How do the lungs and kidneys control acid base balance Flashcards
What’s the normal range for plasma PH? What are the terms for when it is outside this range?
7.35- 7.45
> alkalaemia/ alkalosis
< acidaemia/ acidosis
What effects does alkalaemia have on Ca2+ and what does this do? What effect does it have on K+?
Causes Ca2+ to come out of solution and bind to things like albumin and so lowers the free [Ca2+]
Ca2+ is a divalent cation (has 2+ charge) so acts as a charge shielded to protect excitable cells form getting too excitable
So lowering free Ca2+ means increased neuronal excitability -> paraesthesia (sensory neurones) + tetany (motor neurones) - muscular spasms if this occurs respiratory muscles dyspnoea
V serious: if Ph rises to 7.55 45% mortality, if it rises to 7.65 80% mortality
Also decreases plasma K+ bc K+ ions move into call as H+ comes out antiport & then enhanced excretion of K+ in distal nephron
What effects does acidaemia have on plasma K+ and what effects does this have?
Increases plasma K+ by more K+ leaving cells antiport with H+ & then decreased K+ excretion in distal nephron, effects excitability
(Particularly for cardiac muscles: hyperkalaemia-> membrane potential depolarises -> inactivates Some voltage-gated Na+ channels-> slows upstoke -> arrthymias and potentially Asytole)
Increased H+ affects many enzymes and denatures proteins -> effects muscle contractility, glycolysis, hepatic function
Severe below 7.1
Life threatening below 7
What controls the PCO2 and what disturbs it?
Determined by respiration
Controlled by chemoreceptors
Disturbed by respiratory disease
What controls the [HCO3-] and what disturbs it?
Controlled by the kidney
Disturbed by metabolic and renal disease
What’s the normal concentration of HCO3- in arterial blood?
22-26mmol.l-1
But can be changed to maintain Ph
Explain how the kidneys filter HCO3- and produce it?
- Kidneys recover all filtered HCO3- (80% recovered PCt)
- Proximal tubule makes HCO3- from AA, putting NH4+ into urine
Gluatime makes alpha- ketoglutarate -> HCO3- (enters ECF via Na+ symporter) and NH4+ (enters lumen)
- Distal tubule makes HCO3- from CO2 and H2O, H+ is actively secreted (also at collecting ducts) buffered by phosphate and ammonia in the urine
HCO3- exported out of tubular cell with Na+ symporter basolateral membrane
(Na+ and H+ antiport to let Na+ into tubular cell apical membrane)
Slide 10
What’s the major adaptive response to an increased acid load in healthy individuals? What acts as buffer for the urine and why is it important to have one?
Excretion of ammonia
Ammonium generation
from glutamine in proximal tubule can be increased in response to low PH
NH4+ -> NH3 + H+
- NH3 moves freely into lumen and throughout interstitium
- H+ actively pumped into lumen in DCT & CT
- H+ combined with NH3 -> NH4+ (trapped in lumen)
Phosphate and NH3 act as buffer for H+ in lumen -> H2PO4- ( keep minimum PH urine 4.5 so doesn’t damage urinary tract)
How do acidosis, alkalosis and K+ serum concentration all link?
Acidosis hyperkalaemia
One can cause the other
Alkalosis hypokalaemia
How does hyperkalaemia lead to metabolic acidosis?
Lots of K+ in blood so K+ moves into cells e.g. tubular cells become more alkaline as H+ ions move out of the cells -> increases HCO3- excretion -> metabolic acidosis
How does hypokalaemia lead to metabolic alkalosis?
Low [K+] of blood so K+ moves out of cells down conc grad, H+ at antiport therefore moves into cells making them acidic, this favours HCO3- recovery -> metabolic alkalosis
Why does hyperventilation lead to a respiratory alkalosis? what effect does it have on PO2?
Hyperventilation-> hypocapnia (pCO2 fall)
-> increase in PH -> respiratory alkalosis
(CO2 + H2O H+ + HCO3-)
Normal HCO3- as less excreted by kidney takes 2-3days
Higher PO2 as more fresh air is brought in
Why does hypoventilation lead to respiratory acidosis? What effect does it have on PO2?
Hypoventilation-> hypercapnia (PCo2 rise) -> decreases plasma PH -> respiratory acidosis
(CO2 + H2O H+ + HCO3-)
Normal HCO3- (as kidney excretes more 2-3days)
Decreases PO2 less fresh air brought in
What happens to PCO2, [HCO3-] and PH In compensated respiratory acidosis?
High PCO2
Raised [HCO3-]
Relatively normal PH
What happens to PCO2, [HCO3-] and PH in compensated respiratory alkalosis?
PCo2 low
[HCO3-] low
PH relatively normal (on higher side)
How does metabolic acidosis occur, what would the changes in [HcO3-], PCO2, LH and the anion gap be?
If tissues produce acid it reacts with and removes HCO3- (H+ + HCO3- CO2 + H20)
So fall in HCO3- (attempts to react with all H+)
Extra CO2 is breathed off so PCo2 stays normal
Lowered PH
If increased metabolic acids the anion of the acid replaces HCO3- and anion gap increases but if renal cause of acidosis anion gap stays the same (less HCO3- but replaced by Cl-)
Bc calculated by:
([Na+] + [K+]) - ([Cl-] + [HCO3-])
What is the anion gap? When does it change?
Difference between measure cations and anions
([Na+] + [K+]) - ([Cl-] + [HCO3-])
normally 10-18 mmol.l-1 due to other non-measured anions
Increased if HCO3- is replaced
E.g. if a metabolic acid reacts with HCO3- the anion of the acid replaces HCO3- but in renal causes of acidosis anion gap will be unchanged (less HCO3- but replaced by Cl-)
How does the body compensate for metabolic acidosis? What happens to the levels of [HcO3-], PcO2 and Ph?
Peripheral chemoreceptors (carotid bodies) detect drop in Ph -> stimulate ventilation -> decreased PCO2
Compensated:
Low HCO3-
Lowered PCO2
Nearer normal PH (lower side)
What occurs in metabolic alkalosis? What would PCO2, [HcO3-] and PH be like?
[HCO3-] increases so
[HcO3] high
Normal PCO2 (extra is breathed off)
Increased Ph
What conditions can lead to respiratory acidosis?
Type 2 respiratory failure
- low PO2
- high PCO2
Alveoli can’t be properly ventilated
What conditions can lead to respiratory alkalosis?
- hyperventilation e.g. panic attacks
- low PCO2, rise in PH
- hyperventilation in response to long term hypoxia (type 1 respiratory failure) low PcO2 will initially raise Ph but can be compensated for chronically by fall in HCO3-
What’s the difference between type one and two respiratory failure?
Type 1 involves low O2 with normal/ low CO2 -> respiratory alkalosis
Type 2 involves low O2 with high CO2 -> respiratory acidosis
What conditions may lead to metabolic acidosis?
If anion gap is increased indicates a metabolic production of acid e.g.
- keto-acidosis, diabetes
- lactic acidosis, exercising to exhaustion/ poor tissue perfusion
- uraemia acidosis, advanced Renal failure (reduced acid secretion, build up of phosphate, sulphate and urate in blood)
If anion gap is normal indicates renal problem:
- renal tubular acidosis (rare) type 1 inability to pump out H+ or type 2 problems with HCO3- reabsorption
- severe persistent diarrhoea loss of HCO3-
Replaced by Cl-
Acidosis normally leads to hyperkalaemia, when is this not the case?
Non-renal causes of metabolic acidosis cause increased reabsorption of K+ by kidneys and movement of K+ out of cells
However in diabetic ketoacidosis may be a totals body depletion of K+
(Although K+ moves out of cells due to acidosis and lack of insulin, os optic diuretics means lots K+ lost in urine)
