Acid Base Balance - Pt 1 Flashcards
Describe acid base balance
Metabolic reactions are exquisitely sensitive to pH of fluid in which they occur
Relates to high reactivity of H+ ions with protons
What does acid/ base disturbances lead to?
All sort of metabolic disturbances
pH of ECF is closely regulated
What is the pH of arterialised blood?
Around 7.4 so free H+ conc. of 40 x 10-9moles/l or 40 x10-6mmoles/l
What H+ ions contribute to pH?
Only free H+ ions
H+ conc. is one millionth that of other plasma constituents
Body produces H+
What are the sources of H+?
Respiratory acid
Metabolic acid via metabolism
Describe source of H+ ions from respiratory acid
CO2 + H2O - H2CO3 - H+ + HCO3
Formation of carbonic acid is not usually a net contribution to increase acid because any increase in production leads to increase ventilation
What are the sources of H+ in metabolic acid?
Inorganic acids - S containing amino acids
Organic acids - fatty acids and lactic acid (normal diet - 50-100mmoles of H+)
What are buffers?
Minimise changes in pH when H+ ions are added or removed
Describe the Henderson-Hasselbalch equation
Defines the pH in terms f the ration of A-/HA not the absolute amounts
pH = pK + log A-/HA
What is extracellular buffers?
Most important bicarbonate buffer system
Quantity of H2CO3 depends on amount o CO2 dissolved in plasma, depends on solubility of CO2 and PCO2
What is the ratio of (HCO3)/(H2CO3) in blood at 7.4?
20:1
What is the solubility of CO2 in blood at 37 degrees?
0.03 mmoles/l/mmHg
What is the normal PCO2?
40mmHg
5.3kPa
What is standard bicarbonate?
24mmoles/l
At normal PCO2 40mmHg H2CO3 conc. is 40 x 0.03mmoles/l x 0.225mmoles/l = 1.2 mmoles/l
20:1 ratio so 2.4 mmoles/l
What is the simple Henderson Hasselbalch equation?
pH is proportional to HCO3-/PCO2
What does increase H+ in ECF lead to in equation?
Drives reaction to right so additional H+ are removed from solution so therefore a change in pH is reduced
What happens when reaction is driven to the right?
Increases production of CO2 which increases ventilation and decreases CO2
Greatly increases the buffering capacity of bicarbonate
Does H+ get eliminated from the body?
No - instead bicarbonate has buffered the H+ ions and respiratory has compensated greatly so free H+ ions are prevented from contributing to pH
What happens if there is a decrease in H+ in ECF?
Pulls reaction to left - decreases CO2 which decreases ventilation so increases CO2
What is the aim of the acid base reaction?
Protecting arterial pH
How is H+ ions eliminated from the body?
By the kidneys
This excretion is couples to the regulation of plasma HCO3- conc.
How is plasma conc. of HCO3- regulated?
Renal regulation
What are the other buffers in the ECF?
Plasma proteins Pr- + H+ - HPr
Diabetic phosphate HPO42- + H+ - H2PO4 monobasic phosphate
Describe intracellular buffers
Primary - proteins, organic and inorganic phosphates, and haemoglobin (erythrocytes)
Bone carbonate provides additional source of buffer - chronic acid loads in chronic renal failure
What does buffering of H+ by ICF cause?
Changes in plasma electrolytes so maintain neutrality - movement of H+ is accompanied by Cl- as in red cells or exchanged for K+
In acidosis, what does movement of K+ out of cells into plasma lead to?
Depolarisation of excitable tissues leading to ventricular fibrillation and death
Increase in H+ leads to hyperkalaemia
Why are buffers incredibly important?
50-100 mmoles of H+ from diet and if present as free H+ in body water then pH of 1.2-2.4
H+ is successfully buffered until kidney excretes it
In metabolic acid, how much is buffered in plasma and cells?
43% in plasma - primarily with HCO3-
57% in cells
In respiratory acid, how much is buffered in plasma and cells?
97% in cells
Hb particularly important, rest within plasma proteins
How does the kidney regulate conc. of HCO3-?
Reabsorbing filtered HCO3-
By generating new HCO3-
What do the processes of kidney regulation of HCO3- depend on?
Both depend on active H+ ion secretion from tubule cells into lumen
What is the mechanism of reabsorption of HCO3-?
Active H+ secretion from tubule cells coupled to passive Na+ reabsorption
Filtered HCO3- reacts with secreted H+ to form H2CO3
In presence of carbonic anhydrase on luminal membrane - CO2 and H2O
CO2 freely permeable and enters cell
During the mechanism of reabsorption of HCO3-, what happens to CO2 in cell?
CO2 makes H2CO3 in presence of carbonic anhydrase which dissociates to form H+ and HCO3-
H+ ions are source of secreted H+ ions
HCO3- passes into peritubular capillaries with Na+
Where does the bulk of HCO3- reabsorption occur?
In proximal tubule - 90%
What is the importance of HCO3- reabsorption?
GFR = 180l/day
HCO3- conc. = 24mmoles/l
4320mmoles HCO3- filtered a day
Must be reabsorbed as failure = adding H+ to ECF
No excretion of H+ ions
What is the minimum and maximum urine pH?
Min. = 4.5-5
Max. = 8
Usually net production of 50-100mmoles of H+ a day
What happens if free H+ ions in urine volume of 1l?
pH of 1
But they are buffered
What acts as buffers in urine?
Weak acids and bases - mostly dibasic phosphate HPO42-, also uric acids and creatine
Why is the process called titratable acidity?
As its extent is measured by amount of NaOH needed to titrate urine pH back to 7.4
What is the importance of titratable acidity?
Generates new HCO3- and excretes H+
Only used for acid loads
Describe titratable acidity in distal tubule
Na2HPO4 in lumen - Na reabsorbed in exchange for secreted H+
Monobasic phosphate removes H+ from body
Source of new HCO3- is indirectly CO2 from blood - CO2 enters tubule cell
New HCO3- passes with Na into peritubular capillaries
How is new HCO3- made in distal tubule cells?
CO2 enters tubule cells and combine with H2O to form carbonic acid
Carbonic anhydrase - dissociates H2CO3 into H+ and HCO3-
H+ for secretion and HCO3- leaves with Na
Where does titratable acidity mainly occur?
Distal tubule - phosphate ions are not reabsorbed by proximal tubule Tm mechanism
They become greatly concentrated as removal of 95% initial filtrate
What is the titratable acidity process dependant on?
PCO2 in blood
Generation of new HCO3- and net excretion of H+
What is the response of ammonium excretion?
Adaptive response to acid load - generates new HCO3- and excretes H+
Only used for acids loads
Describe the process of ammonium excretion
NH3 is lipid soluble but NH4+ is not
NH3 moves out into tubule lumen where combines with excreted H+ to form NH4+
Combines with Cl- ions to form NH4Cl which is excreted (distal)
What is the source of H+ in ammonium excretion?
CO2 in blood
What is the difference in distal and proximal tubule ammonium excretion?
Proximal - there is an NH4+/Na+ exchanger so NH4+ ions formed within cells are passed into lumen so net effect is the same
What happens to new HCO3- in ammonium excretion?
Passes into peritubular capillaries with Na ions
What is NH3 produced by?
Deamination of amino acids, primarily glutamine, by action of renal glutaminase within renal tubule cells
Describe the activity of renal glutaminase
pH dependant
When intracellular pH falls there is increase in renal glutaminase activity so more NH4+ produced and excreted
What is the main adaptive response of kidney to acids loads?
Ability to augment NH4+ production
Takes 4-5 days to reach maximal effect because requirements of increased protein synthesis
Takes time to switch off ability to make NH4+ when excess alkali
