3.8. The role of ventilation in the regulation of the pH, in the development and compensation of the acid-base imbalances in the body.

Question 1

I. Alveolar CO2-tension
1. Which organ does pCO2 depend mostly on?

Answer 1

respiration (alveolar ventilation equation)

Question 2

I. Alveolar CO2-tension
2. Which equations we can you to find pCO2?

Answer 2

pCO2 depends mostly on respiration (alveolar ventilation equation), and since we can find pCO2 in the Henderson- Hasselbalch equation as well:
- We can alter the pH of the blood with our respiration (easily and quickly)

Question 3

I. Alveolar CO2-tension
3. How does rate of ventilation determine the pCO2?

Answer 3

• Increase in alveolar ventilation -> lower pCO2
• Decrease in alveolar ventilation -> higher pCO2
• The relationship between the ventilatory rate and the pCO2 is expressed as following:

Question 4

I. Alveolar CO2-tension
4. What are the consequences of changing pCO2 in blood?

Answer 4

• Increase in pCO2 -> lower pH
• Decrease in pCO2 -> higher pH

Question 5

I. Alveolar CO2-tension
5. Why isn’t the key thing for our respiration necessarily O2?

Answer 5

Key thing for our respiration is not necessarily O2, but to maintain pCO2-levels for the pH

Question 6

II. Effect of alveolar ventilation on pCO2 and pO2
1. Characteristics of Hyperventilation

Answer 6

Hyperventilation: when ventilation is more than metabolically necessary
- pCO2 < 40mmHg
- pCO2 decreases => pH↑

Question 7

II. Effect of alveolar ventilation on pCO2 and pO2
2. Characteristics of Hypoventialtion

Answer 7

Hypoventilation: when ventilation is less than metabolically necessary
- pCO2 > 40mmHg
- pCO2 increases => pH↓

Question 8

II. Effect of alveolar ventilation on pCO2 and pO2
3. Can respiration regulate pH? Give examples

Answer 8

Respiration can regulate the pH: can either be the solution to the problem or the cause of the problem
- Ex: in high altitudes, where O2-levels are low, we ventilate a lot (hyperventilation = pH↑)
- pH increase important for saturation of Hb (pushes the Hb-saturation curve to the left)

Question 9

III. Chemoreceptors and acid-base balance
1. What are the 2 types of chemoreceptors participate in acid-base balance?

Answer 9

1. Central chemoreceptors (CCR)
2. Peripheral chemoreceptors (PCR)

Question 10

III. Chemoreceptors and acid-base balance
2A. How can Central chemoreceptors (CCR) regulate pH?

Answer 10

• represents 75% of the ventilation drive at rest
• located in CNS (ventrolateral medulla)
• CCRs senses ([H+]) pH in ECF and CSF, indirectly by measuring the pCO2
  +) There is a BBB here: only CO2 can pass – H+ and HCO3- cannot
  +) CO2 will become H+ and HCO3-, and there will be an increase in HCO3- and H+ in CSF
  o H+ is in nmol-range, while HCO3- are in mmol-range
  => pCO2↑ = pH↓: HCO3- - level cannot change it (short term)
  => Adaptation, due to many mechanism the HCO3- level will increase and decrease the pH to normal values (long term)

Question 11

III. Chemoreceptors and acid-base balance - Central chemoreceptors (CCR)
2B. Why isn’t the HCO3- changing?

Answer 11

o Because there is no other buffer in the CSF, only the CO2/HCO3- -
buffer
o But if a change happens in HCO3-:
- It cannot buffer so much because H+ is increasing (due to CO2)
- HCO3- should counter the pH-changing effect of CO2, but it is
difficult since no others are present

Question 12

III. Chemoreceptors and acid-base balance
3. How can Peripheral chemoreceptors (PCR) participate in acid-base balance?

Answer 12

• Located in the aortic arch (aortic bodies) and carotid bifurcation (carotid bodies)
• Senses pH and arterial pO2 directly (+ CO2-levels)
• Less sensitive to pCO2
  => If the CCRs have adapted to some unusual pCO2-levels, the PCRs can detect that the pH is not normal (very important mechanism)

Question 13

IV. ACID-BASE DISORDERS
1. Integration of pH control systems
a) How does pH control system work?

Answer 13

There is a constant acid challenge in the body. Therefore, we have different lines of defenses
- 1st line of defense: chemical buffering
- 2nd line of defense: respiratory buffering
- 3rd line of defense: renal buffering

Question 14

IV. ACID-BASE DISORDERS
1. Integration of pH control systems
B) How does 1st line of defense: chemical buffering work?

Answer 14

• Chemically buffer the protons that are being produced
• 70mmol of nonvolatile acids are to be buffered
• Works rapidly (second-scale)

Question 15

IV. ACID-BASE DISORDERS
1. Integration of pH control systems
B) How does 2nd line of defense: respiratory buffering work?

Answer 15

• Buffer mainly the CO2 (volatile acid)
• Exhale 15,000mmol of CO2
• Works relatively fast (minute-scale)

Question 16

IV. ACID-BASE DISORDERS
1. Integration of pH control systems
C) How does 3rd line of defense: renal buffering work?

Answer 16

• Acts slowly (hour-scale)
• Production of ‘’new’’ HCO3-
• H+ excreted (combined with urinary buffers)
• NH4+ traps H+
  => Last to processes protect the bladder, without the buffer the environment in the urinary bladder would be very acidic (like in the stomach!)

Question 17

IV. ACID-BASE DISORDERS
2. Acid-base disorders
A. What are Acidosis & Alkalosis?

Answer 17

1. Acidosis = acidemia (pH < 7,35) and/or altered pCO2 +/- act [HCO3-]
2. Alkalosis = alkalemia (pH > 7,45) and/or altered pCO2 +/- act [HCO3-]
   => Acidosis and alkalosis are not about pH of the blood, these are situations that are acid-base disorders

Question 18

IV. ACID-BASE DISORDERS
2. Acid-base disorders
B. What happen if a patient with acid-base disorder goes to the doctor?

Answer 18

• Measure pH (decide if acidosis or alkalosis)
• Then look at pCO2 and HCO3- - levels (respiratory / metabolic)
  => But if both pCO2 – and HCO3- - levels have changed, then we the doctor needs to think about which of these changes would lead to acidosis/alkalosis on its own

Question 19

IV. ACID-BASE DISORDERS
2. Acid-base disorders
C2. What are Causes of RESPIRATORY ACIDOSIS?

Answer 19

• pulmonary diseases, ex: obstructive lung diseases – pulmonary emphysema (lung damaged, ventilation not working, reduced gas exchange)
• high pCO2 in the inhaled air (gas exchange does not function)
• drugs (overdose of opioids => inhibits medullar respiratory centers = lower ventilation) DEADLY!

Question 20

IV. ACID-BASE DISORDERS
2. Acid-base disorders
D2. What are Causes of Respiratory alkalosis?

Answer 20

• voluntary hyperventilation
• high altitude (low pO2 and higher pCO2 => hyperventilate)
• Iatrogenic (induced by doctors) drug side effects (e.g., aspirin => stimulate respiratory centers => hyperventilation)

Question 21

IV. ACID-BASE DISORDERS
2. Acid-base disorders
C3. What are Compensation of RESPIRATORY ACIDOSIS?

Answer 21

Compensation: pH gets closer to 7,4 (renal compensation = slow)
- renal NAE increases -> kidney produces new HCO3-
- increased BB and BE
- increased standard [HCO3-] > 24mM
- increased further in actual [HCO3-]&raquo_space; 24mM
=> as long as the original problem is there, pCO2 remains high (pulmonary emphysema)

Question 22

IV. ACID-BASE DISORDERS
2. Acid-base disorders
D1. What are characteristics parameters of Respiratory alkalosis?

Answer 22

• pH > 7,45
• paCO2 < 40mmHg (pH↑)
• no change in buffer base (BB) and buffer excess (BE)
• unchanged standard [HCO3-]
• decreased actual [HCO3-] < 24mM

Question 23

IV. ACID-BASE DISORDERS
2. Acid-base disorders
D3. What is the Compensation of Respiratory alkalosis?

Answer 23

Compensation: => pH gets closer to 7,4
- renal NAE decreases -> H+ - excretion
- decreased BB and BE
- decreased standard [HCO3-] < 24mM (↓HCO3- -
reabsorption)
- further decrease in actual [HCO3-]

Question 24

IV. ACID-BASE DISORDERS
2. Acid-base disorders
E1. What are the characteristics parameters of Nonrespiratory (metabolic) acidosis?

Answer 24

• pH < 7,35
• unchanged paCO2
• decreased BB (<44mEq/L) and decreased BE (<2,5mEq/L)
• decreased standard [HCO3-] < 24mM
• decrease in actual [HCO3-] <24mM (pH↓)

Question 25

IV. ACID-BASE DISORDERS 2. Acid-base disorders E2. What are the Causes of Nonrespiratory (metabolic) acidosis?

Answer 25

- diabetes (accumulation of keto acids) - renal failure (inability of kidneys to get rid of 70mmole of fixed acid) - diarrhea (lose HCO3- via feces) - physical exercise (increased production of lactate – eat up HCO3-)

Question 26

IV. ACID-BASE DISORDERS 2. Acid-base disorders E3. What is the compensation of Nonrespiratory (metabolic) acidosis?

Answer 26

Compensation: pH gets closer to 7,4 - hyperventilation -> paCO2 < 40mmHg (Kussmaul – respiratory pattern of a diabetic patient => deep respiration + high frequency = ↓paCO2) - renal NAE increases (if it can – diabetes) - partial restoration of BB and BE (if possible) - partial restoration of standard [HCO3-], but still <24mM - complex changes, but still decreased actual [HCO3-] >24mM

Question 27

IV. ACID-BASE DISORDERS 2. Acid-base disorders F1. What are characteristic parameters of Nonrespiratory (metabolic) alkalosis?

Answer 27

- pH > 7,45 - unchanged paCO2 - increased BB (>49mEq/L) and BE (>2,5mEq/L) - increased standard [HCO3-] > 24mM (pH↑) - increased actual [HCO3-] > 24mM

Question 28

IV. ACID-BASE DISORDERS 2. Acid-base disorders F2. What are the causes of Nonrespiratory (metabolic) alkalosis?

Answer 28

- lost gastric acid (by vomiting due to drug overdose -> ↑ [HCO3-] in the blood) - Hyperaldosteronism (increased [aldosterone] -> ↑H+-secretion = alkalosis) - Uncontrolled intake of alkalis (used for ulcers – damaging the stomach = overused)

Question 29

IV. ACID-BASE DISORDERS 2. Acid-base disorders F3. What is the compensation for Nonrespiratory (metabolic) alkalosis?

Answer 29

Compensation: pH gets closer to 7,4 - Hypoventilation -> paCO2 > 40mmHg - renal NAE decreases - partial restoration of BB and BE (if possible) - partial restoration of standard [HCO3-], but still > 24mM - complex changes but still increased actual [HCO3-] > 24mM

Question 30

IV. ACID-BASE DISORDERS 2. Acid-base disorders G1. What are the characteristic parameters of Mixed type acidosis?

Answer 30

- pH << 7,35 - paCO2 > 40mmHg - decreased BB (<44mEq/L) and BE (<2,5mEq/L) - decreased actual [HCO3-] <24mM - complex changes in actual [HCO3-]

Question 31

IV. ACID-BASE DISORDERS 2. Acid-base disorders G2. What are the Causes of Mixed type acidosis?

Answer 31

Causes: more than 1 disease! - E.g., diabetes + chronic obstructive pulmonary disease (COPD) or kidney failure + drug overdose

Question 32

IV. ACID-BASE DISORDERS 2. Acid-base disorders G3. What is the compensation for Mixed type acidosis?

Answer 32

Compensation: -> pH gets closer to 7,4 (options limited + takes time) *** Situation where doctor needs to buy time by adding acids/bases to patient pushing pH to normal, till they find a treatment for the root cause of the underlying problem - Increased ventilation to decrease paCO2 (if possible) - renal NAE increases (if it can) - partial restoration of BB and BE (if possible) - partial restoration of [HCO3-] - complex changes in actual [HCO3-]

Question 33

IV. ACID-BASE DISORDERS 2. Acid-base disorders H. Fill in the table

Answer 33

Question 34

IV. ACID-BASE DISORDERS 3. Anion gap A. What is anion gap?

Answer 34

Anion gap is the difference between measured cations (Na+) and measured anions in plasma. Usually use this technique to diagnose metabolic acidosis.

Question 35

IV. ACID-BASE DISORDERS 3. Anion gap B. How do we use anion gap?

Answer 35

1. Useful value because metabolic acidosis has many causes - Accumulation of ‘’new’’ acids => dissociate to proton and anion (lactate) - Net loss of HCO3- 2. With this technique, we can find the unmeasured anions in the blood = protein, phosphate, citrate, sulfate 3. Usually: AG ≈ 8-16 mEq/L 4. If AG is high or sum of cations is higher than sum of anions, there must be unmeasured anions (ex: proteins) in the plasma => Metabolic acidosis is then due to something that has been produced in the body, which is an acid

Question 36

IV. ACID-BASE DISORDERS 4. Ca2+ and K+ - levels in acid-base disorders A1. Why are Calcium levels affected a lot by pH?

Answer 36

Ca2+-levels are affected a lot by pH, because: - Calcium likes to bind to albumin - If albumin and plasma proteins have more negative charges -> Ca2+ will bind more frequently => Shift from freely available Ca2+ to protein bound Ca2+ (freely available Ca2+↓)

Question 37

IV. ACID-BASE DISORDERS 4. Ca2+ and K+ - levels in acid-base disorders A2. How and when can this Shift from freely available Ca2+ to protein bound Ca2+ (freely available Ca2+↓ happen?

Answer 37

- Plasma proteins are buffers -> buffering means if there is a change in pH, they may bind or release a proton - If pH↑ -> the buffers (plasma proteins) start to release their H+ = more negative charges in their structure => Ca2+-ions will bind = [Ca2+] of freely available↓

Question 38

IV. ACID-BASE DISORDERS 4. Ca2+ and K+ - levels in acid-base disorders A3. Why is it a problem if there are abnormal Ca2+ levels?

Answer 38

- [Ca2+]-ions↓ = threshold for voltage-gated Na+-channels also↓ => Action potentials occur more easily -> causes random body contractions => Deadly if contractions are related to respiratory muscles

Question 39

IV. ACID-BASE DISORDERS 4. Ca2+ and K+ - levels in acid-base disorders B1. Why are K+ levels important?

Answer 39

1. Important molecule in setting the membrane potential. 2. Depends on pH

Question 40

IV. ACID-BASE DISORDERS 4. Ca2+ and K+ - levels in acid-base disorders B2. How can K+ can cause cardiac arrythmia?

Answer 40

Important molecule in setting the membrane potential. If K+-levels change: - Whole GHK- and Nernst-equation changes - If we alter the [K+], then membrane and equilibrium potential changes - Functions which rely on the membrane a lot, can have problems (heart, SA node rely on proper membrane potential-related changes)

Question 41

IV. ACID-BASE DISORDERS 4. Ca2+ and K+ - levels in acid-base disorders B3. How can K+ cause problem in pH regulation?

Answer 41

Potassium levels also depend on the pH-value: - (+) 0,1 pH -> (-) 0,5mM [K+] - Acidosis -> hyperkalemia ([K+]↑) - Alkalosis -> hypokalemia ([K+]↓) During acidosis, the return of K+ into the tubular lumen (via ROMK1) is inhibited => K+-reabsorption↑ -> hyperkalemia [K+]↑