Table of contents
- 1. Definition
- 1.1. Urine Anion Gap
- 1.2. Urine Osmolar Gap
- 2. Problems Created by RTA
- 3. Treatment
- 3.1. Distal RTA
.
Definition
- Metabolic acidosis caused by renal tubular dysfunction.. inability to excrete acid.
- Different Types
- Type II aka PROXIMAL
- A type of Fanconi syndrome (which is any type of proximal tubular dysfunction, different Fanconi syndromes exist that prevent reabsorption of different types of metabolites (AA, glucose, bicarb, etc.)
- Inability to reabsorb HCO3- in the proximal tubule.
- HINT: Also inability to absorb other electrolytes (Potassium [hypokalemia], phosphate [hypoPh], glucose [glycosuria]).
- Type I (most common) aka DISTAL
- Inability to excrete H+ in distal tubule
- If urine pH is HIGH or NORMAL = distal tubule not working to acidify the urine to get rid of extra acid in an acidotic state. = Type 1 RTA
- Causes:
- Cirrhosis
- Autoimmune (SLE, Sjogrens)
- Hephrocalcinosis
- Drugs (Lithium, Amphotericin)
- Others: Hereditary, Sickle Cell
- Type IV (Aldosterone Dependent)
- Hypoaldosteronism (primary, hyporeninemic)
- Drugs (Spironolactone, Amiloride, NSAIDs, ACEi, Heparin)
- Pseudohypoaldosteronism
- Type III
- Extremely RARE form of childhood acidosis.
- This is mixed Type I and Type II due to carbonic anhydrase deficiency.
- Children get mental retardation, cerebral calcinosis, and non-vitamin D rickets.
- This type is generally ignored because it is so rare.
- Type II aka PROXIMAL
- Presentation:
- Present "sick"
- Headache, Nausea/vomiting, Weakness
- Kussmaul Breathing
- Hypokalemia (Type I and Type II)
- Renal Stones (Type I)
- Bone Demineralization (more Type II)
- Present "sick"
- Differentiate:
- Quick Summary:
-
Type Features Treatment Type I (dRTA) Low K+
Urine pH > 5.3
Potassium Citrate (+fluids) Type II (pRTA) Low K+
Urine pH = 5.3 (normal), later < 5.3
Glycosuria, proteinuria, phosphaturia
Potassium Citrate (+fluids)
Type IV High K+
Urine pH < 5.3
Fludrocortisone
Loop Diuretics
-
Type II (pRTA) Type I (dRTA) Type IV Mechanism HCO3- reabsorption
defectH+ secretion defect
in Distal Tubules- Intercalated cell
dysfunction (unable to
reabsorb K+ and secrete
H+)
Hypoaldosteronism Causes Fanconi's Syndrome
(FS is any proximal tubule dysfunction,
pRTA is a type of Fanconi Syndrome)Multiple Myeloma, Amyloidosis
Drugs (Acetazolamide, Tenofovir)
Scleroderma (antibody to H+
ATPase)
Heavy Metal Poisoning
Vitamin D Def.
Hereditary
Autoimmune (SLE, Sjogrens)
Cirrhosis
Nephrocalcinosis
Hypercalciuria
Drugs (Lithium, Amphotericin)
Others (Hereditary, Sickle Cell)
Hypoaldosteronism
- Primary
- Hyporeninemic
- DIABETES!!!!!
Drugs
- Spironolactone
- Amiloride
- Heparin
- ACEi, NSAIDs (hypo-aldo activity)
Pseudohypoaldosteronism
Important
AssociationsBone Demineralization
(Poor phosphate absorption)Renal Stones
(Hypocitraturia)
Labs Bicarb: 12-20 (less severe than dRTA)
Low K+
(glycosuria, low molecular
weight proteinuria, phosphate
wasting)
Urine pH = 5.3 (normal) or LOW
Can rise high if high HCO3- load[Later Urine pH < 5.3]
[Urine variable bc still able to
secrete H+ and reabsorb HCO3-
in distal tubule]
Urine Anion Gap - VariableUrine Chloride HIGH > 100
Bicarb < 10 (SEVERE!)
Low K+
UrinepH > 5.3
Urine Anion Gap POSITIVE
Should be LOW due to extra
NH4+ in acidified urine.Urine Chloride HIGH >100
High K+
Urine pH < 5.3
Urine Anion Gap - POSITIVE
Urine Chloride HIGH >100
Treatment Potassium Citrate Sodium Bicarb
(GI discomfort, Bad taste)Potassium Citrate
Fludrocortisone
(often not enough
mineralcorticoids)
Loop Diuretics
- ALL THESE STATES WILL HAVE HIGH URINE CHLORIDE!!! Often >100 MMOL/L
- Bottom Line: If you see non-anion gap metabolic acidosis (hyperchloremic) in a non-diarrhea patient, think RTA
- Calculate UAG to determine etiology (RTA vs. Diarrhea)
- Bottom Line: Look at serum bicarb and urine pH: very low HCO3 and high pH, think of Type I RTA
- Bottom Line: Correct underlying cause
Urine Anion Gap
- Kidney's ability excrete acid is characterized by urine NH4 (ammionium). We don't have a test for ammonium in urine so we use urine anion gap.
- If urine pH > 6.5 --> bicarb becomes predominant
- Should be calculated to determine etiology of hyperchloremic metabolic acidosis.
- Urine Anion Gap (UAG = (Una + Uk) - Ucl
- POSITIVE UAG = low NH4 (i.e. RTA)
- NEGATIVE UAG = high NH4 (i.e. acid normally excreted - i.e. diarrhea).
- Diarrhea (lose bicarb in gut) --> kidneys are working well (no RTA) --> will have negative UAG.
- If RTA --> positive UAG (if pH < 6.5).
Urine Osmolar Gap
- If low, then lack of NH4 --> consistent with RTA
- Both UAG and UOG help you diagnose RTA, but doesn't tell you the type
- Fractional Excretion of phosphate (FEPhos) = 100x (urine Phos / Serum Phos) / (Urine Cr / Serum Cr)
- Normal = 5-12% excreted
- Fanconi's > 15% excreted
Problems Created by RTA
- Metabolic Acidosis
- Nausea, headache
- Hypercalciuria
- H+ directly inhibits reabsorption of Ca++
- Bone resorption (acts as buffer), osteoclasts activated (RANKL-mediated), release Ca, Na, K+, CO3-, PO4 from bone, which buffer plasma towards physiological pH.
- Hypocitraturia (Type 1)
- Occurs in all metabolic acidosis, but most profound in dRTA.
- Hypocitraturia can also occur in:
- Potassium depletion (cellular acidosis)
- Bacteuria (bacteria metabolize citrate)
- Acidifying conditions (chronic diarrhea, renal insufficiency)
- Hypocitraturia can also occur in:
- Causes calcium stone formation
- --> obstructive uropathy.
- Causes nephrocalcinosis (interstitial calcification)
- --> causes inflammation and interstitial fibrosis.
- Occurs in all metabolic acidosis, but most profound in dRTA.
- Hypokalemia (Type 1 and Type 2)
- GI and/or renal K+ losses.
- Occurs in most forms of chronic metabolic acidosis
- Acutely K+ can equalize by H+/K+ transporter (shifts K+ out of cells)
- Chronically leads to K+ depletion. (H+ ATPase pump fails, causing Na+/K+ Exchager to be dominant force maintaining electroneutrality, causing K+ excretion)
Treatment
Distal RTA
- Need to provide HCO3- to correct acidosis (lose HCO3 from continuous buffering of extra H+)
- Need to tirate HCO3 to daily citrate excretion of (>300 mg/day)
- Potassium Citrate
- Delivers alkali to help with acidosis, corrects hypocitraturia
- Prevents nephrocalcinosis and calcium stones.
- Halts renal failure.
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