Histo: Renal Disease Flashcards by Akash Srinivasan

List the major functions of the kidneys.

Excretion of metabolic waste products and foreign chemicals
Regulation of fluid, electrolytes and acid/base balance
Regulation of blood pressure (renin)
Regulation of calcium and bone metabolism (1,25-dihydroxy vitamin D)
Regulation of haematocrit (EPO)

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List some key anatomical features of the kidneys.

Retroperitoneal
T12-L3
Right kidney lies lower
Mean length = 11cm
Normal weight = 115-170g
1 million nephrons per kidneys

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What proportion of cardiac output goes to the kidneys?

20%

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By what mechanism is blood filtered through the glomerulus?

High hydrostatic pressure (60 mmHg)
Podocytes create a charge-dependent (anionic) and size-dependent barrier
Filtration rate = 125 ml/min

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Describe the role of the following parts of the nephron:

Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
Collecting duct

Proximal convoluted tubule
- Actively absorbs sodium
- Carries out hydrogen exchange to allow carbonate resoprtion
- Co-transport of amino acids, phosphate and glucose
- Reabsorption of potassium
Loop of Henle
- Descending limb and thin ascending limb: permeable to water, impermeable to ions and urea
- Ascending limb: actively resorbs sodium and chloride
- This creates a counter-current multiplier that is aligned with the vasa recta
Distal convoluted tubule
- Impermeable to water
- Regulates pH by active transport of protons and bicarbonate
- Regulates sodium and potassium by active transport (aldosterone)
- Regulates calcium (PTH, 1,25-dihydroxy vit D)
Collecting duct
- Reabsorb water (principal cells, ADH)
- Regulates pH (intercalated cells, proton excretion)

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Describe how immune complex deposition can lead to renal disease.

Complex deposition in the glomerulus results in complement and inflammatory cell activation resulting in damage to the kidney

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List some signs and symptoms of renal disease.

Haematuria
Proteinuria
Uraemia
Hypertension
Oliguria/anuria
Polyuria
Oedema
Colic

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List some genitourinary malformations of the kidney.

Agenesis
Renal fusion
Ectopic kidney
Renal dysplasia
PUJ obstruction
Posterior urethral valve
Vesicoureteric reflux
Ureteral duplication

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Outline the presentation of polycystic kidney disease.

Hypertension
Haematuria
Flank pain

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What is the inheritance pattern of polycystic kidney disease and which genes are implicated?

Autosomal dominant (most of the time)

Genes: PKD1 and PKD2

NOTE: PKD is associated with an increased risk of berry aneurysms (and subarachnoid haemorrhage)

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In which group of renal patients do renal cysts often develop?

Patients with end-stage renal disease who are on dialysis

Cysts are often multiple, bilateral and cortical and medullary

NOTE: cystic disease is associated with increased risk of malignancy (papillary renal cell carcinoma)

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List some causes of acute renal failure.

Pre-renal = failure of perfusion (shock, heart failure)
Renal = ATN, acute glomerulonephritis, thrombotic microangiopathy
Post-renal = obstruction

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What is the most common cause of acute renal failure?

Acute tubular injury

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List some causes of acute tubular injury.

Ischaemia

Toxins (contrast, haemoglobin, myoglobin, ethylene glycol)

Drugs

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Which commonly used class of drugs predisposes to acute tubular injury?

NSAIDs - inhibits vasodilatory prostaglandins which predisposes to ATN

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How does acute tubular injury lead to reduced GFR?

Blockage of tubules by casts
Leakage from tubules into interstitial space
Secondary haemodynamic changes

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What is acute tubulo-interstitial nephritis?

Immune injury to tubules and interstitium

Can be caused by infection and drugs (NSAIDs, antibiotics, diuretics, allopurinol, PPIs)

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Describe the histological appearance of acute tubulo-interstital nephritis.

Heavy interstitial infiltration with eosinophil and granulomas

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What causes crescents to appear in acute glomerulonephritis?

Occurs in severe glomerulonephritis due to proliferation of cells within Bowman’s capsule

List some causes of acute crescentic glomerulonephritis.

Immune complex deposition
Anti-GBM disease (Goodpasture’s)
Pauci-immune (ANCA)

NOTE: these can rapidly lead to irreversible renal failure

List some causes of immune complex-associated crescentic glomerulonephritis.

SLE
IgA nephropathy
Post-infectious glomerulonephritis

What techniques can be used to visualise immune complexes in these diseases?

Immunohistochemistry

Electron microscopy

What are the antibodies directed against in anti-GBM disease?

Against the C-terminal domain of type IV collagen

NOTE: these antibodies can cross-react with the alveolar basement membrane leading to pulmonary haemorrhage and haemoptysis

Describe the immunohistochemistry picture produced in anti-GBM disease,

Linear deposition of IgG on the glomerular basement membrane

What are the main features of pauci-immune crescentic glomerulonephritis?

* Scanty glomerular immunoglobulin depositis * Usually associated with ANCA * Triggers neutrophil activation and glomerular necrosis

What is thrombotic microangiopathy?

* Damage to the endothelium in glomeruli, arteriols and arteries resulting in thrombosis * Red cells can be damaged by fibrin causing MAHA or HUS

List some causes of thrombotic microangiopathy.

* Diarrhoea-associated: *E. coli* - toxins can target the renal epithelium * Non-diarrhoea associated: defects in complement regulation, deficiency of ADAMTS13, drugs, radiation, hypertension, scleroderma, antiphospholipid syndrome

What are the characteristic features of nephrotic syndrome?

* Proteinuria (\>3,5 g/day or \>300mg/mmol PCR) * Hypoalbuminaemia * Oedema * Hyperlipidaemia

List some causes of nephrotic syndrome.

* **Primary glomerular disease (non-immune complex mediated)** * Minimal change disease * Focal segmental glomerulosclerosis * **Primary renal disease (immune complex mediated)** * Membranous glomerulonephritis * **Systemic disease** * SLE * Amyloidosis * Diabetes mellitus

What is minimal change disease?

* most common cause of nephrotic syndrome in children * Glomeruli look normal on light microscopy, but electron microscopy shows loss of foot processes * Generally responds well to steroids and immunosuppression

Describe the histological appearance of focal segmental glomerulosclerosis.

Some glomeruli are partially scarred NOTE: this responds less well to immunosuppression

What is membranous glomerulonephritis?

* Common cause of nephrotic syndrome in adults * Characterised by immune deposits outside the glomerular basement membrane (subepithelial) * Primary disease is autoimmune * It can occur secondary to epithelial malignancy, SLE, drugs and infections

Which antibodies are often found in primary membranous glomerulonephritis?

Antibodies against phospholipase A2 type M receptor (PLA2R)

Describe the typical progression of diabetic nephropathy.

Typically begins with microalbuminuria Progresses to proteinuria and, eventually, nephrotic syndrome

List and describe the stages of diabetic nephropathy.

* Stage 1: thickening of the basement membrane on electron microscopy * Stage 2: increase in mesangial matrix, without noduls * Stage 3: nodular lesions/Kimmelstein-Wilson nodules * Stage 4: advanced glomerulosclerosis

What is amyloidosis?

Deposition of extracellular proteinaceous material exhibiting beta-pleated sheet structure

What are the two types of amyloidosis?

* AA - derived from serum amyloid protein and associated with chronic inflammatory disease * AL - derived from immunoglobulin light chains usually as a result of multiple myeloma

Name two causes of isolated microscopy haematuria.

* Thin basement membrane * IgA nephropathy

How can the cause of asymptomatic proteinuria be confirmed?

Renal biopsy (could be caused by several abnormalities)

What is thin basement membrane disease and what causes it?

* Basement membrane \<250 nm thickness * Caused by a hereditary defect in type IV collagen synthesis * Microscopic haematuria is the only consequence in most cases

What is Alport syndrome?

* X-linked disease caused by a mutation in the alpha-5 subunit of type IV collagen (some forms affect alpha-3 and alpha-4) * Leads to progressive damage resulting in renal failure in middle-age * Often accompanied by deafness and ocular disease

What is IgA nephropathy?

* Most common cause of glomerulonephritis * Caused by mesangial IgA immune complex deposition * 30% will progress to end-stage renal failure NOTE: Henoch-Schonlein purpura is a type of IgA nephropathy

List some causes of chronic kidney disease and state which is most common.

* Diabetes mellitus * Glomerulonephritis * Polycystic kidney disease * Pyelonephritis * Hypertension * Renal vascular disease

What are some diseases associated with chronic kidney disease?

* Ischaemic heart disease * Calcium and phosphate derangement (due to resulting hyperparathyroidism, osteomalacia and osteoporosis)

What are consequences of hypertensive nephropathy?

* Shrunken kidneys with granular cortices * Nephrosclerosis on histology (arterial hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis)

What system is used to classify lupus nephritis?

ISI/RPS classification