Tubulopathies Flashcards
what are the renal tubules responsible for?
- body fluid balance
- acid base balance
- electrolyte regulation
- drug excretion
- reclaiming filtered glucose, amino acids, and peptides
- reclaiming or degrading the little bit of protein filtered
how can you diagnose renal tubular dysfunction or damage?
- you see something in the urine that is always freely filtered but should be completely reabsorbed by the tubules
- you calculate the fractional excretion of a substance
- you measure markers of tubular damage
what is fractional excretion?
- measures the percent of filtered solute that is excreted in the urine
- globally assess tubular function
- to calculate: need blood/serum/plasma creatinine and solute concentrations, and urine creatinine and solute concentrations
how are renal tubular diseases categorized?
- regional versus global
- congenital versus acquired
- isolated versus complex tubulopathies
-carbohydrates
-nitrogen
-electrolytes and minerals
-vitamins
-acid-base
-water
describe glucosuria
- most often due to hyperglycemia, except when it’s not (ALWAYS CHECK BLOOD GLUCOSE)
-normoglycemia glucosuria = renal glucosuria - causes of renal glucosuria:
-SGLT2 inhibition: diabetic cats
-proximal tubular disorder: inherited/primary or acquired
-can be part of complex tubulopathy (Fanconi syndrome) - diagnostic workup:
-confirm persistence of glucosuria and rule out hyperglycemia - possible clinical signs/complications: osmotic diuresis!!
-PU/PD
-recurrent UTIs - treatment: no cure for primary, just manage UTIs
- prognosis: usually not progressive so good prognosis longterm (unless associated with Fanconi’s)
describe consequences of disrupted amino acid reabsorption
vary according to which amino acid being lost but example is cysteine
- loss of cysteine amino acids in the urine
- cysteine amino acids in the urine form crystal molecules
- cysteine molecules precipitate to form crystals if urine is acidic
- cysteine crystals aggregate to form stones (esp if urine is acidic)
describe cystinuria
- inherited proximal tubular defect (in an SLC gene: SLC3A1 and SLC7A9)
-several dog breeds reported
-rare in cats - cysteine relatively insoluble in urine, leads to formation of uroliths in acidic urine
- diagnosis:
-crystals seen on UA
-uroliths seen on rads if larhe enough, US, CT
describe the anion gap
- the difference between measured cations and measured anions
- the body is electrically neutral so in reality the gap does not exist
- it is commonly used to classify cases of metabolic acidosis into:
-those that have unmeasured anions in plasma
–endogenous: ketones, lactate, uremic acids
–exogenous: salicylates, ethylene glycoe
-and those that do not have unmeasured anions in plasma
compare and contrast azotemic kidney disease and renal tubular acidosis
azotemic kidney disease: can cause metabolic acidosis via uremia acidosis
-individual tubular cell function ma be normal but the renal mass is reduced, allowing for accumulation of uremic acids
-high anion gap metabolic acidosis
renal tubular acidosis:
-changes in acid base handling by the renal tubules in the presence of relatively preserved GFR (classically)
-non-anion gap hyperchloremic metabolic acidosis
describe renal contribution to acid base regulation and how this relates to renal tubular acidosis
bicarb reabsorption, 80% in proximal tubule
H+ secretion, mainly in distal nephron (ammonia and phosphate in tubular fluid serve as buffers to accept the H+)
two types of renal tubular acidosis:
proximal renal tubular acidosis (type II):
-inability to reabsorb bicarbonate
distal renal tubular acidosis (type I): inability to excrete H+ (failure to acidify urine)
what is the first step in diagnosing renal tubular acidosis?
- confirmation of persistent hyperchloremic metabolic acidosis
-rule out chronic diarrhea (the most common cause)
-also can be due to chloride intoxication (super rare unless you gave a whole bunch of saline)
-then if rule out both above, consider renal loss of bicarb - suspicion rises in animals with urine pH >5.5 despite metabolic acidosis
-rule out UTI with urease producing bacteria
-proximal RTA can achieve pH <5.5
describe causes and treatment of RTA
causes:
1. primary (gene mutations)
2. secondary to:
-nephrotoxins
-inflammatory/infectious diseases
-diseases/conditions that induce tubular damage
treatment:
1. correction of chronic acidemia is important to prevent clinical signs and catabolic effects on bone
2. oral alkali replacement uses sodium bicarbonate or potassium citrate
describe nephrogenic diabetes insipidus
any disorder in which the urinary concentrating mechanisms cannot respond to ADH
-the kidneys cannot respond to ADH so the collecting duct cannot reabsorb water so the kidneys cannot concentrate urine and animal presents with PU/PD
-causes:
1. acquired:
-toxins (E.coli)
-drugs
-metabolic conditions (hypokalemia and hypocalcemia)
-tubular injury or loss
-changes in medullary concentration gradient (loss of hyperosmolar interstitium)
- congenital: super rare
-deficiencies in ADH receptors
how do you treat nephrogenic diabetes insipidus?
- most are acquired, so treat underlying disease
- if congenital:
-free choice water consumption
-dietary sodium and protein restriction: decrease the amount of solute that must be excreted in the urine, further decreased obligatory water loss
-thiazide diuretics: cause mild dehydration, so animal should increase fluid and sodium uptake in proximal tubular and decrease urine output
describe Fanconi syndrome
a complex tubulopathy with multiple metabolic derangements
-PROXIMAL TUBULAR DISORDER
causes:
1. acquired: various toxicosis causing acute tubular injury
-chicken jerky treats
-gentamycin (nephrotoxic Abx)
-chlorambucil (chemotherapy)
- familial: Basenji dog most common
-genetic test and urine metabolic tests available
disease presentation:
1. Basenji’s: onset at 4-8 years old (could be an issue if already bred the animal)
2. PU/PD, weight loss, poor hair coat, weakness, and dehydration
