Acid-Base Homeostasis Flashcards
(160 cards)
1
Q
Why is acid-base homeostasis important?
A
H+ ions are present everywhere in the body –> maintenance of appropriate conc is critical to normal function
2
Q
How can changes in [H+] affect proteins?
A
Changes can affect the surface charge and physical conformation of proteins, changing their function Can lead to denatured proteins.
3
Q
How can [H+] affect oxidative phosphorylation?
A
The gradient of [H+] between the inner and outer mitochondrial membrane drives oxidative phosphorylation
4
Q
Acid-base homeostasis (in a nutshell).
- How are H+ ions inputted into the body?
- What is the purpose of buffers?
- What are the 2 ways that H+ are removed from the body?
A
- Metabolism
- Maintenance of normal [H+]
- Lungs and kidneys
- Lungs: excretion of CO2 in expired air
- Kidneys: Excretion of H+ in urine
5
Q
Describe how H+ ions are removed by the lungs
A
When CO2 is dissolved in an aqueous solution, it forms carbonic acid (H2CO3)
6
Q
What is plasma [H+] typically kept at?
A
40nmol/L
N.B. H+ ions are produced in mmol quantities, yet must be kept at nmol concentrations.
7
Q
How are H+ ions kept at nmol quantities?
A
- Excretion of H+ in kidneys
- Excretion of CO2 in lungs
- Buffers
8
Q
Where does acid in our bodies come from?
A
- Glucose
- Triglycerides
- Amino acid metabolism
9
Q
How can glucose produce acids?
A
Incomplete metabolism:
- Intermediary anaerobic process
- Glucose –> 2 lactate + 2 H+
10
Q
Where does glucose metabolism mainly take place?
A
In skeletal muscle and RBCs
11
Q
How can triglycerides produce acid?
A
Incomplete metabolism –> ketogenesis
- Triglycerides –> free fatty acids + H+
- Free fatty acids –> ketones + H+
12
Q
What is ketogenesis?
A
Ketogenesis is a metabolic pathway that produces ketone bodies, which provide an alternative form of energy for the body.
13
Q
Where are ketones produced?
A
They are made in the liver from the breakdown of fats. Ketones are formed when there is not enough sugar or glucose to supply the body’s fuel needs.
14
Q
Where are free fatty acids produced?
A
In adipose tissue
15
Q
How can amino acid metabolism produce acids?
A
Ureagenesis:
- Metabolism of neutral amino acids results in the generation of H+
16
Q
What is ureagenesis?
A
Formation of urea, usually referring to the metabolism of amino acids to urea.
17
Q
Are acids H+ donors or acceptors? Bases?
A
- Acids are H+ donors:
- HCl –> H+ + Cl-
- Bases are H+ acceptors
- OH- + H+ –> H2O
18
Q
Example of an acid + base reaction
A
HCl(aq) + NaOH(aq) –> NaCl(aq) + H2O(l)
19
Q
What is pH?
A
Negative logarithm of the hydrogen ion concentration (mol/L)
20
Q
Why is pH used rather than [H+]?
A
pH scale was devised to cope with the wide range of H+ concentrations encountered in chemistry (taking logarithms makes it more manageable).
Use of H+ rather than pH is becoming more prevalent in medicine, as it is a direct reflection of acid-base status.
21
Q
If [H+] > 45 nmol/L (pH <7.35), what does this mean about the patient?
A
They are acidaemic (low blood pH)
22
Q
If [H+] <35 nmol/L (pH >7.45), what does this mean about the patient?
A
The patient is alkalaemic
23
Q
What is acidaemia? How does it differ from acidosis?
A
Acidaemia: low blood pH
Acidosis: abnormal process or condition that lowers arterial pH
24
Q
What are the reference ranges for [H+]?
A
35-45 nmol/L
25
What is the reference range for pH?
7.35 - 7.45
26
What is Ka?
Acid dissociation constant: **the higher the Ka, the greater the dissociation, and the stronger the acid**
27
What is pKa?
* The negative logarithm of Ka
* The pKa is the pH at which a buffer exists in **equal proportions** with its acid and conjugated base
* The lower the pKa, the greater the dissociation, and the stronger the acid
28
What is the equation for pKa?
29
What is the Henderson-Hasselbach equation?
Explains how acids and bases contribute to pH (and therefore [H+])
30
In this reaction, how is CO2 acting as an acid? How is HCO3- acting as a base?
* CO2 acting as acid:
* When dissolved in plasma, CO2 becomes an acid (**carbonic acid; H2CO3**), which readily **dissociates** to release H+
* HCO3- acting as base:
* HCO3- accepts a proton to form carbonic acid, which is converted to CO2 for excretion in the lungs
31
What does blood pH depend on regarding CO2 and HCO3-?
Blood pH depends not on absolute amounts of CO2 or HCO3-, but on the **ratio** of the two
32
Substituting HCO3- and CO2 into the Henderson-Hasselbalch equation:
* What does pCO2 stand for?
* What does a stand for?
* What is the result?
* pCO2: partial pressure of CO2 (kPa)
* a: solubility constant (0.225 for CO2)
* Result: pH is proportional to [HCO3-] / pCO2
33
What does bicarbonate buffering in the blood have a pKa of?
6.1
34
What is the definition of a buffer?
A buffer is a solution which resists change in pH when an acid or base is added.
35
What is the purpose of buffers?
Ensures H+ ions are transported and excreted safely without affecting physiological processes.
The body has a limited capacity to buffer changes in [H+].
36
What are the main buffers in the body?
* Bicarbonate
* Haemoglobin
* Phosphate
* Ammonia
* Proteins
37
How does bicarbonate act as a buffer? Why can it not buffer CO2?
* Mopping up H+ ions
* Cannot buffer CO2 because of the equation
* Buffering by bicarbonate would only result in the production of more CO2
* Equilibration of CO2 therefore requires **non-bicarbonate buffers** (e.g. Hb)
38
What is the principal non-bicarbonate buffer?
Haemoglobin
39
How does Hb act as a buffer?
Important for buffering CO2:
* Reduction of CO2
* Production of HCO3-
* Also reduce Hb to HHb (deoxyhaemoglobin)
40
Mechanism of Hb acting as a buffer:
* CO2 in plasma diffuses into red cell
* Combines with water under the action of carbonic anydrase --\> forms H2CO3
* H2CO3 readily dissociates to release H+ and HCO3- ions
* HCO3- diffuses out into plasma
* Replaced by Cl- from plasma that diffuses into red cell (chloride shift)
* H+ reduces Hb to form HHb
* Byproduct of this is O2 which diffuses out into plasma
41
How does phosphate act as a buffer?
* Monohydrogen phosphate and dihydrogen phosphate form a buffer pair
* Concentrations of these anions are too low in plasma to make an appreciable difference
* Important buffer in urine, where phosphate is present at a much higher concentration
42
Where is phosphate an important buffer?
Urine
43
How does ammonia act as a buffer?
* Ammonia and ammonium ions form a buffer pair
* Vast majority of ammonia in the body is already in ammonium (NH4+) form, limiting its buffering capacity, but some sources still claim that NH3 is an important buffer in urine
* More important role of urinary ammonium excretion is providing a route for ammonium disposal that does not result in the generation of H+ (unlike urea synthesis)
44
What form is the vast majority of ammonia in the body in? How does this affect its buffering capacity?
NH4+ form - limiting its buffering capacity, but some sources still claim that NH3 is an important buffer in urine
45
What is the important role of urinary ammonium excretion?
Provides a route for ammonium disposal that does not result in the generation of H+ (unlike urea synthesis)
46
How do proteins act as buffers?
Proteins contain **weakly acidic and basic groups** due to their amino acid composition, and can therefore **accept and donate H+ ions** to some extent.
47
What is the predominant plasma protein?
Albumin --\> is also the **main protein buffer**
48
How does albumin act as a buffer?
It has a net negative charge, so can “mop up” H+ ions
49
Can bone proteins play a role in buffering?
Yes
50
Explanation of albumin buffer:
* In patient with no acid-base disorder:
* Albumin molecule with negative charges around it
* Some bound H+ ions to those charges
* In patient with acidosis ([H+] increased):
* Extra H+ ions bound to albumin, reducing the plasma conc of H+ ions
* In patient with alkalosis ([H+] decreased):
* Bound H+ ions to albumin are released into plasma
51
What are the main functions in the lungs?
Transfer of O2 from inspired gas into blood and removal of CO2 from the blood to the expired gas
52
What are respiratory control mechanisms extremely sensitive to?
pCO2 --\> the rate of elimination is equal to the rate of production, so that blood pCO2 remains constant
53
Regarding the oxyhaemoglobin dissociation curve, what is on the x and y axis?
x axis: pO2 (kPa)
y axis: saturation of Hb (%)
54
What type of curve is the Oxyhaemoglobin dissociation curve?
Sigmoid
55
Why is the Oxyhaemoglobin dissociation curve sigmoid?
pO2 can decrease significantly before saturation is affected
56
Oxyhaemoglobin dissociation curve shifts to the left/right affect what?
Curve shifts to right or left if specific variables change, affecting the affinity of Hb for O2 and the amount of O2 released to the tissues
57
What is the effect when the Oxyhaemoglobin dissociation curve shifts to the right? What causes the Oxyhaemoglobin dissociation curve to shift to the right?
* A shift to the right results in Hb having a reduced affinity for O2 so **more O2 is available** to tissues
* Shift caused by:
* Body temperature increasing
* Increased in 2,3-DPG (patient is hypoxic or anaemic)
* [H+] increases (Bohr effect)
* CO2 increases
58
What is the Bohr effect?
Increases in the pCO2 of blood or decreases in blood pH result in a lower affinity of Hb for O2.
Occurs because the higher [H+] causes an alteration in amino acid residues on Hb - this stabilises deoxyhaemoglobin in a state that has a lower affinity for oxygen.
59
What is 2,3-DPG?
* An increase in the concentration of 2,3-DPG decreases oxygen affinity of Hb --\> therefore increases O2 available to tissues
* An increase in the red cell 2,3-DPG is found in response to hypoxia or anaemia and a decrease of 2,3-DPG is caused by acidosis
60
What causes the Oxyhaemoglobin dissociation curve to shift to the left? What is the result of this?
* Results in Hb having a higher affinity for O2 so less O2 is available to tissues
* Curve shifts to left when:
* Body temperature decreases
* Decreases in 2,3 DPG
* Decreases in CO2
* Decreases in H+
61
When does a sharp fall in Hb saturation occur?
Below pO2 of 8 kPa
62
Describe how the acid-base balance is kept in the kidneys
* Excretion of H+ ions (distal tubule)
* Reabsorption of bicarbonate (proximal tubule)
* Regeneration of bicarbonate (distal tubule)
63
Describe the composition of urine created by the kidneys
Creates acidic urine containing almost no bicarbonate
64
What area of the kidney does:
* Excretion of H+ ions
* Reabsorption of bicarb
* Regeneration of bicarb
occur?
* Distal tubule
* Proximal tubule
* Distal tubule
65
Why can bicarb not be directly reabsorbed across luminal membranes? What does it rely on instead?
Luminal membranes are impermeable to it. Instead, relies on ability of CO2 to diffuse.
66
Describe the mechanism of renal bicarb reabsorption:
1. H2CO3 generated in tubular cell from CO2 and H2O under action of carbonic anhydrase --\> H2CO3 formed and dissociates into H+ and HCO3- (2)
2. HCO3- formed in the cell then pumped into the plasma (along with Na+ for charge balance) (3)
3. H+ ions formed in the cell then secreted into glomerular filtrate in exchange for Na+ (4)
4. Secreted H+ ions combine with HCO3- ions in filtrate to form H2CO3 and then CO2 (1). The CO2 diffuses into the tubular cell, providing a substrate for the continued formation of H2CO3 (2)
67
Describe the mechanism of renal H+ excretion and HCO3- regeneration
1. H2CO3 generated from CO2 and H2O under action of carbonic anhydrase --\> dissociates into H+ and HCO3- (6)
2. H+ actively secreted into glomerular filtrate in exchange for Na+ (4), where H+ ions are excreted as dihydrogen phosphate (H2PO4-) (1)
3. HCO3- and Na+ ions pumped into plasma
4. Additionally, ammonia is transported into the urine where it forms NH4+, providing a route for ammonia excretion that does not generate H+
68
What is the continued formation of H+ in renal tubular cells accompanied by? How does this maintain buffering capacity?
Stoichiometric generation of bicarbonate --\> excretion of H+ results in bicarbonate regeneration --\> maintains buffering capacity
69
What are mineralocorticoids?
* A class of corticosteroids, which in turn are a class of steroid hormones
* Produced in the adrenal cortex
* Influence salt and water balances (electrolyte balance and fluid balance)
* The primary mineralocorticoid is aldosterone.
70
What is excreted/reabsorbed in the distal tubule? What is the under the control of?
* Excretion of potassium and hydrogen ions in the distal tubule, with concomitant reabsorption of sodium ions
* Under the control of aldosterone
71
How does aldosterone affect sodium reabsorption and potassium/H+ excretion?
Increased aldosterone leads to **increased sodium reabsorption** and **potassium/hydrogen ion excretion**
72
How does this liver affect acid-base?
* **CO2 production** from complete oxidation of carbohydrates and fats
* Metabolism of lactate, ketones and amino acids (consumption of H+)
* **Metabolism of NH4+** to urea via urea cycle (producer of H+)
* Production of **plasma proteins** (e.g. albumin) (buffering)
73
What is the most common acid-base disturbances in liver failure?
Respiratory and metabolic **alkalosis**
74
What is hyperammonaemia?
A metabolic condition characterised by the raised levels of ammonia
75
How can liver failure lead to hyperammonaemia?
* Liver is unable to perform urea cycle, which normally converts toxic ammonia to urea for excretion in urine
* Ammonia stimulates the respiratory centre, causing the patient to hyperventilate and blow off CO2
* Leads to increase in blood pH --\> **respiratory alkalosis**
* Metabolic alkalosis can also arise as a result of reduced production of H+ (due to liver failure)
76
Why must samples for blood gas analysis be heparinised?
Anticoagulant
77
Why must samples for blood gas analysis be well mixed with no air bubbles?
Air bubbles can affect pO2 --\> can increase pH and decrease pCO2
78
Why must samples for blood gas analysis be analysed immediately?
In-vitro glycolysis can cause a time-dependent decrease in pO2 and increase in pCO2
79
Why must samples for blood gas analysis **not** be sent via pneumatic tube system?
Rapid deceleration of sample can affect pO2 and pCO2 if air bubbles present
80
Is a standard blood sample venous or arterial?
Arterial (particulary if interest in pO2)
N.B. Different reference ranges apply for venous and arterial samples
81
What is the principal feature of respiratory acidosis/alkalosis?
Primary disorder caused by altered respiration:
* Acidosis: increased pCO2
* Lungs not getting rid of enough CO2
* Alkalosis: decreased pCO2
* Lungs getting rid of too much CO2 e.g. hyperventilation
82
What is the principal feature of metabolic acidosis/alkalosis?
Primary disorder caused by non-respiratory element
* Acidosis: decreased HCO3-
* Bicarb being **used up** buffering the extra H+ ions
* Alkalosis: increased HCO3-
83
How do we classify acid-base disorders?
1. What is the pH?
1. pH \<7.35 acidosis
2. pH \>7.45 alkalosis
2. Is the primary disorder respiratory or metabolic?
3. Is there any compensation?
84
How can you tell if the primary disorder respiratory or metabolic?
Easiest way to determine this is to look at the pCO2 [4.7 -6.0 kPa]:
* If pH \<7.35 (acidosis):
* If increased pCO2 --\> respiratory acidosis
* If normal (or decreased pCO2 if compensation) --\> metabolic acidosis
* If pH \>7.35 (alkalosis):
* If decreased pCO2 --\> respiratory alkalosis
* If normal (or increased pCO2 if compensation) --\> metabolic alkalosis
85
What is compensation?
Secondary changes in bicarbonate and pCO2 to correct for the primary disorder:
* Changes in bicarbonate concentration (renal regeneration) can occur to compensate for respiratory disorders (slow)
* Changes in pCO2 (respiratory rate) can occur to compensate for metabolic disorders (fast)
86
What is the aim of compensation?
Compensatory mechanisms aim to restore a neutral pH (but full compensation rarely occurs, and over-compensation never occurs)
87
Compensation for acidosis/alkalosis:
88
Summary table for acid-base disorders
89
What are the 2 measurements of bicarb?
* Bicarb (main lab)
* Bicarb (standard)
90
What is bicarb (main lab) measurement?
* 22-29 mmol/L
* Approximation of bicarbonate, calculated in part from CO2
* Sometimes called “total CO2”
91
What is bicarb (standard) measurement?
* 22-26 mmol/L
* Removes respiratory contribution so an **abnormal standard bicarbonate** tells us that there is a **metabolic component** to the disorder
* Uses Henderson-Hasselbalch equation to calculate bicarbonate from pH and “corrected” pCO2 (i.e. “normal” pCO2)
92
What would a normal standard bicarb result indicate?
Purely **respiratory disorder**
93
What would an abnormal standard bicarb tell you?
There is a metabolic component
94
What is base excess (BE)? What does it tell you?
* Amount of acid or alkali needed to titrate blood pH to 7.40 (takes into account all buffers, not just bicarb)
* Tells us if there is a metabolic component to the disorder
95
What would a normal base excess tell you about the disorder?
Purely respiratory disorder
96
What would a negative BE (\<-2.3 mmol/L) tell you?
Metabolic acidosis (i.e. a base deficit)
97
What would a positive BE tell you (\>2.3 mmol/L)?
Metabolic alkalosis (i.e. a base excess)
98
What is an anion gap?
The anion gap is the difference between certain measured cations (positively charged ions) and the measured anions (negatively charged ions) in serum, plasma, or urine.
99
What would an increased anion gap indicate?
Indicates that there are significant amounts of “unmeasured” anions present (e.g. ketones, lactate, salicylate, proteins, and many more)
Can be useful in determining the cause of a metabolic acidosis
100
Why is the anion gap not zero in healthy patients?
As not all anions are measured and included in the calculation
101
How is pH, [H+], pCO2, HCO3- and pO2 affected in metabolic acidosis?
* pH decreased
* [H+] increased
* pCO2 N/decreased
* HCO3- decreased
* pO2 increased
102
What are the signs and symptoms of metabolic acidosis?
* **Nausea**, **vomiting** and **anorexia** frequently present
* Subjective sense of **dyspnoea** caused by **stimulation of the** **respiratory centre**
* Deep laboured breathing pattern, known as **Kussmaul breathing**, in severe acidosis
* Other symptoms caused by underlying disorder
103
What are the 4 main causes of metabolic acidosis?
1. Increased acid formation
2. Acid ingestion
3. Decreased acid excretion
4. Loss of bicarb
104
What are the causing of increased acid formation?
* Ketoacidosis
* Diabetic (DKA)
* Alcoholic (AKA)
* Starvation
* Lactic acidosis
* Type A (tissue hypoxia)
* Type B (metabolic and toxic causes)
* Poisoning
* Salicylate
* Toxic alcohols (e.g. ethylene glycol, methanol, ethanol)
* Inherited organic acidoses
105
What are the causes of decreased acid excretion?
* Uraemia (renal failure)
* RTA type 1 (distal)
106
What can cause a loss of bicarb?
* GI: diarrhoea / fistula
* Renal:
* RTA type 2 (proximal)
* Carbonic anhydrase inhibitors (e.g. acetazolamide)
107
What is the physiological response to metabolic acidosis?
* Buffering
* Compensation
108
How does buffering try to reverse metabolic acidosis?
* Acute ↑[H+] resisted by bicarbonate buffering, causing ↓HCO3-
* Protein buffering important in chronic acidosis
109
How does the respiratory centre compensate in metabolic acidosis?
* Respiratory centre stimulated à hyperventilation (blows off CO2)
* Self-limiting, as generates additional CO2
110
How do the kidneys compensate in metabolic acidosis?
* Urine H+ excretion maximised
* Increased rate of regeneration of bicarbonate
111
How can metabolic acidosis be treated?
Sodium bicarbonate (sometimes):
* Careful administration of IV sodium bicarbonate
* Usually only given if pH \<7.00
* Oral bicarbonate
* CKD, RTA types 1 and 2
112
Why must care be taken when treating metabolic acidosis with sodium bicarbonate?
* Rapid correction impairs O2 delivery
* Rebound alkalosis possible
113
How is pH, [H+], pCO2, HCO3- and pO2 affected in metabolic alkalosis?
* pH increased
* [H+] decreased
* pCO2 N/increased
* HCO3- increased
* pO2 decreased
114
What are the typical signs and symptoms of metabolic alkalosis?
* Usually related to underlying disorder
* More severe alkalosis increases protein binding of Ca2+, leading to hypocalcaemia
* Causes headache, lethargy and neuromuscular excitability, sometimes with delirium, tetany and seizures
* Lowers threshold for arrhythmias
115
What are the 3 main causes of metabolic alkalosis?
1. Administration of bicarb
2. Potassium depletion
3. Loss of H+
116
Why can hypokalaemia cause a metabolic alkalosis?
* **Kidneys**
* Excretion of H+ favoured in order to spare K+ at aldosterone-controlled renal transporter
* **Cells**
* ****K+ ions are transported out of RBCs to increase plasma concentration --\> H+ ions move into cells to maintain electroneutrality. This leads to a decrease in plasma [H+]
117
What can cause a loss of H+?
Vomiting
118
How do buffers try to reverse metabolic alkalosis?
Release of H+ from buffers
119
How can the respiratory centre try to compensate for metabolic alkalosis?
* Reduced respiratory rate in order to retain CO2
* Self-limiting, as an increase in pCO2 stimulates the respiratory centre
120
How can the kidneys try to compensate for metabolic alkalosis?
This is difficult --\> ↓GFR leads to inappropriately high bicarbonate reabsorption. Potassium deficiency contributes to persistence of alkalosis.
121
What is the management for metabolic alkalosis?
Treat underlying cause
Treat factors that sustain alkalosis e.g. replace potassium
122
How is pH, [H+], pCO2, HCO3- and pO2 affected in respiratory acidosis?
* pH decreased
* [H+] increased
* pCO2 increased
* HCO3- N/increased
* pO2 decreased
123
What are the signs and symptoms of respiratory acidosis?
* Usually related to underlying disorder
* Some patients may complain of dyspnoea
124
What are the 2 main causes of respiratory acidosis?
1. Defective control of respiration
2. Defective respiratory function
125
What can cause a defective control of respiration?
* CNS depression
* Anaesthetics, sedatives etc
* Narcotics, opiates etc
* CNS disease
* Trauma
* Haemorrhage
* Infarction
* Tumour
* Infection
* Neurological disease
* Spinal cord lesions
* MND
* Guillain-Barre
126
What can cause a defective respiratory function?
* Mechanical
* Myopathies
* Pneumothorax
* Pleural effusion
* Inadequate mechanical ventilation
* Pulmonary disease
* E.g. COPD, severe asthma etc
* Impaired perfusion (e.g. massive pulmonary embolism)
127
How does buffering try to reverse respiratory acidosis?
Limited buffering by Hb
128
How does the respiratory centre try and compensate for respiratory acidosis?
↑pCO2 stimulates respiratory centre, but disease prevents adequate response
129
How do the kidneys try and compensate for respiratory acidosis?
* Maximal bicarbonate reabsorption (takes a while to reach maximal effect)
* Almost all phosphate excreted as H2PO4- (rather than HPO42-)
* Marked increase in urinary NH4+
130
What is the management for respiratory acidosis?
* Treat underlying cause
* Maintain adequate arterial pO2, but avoid loss of hypoxic stimulus to respiration
* Avoid rapid correction of pCO2 (risk of alkalosis due to persistence of compensation)
131
How is pH, [H+], pCO2, HCO3- and pO2 affected in respiratory alkalosis?
* pH increased
* [H+] decreased
* pCO2 decreased
* HCO3- N/decreased
* pO2 increased
132
What are the signs and symptoms in respiratory alkalosis?
* Usually related to underlying disorder
* More severe alkalosis increases protein binding of Ca2+, leading to hypocalcaemia
* Causes headache, lethargy and neuromuscular excitability, sometimes with delirium, tetany and seizures
133
What are the 3 main causes of respiratory alkalosis?
1. Central
2. Pulmonary
3. Iatrogenic
134
What are the central causes of respiratory alkalosis?
* Head injury
* Stroke
* Hyperventilation
* Drugs (e.g. salicylates)
* Sepsis (cytokines)
* Chronic liver disease (toxins)
135
What are the pulmonary causes of respiratory alkalosis?
Pulmonary embolism
Pneumonia
Asthma
Pulmonary oedema
136
What are the iatrogenic causes of respiratory alkalosis?
Excessive mechanical ventilation
137
How does buffering respond to respiratory alkalosis?
Release of H+ from non-bicarbonate buffers
138
How does the respiratory centre try and compensate for respiratory alkalosis?
Inhibitory effect of ↓pCO2 overwhelmed by primary cause
139
How does the kidneys try and compensate for respiratory alkalosis?
Decreased renal regeneration of bicarbonate (CO2 is substrate, therefore CO2 is preserved)
140
What is the management for respiratory alkalosis?
Treat underlying cause
Rapid symptomatic relief by re-breathing
Sedation or prevention of hyperventilation by mechanical ventilation
141
What are mixed acid-base disorders?
* Mixed disorders: two or more primary acid-base disorders presenting in the same patient
* Can be either additive or counterbalancing
142
What type of mixed disorder can respiratory failure cause? Explain
Additive:
* Respiratory acidosis (↑pCO2) and metabolic acidosis (↑lactic acid)
143
What type of mixed disorder can vomiting and CCF cause? Explain
Additive:
* Metabolic alkalosis (loss of H+) and respiratory alkalosis (↑ resp. rate)
144
What type of mixed disorder can salicylate poisoning cause? Explain
Counterbalancing: Metabolic acidosis and respiratory alkalosis (↑ resp. rate)
145
What type of mixed disorder can vomiting and renal failure cause? Explain
Counterbalancing: Metabolic alkalosis (loss of H+) and metabolic acidosis (↓renal H+ excretion)
146
What is CCF?
congestive cardiac failure
147
Case 1
* What is the pH? --\> 7.59 (alkalotic)
* What is the pCO2? --\> Essentially normal (the alkalosis is not respiratory - ↑HCO3 concurs)
* What is the primary acid-base disorder? --\> Metabolic alkalosis
* Is there any compensation? --\> Not really. pCO2 is essentially normal
* How is this acid-base disorder classified? --\> Non-compensated metabolic alkalosis
* What is the cause? --\> Vomiting (loss of HCl)
* What is the likely cause of the hypokalaemia? --\> Vomiting (indirectly)
148
Why can vomiting cause hypokalaemia?
Gastric fluid is not especially rich in potassium, but it is very rich in H+ ions. Loss of H+ ions from vomiting causes potassium depletion by the following mechanisms:
* **Kidneys:** Excretion of K+ favoured in order to spare H+ ions at aldosterone-controlled renal transporter
* **Cells:** H+ ions are transported out of RBCs to increase plasma concentration --\> K+ ions move into cells to maintain electroneutrality. This leads to a decrease in plasma [K+]
N.B. a metabolic alkalosis can cause hypokalaemia and hypokalaemia can cause a metabolic alkalosis
149
Case 2:
* What is [H+]? --\> 83 nmol/L (acidotic)
* What is the pCO2? --\> pCO2 is high (therefore the acidosis is respiratory)
* What is the primary acid-base disorder? --\> Respiratory acidosis
* Is there any compensation? --\> No. Bicarbonate is not elevated
* How is this acid-base disorder classified? --\> Uncompensated respiratory acidosis
* What is the cause? --\> ↓CO2 excretion
150
Case 3:
* What is the pH? --\> 7.60 (alkalotic)
* What is the pCO2? --\> pCO2 is low (therefore the alkalosis is respiratory in origin)
* What is the primary acid-base disorder? --\> Respiratory alkalosis
* Is there any compensation? --\> Mild. HCO3- is slightly low (metabolic compensation)
* Is the compensation full or partial? --\> pH has not returned to normal, therefore partial
* How is this acid-base disorder classified? --\> Partially-compensated respiratory alkalosis
* What is the cause? --\> Hyperventilation (blowing off CO2), hypocalcaemia caused by alkalosis (note paraesthesia)
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What is paraesthesia?
an abnormal sensation, typically tingling or pricking (‘pins and needles’), caused chiefly by pressure on or damage to peripheral nerves.
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How can acidosis lead to hypercalcaemia?
As H+ binds to albumin to reduce plasma [H+], Ca2+ must be released --\> hypercalcaemia
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How can alkalosis lead to hypocalcaemia?
As H+ is released from albumin to increase plasma [H+], Ca2+ must bind to albumin --\> hypocalcaemia
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Case 4:
* What is the pH? --\> 7.05 (acidotic)
* What is the pCO2? --\> pCO2 is low (therefore the acidosis is not respiratory - ↓HCO3 concurs)
* What is the primary acid-base disorder? --\> Metabolic acidosis
* Is there any compensation? --\> Yes. pCO2 is low (respiratory compensation)
* Is the compensation full or partial? --\> pH has not returned to normal, therefore partial
* How is this acid-base disorder classified? --\> Partially-compensated metabolic acidosis
* What is the cause? --\> Diabetic ketoacidosis (DKA)
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Summary:
* Acid-base homeostasis is maintained by a combination of processes in the lungs, kidneys, liver and GI tract
* When homeostasis is disturbed, buffering and compensatory mechanisms begin in an attempt to return the pH to neutral
* Respiratory disorders can be compensated by metabolic processes
* Metabolic disorders can be compensated by respiratory processes
* Over-compensation does not occur
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What is HCO3- replaced by in the RBC when Hb is acting as a buffer?
Cl-
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What is RTA type 1?
Type 1 (distal) RTA Type 1 is **impairment in hydrogen ion secretion** in the **distal tubule**, resulting in a persistently high urine pH (\>5.5) and systemic acidosis.
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What is RTA type 2?
Type 2 is impairment in bicarbonate resorption in the **proximal** tubules
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Which acid-base disorder will RTA type 1 cause?
Decreased H+ excretion --\> metabolic acidosis
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Which acid-base disorder will RTA type 2 cause?
Decreased bicarb reabsorption --\> metabolic acidosis
