Acid-Base Part II

Question 1

What causes Proximal RTA (Type 2)?

Answer 1

Normally, 80-90% of filtered HCO3- is reabsorbed in the proximal tubule. With Proximal RTA, there is decreased capacity in the PT to reabsorb HCO3-. This increases the destal HCO3- delivery, which overwhelms reabsoption mechanisms downstream (TAL and DT).

Results in HCO3- loss in the urine and a low serum HCO3-.

Eventually, serum HCO3- decreases to the point where the PT, TAL, and DT’s reabsorptive capacity are not overwhelmed. Thus, there is no further HCO3- loss in the urine and the serum HCO3- stabilizes at a lower level (new steady state).

Question 2

What leads HCO3- reabsorption in the kidney?

Answer 2

H+ secretion

Question 3

What is the most common cause of Proximal RTA (Type 2) in children? In adults?

Answer 3

Children- cystinosis

Adults- Fanconi Syndreme, often with secondary cause of multiple myeloma.

Question 4

What are the clinical manifestations of Proximal RTA (Type 2)?

Answer 4

NAGMA with or without proximal tubular dysfunction

Hypokalemia (mild compared to distal RTA (Type 1)

Question 5

How do you dx Proximal RTA (type 2)?

Answer 5

Urine pH can be high or low depending on serum HCO3- level.

Urine anion gap can be positive or negative.

Question 6

How do you calculate Urine Anion Gap? What does it mean if it is positive or negative?

Answer 6

UAG= (urineNA+ + Urine K+) – Urine Cl-

If UAG is negative, it indicates appropriate distal nephron urinary acidification.
If UAG is positive, it indicates inappropriate distal nephron urinary acidification.

Question 7

What causes Distal RTA (Type 1)?

Answer 7

Patients unable to acidify their urine. Results from decreased net H+ ion secreation in the distal nephron: H+/K+-ATPase or H+-ATPase defect.
Gradient defect: abnormally permeable distal tubule and collecting duct allows secreted H+ ions to flow back into tubular cell (can be caused by amphotericin for fungal infections)

Lack of net H+ ion secretion prevents urinary acidification and exretion of ammonium. Also prevents some HCO3- reabsorption in the distal tubule.

Question 8

What are some common etiologies of Distal RTA (Type 1)?

Answer 8

Systemic disease such as Sjogren's Syndrome
Glue sniffing (toluene)

Question 9

What are some associated clinical manifestations of Distal RTA (Type 1)?

Answer 9

Associated with nephrolithiasis or nephrocalcinosis

Question 10

How do you dx Distal RTA (Type 1)?

Answer 10

NAGMA
Unable to acidify urine pH < 5.5
Hypokalemia, usually severe (from urinary K+ wasting)
UAG is positive, indicates inability to acidify urine in distal nephron

Question 11

What is Hyperkalemic RTA (Type 4) characterized by?

Answer 11

Distal nephron dysfunction from impaired renal exretion of H+ and K+ causing a NAGMA and hyperkalemia

Question 12

What are some causes of Hyperkalemic RTA (Type 4)?

Answer 12

Deficiency of circulating aldosterone

 - DM
 - Drugs (NSAIDs, beta-blockers, ACEi, high dose heparin)

Aldosterone resistance in collecting ducts

 - Interstitial renal disease (sickle cell nephropathy, obstructive uropathy, lupus)
 - Drugs (amiloride, triamterene, spironolactone, trimenthoprim)

Either case results in impaired Na+ reabsorption by principle cells and leads to decrease in luminal negativity of CD which impairs acidification as result of decrease driving force for H+ secretion. Resulting hyperkalemia also worsens acidosis by preventing ammoniagenesis in the PT.

Question 13

What are the clinical manifestations of Hyperkalemic RTA (Type 4)?

Answer 13

Usually asymptomatic
NAGMA
Hyperkalemia
Most pts are in their 50-70s with a hx of DM or CKD

Question 14

How do you dx Hyperkalemic RTA (Type 4)?

Answer 14

Variable urine pH, usually >5.5

UAG is positive

Question 15

What causes metabolic alkalosis in a general sense?

Answer 15

Factors that stimulate Na+ reabsorption, secondarily increase H+ secretion and thus stimulate HCO3- reabsorption leading potentially to a metabolic alkalosis

Question 16

What are the main (5) causes of metabolic alkalosis?

Answer 16

Hypokalemia
Vomiting or nasogastric tube suctioning
Diuretics (thiazide and loop diuretics)
Volume depletion (contraction alkalosis)
Mineralocorticoid excess (appropriate or inappropriate)

Question 17

What are some causes of respiratory alkalosis?

Answer 17

Anything that increases respiratory rate or tidal volume:
Exercise, pregnancy
Pneumonia
Pulmonary embolus
Pulmonary edema
Sepsis
CHF
Elevated altitude

Question 18

What causes respiratory acidosis?

Answer 18

Anything that lowers respiratory rate/tidal volume, increases dead space, or worsens airway obstruction:
Acute lung injury
Pneumonia
PE
Interstitial lung disease
COPD

Inadequate ventilatory settings
Increased CO2 production (increased carb diet, hyperthermia, seizures)