Pathology 2 Flashcards
Glomerular lesion terminology
Focal - less than 50% all gloms involved
Diffuse - more than 50%
Segmental - less than 50% of individual glom involved
Global - more than 50% of individual glom
Causes of glomerular diseases
Primary
Secondary to systemic disorder - DM, SLE, vasculitis, amyloidosis, HTN
What happens in primary glomerular disease?
Usually immune mediated
AB against a constituent of the glom e.g. bm
AB against somethign that has been deposited in the glom
Deposition of a circulating Ag-Ab immune complex
This produces an inflammatory response –> tissue damage –> decreased GFR (tubular injury) and production of ECM (sclerosis + obliteration of glom)
Histological alterations in glomeruli
Hypercellularity
BM thickening
Hyalinisation + sclerosis
Acute glomerulonephritis
Haematuria, increased Cr and Ur, oliguria +/- proteinuria
Inflammatory alteration in glomeruli
Causes of acute glomerulonephritis
Postinfectious e.g. children following a streptococcal infection (skin, pharynx) - anti-streptococcal ABs
Necrotising/crescentic - anti-GBM, immune complex mediated, ANCA associated - these are poor prognosis + most need dialysis
Nephrotic syndrome
Massive proteinuria (Causing oedema) Hyperlipidaemia
Hypoalbumin, proteinuria, hyperlipidaemia, oedema
Causes of nephrotic syndrome
Membranous nephropathy
Minimal change disease
FSGS
Membranous nephropathy
Most common cause in adults
Diffuse thickening of GBMs
Subepithelial immune complex deposition
Anti-PLA2R ABs
Minimal change disease
Most common in children 2-6yrs Normal glomeruli on microscopy EM fusion of epithelial foot processes Follows respiratory tract infection Responds to steroids
Causes of haematuria with normal renal function
IgA nephropathy (deposits of IgA in mesangium)
Alports syndrome
Thin glomerular BM disease
Chronic glomerulonephritis
End stage of acute
Chronic renal failure
Small symmetrical kidneys
Diffusely granular surface
Diabetic nephropathy
Leading cause of chronic renal failure
Thickening of GBMs
Mesangial increase +/- nodules
Amyloidosis
Abnormal proteinaceous material deposited in tissues
Congo red +ve + birefringence under polarised light
Primary - light chains - multiple myeloma
Secondary - chronic disease e.g. TB, Crohns
Hypertension in the kidneys
Affects arteries + arterioles
Intimal thickening with narrowing of lumen
Hyalinosis
Leads to ischaemic changes in the kidney - glomerular sclerosis, tubular atrophy, IS fibrosis
Chronic pyelonephritis
Chronic tubulointerstitial inflammation
2 forms: obstructive + reflux nephropathy
Assymetrical irregular kidneys, coarse discrete corticomedullary scar overlying a dilated, blunted or deformed calyx
What are lines of Zahn?
Feature of thrombi that occur particularly when formed in the heart or aorta
Alternating layers of plts + fibrin (pale) and RBCs (darker)
Virchow’s triad
Changes in vessel wall (endothelial damage)
Changes in BF (stasis, turbulence)
Changes in blood composition (many e.g. COCP, Ca, polycythaemia, myeloproliferative disorders)
What are arterial thrombi made up of?
Rapid flow - mainly plts (pale)
Mural or occlusive depending on SIZE of vessel
Predisposing factors usually endo damage
What are venous thrombi made up of?
Slow flow - mainly blood clot (red)
Usually occlusive
Predisposing factors cause abnormalities of BF
What happens when a thrombus is formed?
Resolution (dissolution of clot by fibrinolysis)
Organisation - ingrowth of fibroblasts, capillaries, phagocytes (granulation tissue)
Recanalisation - restore original lumen
OR
Fibrosis - formation of webs, cords
What is an embolus?
Passage of insoluble mass within the blood steam and impaction at a site distant from its point of origin
What are emboli made of?
> 95% are dislodged thrombi
Other: fat, air, tumour, amniotic fluid, infective material
Emboli sites of impaction
Pulmonary arteries - thrombi from veins, R side of heart
Systemic arteries - thrombi from L side of heart + aorta
Causes of ischaemia
Intrinsic disease of vessel e.g. atherosclerosis
Occlusion by thrombus/embolus
External compression of artery
Stages of infarction
- Necrosis 6-12h
- Acute inflammation 24h-7d
- Organisation 3d-2wks
- Scar formation 2wks-3m
Consequences of a pulmonary embolism
- Sudden death - massive embolism
- Pulmonary infarction - pulmonary venous congestion, haemorrhagic, peripheral, wedge shaped (due to venous back pressure)
- Pulmonary HTN
- Asymptomatic
Clinical manifestations of a pulmonary infarct
Haemoptysis - cough up to get rid
Pleuritic chest pain - pain as pleurae laying over it will become inflammed
The peak time at which V wall rupture occurs following MI is:
4-10 days
Dead muscle starts to break down + very weak as no collagen yet so susceptible to rupture
What is gangrene?
Necrosis + superadded bacterial infection
Commonest type of skin cancer
Basal cell carcinoma (75%)
What % of lung cancers are central (carina, main + lobar bronchi)
70%
How do you describe a basal cell carcinoma?
Enlarging annular plaque with focal ulceration and rolled out margin on nose
Where does basal cell carcinoma arise from?
The epidermis
Histological subtypes of BCC
Nodular
Superficial
Infiltrative (aggressive)
Micronodular (aggressive)
What do you see in histology of squamous cell carcinoma?
Keratin pearls + infiltrative nests of malignant squamous cells
Which biopsies are used for which skin cancer?
Skin punch biopsy - basal and squamous cell carcinoma
Excision biopsy - melanoma
Subtypes of melanoma
Superficial spreading (most common - significant epidermal component)
Nodular
What is used to assess the stage of melanoma?
Breslows thickness Clark's scale Microsatellites Mitotic figures Ulceration Vascular invasion
Not size or diameter
Which skin cancer is not associated with metastasis
Basal cell carcinoma
What determines the stage in basal and squamous cell carcinoma?
Size and diameter
What determines the stage in melanoma?
Thickness
How many lung cancers are treated by surgery?
15%
Where does paracetemol cause damage in the liver?
Perivenular/centrilobular - furthest away from portal blood supply where P450 enzymes greatest
Pattern of damage in liver disease
Fatty change - steatohepatitis/fibrosis - cirrhosis
Fatty liver disease histology
Macrovesicular staeatosis - stored as triglycerides that take over the cytoplasm
Steatohepatitis histological features
Hepatocellular injury - fatty change, ballooning, mallory-denk bodies, apoptosis/necrosis
Inflammation
Fibrosis - perisinusoidal, pericellular
what increases the risk of cholangiocarcinoma?
PSC - get premalignant changes due to periods of ucleration + regeneration
Features of liver cirrhosis
Loss of normal lobular architecture
Nodular regeneration
Fibrosis
How does skin heal?
Primary or secondary intention
Primary intention
1 linear incision - can bring 2 ends together
Secondary intention
e.g. leg ulcer - can’t bring together 2 ends so leave open, epidermis grows up + takes longer to heal
Strength of a wound
10% at week 1
50-60% at 1m
70-80% plateau at 3m
What are the 2 ways the liver heals?
Resolution - normal liver
Repair - cirrhosis - failure of resolution –> nodules surrounded by fibrous tissue + lose structural integrity of sinusoids so can’t go back to normal
What regulates liver repair?
Stellate + kupffer cells produce GFs + cytos which stimulate healing
HGF plays key role in stimulating hepatocytes to enter cell cycle
TGF-B one of key regulators of fibrosis
Deposited collagen remodelled by MMPs and TIMPs
what factors influence healing of the liver?
Time course of injury e.g. paracetamol cause liver injury at 1 time point so no cirrhosis v alcohol which is less severe injury over long period so cirrhosis
Anatomic site of injury - damage to parenchyma e.g. alcohol causes cirrhosis with fibrosis mediated by stellate cells in sinusoids
what is hypoplasia?
NOT THE OPPOSITE OF HYPERPLASIA
failure of tissue/organ to reach normal size during development e.g. genetic defects
What is atrophy?
decrease in size of tissue/organ at a stage after initial dvelopment. may be decrease in cell size or number
what is metaplasia?
replacement (potentially reversible) of 1 differentiated cell type by another differentiated cell type
What is dysplasia?
Disordered development
Changes resemble those seen in neoplastic cells - not yet invasive but can progress to invasive carcinoma if not treated
Oncocytomas
Benign
Unformally large cells with eosinophils
Chromophobes
Perinuclear halos
Clear cell carincoma
Large cells with clear cytoplasm
Transitional cell carcinoma
Papillary architecture with layers of urothelium
Papillary
Papillae and eosinophilic cells. Foci of calcification
Which zone of the prostate is BPH in?
Transitional
Which zone of the prostate is cancer in?
Peripheral
Eosinophilic oesophagitis
Hx of allergy + eosinophilia
Dysphagia
Mid oesophagus
Endoscopy: concentric rings ‘trachealisation’ of oesophagus
Coeliac
Villous atrophy
Intra epithelial lymphocytosis
Chronic inflammation in lamina propria
Crypt hyperplasia
UC
Uniform diffuse lesions Superficial - mucosa Associated with PSC Absence of granulomas Cryptitis and crypt abscess formation Crypt mucin depletion
Crohns
Typically ileocaecal junction
Segmental lesions
Deep lesions up to serosa - patchy ulceration, abscesses, fissures, lymphoid hyperplasia, epithelioid granulomas
