ACUTE TUBULAR NECROSIS (ATN)- * MOST COMMON CAUSE OF CLINICAL SYNDROM OF ACUTE RENAL FAILURE.- * CAUSES 1– ISCHAEMIA- 2- NEPHROTOXICITY(chemicals,bacterial toxins)- 3- COMBINATION OF THESE.
• Ex. Of nephrotoxic agents( causing ATN) *- aminoglycoside ( gentamicin) - Cytotoxic agent cisplatin.• - antifungus amphoterici B
Pathogenesis (ATN)-Ischaemic tubular necrosis usually follows a period of shock.- Or the toxic effect from the lumen of the tubule ( causing the ATN).- -tubular cells are vulnerable to ischaemia because they have high oxygen consumption in order to generate energy for solute reabsorption, particularly in the thick ascending limb of the loop of Henle.- - All these causes death of tubular cells, which may shed into the tubular lumen causing tubular obstruction.
- Focal breaks in the tubular basement membrane develop, allowing tubular contents to leak into the interstitial tissue and cause interstitial oedema.( oliguria or anuria phase)- - fractional sodium excretion >1- - urine sodium > 20 mmol/l- Fortunately, tubular cells can regenerate and re- form the basement membrane. If the patientis supported during the regeneration phase,
- During recovery there is often a diuretic phase in which urine output increases rapidly and remains excessive for several days.- This is due in part to the loss of the medullary concentration gradient (delay in returning to normal).- - hypokalaemia may occurred during the diuretic phase.
TREATMENT (ATN)- Establish and correct the underlying cause of the ARF.-If hypovolaemia is present, restore blood volume as rapidly as possible (with blood, plasma or isotonic saline (0.9%), depending on what has been lost).- Optimise systemic haemodynamics. Monitoring of the central venous pressure or pulmonary wedge pressure as an adjunct to clinical examination may aid in determining the rate of administration of fluid.
- correct the hyperkalaemia ( early stage) - correct the acidosis.- diet control.- Dialysis (hemofiltration) may needed.
Traetment of hyperkalemia:1- protective measure= protect the heart ( calcium gluconate)2- shifting measures –shift the potassium from the blood to inside the cell ( insuline with hypertonic glucose, beta agonist, sodium bicarbonate)3- excretory measure (resin)4- Dialysis
• Correct metabolic acidosis. – Restoration of blood volume will correct acidosis by restoring kidney function. – Isotonic sodium bicarbonate (e.g. 500 ml of 1.26%) may be used.
INTERSTITIAL NEPHRITIS• - A group of inflammatory diseases affect renal tubules and the surrounding interstitium.• - The clinical presentation is often renal failure, but electrolyte abnormalities are common, especially hyperkalaemia and acidosis.• - Proteinuria (and albuminuria) is rarely > 1 g/24 hrs .• - low molecular weight proteinuria (e.g. retinol-binding protein, β2-microglobulin, lysozyme) with haematuria and pyuria are common.
ACUTE INTERSTITIAL NEPHRITIS (AIN)- most commonly allergic, particularly to drugs,- - Renal biopsies show intense inflammation, with polymorphonuclear leucocytes and lymphocytes surrounding tubules and blood vessels and invading tubules (tubulitis), and occasional eosinophils (especially in drug-induced disease).- -
- Drug induced AIN:- - only 30% have a generalised drug hypersensitivity reaction (e.g. fever, rash,- eosinophilia)- - eosinophils are found in the urine in up to 70% of patients.- resemble rapidly progressive glomerulonephritis- Many patients are not oliguric despite moderately severe ARF, and AIN should always be considered in patients with non-oliguric ARF.- Renal biopsy is indicated(? % of chronicity)
Management- withdrawal of the drug.( or treat the cause )- - corticosteroids (e.g. prednisolone 1 mg/kg/day) accelerate recovery and may prevent long-term scarring.- - Dialysis is sometimes necessary.
CHRONIC INTERSTITIAL NEPHRITIS( CIN)- -Small size kidneys. (CRF)- - ?? May be diagnosed late and no aetiology to be apparent.- - CRF often moderate ( B. urea<150 mg/dl- - sever increasing of BP,potassium and acidosis- - urinalysis abnormalities are non specific.- - analgesic nephropathy and sickle cell nephropathy can cause renal papillary necrosis and CIN.
Causes of CIN• - causes of AIN if persistent• - glomerulonephritis.• - sever pyelonephritis• - Immune/inflammatory(SLE,chronic rejection of transplaned kidney, sarcoidosis,sjogren synd.)• - toxic (lead,mushrooms,chinese herbs)• - drugs(all drugs causing AIN, analgesic nephropathy,lithium toxicity,ciclosporin,tacrolimus).