Acid-Base Balance

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From the 28-01-14 Human Physiology lecture.

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Question Answer
Acid-base balance in the body is all about the homeostasis of which ion in the body? H+ ions.
Why can H+ ions bind to proteins? Because proteins are negatively charged.
Compare the concentrations of Na+ and H+ ions in the extracellular fluid. Na+ = 140 mM, H+ = 40nM. For every 1 H+ ion, there are 3,000,000 Na+ ions. This may seem like very little H+ but the ions are very reactive.
Each pH change is a ? fold change in [H+]? A 10-fold change, i.e. pH 1 has 10x as many H+ ions as pH 2.
What is the pH of the blood? Around 7.
Why is pH used to express [H+]? For ease: there are such massive differences between values on this scale that it is easier to compare on a continuous pH scale. For instance, pH 1 = 0.1g of H+ ions per litre of water, whereas 0.00000000000001g of H+ ions per litre of water constitute a pH 14 solution.
How is [H+] being expressed in pH? i.e. pH = ... -log10([H+])
What is the survival range of pH? pH 6.8 - 8.0. Although this is only a pH difference of 1.2, it is a 16x difference in [H+], demonstrating the resistance and homeostatic capacity of the body. We could not tolerate a 16x change in [Na+] because the high number of molecules that this comprises would have enormous osmotic effects, whereas the relatively low numbers of H+ ions mean that this is less of an issue.
What is the narrow normal range of the pH of blood that homeostatic mechanisms maintain? pH 7.35 - 7.45. This is a 1.25x difference.
What would the physiological conditions of arterial blood pH decreasing below 7.35 (to 7, 6.5 etc) and increase above 7.45 (to 8, 8.5 etc) be called? Acidosis and alkalosis.
Why is [H+] so important for protein function? H+ ions can bind to anions such as COO- on proteins. Proteins vary in their amino acid sequences and thus the number and types of anions, and this variation is usually crucial to the folding and the shape and therefore the function of proteins. The binding of H+ ions to protein anions, although loose, results in altered charge distribution of the protein, and changes its shape and ability to function. The enzymes involved in ATP production are particularly affected, as well as troponin in muscle contraction (an increase in pH increases cell excitability and results in cramps, a decrease in pH decreases cell excitability and results in coma and inactivity).
List some factors that cause pH in the body to change. CO2 concentration - although it is a weak acid, we produce a lot of it -, amino acid metabolism, phosphate and citrate ingestion, and lactate production.
How are volatile acids excreted from the body? These are low molecular weight and fairly reactive and can be excreted via the respiratory system, e.g. CO2.
How are non-volatile acids excreted? Non-volatile acids are usually of larger molecular weight and less reactive than volatile acids, and are excreted via the renal system rather than the respiratory system.
Which acid is produced by CO2 in the plasma? Carbonic acid.
What is the equation for the production of carbonic acid in the plasma and its ionic dissociation? CO2 + H2O -> H2CO3 -> HCO3- + H+
What is the typical daily load of volatile acids (primarily carbonic acid) that must be excreted? TYpically 15-20 mol/day, which is very large considering that [H+] is around 40nm, and this load is potentially ~1kg of carbonic acid.
What is the daily overall non-volatile acid load that the body must excrete? Typically ~70mM/day - pretty low compared to the volatile load of 15-20 mol/day.
Which two amino acids produce H2SO4 in their metabolism? Cysteine and methionine. It is produced in relatively small amounts but is a very strong acid.
Which three amino acids produce HCl in their metabolism? Lysine, arginine, and histidine.
Which two amino acids produce HCO3- in their metabolism? Aspartate and glutamate.
What are the three main systems that control pH in the body? The extracellular fluid/intracellular fluid buffers (in any aqueous compartment you'll find chemicals which buffer H+ effects to minimise the effect of any change that might occur); the renal system, and the respiratory system.
How do buffers minimise pH change? They exchange strong acids or bases for weak ones, which reduces their impact as they are less likely to dissociate than a strong acid or base.
Give the equation for HCl being buffered in the body. HCl + NAHCO3 -> H2CO3 + NaCl
Give the equation for NaOH being buffered in the body. NaOH + H2CO3 -> NaHCO3 + H2O
What is the most important extracellular fluid buffer? HCO3-
Why would HCO3- being rapidly acting mean that it has a finite buffering capacity? HCO3- is rapidly acting because it is always present in the body, and as such is one of the fast acting systems e.g. when producing H+ ions in exercise, but because it is always present, only a certain amount can be stored in the body so the store is finite.
What is mEq/L? This is the molecular equivalent of a substance per litre of water, which takes charge into account when considering molarity. If the ion is monovalent, mEq/L = mM, if the ion is bivalent, mEq/L = 2x mM.
What is the typical concentration of HCO3- in the blood? 24 mM - not particularly high but higher than the normal H+ concentration of 40nm.
What is the equation for the production of HCO3- ions? CO2 + H2O -> H2CO3 -> H+ + HCO3-
Which chemicals are the two prime determinants of blood pH? CO2 and HCO3-.
How will the below equation be affected by the addition of H+? H2O + CO2 -> H2CO3 -> H+ + HCO3- The equation will shift to the left and the H+ ion concentration will be reduced. The physiological response would be deep breathing, which increases CO2 loss and will also shift the equation to the left, further encouraging decrease in H+ ion concentration.
What is the Henderson-Hasselbalch equation for pH with regard to HCO3- and CO2? pH = 6.1 + log([HCO3-] / 0.03PCO2) ...where P = the partial pressure.
Based on the Henderson-Hasselbalch equation, calculate blood pH from standard HCO3-, and PCO2. pH = 6.1 + log ([HCO3-] / 0.03 PCO2) = 6.1 + log (24 / (0.03 x 40)) = 6.1 + log (20) =6.1 + 1.301 =7.401
With regard to the two main determinants of blood pH (CO2 and HCO3-), what kind of disorder might a change in each be indicative of? A change in PCO2 may be indicative of a respiratory acid-base disorder, whereas a change in [HCO3-] might be indicative of a metabolic acid-base disorder.
What constitutes the largest buffer, despite buffering not being their primary function? Proteins - although H+ ions binding to proteins can be problematic, it can also take them out of solution so that more pH sensitive proteins are protected.
What is a simple equation to show the protein buffering system? COO- + H+ -> COOH
What is the equation for the phosphate buffer system? Clue: it involves disodium hydrogen phosphate. Na2HPO4 + H+ -> NaH2PO4 + Na+
Give an example of a protein buffer that puts the shape change that results from H+ binding to good use. What is the equation for H+ binding? Haemoglobin releases oxygen in acid environments when H+ ions bind to it, for instance in areas of heavy muscle work where lactic acid is being produced and dissociating. HbO2 + H+ -> Reduced Hb + O2
Which is faster at acting on acid-balance balance: the respiratory system or the buffer system? The buffer system is faster and is one of the fastest systems in the body, but the respiratory system is fast-acting too, as it takes ~1 minute for blood to circulate the body.
The respiratory system removes CO2. Use an equation to show how hyperventilation reduces [H+]. CO2 + H2O <-> H2CO3 <-> HCO3- + H+ Hyperventilation reduces CO2 so the equation shifts to the left to compensate for this loss, using up H+ ions and thus reducing the [H+], tackling acidosis.
How does the respiratory system have an infinite capacity for acid-base balance? Because the environment/atmosphere is an infinite reservoir for our CO2 production.
Which is the slowest pH regulation system? The renal system.
How do the kidneys get rid of non-volatile acids? The tubules excrete H+ ions, as well as the anion it was originally bound to, for instance Na+ is bound to Cl- to form NaCl in order to get rid of it.
In urine, what are H+ ions buffered by? Ammonium and phosphate groups, which are waste products anyway, e.g. NH3 + H+ -> NH4+, which is less reactive than H+ alone.
Given that the respiratory system affects the CO2 end of the below equation, where does the renal system affect? CO2 + H2O <-> H2CO3 <-> HCO3- + H+ The HCO3- and H+ end.
Renal reabsorption of HCO3- is indirect unlike direct Na+ reabsorption. How does it occur? H+ ions are being secreted (via a Na+-H+ exchange transporter) and filtered into the tubule lumen, so they are re-associated with HCO3- in there. This reforms H2CO3 which can then dissociate into H2O and CO2. Carbonic anhydrase in the tubule lumen encourages the reaction in this direction. H2O and CO2 now diffuse readily back into the proximal tubule cells. Now, in the proximal tubule cell, carbonic anhydrase can combine these to form H2CO3 which dissociates to form H+ and HCO3-. The H+ is re-secreted via the Na+-H+ transporter in to the tubule lumen to retrieve further HCO3- ions, while the HCO3- ion diffuses passively back into the blood.
Why do the kidneys also produce new HCO3-? 70mmol of non-volatile acid production destroys some HCO3-, as well as other bases, so more must be produced in order to maintain the acid-base balance.
How do the kidneys also produce more HCO3-? In the renal tubule cells, carbonic anhydrase forms H2CO3 from H2O and CO2. This dissociates into H+ and HCO3-. The H+ is transported into the tubule lumen to associate with filtered HPO4^2-, which is then excreted as H2PO4-. The HCO3- is then free to passively diffuse across the tubule cell membrane into the blood - thus, 'new' HCO3- is reabsorbed.
Which two broad categories of acid-base disorder can be attributed to CO2? Respiratory acidosis and respiratory alkalosis.
Name two possible causes of respiratory acidosis. Drugs which depress breathing or emphysema which restricts breathing will both result in a reduced capacity to lose CO2 and an accumulation of CO2 in the blood.
Name two possible causes of respiratory alkalosis. Hyperventilation caused by anxiety/panic attack, or by high altitude. In both cases, the individual is trying to inspire more O2 but expiring too much CO2 simultaneously.
Name two broad categories of acid-balance base disorder that are not attributable to CO2. Metabolic acidosis and metabolic alkalosis.
Name a physiological and a pathological cause for metabolic acidosis. Physiology: exercise = accumulation of H+ ions from lactic acid production, which is not volatile. Diarrhoea results in HCO3- loss as the pancreas secretes an alkaline solution containing HCO3- ions in order to neutralise stomach acid in chyme, but diarrhoea prevents reabsorption of HCO3- ions due to increased gut motility, leading to acidosis.
Name a pathological cause of metabolic alkalosis. Emesis - normally HCl is reabsorbed by the gastric and intestinal lining, but when an individual is vomiting, this cannot occur, and HCl is lost, resulting in metabolic alkalosis.
What is the ratio of H2CO3:HCO3- before the onset of acidosis? 1:20
What is the ratio of H2CO3:HCO3- in respiratory acidosis? 2:20
How does the body compensate for the 2:20 ratio of H2CO3:HCO3- in acidosis? The kidneys must reabsorb HCO3- to re-establish the 1:20 ratio, so the kidneys conserve HCO3- ions and excrete H+ ions in urine, generating acidic urine. However, this does not eliminate the conservation of H2CO3, so a 2:30 ratio is produced instead - not ideal, just compensated.
What is the clinical therapy for acidosis to restore the H2CO3:HCO3- ratio? To restore the metabolic balance, a lactate-containing solution is delivered, which is converted to bicarbonate ions by the liver, restoring a 2:20 H2CO3:HCO3- ratio. This is not the 1:20 ideal ratio, but in conditions such as emphysema, removing the accumulation of H2CO3 is difficult, so eliminating the acidic urine and body's efforts to compensate and produce more HCO3- ions is therapy enough.
What are the primary pH, PCO2, and HCO3- changes in respiratory acidosis? pH - decreases. PCO2 - increases. HCO3- - no change.
What is the ratio of H2CO3:HCO3- in respiratory alkalosis? 0.5:20
How does the body compensate for the altered H2CO3:HCO3- ratio in respiratory alkalosis? The kidneys conserve H+ ions and excrete HCO3- ions, producing alkaline urine. This produces a H2CO3:HCO3- ratio of 0.5:15.
What clinical therapy is given to correct the H2CO3:HCO3- ratio in respiratory alkalosis? A Cl- containing solution is administered to the individual so that HCO3- ions are replaced by Cl- ions. This creates a H2CO3:HCO3- ratio of 0.5:10, the same as the healthy ratio of 1:20, but the pH is corrected by the Cl- ions.
What are the primary changes in pH, pCO2 and [HCO3-] in respiratory alkalosis? pH increasees, pCO2 decreases, and there is no change in HCO3-.
What is there excess presence of in metabolic acidosis? Ketones, chloride, or organic acid ions.
What is the ratio of H2CO3:HCO3- in metabolic acidosis? 1:10
How does the body compensate for metabolic acidosis to normalise the altered ratio of H2CO3:HCO3-? Ventilation becomes hyperactive so that more CO2 can be expired, and the kidneys conserve HCO3- while excreting H+ ions, creating acidic urine.
What is the clinical treatment for metabolic acidosis? A solution containing lactate is administered to the individual. Lactate is broken down into bicarbonate ions in the liver, restoring the 1:20 H2CO3:HCO3- ratio.
What are the primary changes in pH, pCO2 and HCO3- in metabolic acidosis? pH decreases, there is no change to pCO2, and HCO3- decreases.
Why might [HCO3-] change in metabolic alkalosis? As a result of excess Cl- ions, or increased ingestion of sodium bicarbonate.
What is the ratio of H2CO3:HCO3- in metabolic alkalosis? 1:40
How does the body compensate for metabolic alkalosis? Breathing is suppressed to reduce CO2 excretion and increase carbonic acid concentration in the blood, and the kidneys conserve H+ ions and excrete HCO3- in alkaline urine.
What is the clinical treatment for metabolic alkalosis? A Cl- ion containing solution returns the H2CO3:HCO3- ratio to 1:20 by replacing HCO3- ions.
What are the primary changes in pH, pCO2, and [HCO3-] in metabolic alkalosis? pH increases, there is no change in pCO2, and [HCO3-] increases.
No other physiological stress produces as much acid as... ...exercise.
A brisk walk increases the body's volatile acid load by how many times? 4x. However, the [H+] is not detectably changed and increased CO2 is expired to compensate.
Can you maintain the same level of acid-base balance in higher intensity exercise that you can in lower intensity exercise? No, the increase in [H+] is too great and too rapid for the three systems involved.
Why do furry animals tend to go into respiratory alkalosis during exercise? They cannot sweat as they do not have sweat glands, so they tend to lose heat by expiring water vapour. Their increased ventilation is not regulating [H+], so they expire too much CO2 and tend to go into respiratory alkalosis.
Why do humans tend to go into metabolic acidosis when exercising and thermoregulating, rather than respiratory alkalosis like furry animals do? Humans lose heat via sweat, unlike furry animals, so increased ventilation does regulate [H+], unlike in furry animals. As a result, we do not hyperventilate in order to lose heat, and so we tend to be in a controlled metabolic acidosis as we are controlling the level of exercise that we do.
Which is higher during exercise: volatile or non-volatile acid load? Despite large amounts of CO2 being produced, the non-volatile acid load is much higher, and of this around 95% is lactic acid.
How much of the lactic acid produced during exercise dissociates into H+ and lactate at cell pH? 99%
Why is lactic acid produced in exercise? There is a decrease in oxidative phosphorylation in exercise, and an increase in anaerobic respiration. NAD+ is required for glycolysis to produce ATP, but this reduces it to NADH + H+, and O2 is not available in sufficient amounts to oxidise NADH to NAD+. Instead, the conversion of pyruvic acid to lactic acid is used to regenerate NAD+, increasing the concentration of lactic acid.
Detectable changes in lactic acid concentration occur above the anaerobic threshold. What is the anaerobic threshold? It varies according to fitness, but it is usually ~50-60% of a person's VO2max.
With the appearance of lactic acid above the anaerobic threshold, one cannot maintain both pH and pCO2. How might one regulate pH or pCO2? pH may be regulated via hypocapnia (reducing CO2 to make room for the lactate), which leads to chemoreceptor inhibition, decreasing the respiratory drive. However, pCO2 is a potent stimulator of ventilation, so losing CO2 means less stimulation for the respiratory drive, which isn't much good. To regulate pCO2, acidosis leads to stimulation of chemoreceptors which increases the respiratory drive (as H+ acts on the respiratory centre), so ventilation is maintained.
Just above the anaerobic threshold, lactic acid (La) is buffered by HCO3-. What is the equation for this? H+La+ + K+HCO3- <-> H2O + CO2 + K+La+ The strong acid (lactic acid) is exchanged for a weak one (CO2 -> carbonic acid) but CO2 is produced and HCO3- is consumed.
Lactic acid is buffered by HCO3-, producing CO2. This CO2 is expired by the lungs, so isocapnic buffering is achieved. What is the result of the decrease in HCO3-? A shift from respiratory to metabolic acidosis.
At higher workrates, acidosis triggers respiratory compensation. How does this lead to exhaustion if exercise continues? Respiratory compensation leads to decreased pCO2 as more CO2 is exhaled to reduce the acid load in the body. But continued lactic acid production from continued exercise results in a decreased blood pH, which consumes HCO3- (finite), leading to metabolic acidosis. Both the lack of oxidative phosphorylation and the increased H+ ions damaging ATP-producing enzymes affect energy-producing pathways, resulting in exhaustion.
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