Pathology Flashcards
Name some inflammatory disorders of oesophagus
- acute oesophagitis
- chronic oesophagitis
Describe acute oesophagitis
- rare
- corrosive following chemical ingestion
- infective in immunocompromised pts eg. candidiasis, herpes, CMV
Describe chronic oesophagitis
- common
- reflux disease ‘ reflux oesophagitis’
- rare causes include crohns disease
Define reflux oesophagitis
- inflammation of oesophagus due to refluxed low pH gastric gastric content
Describe causes of reflux oesophagitis
- may be due to defective sphincter mechanisms +/- hiatus hernia
- abnormal oesophageal motility
- increased intra-abdominal pressure (pregnancy)
Describe the microscopic of reflux oesophagitis
- basal zone epithelial expansion
- intraepithelial neutrophils, lymphocytes and eosinophils
Describe the complications of reflux
- ulceration (bleeding)
- stricture
- barrets oesophagus
What is barrets oesophagus?
Replacement of stratified squamous epithelium by columnar epithelium
Describe metaplasia in relation to barrets oesophagus
- due to persistent reflux of acid or bile
- may be due to expansion of columnar epithelium from gastric glands or from submucosal glands
- may be due to differentiation from oesophageal stem cells
- protective response, faster regeneration
Describe the macroscopic changes of barrets oesophagus
Red velvety mucosa in lower oesophagus
Describe the microscopic changes in barrets oesophagus
Columnar lined mucosa with intestinal metaplasia
- unstable mucosa
- increased risk of developing dysplasia and carcinoma of the oesophagus
- requires surveillance
Describe allergic oesophagitis
- eosinophilic oesophagitis
- personal / family history of allergy
- asthma
- young
- males
- pH probes negative for reflux
- increased eosinophils in blood
- corrugated (feline) or spotty oesophagus
Name the treatments of allergic oesophagitis
Treatment may include steroids / chromoglycate / Montelukast
Name the benign tumours of the oesophagus
squamous papilloma
- Rare
- papillary
- asymptomatic
- HPV related
Very rare;
- leiomyomas
- lipomas
- fibrovascular polyps
- granular cell tumours
Name malignant tumours of the oesophagus
- squamous cell carcinoma
- adenocarcinoma
Describe the epidemiology of squamous cell carcinoma
- commoner in males
- high risk areas NW france, N Italy
Describe the aetiology of squamous cell carcinoma
- vitamin A, zinc deficiency
- tannic acid / strong tea
- smoking
- alcohol
- HPV
- oesophagitis
- genetic
Describe the aetiology of adenocarcinoma of the oesophagus
- commoner in Caucasians
- incidence increasing in Europe and USA
- commoner in males / obesity
- commonest in lower 1/3 of oesophagus
Describe the pathogenesis of adenocarcinoma of oesophagus
- genetic factors, reflux disease, others
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- chronic reflux oesophagitis
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- barrets oesophagus (intestinal metaplasia)
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- low grade dysplasia
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- high grade dysplasia
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- adenocarcinoma
Describe the mechanism of metastases of carcinoma of the oesophagus
- direct invasion
- lymphatic permeation
- vascular invasion
How may carcinoma of the oesophagus present?
- dysphagia; due to tumour obstruction
- anaemia
- weight loss, loss of energy
- due to effects of metastases
Describe oral squamous cell carcinoma
- variable presentations; white, red, speckled, ulcer, lump
- high risk sites include floor of mouth, lateral border of and ventral tongue, soft palate, retromolar pad / tonsillar pillars
- rare on hard palate, dorsum of tongue
Describe the aetiology of oral squamous cell carcinoma
- tobacco
- alcohol
- betel quid
- nutritional deficiencies
- post transplant
- pt with history of primary orsl SCC, increased risk of developing new second primary
? genetics, chronic infection, viral, HPV
Describe the histopathology of oral squamous cell carcinoma
- considerable variation in appearances, however cytologically malignant squamous epithelium and ALL show invasion and destruction of local tissues
- variants include verrucous and acantholytic
Describe the histopathological features relating to prognosis of SCC
- tumour diameter
- depth of invasion
- pattern of invasion, cohesive versus non-cohesive front
- lymphovascular invasion
- neural invasion by tumour
- involvement of surgical margins
- metastatic disease
- extracapsular spread of lymph node metastases
Name some inflammatory disorders of the stomach
- acute gastritis
- chronic gastritis
Rare;
- lymphocytic
- eosinophilic
- granulomatous
Chronic gastritis can be due to what?
- autoimmune
- bacterial (H. pylori)
- chemical
Describe autoimmune chronic gastritis
- rarest
- anti-parietal and anti-intrinsic factor antibodies
- atrophy and intestinal metaplasia in body of stomach
- pernicious anaemia, macrocytic, due to B12 deficiency
- increased risk of malignancy
- SACDC
Describe h.pylori associated chronic gastritis
- most common type
- bacteria inhabits a niche between the epithelial cell surface and mucous barrier
- gram negative curvilli near rod
- excites early acute inflammatory response
- if not cleared then a chronic active inflammation ensues
- IL8 is critical
H. pylori gastritis increases risk of what?
- lamina propria plasma cells produce anti H.pylori antibodies
- increases risk of;
- duodenal ulcer
- gastric ulcer
- gastric carcinoma
- gastric lymphoma
Describe chemical gastritis
- due to NSAIDs, alcohol, bile reflux
- direct injury to mucus layer by fat solvents
- marked epithelial regeneration, hyperplasia, congestion and little inflammation
- may produce erosions or ulcers
Describe peptic ulceration
A breach in the gastrointestinal mucosa as a result of acid and pepsin attack
Describe chronic peptic ulcers
- ulceration is longstanding and often deep
Sites;
- duodenum (1st part)
- stomach (junction of body and antrum)
- oesophago-gastric junction
- stomal ulcers
Describe chronic duodenal ulcers
- pathogenesis; increased attack and failure of defence
- 50% of patients with duodenal ulceration have increased acid secretion
- many have inappropriately sustained secretion of acid
- excess acid in duodenum produces gastric metaplasia and leads to H.pylori infection, inflammation, epithelial damage and ulceration
- synergism
Describe the pathogenesis of chronic peptic ulcers
- not just due to increased acid production
- failure of mucosal defence is also important
Describe the morphology of peptic ulcers
- 2-10cm across
- edges are clear cut, punched out
Describe the microscopic appearance of peptic ulcers
- layered appearance
- floor of necrotic fibrinopurulent debris
- base of inflamed granulation tissue
- deepest layer is fibrotic scar tissue
Describe complications of peptic ulcers
- perforation
- penetration
- haemorrhage
- stenosis
- intractable pain
Name benign (polyps) gastric tumours
- hyperplastic polyps
- cystic fundic gland polyps
Name malignant gastric tumours
- carcinomas (adenocarcinomas)
- lymphomas
- GI stromal tumours (GISTs)
Describe the epidemiology of gastric adenocarcinomas
- incidence varies widely
- high incidence in japan, china, Columbia and Finland
- in UK proximal tumours of cardia / GOJ increasing and distal tumours deceasing
Describe the aetiology of gastric adenocarcinomas
- H.pylori infection prevalence runs parallel to incidence of gastric cancer in same populations
- pts with anti-h.pylori antibodies have higher risk of cancer
- h.pylori is the major cause of chronic gastritis
Describe the pathology of gastric adenocarcinoma
- h.pylori infection
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- chronic gastritis
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- intestinal metaplasia / atrophy
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- dysplasia
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- carcinoma
Describe the aetiology of gastric adenocarcinoma
- other pre malignant conditions
- pernicious anaemia
- partial gastrectomy
- HNPCC / lynch syndrome
- menetriers disease
Describe the subtypes of gastric adenocarcinoma
- intestinal type; exophytic / polypoid mass
- diffuse type; expands / infiltrates stomach wall
Describe a benign peptic ulcer
Mimics cancer but is more punched out and lacks a raised rolled edge
- all gastric ulcers must be regarded as potentially malignant
Describe the spread of gastric adenocarcinoma
- local; into other organs and into peritoneal cavity and ovaries (kruckenberg)
- lymph nodes
- haematogenous (to the liver)
Describe gastric lymphoma (MALToma)
- derived from mucosa associated lymphoid issue (MALT)
- associated with h.pylori infection
- continuous inflammation induces an evolution into a clonal B cell proliferation, low grade lymphoma
- if unchecked evolves into a high grade b-cell lymphoma
Describe the aetiology of ischaemia of the small bowel
- mesenteric arterial occlusion;
1. mesenteric artery atherosclerosis
2. thromboembolism from heart (eg. A.fib) - non occlusive perfusion insufficiency;
1. shock
2. strangulation obstructing venous return (eg. hernia, adhesion)
3. drugs eg. cocaine
4. hyperviscosity
Describe the pathogenesis of ischaemia of the small bowel
- the mucosa is the most metabolically active part of the bowel wall and therefore the most sensitive to the effects of hypoxia
- the longer the period of hypoxia the greater the depth of the damage to the bowel wall and the greater the likelihood of complications
- in non occlusive ischaemia much of the tissue damage occurs after reperfusion
What is the outcome of mucosal infarct?
Regeneration; mucosal integrity restored
What is the outcome of mural infarct?
Repair and regeneration; fibrous stricture
What is the outcome of transmural infarct?
Gangrene; death if not resected
Describe complications of ischaemia of the small bowel
- resolution
- fibrosis, stricture, chronic ischaemia, mesenteric angina and obstruction
- gangrene, perforation, peritonitis, sepsis and death
Describe meckels diverticulum
- result of incomplete regression of vitello-intestinal duct
- tubular structure, 2 inches long, 2 foot above IC value for 2% of people
- may contain heterotopic gastric mucosa
- may cause bleeding, perforation or diverticulitis which mimics appendicitis
- commonly asymptomatic, incidental finding
Name secondary tumours of the small bowel
- much more common
- ovary
- colon
- stomach
Name primary tumours of the small bowel
- much rarer
- lymphomas
- carcinoid tumours
- carcinomas
Describe lymphomas of the small bowel
- rare all non hodkins in type
- maltomas (B cell) derived
- enteropathy associated T cell lymphomas (associated with coeliac disease)
- treated by surgery and chemotherapy
Describe carcinoid tumours of the small bowel
- rare, commonest site is the appendix
- small, yellow, slow growing tumours
- locally invasive
- can cause intussusception, obstruction
- produce hormone like substances
- if metastases to liver occur a carcinoid syndrome occurs producing flushing and diarrhoea
Describe carcinoma of the small bowel
- rare, associated with crohns disease and coeliac disease
- identical to colorectal carcinoma in appearance
- presents late
- metastases to lymph nodes and liver occur
Describe appendicitis
- common cause of an acute abdomen
- commoner in children but occurs in adults
- vomiting, abdominal pain, RIF tenderness and increased WCC
Describe the aetiology of acute appendicitis
- unknown
- faecoliths (dehydration)
- lymphoid hyperplasia
- parasites
- tumours (rare)
Describe the pathology of acute appendicitis
- acute inflammation (neutrophils)
- mucosal ulceration
- serosal congestions, exudate
- pus in lumen
Acute inflammation must involve the muscle coat
Describe the complications of appendicitis
- peritonitis
- rupture
- abscess
- fistula
- sepsis and liver abscess
Describe the aetiology of coeliac disease
- gliadin a component of gluten is the suspected toxic agent
- but tissue injury may be a bystander effect of abnormal immune reaction to gliadin
- mediated by T cell lymphocytes which exist within the small intestinal epithelium ‘intraepithelial lymphocytes’ (IELS)
What is the normal lifespan of an enterocyte?
72 hours
Name the three zones of the liver
- periportal zone
- mid acinar
- pericentral
Describe the liver and injury
- very resistant to injury
- the liver has a large functional reserve
- some liver insults can produce severe parenchymal necrosis but heal entirely by restitution
- some types of injury leave permanent damage
- some types of injury produce predictable pathological patterns
Describe the pathogenesis of liver disease
- insult to hepatocytes, viral drug toxin, antibody
- grading, degree of inflammation
- staging, degree of fibrosis
- cirrhosis
Name causes of acute onset of jaundice
- viruses
- alcohol
- drugs
- bile duct obstruction
Name consequences of acute liver failure
- complete recovery
- chronic liver disease
- death from liver failure
Describe jaundice classification by site and type
- site; pre-hepatic, hepatic, post-hepatic
- type; conjugated and unconjugated
Describe pre-hepatic jaundice
- too much haem to break down
- haemolysis of all causes
- haemolytic anaemias
- unconjugated bilirubin
Describe hepatic jaundice
- liver cells injured or dead
- acute liver failure (virus, drugs, alcohol)
- alcoholic hepatitis
- cirrhosis (compensated)
- bile duct loss (atresia, PBC, PSC)
- pregnancy
describe post-hepatic jaundice
- bile cannot escape into the bowel
- congenital biliary atresia
- gallstones block CB duct
- strictures of CB duct
- tumours (Ca head of pancreas)
Describe cirrhosis of liver
- final common endpoint for liver disease
- irreversible
- defined by bands of fibrosis separating regenerative nodules of hepatocytes
- macronodular or micronodular (alcoholic)
- alteration of hepatic microvasculature
- loss of hepatic function
Describe complications of cirrhosis
- portal hypertension (porto-caval anastomoses)
- oesophageal varices
- caput medusa
- haemorrhoids
- ascites
- liver failure
Describe alcoholic liver disease
- common pathology
- indication for biopsy; usually to rule out another condition
- pathology depends largely on the extent of alcohol abuse
- pathology also depends upon individual factors
Describe the outcome of alcoholic liver disease
- cirrhosis
- portal hypertension, varices and ascites
- malnutrition
- hepatocellular carcinoma
- social disintegration
Describe non-alcoholic steatohepatitis (NASH)
- non-drinkers
- pathologically identical to alcoholic liver disease
- occurs in patients with diabetes, obesity, hyperlipidaemia
- on the increase
- may lead to fibrosis and cirrhosis
Describe primary biliary cirrhosis
- rare autoimmune disease, unknown aetiology
- associated with autoantibodies to mitochondria
- females (90%)
- indication for biopsy; stage the disease
- may see granulomas and bile duct loss
- outcome: unpredictable
Describe autoimmune hepatitis
- commoner in females
- associated with other AI diseases
- chronic hepatitis pattern
- numerous plasma cells
- autoantibodies to smooth muscle, nuclear or LKM, raised IgG
- may have triggers, including some drugs
Describe chronic drug-induced hepatitis
- similar features to all other types of chronic hepatitis
- may trigger an autoimmune hepatitis
- chronic active process
- causes are too many to list
Describe drugs and the liver
- innumerable drugs can damage the liver
- may be dose related or idiosyncratic
- can cause hepatitis, granulomas, fibrosis, necrosis, failure, cholestasis or cirrhosis
- can mimic any liver disease
Describe primary sclerosing cholangitis
- chronic inflammatory process affecting intra and extra hepatic bile ducts
- leads to periductal fibrosis, duct destruction, jaundice and fibrosis
- associated with ulcerative colitis
- males
- increased risk of malignancy in bile ducts and colon
Name some storage diseases
- haemochromatosis
- wilsons disease
- alpha 1 antitrypsin deficiency
Describe iron and the liver
- haemochromatosis is excess iron within the liver
- primary; genetic condition, increased absorption of iron
- secondary; iron overload from diet, transfusions, iron therapy
Describe primary haemochromatosis
- an iron handling / storage disorder
- inherited autosomal recessive condition
- gene defect v.complex
- excess absorption of iron from intestine, abnormal iron metabolism, worse in homozygotes, men
- iron deposited in liver, asymptomatic for years
- eventually deposited in portal connective tissue and stimulates fibrosis
- cirrhosis if not treated
- predisposes to carcinoma
- also causes diabetes, cardiac failure and impotence
Describe the outcome of haemochromatosis
- outcome depends on genetics, therapy (venesection) and cofactors such as alcohol
- cirrhosis
- hepatocellular carcinoma
Describe wilsons disease
- inherited autosomal recessive disorder of copper metabolism
- copper accumulated in liver and brain (basal ganglia)
- Kayser-Fleischer rings at corneal limbus
- low serum caeruloplasmin
- causes chronic hepatitis and neurological deterioration
Describe alpha 1 antitrypsin deficiency
- inherited autosomal recessive disorder of production of an enzyme inhibitor
- causes emphysema and cirrhosis
- cytoplasmis globules of unsecreted globule of protein in liver cells
Name tumours of the liver
- hepatocellular adenoma
- hepatocellular carcinoma (hepatoma)
- multiple secondary
- metastases from colon, pancreas, stomach, breast, lung, others
Describe cholelithiasis (gallstones)
- defined as hard stone-like or gravel-like material formed within the biliary system most commonly the gallbladder
Describe normal bile
- micelles of cholesterol, phospholipid, bile salts and bilirubin
- stored and concentrated in GB, released by CCK into 2nd part of duodenum through common bile duct and ampulla of vater
Describe the pathogenesis of cholesterol gallstones
- gallstones form when there is an imbalance between the ratio of cholesterol to bile salts disrupting micelle formation
- free crystallisation of cholesterol on micelle surface
Describe risk factors and appearance of cholesterol stones
- cholesterol excess in bile
- female, obesity, diabetes, genetics
Describe pathogenesis of pigment stones
- excess bilirubin cannot be solubilised in bile salts
Describe risk factors for and appearance of pigment stones
- excess bilirubin (pigment stones)
- due to excess haemolysis ie haemolytic anaemias
Describe pathogenesis of gallstones
- gallbladder pH and mucosal glycoproteins may be contributory factors
- infection and inflammation of biliary lining
- most gallstones are a mixture (mixed stones)
- pure cholesterol an pure pigment stones do occur
- calcium carbonate stones do occur
Describe the pathology of gallstones
- acute cholecystitis
- chronic cholecystitis
- mucocoele
- empyema
- carcinoma
- ascending cholangitis
- obstructive jaundice
- gallstone ileus
- acute pancreatitis
- chronic pancreatitis
Describe cholecystitis
- inflammation of gallbladder
- usually associated with gallstones
- acute or chronic
- common
Describe acute cholecystitis
- gallstones obstructing outflow of bile
- initially sterile, then becomes infected
- may cause empyema, rupture, peritonitis
- causes intense adhesions within 2-3 days
Describe chronic cholecystitis
- associated with gallstones
- may develop insidiously or after bouts of acute cholecystitis
- gallbladder wall is thickened but not distended
Describe carcinoma of gallbladder
- rare
- adenocarcinoma
- associated with gallstones
- local invasion of liver
- poor prognosis
Carcinoma of bile ducts (cholangiocarcinoma)
- rare
- associated with ulcerative colitis and primary sclerosing cholangitis
- presents with obstructive jaundice
- adenocarcinoma
Describe pancreatitis
- inflammation of the pancreas may be acute or chronic
- overlap exists between acute and chronic
Describe acute pancreatitis
- adults
- sudden onset, severe abdominal pain
- patients may be severely shocked
- elevated serum amylase
Describe aetiology of acute pancreatitis
- alcohol
- cholelithiasis
- shock
- mumps
- hyperparathyroidism
- hypothermia
- trauma
- iatrogenic
Describe pathogenesis of acute pancreatitis
- bile reflux, duct obstruction due to stone damage to sphincter of oddi all cause pancreatic duct epithelial injury
- loss of protective barrier allows autodigestion of pancreatic acini
- release of lytic pancreatic enzymes proteases and lipases
- intra and peripancreatic fat necrosis (lipases)
- tissue destruction and haemorrhage (proteases)
Describe complications of acute pancreatitis
- death
- shock
- pseudocyst formation
- abscess formation
- hypocalcaemia
- hyperglycaemia
Describe chronic pancreatitis
- relapsing disorder may develop insidiously or following bout of acute pancreatitis
Describe the aetiology of acute pancreatitis
- alcohol
- cholelithiasis
- cystic fibrosis
- hyperparathyroidism
- familial
Describe pathology of chronic pancreatitis
- replacement of pancreas by chronic inflammation and scar tissue
- destruction of exocrine acini and islets
Describe carcinoma of pancreas
- adenocarcinoma
- aetiology unknown
- associated with smoking, diabetes, familial pancreatitis
- poor prognosis
