Histo: Renal Disease Flashcards
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)
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
What proportion of cardiac output goes to the kidneys?
20%
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
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)
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
List some signs and symptoms of renal disease.
- Haematuria
- Proteinuria
- Uraemia
- Hypertension
- Oliguria/anuria
- Polyuria
- Oedema
- Colic
List some genitourinary malformations of the kidney.
- Agenesis
- Renal fusion
- Ectopic kidney
- Renal dysplasia
- PUJ obstruction
- Posterior urethral valve
- Vesicoureteric reflux
- Ureteral duplication
Outline the presentation of polycystic kidney disease.
- Hypertension
- Haematuria
- Flank pain
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)
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)
List some causes of acute renal failure.
- Pre-renal = failure of perfusion (shock, heart failure)
- Renal = ATN, acute glomerulonephritis, thrombotic microangiopathy
- Post-renal = obstruction
What is the most common cause of acute renal failure?
Acute tubular injury
List some causes of acute tubular injury.
Ischaemia
Toxins (contrast, haemoglobin, myoglobin, ethylene glycol)
Drugs
Which commonly used class of drugs predisposes to acute tubular injury?
NSAIDs - inhibits vasodilatory prostaglandins which predisposes to ATN
How does acute tubular injury lead to reduced GFR?
- Blockage of tubules by casts
- Leakage from tubules into interstitial space
- Secondary haemodynamic changes
What is acute tubulo-interstitial nephritis?
Immune injury to tubules and interstitium
Can be caused by infection and drugs (NSAIDs, antibiotics, diuretics, allopurinol, PPIs)
Describe the histological appearance of acute tubulo-interstital nephritis.
Heavy interstitial infiltration with eosinophil and granulomas
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
