L5 - Acid-Base Disorders Flashcards
Acid-Base Parameters
**Check slides
Physiological buffers?
are weak acids or bases • pH of the plasma is tightly regulated • pH of arterial blood is 7.35 – 7.45 (Acidemia – blood pH < 7.35 Alkalemia – blood pH >7.45) • pH of venous blood is 7.32 – 7.38
Examples of Physiologically Relevant Buffer Systems?
1) Phosphate Buffer System
• H2PO4− + H2O ⇌ H3O+ + HPO4−
• Minor role in plasma and erythrocytes
• Most important buffer in urine (titration and excretion of acids)
2) Bicarbonate/Carbonic Acid System:
• Most important buffer system in plasma
3) Proteins:
• Albumin accounts for >90% of the non-bicarbonate buffer value of plasma
(Imidazole groups of Histidine’s (pKa ~7.3), Albumin has 16 histidine)
• Hemoglobin accounts for major part of non-bicarbonate buffer inside RBC
Bicarbonate/Carbonic Acid Buffer System
H+ + HCO3− ⇌ H2CO3 ⇌ CO2 (aq) + H2O
1) HCO3-, second largest fraction of plasma anions (first = Cl-)
• ≈26 mmol/L (which is actually Total CO2)
2) Most CO2 enters RBC to react with H2O to form H2CO3
• Catalyzed by carbonic anhydrase
CO2 (aq) + H2O → H+ + HCO3−
- Increased H+ is “buffered” by Hemoglobin binding to H+ (promotes oxygen release)
- Bohr effect: [H+]inversely proportional to Hb:O2 binding affinity
Bicarbonate Measurement
Total CO2 of plasma = CO2(aq) + HCO3- + CO3(2-) + H2CO3
- Bicarbonate ions (HCO3-) make up ~ 2mmol/L of total CO2
- HCO3- Reference Interval: 22 – 30 mmol/L
Laboratory methods for total CO2 (which we call HCO3-)
involves alkalizing the specimen → converts most species to HCO3- → coupled further to an enzyme
catalyzed reaction
• Can also be estimated based on calculations using H&H equation
Henderson-Hasselbalch Equation?
HA ⇌ A− + H+
pH = pKa + log[A−]/[HA]
CO2 (aq) + H2O ⇌ H2CO3 ⇌ H+ + HCO3−
pH = 6.1 + log[HCO3−]/[CO2 (aq)]
pH = 6.1 + log[HCO3−]/[0.0306 × pCO2]
How do you determine [CO2(aq)]?
Henry’s Gas Law: amount of dissolved gas in liquid is
proportional to its partial pressure above liquid
[CO2(aq)] = α × pCO2
α = solubility coefficient of CO2 (g) = 0.0306
pH compatible with life?
6.80 – 7.80
If [base] = [acid], then?
pH = pKa
Buffers (mixture of weak acid + conjugate base) works best in resisting ±1 pH unit change from the pKa
• Buffers work best when ratio of acid:base = 10:1 to 1:10.
• pH = pKa +log (10:1) or pH = pKa + log (1:10)
Let’s consider pH of arterial blood, which is 7.35 – 7.45
• For pH = 7.4, we require normal ratio of [HCO3-]: [CO2(aq)] is?
20:1
• log 20 = 1.30
Why are blood gases measurements
important?
• Acid-base status of is assessed by values of HCO3- and pCO2measurements to provide ideal respiratory care.
What about pO2(g)?
1) Main reason for arterial blood collection vs. venous blood sample
2) Monitor O2 therapy
• Arterial pO2: 80 - 100 mm Hg Venous pO2: 30 – 50 mm Hg
• Arterial pCO2: 35 – 45 mm Hg Venous pCO2: 40 – 52 mm Hg
• Arterial pCO2 >50 mm Hg (Hypercapnia)
Air exposure leads to decreased or increased pCO2? Why?
1) According to wiki: CO2 makes up 0.0407% of atmospheric air
2) Dalton’s Law: Total Pressure = σ PX
• PCO2 in the air = 760 mm Hg X 0.0407% = 0.309 mm Hg
• PCO2 in the arterial blood ~ 40 mm Hg
Air exposure leads to decreased or increased pO2? Why?
1) According to wiki: O2 makes up 20.946% of atmospheric air
2) PO2 in the air = 760 mm Hg X 20.946% = 159.19 mm Hg
• PO2 in the arterial blood ~ 80 - 100 mM Hg
• PO2 in the venous blood ~ 30 – 50 mm Hg
What organs regulate these molecules? (Bicarbonate/Carbonic Acid Buffer System)
- Lungs readily dispose or retain CO2 based on need
- Renal tubules increase or decrease rate of reclaiming HCO3-
- Kidneys and lungs are main generators and compensators
- Acute acid/base disturbance shift pH away from 7.4
Respiratory Mechanisms of Acid-Base
Regulation?
- External respiration
• Normal respiratory rate = 12 – 15 breaths/min (resting state)
• Involuntary increase in respiratory rate (ventilation) sensed by central and
peripheral chemoreceptors sensitive to pH changes - Gas exchange gradient
• Gradient for O2 is inward and CO2 is outward
Renal Mechanisms of Acid-Base Regulation?
- Na + -H+ Exchanger Channels
- Renal production of NH3 and NH4+ Excretion
- Excretion of H+ as H2PO4-
- Reclamation of Filtered Bicarbonate
Na + -H+ Exchanger Channels? How does Hypokalemia contribute to alkalosis?
1)
• H+ out into the tubular fluid in exchange for Na+
• Na + -H+ Enh5anced in acidosis
2)
• If K+ is depleted, less H+ exchanged for Na+
Renal production of NH3 and NH4+ Excretion? What happens in CKD?
1)
• Renal tubular cells generate NH3 from glutamine and other amino acids
• NH3(g) diffuses into cell membranes to combine with H+ → NH4+
• NH4+ excreted with other anions (e.g. phosphates, Cl-) into urine
2) Decreased renal excretion of NH4+
Excretion of H+ as H2PO4-?
H+ secreted into tubular lumen by Na+ -H+;
• H+ reacts with HPO4(2-) to H2PO4-
• Acidemia increases phosphate excretion
Reclamation of Filtered Bicarbonate?
Diffusion of CO2 into tubular cells to react with H2O in the presence of cytoplasmic carbonic anhydrase to form H2CO3 → H+ and HCO3
GI Tract?
Vomiting and Diarrhea -> acid/base disturbance
• Vomiting → acid loss → more basic environment → alkalosis
• Diarrhea → base loss → more acid environment → acidosis
Acid-Base Disturbances by?
Lungs and Kidney
1) Lungs cause disturbances via CO2
• CO2 increases in respiratory acidosis
• CO2 decreases in respiratory alkalosis
2) Kidneys cause disturbances via HCO3-
• HCO3- increase (by renal retention) causes Metabolic Alkalosis
• HCO3- decrease (by renal excretion) causes Metabolic Acidosis
- If Acidosis or Alkalosis is respiratory, Kidneys will compensate
- If Acidosis or Alkalosis is renal, the Lungs will compensate
Compensation Mechanisms?
1) Lungs compensate for metabolic disturbances by doing to CO2 whatever the kidneys did to HCO3-
• Metabolic Alkalosis: HCO3- increases, lungs retain CO2
2) Kidneys compensate for respiratory disturbances by doing to HCO3- whatever the lungs did to CO2
• Respiratory alkalosis: CO2 decreases, so the kidneys decrease HCO3-
Respiratory Acidosis?
H+ + HCO3− ⇌ H2CO3 ⇌ CO2 + H2O
pH = 6.1 + log[HCO3−]/[CO2]
- Acidosis from increased CO2
- Equilibrium shifts to produce H+
- Compensation: Kidneys help to buffer the H+ by retaining HCO3-
*Summary:
↑CO2, ↑HCO3-, ↓pH
Causes of Respiratory Acidosis?
1) Decreased expiration of CO2
2) Trouble expiring the CO2 because of obstruction
• e.g. foreign object, tumor, or obstructive lung disease
• Damage to the lungs or chest wall (e.g. pneumothorax)
• Problems with muscles of respiration or their neural input
(Myasthenia gravis)
Respiratory Alkalosis?
H+ + HCO3− ⇌ H2CO3 ⇌ CO2 + H2O
pH = 6.1 + log[HCO3−]/[CO2]
- Alkalosis from decreased CO2
- Equilibrium shifts away from H+ to create more CO2
- Compensation: Kidneys can help excrete HCO3-
- Summary:
- ↓ CO2, ↓ HCO3-, ↑ pH
Causes of Respiratory Alkalosis?
Breathing too fast (hyperventilation)
• Hypoxemia (drive for more oxygen) from high altitude or anemia
• Drug induced (salicylate toxicity)
• Pain/anxiety induced
• Stroke induced
• Pulmonary pathology (e.g. pulmonary embolism)
Metabolic Alkalosis?
H+ + HCO3− ⇌ H2CO3 ⇌ CO2 + H2O
pH = 6.1 + log[HCO3−]/[CO2]
• Alkalosis from increased [HCO3-] or decreased [H+]
• Equilibrium shifts away from H+ to create more CO2
• Compensation: Lungs can help to retain CO2
• Summary:
↑ CO2, ↑ HCO3-, ↑ pH
Metabolic Alkalosis: Decreased [H+]?
1) Renal loss of H+
• AldosteRoNe causes Reabsorption of Na+ and Secretion of K+ & H+
• E.g. hyperaldosteronism
2) Shift of H+ into cells
• Hypokalemia causes K+ to redistribute in exchange for H+
• E.g. Diuretics induced hypokalemia
Metabolic Acidosis?
H+ + HCO3− ⇌ H2CO3 ⇌ CO2 + H2O
pH = 6.1 + log[HCO3−]/[CO2]
• Acidosis from decreased [HCO3-] or increased [H+]
• Equilibrium shifts to H+
• Compensation: Lungs can help expire away CO2
• Summary:
↓ CO2, ↓ HCO3-, ↓ pH
Metabolic Acidosis
• Increased Acids [H+]?
• Decreased [HCO3-]?
1) Increased Acids [H+] • Anion Gap (increased) Acidosis • Look at MUDPILES 2) Decreased [HCO3-] • Diarrhea • Renal loss (e.g. diuretics or Renal Tubular Acidosis → HCO3- wasting) • Normal anion gap acidosis
Anion Gap Acidosis vs Non-Anion Gap
Acidosis?
1) Anion Gap Acidosis: high anion gap commonly indicates metabolic acidosis
Anion Gap = [Na+] – [HCO3-] – [Cl-]
• HCO3- consumption
2) Non-anion gap acidosis
• Fall in HCO3- matched with increase in Cl-(hyperchloremia)
• HCO3- consumption is secondary to diarrhea or renal problem
• Causes: Diarrhea, CKD, Renal Tubular acidosis, carbonic anhydrase inhibitor (diuretics)
What are Diuretics?
1) Thiazides (NCC inhibitor): Increase pH
• Chloride Wasting → Metabolic (hypochloremic) Alkalosis
2) Loop diuretics (NKCC inhibitors): increase pH
• Chloride Wasting → Metabolic (hypochloremic) Alkalosis
3) K+ sparing diuretics: decrease pH
• Hyperkalemia → Metabolic Acidosis
4) Carbonic Anhydrase inhibitors: decrease pH
• Reduced production of HCO3
- → Metabolic Acidosis
