GIT Pathology Flashcards
Oral leukoplakia
- older men
- not removed by scraping
- clinical term; vast majority (~90%) of them are
benign; 3 to 7% undergo malignant transformation - buccal mucosa, tongue, floor of mouth
- hyperkeratosis
- dysplasia but no invasion
- Assoc w:
- tobacco use
- HPV (16, 18)
- chronic friction ex. ill fitting dentures
Erythroplakia
- due to EBV -> dysplasia -> malignant transformation in more than 50% of cases
- no hyperkeratosis; poorly circumscribed
- rough shaggy patches on lateral aspects of tongue
Squamous cell carcinoma (oral)
- Right: Keratin whorls
- mutations: p53 & p16 (cyclin)
- Developed from erythroplakia
- HPV 16, 18
- tobacco and alcohol are risk factors
Oral hairy leukoplakia
- no malignant potential
- almost always seen in HIV Pt
- strong assoc w EBV
- white confluent hairy hyperkeratosis
- layers of keratotic squames on underlying mucosal acanthosis (hyperkeratotic)
Hiatal hernia
- in older Pt
- Sx:
- heart burn (sliding-type) most common -> cardia of stomach pressed up towards esopagus -> risk of reflux
- resp problems due to stomach taking up space of lungs
- Dx:
- hour glass appearance
Achalasia/Cardiospasm
- incomplete relaxation of LES in response to swallowing
- functional esophageal obstruction
- 3 main features
- Aperistalsis
- Partial or incomplete relaxation of LES
- incr resting tone of LES
- Primary
- loss or absence of ganglion cells in myenteric plexus
- loss of inhibitory innervation of LES & smooth m. due to loss of NO/VIP
- Secondary (aka pseudoachalasia): impaired fx due to
- Chagas (T. cruzi)
- polio
- paraneoplastic syndrome
- sarcoidosis
- Sx:
- Dysphagia
- Odynophagia
- Reflux of contents
- hallitosis
- Vomiting
- Aspiration pneumonia
- Progressive dilation of esophagus above LES
- Dx:
- HIgh LES pressure on manometry,
- bird-beak sign on barium swallow
- Risk of developing squamous cell carcinoma (5% of cases)
Mallory Weiss syndrome
- longitudinal tears in mucosal wall of esophageal-gastric junction
- frequently in alcoholics & bulimics after a severe bout of retching
- inadequate relaxation of LES during vomiting
- tear may be only mucosal or transmural
- hememetesis -> painful
- usually heals but some times fatal
- **risk of Boerhaave syndrome -> air in mediastinum **(Pathoma)
Esophagitis
- Irritants: alcohol, acids, alkalis
- Infections:
- Allergic: eosinophilic esophagitis
- hyperemia
- presence of inflammatory cells: eos, neutrophils
- elongation of LP papillae
- basal zone hyperplasia
- Uremia
- Anticancers: bisphosphonates
Reflux esophagitis
- Causes:
- CNS depressants
- hypothyroidism
- pregnancy
- nasogastric tube
- alcohol
- tobacco
- **Etiopath: **Reflux of gastric juices is central to the development of mucosal injury in GERD. In severe cases, duodenal bile reflux may exacerbate the damage. Conditions that decrease LES tone or increase abdominal pressure contribute to GERD and include alcohol and tobacco use, obesity, central nervous system depressants, pregnancy, hiatal hernia (discussed later), delayed gastric emptying, and increased gastric volume. In many cases, no definitive cause is identified.
- Sx:
- dyspepsia
- burning sensation
- water brash
- sx worsen after lying down or after a big meal
- nocturnal cough
- Complications:
- bleeding
- stricture formation
- aspiration pneumonitis
- Barrett’s esophagus & adenocarcinoma
Barrett’s esophagus
- more common in white men
- lower 1/3 of esophagus
- non-ciliated columnar cell w Goblet cells
- salmon pink patch, tongue or large area above EG junction
- 30 to 40 x incr of adenocarcinoma
SCC of esophagus
- most common type of esophageal cancer; higher incidence in central Asia and N. China
- middle aged Blacks at higher risk than whites
- Etiology and associations with irritation
- Diet: vitamin deficiency, high nitrite content, fungal contamination
- Lifestyle: smoking, alcohol, urban env., very hot tea
- Esophageal disorders: longstanding esophagitis, achalasia, Plummer-Vinson syndrome (dysphagia, iron deficiency, glossitis, esophageal web, women);
- esophageal squamous cell carcinoma
risk is increased; therefore, it is considered a premalignant
process - associated with koilonychia, glossitic, chelitis,
and splenomegaly
- esophageal squamous cell carcinoma
- Genetic: Celiac disease, ectodermal dysplaisa (Tylosis), racial factors
- Gross: most common in middle 1/3
- Patterns: exophytic, diffusely infiltrative, ulcerated/excavated)
- Metastasis of SCC: direct to trachea or heart OR lymphatics
- Image below:
- Left: Ulcerated mass
- Right: narrowing of lumen
Adenocarcinoma of esophagus
- Lower 1/3 of esophagus
- more common in white men
- Barrett is precursor lesion
- poor prognosis
- Signs and Sx similar to Barrett
- multi-step dysplasia
Pyloric stenosis
- Acquired: chronic antral gastritis, peptic ulcers, malignancy
- Congenital:
- more common in 1st boy
- concentric hypertrophy of circular muscle coat
- Sx: presents 2 wk after birth -> regurg, projectile voimtting (nonbilious), palpable epigastric mass (olive-like), visible peristalsis
- Rx: surgery (myxotomy)
H. pylori
- non-invasive, urease+ bacillus
- mostly in antrum of stomach
- virulence factor = cagA toxin
- Rx: invasive tests (urease test, histopath, PCR) & non-invasive test (urea breath test, serology IgG, IgA), PCR in saliva & faeces)
- assoc w 2 patterns of gastritis
- superficial antral inflammation
- multifocal gastric atrophy
- Risk of developing PUD, gastric lymphoma, gastric carcinoma
Types of Gastritis
- Erosive (shallow ulcer)
- NSAID, oral iron, KCl
- Ethanol
- acute stress
- Chronic (non-erosive) gastritis
- H. pylori
- Pernicious anemia
- Sx: may be asx
- epigastric pain, nausea, vomiting
- hematemesis and melena
- bleeding can be fatal
Acute gastritis
- Etiological factors: anything incr acid production or decr mucosal protection
- NSAIDS: PG normally maintain blood flow, incr. mucus & bicarb secretion, augment epithelial defenses
- Alcohol
- Smoking
- Severe stress
- Trauma
- severe burn (Curling ulcer)
- Uremia
- Ischemia and shock
- Systemic infections
- incr ICP (Cushing ulcer) -> incr Vagal stimulation -> ACh release -> incr acid production
- Reactive Gastropathy:
- common in gastric surgeries that bypass pylorus
- watermelon stomach (GAVE)
- common in Pt on iron supplements
Chronic Gastritis: either from autoimmune or H. pylori causes
Etiology:
- Left image: chronic infection w H pylori;
- Right image: Warthin-Starry silver stain for H. pylori
- immunologic causes: anti-parietal or anti-IF Abs; achlorydia & incr. gastrin levels
- Alcohol and smoking
- post-surgical
- radiation
- Granulomatous (Crohn’s disease, sarcoidosis)
Morphology
- Endoscopy: thick mucosal folds
- Microscopy:
- Inflammatory infiltrate in LP: lymphocytes & plasma cells
- PMN in surface epithelium and glandular lumen
- Reactive lymphoid aggregates, mainly superficial
- intestinal metaplasia and glandular atrophy +/- dysplasia
Fundic type (Type A)
- Etiopath: autoimmune attack on parietal cells in stomach body and fundus
- see autoimmune gastritis card for complete def
Antral type (Type B)
- Gross: loss of rugal folds in antrum
- Micro:
- H. pylori in mucus layer of epithelium -> secretes ureases and proteases -> induce inflammation
- foci of lymphocytes, plasma cells & neutrophils
- intestinal metaplasia
- Etiopath:
- incr risk of duodenal and gastric ulcers, gastric adenocarcinoma, MALT lymphoma
- most common form of gastritis in US
Autoimmune Gastritis
- mainly involves body and fundus
- Etiopath: auto-anti-parietal cells or anti-IF cells Ab
- gland destruction
- atrophy
- Achlorydia
- Pernicious anemia
- Gross: loss of rugal folds in body and fundus
- Micro:
- mucosal atrophy w loss of glands and parietal cell
- lymphocytes and plasma cells in mucosa
- PMN may be present and indicate active inflammation despsite chronicity
- intestinal metaplasia marked by presence ofGoblet cells
Gastric ulcers
- Loss of mucosa that extends through muscularis mucosae or deeper
- Healing time greater than with erosions
- Common (gastric and duodenal)
- Peptic Ulcers
– Exposure to aggressive action of acidic peptic juices
– Chronic, often solitary lesions
Acute Gastric Ulcers
- Severe trauma, major surgeries
- Extensive burns (Curling ulcers)
- Head injuries/ intracranial lesions (Cushing Ulcers)
- Morphology:
- Multiple, small and circular
- Gastric rugae are normal
- Base usually not indurated (no fibrosis)
- Adjacent gastric mucosa normal or with reactive changes
- Etiopath:
– Systemic acidosis and hypoxia (severe trauma and
burns)
– Vagal stimulation (intra cranial lesions)
- Sx: Can present with massive upper GIT bleed
- Usually multiple and asymptomatic
- 5-10% of patients admitted in Intensive Care Unit
Chronic Gastric ulcers: PUD
- Sites (Descending order)
– Duodenum proximal
– Stomach
– Gastro esophageal junction
– Margins of gastrojejunostomy
– Meckel’s diverticulum
– Stomach, duodenum and jejunum in Zollinger Ellison syndrome -> Gastrinoma -> high Gastrin
- Morphology
- 50% < 2cms
- Round to oval, punched out with relatively
straight walls
* Sharp and raised margins but not everted
* Depth varies but may penetrate entire wall
* Smooth and clean base
* Radiating surrounding mucosal folds
* Active ulcer has four zones
* Necrotic fibrinoid debris
* Non specific inflammatory infiltrate (predominantly neutrophilic)
* Granulation tissue
* Fibrosis and collagenous scar
* Typically features of chronic gastritis in adjacent mucosa * Etiopath: balance bw damaging forces and Gastro Duodenal Mucosal Defenses
* incr post-prandial gastrin & decr SST leading to incr basal gastric acid secretion 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) PSYCHOLOGICAL STRESS 6) ZOLLINGER ELLISON SYNDROME
Zollinger-Ellison Syndrome
- Multiple ulcers
- Hypertrophy of Brunner’s glands
Sx:
- Burning epigastric pain 1-3 hours after meals
- Relieved by food and alkali
- Worse at night
- Associated weight loss
- Gastric outlet obstruction
- Complications
- Bleeding
- Perforation
- Gastric outlet obstruction
- Malignant transformation
Reactive Gastropathy
- The NSAID lesion
- Other drugs/medications
– Iron, Kayexalate
- Acid, alkali, alcohol
- Duodenopancreatic reflux
Gastric adenocarcinoma
- Highest occurrence in Japan and S. Korea
- Two distinct subtypes: intestinal & diffuse
- Overall unfavorable prognosis
- Sites: Pylorus/Antrum (50-60%), Cardia 25%, Body and Fundus
- Growth Pattern: Exophytic, Flat, Excavated
- Spread: local, transcoelomic, lymphatic, hematogenous
- Sx:
- Mostly asymptomatic in early stages
- Non specific weight loss, anorexia, abdominal
pain
* Pyloric outlet obstruction * C&C * **Krukenberg tumor; assoc w diffuse type** * Virchow lymph node: L. supraclavicular node * **Sister Mary Joseph nodule:** palpable nodule bulging **peri-umbilical** as a result of metastasis * Prognosis depends upon depth of invasion and nodal status
Intestinal type (LEFT IMAGE)
- In setting of chronic gastritis
- Neoplastic glands resemble intestinal epithelium (colon)
- Associated with H. pylori
- Intestinal metaplasiais precursor lesion
- More common in high- risk populations
- heaped-up margins,
- loss of rugae due to infiltration of tumour
- hyper-glandular, differentiated
- Etiopath: nitrosamines (smoked foods), A blood type,
Diffuse type (RIGHT IMAGE)
- No gland formation, thicker
- not related to H. pylori
- Single cells, sheets, clusters Signet ring cells
- poorly-differentiated
- More common in familial types with young female predominance
- Linitis plastic appearance (leather bottle stomach)
- Etiopath: Genetic -> E-Cadherins, younger women, No intestinal metaplasia
Gastrointestinal Stromal Tumors (GIST)
- Mesenchymal tumors
- Derived from cells of Cajal – the pace maker cells
- Many of these previously misdiagnosed as leiomyomata
- Anywhere in GIT: Esophagus, Stomach, small intestine, large intestine
- Can be benign or malignant: Based on size and mitoses
- Usually submucosal
- Whorls and bundles of spindle shaped cells
- C-kit (CD 117) is the tumor marker
- portal hypertension due to cirrhosis or HCC
- Ddx w Mallory-Weiss (assoc w pain); esophageal varices -> no pain
- Overlying mucosa normal, inflamed or ulcerated
- Usually asymptomatic until rupture
- Cause of death in 50% of patients with advanced cirrhosis
Meckel’s diverticulum
- Incomplete of involution/persistence of vitelline duct aka omphalomesenteric duct; true diverticulum,
- involves all 3 layers of the bowel wall.
- common in anti-mesenteric border
- Rule of 2’s:
· 2% of population
· 2 feet (proximal to ileocecal valve)
· 2 inches in length
· 2 types of common ectopic tissue: gastric and pancreatic
· 2 years is the most common age at clinical presentation
· 2:1 male:female ratio
- Sx: painless rectal bleeding (most common) & feces from vitelline duct
- Complications
- Hemorrhage (most common) and peptic ulcer
- Intestinal obstruction
- Diverticulitis
- Perforation
- Fistula
Celiac Sprue
- young white kids
- Changes more marked in proximal part of intestine:
- Marked atrophy and loss of villi in duodenum (reduced area for absorption) -> malabsorption
- jejunum and ileum spared
- Increased intraepithelial lymphocytes
- Elongated and hyperplastic crypts
- Increased number of lymphocytes, macrophages and plasma cells in lamina propria
- Reversal of changes after gluten free diet
- Sx Children: Ab distention, diarrhea, and failure to thrive
- Sx Adults: chronic diarrhea & bloating
-
Dx:
- Documentation of malabsorption
- Iron deficiency anemia
- Small intestine biopsy showing flattening of villi and hyperplasia of crypts, and incr intraepithelial lymphocytes
- Reversal of changes and signs and symptoms after gluten free diet
- Serologic tests
- Anti gliadin and anti endomysial antibodies
- Anti-tissue Transglutaminase (tTG) antibodies
– Is a specific endomysial antigen.
– Sensitivity of 95% and specificity of 94% in untreated patients
– HLA genotype: HLA DQ2 (majority) and DQ8
- C&C: long-term risk of intestinal T- cell lymphoma, small bowel carcinoma, dermatitis herptiform due to deposition of IgA-mediated destruction of dermal papillae
Tropical sprue (post infectious sprue)
- Tropics & Caribbean
- Symptoms appear months or even years after visit
- Pathogenesis related to bacterial infection
- superimposed on pre-existing small intestine injury
- All parts of small intestine equally involved
- Small intestine may appear near normal
- Difficult to differentiate from celiac disease
- damage is more in jejunum and ileum (Pathoma)
- Folic acid and B12 deficiencies
- Responds to antibiotics
Whipple Disease
- Systemic disease
- Gram+ actinomycete Tropheryma whippelii
- More common in males (10:1)
- Mucosa laden with distended macrophages in
- lamina propria-contain PAS positive granules and foamy macrophages
- May have granulomatous inflammation
Sx
- Signs & sx of malabsorption: weight loss, diarrhea due to effects on SI
- Signs & sx of infection: fever, lymphadenopathy, polyarthritis, skin hyperpigmentation
Dx
- Rod shaped bacilli can be seen on EM
- Treated with antibiotics
Small intestinal obstruction
Intramural
- Congenital atresias
- Inflammatory conditions
Extramural
- hernia
- volvulus
- intussusception
Appendiceal mucocele
- Dilation of lumen due to mucinous secretion
- Lining epithelium may be adenomatous (mucinous cystadenoma) or carcinomatous (cystadenocarcinoma)
- Rupture may lead to diffuse peritoneal mucin (clinically pseudomyxoma peritonei)
Pseudomyxoma peritonei
- Peritoneal studding by mucinous implants
- Range
• Entirely mucinous
– No epithelium • Abundant mucin
– Scant low grade neoplastic epithelium
• Abundant malignant epithelial cells – Signet ring cells
– Infiltrating columnar epithelium
Hirschsprung disease
- Most common cause of congenital intestinal obstruction
- Incidence is 1 in 5000 to 1 in 8000
- M:F is 4:1
- In 10% patients of Down Syndrome
- Absence of ganglion cells in Meissner and Auerbach’s plexus in submucosa
- Rectum is always affected
- Dilatation and hypertrophy proximal to aganglionic segment (congenital megacolon)
Sx:
- Delayed passage of meconium
- Constipation
- Abdominal distension
- Diagnosed by rectal biopsy
C&C:
- Enterocolitis
- Perforation and peritonitis
- risk of rupture
Diverticular disease
- Includes diverticulosis and diverticulitis
- pseduo-diverticulum involving only 2 layers (mucosal & submucosal)
- Common in western world
- 50% in older than 60 years
- Flask like structures ( 95% sigmoid colon) of mucosal outpouchings from lumen through muscular layer
- more common in mesenteric border
Etiopath:
- Lack of dietary fiber leads to sustained bowel
- contractions and increased intraluminal pressure -> Herniation of colonic wall at sites of focal defects
- Not true diverticula
Sx:
- Usually asymptomatic but some times painless bleeding
- Diverticulitis
– Lower abdominal pain (pain in L. iliac fossa)
– Constipation, diarrhea, flatulence -> massive hematochezia
- – Fever
C&C:
- fistula & perforation
- rectal bleeding (hematochezia)
- iron deficiency anemia due to chronic bleeding
Ulcerative colitis
- young white people
- Extends in continuous fashion
- Starts in rectum and then extends proximally to involve
whole of the colon (no SI involvement) -> left lower quad pain -> hematochezia
- Associated with Primary Sclerosing Cholangitis (PSC) and P-ANCA
- HLA-DRB1 association
- 10% cases back wash ileitis
- Broad based ulcers -> diffuse
- Isolated islands of intervening regenerating mucosa bulge create pseudopolyps
- No Fat/vitamin malabsorption
Morphology (Pathoma)
- Gross: pseudopolyps, loss of haustra, toxic megacolon
- Microscopic Left image: red friable mucosa & submucosa layers flaking off, no granuloma formation, Serosa is usually normal
- Microscopic Right image: crypt abscess (exudate; hallmark of UC), loss of goblet cells in in crypts
Sx: stringy mucoid material of bloody diarrhea, pain due to inflammatory
Dx: leadpipe appearance on X-Ray
C&C:
- Toxic megacolon
- Back wash ileitis: mild inflammation of distal ileum
- colon carcinoma
Crohn’s Disease aka Terminal ileitis, regional ileitis and granulomatous colitis
- adolescents and young adult women
- More common in Jews
- Associated with HLA-DR7 and DQ4
- Microscopic: T-cell mediated autoimmune disease; Dense lymphocytic infiltration (blue), deep fissure into thickened muscle, shallow ulcer (creates fistulas and strictures)
- Characterized by
– Sharply delimited & transmural involvement by an inflammatory process; mouth to anus w skip lesions; terminal ileum most common; rectum least.
– Presence of non caseating granulomas
– Mucosal fissuring with formation of fistulas-> knife-like fissures
- Crohn’s disease involves both SI and colon
Morphology
- Granulomas & skip lesions
- Image below right: Mesenteric fat wraps around bowel serosa (creeping fat)
- Mesentery thickened and fibrotic
- Full Wall thickened (edema, hypertrophy, fibrosis and inflammation)
- Long narrow thickened segments of small intestine (unlike tuberculosis strictures which are short in length):
- radiographically- String sign (severe narrowing of loop of bowel) -> stricture
- Sx: General to IBD
- Relapsing disorder
- Attacks of bloody mucoid diarrhea rare
- Right Lower Quad pain, abdominal cramps, Tenesmus
- Flare ups with physical and mental stress
- Fever and weight loss in severe cases
- Features of malabsorption: Loss of surface epithelium -> loss of absorptive fx
- Small intestine - features of subacute intestinal obstruction
C&C:
- Perianal fistula
- increase risk of colon adenocarcinoma (higher risk in UC)
Assoc (Pathoma)
- ankylosing spondylitis
- sacroileitis
- polyarthritis
- erythema nodosum
- uveitis
Extra intestinal manifestations of IBD
- Seen in both CD and UC (though more common with Ulcerative colitis)
- Can develop even before the onset of GI sign symptoms
– Migratory polyarthritis – Sacroileitis
– Ankylosing spondylitis – Erythema nodosum
– Clubbing of finger tips – Sclerosing cholangitis
- Increased risk of developing malignancy (CD Less than UC)
Pseudomembrane colitis
- Associated with broad spectrum antibiotic use
- Caused by Clostridium difficile
- Toxin mediated damage
- Toxin A = enterotoxin –> fluid accumulation in bowel
Toxin B = cytotoxin –> decreases cellular protein synthesis & disrupts microfilament system of the cells –> destruction of cellular cytoskeleton
- Colon, particularly rectosigmoid, has raised yellow plaques
- Fibrinopurulent-necrotic debris (pseudomembranes)
– Surface epithelium denuded
– Superficially damaged crypts distended by mucopurulent exudate which erupts to form a mushrooming cloud
– Coalescence of these clouds leads to pseudo membrane formation
- Sx: Watery diarrhea, Tenesmus (painful defecation), Occult blood in stool may be present –> iron def. anemia
Ischemic bowel disease
- Venous vs. Arterial Insufficiency
- Occlusive vs. Non-occlusive
Occlusive
– Arterial thrombosis in SMA - systemic atherosclerosis, systemic vasculitis, hypercoagulable states, angiographic procedures
– Arterial embolism in SMA- cardiac vegetations, athero- thromboembolism and angiographic procedures
– Venous thrombosis- hypercoagulable states, Oral contraceptives, intraperitoneal, sepsis, post operative etc.
- Non occlusive ischemia- cardiac failure, shock, dehydration
- Miscellaneous- radiation, volvulus, herniation
Chronic ischemic colitis
- Insidious
- Chronic inflammation and fibrosis
- Stricture formation
- Common at water shed areas – Splenic flexure (most common)
- Red infarct due to ischemia -> loss of blood supply -> reperfusion
- Common in elderly
- Intermittent attacks of pain – Intestinal angina (pain due to eating & no blood circulation) & weight loss
- Can mimic Inflammatory bowel disease
Infectious colitis
- Amebic Colitis
– Gradual dysentery, C&C: amebeic abscesses
– Flask shaped ulcer with organisms engulfing red cells (organisms burrow laterally)
• Typhoid
– Fever, headache, abdominal pain, rash and diarrhea – Longitudinal ulcers, typically over Peyer patches
• Tuberculosis
– Chronic abdominal pain
– Multifocal involvement, jejunum to ileum, TI most common
- – Annular circular or oval ulcers, lying transversely
– Single ulcers large, multiple ulcers smaller
– Granulomatous inflammation, often necrotizing
Neoplastic GIT polyps
- Left: Raspberry appearance of polyp (single); Malignant > 2 cm commonly from adenomatous polyp;
- Pedunculated w stalk
- Most common polyp is hyperplastic
- Right: sessile (no stalk) -> more flattened
Adenoma:
- can be classified as tubular, tubulovillous, villous
- pre-malignant
–Left: tubular: nuclear polychromasia -> dysplastic
–Right: villous -> complication: hypokalemia
- “villous is the villain”
FAP
- genetic defect in APC gene (5q21)
- Usually tubular type
- Sometimes in SI and stomach
- Typically 500-2500 mucosal adenomas (minimum number for diagnosis is 100)
- Carcinoma occurs in young individuals
- Prophylactic colectomy is done
Sx: asx for a long time, Osteomas & Turcot syndrome
C&C: progression to adenocarcinoma & intussusception
Gardner Syndrome-Tubular adenomas with multiple osteomas, desmoid tumors and epidermal cysts
Turcot Syndrome-Adenomas and CNS (gliomas)
Colorectal carcinoma
- Occurs in elderly individuals
- Occurs in young individuals in setting of ulcerative colitis and polyposis syndromes
- Risk factors: Obesity, physical inactivity, Diet low in indigestible fiber and rich in animal fat
- Antioxidants protective
- Usually solitary • Multiple cancers
- Ulcerative colitis, polyposis syndromes and HNPCC
- Proximal colon- exophytic polypoidal lesions and obstruction is uncommon
- Distal colon- annular, encircling napkin ring constrictions
Etiopath:
- 2 major pathways:
1. Chromosomal instability pathway (85 to 90% cases)
APC gene
But also K-RAS, p53, DCC, hMSH2
Arise from adenoma-carcinoma sequence
- MSI pathways (10 to 15% cases)
May arise from adenomas or other lesions (SSA or HP)
Defect in DNA mismatch repair genes ex. MLH1, MSH2, MSH6, PMS
Sporadic (85%) or
Familial (15%;) -> HNPCC
Lymphatic spread
Sx:
- Asymptomatic
RIGHT SIDED- fatigue, weakness & iron deficiency anemia (Bulky & bleed easily)
LEFT SIDED- altered bowel habits
Dx:
- Colonoscopy and fecal occult blood testing
- Tumor marker - CEA used for checking for tumour regrowth.
C&C:
- Iron deficiency anemia in elderly man is due to GI malignancy unless proved otherwise.
- incr risk for Strep bovis endocarditis
Carcinoid tumour
Small intestine and appendix
– Most common site in GI tract; mucosal layer
– Often small, occult primary tumors; salt and pepper chromatin
– Can metastasize widely leading to carcinoid syndrome when liver involved
• Carcinoid syndrome
– Wheezing, diarrhea and flushing
• Rectum
– Often small and benign
Appendicitis
- Underlying obstruction of the lumen in 50-80% cases: lypmhoid hyperplasia (children) or fecalith (adults)
- Pathogenesis unclear in non obstructive cases
- inflammation of appendicoeal wallMild fever, Leukocytosis (Neutrophilia )
C&C:
– Perforation
– Peritonitis
– Periappendiceal abscess
– Liver abscess
– Bacteremia
Liver cirrhosis
Defined by 3 characteristics (Trichrome stained image before)
– Bridging fibrous septa
– Parenchymal nodules created by regeneration
– Architectural disruption
Etiology:
- Alcoholic liver Disease (most common)
- Viral hepatitis
- NASH
- Biliary tract diseases
- Hereditary hemochromatosis: liver damage via free radicals -> incr risk of HCC
- Wilson disease
- α1 antitrypsin deficiency
- Cryptogenic cirrhosis
Pathogenesis:
- Diffuse liver process with fibrosis and conversion of normal architecture into structurally abnormal nodules -> representing Ito cells (stellate cells) secreting TGF-Beta to stimulate regeneration & fibrosis.
- Stage in evolution of many chronic liver diseases with consequences unrelated to the primary etiology
- Based on nodule sized, often classified as micronodular (<3mm) or macronodular (>3mm)
- hepatocytes die -> ECM deposition -> vascular fibrosis
Sx: May be silent
- Non specific signs and symptoms
- Usually features of Portal hypertension and Liver failure
Signs of chronic liver disease: jaundice, ascites, parotid swelling, palmar erythemia, clubbing, Depuytren’s contracture, spider angioma & gynecomastia (estrogen), ascites, portal hypertension (cirrhosis specific)
Dx: Prothrombin time (PT) [not PTT] is used to assess the coagulopathy due to liver disease. This is because prothrombin has a short half life and is first to disappear upon onset of liver disease
C&C:
- Significantly increased risk of hepatocellular carcinoma (HCC)
- Portal hypertension
- hepato-renal syndrome
- congestive splenomegaly
- decr protein synthesis leading to hypoalbuminemia & coagulaopathy
- Decreased detox liver fx
- Asterixis: flapping tremor, or liver flap
- Decr estrogen metabolism leading to gynecomastia, spider angioma, palmar erythema
- Jaundice
Primary Biliary Cirrhosis
Disease of middle aged women
Etiopath:
- autoImmune mediated: Anti mitochondrial antibodies in 90%
- Chronic, progressive and can progress to cirrhosis
- Non suppurative, granulomatous destruction of medium sized bile ducts
- Death usually occurs because of liver failure
Gross image: Green indicates bile obstruction
Microscopic image: Portoportoseptal fibrosis
- Left: Regenerating bile ducts with Fibrosis in bw
Right: Destruction of epithelium (long thin arrow), granuloma formation (curved arrow)
Sx: hyperbilirubinemia, pruritus, jaundice
Dx:
- Detection of anti-mitochondrial Ab
- Elevated serum ALP (alkaline phosphatase) - signifies obstructive liver disease
C&C: hepatic decompensation, Sjorgren syndrome, scleroderma, thyroiditis, rheumatoid arthritis, Raynaud phenomenon & celiac disease.
Wilson disease
- Autosomal recessive disorder (Gene on chromosome 13)
- Presentation is rare before 6 years of age
- Characterized by accumulation of toxic levels of Cu in Liver, Brain and Eyes
- BRAIN:
- Deposited in basal ganglia -> neuro manifestations
- EYES:
- Deposits of copper in Descemet membrane of corneal limbu aka. Kayser Fleischer ring
- In some sun flower cataracts
- BLOOD: hemolysis
- In liver variable morphology
– Fatty change
– Acute hepatitis
– Chronic hepatitis-Ultimately cirrhosis – Rarely massive necrosis
Investigations
– Decreased serum ceruloplasmin levels
– Increased hepatic Cu (>250μgm/gm dry weight of liver is diagnostic)
– Increased urinary copper excretion
HCC aka Hepatoma
- Majority cirrhosis associated
- Global distribution strongly related to prevalence of HBV
- Highest frequencies in Taiwan, Mozambique and China
- Male preponderance
- Usually in adults
- Children with metabolic liver disease
Morphology
- Are usually paler than surrounding hepatic parenchyma
- Strong propensity for invading vascular channels (portal vein, IVC)
Histology
– Well differentiated to poorly differentiated
– Trabecular, sinusoidal or pseudoacinar pattern
– Bile production by tumor cells, cytoplasmic inclusions
– Usually cirrhosis in adjacent liver parenchyma
Etiopath:
- High incidence in Asia & Japan; most common primary malignant tumour of liver
- Cirrhosis
- Hepatitis: integration of viral DNA into genome
- Alcohol
- Aflatoxin: p53 transversion
Sx
- Usually masked by underlying liver disease
- Ill defined upper abdominal pain, fatigue, cachexia, asterixis
Dx
- Raised AFP levels in 60-75% (markedly increased)
- Diagnosis-FNAC, biopsy
- Fibrolamellar variant has better prognosis
- Majority are no surgical candidates
– Multicentricity
– Parenchymal dysfunction
C&C
- Budd-Chiari syndrome: thrombosis of hepatic v.
- tendency for hematogenous spread
Cholelithiasis
Risk factors
- Cholesterol stones: Female, fat, forty, fertile; radiolucent
- Westernized world
- Elderly
- Female (OCP & pregnancy)
- obesity
- rapid wt reduction
- GB stasis
- Inborn error of Bile salt metabolism
- Hyperlipidemia syndromes
- Pigment stones: radio-opaque
- Asians
- Rural > urban
- Chronic hemolytic syndromes
- Biliary infections
- GI disorders: Crohn’s disease or ileal resection or bypass, CF of pancreas
Etiopath
- GB hypomotility
- Cholesterol nucleation
- mucus hypersecretion traps crystals
Dx: Murphy’s test (palpate -> pain with inspiration)
C&C
- Empyema
– Perforation
– Fistulas
– Cholangitis
– Pancreatitis
– Gallstone ileus
– Increased risk of carcinoma
GB carcinoma
Most common in seventh decade of life
Slightly more common in females
Gallstones in 60-90% patients (Chronic cholecystitis w dystrophic calcifications)
Other risk factors: Pyogenic and parasitic infections of the biliary tract
Carcinogenic derivatives of bile may play a role
Mostly adenocarcinoma
Most have invaded or spread to liver at diagnosis
Acute pancreatitis
Morphology
Focal fat necrosis in pancreas and peripancreatic tissues and abdominal cavity
Ca++ deposition in these areas
– Appear radiopaque on radiographs
Severe cases
– Necrosis of pancreatic tissue (acini, ducts and islets)
– Hemorrhage (Hemorrhagic pancreatitis)
Etiopath
80% cases associated with GALLSTONES and ALCOHOLISM
Other causes: I GET SMASHED -> activated enzymes -> Acute onset of abdominal pain due to enzymatic necrosis and inflammation of pancreas
Sx
- Pain can vary from mild to very severe
- Usually severe epigastric pain with nausea and vomiting
- Constant, intense and referred to upper back
Dx
- Grey-Turner sign: subq bruises on side of abdomen due to hemorrhage
- Cullen’s sign: peri-umbilical bruising & edema
- Lipase is most specific marker
C&C
- Leucocytosis
- DIC
- Hemolysis
- Peripheral vascular collapse
- Shock with ATN, ARDS
- Hypocalcemia, tetany
- Raised amylase levels in first 24 hours
- Followed by lipase with in 72-96 hours
- Complications
- – ARDS
- – ATN
- – Pancreatic abscess
Chronic pancreatitis
Repeated bouts of mild to moderate pancreatic inflammation with loss of pancreatic parenchyma and its replacement by fibrous tissue
Morphology
- Gross: shrunken pancreas due to fibrosis
- Micoscopic: lymphocytic inflammation; squamous metaplasia
Etiology: acute pancreatitis, alcohol, pancreas divisum
Other causes very rare
– Tropical pancreatitis, Hereditary pancreatitis, CFTR (mutation associated)
Sx
Repeated attacks of moderately severe pain or persistent abdominal and back pain
Possible progression to pancreatic insufficiency and diabetes
– Features of malabsorption, corrected by pancreatic enzyme supplements
Dx:
X-ray for calcifications and
C&C: diabetes, cancer, duct stones, pseudocysts
Carcinoma of the head of the pancreas
Fifth most common cause of death in U.S.
Only convincing association is with smoking
Proposed risk factors like alcohol, diet rich in fats inconsistent
Strong association with familial relapsing pancreatitis (very rare itself
Location
– Head 60-70% – Body 5-10% – Tail 10-15%
Majority ductal-type adenocarcinomas
– Dense stromal fibrosis (desmoplasia)
– Propensity for perineural invasion
Sx
- Carcinoma of head of pancreas/ampulla obstructs bile flow – Obstructive jaundice (painless jaundice)
- Majority silent until till late
- Steatorrhea
- Pain is usually first symptom (because of invasion posterior abdominal wall and nerves
- Trousseau’s sign (migratory thrombophlebitis) in 10: Release of platelet activating factors and procoagulantsfrom tumor
Dx
Tumour marker for screening: CA19-9
C&C:
•perineural invasion -> pain
•Trousseau’s
