Pathology - Renal Flashcards
Define acute kidney injury
rapid decline in GFR (hours to days) with dysregulation of fluid and electrolyte balance and retention of waste products
What are the causes of acute kidney injury
1) ischaemia = thrombosis, hypovolaemia, vasoconstriction, malignant HTN
2) toxic injury to tubules = drugs (aspirin, aminoglycosides), radio-active dye, myoglobin
3) acute tubulointerstitial nephritis = hypersensitivity to drugs, infections, heavy metals
4) obstruction = tumour, clot
What is the typical clinical course of AKI (how does urine output change)
- initiation phase = decreased urine output with elevation of urea <36 hours
- maintenance phase = sustained decreased urine output (40-400ml/day) with salt/water overload, high K+, metabolic acidosis
- recovery phase = rising urine volumes (up to 3L/day) with water/Na+/K+ losses
What are the physiological consequences of impaired renal function
- proteinuria: due to increased permeability of the glomerular capillaries
- uraemia: due to the accumulation of breakdown products of protein metabolism
- acidosis: due to failure to excrete acid products
- abnormal Na+ handling
Why do kidneys lose the ability to concentrate and dilute urine in a patient with impaired renal function
due to disruption of the countercurrent mechanism and loss of functioning nephrons
What are the causes and phases of acute tubular necrosis
causes:
1) ischaemic = shock, circulatory collapse, dehydration
2) direct toxic = drugs (aspirin, contrast), radiation, heavy metal poisoning
phases:
- initiation phase = decreased urine output with elevation of urea <36 hours
- maintenance phase = sustained decreased urine output (40-400ml/day) with salt/water overload, high K+, metabolic acidosis
- recovery phase = rising urine volumes (up to 3L/day) with water/Na+/K+ losses
What are the causes and manifestations of nephrotic syndrome
causes:
- primary glomerular disease = membranous nephropathy in adults and minimal change disease in children
- systemic disease = diabetes, amyloidosis, SLE, infections, malignancy
manifestations: more than 3.5g/day of proteinuria + hypoalbuminaemia + hyperlipidaemia + lipiduria + edema
What is the mechanism of edema in nephrotic syndrome
- proteinuria leads to hypoalbuminaemia which leads to reduced colloid osmotic pressure and systemic edema
- compounded by sodium and water retention due to activation of RAAS
What are the underlying processes involved in nephrotic syndrome
1) derangement of glomerular capillary walls
2) hypoalbuminaemia secondary to above and inability of liver to replace albumin
3) generalised edema secondary to loss of osmotic pressure
4) hyperlipidaemia due to elevated liver synthesis
5) lipiduria due to increased production and increased glomerular permeability (causes frothy urine)
6) hypercoagulable state due to loss of antithrombin III protein
What are the causes and manifestations of nephritic syndrome
causes: post streptococcal glomerulonephritis (acute proliferative glomerulonephritis)
manifestations: haematuria + high urea + oliguria + HTN + proteinuria + edema (not as significant as nephrotic syndrome)
Describe the aetiology, pathogenesis and clinical features of post streptococcal glomerulonephritis
- nephritic syndrome caused by group A beta-haemolytic streptococci, usually 1-4 weeks post pharyngeal or skin infections
- characterised by immune complex deposition in glomerular basement membrane via type III hypersensitivity
- glomerular damage due to immune complex deposition, antigen affinity for glomeruli and complement cascade
clinical: malaise, fever, nausea, oliguria, haematuria, edema, HTN, urine red casts, 90% recover quickly, <1% rapidly progress
How does the clinical course of post streptococcal glomerulonephritis differ in adults to children
in adults - less benign, glomerular lesions last longer, 60% fully recover
What abnormalities are seen in the urine of a patient with glomerulonephritis
haematuria, proteinuria, cellular casts, other debris
What is the pathogenesis, clinical course and morphological features and complications of pre-eclampsia
pathogenesis: placenta ischemia → pro-inflammatory mediators → endothelial cell dysfunction → vasoconstriction/clots
clinical: after 32 weeks gestation, HTN, edema, proteinuria, headache, visual disturbance
morphological changes: placental infarcts, retroplacental haematoma, villous ischaemia, fibrinoid necrosis
complications: eclampsia (convulsions), HELLP (haemolysis, elevated liver enzymes, low platelets)
What are the causes of pyelonephritis and what conditions pre-dispose to pyelonephritis
most commonly gram negative bacilli that normally inhabit the GI tract (e coli, proteus, klebsiella, enterobacter, enterococcus)
predisposition: UTI, instrumentation, vesico-ureteric reflux, pregnancy, female up to 50, males > 50, immunosuppression
What are the steps involved in ascending infection of the urinary tract
1) colonisation of the distal urethra
2) entry of organism into bladder
3) urinary tract obstruction or stasis of urine
4) vesicoureteric reflux through incompetent vesicoureteral orifice
What are the features of chronic pyelonephritis
chronic reflux or obstruction
causes renal scarring and dilated calyces
may cause CKD
What are the causes, clinical features and clinical sequelae of urinary tract obstruction
causes: anywhere in renal pelvis, ureter, bladder, urethra
- intrinsic = calculi, tumours, inflammation (infection), clots, urethral strictures
- extrinsic = tumours, BPH, pregnancy, neurogenic bladder
clinical: pain, unilateral may be subclinical, bilateral may cause polyuria and nocturia (due to inability to concentrate urine)
sequaelae: infection, stone formation, renal failure
Describe the progression of effects of unrelieved obstruction of the ureter
- reduced GFR, progressive dilation of proximal ureter/renal pelvis/calyces (hydronephrosis)
- renal parenchymal atrophy, inflammation leading to fibrosis
- eventually leading to a large thin-walled non-functional structure
What are the types of renal calculi
1) Calcium stone (70%) = calcium oxalate + calcium phosphate
2) Struvite stone (15%) = magnesium + ammonium + phosphate
3) Uric acid stone (5-10%) = common in hyperuricaemia (gout, leukaemia)
4) Cystine stone (1-2%) = caused by genetic defects in reabsorption of amino acids
What conditions in urine favour stone formation (what is the pathogenesis of renal stones)
increased concentration of stone constituents
changes in urinary pH
decreased urine volumes
bacteria
What leads to the formation of struvite calculi
- infections by urea-splitting bacteria (klebsiella) convert urea to ammonia
- resulting in alkaline urine, which precipitates magnesium, ammonium and phosphate salts
What are the complications of ureteric calculi
obstruction ulceration bleeding pain renal infection renal impairment
What is hepatorenal syndrome?
Rapid deterioration in kidney function in individuals with liver cirrhosis or fulminant liver failure, without any
pre-existing kidney disease.
Kidney function can be restored if hepatic failure is reversed (i.e. liver transplant).
Pathophysiology appears to consist of decreased renal perfusion pressure followed by renal vasoconstriction.
Kidneys retain the ability to concentrate urine.
What is malignant hypertension?
Clinical syndrome associated with abnormally high levels of renin
Initial insult - vascular damage to the kidneys, resulting in increased permeability and focal death of cell walls with platelet deposition.
Leads to fibrinoid necrosis of the arterioles, swelling of the intima and vascular thrombosis.
Kidneys become ischaemic
Microscopic “onion skinning appearance”
