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Drug Action I > Block 4: Acid-Base Physiology > Flashcards

Block 4: Acid-Base Physiology Flashcards

1
Q

What is acid-base balance?

A

Regulation hydrogen ion (H+) concentration in body fluids → for normal cell/organ function and survival

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2
Q

How does the H+ influence acid-base balance?

A

Highly reactive where concentration is precisely regulated within a narrow normal range

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3
Q

What is the function of H+ concentration?

A
  1. Alters distribution of electrolytes
  2. Alters activity of enzymes involved in ATP production
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4
Q

How do lungs contribute to acid-base balance?

A

Regulate the elimination of CO2, a source of carbonic acid

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5
Q

How do kidneys contribute to acid base balance?

A

Eliminate H+ and HCO3-

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6
Q

What is tissue perfusion?

A

Ensures delivery of O2 and nutrients → Maintaining aerobic metabolism

Decreased perfusion → anaerobic metabolism and accumulation of lactic acid

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7
Q

What are volatile acids? Example?

A

Can dissociate forming a gas eliminated by the lungs

Carbonic acid (H2CO3)

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8
Q

How leads to CO2 production?

A
  1. Formed during aerobic metabolism
  2. Combines with water to form carbonic acid
  3. H2CO3 dissociates into H+ and bicarb
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9
Q

What happens if there is an accumulation of CO2?

A

↑ Carbonic acid → ↓ pH

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10
Q

What are nonvolatile acids?

A

Not gases → cannot be eliminated from the lungs; eliminated primarily by kidneys

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11
Q

How does nonvolatile acid differ from volatile gases?

A

Lower production → takes longer to reach comparable degree of acidity in kidney failure than respiratory failure

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12
Q

What causes fluctuations of H+?

A
  1. Daily ingestion
  2. Metabolic production
  3. Utilization of acids and bases
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13
Q

What are the types of buffer systems?

A
  1. Chemical
  2. Respiratory
  3. Renal
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14
Q

What is the function of chemical buffers?

A

Intracellular and extracellular buffers that neutralize excess acids and bases

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15
Q

What is the function of respiratory buffers?

A

eliminates carbonic acid (H2CO3) in the form of CO2 in exhaled air

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16
Q

What is the function of renal buffers?

A

regulates the excretion of bicarbonate (HCO3-) and H+ from nonvolatile acids

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17
Q

What is important for local acid-base balance?

A

Good tissue perfusion

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18
Q

What are components of chemical buffers?

A
  1. Consist of a weak acid and a weak base.
  2. Convert strong acids/bases to weak ones.
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19
Q

How long does chemical buffer take to buffer?

A

Max efficiency with an hour after imbalance

React almost immediately

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20
Q

What are the types of chemical buffers?

A
  1. Bicarbonate buffer system
  2. Phosphate buffer system
  3. Intracellular and extracellular proteins
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21
Q

How do you calculate pH of a buffer system?

A

Henderson–Hasselbalch equation

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22
Q

Describe the chemical regulation of bicarb buffer system?

A

The ratio of bicarbonate (HCO3-) to carbonic acid (H2CO3) is 20:1

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23
Q

What is pKa?

A

Dissociation constant of weak acid

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24
Q

What is the ideal buffer system?

A

pKa = pH of solution

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25
Q

What is the purpose for bicarbonate buffer system?

A

pKa=6.1 (and blood pH=7.4) → still an important ECF buffer because:
1. Lungs can regulate the level of carbonic acid
2. Kidneys can regulate the level of bicarb

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26
Q

How does the bone contribute to acid and base balance?

A
  1. H+ ions move into bone to be buffered by hydroxyapatite and carbonates → release of Ca and phosphate from bone
  2. Prolonged ↑ H+ → activate osteoclasts → bone resorption
  3. Electrolyte loss and resorption → bone demineralization and increased risk of fractures
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27
Q

How does respiration regulate acid-base balance?

A
  1. CO2 diffuses from pulmonary capillaries into alveoli and is then eliminated in exhaled air
  2. If CO2 accumulates, then the concentration of H+ in body fluids increases
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28
Q

How control respiratory reg?

A

Brainstem respiratory center → feedback mechanism between it and the lungs

H+ excess trigger a neural reflex

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29
Q

How does ↑ H+ neural reflex?

A
  1. ↑ rate and contraction of respiratory muscles
  2. ↑ breathing rate and depth
  3. Eliminate CO2 → ↓ carbonic acid → ↑ pH
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30
Q

How does the respiratory system compensate for extreme acidosis?

A

Hyperventilation ceases

Reflex fails

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31
Q

How does the respiratory system compensate for extreme alkalosis

A

Ventilation is depressed, leading to:
1. Accululation of CO2 → ↑ carbonic acid → ↓ pH

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32
Q

What is compensatory hypoventilation?

A

Lungs retain CO2 → more carbonic cid

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33
Q

How is hypoventilation not really noticed?

A

Subsequent hypoxemia and hypercapnia stimulate respiration

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34
Q

How long does it take for respiratory reg compensate?

A

Maximal compensation takes 24-48 hours

Chemoreceptors detect H+ changes

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35
Q

What may cause a delay is respiratory reg?

A
  1. Transporting blood
  2. Initiating a relex response
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36
Q

What are the respiratory compensation limitations?

A
  1. If lungs are source of acidosis or alkalosis.
  2. Diminished stimulus to respiratory center
  3. Lung disease
  4. Neuromuscular disease
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37
Q

How does the renal regulate acid-base?

A

Regulates bicarbonate and nonvolatile acids

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38
Q

What is normal pH of urin?

A

Usually acidic
4-8, average: 6

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39
Q

What are the mechanisms of renal reg?

A
  1. Conservation of bicarbonate by tubular reabsorption.
  2. Secretion of H+ into urine; synthesis of new bicarbonate.
  3. Excretion of H+ buffered by ammonia
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40
Q

How does it take longer for the renal system to regulate acid-base?

A

8-12 hours – begin to have effect

4-6 days – maximum effectiveness

Slowest yet most effective → H+ and HCO3- can be excreted if need → capable of completely retuning pH to normal

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41
Q

How causes disruption to renal reg?

A
  1. Kidney impariment
  2. They are a source of the imbalance
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42
Q

Describe how the renal system conserves bicarb ions?

A
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43
Q

Describe how the renal system secrete H+ in the urine and creates new HCO3-?

A
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44
Q

What is the difference between compensation and correction?

A

Compensation: Chemical buffers, renal or respiratory function return pH within normal range → Underlying disease

Correction: Condition responsible for imbalance is controlled or no longer present → pH is within normal range

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45
Q

What is intracellular pH?

A
  1. Major impact on cell function
  2. Affected by changes in both the H+ concentration and ECF
  3. Varies with different cell types
  4. Clinical pHi measurement is not feasible
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46
Q

What are the mechanism for regulating pHi?

A
  1. buffers
  2. HCO3-
  3. Transporters
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47
Q

What are the simple acid-base imbalances? Distinguish the types?

A
  1. Respiratory acidosis
  2. Respiratory alkalosis
  3. Metabolic acidosis
  4. Metabolic alkalosis
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48
Q

What is the difference between respiratory and metabolic imbalances?

A

R: Due to alteration in CO2 elimination by lungs
M: Due to alterations in the level of nonvolatile acids or bases HCO3

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49
Q

How are the clinical manifestation of acid-base imbalances?

A
  1. Effects of acidosis or alkalosis on cell functions.
  2. Effects of underlying disease process causing acid-base imbalance.
  3. Manifestations of respiratory or renal compensation.
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50
Q

What is the normal ratio of bicarb to carbonic acid?

A

20:1

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51
Q

What ions control neuromuscular function?

A

Hydrogen and calcium ions that bind to negative charged plasma intracellular proteins and

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52
Q

How is neuromuscular function affected by acidosis?

A

Reduced NM excitability by ↑ levels of calcium that blocks sodium channels in nerves and muscles → decreases neuromuscular excitability → muscle weakness, weak reflexes

Excess H+ ions bind to negative charges causing fewer sites available for Ca2+

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53
Q

How is neuromuscular function affected by alkalosis?

A

↑ NM excitability → fewer H+ compete with Ca2+ for PB sites → less Ca2+ blocks sodium channels

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54
Q

What are the NM function of alkalosis?

A
  1. Trousseasu
  2. Hyperactive reflexes
  3. Paresthesias
  4. Convulsion
  5. Larynospasm
  6. Tetany
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55
Q

How is the CNS altered by acidosis?

A

Increased cerebral BF → decreased sodium entry → vasodilation of cerebral blood vessels → HA, increased intracranial pressure

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56
Q

How is the CNS altered by alkalosis?

A

Vasoconstriction of cerebral BV → ↓ cerebral BF and O2 delivery → DZ, AX, SZ, Confusion, coma

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57
Q

How does acidosis affect perfusion?

A
  1. Negative ionotropic effect → decrease in cardiac contractility → Decreased perfusion
  2. Increased sympathetic tone initially helps compensative
  3. Increased arterial BP
  4. Decreased responsiveness of adrenergic receptors
  5. Vasodilation from impaired Na entry into cell
58
Q

How does alkalosis affect perfusion?

A

Biphasic effect on cardiac countability

Associated with hypokalemia → increased vascular reactivity → coronary artery vasospasm → MI, angina

59
Q

How does alkalosis affect SVR?

A

Vasodilation and decreased SVR at pH ≤ 7.65

Vasoconstriction and increased SVR at pH > 7.65

60
Q

How does metabolic acidosis effect electrolyte levels?

A

Caused by an excess of inorganic acids or sulfuric acids: Excess H+ enter cells in exchange for movement of K+ out of cells → hyperkalemia

Caused by excess organic acids or ketoacid → H+ and anion move into the cell

61
Q

How can metabolic alkalosis affect electrolyte levels?

A

H+ move out of cells in exchange for K+ movement into cells → Hypokalemia

62
Q

What has respiratory acidosis affect electrolyte levels?

A

↑ serum P

63
Q

What has respiratory alkalosis affect electrolyte levels?

A

↓ serum P

64
Q

What is the relationship of Phosphofructokinase and acid-base balance?

A

Acidosis → PFK depression → imparts glycolysis and ATP production → Decreased ATP → weakness and fatigue

Alkalosis → PFK ↑ → stimulates glycolysis → ↑ use of P

65
Q

How does acidosis affect oxygenation?

A

Hemoglobin–oxygen dissociation curve shifts to right → decreased affinity of Hb and increased unloading of O2 to cells → Beneficial

66
Q

How does alkalosis affect oxygenation?

A

Hemoglobin–oxygen dissociation curve shifts to left → Increased affinity of Hb → Decreased unloading → Adverse effects

67
Q

What are the lab tests we could do to assess acid-base status?

A
  1. Arterial blood gases
  2. Venous blood gases
  3. Base excess
  4. Anion gap
68
Q

What is the most useful test for A-B assessment?

A

ABG

69
Q

What does ABG measure?

A
  1. pH
  2. PaCO2
  3. PaO2
  4. HCO3-
  5. Total CO2 (TCO2)
70
Q

What is acidosis?

A

Pathophysiologic process resulting in excess amount of H+ in the body

71
Q

What is normal pH?

A

7.35–7.45

72
Q

What is acidemia?

A

State of excess H+ and base deficit (low pH) in the blood

73
Q

What is alkalosis?

A

Pathophysiologic process resulting in a deficit of H+ in the body

74
Q

What is alkalemia?

A

State of H+ deficit and base excess (elevated pH) in the blood

75
Q

How can acidosis and alkalosis be present at the same time?

A

Two or more processes may drive pH in opposite directions

A patient’s acid-base status could be abnormal even if pH is within a normal range

76
Q

What is PaCO2?

A

Pressure exerted by CO2 dissolved in arterial blood plasma

77
Q

How affects PaCO2?

A

Below-normal pH and increased PaCO2 indicate respiratory acidosis.

Above-normal pH and decreased PaCO2 indicate respiratory alkalosis.

78
Q

Describe the effects of PaCO2 with compensation?

A

If pH is low because of metabolic acidosis, lungs compensate by decreasing PaCO2

A low PaCO2 level is not the cause of the low pH

79
Q

How does the kidneys compensate for respiratory acid-base imbalance?

A

increasing or decreasing HCO3–.

If pH is low because of respiratory acidosis, kidneys compensate by increasing serum HCO3–.

In that case, increased HCO3– level is not the cause of the low pH because HCO3– is a base.

80
Q

What is total CO2? What is it for?

A

All forms of CO2 in blood

Acid is added to blood sample → CO2 gas liberated and measured

81
Q

What is PaO2?

A

Pressure exerted by O2 dissolved in arterial blood plasma → points out if acidosis is present

82
Q

Describe how PaCO2 and HCO3- levels react to AB imbalances?

A
83
Q

What is an anion gap?

A

Used when the type of imbalance is unclear

Differentiates the cause of metabolic acidosis and identifies acid-base imbalances

84
Q

Anion gap detects _____ amount of anions?

A

Increased

Sum of concentration of all cations equals the sum of concentration of all anions

85
Q

What is are common causes of high anion gaps?

A
  1. Lactic acidosis
  2. Ketoacidosis
  3. Renal failure
86
Q

What are the factors that stabilize a normal anion gap?

A
  1. Chloride ↑
  2. HCO3 below normal

Reciprocal relationship between Cl- and HCO3-

87
Q

What are the characteristics of respiratory acidosis?

A
  1. Elevated PaCO2 (hypercapnia) and H2CO3-
  2. Blood pH <7.35
  3. Ratio of bicarbonate to carbonic acid below 20:1
88
Q

What is acute vs chronic respiratory acidosis?

A

Acute: present before renal compensation

Chronic: present after renal compensation is complete

89
Q

What are the causes of respiratory acidosis?

A

Impaired elimination of CO2 by lungs:
1. Respiratory diseases or conditions
2. CNS dysfunction
3. Neuromuscular disorders
4. Electrolyte imbalances
5. Metabolic conditions

90
Q

How does respiratory disease cause the acidosis (respiratory)?

A
  1. Impaired alveolar ventilation or diffusion of CO2 from blood into alveoli.
  2. Increased production of CO2 without an increase in ventilation
91
Q

How does respiratory acidosis cause CNS dysfunction?

A
  1. Decreased central drive to breathe: neural centers receive input → peripheral chemoreceptors → stimulate breathing
92
Q

What medication can cause respiratory acidosis?

A

General anesthetics, barbs, opioid analgesis

93
Q

What can ↓ central drive to breathe?

A
  1. Increased intracranial pressure
  2. Sleep apnea
  3. Cardiopulmonary arrest
94
Q

How can respiratory acidosis causes NM disorders?

A
  1. Restrict lung expansion
  2. Obstruct airflow

Interfere with innervation or contractility of the muscles of inspiration

Fluid accumulation in the abdominal cavity

95
Q

How can respiratory acidosis causes electrolyte imbalances?

A
  1. Severe hypokalemia → Decreased contraction of respiratory muscles leads to hypoventilation
  2. Severe hypophosphatemia → Decreased availability of phosphate and respiratory muscle contractility → hypoventilation
96
Q

How can respiratory acidosis causes metabolic conditions?

A

increase CO2 production without increased CO2 elimination → increase body temp and overfeeding with carbs

97
Q

What is permissive hypercapnia?

A

↑ in PaCO2

Low tidal volume ventilation

98
Q

What are clinical manifestation of uncompensated respiratory acidosis?

A

Arterial blood pH < 7.35
PaCO2 elevated
HCO3- normal

99
Q

What are clinical manifestation of compensated respiratory acidosis?

A
  1. Increased bicarbonate resorption
  2. Increased H+ excretion
  3. Serum bicarbonate level increases.
  4. pH elevates to normal.
  5. Urine becomes more acidic.
100
Q

What are the characteristics of respiratory alkalosis?

A

CO2 deficit (hypocapnia)

Increases ratio of bicarbonate to carbonic acid above 20:1.

101
Q

What is the difference between the types of respiratory alkalosis?

A

Acute: Presense of hypocapnia before renal compensation
Chronic: Presence of hypocapnia after renal compensation is complete

102
Q

How does hyperventilation cause respiratory alkalosis?

A

increased alveolar ventilation → Increse in CO2

103
Q

How does CNS dysfunction cause respiratory alkalosis?

A

decreased oxygen delivery → activate peripheral chemoreceptors → respiratory centers in brain → excessive CO2 elimination → alkalosis

104
Q

What are causes of respiratory alkalosis?

A
  1. Emotions
  2. Lung disease
  3. Endogenous substances
  4. Brain lesions
  5. Medication: Salicylates
  6. Hypermetabolic states
  7. Mechanical ventilation
105
Q

What are the signs of respiratory alkalosis?

A
  1. Increased neuromuscular excitability.
  2. Increased effort to breath due to increased rate or depth of breathing.
106
Q

What is the clinical manifestations of uncompensated respiratory alkalosis?

A
  1. Arterial blood pH > 7.45
  2. PaCO2 decreased
  3. Serum bicarbonate normal
107
Q

What is the clinical manifestations of renal compensated respiratory alkalosis?

A
  1. Decreased bicarb resorption
  2. Decreased H+ excretion
  3. Decreased serum bicarb levels
  4. pH decreases to normal

Manifestations more severe in acute cases

108
Q

What are the characteristics of metabolic acidosis?

A
  1. Decreased blood pH (due to H+ excess)
  2. Decreased HCO3–
  3. Normal PaCO2
  4. Ratio of bicarbonate to carbonic acid: <20:1
109
Q

What are the causes of metabolic acidosis?

A

1.Elevated anion gap
2. Normal anion gap

110
Q

Describe elevated anion gap metabolic acidosis?

A

Increase production of or decrease elimination of fixed acids

111
Q

Describe normal anion gap metabolic acidosis?

A

Increase base bicarbonate loss or decrease production or renal reabsorption of bicarbonate

112
Q

What are the causes of elevated anion gaps?

A
  1. Lactic acidosis
  2. Diabetic and alcoholic ketoacidosis
113
Q

What is the difference between lactic acidosis types?

A

Type A: Conditions that cause imbalance between oxygen demands and oxygen supply (hypoxia)
Type B: Due to conditions other than hypoxia

114
Q

What is ketoacidosis?

A

abnormal lipid metabolism → increased ketoacid production

115
Q

What is diabetic ketoacidosis?

A

Insulin deficiency and resistance

116
Q

What is alcoholic ketoacidosis?

A

excessive ingestion of alcoholic beverages

117
Q

How can renal failure cause elevated anion gap?

A

Decreased GFR → impaired daily excretion of fixed acids and deceased renal production of ammonia, decreasing ability to excrete H+ buffered in urine

118
Q

How can pregnancy cause elevated anion gap?

A

Decreased perfusion → hemorrhage, sepsis, severe HTN, compression of umbilical cord

119
Q

What are the poisons that cause elevated anion gap?

A

MULEPAK
1. Methanol
2. Uremia (caused by renal failure)
3. Lactic acidosis
4. Ethylene glycol
5. Paraldehyde (and other drugs)
6. Aspirin (and other salicylates)
7. Ketoacidosis

120
Q

How does ethylene glycol cause elevated anion gap?

A
121
Q

What are the cause of metabolic acidosis that have normal anion gap?

A
  1. Loss of HCO3–rich intestinal fluid
  2. Impaired HCO3- resorption in kidneys
122
Q

What causes hyperchloemic metabolic acidosis?

A

When chloride increases, HCO3- decreases → due to ↑ in renal excretion of HCO3 to maintain electrical neutrality in ECF

123
Q

What is type 1 renal tubular acidosis?

A

Defect in H+ pump in DCT → impaired H+ ion secretion into urine → failure of H/K ATPase

124
Q

What is type 2 renal tubular acidosis?

A

Impaired HCO3- resorption in PCT → Involves increased K+ excretion

125
Q

What are clinical manifestation of uncompensated metabolic acidosis?

A
  1. Arterial blood pH < 7.35
  2. PaCO2 normal
  3. Serum HCO3- below normal
126
Q

What are the signs of metabolic acidosis compensation?

A
  1. Increased rate/depth of breathing
  2. Kussmaul respirations (deep/labored breathing)
127
Q

What are the signs of respriratory compensation of metabolic acidosis?

A
  1. CO2 elimination increases.
  2. Serum H2CO3 decreases.
  3. pH rises to normal
128
Q

What are the characteristics of metabolic alkalosis?

A
  1. State of H+ deficit and increased blood pH
  2. Increased HCO3-
  3. Normal PaCO2
  4. Ratio of bicarbonate to carbonic acid: >20:1
129
Q

What are the mechanisms that cause of metabolic alkalosis?

A
  1. Excessive loss of hydrogen ions.
  2. Excessive intake of base.
  3. Excessive renal retention of bicarbonate.
130
Q

What is contraction alkalosis?

A

Loss of ECF volume without comparable HCO3 loss

131
Q

What are the factors that impair renal HCO3 excretion?

A
  1. Circulating fluid volume deficit
  2. Potassium or chloride deficiency
  3. High aldosterone levels
132
Q

What are the common causes of metabolic alkalosis?

A
  1. Loss of gastric fluid (hypochloremic metabolic alkalosis)
  2. Loop and thiazide diuretics
  3. Excessive or too rapid correction of acidosis.
  4. Large amounts of bases
  5. Posthypercapnic metabolic acidosis
  6. Milk alkali syndrome
133
Q

What is posthypercapnic metabolic acidosis?

A

When PaCO2, and thus carbonic acid, is quickly lowered, elevated bicarbonate has less acid to buffer

134
Q

What is milk alkali syndrome?

A

Hypercalcemia and metabolic alkalosis resulting from ingestion of large amounts of milk and antacids containing calcium carbonate

135
Q

What are the clinical manifestations of metabolic alkalosis?

A
  1. Changes in blood gases.
  2. Decreased rate and/or depth of breathing.
  3. Impaired cell oxygenation.
  4. Increased neuromuscular excitability
136
Q

What are the clinical manifestations of uncompensated metabolic alkalosis?

A
  1. Arterial blood pH > 7.45
  2. PaCO2 normal
  3. Serum HCO3- above normal
137
Q

What are the signs of respiratory compensation of metabolic alkalosis?

A
  1. CO2 elimination decreases
  2. Serum H2CO3 increases
  3. pH lowers to normal
138
Q

What is mixed acid-base imbalances?

A

Two or more types of acid–base imbalances

If a change in bicarbonate or PaCO2 exceed the normal limits of compensation, it usually indicates the presence of mixed acid-base imbalance

139
Q

What factors determine the type of acid-base imbalances in a patient?

A
  1. Patient history
  2. Clinical manifestations
  3. Lab tests
140
Q

What is the stepwise approach of analyzing A-B imbalances?

A
  1. Check blood pH (acidemia or alkalemia)
  2. Determine whether the imbalance is of respiratory or metabolic origin on the basis of changes in PCO2 or HCO3-
141
Q

What are the directions that change values of acid-base imbalances?

A

Respiratory
Opposite
RO: Respiratory origin, pH and CO2 change in opposite directions.
Metabolic
Equal
ME: Metabolic origin, pH and HCO3- change in the same direction.
Mixed acid-base imbalances

Drug Action I (32 decks)

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