Histopathology Flashcards
What is the evolution of an MI, in terms of histological findings, between hours-weeks/months after
under 6 hours- histologically normal (CK-MB also normal)
6-24hrs- loss of nuclei, homogenous cytoplasm, necrotic cell death
1-4 days- infiltration of polymorphs then macrophages to clear debris
5-10 days- removal of debris
1-2weeks- granulation tissue, new blood vessels myofibroblasts, collagen synthesis
weeks-months- strengthening, decellularising scar tissue
common causes of heart failure
Ischaemic heart disease
Myocarditis
hypertension
cardiomyopathy
valve disease
arrhythmias
signs of heart failure
LHF
pulmonary oedema
dyspnoea, orthopnoea
wheeze
fatigue
RHF
congestion of systemic and portal venous system
Oedema
ascites
facial engorgement
nutmeg liver
Investigations for HF
BNP/ NT-proBNP
CXR
ECG
Echo
causes of dilated cardiomyopathy
alcohol
thyroid disease
haemachromatosis
idiopathic
viral myocarditis
casues of hypertrophic cardiomyopathy
hypertension
valve disease
???
causes of restrictive cardiomyopathy
sarcoidosis
amyloidosis
radiation induced
describe hypertrophic cardiomyopathy
thick walled heart, heavy and hypercontractile
myocardium cells in dissarray which is arrhythmogenic
autosomal dominant
mutation in the beta-myosin genee most common
cause of sudden cardiac death in young people
HOCM- (obstructive)- septal hypertrophy resulting in outflow obstruction
multisystems affected in acute rheumatic fever
heart: pericarditis, myocarditis, endocarditis (pancarditis)
joints: arthritis, synovitis
skin: erythema marginatum, subcutaneous nodules
CNS:encephalopathy, sydenhams chorea
clinical features of rheumatic fever
develops 2-4 weeks after strep throat
diagnosis: GAS infection +2major or 1major+2minor
JONES’ MAJOR (CASES)
Carditis
Arthritis
Sydenhams chorea
Erythema marginatum
Subcutaneous nodules
MINOR CRITERIA
Fever
raised CRP/ESR
PR prolongation
arthralgia
previous rheumatic fever
malaise
tachycardia
Histological findings in rheumatic fever
Beady fibrous vegetations (verrucae- small warty veg found along closure of valve leaflet)
Aschoff bodies (small giant cell granulomas)
Antischkov myocytes (regenerating myocytes)
Causes of cardiac vegetations
Rheumatic heart disease (verrucae)
Infective endocarditis (large vegetations of colonising bacteria)
thrombotic endocarditis (eg. DIC- small vegetation attached to lines of closure)
Libman-sacks endocarditis (small warty vegetations that are sterile and rich in platelets)- SLE
non bacterial thromboemboli
Causative organisms of IE and RFs
staph aureus –> IVDU (tricuspid), cannulae, central lines, cellulitis
Strep viridans –> poor dental hygeine/ dental surgery
Strep pyogenes
staph epidermidis –> prosthetic valves
steptococcus bovis –> colon cancer
HAECK
Dukes criteria of IE
Major
- positive blood culture of typical IE organism or 2 positive cultures 12hrs apart
- positive finding on echo
Minor
- evidence of immune phenomena(osler, roth)
- evidence of thromboembolic phenomina (janeways, septic abscess, splinter, splenomegaly)
- fever
- risk factor (IVID, prosthetic valve, valve abnormalities)
- positive culture not meeting major criteria
Treatment of acute IE
Flucloxacillin (MSSA)
gentamycin+ rifampicin + vancomycin (MRSA)
Treatment for subacute IE
benzylpenicillin+ gentamycin or vancomycin for 4 weeks
what classification is used to assess severity of GORD
Los Angeles Classification
obese people have GORD and people in LA are obese
what is the progression of disease from GORD-> cancer
GORD –> metaplasia (barretts) –> dysplasia –> adenocarcinoma
where is adenocarcenoma of the oesophagus found
distal 1/3
associated with barretts
where is SCC of oesophagus found
middle 1/3 (50%)
upper 1/3 (20%)
lowe 1/3 (30%)
common lung infectious organism in people with CF
Pseudomonas aeruginosa
what is cystic fibrosis?
Autosomal recessive condition casued by a mutation in the CFTR gene which is responsible for Cl transport
Results in abnormally thick secretions
what is the FEV1/FVC ratio in restrictive disease
FEV1 relatively large but FVC reduced
FEV1/FVC >70%
Clinical findings in interstitial lung disease
fine end inspiratory crackles
chronic SOB
pulmonary HPTN and cor pulmonale
ground glass/ honeycomb appearance on CTCAP
histological stages of pneumonia
1- consolidation
2- red hepatisation (neutrophilia)
3- grey hepatisation (fibrosis)
4- resolution
Most common types of lung tumours
1- SCC (30-50%)
2- adenocarinoma (20-30%)
3- small cell carcinoma (20-25%)
4- large cell carcinoma (10-15%)
features of SCC of the lung
- most commonly associated with smoking
- p53/c-myc mutation associations
- proximal bronchi
Histology
-keritinisation
- intracellular prickles (desmosomes)
- can produce PTHrP –> hypercalcaemia
progression
epithelium –> hyperplasia –> squamous mataplasia –> angiosquamous dysplasia –> carcinoma in situ –> invasive carcinoma
Features of lung adenocarinoma
-lung cancer most commonly associated with non-smokers
-malignant epithelial tumor with glandular differentiation or mucin production
-starts peripherally and mets early
histology
- glandular differentiation
progression
- atypical adenomatous hyperplasia –> non mucinous BAC –> mixed pattern adenocarcinoma
features of small cell lung cancer
- central
- arises from neuroendocrine cells so associated with ectopic ACTH and ADH secretion
(cushings, SIADH) - associated with lambert eaton syndrome (40% of LEMS have SCLC)
- smoking
-p35 and RB1 mutations - mets early to bone, liver, brain and adrenals
histology
- oat cells
Large cell carcinoma
-poorly differentiated malignant epithelial tunour
-poor prognosis
examples of paranoplastic synromes and what cancer they are associated with
Hyperparathyroidism, hypercalcaemia –> PTHrP secretion (squamous cell carcinoma)
SIADH –> ectopic ADH (small cell lung cancer)
Cushings syndrome –> ectopic ACTH (small cell lung cancer)
carcinoid tumour (lung or GIT) –> serotonin secretion
struma ovarii- ovarian tumour which secretes thyroxine
describe mesothelioma
cancer arising from either parietal or visceral pleura
- spreads widely in pleural space
- extensive pleural effusion, chestpain, dyspnoea
- asbestos related with 25-45 latent period
Classess of pulmonary hypertension
class 1 - pulmonary arterial hypertension
class 2 - pulHPTN due to left heart disease
class 3- due to lung disease (eg. IDL)
class 4 - unclear multifactorial problems
hisologial findings of pulmonry oedema
intraalveolar fluid
iron laden macrophages (heart failure cells- the iron lady had no heart)
investigations for coeliac
ABs:
- anti-endomysin Abs (best)
- anti- transglutaminase
- anti-gliadin
gold standard:
- endoscopy and duodenal biopsy –> crypt hyperplasia and villous atrophy with increased intraepithelial lymphocytes
Cancer associated with coeliac
Enteropathy T cell lymphoma
(chronic T cell stimulation)
Cancer associated with chronic H pylori infeciton
Mucosal associated lyphoid tissue (MALT) lymphoma
Extra GI manifestations of IBD
Malabsorption and iron deficiency –> angular stomatitis
Eyes –> anterior uveitis, conjunctivitis
skin –> erythema nodosum, pyoderma gangrenosum, erythema multiforme
Joints –> migratory asymmetrical polyarthropathy of large joints, sacroiliitis, myositis, ankylosing spondylitis, clubbing
liver –> pericholangitis, primary sclerosing cholangitis (UC>CD) inc risk of cholangiocarcinoma
Key difference between UC and CD interms of smoking
CD- smoking worsens condition
UC- smoking improves symptoms/ protective
Key features of chrons disease
can be anywhere along the GIT (mouth to anus)
skip lesions
cobblestone appearance
Transmural inflammation
non caseating granulomas (ddx TB colitis)
apthous ulcer - first lesion –> serpentine ulcers when join together
Complications of chrons
Bowel strictures
fistulae
abscess formation
perforation
Features of UC
slightly more common than chrons
white>non-white. 20-25yrs
distal portion of GIT affected
continuous involvement of mucosa
superficial inflammation
pseudopolyps (islands of regenerating mucosa)
BLOODY diarrhoea
smoking improves sx
backwash ilitits only if whole colon affected and it moves to ilium
Complications of UC
Toxic megacolon
severe haemorrhage
adenocarcinoma (20-30x risk)
Which Abx are associated with C. diff infection
the 4 Cs
Cephalosporins
Clindamycin
Ciprofloxacin
Co-amoxiclav
Treatemnt and Mx of C. diff infection
Vancomycin or metronidazole
move to a side room
What is carcinoid syndrome
group of tumours arising from enerochromaffin cells which causes over production of 5-HT
found in the bowl, lungs, ovaries and testes
Clinical features of carcinoid syndrome and carcinoid crisis
Bronchoconstriction
flushing
diarrhoea
crisis:
lifethreatening vasodilation, hypotension
tachycardia
bronchoconstriction
hyperglycaemia
investigations for carcinoid syndrome
24hr urnine 5-HIAA (main metabolite of H-HT)
Treatment of carcinoid syndrome
ocretide (somatostatin analogue)
Outline the Dukes staging of colorectal cancer
(NB this is out dated)
A- confined to mucosa
B1- extending to muscularis propria
B2- transmural invasion but no nodal involvement
C1- extendning to muscularis propria with LN mets
C2- transmural invasion with LN mets
D- distant mets
Descripe the pathophysiology of FAP
Familia adenomatous polyposis
mutation in the APC tumor suppressor gene gene C5q1 - 30% autosomal recessive mutation in DNA mismatch repair genes)
> 100 polyps seen on colonoscopy for diagnosis
all will progress to adenocarcinoma if not treated
increased risk of ampulla of vater and stomach neoplasia
Describe lynch syndrome
Hereditary non-polyposis colorectal cancer
autosomal dominant mutation in mismatch repair genes
few polyps but fast progression to malignancy <50yrs
carcinoma commonly found in caecum
also associated with extracolonic cancers ENDOMETRIAL, prostate, ovarian, small bowel, transitional cell and stomach carcinomas
macrovascular complications of diabetes
Ischaemic heart disease
Peripheral vascular disease
CVA
Microvascular complications of DM
Diabetic retinopathy
glomerulonephritis
peripheral neuropathy- ulcers
Histological findings in acute pancreatitis
coagulative necrosis
histological findings of chronic pancreatitis
fibrosis and loss of exocrine tissue parenchyma, duct dilation with thick secretions, calcification
Histological findings in acute hepatitis
spotty necrosis
Histological findings in chronic hepatitis
- portal inflammation
- interface hepatitis (piecemeal necrosis)
- lobular inflammation
- bridging of the portal vein to the central vein
what is basophilic stippling and what is it a sign of?
aggregation of ribosomal material
present in beta-thalassaemia and lead poisoning
How does Reyes syndrome present
usually following URTI and aspirin consumption in children
acute encephalopathy secondary to severe impairment of liver function
what is budd chiari syndrome
occlusion of the portal vein either due to compression or thrombosis
Describe haematochromatosis
excessive deposition of iron due to increased absorption from the gut
iron accumulates as haemosiderin in various organs
hyperpigmentation of the skin
Describe Wilsons disease
mutation in copper transport ATPase gene on chromosome 13
failure of the liver to secrete copper-ceruloplasmin complex into the plasma
overspil of copper into the blood results in:
- liver disease
- parkinsonism
- kayser fleischer rings
complications of alpha1 antitrypsin deficiency
failure in production on protease inhibitor alpha 1 anti trypsin
causes hepatitis from accumulation of alpha1 trypsin globules
what is zollinger-ellison syndrome
gastric hypersecretion leading to multiple peptic ulcers
diarrhoea
What is fibrous dysplasia and some features
disorder of children and young adults
(woman <30y)
fibrous and boney tissue lesions in the ribs, femur, tibia or skull
‘soap bubble’ appearance on Xray indicative of osteolysis
presents as bone pain and weakness
Histology:
- loose fibrous tissue with metaplaplastic woven bone trabeculae –> ‘CHINESE LETTERS’ formation
3 forms-
polyostotic
McCune-Albright syndrome (endocrine manefestaions)
shepherds crook deformity
Describe McCune Albright syndrome
rare disorder that affects bone, skin and endocrine systems
features:
fibrous dysplasia of bone
cafe au lait spots
multiple endocrine dysfunction
Which method of cyto-pathology is used in cervical smear
liquid based cytology
Histopathology in chronic bronchitis
hypertrophy of mucus glands and goblet cell hyperplasia
–> copious amounts of mucus
histological findings in squamous cell carcinoma
if well differentiated show keratin pearls and cell junctions (desmosomes) –> characteristic itercellular ‘prickles’
what skin manefestation is associated with coaeliac disease
dermatitis herpetiformis
histological finding of lichun planus
hyperkeratosis with SAW TOOTHING of rete ridges and basal cell degeneration
lichenoid chronic inflammatory infiltrate
what condition is likely if white cell casts are found on urinanalysis
acute pyelonephritis
what condition is likely if red cell casts are found on urinanalysis
Glomerulonephritis
Congo red and apple green birefringence positive result sign of
Amyloidosis
Positive fontana stain
melanoma (stains melanin)
Rhodanine stain positive sign
golden brown against blue counterstain
Wilsons disease
Positive prussian blue stain
Haemachromatosis
Positive Perl’s stain
Haemachromatosis
Positive cytokeratin stain
Carcinoma
(positive for epithelial cells)
Positive Ziehl-Neelson stain
stains acid fast bacilli - TB
Bright yellow when stain with Rhodamine-Auramine
TB
Gomori’s methanamine silver stain with flying saucer shaped cysts
Pneumocystic jirovecii
Positive modified kinyoung acid fast stain
cryptosporidium parvum
India ink stain showing cells surrounded by halos
cryptococcus neoformans
Giemsa stain showing cytoplasmic inclusions
Chlamydia psittaci
Positive Fite stain
Mycobacterium leprae
(dont fight with my leopard)
Histology features of sarcoidosis
multisystem disease of unknnown cause
characteriseed by non-caseating granulomas
Histology: schaumann and asteroid bodies
features, RFs and clinical signs of sarcoidosis
RFs
- afro-carribeans
- F>M, 40-60yrs
SOB, cough, chest pain, night sweats.
CXR findings:
- bilateral hilar lymphadenopathy
- pulmonary infiltrates -> fine nodular shadowing
Extrapulmonary manifestations of sarcoidosis
SKIN: erythema nodosum (tender red nodules on shins), lupus pernio (purple leasons around nose), skin nodules
LN: lymphadenopathy, painless and rubbery
JOINTS: arthritis, bone cysts
EYES: anterior uveitis (painful and misting of vision), posterior uveitis (progressive visual loss), keratoconjunctivitis, lacrimal gland enlargement
Hepatosplenomegaly
leukopenia, anameia
hypercalcaemia
HEART: dysrhythmias, restrictive cardiomyopathy
FLAWS symptoms
Investigation findings of sarcoidosis
raised Ca2+ (ectopic a1hyroxylase released by activated macrophages)
raised ESR
raised ACE
non-caseating granuloma on histology
restrictive pulmonary findings on spirometry
What is amyloidosis
multisystem disorder caused by abnormal folding of proteins that deposit as amyloid fibrils in tissue, disrupting their normal function
lots of forms eg:
- beta pleated sheet structure
- resistant to enzyme degredation
what is the most common type of amyloidosis?
AL amyloidosis
deposition of Ig light chain
monoclonal Ig
free light chains in serum and urine (bence jones protiens)
increased bone marrow plasma cells
SIMILAR TO MULTIPLE MYELOMA
describe AA amyloidosis
formed from serum amyloid A acute phase protein
build up secondary to chronic infection and inflammation
eg. RA, IBD, TB, lymphoma
what is haemodialysis associated amyloidosis?
deposition of beta2 microglobulin
usually occurs in someone with long standing chronic renal failure esp if on peritoneal dialysis
associated with carpal tunnel syndrome
What is familial amyloidosis
most common Familial mediterranean fever
characterized by recurrent episodes of fever and serositis (chest, abdomen, joints), leading to painful attacks early during childhood. Amyloidosis is the most fatal complication of FMF
clinical features of amyloidosis
multi organ features
KIDNEY: nephrotic syndrome
HEART: restrictive cardiomyopathy, conduction defects, HF, cardiomegaly
hepatosplenomegaly
macroglossia (10%)
neuropathies eg. carpal tunnel syndrome
examples of large cell vasculitides
Takayasu’s arteritis
Giant cell arteritis (temporal arteritis)
Describe features of takayasu’s arteritis
affects branches of aortic arch
FLAWS
pulseless phases
claudication
cold hands
high rates in japanese women
Describe features of GCA
Elderly >50yrs
scalp tenderness eg. when brushing hair
temporal headache
jaw claudication
blurred vision
Ix: raised ESR, temporal artery biopsy
histological findings in GCA
granulomatous transmural inflammation, giant cells and skip lesions
Management of GCA
IMMEDIATE oral prednisolone
give some examples of medium cell vasculitides
Polyarteritis nodosa
Buerger’s disease
?kawasakis (systemic vasculitis)
describe the features of polyarteritis nodosa
renal involvement
spares the lungs
30% have underlying hep B
microaneurysms on angiography (string of pearls/ rosary bead appearance)
‘poly nodes- stings of pearls’
histology: fibrinoid necrosis and neutrophil infiltration
what is string of pearls/ rosary appearance characteristic of?
polyarteritis nodosa
describe the features of buerger’s disease
Seen in heavy smokers
usually men <35
inflammation of arteries of extremitis- usually tibial and radial
pain, ulceration of toes, feet and fingers
angiogram: corkscrew appearance from segmental occlusive lesions
what is a corkscrew appearance on angiogram characteristic of?
Buerger’s disease
give some examples of small cell vasculitides
Granulomatosis with polyangiitis
eosinophilic granulomatosis with polyangitis
microscopic polyangitis
henloch- schonlein purpura
saddle node, haemoptysis and haematuria
granulomatosis with polyangiitis
Describe the features of granulomatosis with polyangiitis
triad of upper resp tract symptoms, lower resp tract symptoms and kidney features
ie: epistaxisi, saddle nose
pulmonary haemorrhage –> haemoptysis
crescenteric glomerulonephritis –> haematuria and proteinuria
cANCA
features of eosinophilic granulomatosis with polyangiitis
ASthma, allergic rhinitis, eosinophilia, later systemic involvement
pANCA +ve
features of microscopic polyangiitis
pulmonary haemorrhage
rapidly progressive glomerulonephritis
pANCA =ve
Features of HSP
IgA mediated
3-15yrs
preceeding URTI
purpuric rash on buttocks and lower limbs
abdo pain (bleeding)
arthralgia
glomerulonephritis
what is a ‘wire-loop’ appearance of the glomeruli characteristic of
SLE
Histological features of SLE
- wire-loop appearance of glomeruli
- CNS small vessel angiopathy
- onion skin lesions in the spleen
- Libman- Sack endocarditis
clinical features of SLE
SOAP BRAIN MD
- Serositis
- Oral ulcers
- Arthritis
- Photosensitivity
- Blood disorders (AIHA, AITP, leucopenia)
- Renal involvement
- ANA +ve
- Immune phenomena
- Neuro symptoms
- Malar rash
- Discoid rash
antibodies present in SLE
anti-ANA (anti-dsDNA, anti-Sm)
anti-smith (most specific)
anti-histone (+ve if drug induced)
onion skin thickening of arterioles
limited scleroderma (CREST syndrome)
difference between diffuse and limited scleroderma
limited- only distal skin involvement. organ involvement rare. associated with pulmonary HPTN
diffuse- distal and proximal skin changes. widespread organ involvement, early heart, renal and GI . Associated with pulmonary fibrosis
cutaneous features of dermatomyositis
- heliotrope rash with eyelid oedema
- grotton papules (erythema of knuckles with raised scaley erruptions)
- systemic V shaped rash
- facial rash
drop out capillaries and myofibre damage on histology is characteristic of..
dermatomyositis
which cells in the pancreas secrete the enzymes
acinar cells
Describe acute pancreatitis
acute inflammation causing aberrant release of pancreatic enzymes
Causes of acute pancreatitis
duct obstruction:
- GALL STONES (50%)
- TRAUMA
- TUMORS
metabolic/toxic
- ALCOHOL (33%)
- DRUGS (eg. thiazides)
- HYPERCALCAEMIA
- HYPERLIPIDAEMIA
poor blood supply
- SHOCK (ischaemia)
- HYPOTHERMIA
infection/inflammations
- VIRUSES (eg. mumps)
autoimmune
- IgG4 related disease
idiopathic
how does duct obstruction by gallstones cause acute pancreatitis?
reflux of bile up pancreatic duct followed by damage to acini and release of proenzymes
patterns of damage in actute pancreatitis
Periductal- necrosis of acinar with obstructive casues
perilobular - furthest away from blood supply so most affected by ischaemic causes
pan lobular - both
discribe the process of pancreatitis
Activated enzymes –> acinar necrosis –> enzyme release
lipases –> fat necrosis (bind to Ca which forms soaps, yellow white foci on histo)
complications of acute pancreatitis
pancreatic: pseudocysts, abscess
systemic: shock, hypoglycaemia, hypocalcaemia (fat necrosis)
acute pancreatitis with notmal calcium possible cause
caused by hypercalcaemia initially and then Ca brought back down to normal by fat necrosis
casues of chornic pancreatitis
Metabolic:
- ALCOHOL (80%)
- HAEMACHROMATOSIS
duct obstruction
- GALL STONES
- ABNORMAL PANCREATIC DUCT ANATOMY
- CYSTIC FIBROSIS
Tumours
AUTOIMMUNE
Pathogenesis of chronic pancreatitis
Similar to acute
chronic inflammation with parynchyman fibrosis and loss of parencyma
duct strictures with calcified stones with secondary dilations
FIBROSIS AND SCARRING
associated with atrophy of the acini
CALCIFICATION
complications of chronic pancreatitis
malabsorption
DM
pseudocysts
carcinoma
what are pancreatic pseudocysts
associated with both acute and chronic pancreatitis
lined by fibrous tissue (no epithelial lining)
fluid rich in pancreatic enzymes or necrotic material
connect with ducts
risks
compresion of surrounding structures
infected
perforate releasing enzymes
what is IgG4 related disease
characterised by large numbers of IgG4 positive plasma cells
may involve pancreas, bile ducts and other parts
diagnosis by immunohistochemistry
responds well to steroids
Tumours of the pancreas
carcinomas
- DUCTAL (85%)
- ACINAR
cystic neoplasms
- SEROUS CYSTADENOMA
- MUCINOUS CYSTIC NEOPLASM
pancreatic neuroendocrine tumours
Most common carcinoma of pancreas and breast
ductal
risk factors of pancreatic carcinoma
smoking
raised BMI
chronic pancreatitis
diabetes
two preceding lesions of pancreatic carcinoma
Pancreatic intraductal neoplasia (PanIN)
Intraductal mucinous papillary neoplasm
what is the most common mutation in pancreatic carcinoma
K-ras 95%
features of carcinoma of the pancreas
gritty and grey
invades adjacent structures
tumours of head present earlier
adenocarcinomas
most common site of pancreatic carcinoma
head (60%)
ductal
how can pancreatic carcinomas metastasis (routs of invasion)
bile ducts, duodemum
lymphatic spread
blood to the liver
serosa to the peritoneoum
describe cystic adenomas of the pancreas
contain serous or mucin secreting epithelium
usually benign
describe pancreatic endocrine neoplasms
usually non secretory
contain neuroendocrine markers eg. chromogranin
may be associated with MEN1
insulinomas most common kind
what is an example of a neuroendocrine marker
chromogranin
(stain used to diagnose insulinoma)
describe gallstones (RFs and types)
RFs:
F>M
native americans
disorders of bile metabolism
oral contraceptive (oestrogen)
rapid weight loss
types:
- cholesterol gall stones (more than 50%)- single and radiolucent
- pigment stones (contain Ca salts of unconjugated bilirubin) - usually multiple and radio-opaque on AXR
complications of gall stones
obstruction - jaundice
cholecytstits
gall bladder cancer
pancreatitis
describe chronic cholecystitis
chronic inflammation
FIBROSIS and thickening of wall
diverticulae- ROKITANSKY-ASCHOFF SINUSES
90% of pts with chron chol have gall stones
what are ROKITANSKY-ASCHOFF SINUSES
out pocketing from diverticulae
generic complications og GI disease
diarrhoea, constipation
bleeding
perforation
fistula
obstruction
systemic illness
congenital GI diseases
bowel atresia/ stenosis - failure of development of normal lumen of the gut
duplucation
describe hirschsprungs disease
abscence of ganglion cells in submucosal and mysenteric plexus
starts in rectum
80% male
association with T21
RET proto-oncogene mutation
mutation in hirschprungs disease
RET proto-oncogene mutation
mechanical disorders of bowel
adhesions
herniation
extrinsic mass
volvulus (twists of bowel at mesenteric base around vascular pedicle)
diverticular disease
describe diverticular disease
low fibre diet
high intraluminal pressure
90% in left colon
outpouching of bowel
pseudodiverticula if doesnt contail all of the layers of bowel
complications of diverticular disease
pain
diverticulitis
perforation
fistula
obstruction
causes of acute and chronic inflammatory disorders of large bowel
acute
- infection (CMV, salmonella, entamoeba hystolitica, candida)
- drug/ toxin (esp Abx)
- chemo
- radiation
chronic
- IBD
- TB
examples of infective colitis
CMV- especially in immunocompromised eg. pts with IBD on medication
salmonalla
entamoeba hystolitica
candida
pseudomembranous colitis
following Abx therapy disrupting the microbiome allowing c diff to flourish
c. dif releases toxin
diagnosis look for c. dif toxin in stool assay
‘mushroom cloud’ on histology
pathology in splenic flexure likely to be casued by..
ischaemia
RFs for IBD
genetic predisposition to abnormal host immunoreactivity
infection (mycobacteria, measles)
microbiome
what organ contains the highest concentration of neuroendocrine cells
GUT
examples of non-noeplastic polyps
hyperplastic and sessile serrated lesions (flat on bowel)
pedunculated polyp- stalk ataching
inflammatory polyps
hamartomatous- malformed architexture of normal tissue (juvenile polyposis, peutz jeghers)
describe peutz jeghers
hamartomatous polyps
characteristic pigmentation around the lips soles and palms
autosomal dominant- LKB1
describe adenomas of large bowel
look darker than normal tissue
epithelial proliferation and dysplasia
types:
tubular
tubulovillus
villous- hypoproteinaemic hypokalaemia becuase they leak K and protein
RFs for adenomas to develop into cancer
size
number of polyps
villous adenoma
high degree of dysplasia
most common sites for adenoma and carcinoma
rectum and sigmoid
familial polyp syndromes
Peutz jeghers
FAP
lynch syndrome (HNPCC)
where is the mutation in FAP
chromosome 5q21 mutation in APC TSG
what is gardiners syndrome
FAP plus extra-intestinal manifestations
eg. osteomas
desmoid tumours
RFs of colorectal carcinoma
familial
low fibre, high fat diest
obesity
poor exercise
chronic IBD
adenoma
describe the TNM staging of colorectal cancer
Tumour, nodes, metastasis
what is a normal villous: crypt ratio
3-5:1
what is a normal number of lymphocytes in the small bowel
less than 20 intraepithelial lymphocytes/ 100 epithelial cells
characteristic findings of coeliac on biopsy
crypts increase (hyperplasia)as they are regenerating and replacing damaged epitheliasal cells
villous atrophy as damaged
increased intraepithelial lymphocyets
other causes of villous atrophy
drug associated enteropathy
giardia
H pylori gastritis
other causes of increase intra epithelial lymphocytes
food hypersensitivity
infection eg. giardia, H pylori
NSAIDS
RA, SLE, autoimmune enteropathy
management of coeliac
dietary management (exclue wheat, barley and rye)
advice RE long term complications: malabsorption, lymphoma, osteomalacia
MDT: pt support groups, dieticians, family support, gastroenterologist
Renal disease associated with Abs to phospholipase A2 receptor
membranous glomerulonephritis (nephrotic syndrome)
types of nephrotic syndrome
minimal change disease
membranous glomerulonephritis
focal segmental
types of nephritic syndrome
-post strep glomerulonephritis
-IgA nephropathy (Bergers)
-rapidly progressive disease
-Alports syndrome
-thin BM disease
pancreatic cancer tumour marker
CA19-9
complications of MI
contractile dysfunction -> cardiogenic shock
congestive cardiac failure
arrhythmias
mitral regurg (due to LV infact causing papillary muscle dysfunction)
dresslers pericarditis (weeks/months after)
Histological finding:
whirls of shed epithelium (curschmann spirals), eosinophils and charcot-Leyden crystals
Asthma
ground glass/ honeycomb appearance in CT
interstitial lung disease
types of interstitial lung disease and examples
FIBROSING
-idiopathic pulmonary fibrosis
- pneumoconiosis
- drug induced (eg. methotrexate, chemo)
GRANULOMATOUS
- sarcoidosis
- extrinsic allergic alveolitis
- vasculitides (GPA, churg-strauss, microscoping polyangiitis)
features of idiopathic pulmonary fibrosis
40-70y M>F
progressive exertional dyspnoea
non-productive cough
signs:
fine end-expiratory crackles
pulmonary hypertension +/- cor pulmonale(RHF)
clubbing
honeycomb/ ground glass appearance on CT (hyperplasia of type 2 pneumocytes causing cyst formation)
lung disease associated with coal miners
pneumoconiosis
- asbestososis mesothilioma/ adenocarcinoma or fibrosis
Causes of granulomatous lung lesion
Infectious:
TB
cryptococcus
aspergillus
pneumocystis
chronic granulomatous disease (inherited immune deficiency in NADPH)
non-infecitous:
Sarcoidosis
granulomatosis with polyangiitis
treatment of H.pylori
Triple therapy:
PPI
clarythromycin
amoxicillin
what do the different endocrine cells of the pancreas secrete
alpha cells- glucagon
beta- insulin
delta- somatostatin
D1- vasoactive peptide stimulates secretion of H20 into the pancreas
Pancreatic polypeptide- self regulates secretion
what exocrine enzymes does the pancreas secrete
amylase
lipase
proteases
different patterns of damage to the pancreas and associated causes
periductal- necrosis of acinar cells near ducts- suggests obstructive cause
perilobular- necrosis of edge of lobules (furthest away from blood supple)- suggest ischaemic causes
panlobular
what is the most sensitive marker of acute pancreatitis
serum lipase
managament of pancreatic carcinoma
whipples procedure (removal of tumour)
palliative chemotherapy with 5-Fluorouracil
Testicular tumours and tumour markers
germ cell:
seminoma - bHCG, LDH
yolk sac- AFP
choriocarcinoma - bHCG
teratoma- ?
what is spotty necrosis a sign of in the liver
acute hepatitis
what are the histopathological findings of chronic liver disease
- portal inflammation
- piecemeal necrosis (cannot see the border between portal tract and parenchyma)
- lobular inflammation
- bridging from portal vein to central vein- intrahepatic shunting
histopathology of cirrhosis
hepatocyte necrosis
fibrosis
nodules of regenerating hepatocytes
disturbance of vascular architecture
what is used to indicate the prognosis of liver cirrhosis and what does it involve?
Modified child pugh score (ABCDE)
Albumin
Bilirubin
Clotting (PT)
Distension (ascites)
Encephalopathy
causes of micronodules (regenerating nodules in the liver)
alcoholic hepatitis, biliary tract disease
causes of macronodules
(regenerating nodules in the liver)
viral hepatitis, wilsons disease, alpha A1 antitrypsin deficiency
how to score the components of the child pugh score
Albumin:
>35- 1
28-35 -2
<28 - 3
Bilirubin
<34 - 1
34-50 - 2
>50 - 3
Clotting PT
<4 - 1
4-6 - 2
>6 - 3
distension
none -1
mild -2
moderate/severe -3
Encephalopathy
none -1
mild -2
marked -3
sore <7 (45% 5yr survival)
7-9 (20% 5yr survival)
>9 (<20% 5yr survival)
describe the stages of alcoholic liver disease
- fatty liver
large, pale, yellow and greasy liver
accumulation of fat droplet in the hepatocytes
fully reversible if alcohol avoided - alcoholic hepatitis
large, fibrotic liver
hepatocyte balloning and necrosis due to accumulation of fat water and proteins
MALLORY DENK BODIES
fibrosis - alcoholic cirrhosis
shrunken, non fatty, brown
micronodular cirrhosis
bands of fibrous tissue
what causes NAFLD and what are the features
obesity with hyperlipidaemia
DM a risk factor
- simple steatosis- fatty infiltration
- non-alcoholic steatohepatitis- can progress to cirrhosis
what is the most common type of liver cancer
secondary metastases
(GI, breast, bronchus)
types of liver cancer
BENIGN
hepatic adenoma
haemangioma
MALIGNANT
hepatocellular carcinoma- AFP
cholangiocarcinoma - adenocarcinoma arising from bile ducts, 90% associated with gall stones
haemangiosarcoma - vascular endothelium, highly invasive
hepatoblastoma
secondary tumours
inherited causes of cirrhosis and their inheritance pattern
Haemachoromatosis- AR
Wilsons - AR
alpha a1- antitrypsin deficiency- AD
describe haemachoromatosis
AR
mutation in HFE gene at 6p21.3
increased gut Fe absorption which deposits in the liver, heart, pancreas, adrenals, pituitary, joints and skin
PRUSSIAN BLUE stain in histology
Signs
skin bronzing
DM
hepatomegaly
cardiomyopathy
high Fe, high ferritin, low TIBC, >45% transferrin saturation
Rx
venesection
desferrioxamine
describe wilsons disease
v. v rare
present 11-14yrs
AR
mutation in ATP7B which encodes for copper transporting ATPase
low Cu excretion and deposition in liver, CNS and iris
Rhodanine stain in histology
mallory bodies
signs
liver disease
parkinsonism, psychosis, dementia
kayser fleischer rings
low caeruloplasmin, low serum Cu, high urinary Cu
Rx
life long penicillamine
describe alpha a1 antitrypsin deficiency
AD
failure to secrete A1AT into the blood so it accumulates in the hepatocytes
lack of A1AT in lungs -> emphysema
stain with periodic acid schiff
signs
neonatal jaundica
emphysema and chronic liver disease
low serum A1AT
absent alpha globulin band on electrophoresis
Kimmelstiel Wilson nodules found in a renal biopsy are associated with what underlying disease?
diabetes
what is the composition of bone?
65% inorganic- calcium hydroxyapatite (99% Ca, 85% phos, 65% Na and Mg)
35% organic- bone cells and protein matrix
describe bone geography
from outermost layer to inner
periosteium –> matrix –> cortex
proximal
diaphysis –> metaphysis –> epiphysis
what are the bone cells
osteoblasts- build bone (single nucleus)
osteoclasts- chew bone (multinucleated, large cell, macrophage family)
osteocytes - sit in lacunae
describe the activation of osteoclasts
osteoblasts RANKL binds to RANKR on osteoclast precursor cells
this upregulates NFKb and triggers maturation into fully functioning osteoclast
where do you take a bone biopsy from to investigate metabolic bone disease
ileac crest
RFs for osteoporosis
> age
post menopausal
smoking
XS alcohol
female
long term immobility
poor diet
low BMI
thyroid disease
steroids
cushings
drugs eg: GNRH antagonists
what is a distal radial fracture called?
Colles fracture
what is a brown cell tumour and what is it characteristic of
hyperparathyrosididm
many multinucleated giant cells with haemorrhage
aka Osteitis fibrosa cystica (increased bone resorption)
what is a key feature of pagets on histology
Huge osteoclasts with >100 nuclei
Mosaic pattern of lamellar bone (like a jigsaw puzzle)
chinese lettering on histology
soap bubble lytic lesions
shepherds crook deformity
fibrous dysplasia
features of endrochondroma
affects hands and fingers
O ring sign
cotton wool calcification of matrix
features of osteosarcoma
adolescence
M>F
knees
Xray- sunburst appearance, codmans triangle (uplifting of periosteum)
Histo- malignant mesenchymal cells
Bloods- raised ALP
features of osteochondroma
> 40s
axial skeleton/ femur/ tibia/ pelvis
histo- malignant chondrocytes
Xray- lytic lesions with fluffy calcification
Features of ewings sarcoma
<20yrs
F>M
Histo: sheets of small round cells
CD99+
t(11;22) EWS:Fli1 translocation
XRAY: onion skinning of periosteium
McCune albright syndrome
fibrous dysplasia
precocious puberty
cafe au lait spots
Gardiners syndrome
multiple GI polyps
multiple osteomas
epidermal cysts
common infectious agents of osteomyelitis and sites
adult- 90% staph aureus
jaw and vertebrea- 2 to dental absecess
toe- 2 to diabetic foot
children- Haemophilus influenzae, GBS
Sickle cell patients - salmonella
Immunosuppressed- TB- spine (Potts disease: psoas abcess and skeletaldeformity)
congenital- syphilis
IVDU- pseudomonas
Xray features of osteoporosis
LOSS
Loss of joint space
Osteophytes
Subchondral sclerosis
Subchondral cysts
typical joints affected in osteoarthritis
Knees
hip
back
Distal interphalangeal joints (DIPJ)- Heberdens nodes
Proximal interphalangeal joints (PIPJ)- Bouchards nodes
special giant cells seen in RA
Grimly-Soholoff cells
process of fracture healing
- organisation of haematoma and periosteum proliferation
- fibocartilaginous callus deposition
- mineralisation of fibrinous deposition
- remodelling
types of fracture
simple
compound
greenstick
comminuted
impacted
crystal type in gout and pseudo gout
gout: urate crystals- negatively birefringent needles
Pseudogout: calcium pyrophosphate crystals - positively birefringent
Pseudo-Pos
Xray features of gout and pseudogout
gout: rat bite erosions
pseudo: white lines of chondrocalcinosis
most common cancers world wide (male and female combined)
- breast (15%)
- prostate (14%)
- Lung (13%)
- bowel (11%)
commonest cause of acute interstitial nephritis
drugs
The ECG leads V1 and V2 represent which specific region of the heart?
septal region
medication associated with hepatocarcinoma
OCP
mucin producing cancer
adenocarcinoma
whats the term given to non turbulent blood flow
laminar flow
how many grams of glucose is given in an OGTT
75g
what histological type of bladder cancer most common?
transitional cell
What histopathological description is given to cells that have lost their intercellular connections between neighbouring cells?
acantholysis
What monoclonal antibody therapy targets human epidermal growth factor receptor 2 and is used in the treatment of breast cancer?
trastuzumab
trust us you mab
defective protein in adult polycystic kidney disease
polycystin 1
PKD1 gene
found on chromosome 16
painless palpable mass and jaundice - what is the name of this sign?
Courvoisier’s sign
What is the most common histochemical stain used to visualise cells for light microscopy, such as that used for diagnosis of cancers?
Haematoxylin and eosin stain
presence of which receptor is associated with poor breast cancer prognsosis?
HER2
