Acid-Base Disorders Part 2 (Andelin) Flashcards
How is acidosis associated with hyperkalemia?
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)
How is alkalosis associated with hypokalemia?
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)
High anion gap metabolic acidosis differential diagnosis?
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)
Ethylene Glycol toxicity
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.
Methanol toxicity
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.
Fomepizole
Drug used as treatment for both ethylene glycol (antifreeze) and methanol (moonshine) toxicity.
Fomepizole inhibits alcohol dehydrogenase (ADH)
Pyroglutamic acidosis (5-Oxoproline)
Chronic acetaminophen use (females with chronic illness).
Causes HAGMA. Order a BMP (anion gap) and ABG. Treatment is IV fluids. (may need N-acetylcysteine)
inhibits alcohol dehydrogenase (fomepizole)
L- Lactic acidosis
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.
D - Lactic acidosis
Uncommon (mostly seen in short bowel syndrome); HAGMA; Order BMP, ABG and D Lactic acid test.
Aspirin (salicylate) overdose
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)
Diabeteic Ketoacidosis (DKA)
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)
Treatment for DKA
Treat with IV fluids, IV insulin, follow anion gap and monitor potassium (watch for hypokalemia)
Treat with IV bicarbonate for aspirin (salicylate) toxicity
What does RTA mean?
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
RTA type 2
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
Fanconi syndrome
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
Causes of Fanconi syndrome
Type 2 RTA
Hereditary- Cystinosis
Acquired- Multiple Myeloma or Meds
Causes of RTA type 2
Proximal RTA causes:
Fanconi syndrome
Carbonic Anhydrase inhibitors
Carbonic Anhydrase inhibitors
can cause proximal RTA (type 2)
acetazolamide - causes impaired bicarbonate reabsorption at PCT (used in high altitude respiratory alkalosis)
Clinical presentation of RTA 2
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)
Diagnosis of RTA 2
NAGMA -duRhaam
Diagnosis: urine pH (may be high or low depending on serum HCO3; high only if PCT over exceeds its reabsorption abilities)
RTA type 1
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
Causes of RTA 1
Distal RTA
Autoimmune (sjogren’s)
Amphotericin B toxicity
Clinical presentation of RTA 1
rare disorder; NAGMA; associated with nephrolithiasis (calcium phosphate); hypokalemia (severe urinary K+ wasting)
Diagnosis: high urine pH (cannot acidify the urine-lacking secreted H+)
Diagnosis of RTA 1
Diagnosis: high urine pH (cannot acidify the urine-lacking secreted H+)
RTA type 4
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.
Pathophysiology of RTA 4
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.
How does hyperkalemia worsen RTA 4
Hyperkalemic RTA (principle cells in CD); resulting hyperkalemia worsens acidosis by preventing ammoniageneis (new ammonium) in the proximal tubule. This impairs urinary acidification
Causes of RTA 4
Hyperkalemic RTA (principle cells in CD)
Deficiency of circulating aldosterone
Aldosterone resistance in collecting ducts
Clinical manifestation of RTA 4
Usually asymptomatic
NAGMA; Hyperkalemia
Most patients are in their 50-70s with hx of diabetes or CKD
Diagnosis of RTA 4
Variable urine pH (usually < 5.5) and increased serum potassium (hyperkalemia)
Acidemia (decreased pH) + Normal Anion Gap (NAGMA) + No Kidney Injury and no Diarrhea should lead you to what differential diagnosis?
Renal Tubular Acidosis (RTA); most common is RTA Type 4 (“hyperkalemic”)
High Urine Chloride (>20 mEq/L) Metabolic Alkalosis Differential Diagnosis
Saline-resistant metabolic alkalosis:
Hyperaldosteronism
Bartter syndrome
Gitelman syndrome
Liddle syndrome
Hyperaldosteronism
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)
Bartter Syndrome
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)
Gitelman Syndrome
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.
Liddle Syndrome
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.
Treatment of hyperaldosteronism
Treatment: Spironolactone (mineralocorticoid receptor blocker)
Clinical manifestation of Bartter syndrome
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)
Clinical manifestation of Gitelman Syndrome
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.
Bartter vs. Gitelman Syndromes in calciuria.
Bartter Syndrome (“babies”) - hypercalciuria
Gitelman Syndrome (adults) - hypocalciuria (also will hae hypomagnesemia)
What should be on your differential in patients who present at a young age with HTN and electrolyte abnormalities?
Liddle Syndrome. AD disorder. Clinical manifestation;: resistant HTN, Hypokalemia and NAGMA (saline resistant)
Clinical manifestation of Liddle Syndrome
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.
Mutation in ENaC
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.
Diagnosis of Liddle syndrome
Diagnosis: low aldosterone (“liddle”) and renin levels.
Treatment of Liddle syndrome
Treatment: Amiloride or Trimterene (block Na+ ch) with a low salt diet.
