Acid Base

Question 1

What is the anion gap used for?

Answer 1

The Anion Gap (AG) is a derived variable primarily used for the evaluation of metabolic acidosis to determine the presence of unmeasured anions.

Question 2

What is the tx for metabolic acidosis?

Answer 2

• Treat underlying cause(s)
• Bicarbonate (especially w/ nl AG acidosis) – Na or K bicarbonate (or bicarbonate former) depending on etiology and electrolyte values.

Question 3

Explain the lab abnormalities seen w/each of these labs w/metabolic alkalosis:

• ABG
• Lytes
• BUN
• Hct
• Urine [Cl-]

Answer 3

• ABG: increased pH, [HCO3-], and PCO2
• Electrolytes: elevated [HCO3-], decreased [Cl-], usually low [K+], slight increase in anion gap (increased negative charges on albumin, increased lactate due to increased intracellular pH)
• BUN: frequently increased (volume depletion)
• Hematocrit: frequently increased (volume depletion)
• Urine [Cl-]: very helpful in differential diagnosis (value < 10 mmol/L indicates volume/chloride depletion)

Question 4

How is metabolic alkalosis treated?

Answer 4

• Potassium administration
• Acetazolamide
• Volume repletion
• Intravenous HCl or NH4Cl (rarely done)

Question 5

Why does a loss of HCl from the body lead to a metabolic alkalosis? (explain)

Answer 5

• HCl is normally titrated by pancreatic sodium bicarbonate
  HCl + NaHCO3 –> NaCl + CO2 + H2O
• However, if HCl is lost from the body (was normally there) because of vomiting or gastric drainage, there is a net gain of bicarbonate

Question 6

Once metabolic alkalosis has occurred, its maintenance must indicate a failure of the kidneys to excrete the excess bicarbonate.
Explain the 2 way how this can occur. (Which mech must it be in the absence of renal failure?)

Answer 6

• Decreased filtered load of bicarbonate (due to a decrease in GFR)
• Increase in tubular bicarbonate reabsorption or decrease in bicarbonate secretion (must be this is absence of renal failure)

Question 7

How can Cl- be lost thru the skin?

Answer 7

Cystic fibrosis – loss of chloride in excess of bicarbonate in sweat.

Question 8

What can 2 overall causes lead to a high-AG metabolic acidosis? (give eg’s of each)

Answer 8

Overproduction of an endogenous organic acid
(H+A-), where A- is the acid anion (e.g., with lactic acidosis A- = lactate)
- Ketoacidosis; Toxin ingestion; Methanol (formate); Ethylene glycol (glyoxylate, oxylate)

Failure to excrete inorganic anions
- Renal failure (phosphate; sulfate);

Question 9

How does K+ administration work to treat metabolic alkalosis?

Answer 9

K+ moves into cell, H+ moves out, and that will titrate some of the bicarb

Question 10

What is the Henderson-Hasselbalch equation?

*What is the abbreviated version that is useful to us?

Answer 10

pH = pKa + log[HCO3-]/[H2CO3]

[H+] = 24 x PCO2 / [HCO3-]

Question 11

Define contraction alkalosis.

Answer 11

Refers to the increase in blood pH that occurs as a result of fluid losses (volume contraction). Na+ flows to distal sites where it is collected in exchange for H+

• May be due to compensatory mechs related to V loss, leading to aldo release and H+ secretion. Also Na/H exchange at PCT.
• The change in pH is especially pronounced with acidic fluid losses caused by problems like vomiting.

Question 12

What channel is present on the luminal membrane of beta-intercalated cells?
What channel is on the basolateral membrane?

Answer 12

• Luminal: HCO3-/Cl- antiport (bicarb excreted!)

- Basolateral: H+ pump (H+ reabsorbed!)

Question 13

What types of collecting duct cells have H+ pumps and Na+/H+ pumps?
What side of the cell?

Answer 13

Alpha-intercalated cell

Luminal

Question 14

What are 2 ways by which Cl- could be lost in the stool?

give the names of the 2 dz’s a/w each mechanism

Answer 14

• Secretion of chloride into stool (villous adenoma)

- Failure of gut reabsorption of chloride (congenital chloridorrhea)

Question 15

How do you derive pH from H+?

Answer 15

pH = -log[H+]

Question 16

Why does overproduction of an endogenous organic acid lead to an AG metabolic acidosis?

Answer 16

H+ added to the blood, leading to acidosis. There is increased anion being added to the blood as well, so anion gap increases.

Question 17

What are some of the sx of metabolic alkalosis?

Physical signs?

Answer 17

None, but sometimes cramps

• HTN (primary mineralocorticoid excess), hypoventilation, tetany, increased DTRs, cardiac arrhythmias

Question 18

For every pH change of ___, there will be a doubling or a halving of the [H+].

Answer 18

0.3

Question 19

What are the 3 overall causes of metabolic alkalosis?

Answer 19

1. Net loss of H+ from ECF
2. Net addition of HCO3- to ECF
3. Chloride depletion (leads to increased bicarb)

Question 20

Would CA inhibitors lead to an AG or non-AG metabolic acidosis?

Answer 20

non-AG (loss of bicarb but compensatory increase in Cl-)

Question 21

Why does failure to excrete inorganic anions lead to an AG metabolic acidosis?

Answer 21

Excess H+ is being buffered by phosphate/sulfate in the blood. If you can’t excrete them, acid builds up, leading to acidosis. There is an anion gap due to the leftover anions.

Question 22

What ion deficit is in the definition of metabolic acidosis and alkalosis?

What adaptation is seen?

Answer 22

HCO3- (bicarb)

• Increase or decrease in CO2 (respiratory) to maintain near-nl pH

Question 23

How can Cl- be lost in the kidney?

Answer 23

Diuretics: you lose Cl-, but this is what macula densa senses.

Question 24

In chloride-resistant metabolic alkalosis, what are the 2 general conditions that can cause it?

Answer 24

Consider mineralocorticoid excess states – can be either primary (low renin) of secondary (high renin).

Question 25

``` Which RTA has a urine pH > 5.5? (basic) Which RTA is a/w stones? Which RTA is hyperchloremic? Which RTA is hyperkalemic? What is the plasma bicarb level for each? ```

Answer 25

- I - I - I, II, IV - IV I: <10meq/L II: 12-20meq/L IV: >17meq/L

Question 26

How can administration of huge amounts of nl saline lead to a metabolic acidosis? Is it AG or non-AG?

Answer 26

Dilutional acidosis: increasing Cl-, bicarb has to go down to maintain electrical neutrality - Non-AG

Question 27

Bicarb is primarily reasborbed at the ___________. What other ion is part of it's transport?

Answer 27

PCT (Comes in as CO2) Apical membrane: cotransport w/Na+

Question 28

Name the 3 mechanisms by which the kidney excretes acid. | Which is most important?

Answer 28

1. Free hydrogen ion (H+) excretion (lowers urine pH); least important 2. Titratable acid excretion: secreted H+ combines with poorly reabsorbable anions such as PO43- 3. Excretion of ammonium ion (NH4+). The kidney generates ammonia (NH3) which combines with secreted H+ and is excreted as ammonium (NH4+) ion; This is most important

Question 29

What's the formula for anion gap? | What is the nl range?

Answer 29

Anion Gap = Na+ - (Cl- + HCO3-) Unmeasured anions - unmeasured cations = AG 10-12 meq/L

Question 30

What are the 3 major causes of H+ loss?

Answer 30

1. GI loss 2. Renal loss 3. Shift into cells

Question 31

Name the primary defect behind the 3 types of RTA, and where in the nephron they occur?

Answer 31

I: Impaired ability to excrete H+ in the DCT II: Impaired HCO3- reabsorption in the PCT IV: Decreased secretion of or effect of aldosterone

Question 32

How could cellular ionic homeostatic changes account for a metabolic alkalosis? (explain)

Answer 32

Shift of K+ out of cells into the extracellular fluid (ECF) in exchange for H+ ("loss" of H+ into the cells) - Helps us avoid severe hypokalemia

Question 33

In metabolic alkalosis, what is the predicted CO2 compensation for each numerical gain of bicarb?

Answer 33

HCO3- x 0.7

Question 34

How does acetazolamide work to treat metabolic alkalosis?

Answer 34

Leads to bicarb loss in urine

Question 35

What's another name for non-AG metabolic acidosis? | What are some causes of this?

Answer 35

Hyperchloremic - GI loss of bicarb (diarrhea) - Renal loss of bicarb - Failure to excrete acid - Administration of acid (HCl, NH3Cl) - Administration of large amounts of saline

Question 36

How could HCO3- be gained exogenously? | Would this lead to an alkalosis or acidosis?

Answer 36

- Addition of alkali (which are converted to bicarb in the blood): bicarb itself, lactate, citrate, acetate (not their acidic forms!)

Question 37

In metabolic acidosis, what is the predicted CO2 compensation for each numerical loss of bicarb?

Answer 37

HCO3- x 1.2

Question 38

Which is the mech behind RTAs type 1, 2, and 4?

Answer 38

1: Defect in the luminal H+/ATPase of the DCT 2: Impairment in proximal HCO3- reabsorption 4: Aldosterone deficiency or resistance