Stomach - Pathoma

Gastroschisis
  • Congenital malformation of abdo wall
  • Exposed abdo contents
  • Defect usually small cf omphalocele
  • 2-3% risk for future pregs
  • Failure of sup, inf and 2 lateral folds coming in
Omphalocele
  • Persistent herniation of boewl into umbilical cord
    • Because in normal dev intestines start herniated, turn 90deg and come back in
    • Here, failure to come back in
  • Exomphalos - adbo muscles fail to form properly
  • "Bubble" = peritoneum + amnion
Pyloric stenosis
  • Congenital hypertrophy of pyloric smooth muscle
  • M > F
  • Stenosis develops due to thickened muscle
    • Present 2 weeks after
    • Stenosis occurs
    • Projectile nonbilious vomiting - as bile enters duodenum (after the pylorus!)
    • Visible peristalsis against block
    • Ex: feel olive-like mass in abdo
  • Rx
    • Myotomy - cut away muscle

Gastritis
  • Acute
    • Stomach damaged by its acid
    • Associated with acute physiological stress
      • Inc cortisol incs acid production
      • Get acute ulcers 
      • May bleed
      • This is why ICU pts on PPIs
    • Either
      • Inc acid prodn
      • Dec protection by mucosa:
        • Foveolar cells (mucosal epithelium) makes bicarb and mucous
        • Blood supply gives nutrients to these cells and also takes away any acid escaping through and buffers
    • Risks
      • Severe burns - Curling ulcer
        • Due to resultant hypovolaemia 
        • Thus dec blood flow and nutrients to stomach mucosa
        • So dec protective capacity
      • NSAIDs
        • Blocks prostaglandin production
        • These dec acid prodn, stim bicarb and mucous, inc blood flow to barrier
        • So these all dec
      • EtOH+++
        • Damage mucosa
      • Chemo
        • knock out turning over cells
        • can't regen mucosa
      • Inc inracranial pressure - Cushing ulcer
        • Causes inc vagal stimulation
        • So inc ACh to parietal cells
        • So inc acid production
          • (Parietal cell makes acid
          • Has 3 R's:
          • ACh - inc acid
          • Gastrin - inc acid
          • Histamine - inc acid)
      • Shock
        • Stress ulcers - multiple - give PPIs to most on ICU!
        • End organ hypoperfusion
    • Results
      • Superficial inflmn
      • Erosion - epithelium lost only
      • Shallow
      • Punched out
      • Ulcer - also lose mucosa
  • Chronic
    • Appearance
      • Slough
      • Acute inflammation - neutrophils
      • Chronic - granulation tissue - lymphocytes
      • Scar
      • Gross
        • Punched out
        • Flat edges
        • Flat surface 
    • Autoimmune
      • Destruction of parietal cells
      • Most of which are in body and fundus
      • T cell mediated = Type 4 hypersens
      • Abs vs intrinsic factor or parietal cells
        • These don't cause damage - T cells do
        • Are "due to damage"
        • Can use to test for this problem
      • Atrophy of mucosa
      • Dec acid production - achlorhydria
        • So inc gastrin levels (normally counteracted by -ve feedback from acid)
        • Gastrin made by G cells in antrum - so these hypertrophy
      • Also get megaloblastic (big and segmented nuclei) (pernicious) anaemia
        • Abs destroy intrnsic factor (from parietal cells)
        • So IF can't bind Vitamin B12
        • So terminal ileum can't absorb the IF-VitB12 complex
        • Most common cause of Vit B12 deficiency!
          • Peripheral neuropathy esp proprioception - subacute combined degeneration of the cord due to Vit B12
      • Inc risk of gastric adenocarcinoma
        • Chronic inflmn causes intestinal metaplasia
        • Due to inflammatory infiltrate
        • Metaplasia due to lymphocytes signalling as if peyer's patches so stomach changes to be like intestinal cells around peyer's patches!!
        • Get goblet cells which should not be here (but should be in intestines)
    • H. pylori 
      • 90% of gastritis
      • acute and chronic
      • Makes 
        • ureases (urea to ammonia+CO2 which is toxic to epithelial cells but protects bug from acid) 
          • Carbon Urea Breath Test:
          • drink 14C or 13C labelled  urea - bug turns into CO2, labelled CO2 exhaled
        • proteases 
        • VacA (vacuolating cytotoxin ?A - damage epithelium, causes apop, disrupts tight junctions)
        • CagA
        • phosoplipases
      • Causes inflammation
      • These all weaken degences
      • Antrum most common site
      • Sit on top of eipthelium (non invasive) but uses flagella to swim into mucin
        • BabA binds epithelial Lewis b Ag's
        • SabA binds mucosal sialyl-Lewis x Ag's

      • Present
        • Epigastic abdo pain
        • Inc ulceration risk
        • Inc inflammatory & hyperplastic gastric polyp risk
          • 50-60yo's
        • Inc adenocarcinoma risk
          • Get intestinal metaplasia - goblet cells so "gland Ca - adenocarcinoma"
        • Inc MALT lymphoma risk
          • Chronic inflammation causes germinal centres to form
          • Post germinal centre B cells thus present
          • Marginal zone around germinal centre only forms when chronic - from post germinal centre B cells
          • Marginal zone may become MALT lymphoma
      • Rx
        • Triple Therapy
        • Resolve gastritis / ulcer and reverses intestinal metaplasia (thus remove risk of Ca)
        • Negative urea breath test and no Ag in stool to confirm eradication
          • Other tests: gastroscopy, biopsy+rapid ureas test/culture, urine ELISA
    • Chemical
      • bile
      • NSAIDs
      • Excess acid
Peptic Ulcer Disease
  • Solitary mucosal ulcer
  • Proximal Duodenal Ulcer - 90%
    • Nearly always due to H pylori
    • Alt: Zollinger Ellison syndrome - rare
      • Gastrinoma - so make too much gastrin
      • Via blood, goes to parietal cells
      • Makes xs acid
      • May be multiple ulcers and may extend down duodenum
      • Multiple endocrine neoplasia 1 - MEN1
      • Lots of punched out ulcers
      • Duodenum so acidic that denature own enzymes so malabsorption 
    • Present
      • Epigastic pain
      • Better with meals
    • Dx
      • Endoscopic biospy
      • See ulcer on histo
      • Hypertrophy of Brunner glands - make bicarb rich mucous to protect from acid
    • Rupture - if posterior (less common cf anterior):
      • Gastroduodenal Artery bleed!!
      • Acute pancreatitis

  • (Distal Stomach) Gastric Ulcer - 10%
    • 70% = H pylori
    • 20% = NSAIDs
      • Dec Bicarb
      • Dec cell turnover
      • Dec blood flow
    • Also bile reflux etc
    • Presents
      • Epigastric pain
      • Worse with meals
    • Most common site = lesser curvature of antrum
      • So rupture risks bleed from Left Gastric Artery
  • DDx
    • Dudodenal ulcers nearly never malignant - duodenal carcinoma vvvvv rare!
    • Gastric ulcers may be due to gastric carcinoma
      • Benign features:
        • Small
        • Punched out
        • "Flat" border
      • Malignant features: 
        • Larger
        • Rougher - not punched out
        • Piling up of surrounding border - although may get in benign
          • Don't confuse with ruggae

Fundic gland polyps
  • Sporadic and in FAP pts
  • PPIs inc risk
    • Break -ve feedback
    • So inc gastrin
    • So oxyntic gland growth
  • Presents
    • aSx
    • Nausea, comit
    • pigastric pain

EPITHELIAL GASTRIC CANCERS (CARCINOMAS)

Gastric Carcinoma (an adenocarcinoma)
  • Malignant prolif surface (columnar) epithelial cells
    • Risk of transformation much worse than for adenocarcinomas of the intestines
  • Most sporadic 
    • p53 muts
    • APC (so FAP folks also at risk!)
    • Familial: loss of fn CDH1 mut/silencing (codes for E cadherin)
  • Presents late
    • Weight loss
    • Abdo pain
    • Ascites 
    • Anaemia
    • Chronic DIC
      • Mucin made leaks into blood
    • Rarer:
      • Acanthosis nigricans - thick, dark skin esp in axillae
      • Leser-Trélat sign - explosive onset of multiple seborrheic keratoses over skin - paraneiokastic
  • Spread
    • Peritoneal mets 
    • To lymph nodes
      • Esp Virchows - left supraclavicular
    • Liver
    • Periumbilical
      • Sister Mary Joseph Nodule
      • caused by Intestinal Type
    • Ovaries - bilateral
      • Krukenbury tumour
      • caused by Diffuse Type
  • Intestinal Type
    • Large irreg ulcer
    • Heaped margins, may be polypoid 
    • Most @ lesser curvature of antrum
    • Due to chronic inflammation
    •  Types
      • A - autoimmune
      • B - bacteria - H pylori
      • C - chemical
    • Risks
      • Intestinal metaplasia
        • Chronic autoimmune or H pylori gastritis [IL-1beta,8,10,TNF]
      • Nitrosamines in smoked foods
        • Big in Japan
      • Blood type A
  • Diffuse Type
    • Wall thickening - leather bottle stomach with thick ruggae - linitis plasticsa
      • Can cause loss of ruggae in areas
    • Signet ring cells - diffusely infiltrate wall
    • No E cadherin - hence diffusely distribute
    • So Ca +  a rxn to it
      • = desmoplasia
      • Thus linitis plastica = thickening of stomach wall
    • Not H pylori / intestinal metaplasia / nitrosamine associated
    • Also get early satieity
      • Wall thickened so can't stretch
      • So feel full on little food

STROMAL / MESENCHYMAL GASTRIC CA

Leiyomyoma

GIST GastroIntestinal Stromal Tumour
  • cKIT mut
    • Imatinib - tyrosin kinase inh
      • Also if PDGFRA mut
      • Can develop resistance
  • Interstitial cells of Cajal
  • Types
    • Spindle shaped cells - bundles
    • Epitheloid
    • Mixed
  • Stromal so covered by intact mucosa
  • Cut surface: white, whorled, fleshy
  • Presents
    • Mass effect
    • If ulcerates
      • Anaemia
    • Often incidentaloma!
LYMPHOID

MALT lymphoma
  • Translocation
  • Due to H pylori
    • Will regress if Rx H pylori
    • UNTIL translocation mut - then no going back
B cell lymphomas - HL, NHL (High, Low grades)

T cell lymphomas

CARCINOID
  • only 10% of GIT carcinoid tumours are in the stomach
    • (others:
      • 10% Duodenum - gastrin, somatostain, CCK - Zollinger-Ellison [25%MEN1], NF-1, sporadic
      • 40% Jejunum, Ileum - most aggressive - 5HT, sub P, polypeptide YY
      • 25% Appendix (only one that affects "young") - 5HT, polypeptide YY
      • 25% Colorectal - 5HT, polypeptide YY)
  • In body or fundus
  • 5HT
  • Somatostatin
  • Histamine
  • Sx
    • Gastritis
    • Ulcer
    • aSx
  • Assoc
    • Atrophic gastritis
    • MEN-I
HYPERTROPHIC GASTROPATHY
  • Zollinger-Ellison - see bowel notes
  • Ménétrier disease
    • Rare
    • xs TGF alpha
    • Fundus, body
    • Diffuse foveolar epithelium hyperplasia
    • Presents
      • Hypoproteinaemia (-> oedema)
      • Consitutional
    • Kids: post resp infection
    • Adults: inc gastric adenocarcinoma risk
Robbins Basic Pathology, Robbins Pathologic Basis of Disease, Robbins Review of Pathology (MCQs - very path-y), Robbins Flash Cards, Baby Robbins, Robbins Atlas - some exact same images come up in the exam, 100 Cases in ClinicalPathology - possibly the best Qbank for the practical