Renal Tubular Acidosis

[liveonearth]

BUN: blood urea nitrogen
urea formed in liver post protein metabolism, along with CO2
urea excretion varies with protein intake
BUN test used as index of glomerular fx
rapid prot catabolism and decr renal fx-->elevated BUN
rate of rise influenced by degree of necrosis, catabolism, excretion
markedly increased is severely impair glom fx
chronic renal dz: BUN correlates better with sx of uremia than serum creatinine
Normals: adults 6-20mg.dL, Elders slightly higher, children slightly lower
Critical: >100mg/dL
Incr: fever, DM, incr adrenal gland activity, renal dz, CHF, dehydration, hyponatremia, shock stress, MI, UT obstrx, GI hemorrhage, burns, cancer, anabolic steroid use, more muscle mass
Decr: liver failure, acromegaly, malnutrit, low prot diet, impaired absorption (celiac), nephrotic syn (occ), SIADH, late preg, less muscle mass, overhydration (late preg), drugs
SX of incr: confusion, disorientation, convulsion

CREATININE
byproduct of breakdown of mm creatine phosphate dt energy metabolism
produced at constant rate dt muscle mass
rises later than bun in renal failure
an incremental rise of 1.0-1.5 in creatinine each day is an ominous sign
a creatinine of 5.5-6.0 is renal failure

always check before giving nephrotoxic chemotherapies: methotrexate, cisplatin, cyclophosphamide, mithramycin, semustine, also before intense heavy metal chelation
renal dysfx reduces excretion-->incr levels
used as approximation of GFR

fancy equation p375 fischbach to est GFR--do I need to use this? major math. =-]
Normals: men .9-1.3mg/dL, women .6-1.1, 3-18yo .5-1.0, 0-3yo .3-.7
Critical: 10mg/dL or 890nmol/L in nondialysis pts
Incr: renal dysfx, chronic nephritis, UT obstrx, mm dz (gigantism, acromeg, myasthenia gravis, muscular dystrophy, poliomyelitis), CHF, shock, dehydration, rhabdomyolysis, hyperthyroid, ketoacidosis, ascorbic acid, cephalosporins, v high prot diet
Decr: small person, decr mm, severe liver dz, inadequate prot in diet, preg, compounds with bilirubin, glucose, histidine, quinidine

RATIO CHANGE DDX
NORMAL Bun/creat ratio: 10:1 to 20:1
Incr ratio (>20:1) with normal creatinine: prerenal azotemia, heart fail, salt depletion, dehydration, tissue breakdown, GI hemorrhage, excess prot intake or breakdown on top of impaired renal fx
Incr ratio with elevated creat: UT obstrx, prerenal azotemia with renal dz
Decr ratio with decr BUN: acute tubular necrosis, decr urea syn dt severe li dz or starvation, dialysis, SIADH, preg
Decr ratio (<10:1) with incr CREAT: phenacemide therapy, rhabdomyolysis, musclar pts c renal fail

RTA-->metabolic acidosis dt renal insufficiency
insuff recovery of bicarb (proximal) or insuff secret of H+ (distal)
term RTA is reserved for pts w poor urinary acidification in otherwise well-functioning kidneys
several types, syndromes, causes

TYPE I DISTAL
the classical form, dRTA, first described
urine not more acid than 5.3
failure of acid secretion by alpha intercalated cells of cortical collecting duct of distal nephron
DX via LABS: Normal anion gap metabolic acidosis/acidemia
hypokalemia
urine >5.3pH, incr Ca+, low citrate-->urinary stones
nephrocalcinosis, bone demineralisation-->rickets/osteomalacia
systemic acidemia = < serum bicarbonate of 20 mmol/l
IF incomplete dRTA, oral acid loading challenge: can they acidify urine???
test usually performed is short ammonium chloride test. capsules
can also use furosemide and fludrocortisone has been described
SX: Asx, loin pain, hematuria,
COMPLIC: stones, failure to thrive, rickets, renal failure, death
?? Tiny Tim in Charles Dickens' A Christmas Carol
ETIO: AI, Sjögren's, SLE, RA, hypergammaglobulinemia
Cirrhosis, nephrocalcinosis, transplant, sickle
toxins (ifosfamide, toluene, lithium amphotericin B), chronic obstrx
ETIO Hereditary: mutations of Band 3[8] the basolateral bicarbonate transporter of the intercalated cell
autosomal dominant in western Europeans, or autosomal recessive SE Asians more low K+
also autosomal mutations that mb assoc sensorineural deafness
TX: oral bicarb for acidemia, potassium citrate to bring up K+ and prevent stones, inhibit Ca+ excretion

TYPE 2 PROXIMAL RTA
dt bicarb wasting in prox tubule
normal distal intercalated cells
acidemia is less severe than dRTA
urine can acidify to a pH of less than 5.3
several causes, occ present as a solitary defect, usu assoc c dysfx of prox tub named Fanconi's
Faconi's syndrome: acidemia, bone mineralization dt phosphaturia, glycosuria, aminoaciduria, uricosuria, proteinuria
ETIO: cystinosis, galactosemia, glycogen storage dz type I, fructose intolerance,
Lowe syndrome, tyrosinemia, (all hereditary), Wilson's,
Acquired disorders: amyloidosis, multiple myeloma, paroxysmal nocturnal hemoglobinuria
Toxins: HAART, ifosfamide, lead, cadmium
TX: oral bicarbonate supplementation
this will increase urinary bicarbonate wasting and may well promote a bicarbonate diuresis
amount of bicarbonate given may have to be very large, to stay ahead of urinary losses
may exacerbate urinary potassium losses
may precipitate hypokalemia

reversal of the chronic acidosis should reverse bone demineralization

TYPE 3 COMBINED RTA
both distal and proximal
rare, observed in 60-70s, transient phenomenon, infants and children with dRTA
mbdt high salt intake
no longer observed
aka juvenile RTA

another form: inherited carbonic anhydrase II deficiency-->autosomal recessive syndrome
osteopetrosis, renal tubular acidosis, cerebral calcification, and mental retardation
very rare, 70% of world cases in Magreb region of North Africa

TYPE 4
hyperkalemia
not a tubular disorder
associated with a mild (normal anion gap) metabolic acidosis
low aldosterone-->decr proximal tubular ammonium excretion-->decr urine buffering-->hyperkalimia normal pH urine
ETIO: adrenal insufficiency, CAH, ald synthase def, decr angiotenisin 2 and intra-adrenal dysfx-->hypourinemic hypoald, diabetic nephropathy and other renal dysfx, ACE inhib, NSAIDS, cyclosporine, Ald resistance, more drugs: Amiloride, Spironolactone, Trimethoprim, Pentamidine

ALDOSTERONE ASIDE
aldosterone = yellow mineralocorticoid from outer adrenal: zona glomerulosa
acts on the distal tubules and collecting ducts of the nephron
-->conserv sodium, secret potassium, retain water-->incr BP
ald activity reduced in Addison's disease, increased in Conn syndrome

TX for Aldosterone deficiency: mineralocorticoid (such as fludrocortisone)
& mb a glucocorticoid for cortisol deficiency, if present

Hyporeninemic hypoaldosteronism is txable c fludrocortisone but HTN and edema mb problem so need thiazide, bendrofluazide or loop diuretic (furosemide) to control hyperkalemia

ACUTE TUBULAR NECROSIS
etio: ischemia, toxins, DIC, urinary obstx
accounts for ~50% of acute renal failure in hospital pts
reversible
toxins: gentamycin, radiographic contrast, heavy metals (mercury), solvents (carbon tetrachloride)
ischemia: vascular, blood or BP issue
SOURCES
wikipedia accessed 2/6/11 http://en.wikipedia.org/wiki/Renal_tubular_acidosis
Fischbach's Manual of Lab and Dx Tests, 8th Ed