Pathology - Renal

Question 1

Define acute kidney injury

Answer 1

Rapid decline in GFR (hours to days) with dysregulation of fluid and electrolyte balance and retention of waste products

Question 2

What are the causes of acute kidney injury

Answer 2

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

Question 3

What is the typical clinical course of AKI (how does urine output change)

Answer 3

• 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

Question 4

What are the physiological consequences of impaired renal function

Answer 4

• 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
• electrolyte and water imbalance

Question 5

Why do kidneys lose the ability to concentrate and dilute urine in a patient with impaired renal function

Answer 5

due to disruption of the countercurrent mechanism and loss of functioning nephrons

Question 6

What are the causes and phases of acute tubular necrosis

Answer 6

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

Question 7

What are the causes and manifestations of nephrotic syndrome

Answer 7

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

Question 8

What is the mechanism of edema in nephrotic syndrome

Answer 8

• 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

Question 9

What are the underlying processes involved in nephrotic syndrome

Answer 9

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

Question 10

What are the causes and manifestations of nephritic syndrome

Answer 10

causes: post streptococcal glomerulonephritis (acute proliferative glomerulonephritis)
manifestations: haematuria + high urea + oliguria + HTN + proteinuria + edema (not as significant as nephrotic syndrome)

Question 11

Describe the aetiology, pathogenesis and clinical features of post streptococcal glomerulonephritis

Answer 11

• 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, mild proteinuria, oedema, HTN, urine red cell casts, 95% recover quickly, 4% chronic, 1% rapidly progress

Question 12

How does the clinical course of post streptococcal glomerulonephritis differ in adults to children

Answer 12

in adults - less benign, glomerular lesions last longer, 60% fully recover

Question 13

What abnormalities are seen in the urine of a patient with glomerulonephritis?

Answer 13

haematuria, proteinuria, cellular casts, other debris

Question 14

What is the pathogenesis, clinical course and morphological features and complications of pre-eclampsia

Answer 14

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)

Question 15

What are the causes of pyelonephritis and what conditions pre-dispose to pyelonephritis

Answer 15

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

Question 16

What are the steps involved in ascending infection of the urinary tract

Answer 16

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

Question 17

What are the features of chronic pyelonephritis

Answer 17

chronic reflux or obstruction
causes renal scarring and dilated calyces
may cause CKD

Question 18

What are the causes, clinical features and clinical sequelae of urinary tract obstruction

Answer 18

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

Question 19

Describe the progression of effects of unrelieved obstruction of the ureter

Answer 19

• 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

Question 20

What are the types of renal calculi

Answer 20

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

Question 21

What conditions in urine favour stone formation (what is the pathogenesis of renal stones)

Answer 21

increased concentration of stone constituents
changes in urinary pH
decreased urine volumes
bacteria

Question 22

What leads to the formation of struvite calculi

Answer 22

• infections by urea-splitting bacteria (klebsiella) convert urea to ammonia
• resulting in alkaline urine, which precipitates magnesium, ammonium and phosphate salts

Question 23

What are the complications of ureteric calculi

Answer 23

obstruction
ulceration
bleeding
pain
renal infection
renal impairment

Question 24

What is hepatorenal syndrome?

Answer 24

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.

Question 25

What is malignant hypertension?

Answer 25

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”