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Questions and Answers
Progressive renal failure results in the slow loss of nephrons over time.
Progressive renal failure results in the slow loss of nephrons over time.
True
When the GFR falls below 40 ml/min, ammonium secretion begins to increase.
When the GFR falls below 40 ml/min, ammonium secretion begins to increase.
False
Renal tubular acidosis (RTA) is due to defects in which of the following processes? (Select all that apply)
Renal tubular acidosis (RTA) is due to defects in which of the following processes? (Select all that apply)
Type 1 RTA is also known as:
Type 1 RTA is also known as:
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Type 1 RTA is associated with hypokalemia.
Type 1 RTA is associated with hypokalemia.
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Type 2 RTA commonly occurs as a part of:
Type 2 RTA commonly occurs as a part of:
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Type 3 RTA is:
Type 3 RTA is:
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Type 4 RTA is also known as hyperkalemic RTA.
Type 4 RTA is also known as hyperkalemic RTA.
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What is the normal range for the anion gap?
What is the normal range for the anion gap?
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The anion gap is used in the diagnosis of metabolic alkalosis.
The anion gap is used in the diagnosis of metabolic alkalosis.
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Which of the following is NOT a cause of increased anion gap metabolic acidosis?
Which of the following is NOT a cause of increased anion gap metabolic acidosis?
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The urinary anion gap is used to differentiate between renal and non-renal causes of non-anion gap metabolic acidosis.
The urinary anion gap is used to differentiate between renal and non-renal causes of non-anion gap metabolic acidosis.
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The osmolar gap is a mathematical calculation that always provides accurate results.
The osmolar gap is a mathematical calculation that always provides accurate results.
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Which of the following is NOT a main cause of an osmolar gap?
Which of the following is NOT a main cause of an osmolar gap?
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What is the normal range for arterial pH?
What is the normal range for arterial pH?
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A high osmolar gap is an indirect indicator of the presence of an abnormal solute in significant amounts.
A high osmolar gap is an indirect indicator of the presence of an abnormal solute in significant amounts.
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Kussmaul breathing is characterized by shallow and slow respirations.
Kussmaul breathing is characterized by shallow and slow respirations.
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Which of the following is a clinical feature of metabolic alkalosis?
Which of the following is a clinical feature of metabolic alkalosis?
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Hypokalemia is commonly seen in both metabolic acidosis and metabolic alkalosis.
Hypokalemia is commonly seen in both metabolic acidosis and metabolic alkalosis.
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The RAAS system is activated in hypovolemia to conserve water and sodium.
The RAAS system is activated in hypovolemia to conserve water and sodium.
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Which of the following is a common cause of vomiting-induced metabolic alkalosis?
Which of the following is a common cause of vomiting-induced metabolic alkalosis?
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A high anion gap indicates that the kidney is effectively regulating acid-base balance.
A high anion gap indicates that the kidney is effectively regulating acid-base balance.
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What type of acid-base disorder is commonly observed in diabetic ketoacidosis?
What type of acid-base disorder is commonly observed in diabetic ketoacidosis?
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Hypokalemia will worsen the symptoms of diabetic ketoacidosis.
Hypokalemia will worsen the symptoms of diabetic ketoacidosis.
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The presence of ketones in the urine can be a sign of diabetic ketoacidosis.
The presence of ketones in the urine can be a sign of diabetic ketoacidosis.
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In diabetic ketoacidosis, hyponatremia is often caused by excessive fluid intake.
In diabetic ketoacidosis, hyponatremia is often caused by excessive fluid intake.
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Treatment for diabetic ketoacidosis involves fluid replenishment with glucose-containing solutions.
Treatment for diabetic ketoacidosis involves fluid replenishment with glucose-containing solutions.
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A patient with diabetic ketoacidosis and proteinuria should be evaluated for kidney function.
A patient with diabetic ketoacidosis and proteinuria should be evaluated for kidney function.
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What is the primary role of the collecting duct H-ATPase in metabolic alkalosis?
What is the primary role of the collecting duct H-ATPase in metabolic alkalosis?
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Study Notes
Renal Causes of Acidosis
- Renal failure leads to a slow loss of nephrons over time.
- Initially, remaining nephrons increase ammonium secretion.
- When glomerular filtration rate (GFR) falls below 40 mL/min, ammonium secretion decreases.
- Part of the acid load is retained and bicarbonate buffering results in a lower plasma bicarbonate level.
- Much of the H+ is buffered in cells and bone.
Renal Tubular Acidosis (RTA)
- RTA is a group of disorders where the kidneys produce the acidosis.
- RTA is due to defects in renal H+ secretion or bicarbonate reabsorption.
- Two types of RTA:
- Impairment of tubular bicarbonate reabsorption, causing bicarbonate loss in the urine.
- Inability of tubular mechanisms to secrete sufficient H+ into the urine.
Type 1 RTA
- Also called distal RTA.
- A defect in type A intercalated cells.
- Decreased H+ excretion and inability to lower urine pH below 5.6 to 6.0.
- Can excrete enough ammonium to maintain balance.
- Higher urine pH reduces the ability of titratable acids and ammonia to trap H+ in the tubule.
- Associated with hypokalemia.
- Four different mechanisms could cause Type 1 RTA:
- Apical H-ATPase not working due to acquired or genetic defects.
- Basolateral Cl-bicarbonate exchange mutations.
- Apical membrane or tight junctions fail to stop back diffusion of H+ out of the tubules.
- Decreased Na reabsorption by principal cells of cortical collecting duct disrupts the negative potential of the lumen, leading to a disruption of H+ retention in the lumen, also impairs K secretion.
Type 2 RTA
- Also called proximal tubule RTA.
- Impairment of proximal tubule bicarbonate reabsorption, leading to bicarbonate loss in the urine.
- Usually part of generalized proximal tubule failure, such as in Fanconi syndrome.
- Self-limiting.
- Ability to reabsorb bicarbonate is reduced from the normal 26 mEq/L to 17 mEq/L.
- Plasma bicarbonate falls to 17 mEq/L.
- Patient can then excrete the daily acid load.
- New steady state where plasma bicarbonate remains low.
- Patient has acidemia.
- Acidemia can contribute to bone mineral loss over time.
Type 3 RTA
- Extremely rare.
- A combination of type 1 and type 2 RTA.
Type 4 RTA
- Also called hyperkalemic RTA.
- Due to hypoaldosteronism or pseudohypoaldosteronism (failure to respond to aldosterone).
- Produces a mild metabolic acidosis.
- Aldosterone normally stimulates distal H+ secretion and K secretion.
- Low aldosterone reduces H+ and K secretion, resulting in acidosis and hyperkalemia.
Determining the Causes of Metabolic Acidosis
- Anion gap is used in diagnosis.
- Plasma HCO3- is reduced.
- If Na+ levels are unchanged, anions must increase (either Cl- or an unmeasured anion).
- Hyperchloremic metabolic acidosis: Cl- levels increase, anion gap is normal (while HCO3- is reduced).
- If Cl- levels are unchanged, an unmeasured anion (e.g. lactic acid, ketoacids) has increased, and the anion gap is increased.
- The anion gap helps determine the cause of metabolic acidosis.
Anion Gap in Metabolic Acidosis
- Anion gap used in diagnosis of the causes of metabolic acidosis.
- Plasma HCO3- is reduced.
- If Na+ levels are unchanged, anions must increase (either Cl- or an unmeasured anion).
- Hyperchloremic metabolic acidosis: Cl- levels increase, anion gap is normal (while HCO3- is reduced).
- If Cl- levels are unchanged, an unmeasured anion (e.g., lactic acid, ketoacids) has increased, and the anion gap is increased.
Metabolic Acidosis Associated with Normal or Increased Plasma Anion Gap
- Includes conditions like diabetes mellitus (ketoacidosis), lactic acidosis, chronic renal failure, aspirin poisoning, methanol poisoning, ethylene glycol poisoning, and starvation.
- Includes also diarrhea, renal tubular acidosis, carbonic anhydrase inhibitors, and Addison's disease (aldosterone deficiency).
Urinary Anion Gap
- Urinary ion gap = (Na+ + K+) – CI-.
- Measured cations are Na+ and K+ and the anion is CI-.
- Major unmeasured ions are bicarbonate and NH4+.
- Normally a positive or near zero gap.
- In metabolic acidosis, excess H and NH4+ Cl excretion increases.
- An approximate measure of ammonium excretion as the Cl- increase generates a negative AG.
- Allows differentiation of renal vs non-renal causes of non-anion gap metabolic acidosis.
- Increased urinary anionic gap suggests low NH4+ (renal tubular acidosis).
- Decreased urinary anionic gap suggests high NH4+ (diarrhea).
Osmolar Gap
- Osmolar gap = measure serum osmolality – calculated osmolarity.
- Calculated osmolarity = 2[Na] + [glucose] + [urea] (all in mmol/L).
- Normal osmolar gap <10 mOsm/kg.
- Serum osmolality (mOsm/kg) measured by freezing point depression.
- Individual components are measured in osmolarity (mOsm/L).
- A high osmolar gap is indirect evidence of an abnormal solute in significant amounts.
Osmolar Gap: Causes for an Osmolar Gap
- Alcohols (ethanol, methanol, ethylene glycol, isopropyl alcohol, propylene glycol, acetone).
- Sugars (mannitol, sorbitol).
- Lipids (hypertriglyceridemia).
- Proteins.
Clinical Approach to Acid-Base Disorders
- Determine pH (acidosis or alkalosis).
- Direction of PCO2 and [HCO3-] changes (respiratory or metabolic).
- Degree of compensation (simple or mixed acid-base disorder).
- Calculate the ion gap (useful for metabolic acidosis, with or without alkalosis).
- Determine underlying causes.
- Therapy.
Metabolic Acidosis Clinical Features
- Acidosis: increased ventilation with pH <7.20 extremely deep and rapid (Kussmaul's) breathing.
- Potassium shifted out of cells and renal K+ excretion increases.
- Normal to increased serum K+ observed.
- Chronic acidosis: hypercalciuria and bone disease, the bone acts as a buffer and calcium leached out over time.
- Severe metabolic acidosis can lead to hypotension, pulmonary edema, and eventually cardiac issues.
Metabolic Alkalosis Clinical Features
- No specific symptoms or signs.
- Suspected if patient has muscle cramps, weakness, arrhythmias or seizures (pH >7.6).
- Especially if associated with an appropriate clinical scenario (diuretic use, vomiting).
Systemic Effects of Alkalosis
- Opposite of acidosis.
- Minor effects on cardiovascular system.
- Impairs oxygen delivery.
- Chronic non-respiratory alkalosis: potassium depletion and hypokalemia (decreased tubular H+ secretion leads to increased tubular K+ secretion).
Acid-Base Disorders
- Clinically common due to underlying condition(s).
Case 1: Severe Vomiting
- Severe vomiting due to gastroenteritis for 2 days.
- Can eat only small amounts of soup.
- Blood pressure (BP) 110/70 mm Hg supine, 95/60 mm Hg.
- Lost 2.1 kg.
- Initial blood work: BUN 11 mmol/L, creatinine 105 µmol/L, Na 141 mEq/L, K 3.2 mEq/L, Cl 90 mEq/L, Total CO2 36 mEq/L, arterial pH 7.50, pCO2 48 mm Hg.
- Urine Na 10 mEq/L, urine pH 5.0.
Total CO2 as a Measure of Bicarbonate
- Total CO2 (TCO2) consists of bicarbonate (HCO3-), dissolved carbon dioxide (CO2), and carbonic acid (H2CO3).
- The dissolved carbon dioxide (dCO2) is calculated from pCO2 and typically about 3 mmol/L higher than pCO2.
- Bicarbonate (90-95%) represents the majority of total CO2.
Vomiting-Induced Metabolic Alkalosis
- Vomiting (loss of HCl from the stomach) causes metabolic alkalosis.
- Easily determined based on history.
Prerenal Renal Failure
- BUN and creatinine elevated indicating reduced renal function in prerenal failure.
- Reduced blood flow lowers GFR (could be from dehydration or hypovolemia).
Alkalosis Initiated by Loss of Gastrointestinal HCl
- Normally, gastric acid is balanced by pancreatic bicarbonate secretion.
- Without the acid, bicarbonate secretion is not induced.
- For every mole of H+ lost, a mole of bicarbonate is retained in circulation.
- Correction by urinary excretion of excess bicarbonate would normally correct the alkalosis.
Hypovolemia and Maintenance of Alkalosis
- Hypovolemia is necessary to maintain the alkalosis.
- RAAS system is activated.
RAAS Activation and Bicarbonate Conservation
- RAAS activates sodium and water retention.
- Takes several days for RAAS system to fully conserve bicarbonate.
- Initially, some excess bicarbonate is excreted with Na and K, only Cl is appropriately conserved.
- Hypokalemia is due to K loss at this stage (although K loss from stomach is minor).
- After a few days, if hypovolemia and Cl loss sufficient, all the bicarbonate is reabsorbed.
- This increases the alkalosis.
Metabolic Alkalosis in Hypovolemic Patients
- In hypovolemic patients, aldosterone is released, associated with sodium retention and increased bicarbonate reabsorption.
- If volume depletion sufficient, all bicarbonate reabsorbed.
- Urine sodium is low (10 mEq/L) and urine is paradoxically acidic (pH 5.0).
Role of Chloride in Metabolic Alkalosis
- Chloride depletion can increase distal bicarbonate reabsorption, increase H+ secretion, and reduce bicarbonate secretion.
- Two mechanisms:
- Collecting duct H-ATPase is associated with passive co secretion of Cl to maintain electroneutrality. Low Cl enhances the gradient for Cl secretion, indirectly promoting H+ secretion.
- Type B intercalated cells normally secrete bicarbonate into the lumen (basolateral H-ATPase and luminal Cl-HCO3- exchanger). Bicarbonate secretion driven by luminal Cl, but with reduced Cl concentrations, the bicarbonate secretion is reduced.
Treatment of Alkalosis
- Fluid replacement with NaCl and KCl corrects alkalosis by allowing bicarbonate excretion as Na bicarbonate.
Case 2: Diabetic Ketoacidosis
- 28-year-old man with type 1 diabetes presenting with abdominal pain and 5 days of vomiting.
- Vomit is brown/green liquid with no blood.
- Temperature 37.2°C, pulse 125, blood pressure 85/50, respiratory rate 32/min, oxygen saturation 95%, glucose 26.1 mmol/L (random <6.9 mmol/L).
- Laboratory results: Na 130 mmol/L, K 7.1 mmol/L, Urea 30.3 mmol/L, Creatinine 368 µmol/L, Cl 102 mmol/L, arterial pH 7.12, pCO2 19.5 mm Hg, HCO3 10 mmol/L.
Other Possibilities
- This case has no mention of limited (oliguria) or no urine production (anuria) in a case where hypovolemia is truly severe.
- Some tissues would not be perfused and therefore oxygen deprived in the presence of low oxygen.
- Tissues would switch to producing lactic acid, adding another acid to the blood.
Acid-Base Disorders Summary
- Determine the nature of the acid-base disorder (acidosis/alkalosis, metabolic/respiratory, simple or mixed).
- Determine the cause (history and laboratory results).
- Correcting the cause can correct the disorder.
Diabetic Ketoacidosis Summary
- Leads to reduced level of consciousness, abdominal pain, fever, polyuria/polydipsia, severe acidosis causing gastric atony (gastroparesis).
- Likely cause of vomiting.
Hyperkalemia in Diabetic Ketoacidosis
- Diabetic with poorly controlled blood sugars has possible total body K low, but K is in the wrong space (outside cells).
- Acidosis pushes K out of cells as H+ is buffered in cells.
- Lack of insulin pushes K into the ECF causing hyperkalemia.
- Hyperkalemia is typical at presentation, but hypokalemia might occur after insulin started.
- Na+, K+, Mg2+, phosphates, and water are all depleted due to hyperglycemia-induced osmotic diuresis.
Additional Considerations in Diabetic Ketoacidosis
- Low blood pressure (BP) and elevated urea/creatinine indicate poor kidney function.
- High glucose and glucosuria lead to excessive urination (loss of fluids).
- Vomiting further reduces fluids.
- Hyponatremia (low Na) is common.
- Hypovolemia activate RAAS, leads to fluid retention.
- Dehydration and lack of insulin are life-threatening, so replenish fluids (saline with K) at established rates.
Treatment Considerations
- Treat with insulin until ketosis resolves.
- Dipstick shows protein in the urine, which might be a sign of nephropathy complication.
- Patient should have his GFR determined to test for renal function.
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Test your knowledge on renal physiology concepts including progressive renal failure, renal tubular acidosis, and the anion gap. This quiz covers key definitions and associations that are crucial for understanding kidney function and disorders. Perfect for students in medical or health sciences courses.
