renal pathology Flashcards

Question

summarise acute tubulo-interstitial nephritis

Answer 1

Immune injury to tubules and interstitium Can also be due to infection and drugs * NSAIDs * Antibiotics * Diuretics * Allopurinol * Proton Pump Inhibitors Heavy interstitial inflammatory infiltrate with tubular injury * Can see eosinophils, granulomas – **drugs are the most common cause**

Answer 2

**Acute inflammation of glomeruli** Presents with * oliguria * **urine casts containing erythrocytes and leucocytes** – because of inflammation in glomeruli When sufficient to cause acute renal failure, there are almost always **crescents** - **Proliferation of cells within Bowman’s space**

Answer 3

when **most glomeruli have cresents** caused by: * Immune Complex * Anti Glomerular Basement Membrane Disease * Pauci-immune (anti-neutrophil cytoplasm antibodies) – means could be some immune complex deposition eg in ANCA vasculitis Leads rapidly to irreversible renal failure **Correct diagnosis and treatment are urgent**

Answer 4

caused by: * SLE * IgA nephropathy * Post-Infectious Glomerulonephritis Immune complexes can be identified and localised with **immunohistochemistry and electron microscopy** Final diagnosis depends on specific findings interpreted within the appropriate **clinical context**.

Answer 5

*Rare and severe disease* **antibodies directed against the glomerular basement membrane** Ab against **C-terminal domain of Type IV collagen** May **cross-react with alveolar basement membrane -> pulmonary haemorrhage** Antibody may be detected with **serology** **Linear deposition of IgG** demonstrable on **glomerular basement membrane** **silver stain**

Answer 6

Only **scanty glomerular immunoglobulin deposits** Usually **ANCA-associated** Trigger **neutrophil activation and glomerular necrosis** Vasculitis elsewhere Cresental necrosis

Answer 7

**Damage to endothelium** in glomeruli, arterioles, arteries **leading to thrombosis** Loops are full of thrombus Arterioles are blocked with cellular material and thrombin Red cells may be damaged by fibrin -> * Microangiopathic haemolytic anaemia * Haemolytic Uremic Syndrome

Answer 8

Diarrhoea associated * Bacterial gut infection such as with **E. coli** * Toxins released that target renal endothelium Non-Diarrhoea associated * Defects in regulation of complement * Deficiency in ADAMTS13 * Drugs (calcineurin inhibitors) * Radiation * Hypertension * Scleroderma * Antiphospholipid Antibody Syndrome (+/- SLE)

Answer 9

Breakdown in selectivity of glomerular filtration barrier leading to protein leak Proteinuria (>3.5g/day) Hypoalbuminemia Oedema Hyperlipidaemia

Answer 10

Primary Glomerular Disease, Non-Immune Complex Related * Minimal Change Disease * Focal Segmental Glomerulosclerosis Primary Renal Disease, Immune Complex Mediated * Membranous Glomerulonephritis Systemic Disease * Diabetes mellitus * Amyloidosis * SLE

Answer 11

* Glomeruli look **normal by light microscopy** * **Effacement of foot processes** on electron microscopy * Common cause of nephrotic syndrome in **children** * Generally **responds to immunosuppression**

Answer 12

def: **Some glomeruli are partially scarred** Less likely to respond to immunosuppression – once have scarring it is less likely to go away **No immune complexes** Must exclude possible other diseases that can produce a similar appearance * These tend not to be nephrotic * IgA nephropathy * Lupus

Answer 13

Associated with **immune deposits (IgG and C3)** on outside of glomerular basement membrane **Subepithelial -> impair function of podocytes** Common cause of nephrotic syndrome in **adults** **Primary disease is autoimmune** * Antibody against phospholipase A2 type M receptor **(PLA2R)** in 75% of cases Need to exclude secondary disease * Epithelial malignancy, * drugs, * infections, * SLE Interpret findings in clinical and serological context

Answer 14

30-40% of diabetics High glucose levels thought to be directly injurious Typically starts as microalbuminuria -> proteinuria -> nephrotic syndrome

Answer 15

Nodular Glomerulosclerosis * Stage 1 – Thickening of basement membrane on EM * Stage 2 – Increase in mesangial matrix, without nodules * Stage 3 – Nodular lesions / Kimmelstiel-Wilson * Stage 4 – Advanced glomerulosclerosis

Answer 16

Abnormally folded protein material **Deposition of extracellular proteinaceous material exhibiting β-sheet structure** Commonest forms in kidney are * **AA**, derived from serum amyloid associated protein (SAA), an acute phase protein; patients tend to have a **chronic inflammatory state** * **AL,** derived from immunoglobin light chains; **80% of patients have multiple myeloma**

Answer 17

Microscopic Haematuria * Thin basement membranes * IgA Nephropathy Asymptomatic Proteinuria * May be associated with a broad range of glomerular structural abnormalities or immune complex deposition * Diagnosis often requires renal biopsy for histology, immunohistochemistry and electron microscopy

Answer 18

Hereditary **defect in Type IV collagen synthesis** Basement membrane **less than 250nm thickness** Haematuria is only consequence in most cases

Answer 19

**X-linked dominant** mutations affecting **⍺5 subunit** Forms exist in which mutation affects ⍺3 or ⍺4 subunit Typically **progressive, renal failure in middle age** Often have **deafness, ocular disease** Show **normal or thickened BM – but look like branching tissue**

Answer 20

*Commonest glomerulonephritis* **IgA predominant mesangial immune complex deposition** Aetiology not well understood in primary form Secondary forms observed in liver, bowel and skin disease Can be **seen with small-vessel vasculitis (Henoch-Schönlein Purpura)** 30% develop end stage renal failure

Answer 21

Oxford Classification (MEST-C) – *scoring in any of these = worse px – higher = more likely end stage renal failure* * M – how many cells in mesangium – 1 = too much, 0 = right amount * E – endocapillary proliferation * S – segmental scarring * T – tubular atrophy less than 25% 25-50% >50% * C – cresents – yes in some, yes in a lot, no

Answer 22

ischaemic heart disease * Hypertension, * hyperlipidaemia, * calcification of blood vessels Association with calcium and phosphate metabolic derangement * Hyperparathyroidism * osteomalacia * osteoporosis Not always clear which is the driver and what is the cause

Answer 23

Diabetes – 27.5% Glomerulonephritis – 14.1% Polycystic Kidney Disease – 7.4% Pyelonephritis – 6.5% Hypertension – 6.8% Renal Vascular Disease – 5.9% Other / Uncertain – 31.7%

Answer 24

Pathophysiology is not fully understood Narrowing of arteries and arterioles -> scarring and ischaemia of glomeruli Hypertension in glomeruli -> altered haemodynamic environment, stress and segmental scarring Shrunken kidneys with granular cortices **Histopathology may show “nephrosclerosis”** * Arteriolar hyalinosis, * arterial intimal thickening, * ischaemic glomerular changes, * segmental and global glomerulosclerosis

Answer 25

* SLE is a systemic autoimmune disease * Affects the kidney, skin, joints, heart, serosal surfaces and the central nervous system * common * > women * Deposition of immune complexes in the kidney is common * Anti-nuclear and Anti-dsDNA antibodies are typical

Answer 26

Highly variable disease Depending on site, speed and intensity of immune complex deposition, may present as: * Acute Renal Failure * Nephrotic Syndrome * Isolated Urinary Abnormality * Chronic Kidney Disease