Lecture 4: Hyperchloremic Acidosis (aka Non-anion gap)

Question 1

A pH < ____ is considered acidosis

Answer 1

pH 7.36

Question 2

In urine studies what is the primary unmeasured anion?

Answer 2

NH₄

Question 3

How do you calculate urine anion gap (UAG)?

Answer 3

UAG = [Na⁺ + K⁺] - [Cl^-]

Question 4

When Cl^- > Na⁺ + K⁺ the urine anion gap is negative and indicates what about NH₄⁺ and the cause of the acidosis?

Answer 4

NH₄ is appropriately secreted and suggests non-renal cause for acidosis

Question 5

When urine anion gap (UAG) is positive, what does this suggest about the cause of the acidosis?

Answer 5

Renal cause

Question 6

Major presenting sx’s of pyelonephritis w/ obstructive uropathy?

Answer 6

• Fever
• Vomiting
• Foul smelling urine
• Renal colic

Question 7

Hyperchloremic metabolic acidosis due to inadequate NH₃ production, caused by renal failure, hypoaldosteronism, or pseudohypoaldosteronism will have what urine pH and UAG finding?

Answer 7

• Urine pH <5.5
• Positive UAG

Question 8

A fractional excretion of HCO₃ > 15% leading to hyperchloremic metabolic acidosis is due to what disorder?

Answer 8

Proximal RTA = type 2

Question 9

Which urine pH and UAG finding is associated with distal RTA = type 1?

Answer 9

• Urine pH >5.5
• Positive UAG

Question 10

What are 5 disorders causing extrarenal loss of base acid load and are associated with a negative UAG?

Answer 10

• Diarrhea
• Pancreatic fistula
• Ureteral diversions
• NH₄Cl/HCL
• NaCl load

Question 11

What are 2 causes of hyprchloremic metabolic acidosis that will have a high urine osmole gap?

Answer 11

• Toulene ingestion
• DKA

Question 12

What type of RTA is associated with a urine pH >5.5, positive UAG, and hypokalemia?

Answer 12

Distal RTA = type 1

Question 13

RTA with urine pH >5.5, positive UAG, and hyperkalemia can be due to what 2 disorders?

Answer 13

1. Generalized tubular defect
2. Ureteral obstruction

Question 14

Which type of RTA is associated with positive UAG and hyperkalemia?

Answer 14

RTA type 4

Question 15

What are 5 major causes of RTA type 4?

Answer 15

1. Hypoaldosteronism
2. PHA type 1 (AD)
3. PHA type 1 (AR)
4. Gordon’s syndrome (PHA II)
5. Kidney failure

Question 16

Which type of RTA is associated w/ hyperkalemia and positive UAG?

Answer 16

Proximal RTA = type 4

Question 17

Major urine findings of RTA type 2 (aka proximal RTA)?

Answer 17

• Glycosuria
• Aminoaciduria
• Phosphaturia
• Bicarbonaturia

Question 18

Classic distal RTA type 1 is an inability of the distal tubule to?

Answer 18

Acidify the urine

Question 19

Classic distal RTA type 1 is associated with what 3 drugs?

Answer 19

• Lithium
• Toluene
• Amphotericin

Question 20

Pts with RTA type 1 (aka classic distal) have hypocitraturia and hypercaliuria so they are prone to what?

Answer 20

• Nephrolithiasis = calcium oxalate stones
• Nephrocalcinosis
• Bones problems —> rickets (children) and osteoporosis/malacia (adults)

Question 21

Which type of RTA has decreased ammoniagenesis due to hyperkalemia?

Answer 21

RTA type 4 (hypoaldosteronism)

Question 22

Due to the low aldosterone in RTA type 4 there is less Na⁺ reabsorbed and the lumen is less negative, so how is the pH maintained at a normal level?

Answer 22

Hydrogen pump is still effective

Question 23

RTA type IV is made worse by which drugs?

Answer 23

• Drugs affecting RAAS: ACE inhibitors, ARBs and NSAIDs
• Especially K⁺-sparing diuretics (i.e., amiloride, triamterene, and spironolactone)

Question 24

RTA type IV is usually a presumptive diagnosis and must be proven by what 2 levels?

Answer 24

Low renin and low aldosterone

Question 25

What are some of the major causes of hypoaldosteronism?

Answer 25

- **Hypo**reninemic hypoaldosteronism: **RTA type 4** - **Drugs**: ACE inhibitors, ARBs and Heparin - **CKD** and **DM**

Question 26

How is the diagnosis of RTA type 2 made?

Answer 26

- Delivering HCO₃^- and measuring fractional excretion of HCO₃^- - UFE HCO₃^- **\>15%** with bicarb challenge

Question 27

Carbonic anhydrase deficiency can cause what type of RTA?

Answer 27

RTA type 2

Question 28

Wilson disease is associated with what type of RTA?

Answer 28

RTA type 2

Question 29

Lead poisoning may lead to what type of RTA?

Answer 29

RTA type 2

Question 30

List 4 drugs which may cause RTA type 2?

Answer 30

- Aminoglycosides - Carbonic anhydrase inhibitors - Topiramate - Acetazolamide

Question 31

What are 2 hormonal causes of RTA type 2?

Answer 31

1. Hyperparathyroidism 2. Vitamin D deficiency

Question 32

Generalized tubular defect leading to hyperchloremic acidosis is associated with the impaired secretion of what 2 ions? Which serum level is elevated?

Answer 32

- **Impaired** secretion of: **H⁺** and **K⁺** - Elevated **serum K⁺**

Question 33

What are 3 underlying disorders which may cause a generalized tubular defect and NAGMA?

Answer 33

1. Sickle cell anemia 2. SLE 3. Obstructive uropathy

Question 34

Which urine pH and UAG value are associated w/ diarrhea leading to NAGMA?

Answer 34

- Urine pH **\>5.5** - **Negative** UAG

Question 35

How does chronic progressive kidney disease lead to NAGMA?

Answer 35

- **Decrease** in ammoniagenesis proportionate to loss of nephrons - GFR \<40 unable to secrete daily load of acid - Less ammonia --\> less anion secretion \*Urine pH \<5.5 and positive UAG

Question 36

Which ions are lost in the stool (i.e., net effect) during diarrhea, which leads to NAGMA? How is the urine pH increased?

Answer 36

- HCO₃^- loss and K⁺ loss - **HYPO**kalemia and **HYPO**bicarbemia - Hypokalemia causes increased renal production of NH₄ providing urinary buffer that increases urine pH

Question 37

Using the "Proud American Veterans Love GM" mnemonic what are the common causes of Chronic Tubulointerstitial Disease?

Answer 37

- **P**rostate (obstructive uropathy) - **A**nalgesics - **V**U reflux - **L**ead (heavy metals) - **G**out - **M**yeloma

Question 38

Muscle weakness or paralysis, fatigue, constipation, and myalgia are associated with low levels of what ion?

Answer 38

**HYPO**kalemia