC BOWEL DISEASES
溃疡性结肠炎
April,2008
Isolated island of regenerating mucosa bulge upward to create pseudopolyps 假性息肉 .
Without Linear fissures and fistulas formation.
PATHOLOGY:
April,2008
Chronic relapsing inflammatory disease which affects only large bowel .
Limited to the mucosa and submucosa except in the most severe cases.
Neutrophilic infiltration and the crypt abscesses( 隐窝脓肿 )—shallow & irregular ulcers,may coalesce each other.
Psedopolyps Heal with little fibrosis. Increased risk to carcinoma in long-term case
s.
Ulcerative Colitis 溃疡性结肠炎
IDIOPATHOLOGIC BOWEL DISEASES
April,2008
Items 克隆氏病， CD 溃疡性结肠炎， UC
Granuloma Yes Absent
Ulcer Deeper SubmucosalSerosal surface Dull Normal
Thickening wall Yes No
Skip lesion Yes No
Cancer change Few More
Gastrointestinal Carcinoma
Stomach Carcinoma p227Colorectal Carcinoma p237Esophageal Carcinoma P217
胃癌，结直肠癌，食道癌
April,2008
胃癌Gastric Carcinoma
Global incidence•The second leading cancer killer in the world
•The most important and most common malignant tumor in stomach
Malignant tumor of the gastric epithelia
April,2008
High incidence areas: East Europe and Asia (70% cases)
Middle :Andean region of South America and Central America.
Low incidence areas:United States and Africa
April,2008
• Dietary factors 饮食因素• Nitrosamines 亚硝胺• Infection of H.pylori 幽门螺杆菌• Chronic gastritis with intestinal met
aplasia 慢性胃炎和肠上皮化生
Etiology and Pathogenesis
April,2008
Chronic gastritis:
Gastric
Carcinogen,1994,IARC
Inflammatory chemical agents (free radicals)
Glandular atrophy
High cell turnover
Genomic DNA damage
Hypochlorhydria
dysplasia
Etiology &Pathogenesis
About 1% of infected cases will develop cancer
• H.pylori
April,2008
Intestinal Metaplasia, around the cancerous ulcer
Positive reaction(RED) with alkaline phosphatase stain 碱性磷酸酶染色显示化生区域
April,2008
fundus
body
Pyloric antrum
Locations :
Pyloric antrum: 50% to 60%
Cardia: 25%
Morphology
Lesser curvature :40%
Greater curvature: 12%
lesser curvature of the antropyloric region.
April,2008
is a carcinoma limited to the mucosa or the mucosa and submucosa, regardless of nodal status.
Morphology
Early gastric carcinoma
10yr survival rate=90%
早期胃癌
Mass scaning
Endoscope surveillance
April,2008
Advanced Gastric Carcinoma进展期胃癌
3 growth types grossly :1. Exophytic: Polypoid
or fungating type 息肉型2. Excavated: Ulcerati
ng type 溃疡型3. Flat or 浸润型 depress
ed:Diffuse or infiltrating (linite plastica)
extend beyond the submucosa into the muscular wall.
1
3
2
Depents on the growth direction of the main tumor body
April,2008
Polypoid or fungating type
Morphology
• tumor mass protrudes into the gastric lumen.
April,2008
Excavated type
A shallow or deep erosive crater in the gastric wall
Morphology
April,2008
• Cancerous ulcer is large, irregular in shape and is usually more than 4 cm in diameter.
• Margin is heaping up and harder.
• Base is with hemorrhage and necrosis.
April,2008
Flat or depressed type• No obvious mass• linitis plastica
( 革囊胃 ). a diffusely infiltrat
es the entire gastric wall without forming an intraluminal mass.
Morphology
A leather bottle stomach
April,2008
Microscopically mostly it is adenocarcinoma
Gastric adenocarcinoma exhibits two morphological types :
Intestinal variant : differentiated; from the cells having intestinal metaplasia in chronic gastritis; better prognosis ;more common; old adult.
Diffuse variant : Poorly differentiated, from the native gastric mucosal cells. Poor prognosis.young A.
Morphology
Lauren’s classification
April,2008
Intestinal variant
adenocarcinoma
◊ Most common in high risk areas
◊ Usually arise on a background of intestinal metaplasia
◊ Controversial prognostic significance
April,2008
Diffuse variant
adenocarcinoma
Signet-ring cell Ca.
印戒细胞癌
Diffuse variantDiffuse infiltration of isolated or small group of tumour cells
April,2008
Metastasis :
Special Sites :
Left supraclavicular Node 左锁骨上淋巴结(Above suprasternal notch and clavicles )
Ovary in female
1.Lymphatic spread2.Hematogenous spre
ad3.Seeding the periton
eal cavity
Spread Local spread:
April,2008
Ovaries, Krukenberg tumor,
metastatic tumor either by implantation or
by lymphatic spread
Question often asked by gynecologists( 妇科医生 ): primary or secondary tumor?
April,2008
Gastric Carcinoma
Geographical differences in distribution Closely associated with H.pylori infection. Common in the antral area,lesser curvature. Depth-depended prognosis. Spread by lymph,blood and seeding. Highly malignancy with discouraging 5yr su
rvival.
Special words:
Early gastric carcinoma
Linitis plastica
Krukenberg’s tumor
April,2008
This is a gastrectomy specimen from a patient showing a ulcerated lesion in the body of the stomach. Benign or malignant?
April,2008 Describe the lesion showed in picteures undermicroscope
April,2008
Make diagnosis
April,2008
•Definition
Colorectal Carcinoma
A malignant epithelial tumour of the colon or rectum. Only tumours that have penetrated through muscularis mucosae into submucosa are considered malignant at this site.
April,2008
Epidemiology and Etiology• One of the commonest forms of malignancy in developed countries.
• Environmental factors play the most important etiological role.
Colorectal Carcinoma
April,2008
Diet and lifestyle high-fat, high protein, low-fiber diet deficiency of Vitamine A 、 C 、 E Chronic inflammation:CD&UC Genetic factors : APC and DNA mismatch repair genes.
Epidemiology and Etiology
April,2008
Altered bacteria flora
Increased fecal retention
Increased synthesis of bile acid
High concentration of potential carcinogens
High fat,high protein,
low fiber Diet
April,2008
Morphology
Rectum& distal sigmoid :25%
Proximal sigmoid :25%
Descending colon:15%
Right colon:30%
Location:
April,2008
Ulcerous Carcinoma
Rectal bleeding
Morphology
April,2008
Carcinomas in the left colon__descending and sigmoid colon tend to be annular, encircling lesions that produce constrictions of the bowel and narrowing of the lumen.
Stenosing type
Astriction 便秘
Morphology
April,2008
Polypoid and large fungating cancers are more common in the right colon.
Polypoid Type
Abdominal mass
Occult bleeding in stool.—iron deficiency anemia
Morphology
April,2008
adenocarcinomaMorphology
N
T
April,2008
Cancerous cells Sometimes may produce mucin to give a gelatinous appearance of the cut surface of this mucinous( colloid ) carcinoma.
adenocarcinoma
Morphology
WORSE PROGNOSIS
April,2008
It doesn’t spread via lymph or blood before it penetrate through the muscularis mucosae--can be cured by resection of the lesion !
Lymphatic spread to the regional LN
Hematogenous spread to the liver, lungs etc. THE EXTENT OF SPREAD
THROUGH THE BOWEL WALL AND THE PRESENCE OF LYMPH NODE METASTASES ARE THE MAJOR PROGRESTIC FACTORS.
spread
April,2008
prognosis
TNM Staging of Colon Cancers
Tumor(T) lymph Nodes(N) Distant Metastasis(M)
0 =none evidentIs =in situ(limited to mucosa)1 =invasion of submucosa2 =invasion of muscularis propria3 =invasion of subserosa or nonperitonealized pericolic fat 4 =invasion of contiguous structures
April,2008
5-YEAR SURVIVAL RATES T1 =97% T2 =90% T3 =78% T4 =63% Any T;N1; M0 =66% Any T;N2; M0 =37% Any T&N; M1 =4%
April,2008
Colorectal carcinoma Reverse distribution pattern compare
d to gastric carcinoma Also related closely to diet 3 growth types—relate to clinical feat
ures Adenocarcinoma TNM staging
April,2008
Esophageal Carcinoma, p553
Compare to colorectal Ca •Similar growth patterns•Clinical symptoms
Related to the growth patterns•Different histological appearance__squamous carcinoma
April,2008
April,2008
Keratin pearl
Intercellular bridge
Squamous carcinomaWell-differentiated
April,2008
MetastasisThese lesions tend to spread by direct continuity, form a fistula between esophagus and the trachea.
Lymphatic spread to the regional LN
Hematogeneous spread to the liver or lungs, etc.
April,2008
Common points in the esophagus, stomach & colon carcinoma :• the causes may relate to the foodstuff• the locations are within or close to the termination(narrow sites).• grossly 3 forms : polypoid, ulceration & diffuse ( or annular ) infiltration• microscopically adenocarcinoma ( poor or well differentiation ) or squamous carcinoma• the spread routes are almost the same• clinical features : partial obstruction, hemorrhage, damage the local tissue, weight loss .
April,2008
Case report A 48 yr old woman, with repeated diarrhea
and lower right abdominal pain for 3mths. Coloendoscopic examination reveal a polyp
oid tumor protruding into the colon lumen, with surface hemorrhage and broad base.
Right hemicolectomy was performed and the tumor was found infiltrating within the muscularis propria, with enlargement of 3 regional lymph nodes.
April,2008
Case report
Try to staging her neoplasm
April,2008
After the surgery resection, the patient received chemotherapy.
One year later, there was a solid nodules found in her liver.
This was treated with cryoablation as well as the resection of partial liver.
Again chemotherapy. Recurrent multiple liver tu
mors 2 yr later
Case report
April,2008
Case report
Also had multiple vertebrae destructions.
She died 3 yrs after the primary carcinoma was resected.
Try to indicate the spread routes
April,2008
Take care of your lifestyle
Prevent gastrointestinal cancers through everyday’s diet!
April,2008
ADVANCED READING Robbins Basic Pathology 7th edition Rubin’s Pathology 5th edition