151 - Tubular Damage Flashcards
Normal interstitium in kindey
Very thin, difficult to see
Acute reason for tubular interstitial swelling
Oedema
Chronic reason for tubular interstitial swelling
Fibrosis, scarring
Are tubulointerstitial or glomerular diseases more common?
Tubulointerstitial
Most important tubulointerstitial diseases
1
2
3
1) Acute tubular necrosis
2) Acute pyelonephritis
3) Acute or chronic tubulointerstitial disease
Acute pyelonephritis
Acute pyelonephritis
Acute tubular necrosis 1 2 3 4
1) Usually due to ischaemia (or acute hypo-perfusion of kidney)
2) Epithelial cells die, detach from tubular basement membrane, slough off into lumen
3) GFR falls because tubules aren’t working
4) Reversible lesion. With support, can fully recover
Blood effects of ATN
Without functioning epithelium the tubule can no longer fulfil its functions: the glomerular filtration rate falls, electrolyte balance fails, urea and creatinine accumulate in blood
What is associated with recovery from ATN?
Phase of increased urine production
Supportive therapy that might be needed when recovering from ATN
Dialysis
Most vulnerable areas of kidney to infarction
As blood supply falls tubular epithelium dies before other components of the kidney: glomeruli, blood vessels and interstitium survive longer
Things that must be considered when trying to explain poorly-functioning renal transplants 1 2 3 4
–Problems due to the transplantation procedure (particularly ischaemia)
–Early rejection (can happen very early)
–Drug toxicity (many immunosuppressive drugs unfortunately potent nephrotoxins)
–Recurrent primary disease (though it would be very early )
Difference between hypoperfusion and ischaemic ATN
Hypoperfusion is where there is too little blood (EG: lost blood, hypotension), and there is transient acute kidney failure. If the tubular epithelium survives, it is not ATN.
Ischaemic ATN is where there is prolonged hypoperfusion, leading to death of tubular epithelial cells.
Toxic tubular necrosis
1
2
3
•Very similar appearance and outcome to Ischaemic ATN
•Seen with toxins that affect tubular epithelium
–Heavy metals (esp. mercury)
–Some antibiotics
–Some cancer chemotherapy drugs
•Many act by disturbing mitochondrial function and oxidative phosphorylation
Acute interstitial nephritis
1
2
3
- Interstitium and tubules infiltrated by inflammatory cells (lymphocyte-mediated), often with many eosinophils
- Often fever, maybe a rash
- Very often due to drug allergy (e.g. antibiotics)
How does acute interstitial nephritis present?
Usually presents as acute renal failure, sometimes with some blood or protein in urine
Examples of organs where acute inflammation is lymphocyte-mediated, not neutrophil-mediated
Liver and kidneys
Pyelonephritis
Bacterial infection of the kidney that affects the:
–Parenchyma of the kidney
–Calyces
–Renal pelvis
How do organisms reach the kidney to cause pyelonephritis?
Ascend from the lower urinary tract to reach the kidney
Variable features of pyelonephritis
Can be acute or chronic.
Can occur with or without blockage to urine flow.
Type of bacteria that often cause pyelonephritis
G- –E. coli –Klebsiella sp. –Proteus sp. –Pseudomonas sp.
Typical presentation of acute pyelonephritis in adults 1 2 3 4 5
–Acute onset
–Fever, chills, lumbar tenderness and pain
–Discomfort when urinating (and frequency)
•Renal function usually preserved. Hypertension not a component
•Urine contains organisms, white blood cells
Presentation of acute pyelonephritis in children
In children symptoms often less clearly renal – abdominal pain, vomiting, fever
What often kills in acute pyelonephritis?
Extremely high fever (with rigors, delirium, sweats)
Difference in inflammation between pyelonephritis and interstitial nephritis
In interstitial nephritis, whole kidneys is full of lymphocytes and eosinophils.
In pyelonephritis, there are inflammatory foci of lymphocytes, neutrophils. Not the blanket coverage with immune cells that you get in interstitial nephritis
What can lead to chronic pyelonephritis?
Obstruction, repeated infection.
Appearance of chronic pyelonephritis
Results in interstitial scarring, tubular atrophy, depressed ‘saddle shaped’ scars visible on the renal surface
Analgesic nephropathy
Longterm use of compound analgesics (phenacitin, caffeine, aspirin).
Drugs have now been banned
End stage kidney disease
End result of some kidney diseases that don’t resolve.
Kidneys aren’t able to perform function, particularly maintenance of creatinine, urea levels in the blood.
Treatment for end stage kidney disease
1
2
1) Transplant
2) Dialysis
Without these, death.
Common features of long-term, irreversible renal diseass
Glomerular scarring, tubular atrophy, interstitial fibrosis.
Macroscopically the result is a shrunken, pitted and scarred kidney.
Leads to chronic renal failure
Presentation of chronic renal failure 1 2 3 4
•Insufficient glomerular filtration to
–Eliminate metabolic wastes
–Maintain water and solute homeostasis
•GFR
Proportion of causes of chronic renal failure in Australia
–32% diabetic nephropathy
–24% glomerulonephritis
–14% hypertension
– other include Analgesic Nephropathy, inherited conditions, chronic pyelonephritis, reflux nephropathy
Why is chronic renal failure hard to pick up early?
Can lose 80-85% of kidney mass without showing symptoms.
By the time symptoms show, patient is in serious renal failure
