Acid base physiology Flashcards
Normal blood pH and extreme range of pH?
normal= 7.37 - 7.42 Extreme = 7.0-7.8
Mammalian bodies produce large amounts of acids through which processes?
oxidative metabolism which produces CO2
Protein catabolism
Acid production by the body what are the two different types?
- oxidative metabolism
13,000-20,000 mmols CO2 daily
H2O + CO2 H2CO3 H+ + HCO3-
carbonic acid is in equilibrium with dissolved CO2 its a volatile acid - Protein catabolism
- 40-60mmol of non carbonic acid produced daily
- oxidation of sulphur containing amino acid residues to produce sulphuric acid
- Because non-carbonic acids are not in equilibrium with a volatile component = non-volatile or fixed acids
non-volatile acids may increase markedly
a) in ischaemia or extreme exercised due to formation of lactic acid
b) in diabetes due to the formation of acetoacetic acid and beta hydroxybutyrate
What is a volatile acid
one that can be exerted from the body by ventilation and therefore is an acid produced from carbon dioxide
buffering of a non-volatile acid
with the addition of Hal to plasma, pH drops gradually from 7.4 to 7.14. Addition of the same amount of Hal to an equivalent volume of stilled water produces a drop in pH that would prove fatal in vivo
what system is particularly effective at buffering fixed acids?
the bicarbonate buffer system (shown in the equation a couple of slides up)
effectively the protons are removed from the HCO3, and combined with bicarbonate to become dissolved carbon dioxide and water, which can be removed by excreting CO2 in the lungs at the cost of lost bicarbonate
bicarbonate buffer is determined by level of Pco2 and amount of bicarbonate ions
what is the useful form of then henderson hasslebach equation?
pH = 6.1 + Log10([HCO3-]/[0.03*Pco2])
what body components provide effective short term buffering (seconds to minuets)
Blood and extracellular fluid
what are the long term buffers of of non-volatile acids?
H+ also combines with intracellular proteins and organic phosphates in the tissue and bone. H+ is transported across the cell membrane in exchange for Na+ and K+. The time course of the process is relatively slow (hours to days)
The isohydric principle
“All buffers are in equilibrium with each other”
for a homogenous solution of multiple buffer systems at equilibrium:
The pH can be evaluated from the status of any buffer system.
This is reasonably accurate for blood and interstitial phases (acute changes) but less so for the intracellular phase which is not homogenous with the extracellular fluid.
How well does the bicarbonate buffer work when the respiratory system is increasing the amount of CO2 in the blood?
a buffer cannot buffer itself: if HCO3- were to react with H+ produced from the dissociation of H2CO3 this would just produce H2CO3 again - reversing the reaction is not buffering
Why is the Henderson hasslebach equation useful in a physiological sense?
Status of the buffer system can be readily characterised using standard measurements of blood chemistry
Addition of a non-volatile acid on the henderson hasslebach graph leads to
a fall in pH and [HCO3-]. The acid is buffered in the form of carbonic acid and dissolved carbon dioxide which is readily removed in the lungs
How do we buffer carbon dioxide?
DRAW THE DIAGRAM
CO2 generated by tissue metabolism rapidly equilibrates in the interstitial fluid and diffuses into the blood at the arterial end of the capillaries where it readily enters red blood cells
The hydration of CO2 is markedly greater within red cells where catalysed by carbonic anhydrase present in erythrocytes. So HCO3- is formed rapidly in red cells and this diffuses into the plasma. The H+ formed is retained within red cells because the cell membrane is relatively impermeable to cations; Charge balance is maintained by shift of Cl0 ions across the red cell membrane.
Additional H+ formed by combination CO2 with haemoglobin to form carbamino haemoglobin. The H+ formed as a result binds to haemoglobin facilitating the release of oxygen from deoxy haemoglobin.
The red blood cell buffering system only accounts for 6% of all the bodies buffers? How can it be such an efficient buffer then?
Red blood cells are a transport system that is efficient linked with the lungs. Therefore the buffering doesnt need to be huge because the carbon dioxide is quickly whisked away to the lungs to be breathed off?
The blood buffer line:
- Shows
- Changes with
Whole blood fully saturated with oxygen was exposed to CO2 at Pco2 values between 23 and 85 mmHg and the resultant pH and HCO3- are proportional
Effectiveness for blood as buffer decreases when haemoglobin concentration is reduced = reduction in gradient of blood buffer line.
Addition of small amounts of acid or base to whole blood results in translation downward and upward respectively of the blood buffer line
How are base excess and deficit defined?
Base excess: measure by titration of a blood sample with a strong acid (Hal or its equivalent) to pH 7.40 at Pco2 of 40mmHg and at 37degrees Base deficit (negative base excess) is measured by titration of a blood sample with NaOH to pH 7.4 at a Pco2 of 40mmHg and at 37degrees
Acute response to acid base disturbance: Draw the graph and label 1. respiratory acidosis 2. Respiratory alkalosis 3. Metabolic acidosis (base deficit) 4. Matabolic alkalosis (base excess)
check book
Respiratory regulation of blood carbon dioxide levels
Normal circumstances:
CO2 and carbonic acid produced by an increase in aerobic metabolism will be rapidly buffered, transported to the lungs and eliminated. As with an increase in non-volatile acid production, buffered by the bicarbonate system - carbonic acid and dissolved CO2 rapidly cleared by the lungs.
BUT to maintain acid base the kidney must excrete acid equivalent to the non-volatile acid produced by the body and replace the bicarbonate that is lost.
Normal lungs have capacity to respond to inc or dec in acid production.
Respiratory control mechanisms match alveolar ventilation to carbon dioxide levels i the blood. Increase in Paco2 (and decreased pH and PaO2) = increase in respiratory drive via peripheral chemoreceptors (aortic and carotid bodies, are most affected) and central chemoreceptors (brain stem, are most sensitive)
Renal auto regulation- goals
The status of the bicarbonate buffer system determines the change in pH that occurs as a result of acid base at steady state. Regulating the ration of bicarbonate to carbonic acid will tend to regulate pH.
maintenance and control of the conjugate base is accomplished through the kidneys. Involves:
1) reabsorption of all HCO3- that is filtered by the kidneys
2) regeneration of all the HCO3- lost by excretion of the lungs when non-volatile acids are buffered by the bicarbonate system
How does reabsorption of filtered bicarbonate in the proximal tubule occur
DRAW DIAGRAM
Bicarbonate ions are filtered freely by renal glomeruli
Bicarbonate combines with secreted hydrogen ions in the renal tubule to form carbonic acid then dissociates to CO2 and water. Catalysed by carbonic anhydrase (brush border of renal tubular cells). CO2 readily crosses into the tubular cells down the concentration gradient, inside the cell CO2 recombines with water and via carbonic anhydrase to form carbonic acid, which further dissociates to bicarbonate and hydrogen ions, the bicarbonate passes back into the blood stream whilst H+ passes back into the tubular fluid in exchange for sodium
Explain how the kidneys can produce new bicarbonate
Occurs in the prox, distal tubules and collecting ducts. Involves active transport of hydrogen ions into tubular lumen where they combine with phosphate ions and ammonia
Define metabolic acidosis
- can occur as a result of?
- excess nonvolatile acid production due to diabetic ketoacidosis
- accumulation of lactic acid in renal failure
- loss or bicarbonate e.g. with diarrhoea
metabolic alkalosis
- can occur as a result of?
- Addition of nonvolatile alkali to the body e.g. through ingestion of antacids
- loss of nonvolatile acids due to vomiting or nasogastric constriction
Respiratory acidosis causes
Inadequate alveolar gas exchange relative to carbon dioxide production,
- inadequate ventilation (drug induced depression of the respiratory centres)
- Impaired gass diffusion (COPD or Pulmonary oedema)
Respiratory alkalosis
excessive alveolar gas exchange relative to carbon dioxide production. Hyperventilation may be due to endogenous or drug induced stimulation of the respiratory centres,
anxiety or fear
Examples of mixed disorders
e.g. in heart failure respiratory acidosis due to impaired gas diffusion and reduced cardiac output –> systemic oxygen delivery, aerobic metabolism and lactic acidosis, therefore is a combined respiratory and metabolic acidosis
Draw the graph for acute acid base disturbances with the 4 types of alkalosis / acidosis present
refer to book
What will happen on the graph of you get an acute respiratory acidosis and then compensated metabolic alkalosis?
Shift along the blood buffer line to the left, and then an upwards shift for compensation with increased bicarbonate
reasons why metabolic compensation might not occur in cases of respiratory acidosis. What would you expect the levels to be in a normal person?
renal problems???
For a patient with COPD, with a PaCO2 of 55mmHg we would expect HCO3- to be elevates to more than 30mmol/L and pH close to 7.4
these arterial blood gasses suggest that there is an ongoing metabolic acidosis in addition to the chronic respiratory acidosis
PaO2 is extremely low in this patient which is likely limiting oxygen delivery to tissues lactic acidosis is therefore a real possibility
what measurement can be used to reduce the range of possible candidates for metabolic acidosis?
blood electrolyte data using the anion gap
Describe the anion gap
the difference between plasma concentrations of Na+ and the major anions Cl- and HCO3-
Under normal circumstances the anion gap is 8-16mM/L
useful way to identify the cause of metabolic acidosis
- If the anion of the nonvolatile acid is Cl- (diarrhoea or renal dysfunction) gap will be normal. Because as you generate excess protons and chloride ions, protons buffered by bicarbonate, so increase in chloride ion concentration which is offset by a decrease in bicarbonate ion concentration as the hydrogen ions are buffered.
- If anion of nonvolatile acid not Cl- (e.g. lactate or beta hydroxybutyrate) anion gap will inc. Chloride ions will stay the same and bicarbonate will decrease, because you’re not seeing the counter ions in this particular equation, the anion gap will increase. (if so need to test other ion levels to be sure this is the case)
What do respiratory diseases such as bronchitis do to gas transfer?
Diffusion distance increased
Discuss the alveolar gas equation
Enables the ALVEOLAR partial pressure of oxygen to be estimated from PaCO2 (PaCO2 = PACO2)
PAO2 is the residual partial pressure left after the affects of moistening of air in the airways and exchange of oxygen for carbon dioxide.
Typically a small gradient for partial pressure between alveoli and pulmonary capillaries and a normal value for PaO2 might be 100mmHg.
PaO2 = PIO2 - (PACO2 / R) + F
where R is the expiratory exchange ratio and F a correction factor
Do a estimate of the alveolar gas equation for a patient with a high carbon dioxide level…
PAO2 = 150 -55/0.8 +2 = 83mmHg
We have a higher level of carbon dioxide, so the respiratory exchange for carbon dioxide is greater, leaving less??? in the alveoli for transfer to the pulmonary capillaries,
Its a straightforward inverse relationship, you push the carbon dioxide level up and you lover the oxygen level… in this case the alveolar partial pressure of oxygen is 83mmHg which is still very different from what we are seeing in the arterial blood:
A-a gradient = 83-45
= 38mmHg
Step by step list of what to look at when interpreting arterial blood gasses?
- pH - normal, academic or alkalaemic
- Pco2, [HCO3-] and BE, acidosis, alkalosis, respiratory or metabolic AND compensated, uncompensated, simple or mixed.
- anion gap - normal? increased?
- PO2 - Normal, low or high (relative to FIO2 and therefore alveolar PO2)
What are the two things that can drive PO2 down
One is if CO2 is elevated, the other if there is impaired diffusion
What is the significance of hypo/hyperkalemia
cardiac muscle.. hypo and hyperkalemia increase the chance of occurrence of life threatening reentrant arrhythmia (VT, VF)
