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kidney function IV: acid base regulation Flashcards

1
Q

What are the three main effects of pH changes in the body?

A

Influence protein stability and function.

Affect nerve and muscle excitability.

Influence electrolyte distribution (e.g., renal K⁺ excretion and K⁺ movement between compartments).

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2
Q

What are the key components of acid excretion in the body?

A

Metabolic acid production and H⁺ intake contribute to acid load.
Acid excretion occurs via:
- Lungs (removal of CO₂).
- Kidneys (excretion of H⁺ and reabsorption of HCO₃⁻).

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3
Q

What is a major source of hydrogen ion gain in the body?

A

Generation of hydrogen ions from CO₂.

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4
Q

How does hypoventilation affect hydrogen ion balance?

A

Hypoventilation leads to CO₂ retention, increasing hydrogen ion concentration and causing acidosis.

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5
Q

How does a high-protein diet contribute to hydrogen ion gain?

A

It leads to the production of nonvolatile acids from the metabolism of protein and other organic molecules, generating 40-80 mmol/day of H⁺.

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6
Q

How does diarrhea contribute to acid-base imbalance?

A

Loss of bicarbonate in diarrhea or other non-gastric GI fluids results in a gain of hydrogen ions.

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7
Q

How does vomiting lead to hydrogen ion loss?

A

Vomiting results in the loss of stomach acid (H⁺), leading to alkalosis.

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8
Q

How does loss of bicarbonate in the urine contribute to acid-base balance?

A

Loss of bicarbonate in the urine results in a gain of hydrogen ions, contributing to acidosis.

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9
Q

What role does hyperventilation play in hydrogen ion balance?

A

Hyperventilation leads to excessive CO₂ loss, reducing hydrogen ion concentration and causing alkalosis.

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10
Q

What is the definition of pH?

A

pH = –log [H⁺].

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11
Q

What is the normal plasma pH range?

A

7.35-7.45 or 35-45 nM H⁺.

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12
Q

What is a respiratory or volatile acid?

A

CO₂ production (oxidative metabolism) excreted by the lungs

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13
Q

What is a non-respiratory or non-volatile acid?

A

other acids (e.g., phosphoric acid) excreted by the kidneys.

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14
Q

At what level are plasma acid levels regulated?

A

At the nanomolar (nM) level.

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15
Q

How does acid production compare to plasma acid regulation?

A

Acid production occurs in the millimolar (mM) range, whereas plasma acid levels are regulated at the nanomolar (nM) level.

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16
Q

Why are buffers required in acid-base balance

A

To prevent large swings in [H⁺].

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17
Q

What is the definition of a buffer?

A

A buffer is any substance that can reversibly bind H⁺.

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18
Q

What is a buffered solution?

A

A mixture of a weak acid and its conjugate base.

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19
Q

What is the general form of the buffering reaction?

A

Buffer + H⁺ = HBuffer.

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20
Q

What happens when [H⁺] increases?

A

The reaction shifts to the right.

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21
Q

What happens when [H⁺] decreases?

A

The reaction shifts to the left.

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22
Q

What is the most important physiological buffer?

A

The bicarbonate system.

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23
Q

What is the equation for the bicarbonate buffer system?

A

HCO₃⁻ + H⁺ ⇌ H₂CO₃ ⇌ CO₂ + H₂O

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24
Q

What is the general pH of intracellular fluid and organelles?

A

Less than 7.35, except for mitochondria.

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25
26
What equation determines the pH of a buffer solution?
27
28
What does the Henderson-Hasselbalch equation allow us to calculate?
It allows calculation of any one of: pH, pCO₂, [HCO₃⁻], if the other two are known.
29
What two factors determine buffer effectiveness?
Concentration and pK of the buffer.
30
31
What is the normal range for arterial pCO₂?
4.0 - 6.0 kPa (Average: 5.3 kPa).
32
19 - 24 mM (Approximate average: 25 mM).
33
22 - 28 mM (Approximate average: 25 mM).
34
What is the normal range for arterial pH?
7.35 - 7.45 (Normal value: 7.4).
35
What is the typical pH range of urine?
Urine is usually acidic, but the pH can range from 4.4 to 8.
36
What is the pK value of ammonia as a buffer?
9.2
37
What is the pK value of phosphate as a buffer?
6.8
38
What is the pK value of bicarbonate as a buffer?
6.1
39
What is the pK value of urate as a buffer?
5.8
40
What is the pK value of citrate as a buffer?
5.5
41
What is the pK value of proteins (His residues) as a buffer?
~6
42
What are the two key processes involved in acid-base balance?
Matching output to input (excretion). Regulating the ratio of base to weak acid in buffer systems (e.g., bicarbonate to carbonic acid).
43
What does the kidney regulate in acid-base balance?
Bicarbonate (HCO₃⁻)
44
What do the lungs regulate in acid-base balance?
pCO₂ (partial pressure of carbon dioxide)
45
What is the relationship between pH, bicarbonate, and pCO₂?
pH is proportional to [HCO₃⁻] / [pCO₂]
46
How do the lungs regulate pCO₂ in acid-base balance?
Increased acid (H⁺) leads to increased pCO₂. This stimulates respiration, causing CO₂ elimination from the body.
47
How do the kidneys regulate bicarbonate in acid-base balance?
Reabsorbing bicarbonate (HCO₃⁻) to maintain buffer levels. Excreting excess H⁺ to prevent acidosis.
48
Where does bicarbonate (HCO₃⁻) reabsorption occur in the kidney?
1. Proximal tubule 2. Ascending loop of Henle 3. Cortical collecting ducts (intercalated cells type A)
49
What happens to HCO₃⁻ and H⁺ after they are formed from H₂CO₃?
HCO₃⁻ is reabsorbed into the blood. H⁺ is secreted into the filtrate.
50
What are the key transporters involved in H⁺ secretion?
Na⁺-H⁺ countertransporters H⁺-ATPase pumps H⁺-K⁺-ATPase pumps
51
When is H⁺ secretion not excreted?
If HCO₃⁻ is available in the lumen, H⁺ reacts with it and is not excreted.
52
What is H⁺ excretion combined with?
Non-bicarbonate buffers, such as monohydrogen phosphate (HPO₄²⁻).
53
What would happen if H⁺ was not buffered in the urine?
Urine pH would drop below 5.
54
What is the result of H⁺ excretion?
Addition of new HCO₃⁻ to the plasma.
55
What additional mechanism adds new HCO₃⁻ to plasma?
Glutamine metabolism.
56
What are the products of glutamine metabolism in the renal tubular cells?
Ammonium ions (NH₄⁺) and bicarbonate (HCO₃⁻).
57
How is NH₄⁺ excreted in the urine?
NH₄⁺ is secreted into the tubular lumen in exchange for Na⁺.
58
What transporter helps glutamine enter the renal tubular epithelial cells?
Glutamine-amino acid exchanger (LAT2).
59
What can NH₄⁺ be considered as in terms of its components?
NH₄⁺ can be considered as NH₃ (ammonia) and H⁺.
60
What are the three main mechanisms that maintain a constant pH?
1. Chemical buffers 2. Brainstem respiratory center 3. Renal mechanisms.
61
how fast do chemical buffers work?
They work in seconds.
62
What are the main chemical buffers in the body?
- Bicarbonate in ECF - Phosphate in ICF - Phosphate or ammonia in urine
63
How does the brainstem respiratory center regulate pH?
It responds to changes in arterial pCO₂, pO₂, and/or [H⁺] by adjusting ventilation to retain or expel CO₂.
64
How fast does the brainstem respiratory center work?
In minutes.
65
How do renal mechanisms help regulate pH?
For each H⁺ secreted, HCO₃⁻ is reabsorbed or new bicarbonate is added to plasma.
66
How fast do renal mechanisms work?
They work in hours to days.
67
What is acidemia?
Acidemia occurs when plasma pH is less than 7.35.
68
What is alkalemia?
Alkalemia occurs when plasma pH is greater than 7.45.
69
What are the two types of acid-base disorders?
Respiratory and Metabolic.
70
What causes respiratory acidosis or alkalosis?
A respiratory problem.
71
What causes metabolic acidosis or alkalosis?
A non-respiratory problem.
72
What controls bicarbonate (HCO₃⁻) levels in the body?
The kidneys control HCO₃⁻, and it is altered in metabolic disorders.
73
What controls partial pressure of carbon dioxide (pCO₂) in the body
Respiration controls pCO₂, and it is altered in respiratory disorders.
74
What happens to pH, pCO₂, and HCO₃⁻ in respiratory acidosis?
75
What happens to pH, pCO₂, and HCO₃⁻ in respiratory alkalosis?
76
What happens to pH, pCO₂, and HCO₃⁻ in metabolic acidosis?
77
What happens to pH, pCO₂, and HCO₃⁻ in metabolic alkalosis?
78
What is compensation in acid-base disorders?
The body attempts to return the pH to normal when a primary acid-base disorder occurs.
79
What is respiratory acidosis caused by?
Insufficient CO₂ excretion by the lungs (alveolar hypoventilation).
80
What are the characteristics of acute respiratory acidosis?
PaCO₂ > 5.3 kPa pH < 7.35 Abrupt failure in ventilation Examples: Drug-induced respiratory depression (e.g. narcotics, barbiturates) Airway obstruction (e.g. asthma)
81
What are the characteristics of chronic respiratory acidosis?
PaCO₂ > 5.3 kPa pH ≤ 7.35 HCO₃⁻ > 30 mM Examples: Airway obstruction (e.g. COPD) Lung damage (e.g. fibrosis) Chest wall disorders (e.g. pectus carinatum) Neuromuscular disorders (e.g. ALS)
82
What is an important note about respiratory acidosis?
Patients are likely hypoxic (low PₐO₂). Correction cannot come from a respiratory change.
83
How do chemical buffers respond to respiratory acidosis?
Work in seconds to attenuate changes in pCO₂ and acidemia.
84
What is the role of chemical buffers in attenuating pCO₂ changes?
85
How do chemical buffers help in attenuating acidemia?
The reaction is reversible: - More H⁺ ions shift the reaction left, reducing free H⁺ concentration.
86
What is the overall result of chemical buffer action in respiratory acidosis?
CO₂, H⁺, and HCO₃⁻ levels are raised. However, changes are smaller than they would be without buffering.
87
How does the brainstem respiratory center compensate for respiratory acidosis?
Works in minutes to adjust ventilation and expel CO₂. However, since ventilation is an issue in respiratory acidosis, correction cannot come from a respiratory change.
88
How do the renal mechanisms compensate for respiratory acidosis?
Works in hours to days. For each H⁺ secreted, HCO₃⁻ is reabsorbed. Glutamine metabolism increases, contributing to acid excretion. Urine becomes highly acidic (pH = 4.4) to compensate for excess CO₂ retention. Plasma HCO₃⁻ levels increase to buffer the acidemia
89
What defines metabolic acidosis?
A fall in plasma bicarbonate (HCO₃⁻) concentration and pH < 7.35.
90
What are the two main mechanisms of metabolic acidosis?
True HCO₃⁻ deficit (normal anion gap) H⁺ gain (increased anion gap)
91
What conditions cause metabolic acidosis due to true HCO₃⁻ deficit?
Renal tubular acidosis (kidneys) Diarrhea (gastrointestinal loss)
92
What causes metabolic acidosis due to H⁺ gain
Exogenous acid (NH₄Cl, toxins) Diabetic ketoacidosis Lactic acidosis Uremic acidosis
93
How does diabetic ketoacidosis contribute to metabolic acidosis?
Ketone bodies increase acid load and bicarbonate is lost in urine.
94
What is the anion gap?
The difference between measured cations (Na⁺, K⁺) and measured anions (Cl⁻, HCO₃⁻), representing unmeasured anions in plasma.
95
What is the formula for calculating the anion gap?
96
What are examples of unmeasured anions contributing to the anion gap?
Proteins, phosphate, citrate, sulfate.
97
How are ions classified in anion gap calculations?
Sodium (Na⁺): Measured cation Bicarbonate (HCO₃⁻) & Chloride (Cl⁻): Measured anions Anion gap: Represents unmeasured anions in plasma
98
What does the anion gap help identify?
The cause of metabolic acidosis.
99
What characterizes normal anion gap metabolic acidosis?
Loss of bicarbonate (HCO₃⁻) is compensated by an increase in chloride (Cl⁻), keeping the anion gap unchanged.
100
What characterizes high anion gap metabolic acidosis?
A drop in bicarbonate (HCO₃⁻) is not compensated by chloride (Cl⁻), leading to an increased anion gap due to unmeasured anions.
101
What is the primary chemical buffer reaction in metabolic acidosis?
102
What happens to blood pH when H⁺ increases?
pH decreases, leading to a reduction in bicarbonate (HCO₃⁻).
103
How does respiratory compensation for metabolic acidosis occur?
Increased ventilation → ↓ pCO₂ → Partial compensation for acidosis.
104
How does renal compensation for metabolic acidosis occur?
↑ H⁺ secretion, increased glutamine metabolism, and HCO₃⁻ reabsorption to restore balance.
105
How do pH, PaCO₂, and HCO₃⁻ change in metabolic acidosis compensation?
106
What causes respiratory alkalosis?
Excessive respiratory drive leading to excess CO₂ loss (e.g., hyperventilation, fever, aspirin overdose, altitude response).
107
How does respiratory alkalosis affect CO₂ levels?
pCO₂ falls (<5.3 kPa, hypocapnia).
108
What is the chemical buffer response to respiratory alkalosis?
109
What is the respiratory compensation for respiratory alkalosis?
Reduce ventilation (if possible) to retain CO₂.
110
What is the renal compensation for respiratory alkalosis?
111
How do pH, PaCO₂, and HCO₃⁻ change in respiratory alkalosis compensation?
112
What characterizes metabolic alkalosis?
pH > 7.45 with high plasma HCO₃⁻.
113
What are the causes of metabolic alkalosis?
Repeated vomiting → loss of gastric acid Excess aldosterone → stimulates H⁺-ATPase pump Excess alkali ingestion (e.g., bicarbonate, citrate, lactate)
114
How do chemical buffers respond to metabolic alkalosis?
↓ H⁺ concentration → ↑ pH ↑ HCO₃⁻ in plasma Reaction shifts left: H⁺ + HCO₃⁻ → H₂CO₃ → H₂O + CO₂
115
What is the respiratory compensation for metabolic alkalosis?
Inhibits respiration Retains CO₂ in the body Hypoxia may stimulate respiration
116
What is the renal compensation for metabolic alkalosis?
Kidneys excrete excess HCO₃⁻.
117
How do pH, PaCO₂, and HCO₃⁻ change in metabolic alkalosis?
118
What are the 2 roles of Type B intercalated cells in metabolic alkalosis?
Remove bicarbonate (HCO₃⁻) into urine Acidify plasma
119
What is the function of Pendrin in renal compensation for metabolic alkalosis?
Pendrin is an exchanger protein that secretes HCO₃⁻ into the tubular lumen while reabsorbing Cl⁻.
120
How does the liver regulate glutamine production in response to acid-base balance?
Acidosis → Liver increases glutamine production → More bicarbonate added to plasma. Alkalosis → Liver reduces glutamine production → Less bicarbonate added to plasma.

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