Pathology - Kidney Flashcards
Why is ATN important?
It is the most common cause of renal failure: accounting for 50% of cases of ARF in hospitalised patients.
The potential reversibility of ATN means that proper management may be the difference between life and death.
What is ATN?
Acute tubular necrosis is a clinicopatholgic entity characterised by destruction of tubular epithelial cells and clinically by acute diminution or loss of renal function.
What are the four causative categories of ATN?
- Ischaemia: PaN, malignant HTN, HUS, shock
- Direct toxic injury: drugs, dyes, myoglobin, haemoglobin
- Acute tubulointerstitial nephritis: hypersensitivity reaction
- Urinary obstruction
What are the predominant patterns of injury in ATN?
Ischaemic ATN
Nephrotoxic ATN
What insults give rise to nephrotoxic ATN?
Drugs such as Gentamicin
Radiographic contrast agents
Poisons and heavy metals (Mercury)
Organic solvents (CCl4)
Which early sign of cellular injury contributes strongly to ATN?
Reversal of cell polarity.
NaKATPase is redistributed to the luminal membrane causing increased sodium delivery to the tubules and thus increased vasoconstriction via tubuloglomerular feedback.
What causes luminal tubule obstruction in ATN?
What is the effect of this?
Necrosed or apoptotic cells slough off into the lumen causing increased luminal pressure and decreased GFR. In addition, luminal fluid is forced into the interstitium increasing interstitial pressure and further damaging the tubule.
What causes the intrarenal vasoconstriction seen in ATN?
3 mechanisms
- Increased sodium delivery to MD results in reduced GFR
- Damaged endothelium releases endothelin and cannot produce NO/PGI2.
- Mesangial contraction due to direct ischaemia.
What is the morphological appearance of ATN?
ATN is characterised by focal tubular necrosis at multiple points along the nephron, with large skip areas between often accompanied by rupture of the basement membrane and occlusion by casts.
What are the 3 phases of ATN?
- Initiation - Injury and slight oligouria
- Maintenance - Worsening oligouria 40-400ml/day
- Recovery - up to 3L of urine per day
Do all patients with ATN have oligouria?
No. Up to 50% may not have oligouria.
Non-oligouric ATN occurs often with nephrotoxins and follows a more benign course.
Breakdown of kidney stone types and frequencies:
Calcium oxalate and phosphate - 70%
Struvite (magnesium ammonium phosphate) - 15-20%
Uric acid 5-10%
Cystine 1-2%
Causes and risk factors of calcium oxalate stones?
About 5% have hypercalcaemia and hypercalciuria, caused by hyperparathyroidism, diffuse bone disease, sarcoidosis or other hypercalcaemia states.
About 55% have hypercalciuria without hypercalcaemia which may be intestinal, renal, or idiopathic.
As many as 20% of oxalate stones are associated with hyperuricosuric calcium nephrolithiasis where nucleation of calcium oxalate occurs by uric acid crystals in the collecting ducts.
5% are associated with hyperoxaliuria which may be primary (hereditary) or secondary (intestinal overabsorption)
Causes and risk factors for magnesium ammonium phosphate stones?
Largely formed after infections by urea-splitting bacteria (proteus, staph) which convert urea to ammonia. The resultant alkaline urine causes precipitation of magnesium ammonium phosphate salts.
These may form staghorn calculi as the amount of urea excreted may be huge.
Causes and risk factors for uric acid stones?
Common in patients with hyperuricaemia (gout) and diseases involving rapid cell turnover (leukaemia).
However, more than half have no identifiable hyperuricaemia. Urinary pH tends to be low in these patients as Uric acid cannot dissolve in acidic urine.
Causes of Cystine stones?
Genetic defects in the renal reabsorption of AA, including cystine. These stones form at a low urinary pH.
Name 6 stone inhibitors:
Pyrophosphanate Diphosphanate Citrate Glycosaminoglycans Osteopontin Nephrocalcin
Small, discrete, renal tumour found in 7-22% of autopsies?
Renal papillary adenoma.
Renal tumour found in association with Tuberous Sclerosis?
AML. Present in 25-50% of patients with TS.
What is an Oncocytoma?
A renal tumour, considered benign. Accounts for 5-15% of surgically resected renal tumours.
Made up of large, eosinophilic cells, with small benign nuclei. Arise from collecting ducts.
Epidemiology of RCC?
Occur in the 6-7th decades of life. More common in men 2-3:1
Smoking is the biggest RF. Obesity, HTN, unopposed oestrogen, and asbestos, petrol, heavy metal exposure also RF.
Autosomal-dominant familial cancers account for 4%
What is the role of vHL in RCC?
The vHL gene (on 3p) codes for a protein involved in targeting other proteins for destruction. When mutated, HIF-1 (normally a vHL victim) levels remain high and this constitutively expressed protein increases production of VEGF and TGF-b.
Insulin-like GF is also normally a target of vHL!
What are the different types and frequencies of RCC?
- Clear cell 70-80%
- Papillary carcinoma 10-15%
- Chromophobe renal carcinoma 5%
- Collecting duct (Bellini) carcinoma 1%
Which protooncogene is associated with papillary RCC.
MET, which normally serves as a tyrosine kinase receptor for hepatocyte growth factor.
Psammoma bodies are associated with which RCC?
Papillary RCC
List the paraneoplastic syndromes caused by RCC?
9 to list
Polycythaemia Hypercalcaemia Hypertension Hepatic dysfunction Feminisation or masculinisation Cushing's syndrome Eosinophilia Leukaemoid reactions Amyloidosis.
Frequency, presentation, and prognosis of Urothelial carcinoma of the renal pelvis?
5-10% of primary renal tumours
Become clinically apparent at a small size as they fragment and bleed, or cause obstruction due to their location. Occur more frequently in patients with analgesic nephropathy.
Prognosis is poor; 10% for high grade, 50-70% for low grade at 5 years. This is due to their invasive nature.
