1. TUBULO-INTERSTITIAL DISEASES

2. NEPHRONS
Which involve;
• The glomerulus
(afferent
arteriole, efferent
arteriole , bowman's
capsule)
• Proximal convoluted
tubule
• Loop of henle
• Distal convoluted tubule
• Collecting tubule

3. • -Acute tubular necrosis (ATN)
- Acute interstitial nephritis ( AIN)
• - Chronic interstitial nephritis (CIN)

4. 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.

5. • Ex. Of nephrotoxic agents( causing ATN)
*- aminoglycoside ( gentamicin)
- Cytotoxic agent cisplatin.
• - antifungus amphoterici B

6. 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.

7. - 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 patient
is supported during the regeneration phase,

8. - 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.

10. 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.

11. - correct the hyperkalaemia ( early stage)
- correct the acidosis.
- diet control.
- Dialysis (hemofiltration) may needed.

12. 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

13. • 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.

14. 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.

15. 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).
- -

17. CAUSES OF ACUTE INTERSTITIAL
NEPHRITIS
- Allergic (
- penicillin,NSAIDs,allopurinol,others)
- Autoimmune nephritis
- - Infection ( pyelonephritis,TB,)
- - Toxic ( myeloma light chains,mushrooms).

18. - 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)

19. 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.

20. 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.

21. 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).

22. Causes (cont.)
- congenital/developmental ( vesico-ureteric
reflux, sickle cell aneamia,wilson’s dis.)
- Metabolic (
amyloidosis, hypokalemia,hypercalciuria,hyperoxalu
ria)
-

23. Management of CIN
• - searching for the cause and remove it or
treat it ( if possible).
• - As the treatment of CRF.