Week 3 - G - Physiology 7 - Acid base balance 1 (H2CO3, TA, NH4+) Flashcards
Acid base balance – relates to the regulation of the free (unbound) hydrogen ion concentration What does the pH normal range of blood vary between in a person? (which is the number for venous and which for arterial)
Varies between 7.35-7.45 Venous blood at 7.35 and arterial at 7.45
What is the equation used to calculate the pH? (involving hydrogen ions)
pH = -log [H+] pH = log (1/[H+])
If the pHdrops below 7.35 or rises above 7.45 what is the patient said to be?
If the blood pH drops below 7.35 then the person is said to be acidic, if above 7.45 then alkalotic
pH of ECF tightly controlled close to 7.4 (40 x 10-9M of hyrogen ions (40nmol H+) What does an increase in [H+] do to pH? What do small changes in pH cause to hydrogen?
Increase in hydorgen ion concentration decreases pH Small change in pH causes a large change in hydrogen ion concentration - pH 7.0 = 100 nmol/l pH 7.8 = 16 nmol/l
Why can a severely acidotic person relapse into a coma? (say in diabetic ketoacidosis)
Severe acididotic conditions depress the central nervous system and therefore can drive someone into a coma
Alkalosis can lead to overexcitability of the peripheral NS and later the CNS. What can over-excitability of sensory nerve fibres and motor nerve fibres cause?
over-excitbaility of sensory nerve fibres can cause tingling in the hands and feet (pins and needles) Overexcitability of the motor fibres can cause muscle spasms
What effect can a change in pH have on enzymes?
Change in H+ concentration will affect the pH and therefore can denature enzymes as it affects the folding of enzymes
Hydrogen ions are being conitinually added to the body fluid mainly as a result of metabolism Always trying to match input to output What are the 3 ways in which hydrogen is continually added to the body?
Carbonic acid formation – most major cause (normally respiratory system regulates this) Inorganic acids produced during breakdown of nutrients Organic acids resulting from metabolism
What are inorganic and organic acids?
Organic acids are carboxylic acids mainly Inorganic acids are like phosphoric acid, or sulphuric acid
Strong acids dissociate completely in solution Weak acids dissociate partially in solution Give an example of a weak acid in a major buffering system?
Carbonic acid - buffer systems are usually weak acids
Buffer system consists of a pair of substances – one can yield free H+ as the [H+] decreases the other can bind free H+ when [H+] increases What is the buffering capacity defined as?
The extent to which a buffering solution can counteract the addition of an acid or a base
What would the first line defence in a change in hydrogen concentration in the body be?
This would be the buffer system
HA ⇄ H+ + A- If acid is added, what way does equilibrium shift and why? If base (e.g. B-) is added to this system, equilibrium shifts to the right? Remember the buffering is all to try and maintain the pH levels
Excess hydrogen ions binds to A- to cause equilibrium to shift to the left and fall in pH is buffered If base is added, the ions bind to the H+ causing equailibrium to shift to the right and further dissociation of HA to limit rise in pH (buffered)
What does thee dissociation constant K, at equlibrium equal?
the disocciation constant equals the vocnentration of reactants divided by the concentration of the product K= [H+][A-]/ [HA]
What is the henderson hasselback equation?
pH = pK + log [A-]/[HA]
Write down the equation for the most important physiological buffer system
CO2 + H2O ⇄ H2CO3 ⇄ H+ + HCO3- This is the CO2, HCO3- buffer system
What are the two organs that function for the most important buffer system?
CO2 + H2O ⇄ H2CO3 ⇄ H+ + HCO3- Kidneys and the lungs Lungs for CO2 and kidneys fro HCO3- (carbon dioxide and biacarbonate)
H2CO3 is formed from carbon dioxide and water What enzyme catalyzes this?
Carbonic annyhdrase H2CO3 is known as carbonic acid
Remember henderson hasselbach equation is pH = pK + log base/acid So rewrite this for the buffer system?
ph = pK + log [HCO3-]/[H2CO3]
Concentraion of carbonic acid is related to the partial pressure of carbone dioxide Need to know the partial pressure of carbon dioxide and how much is physically dissolve in the blood (solubility coeefficent) Therefore when calculating the pH of the blood it is equal to: Kidneys divided by lungs Lungs divided by kidneys Neither?
pH = pK + kidneys divded by the lungs
What is the normal bicarbonate range for concentration?
The normal range for bicarbonate is usaly around 23-27 mmol/l
the kidneys are important in regulating the levels of HCO3- in the blood Variable reabsorption of filtered HCO3- Kidneys can add “new” HCO3- to the blood i.e. [HCO3-]renal vein > [HCO3-]renal artery What do both of these depend upon?
Both the variable reabsorption of filtered HCO3- and the kidney adding new HCO3- to the blood depend on the H+ secretion into the tubular lumen
How would the rate of filtration of HCO3- be calculated?
Rate of filtration = GFR x [HCO3-]plasma
Caluclating the rate of filtration of bicarbonate per day GFR = 125ml/min and [HCO3]plasma is 24mmol/l Calculate the rate of filtration
Rate of HCO3- filtration = GFR x [HCO3-]plasma = 125 ml/min x 24 mmol/l = 180 l/day x 24 mmol/l = 4320 mmol/day
Why is it important that the filtered bicarbonate is reabosrbed?
Because if it was not reabsorbed it would be the same as adding 4litres of HCl to the body per day
the level of what substance drives hydrogen ion secretion? What enzyme catalyzes the conversion of CO2 + H2O to H2CO3?
It is the level of carbon dioxide which drives the hydrogen ion secretion Carbonic annyhdrase catalyses this conversion
Hydrogen ion secretion drives the reabsorption of bicarbonate ions Is there a transport mechanism for bicarbonate at the apical membrane and if so what is it?
For some reason there is no transport mechanism at the apical membrane for the reabsorption of bicarbonate ions from the tubular fluid directly into the tublar cell, so instead need the indirect mechansim of recycling water and Co2 produced in the tubular lumen for bicarbonate into the ECF
What happens in the tubular cell to carbonic acid? Describe how this results in hydrogen in the tubular lumen and bicarbonate in the interstitium
Carbonic acid dissociates into H+ and HCO3- HCO3- leaves the tubular cell at the basolateral membrane via the Na+/HCO3- co transporter H+ leaves the tubular cell at the apical membrane into the tubular lumen via the Na+/H+ exchanger
What does the hydrogen combine with in the filtrate?
The hydrogen combines with the bicarbonate in the filtrate to form carbonic acid which dissociated into CO2 and H2O
In addition to conserving filtered HCO3-, the kidneys can generate “new” HCO3- to regenerate buffer stores depleted by an acid load. What is the next most plenitful buffer in the filtrate that can bind with H+?
Phosphate
In the process of filtered phosphate, the process of generation of carbonic acid remains the same due to recycling of CO2 from the interstitial fluid What happens once the hydorgen enters the tubular lumen via the sodium/hydrogen exchanger?
Hydrogen binds to he filtered (hydrogen)phosphate to form phosphoric acid which is excreted in the urine
Measuring amount of strong base (NaOH) added to titrate the urine pH back to 7.4 is how the value of the phosphoric acid in the urine is calculated and hence how much hydrogen is filtered What is this back titrated acid known as?
The amount of H+ excreted as (largely) H2PO4- can be measured as “titratable” acid;
How many new bicarbonate ions are generated for each hydrogen ion present in the titratable acid? Say there is 20mmol/l of titratble acidhow much bicarbonate was generated?
For every mmol/l of titratable acid, 1mmol/l is hydogen ion and therfore 1mmol/l of bicarb was generated Therefore 20mmol/l of titratable acid = 20mmol/l off new bicarbonate ion was generated
Measurement of titratable acid does not measure NH4+: a separate ammonium ion determination is necessary In a severely acidotic patient, what is broken down into ammonia?
In a severely acidotic patient glutamine is broken down into ammonia by the enzyme glutaminase
Why is glutamine broken down to ammonia in severely acidotic conditions? (how does ammonia help lower the H+ concentration in the blood)
In severely acidotic conditions the H+ filtered into the lumen of the cell joins with the ammonia (NH3) to form ammonium (NH4+) which is excreted in the urine
Where is the enzyme glutaminase produced? For every mole of ammonium produced, how much new bicarbonate is generated?
Glutaminase is produced in the liver For every mole of ammonium produced, this accounts to 1mmol/l H+ ion which means one new bicarbonate ion generated
What are the three things discussed then that H+ secretion from the tubule causes?
Drives the reabsorption of HCO3- Forms acid phosphate (phosphoric acid) for excretion and Forms ammonium ions for excretion
At a urine flow rate of one litre per day the HCO3- excreted would be 20mmol.day rate of excretion = Vu (urine flow rate) x Urine concentration of substance ([HCO3-]urine) Therefore is 4320mmol/day filtered and 20mmol/day excreted, how much bicarb is reabsorbed per day?
4300 mmol/day of bicarbonate is reabsorbed into the blood
To calculate the titratable acid exreted we measure the concentration of titratable acid (TA) in the urine ([TA]u) and this equivaltes to ~ 20mmol/day For ammonium excreted we calculate the levels of ammoinum in the urine ~ 40mmol/day How much new bicarbonate is generated per day then?
New bicarbonate generated is equal to the mmol/day of titratable acid + ammonium in the urine = 60mmol/day
4320mmol/day HCO3- filtered in glomerulus 20mmol/day HCO3- in urine 20mmol/day TA excretion 40mmol/day NH4+ excretion What is the quantity of hydorgen ions secreted each day? What is the quantity excreted?
Quantity secreted - 4360mmol/day [H+] 4300 is secreted for the HCO3- filtrate in tubular lumen but this CO2 and H20 is rebaosrbed for the process Quantity excreted - 20 + 40 = 60mmol/day [H+] The vast majority of H+ secretion is used for HCO3- reabsorption to prevent generation of acidosis Excretion of TA and NH4+ simultaneously rids the body of acid load and regenerates buffer stores (alkalinizes the body)
