Week 6 Acid Base Balance Flashcards
what is the normal range for plasma pH and H ions and what are deviations from a normal pH called?
pH 7.35-7.45
44.5-35.5 nmol.L
pH below 7.35- acidaemia
pH above 7.45- alkalaemia
what determines plasma pH (state and explain the equation)?
ratio of [HCO3-] and pCO2 henderson- hasselbalch equation: pH = pK + log ( [HCO3-] / pCO2 x 0.23) pK is a constant at 6.1 20x as much HCO3 (25mmol.L) as dissolved CO2 (1.2mmol.L) log20 = 1.3 pH = 6.1 + 1.3 = 7.4
how does ventilation affect acid base balance?
hypoventilate- dont blow off enough CO2= hypercapnia= high pCO2- fall in plasma pH = RESPIRATORY ACIDAEMIA
hyperventilate- blow off more CO2= hypocapnia= low pCO2 (ratio in favour of HCO3)- rise in pH= RESPIRATORY ALKALAEMIA
what determines the pCO2 and HCO3- and controls them and what disturbances affect these?
pCO2 determined by respiration
controlled by chemoreceptors
disrupted by respiratory disease- if cannot ventilate lungs enough cannot blow off enough CO2
HCO3- determined by kidneys
controlled by kidneys
disrupted by metabolic and renal disease
what affects does alkaleamia have on Ca and what does this lead to?
lowers free Ca by causing Ca ions to come out of solution = increases neuronal excitability
pH >7.45 = paraesthesia and tetany
45% mortality is raises above 7.55
80% above 7.65
what affect does acideamia have on K and H inside cell and what can this lead to?
K H exchanger on cells- H taken in to cell to buffer pH and K transported out= increases plasma K= increased excitability- particularly to cardiac muscle= arrhythmia
increased H disrupts enzymes, effects muscle contractility, glycolysis and hepatic function
affects severe if pH
what do peripheral and central chemoreceptors detect and and what response is generated?
central chemoreceptors detect pCO2 as it can pass across blood brain barrier- changes ventilation rate to correct respiratory changes in pCO2- slower response but 80% of effect
peripheral chemoreceptors- detect changes in pCO2 and pH of plasma - responds rapidly but has smaller effect
what is metabolic and respiratory acidosis/alkalosis compensated by and how is this achieved?
- Metabolic acidosis= more H which is joined with HCO3 to create CO2 and H2O so HCO3 is low- compensated by HYPERVENTILATING to blow off more Co2 to retain CO2:HCO3
- fall in pH detected by peripheral receptors - stimulates resp neurones in medulla- increase ventilation - metabolic alkalosis (vomiting) = less H- rise in pH- only partially compensated by HYPOVENTILATING to retain CO2 as cannot compromise o2 getting into body
- ** KIDNEYS can also CORRECT metabolic disturbances in pH by varying excretion of [hco3] and if required making more of it
- respiratory acidosis- more Co2, compensated by KIDNEY increasing [HCO3]
- respiratory alkalaemia- less CO2- compensated by KIDNEYS decreasing [HCO3]
describe renal control of [HCO3]- filtration,?
large quantities of [HCO3] filtered at glomerulus- 4500mmol per day
- can loose HCO3 easily by not reabsorbing as much
to increase [HCO3] must reabsorb all and make more
how does the kidney make new HCO3- as a result of metabolism?
Kidneys have high metabolic rate so produce lots of Co2-> reacts with H2O producing H+ and HCO3- = HCO3 enters plasma and H enters urine
describe HCO3 reabsorption in PCT
80% reabsorbed in PCT,
- driven by Na gradient from NA,K ATPase on basolateral membrane- Na out and K in
- NHE- Na, H exchanger on apical membrane moves Na into cell and H into lumen
- H in lumen reacts with HCO3 via carbonic anhydrase to produce H20 and Co2-> CO2 freely moves back into cell
- in cel CO2 binds to H2O to create H and HCO3-> H feeds back into NHE and HCO3 cotransported via Na by Na-2HCO3 cotransporter into ECF
**carbonic anhydrase present on apical membrane and in tubular cells
how is new HCO3 created in the PCT?
can also make HCO3 from amino acids in proximal tubule
- glutamaine metabolised to a-ketoglutarate and ammonium (NH4) which is further metabolised to hydrogen carbonate (HCO3) and ammonia (NH3) + H
- HCO3 enters ECF cotransported with Na,
- ammonia is not charged so can freely cross apical membrane into lumen unlike ammonium and therefore enters urine- once in lumen ammonia binds to H to create ammonium which cannot pass back in
how is new HCO3 created in the DCT?
by DCT all HCO3 has been reabsorbed
metabolic activity in cells produce Co2 which reacts with H20 to make H and HCO3-> HCO3 goes into ECF via HCO/Cl exchanger
- in a- intercalated cell- H cannot be removed via NHE as isnt a gradient of Na from lumen to drive this so have to use H pump - H ATPase which actively secretes H into lumen
- H is buffered in lumen by filtered HPO4 (phosphate) and also by excreted NH3 (ammonia) which is produced by glutamine
what control H secretion?
kidneys control acid secretion- tubular cells detect changes in intracellular pH- IF ECF [HCO3] is low more HCO3 moves out of cell into ECF= more H in cell (acidic)
decreased pH enhances:
- activity of Na/H exchanger- more H moved out in PCT
- ammonium production in PCT- glutamine broken down
- H ATPase activity in DCT
- increased capacity to export HCO from tubular cells into ECF
give some examples of causes of metabolic acidosis and what can it lead to?
exercise, diabetic ketoacidosis
can cause cardiogenic shock- increased lactic acid
describe the anion gap and how it is affected by metabolic acidosis
acidosis eg exercise etc= produces acids such as lactic acid, ketoacid which are associated with a different anion to HCO3
normal anions are- HCO3 and Cl
- when exercise H and lactate etc is produced-> H reacts with HCO3 to form CO2 which is breathed out
- therefore some HCO3 anion is replaced by the lactic acid = anion gap
ANION GAP- calculated as difference between cations (Na/K) and anions (HCO3/Cl)
- anions are usually 10-15mmol.L less than cations
- gap increases if unaccounted anions replace HCO3- not if Cl replaces it as this would result in no change (renal disease)
give an example of when a metabolic acidosis would and would create an anion gap?
some renal disease replaces HCO3 with Cl so no gap generated
Diabetic ketoacidosis would see an increase in gap
what happens to H excretion and HCO3 reabsorption in metabolic alkalosis and when is this problematic?
metabolic alkalosis- excessive vomiting= rise in pH
so dont reabsorb as much HCO3 and excrete less H
if volume depletion- wanting to retain Na in order to retain H20
- difficult to loose HCO3 with high rate of Na recovery because of HCO3/Na cotransporter on basolateral membrane in PCT
also favours H excretion via NHE on basolateral membrane working to move Na in
- in this instance priority is fluid replenishment and pH fixed later
how does acid base changes affect K and vice versa?
metabolic acidosis- H moves into normal cells to reduce H in ECF-> as H moves in K is moved out increasing K in ECF= hyperkaleamia
- also get more K reabsorption in DCT as pump H into lumen and K comes in at same time
metabolic alkalosis- less H in ECF so moves out of cell in exchange for K moving in= hypokalaemia as less K in ECF
- also less K reabsorption in nephron
also hypokalaemia= intracellular pH of tubular cells more acidic- K pumped out so H moved into cell = favours H excretion and HCO3 recovery= metabolic alkalosis
hyperkalaemia= intracellular pH of tubular cells more alkaline- K moved into cell so H moved out of cell- favours HCO3 excretion= metabolic acidosis
