Acid/Base

Question 1

How does the body control acid/base balance?

Answer 1

• The kidneys and the respiratory system work together to maintain acid/base balance.
• It is very important that the body controls H⁺ concentration in ECF, because sites on membrane proteins protonate and deportonate in response to changes in pH, effecting the behaviour of the proteins
• Maintainence of acid/base comes down to two processes

1. Proper excretion of acid and base (respiratory and kidney)
2. Maintaining buffer system

Question 2

How are plasma H⁺ concentrations altered?

Answer 2

1. Metabolism of ingested food
2. Secretions of GI tract
3. Generation of acids and bases from metabolism of stored fat and glycogen
4. Changes in production of CO₂

Question 3

Acid/base equation

Answer 3

• Acid ⇌ conjugate base + H⁺
• [H⁺​] = K[acid]/[base] k= dissociation constant
• pH = pKa + log[base/acid]

Question 4

Buffers

Answer 4

• Weak acids make up our buffers - buffers limit the change in pH that occurs if you add another acid or base
  
  • Add acid = H⁺ released by that acid combines with the conjugate base restricting an increase in free H⁺
  • Add base = the free H⁺ removed by the base are replaced by H⁺ the dissociates from the acid
  • Remeber! Buffers do not eliminate acid or base from the body. They only limit their effects on blood pH

Question 5

Most important buffer system in the body

Answer 5

• CO₂- bicarbonate buffer system
  
  • CO₂ acts like a weak acid (because it readily combines with water to form carbonic acid H₂CO₃)
  • Carbonic acid dissociates into a proton and its conjugate base (bicarbonate)
  • CO₂ + H₂O ⇌ HCO₃^- + H⁺
  • Addings H⁺ is essentially equal to removing bicarbonate
  • Concentration of CO₂ stays pretty constant because respiratory rate is matched to metabolic production
  • When H⁺ is added (or bicarbonate is removed) the body needs to generate new bicarbonate to replaced what was lost

Question 6

Renal transport of acids and bases - proximal tubule

Answer 6

• Kidneys filter over 4000mmol bicarb/day. Most of this is reabsorbed in the proximal tubule (80-90%) by the following mechanism
  
  1. Na/H antiporter secrets H⁺
  2. H⁺ in filtrate combines with filtered bicarb to form CO₂ and H₂O
  3. CO₂ diffuses into the cell and combines with water to form H⁺ and HCO₃^-
  4. H⁺ produced from above reaction is secreted again and is excreted
  5. Bicarb is released into the insterstitum via Na/HCO3 symporter
  6. Glutamine inside the cell is metabolized to ammonium and HCO₃^-
  7. NH₄⁺ is secreted and excreted
  8. HCO₃^- is reabsorbed
• Bicarb is reabsorbed by combining it with secreted H⁺ and turning it into CO₂ and water, while simultaneously generating intercellular bicarb and transporting it to the interstitium

Question 7

Renal transport of acids and bases -Distal Tubules

Type A intercalated cells

Answer 7

• Type A intercalated cells
  
  • Function in acidosis
  • H⁺ is excreted (via ATPases on apical side) and HCO₃^- and K⁺ are reabsorbed
  • New bicarb is formed from H₂O and CO₂ - it is NOT just reabsorption of filtered bicarb
  • The H⁺ that is excreted in the urine attaches to bases (like phosphate) andis excreted. H⁺ must be excreted with non-bicarb base, or else it would just recombine with newly formed bicarb.

Question 8

Renal transport of acids and bases -Distal Tubules

Type B intercalated cells

Answer 8

• Type B intercalated cells
  
  • Function in alkalosis
  • HCO₃^- and K⁺ are excreted; H⁺ is reabosorbed (via ATPases on basolateral side)

Question 9

Kidneys response to base loads

Answer 9

• Kidneys reabsorb most of the filtered bicarbonate, but excrete just enough into the urine to match the input of base. The kidneys do this by:
  
  • Allowing some of the filtered bicarb to pass through to the urine
  • Secrete the bicarb via type B intercalated cells in the distal nephron (bicarb is excreted out and H⁺ is reabsorbed).

Question 10

Kidneys response to acid loads

Answer 10

• Generating bicarb from water and CO₂ stimulaneously generates H⁺. So, H⁺ must be separated from the bicarb and excreted, or else the components will recombine and accomplished nothing. The kidneys do this by:
  
  • Filtered bicarb is reabsorbed
  • Kidney’s secrete additional H⁺ via ATPase in type A intercalated cells. This attaches to bases in tubular fluid other than bicarb and is excreted.
  • Bicarb generated inside the cell is transported into the blood via CI-HCO₃ antiporters, replacing the bicarb that was lost when acid entered the body
• H⁺ must be excreted as nonbicarb base, or else they would just recombine with newly generated bicarb.

Question 11

Acid excretion and Phosphate

Answer 11

• Phosphate is an important source of nonbicarb base allowing for the excretion of H⁺
• Free plasma phosphate exists as a mixture of weak acid and base. At a normal pH 80% of the filtered phosphoate is in base form. Most of the phosphate is reabsorbed at the proximal tubules, but some continues on to the distal nephron. As H⁺ are secreted, the remaining phosphate base takes up the secreted H⁺ and is excreted.

Question 12

Importance of ammonium in acid secretion

Answer 12

• Excretion of hydrogen ions as ammonium is very important in acid/base balance
• More H⁺ can be excreted via ammonium then via filtered bases
• Furthermore, filtered bases cannot be changed to serve the needs ot acid-base balance, but ammoniagenesis can be increases in response to acid loads (large acid loads are excreted mainly in form of ammonium.

Question 13

Glutamine and ammonium

Answer 13

• The amino acid glutamin can be thought of as containing the 2 components from which it was synthezied - base component (bicarb) and acid component (ammonium).
• The liver synthesizes more glutamine in response to low pH and proxmical tubules take up more gluamine in response to low pH (to increase bicarb production). High pH does the opposite
• Gluatmine is taken by proximal tubules cells where it is converted into bicarb and ammonium (NH₄⁺). The ammonium is secreted into the lumen and bicarb is reabsorbed into the blood.
  
  • If NH₄⁺ is secreted you see net bicarb production
  • If NH₄⁺ is reabsorbed, it is metabolized by the liver back into urea and H⁺, consuming bicarb in te process. Result is no net bicarb production

Question 14

How do you quantify renal acid-base excretion

Answer 14

• Can quatify excretion of acid/base equivalents by looking at 3 quantities in urine
  
  1. Amount of titratable acidity - amount of acid taken up by urinary bases other than ammonium
  2. Amount of ammonium
  3. Amount of bicarb
• Net acid excretion = titratable acid excreted + NH₄⁺ - bicarb excreted

Question 15

How does kidney regulate handling of acid and base loads

Answer 15

• Kidneys respond to acid-base loads by moving transporters for H⁺ and bicarb back and fortj between intracellular vesicles and surface membranes
• Acid loads = increase number of H-ATPases at apical membrane of A intercalated cells and increase CI-HCO₃ antiporters on basolateral side
• Base loads = increase number of CI-HCO₃ antiporters at apical membrane of B intercalated cells and increase H-ATPases on basolateral side
• Overtime acid/base loads can lead to conversion between A and B intercalated cells
• Adjustments are made in response to bicarb, pH, and PCO₂

Question 16

Acid/Base disorders

Answer 16

• Acid/base disorders manifest as deviations in levels of arterial PCO₂, bicarb, or both
• There are 4 categories of acid/base disorders
  
  1. Respiratory acidosis - High pCO₂
  2. Respiratory alkalsis - Low pCO₂
  3. Metabolic acidosis - Low bicarb
  4. Metabolic alkalosis - high bicarb

Question 17

Acid base disorders and compensation

Answer 17

• Generally, in acid/base disorders you expect to see compensation - i.e., when either pCO₂ or bicarb levels change, the body changes the other variable in the same direction
• Compensation does NOT equal correction, because even if pH is returned to normal, both pCO₂ and bicarb values are abnormal

Question 18

Approach to Acidosis

Answer 18

Question 19

Approach to Alkalosis

Answer 19

Question 20

Approach to acid/base disorders

Answer 20

1. History and Physical - Look for acid base clues
   
   • Metabolic alkalosis - vomiting, diuretics, hyperaldoesteronism
   • Metabolic Acidosis - history pf DM1 (DKA), recent binge drinking, diarrhea, addisons disease, small bowel issues
   • Respiratory acidosis - hypoventilation (acute: drugs, pain, trauma to chest, upper airway obstruction, hypotension; chronic: long-standing disorders of the lung-COPD).
   • Respiratory alkalosis - hyperventilation (anxiety, brainstem injury, hypoxia - pulmonary disease, high altitude).
2. Look at lab results - acidosis?, alkalosis?, respiratory?, metabolic?, appropriate compensation?
3. If metabolic acidosis - what is the anion gap?
   
   • If AG is elevated look at the delta-delta and osmolar gap
   • If AG is normal look at urine net charge
4. If metabolic alkalosis - look at urinary chloride to determine if patient is volume deplete or not

Question 21

What does the anion gap tell you?

Answer 21

• A normal anion gap is ≤ 12mEq/L (16 if including K)
  
  • (Na + K) - (Cl + HCO₃^-)
  • Useful in distinquishing between bicarb loss (normal AG) and acid accumulation (elevated AG)

Question 22

Causes of Elevated Anion Gap

Answer 22

• G - Glycols
  
  • Ethylene and propylene
• O - Oxoprotine
  
  • Chronic acetaminophen use
• L - L-lacate
  
  • Hypoxia
• D- D-lacate
  
  • Short bowel syndrome
• M - Methanol
  
  • Antifreeze, solvents, cleaners
• A - Aspirin
  
  • Salcylate toxicity
• R - Renal failure
  
  • Advanced kidney disease (uremia)
• K - ketoacidosis
  
  • DKA, ethanol, starvation

Question 23

Osmolar gap

Answer 23

• Look at the osmolar gap is the AG is elevated.
• 2Na + Glu (normal = 270-285 msom/kg)
• Elevated osmolar gap indicates methanol or ethylene glycol

Question 24

Causes of normal anion gap metabolic acidosis

Answer 24

• Most common cause is diarrhea, followed by renal tubular acidosis
• Look at urine net charge
  
  • Urine Na + K < CI = GI bicarb loss
    
    • Diarrhae
    • Fistula
  • Urine Na + K > CI = renal loss
    
    • Loss of bicarb due to decrease proximal tubular reabsorption (renal tubular acidosis)
    • Failure to generate new bicarb (decrease ammonia excretion)

Question 25

Causes of metabolic alkalosis

Answer 25

* Administration of bicarb * Loss of acid via * GI tract - vomiting * Kidneys - diuretics, hyperaldoesteronism * Meausure urinary chloride * U_CI \<20 = Volume depletion (is circulation volume is deplete kidneys reabsorb CI). Contraction alkalosis - loss of ECF volume (CI reponsive) * Vomiting * Diuretics (late) * U_CI \> 20 = no volume depletion. CI resistant * Diuretics (early) * Bartters syndrome * Alkali load * Severe hypokalemia