Lecture 9 - Acid base balance Flashcards
Plasma pH
7.35 - 7.45
H+ ion concentration
Low an tightly regulated
pH greater than 7.45
Alkaemia
pH lower than 7.35
Acidaemia
Alkaemia
Lowers free calcium - dangerous
- Less H+ ions bound to plasma proteins
- More -vely charged sites are available on the plasma protein
- Ionised free Ca2+ binds to plasma proteins (chelated) therefore less Ca2+ available
- Ca2+ also binds to bone and leaves the ECF causing hypocalcaemia
Hypocalcaemia
Increases neurone excitablity
- Tetany
- Paraesthesia
pH 7.55
45% mortality
pH 7.65
80% mortality
Acideamia
Increases plasma K+ ion concentration - hyperkaleamia
Denatures proteins therefore impaired:
- muscle contraction
- glycolysis
- hepatic function
pH 7.1
Severe effects and life threatening below 7.0
Buffer system
CO2 + H20 –> H2CO3- –> H+ + HCO3-
Using carbonic anhydrase
pH dependent on how much CO2 is converted to H+
Increased CO2
Pushes reaction to the right producing more H+
Increased HCO3-
Pushes reaction to the left producing more CO2 which is breathed away
What determines plasma pH
Determined by the HCO3- : pCO2 ratio (20:1)
HCO3- controlled by kidneys
pCO2
Detected by chemoreceptors Controlled by ventilation
Disrupted by respiratory disease
HCO3-
HCO3- made in RBC
Controlled by kidneys
Disturebed by metabolic and renal disease
Kidneys
Produces and recovers HCO3-
Excretes H+
Lungs
Alveloar ventilation diffuses CO2 out of blood to maintain concentration gradient
HCO3- concentration in RBC
25 mmol/L
22-26 mmol/L
Can change to maintain pH
HCO3- production and recovery
Kidneys recover all HCO3-
PCT makes 2HCO3- from glutamine and excreting NH4+ into urine
DCT makes 2 HCO3- from CO2 and H2O
(H+ bufffered by phosphate and ammonia in the urine)
PCT HCO3- recovery
80 - 90% recovered by PCT
- NHE excretes H+ into the lumen for every Na+ into the cell
- HCO3- filtered in the glomerulus into the lumen binds to H+ to form CO2
- CO2 diffuses into the cell transcellularly
- CO2 is converted to H+ (which is excreted again) and HCO3-
- HCO3- enters plasma via Na+/HCO3- co transporter therefore Na+dependent
PCT HCO3- production
- Glutamine is converted to alpha ketoglutarate and ammonium (NH4+)
- Ammonium is converted to ammonia (NH3) which freely diffuses into the lumen and H+ which is secreted into the lumen using NHE
- NH3 + H+ -> NH4 in lumen as ammonia acts as buffer
- Alpha ketoglutarate produces 2 HCO3- molecules
- HCO3- molecules diffuse into the blood via Na+/HCO3- channel
DCT and CT
- Alpha intercalated cells actively secret H+ into the lumen using H+ ATPase
- Ammonia and hydrogen phosphate buffer the H+ in the lumen
- CO2 and water (from metabolism) inside the intercalated cell produce HCO3-
- HCO3- enters the blood via HCO3-/ Cl- antiporter therfore non Na+ dependent
Increased acid load and low pH in healthy individual
Increased excretion of ammonium in urine as ammonia buffers H+
Ammonium generation from glutamine is increased in the PCT
NH3 freely moves in urine and interstitium as not charged
NH4+ in thick ascending limb
Can be taken up by thick ascending limb where it travels to the collecting ducts.
Dissociates into NH3 and H+ where it can be excreted into the lumen
Minimum pH of urine
4.5
Due to H+ buffering system excreting H+
No HCO3- as also reabsorbed
Hyperkalaemia
Caused by metabolic acidosis
H+ moves into body cells and K+ moves out into blood
In nephron cells, H+ is excreted into lumen and K+ is taken up
Causes cardiac arrythmias
Hypokalaemia
Caused by metaboloc alkalosis
H+ moves out of cells and K+ moves in
In distal nephron, H+ is absorbed and K+ is excreted
Hypoventilation
Causes hypercapnia
Increased CO2
Decreases pH
Respiratory acidosis
Hyperventilation
Causes hypocapnia
Decreased CO2
High pH
Respiratory alkalosis
Compensation of respiratory acidosis and alkalosis
Acidosis - Kidneys produce more [HCO3-]
Alkalosis - Kidneys decrease [HCO3-]
Takes 2-3 days so gradual respiratory disease is well compensated but acute cases are not
Metabolic acidosis
Tissues produce acid e.g. lactic acid and ketoacidosis
Acids react with HCO3- decreasing the concentration
Decreases pH
Compensation of respiratory metabolic acidosis
Peripheral chemoreceptors detect pH drop in the carotid body
Stimulates an increase in ventilation proportional to HCO3- loss
Anion gap
([Na+] + [K+]) - ([Cl-] + [HCO3-])
Other anions are not measured e.g. proteins
Gap increased if HCO3- is replaced by other anions e.g. lactate
Tissues produce e.g. lactic acid in MI that reacts with HCO3- and replaces it with another anion. HCO3- decreases therefore the anion gap increases
Renal cause of metabolic acidosis
Anion gap is unchanged
As HCO3- produced less
But Cl- produced instead
metabolic alkalosis
Increase in HCO3-
Cannot be compensated efficiently as body must preserve oxygen supply to brain so can’t hypoventilate proportionally
Therefore kidney excretes HCO3-
Type 2 respiratory failure
Low O2
High pCO2
Compensated by increase of HCO3-
Causes of type 2 resp failure
Hypoventilation Severe COPD Severe asthma Drug overdose Neuromuscular disease
Conditions causing respiratory alkalosis
Hyperventilation
Panic attacks
Anxiety
Type 1 respiratory failure
Low O2
Low CO2
Hyperventilation in repsonse to long term hypoxia
Initial rise in pH
Compensated for by fall in HCO3-
Conditions causing metabolic acidosis with increased anion gap
- Ketoacidosis - diabetes
- Lactic acidosis - exercise to exhaustion
- Poor tissue perfusion - MI releases lactic acid
- Uraemic acidosis - advanced renal failure causes a decrease in H+ secretion
Uraemic acidosis
Build up in blood of :
- phosphate
- H+
- sulfate
- urate
Conditions causing metabolic acidosis with normal anion gap
Renal tubular acidosis
- Type 1 - distal inability to pump out H+
- Type 2 - proximal problems with HCO3- reabsorption
Severe persistant diarrhoea - loss of HCO3- replaced by Cl-
Diabetic ketoacidosis
Normally get hyperkalaemia however, total body depletion of K+
- K+ moves out of body cells due to acidosis and lack of insulin
- Osmotic diuresis due to less Na+ reabsorption means K+ lost in urine
Conditions causing metabolic alkalosis
Vomiting - loss of H+
Mechanical drainage of stomach into duodenum - lack of secretion of HCO3- to neutralise H+ as no H+
Volume deplete
Normally easy to correct metabolic alkalosis as downregulate NHE
However, if volume deplete can’t downregulate as need to retain water with Na+ absorption
