Acid Base Regulation Flashcards
Define acid. Give an example.
Any chemical that can donate H+ (proton) e.g. HCL -> H+ + Cl-
Define base. Give an example.
Any chemical that can accept H+ e.g. NaOH -> Na+ + OH- which allows OH-+ H+ -> H2O
What is the difference between a strong and weak acid? Give examples.
Strong acid: completely dissociates in water releasing large amounts of H+ e.g. HCl -> H+ + Cl
Weak acids: incompletely dissociates in water + reaches equilibrium with its conjugate base forming a buffer pair that responds to changes in [H+] by reversibly binding H+ e.g. H2CO3 H+ + HCO3-
How do you measure acidity (pH scale)?
[H+] in mol/L but because there is a wide range of these values, you should take the negative logarithm to base 10 [H+] = pH range between 1-14
What is the relationship between pH and H+ concentration?
Inverse relationship where a 1 unit pH change is equivalent to a 10-fold increase in [H+] - as [H+] increases, pH decreases
What is the average pH of blood?
7.4 (7.36-7.44) = [H+] between 36-44 nanomoles/litre
Survival for short periods is possible at pH values ranging between?
6.8-8.0
Why is the regulation of H+ concentration more complex and tightly regulated than for other ions?
H+ is small + charged thus affecting protein function:
- Alters protein activity especially enzymes; body wide effect where many physiological processes sensitive to small change in [H+]
- Alters binding of other ions e.g. low [H+] increases Ca2+ binding to albumin
What processes are usually sufficient to maintain ion concentration?
Balance of intake, production + excretion to maintain homeostasis (kidney has a role)
What is acid-base regulation?
Control of [H+]
Why is it a bad thing if ion binding is altered in the body?
The body will think that the levels are different to what they are + try to correct this
What are the 2 sources of H+ in the body?
- Volatile acids (more easily vapourised)
2. Non-volatile (fixed/non-respiratory acids)
What is a volatile acid?
An acid that can leave solution + enter the atmosphere via lung excretion
H+ generated from aerobic metabolism + CO2 production by tissues (H2CO3)
What is a non-volatile acid?
Organics acids (H+) e.g. lactic or keto acids formed in certain circumstances from other metabolic processes + excreted by the kidneys
What are the 3 main mechanisms to maintain H+ concentration and thus, minimise changes in pH?
- Buffer systems: rapid chemical reaction that minimises sudden changes in pH (unable to change overall body H+)
- Lungs: RAPIDLY adjust excretion of CO2
- Kidneys: SLOWLY adjust urine excretion of H+ altering body HCO3- levels
Why are buffer systems only a good short-term mechanism to maintain pH?
They mop up H+ but cannot excrete it out of body so make pH appear maintained short-term but eventually will run out of ways to mop H+ up
What is a buffer? How does they work?
Any substance that reversibly binds H+ i.e. weak acid
Buffer + H+ HBuffer
So if H+ added, buffer binds it to form Hbuffer removing H+ however, if H+ removed, Hbuffer releases H+ adding H+
What are the 3 main buffer systems in the body?
- Bicarbonate (most important in EC): HCO3- + H+ H2CO3
- Phosphate (IC + urine): HPO42- + H+ H2PO4-
- Protein (mainly IC): Pr- + H+ HPr
What are the 3 types of protein buffer systems?
- Hb (RBC)
- AA (proteins)
- Plasma protein (albumin)
Explain the bicarbonate buffer system.
H+ + HCO3- (kidneys) H2CO3 (carbonic anhydrase/dehydratase) H2O + CO2 (lungs)
Connects the lungs control of [CO2] to kidneys control of [HCO3-] in acid-base balance -> shows how systems can compensate for each other
What is the Henderson-Hasselbalch (H-H) equation? What does it allow us to work out?
pH = pK + log10[HCO3-]/[CO2]
pK = constant [HCO3-] = from kidneys [CO2] = from lungs - measured from pCO2
Allows us to calculate pH based on measurements of [HCO3-] + [CO2] ratio (2 concentrations easily measured in arterial blood)
In arterial blood, what should ratio of HCO3- and CO2 concentration be roughly?
20:1
What are the 2 ways the body maintains pH?
- Functional ability of lungs to maintain [CO2] i.e. rapid response (mins-hrs) alters CO2 elimination via change in ventilation to restore pH
- Functional ability of kidneys to maintain [HCO3-] i.e. slow response (hrs-days) alters HCO3- production + H+ excretion to restore pH
pH is dependent on the __ of HCO3- and CO2 concentrations not the ___.
Ratio Amounts (i.e. do not have be identical in concentration)
How can HCO3- and CO2 concentration change in order to decrease or increase pH?
Decreased pH: Increased [CO2] or decreased [HCO3-] or both
Increased pH: Decreased [CO2] or increased [HCO3-] or both
How can the kidneys control acid-base balance and therefore, pH?
Control ECF pH via 2 mechanisms (both rely on kidneys ability to secrete H+):
- Excretion of H+ (non-volatile acid production) in urine -> urine usually acidic (+ production of new HCO3- in turn)
- Reabsorption of filtered HCO3- to avoid reduction in [HCO3-]
H+ loss = HCO3- gain
Is there normally HCO3- in the urine? Why?
No
Because then less would be available to bind H+ in plasma, adding H+ to plasma and decreasing plasma pH
How much of the filtered HCO3- must be reabsorbed and where does this occur?
Must reabsorb 100%
Majority of reabsorption occurs in proximal convoluted tubule (small amount in late distal + collecting tubules)
How is HCO3- reabsorbed from the tubular lumen of the kidneys?
- HCO3- converted to H2CO3 (using secreted H+) + then CO2 + H2O (cannot be reabsorbed directly)
- CO2 + H2O transported into tubular cells + converted back to H2CO3 via carbonic anhydrase
- H2CO3 dissociates back into HCO3- + H+ -> H+ stays in cell to be secreted again whilst HCO3- co-transported with Na+
= no net gain/loss of H+ or HCO3- = no change in acid-base status despite H+ secretion as its just cycling round + reclaiming HCO3- that was already in blood
How is H+ secreted in the kidneys? Where does this occur?
Uses H+/K+ ATPase transporters in type A intercalating cells to pump H+ into tubular lumen = generates 800-fold H+ gradient + a min urine pH of 4.5
Late distal + cortical collecting tubules
Why are buffers needed in the urine?
Comfort
Allow sufficient H+ to be excreted in urine to secrete all 70-100mmol of non-volatile H+
To stop H+/K+ ATPase switching off (stops working when there is high [H+])
What are the 2 main urinary buffers?
- Phosphate
2. Ammonia
Why is it important to generate new HCO3- in the kidneys?
Some is consumed buffering non-volatile acids produced each day but it needs to return to blood so H+ can bind it instead of H+ increasing + pH decreasing
How does the urinary phosphate buffer work?
Filtered phosphate has 2 forms that create a buffer pair in tubular fluid: monoprotic (HPO42-)+ diprotic (H2PO4)
Excess of HPO42- can pick up excess secreted H+ in lumen excreting it in urine -> leads to HCO3- production which passes into blood
HPO42- + H+ H2PO4-
In terms of the urinary phosphate buffer, what does H+ combine with when excreted? What process occurs at the same time?
NaHPO4-
HCO3- passes into interstitial fluid
How does the urinary ammonia buffer work?
Ammonia + ammonium form a buffer pair:
NH3 + H+ NH4+
NH3 secreted mainly in collecting duct + picks up excess secreted H+ excreting it in urine as NH4+ (in turn HCO3- is produced + goes into interstitial fluid then blood)
How is ammonium (NH4+) synthesized? What then happens to it?
From glutamine via glutaminase in PCT cells
Broken down to glutamate + then α-ketoglutarate
How is the urinary ammonia buffer regulated?
Responds to body’s acid-base status -> decrease in pH stimulates renal glutamine metabolism leading to increased H+ excretion (+ vice versa)
Why are renal responses to pH slower than in the lungs?
Because the kidneys response requires protein synthesis + breakdown
What 4 factors stimulate H+ secretion in the kidneys?
- Increased pCO2 in ECF
- Decreased pH of ECF
- Increased aldosterone
- Hypokalaemia
Define acidosis.
Any process that results in blood becoming more acidic than normal i.e. lower pH via addition if acid/loss of alkali
Can have respiratory or metabolic causes
Define alkalosis.
Any process that results in blood becoming more alkaline than normal i.e. higher pH via addition of alkali/loss of acid
Can have respiratory or metabolic causes
What will happen if a disease alters the ratio of HCO3- concentration to CO2 concentration?
Change in pH i.e. acidosis or alkalosis (signify underlying disease)
What is a metabolic problem?
Primary problem affecting [HCO3-]
What is a respiratory problem?
Primary problem affecting CO2 excretion
What is compensation?
When a change in either [HCO3-] or [CO2] is compensated by via the other parameter changing in order to minimise the change in pH attempting to restore it back to normal
If a disease is compensated for, what will you see in terms of HCO3- and CO2 concentration?
Both [HCO3-] AND [CO2] will lie outside normal ranges in same direction i.e. both will be raised/lowered
What can cause a respiratory acidosis?
Any disorder affecting lungs, chest wall, nerves, muscles or CNS leading to inappropriate reduction in ventilation thus, increasing [CO2]
What can cause a respiratory alkalosis?
Any disorder leading to inappropriate increase in ventilation e.g. anxiety + hyperventilation or high altitude leading to decreasing [CO2]
What can cause a metabolic acidosis?
Addition of exogenous acid e.g. methanol or endogenous acid e.g. lactic/keto acids
Failure of H+ secretion e.g. decreased kidney function
Loss of HCO3- e.g. severe prolonged diarrhoea
-> decreasing [HCO3-]
What can help narrow the underlying differential diagnosis of a metabolic acidosis?
Anion gap
What can cause a metabolic alkalosis?
Addition of alkali
Excess loss of H+ e.g. severe prolonged vomiting
Excess aldosterone e.g. due to dehydration - stimulates H+ secretion in distal tubule
-> increased [HCO3-]
How can you treat metabolic acid-base disorders?
- Treat + correct underlying problem whenever possible most importantly
- Use substances to neutralise acid or base OCCASIONALLY e.g. sodium bicarbonate to treat acidosis or ammonium chloride for alkalosis
How should you interpret acid-base changes?
- Look at pH
- Look at [HCO3-] + pCO2
- Look for compensation evidence
What does it mean if HCO3- + CO2 concentration are both out of range but in OPPOSITE directions?
Mixed metabolic and respiratory disorder
What will a blood gas show in a respiratory acidosis? What if its compensated for?
Increased pCO2
Compensation: increased pCO2 + increased [HCO3-]
What will a blood gas show in a respiratory alkalosis? What if its compensated for?
Decreased pCO2
Compensation: decreased pCO2 + decreased [HCO3-]
What will a blood gas show in a metabolic acidosis? What if its compensated for?
Decreased [HCO3-]
Compensation: decreased [HCO3-] + decreased pCO2
What will a blood gas show in a metabolic alkalosis? What if its compensated for?
Increased [HCO3-]
Compensation: increased [HCO3-] and increased pCO2
