Histopath - Liver & GI Flashcards
Granuloma - definition & diseases seen in
Organised collection of activated (epithelioid) macrophages
Seen in:
- TB
- Leprosy
- Cat-scratch disease
- Idiopathic reaction in sarcoid
General features of squamous cell carcinoma
Keratin production
Intercellular bridges
General features of Adenocacrcinoma
Mucin production
Glands
Histochemical stains
Fontana - melanin
Congo Red - ‘apple green birefringence’ (amyloid)
Prussian Blue - Iron (haemochromatosis)
Haematoxylin & Eosin - H stains basic parts purple/blue, E stains acidic parts red/pink
Rhodamine vs Rhodanine stains
RhodaMine = TB stain
RhodaNine = Wilson’s disease
- golden brown colour on blue counterstain
Histological features of EtOH liver disease
Fatty liver
- large droplet fatty change
- ‘large, pale, yellow, greasy’
Alcoholic hepatitis
- mainly zone 3
- fatty change
- ballooning +/- Mallory Denk bodies
- neutrophil polymorphs
- pericellular fibrosis
- megamitochondria
- ‘large + fibrotic’
Liver failure
- micro nodules of regenerating hepatocytes
- surrounding fibrous cuff
- +/- fatty change if currently drinking
- ‘shrunken + brown’
Acute & Chronic hepatitis histological features
Acute hepatitis
- spotty necrosis
- usually concentrated around portal triad
Chronic hepatitis
- viral = zone 1
- portal inflammation
- interface hepatitis ‘piecemeal necrosis’ (even though death is by apoptosis)
- lobular inflammation (resembles acute spotty necrosis)
Overdose rule?
If PT (in seconds) > number of hours since OD --> transfer to specialist liver unit for transplant
Pattern of nodule size in liver disease
MICROnodulae = alcoholic hepatitis, insulin resistance
MACROnodular = viral hepatitis, Wilson’s, Alpha-1-antitrypsin deficiency
Primary biliary cholangitis diagnostic features
Histology:
- Bile duct loss
- Chronic inflammation
- granulomas
Other: Anti-mitochondrial antibodies e.g. anti M2 = gold standard
Primary sclerosing cholangitis diagnostic features
Histology:
- concentric fibrosis
- ‘onion skinning’
Bile duct imaging e.g. ERCP, MRCP
pANCA Ab detection
Autoimmune hepatitis diagnostic features
Histology:
- extensive inflammatory infiltrate
- abundant plasma cells
- pale perinuclear area
Anti-smooth muscle actin Abs
Anti liver-kidney microsomal Ig
Hepatic granulomas - causes?
Specific: PBC, drugs
General: TB (caseating), sarcoid (non-caseating)
Normal range of bilirubin
5-17
Pre-hepatic causes of raised bilirubin
UNconjugated
Haemolytic anaemia
Hepatic causes of raised bilirubin
Hepatitis - viral, EtOH
Cirrhosis
Post hepatic causes of high bilirubin
Obstruction - gallstones, ca. head of pancreas
Ix needed for pre-hepatic (unconjugated) hyperbilirubinaemia
FBC
Blood film
Coomb’s test?
Genetics of Gilbert’s
Autosomal recessive
Pathogenesis + presentation of Gilbert’s
UDP glucoronyl transferase activity reduced to 30%
Causes slight jaundice
Worse when fasting/stressed
No bilirubin in urine (unconjugated bilirubin highly bound to albumin)
Best measure of liver (synthetic) function?
Pro-thrombin time (PT)
Also:
albumin, PTTK, Bilirubin
Enzymes (GGT, ALP, ALT, AST) only show location of damage not degree.
Clinical features of Chronic stable liver disease
Palmar erythema
Spider naevi (>5)
Dupuytren’s contracture
Gynaecomastia
Clinical features of portal HTN
Porto-systemic anastomoses
- caput medusae
- oesophageal varices
- rectal varices
Splenomegaly
Scrotal oedema
Shifting dullness (ascites)
Clinical feature of decompensated liver failure
Hyperammonaemia
- Flapping tremor
- confusion
Jaundice (accumulation of bile salts)
Hepatic coma, death
Role of Stellate cells in liver?
Store vitamin A
Differentiate into myofibrobasts when there is damage to liver –> make collagen, form scars
Inflammatory adaptations in liver
Loss of microvilli
Stellate cells activate
Deposition of collagen (scar matrix) in space of Disse
Loss of fenestrae - endothelial cells become continuous
Result = blood does not interact with hepatocytes
Most important RF for hepatocellular carcinoma
Cirrhosis
Classification of chronic hepatitis
Grade = severity of inflammation Stage = severity of fibrosis
Stage more important than grade for prognosis.
What are mallory denk bodies?
Collapsed cytoskeleton in swollen hepatocytes
Present in EtOH hepatitis
Haemochromatosis pathogenesis
Mutation om Chr6 (HFe)
Increased GI iron absorption (with no way to excrete it)
Wilson’s disease pathogenesis
Mutation on Chr 13
Often >1 mutation
Failure of excretion of copper into bile by hepatocytes –> accumulation in liver, CNS
Tx for Wilson’s disease
Zinc
Trientine
Histological Ix for Wilson’ disease
Rhodanine stain - copper in hepatocytes (brown on blue counterstain)
Histology of alpha anti-trypsin 1 deficiency
Intra-cytoplasmic inclusions (misfiled protein)
Macronodular hepatitis
Cirrhosis
Macroscopic appearance of liver adenoma
Sharp demarcation
Most common type of liver malignancy?
Metastatic
Receives blood from pancreas, stomach, large bowel etc. via portal circulation
Tumour marker for primary hepatocellular carcinoma?
Alpha foeto protein (AFP)
Associations with Primary cholangiocarcinoma
Primary sclerosis cholangitis (PSC)
Worm infections (North Thailand)
Cirrhosis
Cause of nutmeg liver?
Congestive heart failure
Hirschsprung’s disease pathogenesis
Absence of ganglion cells from Auerbach (mesenteric) and Meissner (submucosal) plexus of rectum and distal colon.
Uncoordinated peristalsis causes functional obstruction
Diagnostic Ix for Hirschsprung’s
Full thickness rectal biopsy
- Hypertrophied nerve fibres but no ganglia
Locations of volvulus
Small bowel (infants) Sigmoid colon (elderly)
Definition of volvulus?
Complete twisting of loop of bowel
at mesenteric base
around vascular pedicle
Pathogenesis of diverticular disease
High intra-luminal pressure forces mucosa through ‘weak points’ of bowel
Most common location for diverticular disease
Left colon (90%)
Histology of pseudomembranous colitis
Macroscopic:
- erytemaotus
- ‘wet cornflake’ lesions (pseudomembranes)
most common vascular disorder of intestinal tract?
Ischaemic colitis / infarction
Usual location of ischaemic colitis / infarction
Watershed zones (where previous and next blood supply poorly overlap –> area with poor supply vulnerable to ischaemia)
Splenic flexure - SMA, IMA
Rectosigmoid - IMA, internal iliac artery
Usual location of ischaemic colitis / infarction
Watershed zones (where previous and next blood supply poorly overlap –> area with poor supply vulnerable to ischaemia)
Splenic flexure - SMA, IMA
Rectosigmoid - IMA, internal iliac artery
Causes of ischaemic colitis / infarction
Arterial occlusion - atheroma, thrombosis, embolism
Venous occlusion - thrombus, hyper coagulable state
Small vessel disease - DM, cholesterol emboli, vasculitis
Low flow states - CCF, haemorrhage, shock
Obstruction - hernia, intussusception, volvulus, adhesions
Key histological features of Crohn’s
Mouth - anus Skip lesions Transmural inflammation Non caseating granulomas Sinus / fistula common
Key histological features of UC
Rectum + colon \+/- mild 'backwash ileitis' and appendiceal involvement Continuous Mucosal inflammation only Shallow ulcers Bowel wall normal thickness
Complications of UC
Toxic megacolon
Adenocarcinoma - 20-30x risk
Severe haemorrhage
Complications of Crohn’s
Fat wrapping
Thick ‘rubber hose’ bowel wall, narrow lumen
Linear ulcers, fissures
Abscesses
Adenocarcinoma (less than UC)
Derm manifestations of UC & Crohn’s
Crohn’s: Pyoderma gangrenosum, erythema multiforme, erythema nodosum
UC: Pydoerma gangrenosum, erythema nodosum
Non Neo-plastic polyps
Hyperplastic - very common, no progression (for exam purposes)
Inflammatory ‘pseudopolyps’ - areas of regenerating mucosa which project into lumen, seen in UC
Hamartomatous - juvenile, Peutz-Jeghers
Neoplastic polyps
Tubular
Tubulovillous
Villous
Risk factors for cancer (from polyp)
Size - >4cm approx 45% invasive malignancy
Proportion of villous component
Degree of dysplastic change
Familial adenomatous polyposis - genetics & pathogenesis
Autosomal dominant
Chromosome 5q21 - APC tumour suppressor gene
Minimum 100 polyps (usually colorectal adenomatous)
Virtually 100% develop ca. within 10-15 yrs
Garnder’s syndrome - key features
Subtype of Familial adenomatous polyposis
Distinct extra-intestinal features
- multiple oestomas of skull, mandible
- epidermoid cysts
- desmoid tumours
- dental caries, unerupted supernumerary death
- post surgical mesenteric fibromatoses
Hereditary non polyposis colon cancer - genetics, pathogenesis
Autosomal dominant, uncommon
Involves 1 of 4 DNA mismatch repair genes –> DNA replication errors
Onset of colorectal ca. at early age
Type & distribution of cancer in HNPCC (Lynch syndrome)
high % proximal to splenic flexure
Poorly differentiated + mutinous carcinoma more common
+ extracolonic cancer: endometrial, prostate, breast, stomach
Most common type of lower GI cancer
Adenocarcinoma - 98%
RF for Lower GI cancer
Diet - low fibre, high fat
Lack of exercise, obesity
Familial
Chronic IBD
Tumour marker for lower GI cancer
Carcinoembryonic antigen (CEA)
Staging system for lower GI cancer
Duke’s
A = limited to mucosa
B1 = extending into muscular propria B2 = transmural invasion, no LN
C1 = extending into muscular propria, LN involvement C2 = transmural invasion, LN involvement
D = distant mets
Layers of normal oesophagus
Epithelium
Submucosa
Muscular extra
Normal stomach - features of body
Lined by gastric mucosa columnar epithelium - foveolar, mucin secreting
Specialised glands in lamina propria - produce acid, IF.
Muscular mucosae
No goblet cells!
Normal stomach - features of antrum
Lined by gastric mucosa columnar epithelium - foveolar, mucin secreting
Non specialised glands in lamina propria - gastric pits
Muscular mucosae
Normal duodenum features
Glandular epithelium with goblet cells - ‘intestinal type’
Villous architecture - villous:crypt ratio of >2:1
Features of acute oesophagitis
Neutrophils
Most common cause of acute oesophagitis
GORD / reflux
Barrett’s oesophagus types
Without goblet cells - gastric type metaplasia
With goblet cells - intestinal type metaplasia, more likely to progress to ca.
Barrett’s oesophagus - basic process/pathogenesis
Squamous epithelium replaced by metaplastic columnar epithelium
Most common oesophageal ca.?
Adenocarcinoma (in ‘developed’ countries)
Squamous cell carcinoma (in ‘developing’ countries)
Adenocarcinoma of oesophagus - key features
Associated with reflux
Lower oesophagus
Gland formation + mucin production (hallmarks of adenocarcinoma)
Squamous cell carcinoma of oeseophagus - key features
Associated with EtOH & smoking
mid-lower oesophagus
Keratin production (+ intercellular bridges)
Causes of oesophageal varices
Cirrhosis - most common
+ portal vein thrombosis
Causes of acute gastritis
Chemical - aspirin, NSAIDs, alcohol, corrosives
Infection - Helicobacter pylori
Causes of chronic gastritis
Autoimmune - anti-parietal Abs, mainly affects body of stmach
Bacterial - H. pylori, affects antrum
Chemical - NSAIDs, reflux, affects antrum
Biopsy finding in H. pylori infection
Gastric ulcer
Chronic gastritis +/- acute activity
Complications of H. pylori infection
CLO-IM dysplasia
Adenocarcinoma
Lymphoma (MALToma)
Definition of ulcer
Defect through muscularis propria
Most common type of gastric cancer?
Adenocarcinoma (95%)
Morphological categories of gastric adenocarcinoma
Intestinal - well differentiated
Diffuse - poorly differentiated (linitis plastica), includes signet ring cell carcinoma!
Other (non adenocarcinoma) gastric cancer types
Squamous cell carcinoma
Lymphoma - MALToma
Gastrointestinal stromal tumour (GIST)
Neuroendocrine tumour
Pathogenesis of duodenitis
Increased acid production in stomach
Spills over into duodeum
Chronic inflammation, gastric metaplasia
NOTE: once gastric type cells present, duodenum is vulnerable to H. Pylori
Causative organism of Whipple’s disease
tropheryma whipellii
Rare bacterial infection seen in duodenum
Biopsy evidence of coeliac disease
Villous atrophy
Crypt hyperplasia
Increased intraepithelial lymphocytes (normal <20 per 100 enterocytes)
NOTE: will only show this if currently eating gluten
Coeliac-associated cancer
In duodenum
T cell origin ‘enteropathy associated T cell lymphoma’ (EATL)
Functional cells of pancreas?
Acinar cells
- produce enzymes
- have abundant rough ER + Golgi
Definition of acute pancreatitis
Acute inflammation of pancreas
caused by aberrant release of pancreatic enzymes
Causes of acute pancreatitis
Duct obstruction
- Gallstones - 50%
- Trauma - fibrotic scarring, narrowing
- Tumours
- EtOH
Metabolic/toxic
- Alcohol - 33%
- Drugs e.g. thiazides
- Hypercalcaemia
- Hyperlipidaemia
Poor blood supply - shock, hypothermia
Infection - mumps
Autoimmune
Idiopathic - 15%
Pathophysiology of acute pancreatitis (from gallstones)
Gallstone stuck distal to where common bile duct + pancreatic duct join
Reflux up pancreatic duct
Damage to acini + release of pro-enzymes which become activated
Activated enzymes cause acinar necrosis –> further enzyme release
Histology of fat necrosis in acute pancreatitis
Macroscopic:
Necrosis forms free fatty acids
Ca2+ ions bind to free fatty acids, forming soaps
Seen as yellow/white foci
Microscopic
Blue = histological correlates of white/yellow foci
Pathophysiology of acute pancreatitis (due to EtOH)
Spasm/oedema of Sphincter of Oddi + formation of protein-rich pancreatic fluid
Fluid obstructs pancreatic ducts
Patterns of injury in acute pancreatitis
Periductal - necrosis of acinar cells near ducts (obstruction)
Perilobular - necrosis at edges of lobules (ischaemia)
Panlobular - progressive periductal + perilobular damage
Causes of chronic pancreatitis
Metabolic/toxic
- alcohol 80%
- haemochromatosis
Duct obstruction
- gallstones
- abnormal pancreatic duct
- CF ‘mucoviscoidosis’
Tumours
Autoimmune
Complications of chronic pancreatitis
Malabsorption
Diabetes mellitus (late - neuroendocrine cells survive relatively well)
Pseudocysts
Increased risk of ca. of pancreas
Pancreatic pseudocyst - key features
Lined by fibrous tissue - not epithelial lining
Contain fluid rich in pancreatic enzymes OR necrotic material
Usually connect with pancreatic ducts
Possible outcomes of pancreatic pseudocyst
Perforate
Become infected
Compress adjacent structures
Resolve
Key features of Autoimmune pancreatitis
Large no. of IgG4 + plasma cells
Involves pancreas, bile ducts + almost any other body part
Most common pancreatic neoplasm?
Ductal carcinoma - 85%
Risk factors for pancreatic ductal carcinoma
Smoking
BMI, dietary factors
Diabetes
Chronic pancreatitis
Pathogenesis of pancreatic ductal carcinoma
Arise from dysplastic lesions
- pancreatic intraductal neoplasms (PanIN)
- intraductal mucinous papillary neoplasm
K-Ras mutation in 95%
Tumour marker for pancreatic ductal carcinoma
Carbohydrate antigen 19-9 (CA19-9)
Distribution of pancreatic ductal carcinoma
Head 60% - may present earlier due to obstruction of biliary tree
Body
Tail
Diffuse
Histology of pancreatic ductal carcinoma
Adenocarcinoma so mucin production + glands
Set in desmoplastic stroma (storm that arises in response to cancer - fibrous reaction)
Perineural invasion - characteristic
Pancreatic endocrine neoplasms - key features
Usually NON secretory
But can release glucagon, insulin etc.
Difficult to predict behaviour.
May be associated with MEN 1
Most common secretory tumour
Insulinoma
Risk factors for gallstones (cholelithiasis)
Increase age ‘forty’
Female
Ethnicity & geography - Native American
Hereditary disorders of bile metabolism
Drugs - COCP
Acquired disorders - rapid weight loss (increased excretion of lipids)
Pigment gallstones - characteristics
Contain calcium salts of unconjugated bilirubin
Multiple
Mostly radio-opaque
features of chronic cholecystitis
Chronic inflammation - lymphocytes
Fibrosis
Thickened wall (normal <2mm)
Diverticula e.g. Rokitansky-Aschoff sinuses
90% associated with gallstones
Most common cause of gallbladder ca.
Gallstones - 90% associated
