B2 W1: Acid-Base Regulation Flashcards
1
Q
What are the two main categories of acids produced in the body, and how are they excreted?
A
- Volatile acids, primarily from CO₂ production, are excreted by the lungs.
- Non-volatile (fixed or non-respiratory) acids are produced from other metabolic processes and excreted by the kidneys.
2
Q
Why is the regulation of H⁺ concentration arguably more complex and tightly controlled than for other ions?
A
H⁺ ions are small and charged, so they can have profound effects on protein function throughout the body.
3
Q
List the three main mechanisms for minimising pH changes in the body.
A
- Buffer systems provide rapid, chemical buffering.
- The Lungs rapidly adjust CO₂ excretion.
- The Kidneys slowly adjust H⁺ excretion and bicarbonate levels.
4
Q
What is the function of a buffer?
A
A buffer reversibly binds H⁺ to minimise changes in pH.
5
Q
What are the three main buffer systems in the body, and where do they primarily function?
A
- Bicarbonate (extracellular)
- Phosphate (intracellular and urine)
- Protein (mainly intracellular, example: haemoglobin in erythrocytes).
6
Q
What makes the bicarbonate buffer system particularly important in acid-base balance?
A
It interacts with both the lungs, which control CO₂, and the kidneys, which control bicarbonate.
7
Q
What is the Henderson-Hasselbalch equation, and what does it tell us?
A
- pH = pK + log₁₀ ([HCO₃⁻]/[CO₂])
- It allows us to calculate pH based on bicarbonate and CO₂ concentrations.
- pH is the measure of acidity or alkalinity
- pK is the negative logarithm of the dissociation constant for carbonic acid (a constant value of 6.1)
- [HCO₃⁻] is the concentration of bicarbonate ions
- [CO₂] is the concentration of dissolved carbon dioxide
8
Q
What is the typical ratio of bicarbonate to CO₂ in arterial blood?
A
20 : 1
9
Q
Which organ provides a rapid response to acid-base changes, and how?
A
- The lungs
- By adjusting the ventilation rate to alter CO₂ elimination.
10
Q
Which organ provides a slower response to acid-base changes, and how?
A
- The kidneys
- By adjusting bicarbonate production and H⁺ excretion in the urine.
11
Q
What are the two possible causes for a decrease in pH (acidity)?
A
An increase in CO₂ or a decrease in bicarbonate.
12
Q
What are the two possible causes for an increase in pH (alkalinity)?
A
An increase in bicarbonate or a decrease in CO₂.
13
Q
What is the primary function of a buffer system?
A
To reversibly bind H⁺ ions, minimising changes in pH.
14
Q
How do buffer systems respond to the addition or removal of H⁺ ions?
A
- If H⁺ is added, the buffer binds it, shifting the reaction equilibrium to the right.
- If H⁺ is removed, the buffer releases H⁺, shifting the equilibrium to the left.
15
Q
Do buffer systems permanently remove H⁺ ions from the body?
A
- No, they only temporarily bind H⁺ to minimise fluctuations.
- They do not excrete H⁺ from the body.
16
Q
What factors limit the effectiveness of a buffer system?
A
The amount of buffer present and the magnitude of the pH change
17
Q
Where does the bicarbonate buffer system primarily function?
A
It is mainly an extracellular buffer system.
18
Q
Briefly describe the components and equilibrium of the bicarbonate buffer system.
A
- It involves the reversible reaction between H⁺ and bicarbonate ions on one side and carbonic acid on the other.
- CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻
- Carbonic acid is an intermediate that readily forms CO₂ and water.
19
Q
What is the significance of the phosphate buffer system in terms of location?
A
It functions as a buffer system both intracellularly and in the urine.
20
Q
How do the two forms of phosphate involved in buffering differ?
A
- One form has a single hydrogen ion bound (monoprotic), the other has two hydrogen ions bound (diprotic).
- This difference in hydrogen ion binding alters their charge.
21
Q
Where are protein buffer systems primarily located, and what is an example?
A
- Mainly intracellular.
- Haemoglobin in red blood cells is an important example of a protein buffer system.
22
Q
Which buffer system is considered the most crucial for acid-base balance, and why?
A
The bicarbonate buffer system is the most important because it interacts with both the lungs (which regulate CO₂) and the kidneys (which regulate bicarbonate).
23
Q
Which buffer system is considered the most important extracellular buffer?
A
The bicarbonate buffer system
24
Q
How does the bicarbonate buffer system interact with the kidneys and the lungs?
A
- The kidneys regulate the bicarbonate element
- The lungs control the carbon dioxide element
25
What equation demonstrates the relationship between pH, bicarbonate, and CO₂?
The Henderson-Hasselbalch equation:
* pH = pK + log₁₀ ([HCO₃⁻]/[CO₂])
## Footnote
- pH is the measure of acidity or alkalinity
- pK is the negative logarithm of the dissociation constant for carbonic acid (a constant value of 6.1)
- [HCO₃⁻] is the concentration of bicarbonate ions
- [CO₂] is the concentration of dissolved carbon dioxide
26
What are the typical concentrations of bicarbonate and CO₂ in arterial blood, and what is the resulting pH?
* Bicarbonate is typically around 25 millimolar
* CO₂ is about 1.2 millimolar
* The resulting pH is 7.4.
27
What happens if the normal 20:1 ratio of bicarbonate to CO₂ is disrupted?
Any changes in this ratio will lead to changes in pH.
28
What is the role of the lungs in maintaining pH balance?
The lungs can rapidly adjust CO₂ elimination through changes in ventilation rate to help restore pH.
29
How do the kidneys contribute to maintaining pH balance?
The kidneys provide a slower response by adjusting bicarbonate production and H⁺ excretion in the urine to restore pH.
30
Give examples of how changes in CO₂ and bicarbonate can lead to acidosis.
* Increased CO₂ reacting with water can lead to acidosis by increasing H⁺ concentration.
* Low bicarbonate levels can also cause acidosis.
31
Give examples of how changes in CO₂ and bicarbonate can lead to alkalosis.
Increased bicarbonate can lead to alkalosis, as can low CO₂ levels due to reduced H⁺ production.
32
How do the kidneys regulate extracellular fluid pH?
They adjust:
* the amount of **H⁺ excreted** in the urine
&
* the amount of **bicarbonate reabsorbed** from the filtrate back into the blood.
33
How much H⁺ must the kidneys excrete daily to maintain acid-base balance, and what is the typical urine pH as a result?
* They must excrete 70 to 100 mmol/day of H⁺, equivalent to the amount produced from non-volatile acids.
* This results in a mildly acidic urine.
34
Why is the reabsorption of bicarbonate from the filtrate important?
Bicarbonate loss in the urine is equivalent to adding acidity to the plasma because bicarbonate is needed to buffer H⁺ ions.
35
How much bicarbonate is filtered into the urine each day, and where is the majority reabsorbed?
Approximately **4500 mmol/day** is filtered, and the majority is reabsorbed in the **proximal convoluted tubule**.
36
Why is carbonic anhydrase and secreted H⁺ necessary for bicarbonate reabsorption in the proximal tubule?
* Bicarbonate cannot be directly transported across the luminal membrane.
* Therefore, carbonic anhydrase within the cell converts CO₂ and water to carbonic acid (CO₂ + H₂O ⇌ H₂CO₃), which then dissociates into bicarbonate and H⁺ (H⁺ + HCO₃⁻).
* The bicarbonate is reabsorbed, while the H⁺ is secreted into the lumen.
37
Describe the cyclical process of bicarbonate reabsorption in the proximal tubule.
* Secreted H⁺ reacts with filtered bicarbonate in the lumen, forming carbonic acid, which then breaks down into CO₂ and water.
* The CO₂ diffuses back into the cell, replenishing the CO₂ used to generate H⁺ and bicarbonate.
38
Where does the remaining 5-10% of bicarbonate reabsorption occur, and how does the mechanism differ?
* It occurs in the **late distal and collecting tubules**, primarily through **Type A intercalated cells**.
* These cells use H⁺ pumps (H⁺ ATPase or H⁺/K+ ATPase) to secrete H⁺ into the lumen, rather than relying on Na+ co-transporters.
39
What stimulates the activity of H⁺ secretion in the late distal and collecting tubules?
**Aldosterone** and **low potassium** levels can stimulate H⁺ secretion in these segments.
40
Why are urinary buffers important for H⁺ excretion?
They help to neutralise the acidity of the urine, enhancing patient comfort, and allowing for sufficient H⁺ excretion to maintain acid-base balance.
41
What are the two main urinary buffers, and how do they function?
* Phosphate: Filtered phosphate in the form of HPO₄²⁻(monoprotic) can bind with secreted H⁺, forming H₂PO₄⁻ (diprotic) which is then excreted.
* Ammonia: Ammonia (NH3) is produced from glutamine metabolism in the proximal tubule and secreted into the collecting duct, where it binds with H⁺ to form ammonium (NH4+), which is excreted.
42
How does the excretion of H⁺ in the urine lead to new bicarbonate production?
* The H⁺ excreted comes from the dissociation of carbonic acid within the renal tubular cells.
* The remaining bicarbonate from this dissociation is reabsorbed into the blood, effectively generating "new" bicarbonate.
43
What factors primarily stimulate H⁺ secretion by the kidneys?
An increase in partial pressure of CO₂ in the extracellular fluid and a decrease in extracellular pH.
44
How can aldosterone levels and potassium status influence H⁺ secretion?
Increased aldosterone and hypokalemia (low potassium) can stimulate certain mechanisms of H⁺ secretion.
45
Why are urinary buffers important for H⁺ excretion?
They neutralise the acidity of the urine, making it more comfortable for the patient, and allowing for sufficient H⁺ excretion to maintain acid-base balance.
46
What are the two main urinary buffers?
**Phosphate** and **Ammonia.**
47
Describe how the phosphate buffer system works in the urine.
* Filtered phosphate exists in two forms: monoprotic (HPO₄²⁻) and diprotic (H₂PO₄⁻).
* The monoprotic form can bind with secreted H⁺, forming the diprotic form, which is then excreted.
48
How does the excretion of H⁺ bound to phosphate lead to new bicarbonate production?
* When H⁺ is excreted bound to phosphate, the bicarbonate counter-ion that the H⁺ came from is retained in the blood.
* This process effectively generates "new" bicarbonate.
49
What is the source of ammonia for the ammonia buffer system in the urine?
Ammonia (NH₃) is produced from the metabolism of the amino acid glutamine in the proximal convoluted tubule cells.
50
Describe the role of glutaminase in ammonia production.
Glutaminase is an enzyme found in proximal tubule cells that breaks down glutamine to glutamate, which is ultimately converted to alpha-ketoglutarate, producing ammonium in the process.
51
How and where is ammonia secreted into the urine?
Ammonia is secreted into the collecting duct, where it binds with excess H⁺ and is excreted in the urine as ammonium (NH₄⁺).
52
How does the ammonia buffer system contribute to new bicarbonate production?
When H⁺ is excreted bound to ammonia, the bicarbonate that was originally associated with the H⁺ is retained in the blood, effectively generating "new" bicarbonate.
53
What is a key advantage of the ammonia buffer system compared to the phosphate buffer system?
* The ammonia buffer system can respond to the body's acid-base status.
* A decrease in pH stimulates renal glutamine metabolism, leading to increased production and excretion of NH₄⁺ and increased generation of new bicarbonate.
54
What is an acid-base disorder?
It is a disease process that alters the ratio of bicarbonate to CO₂, which is typically around 20:1, leading to a change in pH.
55
What is acidosis?
Acidosis is any process that results in the blood becoming more acidic (lower pH), which can be caused by the addition of acid or loss of alkali.
56
What is alkalosis?
Alkalosis is any process that results in the blood becoming more alkaline (higher pH), which can be caused by the addition of alkali or loss of acid.
57
What are the two categories of acid-base disorders, based on their primary cause?
They can be classified as either respiratory or metabolic.
58
What is the primary problem in metabolic acid-base disorders?
The primary problem affects bicarbonate levels.
59
What are the two types of metabolic disorders?
* Metabolic acidosis (not enough bicarbonate)
* Metabolic alkalosis (too much bicarbonate).
60
What is the primary problem in respiratory acid-base disorders?
CO₂ excretion is impacted
61
What are the two types of respiratory disorders?
* Respiratory acidosis (excessive accumulation of CO₂)
* Respiratory alkalosis (a lack of CO₂).
62
What is the concept of compensation in acid-base disorders?
Since pH is determined by the ratio of bicarbonate and CO₂, an abnormality in one can be partially compensated for by a change in the other, minimizing the pH change.
63
How do compensated disorders present in terms of bicarbonate and CO₂ levels?
In compensated disorders, both bicarbonate and CO₂ concentrations lie outside their normal ranges and move in the same direction (both raised or both lowered) to maintain the ratio as close to normal as possible.
64
Describe an example of compensation for respiratory acidosis.
* In respiratory acidosis, high CO₂ levels lead to a lower pH.
* The kidneys compensate by increasing bicarbonate production to counteract the acidity, bringing the pH closer to normal.
65
What are common causes of respiratory acidosis?
Problems affecting the lungs, chest wall, nerves, or muscles, leading to CO₂ retention.
66
How does compensation occur in respiratory acidosis?
Compensation is slow (takes days) and involves the kidneys increasing bicarbonate production.
67
What is respiratory alkalosis, and what causes it?
Respiratory alkalosis is a raised pH due to decreased CO₂. It is caused by disorders/scenarios leading to an inappropriate increase in ventilation such as
* Hyperventilation
* Anxiety
* High altitude.
68
How does compensation occur in respiratory alkalosis?
Compensation is slow and involves the kidneys decreasing bicarbonate production.
69
What is metabolic acidosis, and what are some possible causes?
Metabolic acidosis is a low pH due to decreased bicarbonate. It can be caused by:
* The addition of acids (lactic acid, ketoacids)
* Failure of H⁺ excretion
* Loss of bicarbonate.
70
How does compensation occur in metabolic acidosis?
Compensation can be relatively rapid and involves the lungs increasing ventilation to decrease CO₂ concentration.
71
What is metabolic alkalosis, and what are some possible causes?
Metabolic alkalosis is a raised pH due to increased bicarbonate. It can be caused by:
* The addition of alkali
* Excessive loss of acid (e.g., severe prolonged vomiting)
* Hormonal issues
* Dehydration leading to excess aldosterone
72
How does compensation occur in metabolic alkalosis?
Compensation can be relatively rapid and involves the lungs decreasing ventilation to increase CO₂.
73
Describe the three-step process for interpreting acid-base disorder test results.
* Step 1: Assess the pH - is it normal, low (acidosis), or high (alkalosis)?
* Step 2: Determine which of the measured values (bicarbonate or CO₂) best explains the observed pH change.
* Step 3: Look for evidence of compensation by examining if the other parameter (bicarbonate or CO₂) has moved out of its normal range in the same direction as the primary problem to minimize the pH change.
74
What is the underlying principle behind compensation in acid-base disorders?
* Compensation relies on the fact that pH is determined by the ratio of bicarbonate to CO₂.
* If one component of the ratio deviates from normal, the other component can adjust to minimize the change in pH.
75
In compensated acid-base disorders, what is the relationship between bicarbonate and CO₂ levels?
* Both bicarbonate and CO₂ concentrations will be outside their normal ranges but will move in the same direction (both increased or both decreased).
* This coordinated shift helps to maintain the bicarbonate-to-CO₂ ratio and minimizes pH changes.
76
How do the lungs compensate for metabolic acidosis?
The lungs **increase ventilation**
* More CO₂ is expelled, decreasing its concentration in the blood which helps to counteract the decrease in bicarbonate that is causing the acidosis.
* This is a relatively rapid compensatory response.
77
How do the lungs compensate for metabolic alkalosis?
The lungs **decrease ventilation**
* Leading to an increase in CO₂ levels which helps to counteract the increase in bicarbonate that is causing the alkalosis.
* This is a relatively rapid compensatory response.
78
How do the kidneys compensate for respiratory acidosis?
* The kidneys increase bicarbonate production and reabsorption.
* This helps to buffer the excess H⁺ ions caused by the elevated CO₂ levels.
* This response is slower and takes days to develop.
79
How do the kidneys compensate for respiratory alkalosis?
* The kidneys decrease bicarbonate production.
* This helps to counteract the alkalosis caused by the low CO₂ levels.
* This is a slow compensatory response that takes days to become fully effective.
80
In a case of respiratory acidosis, what direction would bicarbonate levels move to compensate?
Bicarbonate levels would increase to compensate for the acidosis.
81
In a case of metabolic alkalosis, how would CO₂ levels change to compensate?
CO₂ levels would increase to compensate for the alkalosis.
82
What is the most important approach to treating metabolic acid-base disorders?
The preferred approach is to identify and treat the underlying cause of the disorder, as this addresses the root of the problem.
83
What is a less preferred, alternative approach to treating acid-base disorders, and why is it not the primary choice?
* Directly neutralizing the acid or base imbalance with agents like sodium bicarbonate (for acidosis) or ammonium chloride (for alkalosis) is a less preferred approach.
* It is not the primary choice because it doesn't address the underlying cause of the disorder and can have potential side effects.
84
Provide an example of a situation where directly neutralizing the acid-base imbalance might be considered.
The decision to use neutralising agents is typically made by senior medical professionals and might be considered in severe cases where rapid correction of the pH is critical while the underlying cause is being addressed.
85
Why is identifying and correcting the underlying problem so crucial in the treatment of acid-base disorders?
* Correcting the underlying problem is crucial because it prevents recurrence of the acid-base imbalance and addresses the broader health issue that initially led to the disorder.
* For instance, treating an infection that caused lactic acidosis is more effective than simply administering sodium bicarbonate.
86
What is the first step in interpreting acid-base disorders based on test results? What can it tell you?
* Examine the pH value.
* If it's normal, there may not be an acid-base disorder.
* If it's low, it indicates acidosis
* If it's high, it signifies alkalosis.
87
After assessing the pH, what is the next step in the systematic approach?
* Analyse the bicarbonate concentration and the CO₂ (usually partial pressure of CO₂) value.
* Determine which of these parameters best explains the observed change in pH.
88
How do you link the changes in bicarbonate and CO₂ to the observed pH change?
* Consider that a raised bicarbonate level tends to increase pH, while a raised CO₂ level tends to decrease pH, and vice versa.
* Think about which parameter's change aligns with the direction of the pH shift.
89
If the change in CO₂ best explains the pH change, what type of disorder is it?
This indicates a primary respiratory disorder.
90
If the change in bicarbonate best explains the pH change, what type of disorder is it?
This indicates a primary metabolic disorder.
91
After identifying the primary disorder (respiratory or metabolic), what is the next step?
Evaluate the other parameter (bicarbonate for respiratory disorders, CO₂ for metabolic disorders) to assess for compensation.
92
What indicates the presence of compensation?
Compensation is present if the other parameter has moved outside its normal range in the same direction as the primary change, aiming to minimise the pH change.
93
If both CO₂ and bicarbonate are decreased, how do you differentiate between respiratory alkalosis and metabolic acidosis?
* The key differentiator is the pH change.
* Respiratory alkalosis will present with an increased pH (alkaline), while metabolic acidosis will present with a decreased pH (acidic).
94
In the case of a patient on high-flow oxygen why would a PaO₂ in the normal range be abnormal?
- A PaO₂ in the normal range is abnormal because it should be higher.
- The expected partial pressure of oxygen of a patient on oxygen should be approximately 10 kilopascals less than the percentage of inspired oxygen concentration.
- For example, if a patient is on 40% oxygen, then you would expect their PaO₂ to be around 30 kilopascals.
- If it's less than that, then the patient may still be in respiratory failure.
## Footnote
- For example, if a patient is on 40% oxygen, then you would expect their PaO₂ to be around 30 kilopascals.
- If it's less than that, then the patient may still be in respiratory failure.
95
What is the expected partial pressure of oxygen of a patient on oxygen?
* The expected partial pressure of oxygen of a patient on oxygen should be approximately 10 kilopascals less than the percentage of inspired oxygen concentration.
* If it's less than than this, then the patient may still be in respiratory failure.
## Footnote
- For example, if a patient is on 40% oxygen, then you would expect their PaO₂ to be around 30 kilopascals.
- If it's less than that, then the patient may still be in respiratory failure.
