L5 - Renal Pathology Flashcards
What are the primary functions of the kidney?
The kidney filters blood, excretes waste products, regulates water and salt balance, maintains acid–base balance, and functions as an endocrine organ.
How much blood does the kidney filter daily and what is the approximate urine output?
Approximately 1700 litres of blood are filtered daily, producing around 1 litre of urine.
What anatomical structure is essential for blood filtration in the kidney?
The glomerulus, an anastomosing network of capillaries, is central to the filtration process.
Why is the glomerular barrier function critical?
It allows water and small solutes to pass while preventing the loss of large protein molecules.
What defines nephrotic syndrome clinically?
Nephrotic syndrome is characterised by heavy proteinuria (>3.5g/day), hypoalbuminaemia, severe oedema, hyperlipidaemia, and lipiduria.
How does minimal change disease (MCD) present histologically?
MCD shows normal light microscopy with diffuse podocyte foot process fusion on electron microscopy.
What are the key features of membranous glomerulopathy?
It is marked by subepithelial electron-dense deposits along the basement membrane, with an antigen–antibody mediated pathogenesis.
What distinguishes focal segmental glomerulosclerosis (FSGS) from other causes of nephrotic syndrome?
FSGS involves segmental scarring of some glomeruli and is often associated with conditions like HIV, obesity, or hypertension.
What is the renal impact of diabetic glomerulopathy?
It leads to thickening of the basement membrane and increased mesangial matrix due to hyperglycaemia and advanced glycation end-products.
How is amyloidosis identified in the kidney?
Amyloidosis is demonstrated by the deposition of amorphous eosinophilic material that shows apple-green birefringence under polarised light after Congo red staining.
What are common features of lupus nephritis in systemic lupus erythematosus (SLE)?
SLE shows a range of histological patterns with immune complex deposition, and is associated with a positive ANA and anti-dsDNA on immunofluorescence.
How can chronic glomerular diseases progress to renal failure?
Ongoing damage from proteinuria, inflammatory processes, and scarring ultimately lead to chronic renal insufficiency.
What are typical clinical manifestations of acute nephritic syndrome?
Haematuria, mild to moderate proteinuria, and hypertension are characteristic.
How is chronic renal failure identified clinically?
Chronic renal failure may be asymptomatic initially but is later recognised by reduced glomerular filtration rate and accumulation of metabolic waste.
What role do electron microscopy and immunofluorescence play in renal pathology?
They provide detailed insights into glomerular ultrastructure and immune complex deposition, essential for diagnosing specific glomerulopathies.
Why is precise diagnosis of glomerular disease critical for patient management?
Accurate diagnosis directs appropriate therapy, which can improve prognosis and prevent progression to end-stage renal disease.
How does the composition of the glomerular basement membrane contribute to its selectivity?
Its network of collagen, laminin, and proteoglycans forms a charge- and size-selective barrier essential for filtration.
What ultrastructural change is diagnostic for minimal change disease?
Diffuse effacement of podocyte foot processes seen on electron microscopy.
How do immunofluorescence patterns help distinguish membranous glomerulopathy?
Granular immunoglobulin deposits along the capillary wall indicate immune complex deposition.
What role does podocyte injury play in the development of proteinuria?
Damage disrupts the slit diaphragm, leading to leakage of protein into the urine.
How does focal segmental glomerulosclerosis (FSGS) contribute to chronic kidney disease?
Progressive scarring in parts of some glomeruli reduces overall filtration capacity, leading to renal insufficiency.
What are the key electron microscopic features in diabetic glomerulopathy?
A thickened basement membrane, mesangial expansion, and sometimes nodular glomerulosclerosis.
How does amyloidosis present differently from other glomerular diseases on electron microscopy?
Amyloid deposits appear as non-branching fibrils approximately 7.5–10 nm in diameter.
What clinical criteria help define acute nephritic syndrome?
Haematuria, hypertension, and moderate proteinuria are the hallmarks of acute nephritic syndrome.
What is the primary functional unit of the kidney?
The nephron
What three layers make up the glomerular filtration barrier?
Fenestrated endothelium, glomerular basement membrane, podocytes
Which part of the nephron is responsible for the majority of sodium reabsorption?
Proximal convoluted tubule
What is the main function of the proximal tubule?
Reabsorption of water, electrolytes, and nutrients; secretion of waste products
What is the role of the loop of Henle in urine concentration?
Establishes a concentration gradient to facilitate water reabsorption in the collecting duct
What hormone regulates water reabsorption in the collecting duct?
Antidiuretic hormone (ADH)
Which ion is most important in regulating extracellular fluid volume?
Sodium (Na⁺)
What is the role of the juxtaglomerular apparatus?
Regulates blood pressure via renin secretion
How does the kidney contribute to acid–base homeostasis?
Excretes hydrogen ions and reabsorbs bicarbonate to maintain pH balance
What is the role of aldosterone in renal physiology?
Increases sodium reabsorption and potassium excretion in the distal tubule
What are the histological features of acute tubular injury?
Tubular epithelial necrosis, loss of brush border, and granular casts
How does hypertension contribute to kidney disease?
Causes endothelial damage, leading to glomerulosclerosis and nephron loss
What are the common causes of acute kidney injury?
Ischaemia, nephrotoxins, sepsis
What distinguishes nephritic syndrome from nephrotic syndrome?
Nephritic syndrome presents with haematuria, hypertension, and mild proteinuria, whereas nephrotic syndrome is characterised by heavy proteinuria, hypoalbuminaemia, and oedema
What is the most common cause of nephrotic syndrome in adults?
Focal segmental glomerulosclerosis (FSGS)
What immune mechanism underlies membranous nephropathy?
Immune complex deposition along the basement membrane
What is the characteristic finding in post-infectious glomerulonephritis?
Subepithelial humps of immune complexes
Which type of hypersensitivity reaction is involved in anti-GBM disease?
Type II hypersensitivity reaction
How does IgA nephropathy typically present?
Episodic haematuria, often following an upper respiratory infection
What is the characteristic light microscopic finding in rapidly progressive glomerulonephritis (RPGN)?
Crescents composed of fibrin and macrophages within Bowman’s space
How is Alport syndrome diagnosed?
Genetic testing for mutations in COL4A5 and characteristic lamellated basement membranes on electron microscopy
What are the characteristic features of thrombotic microangiopathies affecting the kidney?
Endothelial injury, thrombosis, and microangiopathic haemolytic anaemia
What are the primary causes of haemolytic uraemic syndrome?
Shiga toxin-producing Escherichia coli (STEC) infection, complement dysregulation
How does sickle cell disease affect renal function?
Medullary infarction, haematuria, proteinuria, and papillary necrosis
Which glomerular disease is most commonly associated with HIV infection?
Collapsing focal segmental glomerulosclerosis (FSGS)
What renal changes are seen in multiple myeloma?
Cast nephropathy due to light chain deposition
How do NSAIDs contribute to kidney injury?
Acute interstitial nephritis, renal papillary necrosis
What is the renal impact of lithium therapy?
Nephrogenic diabetes insipidus, chronic tubulointerstitial nephropathy
Which systemic disease is most commonly associated with crescentic glomerulonephritis?
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
What is the pathophysiology of hypertensive nephrosclerosis?
Hyaline arteriolosclerosis, glomerular ischaemia, interstitial fibrosis
How does chronic kidney disease (CKD) affect bone metabolism?
Hyperphosphataemia, decreased vitamin D activation, secondary hyperparathyroidism
What is the most common cause of end-stage renal disease?
Diabetes mellitus
What laboratory findings indicate acute kidney injury?
Elevated serum creatinine, blood urea nitrogen (BUN), and metabolic acidosis
How does the kidney compensate for decreased perfusion in prerenal AKI?
Activation of the renin-angiotensin-aldosterone system to increase blood pressure and sodium retention
What is the significance of muddy brown casts in urine microscopy?
Granular casts composed of necrotic tubular epithelial cells
How does chronic kidney disease lead to secondary hyperparathyroidism?
Phosphate retention stimulates parathyroid hormone (PTH) secretion, leading to bone resorption
What are the main clinical features of uraemia?
Fatigue, anorexia, nausea, pruritus, pericarditis
Which imaging modality is most useful for diagnosing renal artery stenosis?
Doppler ultrasound, magnetic resonance angiography (MRA)
What is the most common cause of drug-induced acute interstitial nephritis?
NSAIDs, antibiotics (e.g., beta-lactams), proton pump inhibitors
How does myoglobinuria cause acute kidney injury?
Myoglobin is toxic to renal tubules, causing acute tubular necrosis
What is the pathogenesis of contrast-induced nephropathy?
Vasoconstriction and oxidative stress from contrast media exposure
What are the primary indications for kidney biopsy?
Unexplained proteinuria, haematuria, or renal dysfunction
Which metabolic derangements are common in chronic kidney disease?
Hyperkalaemia, metabolic acidosis, hypocalcaemia, hyperphosphataemia
What is the role of erythropoietin in renal disease?
Stimulates red blood cell production in response to hypoxia
How does nephrotic syndrome contribute to hypercoagulability?
Urinary loss of antithrombin III and increased fibrinogen levels promote clot formation
What is the pathogenesis of lupus nephritis?
Immune complex deposition and complement activation
Which autoantibody is most specific for lupus nephritis?
Anti-dsDNA
What are the histological classes of lupus nephritis?
Class I (minimal), II (mesangial), III (focal proliferative), IV (diffuse proliferative), V (membranous), VI (advanced sclerosis)
What is the key finding in pauci-immune glomerulonephritis?
Pauci-immune crescentic glomerulonephritis shows no immune deposits on immunofluorescence
How does the kidney contribute to systemic hypertension?
Increases blood volume by regulating sodium and water retention
What are the most common causes of papillary necrosis?
Diabetes mellitus, sickle cell disease, analgesic nephropathy
What is the typical presentation of renal cell carcinoma?
Flank pain, haematuria, and an abdominal mass
Which paraneoplastic syndromes are associated with renal cell carcinoma?
Paraneoplastic erythrocytosis, hypercalcaemia, hypertension
What are the histological subtypes of renal cell carcinoma?
Clear cell carcinoma, papillary carcinoma, chromophobe carcinoma
Which genetic syndrome is associated with multiple renal cysts?
Von Hippel–Lindau syndrome
What is the most common cause of autosomal dominant polycystic kidney disease?
PKD1 or PKD2 gene mutation leading to cyst formation
How does medullary sponge kidney differ from polycystic kidney disease?
Medullary sponge kidney is non-hereditary and characterised by cystic dilation of collecting ducts
What is the typical presentation of nephrocalcinosis?
Nephrolithiasis and nephrocalcinosis
Which renal disease is most commonly associated with hyperuricaemia?
Gouty nephropathy, urate nephrolithiasis
What are the key histological features of chronic pyelonephritis?
Tubular atrophy, thyroidisation of tubules, interstitial fibrosis
How does vesicoureteral reflux contribute to renal pathology?
Chronic reflux leads to scarring and atrophy of renal parenchyma
What is the most common bacterial cause of acute pyelonephritis?
Escherichia coli
What are the characteristic findings in xanthogranulomatous pyelonephritis?
Foamy macrophages, giant cells, chronic inflammation
What is the most common cause of obstructive uropathy in older men?
Benign prostatic hyperplasia (BPH)
How does urinary tract obstruction lead to renal dysfunction?
Hydronephrosis, decreased glomerular filtration rate (GFR)
What is the characteristic finding in renal papillary necrosis?
Coagulative necrosis of renal papillae
What is the role of the renin-angiotensin-aldosterone system in kidney disease?
Regulates blood pressure and fluid balance through renin and aldosterone
How do ACE inhibitors affect renal function?
Dilate efferent arterioles, decreasing glomerular pressure
Which renal condition is commonly associated with sarcoidosis?
Granulomatous interstitial nephritis
What is the role of podocyte injury in nephrotic syndrome?
Disruption of podocyte slit diaphragm leads to increased permeability to proteins
How does C3 glomerulopathy differ from immune complex-mediated glomerulonephritis?
C3 glomerulopathy results from alternative complement pathway dysregulation
What is the typical presentation of fibromuscular dysplasia in the kidney?
Young woman with hypertension, renal artery stenosis
How does the kidney regulate phosphate balance?
Regulates phosphate excretion and vitamin D metabolism
What is the role of FGF23 in phosphate homeostasis?
Inhibits phosphate reabsorption and vitamin D activation
How does renal osteodystrophy develop in CKD?
Osteitis fibrosa cystica, adynamic bone disease
What are the characteristic findings in thin basement membrane disease?
Uniformly thin glomerular basement membrane
What is the genetic inheritance pattern of Alport syndrome?
X-linked dominant inheritance
Which renal pathology is associated with ANCA-positive vasculitis?
ANCA-associated vasculitis (e.g., granulomatosis with polyangiitis)
How does chronic kidney disease contribute to cardiovascular disease?
Increases cardiovascular risk via hypertension, dyslipidaemia, and vascular calcification
What is the pathophysiology of renal anaemia?
Deficient erythropoietin production, leading to normocytic anaemia
Which electrolyte disturbances are common in end-stage renal disease?
Hyperkalaemia, hyperphosphataemia, metabolic acidosis, hypocalcaemia
What are the histological findings in acute tubulointerstitial nephritis?
Interstitial oedema, eosinophilic infiltrate, tubulitis
How does Fanconi syndrome affect renal tubular function?
Proximal tubular dysfunction, leading to loss of glucose, amino acids, phosphate, and bicarbonate
What is the typical presentation of Bartter syndrome?
Hypokalaemia, metabolic alkalosis, polyuria, failure to thrive
Which genetic mutation is associated with Gitelman syndrome?
SLC12A3 gene mutation affecting thiazide-sensitive sodium chloride cotransporter
What are the renal complications of obstructive sleep apnoea?
Hypertension, proteinuria, nocturia
How does hyperaldosteronism affect renal function?
Hypernatraemia, hypokalaemia, metabolic alkalosis
What are the renal manifestations of tuberous sclerosis?
Renal angiomyolipomas, cysts, and increased risk of renal cell carcinoma
What is the main difference between nephrogenic diabetes insipidus and central diabetes insipidus?
Nephrogenic DI results from renal insensitivity to ADH; central DI results from lack of ADH production
What is the effect of volume depletion on renal autoregulation?
Increases renal vascular resistance to maintain perfusion
What are the primary causes of renal infarction?
Thromboembolism, trauma, vasculitis, atherosclerosis
How does sickle cell trait differ from sickle cell disease in renal pathology?
Milder renal involvement compared to sickle cell disease, with a lower risk of infarction
What is the role of endothelin in kidney disease?
Vasoconstriction and fibrosis in renal vasculature
Which renal pathology is associated with monoclonal gammopathy of renal significance (MGRS)?
Monoclonal light chain deposition causes glomerular or tubulointerstitial damage
