Acid-Base Disorders Part 2 (Andelin)

Question 1

How is acidosis associated with hyperkalemia?

Answer 1

Caused by a transcellular shift of cations (H+ and K+) into and out of cells so that electro-neutrality is maintained.

In acidosis, H+ enter the cells and K+ exit the cells (entering the blood serum = hyperkalemia)

Question 2

How is alkalosis associated with hypokalemia?

Answer 2

Caused by a transcellular shift of cations (H+ and K+) into and out of cells so that electro-neutrality is maintained.

In alkalosis, H+ exit the cells and K+ enter the cells (leaving the blood serum = hypokalemia)

Question 3

High anion gap metabolic acidosis differential diagnosis?

Answer 3

GOLD MARK
G - Glycols
O - Oxoproline (chronic acetaminophen use)
L - L type Lactic acidosis
D - D type Lactic acidosis (short bowel syndrome)
M - Methanol
A - Aspirin/salicylate toxicity
R - Renal failure
K - Ketoacidosis (DKA)

Question 4

Ethylene Glycol toxicity

Answer 4

ingredient in antifreeze; ingested because of its sweet taste in children and can be a suicide attempt in adults.

Causes HAGMA; AKI/flank pain/hematuria due to calcium oxalate crystals; oxidized to toxic metabolites (oxalic acid). Order a BMP (anion gap) and ABG. Treatment is Fomepizole.

Question 5

Methanol toxicity

Answer 5

Can be accidental or intentional ingestion (Moonshine).
Causes HAGMA; blurred vision/vision loss, halos (retinal toxicity); oxidized to toxic metabolites (formic acid). Order a BMP (anion gap) and ABG. Treatment is Fomepizole.

Question 6

Fomepizole

Answer 6

Drug used as treatment for both ethylene glycol (antifreeze) and methanol (moonshine) toxicity.

Fomepizole inhibits alcohol dehydrogenase (ADH)

Question 7

Pyroglutamic acidosis (5-Oxoproline)

Answer 7

Chronic acetaminophen use (females with chronic illness).
Causes HAGMA. Order a BMP (anion gap) and ABG. Treatment is IV fluids. (may need N-acetylcysteine)

Question 8

Answer 8

inhibits alcohol dehydrogenase (fomepizole)

Question 9

L- Lactic acidosis

Answer 9

Common in hospitalized patients (sepsis); HAGMA and septic shock (if cause); due to hypoperfusion, increased production or decreased utilization of lactic acid; Order BMP, ABG and L Lactic acid test.

Question 10

D - Lactic acidosis

Answer 10

Uncommon (mostly seen in short bowel syndrome); HAGMA; Order BMP, ABG and D Lactic acid test.

Question 11

Aspirin (salicylate) overdose

Answer 11

Suicide attempt or unintentional OD; mixed acid-base disorder that presents as respiratory alkalosis (early) and metabolic acidosis (late).

Hyperventilation, tinnitus and fever due to impaired oxidative phosphorylation. Order BMP, ABG and check salicylate levels. Treat with IV bicarb (traps ionized form of salicylate)

Question 12

Diabeteic Ketoacidosis (DKA)

Answer 12

Most common complication of DM1. HAGMA; presents with Kussmaul respirations (Increased RR), fruity breath, high BG, due to lack of insulin causes prevention of glucose metabolism so there is a switch to metabolizing FAs and producing ketones. Order BMP, ABG, BG, check serum and urine for elevated ketones. Treat with IV fluids, IV insulin, follow anion gap and monitor potassium (watch for hypokalemia)

Question 13

Treatment for DKA

Answer 13

Treat with IV fluids, IV insulin, follow anion gap and monitor potassium (watch for hypokalemia)

Question 14

Answer 14

Treat with IV bicarbonate for aspirin (salicylate) toxicity

Question 15

What does RTA mean?

Answer 15

Renal Tubular Acidosis
Causes Normal Anion Gap Metabolic Acidosis (NAGMA)
duRhaam

Impairment of net acid secretion by the kidneys, leads to NAGMA and cannot be diagnosed in the setting of AKI

Question 16

RTA type 2

Answer 16

Proximal RTA
decreased ability of the PCT to reabsorb HCO3 (85% is usually reabsorbed) results in HCO3 loss to the urine (urine pH > 5.5) makes alkaline urine. When serum HCO3 drops, less is filtered and the resorption ability of PCT is not overwhelmed and can reabsorb some of the bicarb to keep urine at a normal pH < 5.5

Question 17

Fanconi syndrome

Answer 17

Cause of RTA type 2 (proximal RTA)
generalized reabsorption defect in PCT
Will be normal serum glucose with high urine glucose**
Growth retardation in children
Causes: Hereditary- Cystinosis and Acquired- Multiple Myeloma or Meds

Question 18

Causes of Fanconi syndrome

Answer 18

Type 2 RTA
Hereditary- Cystinosis
Acquired- Multiple Myeloma or Meds

Question 19

Causes of RTA type 2

Answer 19

Proximal RTA causes:
Fanconi syndrome
Carbonic Anhydrase inhibitors

Question 20

Carbonic Anhydrase inhibitors

Answer 20

can cause proximal RTA (type 2)
acetazolamide - causes impaired bicarbonate reabsorption at PCT (used in high altitude respiratory alkalosis)

Question 21

Clinical presentation of RTA 2

Answer 21

this is very rare; NAGMA -duRhaam. Hypokalemia; worsens with alkali treatment*
Diagnosis: urine pH (may be high or low depending on serum HCO3; high only if PCT over exceeds its reabsorption abilities)

Question 22

Diagnosis of RTA 2

Answer 22

NAGMA -duRhaam
Diagnosis: urine pH (may be high or low depending on serum HCO3; high only if PCT over exceeds its reabsorption abilities)

Question 23

RTA type 1

Answer 23

Distal RTA (alpha intercalated cell)
decreased H+ net secretion in the distal nephron due to a H+/K+ ATPase or H+ATPase defect. Lack of H+ secreted prevents NH4 (ammonium) from being eliminated from the body and allows acid to build up (acidosis). Urine will have a high pH > 5.5

Question 24

Causes of RTA 1

Answer 24

Distal RTA
Autoimmune (sjogren’s)
Amphotericin B toxicity

Question 25

Clinical presentation of RTA 1

Answer 25

rare disorder; NAGMA; associated with nephrolithiasis (calcium phosphate); hypokalemia (severe urinary K+ wasting)
Diagnosis: high urine pH (cannot acidify the urine-lacking secreted H+)

Question 26

Diagnosis of RTA 1

Answer 26

Diagnosis: high urine pH (cannot acidify the urine-lacking secreted H+)

Question 27

RTA type 4

Answer 27

Hyperkalemic RTA (principle cells in CD)
Hypoaldosteronism (no aldosterone produced) or aldosterone resistance (aldosterone present but cells are unable to use it)
Impaired renal excretion of H+ and K+, leads to NAGMA and hyperkalemia.

Question 28

Pathophysiology of RTA 4

Answer 28

Hyperkalemic RTA (principle cells in CD)
Hypoaldosteronism (no aldosterone produced) or aldosterone resistance (aldosterone present but cells are unable to use it)
Impaired renal excretion of H+ and K+, leads to NAGMA and hyperkalemia. Impaired NA reabsorption leads to: decrease luminal charge of CD, decrease driving force for H+ secretion and impairs urinary acidification.

Question 29

How does hyperkalemia worsen RTA 4

Answer 29

Hyperkalemic RTA (principle cells in CD); resulting hyperkalemia worsens acidosis by preventing ammoniageneis (new ammonium) in the proximal tubule. This impairs urinary acidification

Question 30

Causes of RTA 4

Answer 30

Hyperkalemic RTA (principle cells in CD)
Deficiency of circulating aldosterone
Aldosterone resistance in collecting ducts

Question 31

Clinical manifestation of RTA 4

Answer 31

Usually asymptomatic
NAGMA; Hyperkalemia
Most patients are in their 50-70s with hx of diabetes or CKD

Question 32

Diagnosis of RTA 4

Answer 32

Variable urine pH (usually < 5.5) and increased serum potassium (hyperkalemia)

Question 33

Acidemia (decreased pH) + Normal Anion Gap (NAGMA) + No Kidney Injury and no Diarrhea should lead you to what differential diagnosis?

Answer 33

Renal Tubular Acidosis (RTA); most common is RTA Type 4 (“hyperkalemic”)

Question 34

High Urine Chloride (>20 mEq/L) Metabolic Alkalosis Differential Diagnosis

Answer 34

Saline-resistant metabolic alkalosis:
Hyperaldosteronism
Bartter syndrome
Gitelman syndrome
Liddle syndrome

Question 35

Hyperaldosteronism

Answer 35

A cause of High Urine Chloride (>20 mEq/L) Metabolic Alkalosis. Increased Na+ resorption and H+ and K+ secretion. Leads to HTN, hypokalemia and metabolic alkalosis.
Primary- bilateral adrenal hyperplasia/adrenal adenoma
Secondary- activated of RAAS
Treatment: Spironolactone (mineralocorticoid receptor blocker)

Question 36

Bartter Syndrome

Answer 36

A cause of High Urine Chloride (>20 mEq/L) Metabolic Alkalosis. AR disorder with mutation in co-transporter NKCC2* typically seen in prenatal or neonatal patients (unlikely see this in an adult)

Question 37

Gitelman Syndrome

Answer 37

A cause of High Urine Chloride (>20 mEq/L) Metabolic Alkalosis. AR disorder with Na+/Cl- cotransporter that affects reabsorption of NACl. More common than Bartter syndrome (“babies”) and seen late childhood or adulthood.

Question 38

Liddle Syndrome

Answer 38

A cause of High Urine Chloride (>20 mEq/L) Metabolic Alkalosis. AD disorder with a stimulation mutation in Na+ ch (ENaC) leads to INCREASED activity so INCREASED Na+ reabsorbed. Pts typically present at a young age with HTN and electrolyte abnormalities.

Question 39

Treatment of hyperaldosteronism

Answer 39

Treatment: Spironolactone (mineralocorticoid receptor blocker)

Question 40

Clinical manifestation of Bartter syndrome

Answer 40

AR mut in NKCC2 in prenatal or neonatal pts
Severe hypokalemia, metabolic alkalosis (saline resistant), low to normal BP, hypercalciuria* and nephrocalcinosis (similar to loop diuretics)

Question 41

Clinical manifestation of Gitelman Syndrome

Answer 41

AR disorder with Na+/Cl- cotransporter in adults.
Severe hypokalamia, metabolic alkalosis (saline resistant), low to normal BP, hypocalciuria* and hypomagnesemia.

Likely seen with chronic thiazide diuretics.

Question 42

Bartter vs. Gitelman Syndromes in calciuria.

Answer 42

Bartter Syndrome (“babies”) - hypercalciuria
Gitelman Syndrome (adults) - hypocalciuria (also will hae hypomagnesemia)

Question 43

What should be on your differential in patients who present at a young age with HTN and electrolyte abnormalities?

Answer 43

Liddle Syndrome. AD disorder. Clinical manifestation;: resistant HTN, Hypokalemia and NAGMA (saline resistant)

Question 44

Clinical manifestation of Liddle Syndrome

Answer 44

Resistant HTN, Hypokalemia and NAGMA (saline resistant). Diagnosis: low aldosterone (“liddle”) and renin levels. Treatment: Amiloride or Trimterene (block Na+ ch) with a low salt diet.

Question 45

Mutation in ENaC

Answer 45

Liddle Syndrome. AD disorder. Clinical manifestation;: resistant HTN, Hypokalemia and NAGMA (saline resistant). Patients who present at a young age with HTN and electrolyte abnormalities.

Question 46

Diagnosis of Liddle syndrome

Answer 46

Diagnosis: low aldosterone (“liddle”) and renin levels.

Question 47

Treatment of Liddle syndrome

Answer 47

Treatment: Amiloride or Trimterene (block Na+ ch) with a low salt diet.