Tubulo-intestitial disease Flashcards
Definition of tubulo disorders
nephritis affecting renal tubules and interstitual disease
Classfication
Proximal tubulopathies
- Renal tubular acidosis – type 2 RTA
- Fanconi’s syndrome
- Cystinosis
Loop of henle
-bartters syndrome
Distal tubulopathies
-gitelman syndrome
Collecting ducts
-nephrogenic diabetes insipidous
Renal tubular dysfunction- Where is the problem?
Electrolyte disturbance/loss
- Na, K, Cl, PO4
- Aminoaciduria
- Glycosuria
Acid-Base disturbance → metabolic acidosis
- HCO3 loss – proximal tubule
- Failure of H+ excretion – distal tubule
Renal concentration defect – collecting duct
-Polyuria
Fanconis syndrome definition
Diffuse proximal tubular dysfunction
Clinical feautures of fanconis
Polyuria/polydipsia Volume depletion FTT Constipation Rickets
Pathophysiology of fanconis
Loss of
- AA
- Glucose
- PO4
- HCO3-
in the urine
Causes of fanconis syndrome
Idiopathic Genetic -Wilsons -drugs -Multple myelome
Nephropathic cystinosis incidence
1 in 100000 children
Genetics of nephropathic cystinosis
AR inheritance
CTNS gene mutation on chromosome 17p13
Defect in lysosomal cystine transport leading to excessive intracellular cystine accumulation
Pathophysiology of nephropathic cystinosis
Raised white cell cystine levels: diagnostic
Impaired proximal tubular reabsorptive capacity
- hypokalaemia, hypophosphataemia, metabolic acidosis, glycosuria, and aminoaciduria (Fanconi syndrome)
- sodium wasting
- ADH resistance (nephrogenic diabetes insipidus)
Progressive glomerular renal failure
Clinical features of nephropathic cystinosis
Fanconi’s syndrome Extra-renal disease -Corneal cystine crystal deposits – photophobia -Skeletal - Growth retardation -Hypothyroidism -Hepato-splenomegaly - hypersplenism -Neurological: deterioration/cerebral atrophy -Pubertal delay and infertility -Pancreatic insufficiency - DM
Renal Failure
management of nephropathic cystinosis
Supportive:Fluid and electrolyte replacement
Specific: Mercaptamine – cystine depletion
- Systemic oral therapy: Monitor white cell cystine levels
- Topical cysteamine eye therapy
Other: Indomethacin – to reduce polyuria
CKD treatment
NB: Transplantation – does not correct underlying disorder
barrters syndrome genetics
AR
Defects in NKCC2; KCNJ1; CLCNKB genes identified
Pathophysiology of barrters syndrome
Defect in Na+-K+-2Cl- co-transporter
Thick ascending limb of Loop of Henle
LAB presentation of barrters syndrome
Plasma magnesium – normal
Urinary Chloride - high
Urinary Calcium - normal/high
Hyperreninaemia – normal BP
Hypochloraemic hypokalaemic alkalosis
low chloride low potassium alkalotic picture!!
Similar picture with Furosemide
(Loop Diuretics)
clinical features of barters
In-utero
- Polyuria– polyhydramnios
- IUGR
- Premature delivery
Neonate
- Polyuria
- Electrolyte disturbance
- Poor growth
- Hypercalciuria and nephrocalcinosis
Childhood
- Polyuria
- Electrolyte disturbance
- Episodes of dehydration
Adults
-Electrolyte disturbance
Management of bartters syndrome
K+ replacement
Fluid replacement
Indomethacin
- PG syntethase inhibitor –
- Reduces renal salt, water and potassium loss – reducing GFR
Psuedo-Bartters syndrome definition
Hypocholaemic hypokaelmic alkalosis
But apparently low urinary levels:
- urine chloride
- urine sodium
Causes of psuedo-bartters syndrome
Cystic fibrosis – sweat losses of NaCl and water
Congenital chloride diarrhoea – gut loss
Laxative abuse – gut loss
Cyclical vomiting
Gitelman syndrome
Compare to Bartter’s syndrome
AR
Defect in distal tubule Na-Cl co-transporter
Hypokalaemic metabolic alkalosis
Plasma magnesium - low
Urinary calcium – low
Similar picture with Thiazide Diuretics
Nephrogenic diabetes insipidus genetics
X-linked/AR inheritance
Nephrogenic diabetes insipidous causes
Arginine Vasopressin receptor defect
Aquaporin-2 water channel
defect -Located in collecting duct
Resistance to ADH / Arginine Vasopressin – leading
defective urinary concentration
Hypernatremic dehydration
Treatment of nephrogenic diabetes insipidus
Fluid intake
Low solute load
Thiazide diuretic/indomethacin
Tubulo-interstinital nephritis causes
Inflammation of tubulo-interstitium
Presumed to be immune-mediated
Sparing of glomeruli and vessels
Usually secondary to drugs/infections/other causes
Spectrum of pathology –
Acute and reversible nephritis – to – Chronic and irreversible disease
Clinical features of tubulo-interstiial nephritis
ARF
- No HT;
- No proteinuria
CRF
Tubulopathy
Proximal -Fanconi syndrome, Renal tubular acidosis
Distal tubular cell injury -Acidosis and hyperkalaemia
Collecting duct damage -Urinary concentrating defect-Potassium wasting
Causes of tubulo-interstitial nephritis
Idiopathic
Drugs (NSAIDS, anti0microbials, antiviral)
Infections
Tubulo-interstial nephritis with uveitis – TINU
Systemic disease:Sarcoidosis
Lymphoma/leukaemia, IBD
Other-Heavy metals
DRUGS MOST IMPORTANT CAUSE
Management of tubulo-interstitual nepritits
Acute
- remove drug
- steroids?
Treat primary disease process
Minimise proteinuria
Suppression of inflammation
Management of CKD
