Resp: pH syndromes Flashcards
What is the main role of CO2 in blood?
-Acts as part of the pH buffering system
Only 8% of the total CO2 is transported
What is hypercapnia?
Rise in pCO2
What is hypocapnia?
Fall in pCO2
How does exercise affect the partial pressure of CO2 and O2?
- pO2 drops and pCO2 rises
- Breathing more will restore both
What is hyperventilation?
Ventilation increase without change in metabolsim
What is hypoventilation?
-Ventilation decrease without change in metabolism
What happens to pCO2 and pO2 in hyperventilation?
- pO2 will rise
- pCO2 will fall
What happens to pCO2 and pO2 in hypoventilation?
- pO2 will fall
- pCO2 will rise
What happens if the pO2 changes without a change in CO2?
Correction of the pO2 will cause the pCO2 to drop
This leads to hypocapnia
Control system are in place to prevent marked hypoxia. True/False
True
What is the effect of CO2 on plasma pH if bicarbonate remains unchanged?
- If pCO2 increase then pH falls
- If pCO2 decreases then pH rises
Small changes in pCO2 lead to large changes in pH.
What are the effects of pH falling and pH rising?
- If pH falls below 7.0 then enzymes become denatured
- If pH rises above 7.6 free calcium concentration drops leading to tetany
What are the effects of hypercapnia on plasma pH?
-Respiratory acidosis due to fall in plasma pH
What are the effects of hypocapnia on plasma pH?
-Respiratory alkalosis due to rise in plasma pH
How does the kidney compensate for respiratory acidosis?
- Kidneys increase reabsorption of HCO3-
- This compensate for the the increase in pCO2
(can take 2-3 days)
How does the kidney compensate for respiratory alkalosis?
- Kidneys decrease reabsorption of HCO3-
- This compensates for the decrease in pCO2
(can take 2-3 days)
How does metabolic acidosis occur?
- If tissues produce acid, this reacts with HCO3-
- Fall in [HCO3-] leads to fall in pH
- This causes metabolic acidosis
How is metabolic acidosis compensated for?
- Compensated for by changing ventilation
- Increased ventilation lowers pCO2
- Restores pH towards normal
How does metabolic alkalosis occur?
- If the plasma HCO3- rises
- Plasma pH rises
- Causes metabolic alkalosis
How is metabolic alkalosis compensated for?
-Decreasing ventilation so that pO2 falls and pCO2 increases
How are the respiratory pathways controlled?
- Sensors located in CNS and the periphery feed information back to the control centre for processing
- Ventilation is adjusted as necessary
What are the examples of peripheral chemoreceptors?
Carotid and aortic bodies
Sensitive to O2
What stimulates the peripheral chemoreceptors and what does it lead to?
Large falls in pO2 stimulate the peripheral chemoreceptors. This leads to
- Increased breathing
- Changes in the heart rate
- Changes in blood flow distribution which increases the flow to the brain and kidneys
What is the sensitivity of the peripheral chemoreceptors to the pCO2?
Relatively insensitive to pCO2
What is the sensitivity of the central chemoreceptors to the pCO2?
Sensitive to the pCO2
Where are the central chemoreceptors found?
Medulla of the brain
Why isn’t the central chemoreceptor affected by bicarbonate ions and H+ but it is affected by CO2?
- The ECF and CSF is impermeable to HCO3- and H+ due to the blood brain barrier
- The blood brain barrier is selective permeable to CO2 however
How do the central chemoreceptors work?
- Respond to changes in the pH of cerebrospinal-spinal fluid
- CSF is operated from blood by the blood brain barrier
- CSF [HCO3-] is controlled by choroid plexus cells
- CSF pCO2 is determined by arterial pCO2
How is CSF pH determined?
- Determined by ratio of [HCO3-] to pCO2
- [HCO3-] fixed in the short term as the blood brain barrier is impermeable to HCO3-
- Falls in pCO2 lead to rise in CSF pH
- Rises in pCO2 lead to falls in CSF pH
- Persisting changes in pH corrected by choroid plexus cells which change the [HCO3-]
How do the central chemoreceptors counteract an increase in the pCO2?
- Elevated pCO2 drives the CO2 into the CSF across the blood brain barrier
- CSF [HCO3-] is initially constant
- CSF pH falls
- Fall in CSF pH detected by central chemoreceptors
- Drives increased ventilation
- This lowers the pCO2 to restore the CSF pH
What is the action of the choroid plexus?
- Determine what is normal
- CSF [HCO3-] determine which pCO2 is associated with normal CSF pH.
- CSF [HCO3-] therefore sets the control system to a particular pCO2
- Can be reset by changing CSF [HCO3-] with persistent hypercapnia
How does persisting hypoxia affect the central chemoreceptors?
- Hypoxia is detected by the peripheral chemoreceptors which will trigger increase in ventilation
- pCO2 will fall further and this causes decrease in ventilation
- CSF composition compensates for the altered pCO2
- Choroid plexus cells selectively add H+ or HCO3- into the CSF
- Central chemoreceptors accept the pCO2 as normal
How does persisting hypoxia and hypercapnia affect the central chemoreceptors?
- Hypoxia and hypercapnia lead to respiratory acidosis
- Decreased pH of CSF
- Peripheral and central chemoreceptors stimulate breathing
- CO2 diffuses into CSF and CSF pH drops
- Persistently CSF acidity harmful to neurons
- Low CSF pH corrected by choroid plexus cells which secrete HCO3- in to CSF
- The CSF pH returns to normal; central chemoreceptors no longer stimulated
- pCO2 in the blood is still high but central chemoreceptors now unresponsive to this pCO2 i.e. Central chemoreceptors have ‘reset’ to a new higher CO2 level
- The persistent hypoxia stimulates peripheral chemoreceptors
- Respiratory drive is now driven by hypoxia (via peripheral chemoreceptors)
What is alkalaemia and acidaemia?
Alkalaemia = >7.45 Acidaemia = <7.35
What is the effect of alkalaemia?
- Lower free calcium by causing Ca2+ to come out of solution
- This increase neuronal excitability
- Can lead to paraesthesia and tetany
Higher mortality compared to acidaemia
What is the effect of acidaemia?
- Causes an increase plasma potassium ion concentration affects excitability particularly in heart muscle and can cause arrhythmia
- Can denature enzymes high can affect muscle contractility, glycolysis and hepatic function
- Severe effect below 7.1 and life threatening below 7
How are pCO2 and HCO3- disturbed ?
pCO2 is disturbed by respiratory disease
HCO3- is disturbed by metabolic and renal disease
Why doesn’t acid produced by metabolism deplete HCO3-?
- Kidney recovers all filtered HCO3-
- Proximal tubule make HCO3- from amino acids, putting NH4+ in the urine
- Distal tubule makes HCO3- from CO2 and H2O. The H+ is buffered by phosphate and ammonia in the urine when excreted
What is the process for recovery of HCO3-?
- HCO3- filtered at the glomerulus
- Mostly recovered in PCT
- H+ excretion is linked to Na+ entry in PCT
- H+ react with HCO3- in the lumen to form CO2 which enters the cell
- CO2 converted back to HCO3- which enters the ECF
Describe the creation of HCO3- in the proximal tubule?
- Glutamine is convert to alpha ketoglutarate
- Produces HCO3- and ammonium
- HCO3- enters the ECF
- NH4+ enters lumen
Describe the formation of HCO3- in the distal tubule
- Distal tubule and collecting ducts also secrete H+ produced from reaction of CO2 with water
- H+ ions are actively secreted
- H+ buffered by ammonia and phosphate. NH4+ and H2PO4- created
- No CO2 is formed to re-enter the cell
- Allows HCO3- to enter plasma
What is the kidney response to an increased acid load in an individual?
- Ammonium generation from glutamine in proximal tubule can be increased in response to low pH
- Ammonium splits to form NH3
- NH3 moves into lumen and throughout the interstitum
- H+ actively pumped into lumen in DCT and CT
- H+ combines with NH3 to form NH4+. This is trapped in lumen
- Ammonium can’t move back into the cell
- Increased excretion of ammonium as a result
-NH4+ can also be taken up in TAL and transported to interstitum and dissociated to H+ and NH3. This moves into the lumen of collecting ducts
What are the features of urine in terms of cations and anions?
- Minimum pH is 4.5
- No HCO3-
- Some H+ is buffered by phosphate
- Some H+ has reacted with ammonia to form ammonium
What is the effect of acidosis on potassium?
- Potassium ions move out of cells
- Decreased potassium excretion in distal nephron
- Hyperkalaemia
What is the effect of alkalosis on potassium?
- Potassium ions move into cells
- Enhanced excretion of potassium in distal nephron
- Hypokalaemia
What is the effect of hypokalaemia on intracellular pH of tubular cells?
- H+ move into the cells
- Favours K+ excretion and HCO3- recovery
- Metabolic alkalosis
What is the effect of hyperkalaemia on intracellular pH of tubular cells?
- H+ ions move out of the cells
- This favours HCO3- excretion
- Metabolic acidosis
What are the characteristics of uncompensated respiratory acidosis?
- High CO2
- Normal HCO3-
- Low pH
What are the characteristics of uncompensated respiratory alkalosis?
- Low pCO2
- Normal HCO3-
- Raised pH
What are the characteristics of compensated respiratory acidosis?
- High pCO2
- Raised HCO3-
- Relatively normal pH
What are the characteristics of compensated respiratory alkalosis?
- Low pCO2
- Lowered HCO3-
- Relatively normal pH
What is the anion gap?
- Difference in measured anions and cations
- Normally 10-18 mmol/l
When is the anion gap increased?
- If HCO3- is replaced by other anions
- If a metabolic acid reacts with HCO3-, the anion of the acid replaces HCO3-
What is the effect of Renal causes of acidosis on the anion gap?
- In renal causes of acidosis anion gap will be unchanged
- Not making enough HCO3- but it is replaced by Cl-
What are the features of uncompensated metabolic acidosis?
- Normal pCO2
- Low HCO3-
- Low pH
- Increased anion gap if HCO3- is replaced by another organic anion from an acid
- Normal anion gap if HCO3- is replaced by Cl-
What are the characteristics of compensated metabolic acidosis?
- Low HCO3-
- Lowered pCO2
- Nearer normal pH
What are the characteristics of uncompensated metabolic alkalosis?
- Normal pCO2
- Raised HCO3-
- Increased pH
What is type 2 respiratory failure?
- Low pO2 and High pCO2
- Alveoli cannot be properly ventilated
What are causes of type 2 respiratory failure?
- Severe COPD
- Severe asthma
- Drug overdose
- Neuromuscular disease
How can type 2 respiratory failure be compensated for?
Increase in HCO3-
-Chronic conditions can be well compensated to the near normal
What are conditions that can cause respiratory alkalosis?
Hyperventilation caused by Anxiety/panic attacks (acute setting)
Hyper ventilation in response to long-term hypoxia (type 1 respiratory failure)
What are conditions that cause metabolic acidosis?
- Keto acidosis in diabetes
- Lactic acidosis (exercising to exhaustion, poor tissue perfusion)
- Uraemic acidosis (advanced renal failure)
What are conditions leading to metabolic acidosis with a normal anion gap?
- Renal tubular acidosis. Problems with transport mechanism in the tubules
- Severe persistent diarrhoea which can lead to metabolic acidosis due to loss of HCO3-. Replaced by Cl-
What happens in diabetic acidosis to potassium?
- K+ moves out of cells
- Osmotic diuresis means K+ is lost in urine
- Total body depletion of K+
What are conditions leading to metabolic alkalosis?
- Severe prolonged vomiting or mechanical drainage of the the stomach leads to loss of H+. Stomach secretes more H+ and produces HCO3- in this process.
- Potassium depletion/mineralcoritcoid excess
- Certain diuretics
How is metabolic alkalosis corrected?
- Rise in pH of tubular cells leads to fall in H+ excretion and reduction in HCO3- recovery
- Problems can occur is there is also volume depletion
Why can problems occur with correction of metabolic alkalosis if there is volume depletion?
- High Na+ recovery rate so capacity to loss HCO3- is reduced
- Recovering Na+ favours H+ excretion and HCO3- recovery
