Lecture 54 – acid-base regulation

Question 1

Define pH

Answer 1

o pH is a measure of [H+] in aqueous solution
o pH = -log10[H+]
o or log10(1/[H+]
o increasing [H+] = decreased pH vice versa

Question 2

Henderson-Hasselbalch equation

Answer 2

pH = pKa + log10([conjugate base-]/[acid]

Question 3

henry’s law and the Henderson-Hasselbalch equation

Answer 3

o the ability of a gas to dissolve in solution is dependent on
 the partial pressure of the gas
 the solubility of the gas in the solution
o if a = the solubility (constant) of CO2 we can say
 [H2CO3]aq = aPaqCO2
 Then can sub into Henderson-Hasselbalch equation

Question 4

Defining an acid

Answer 4

o An acid is defined as an ionic molecule that dissociates to form hydrogen ions in solution
o Acids bind to conjugate base/bases (which are anions). On the pH scale for every 1 unit increase in pH there is a tenfold decrease in [H+].

Question 5

Dissociate constant Ka

Answer 5

o The dissociation constant (Ka) of an ionic molecule is the ratio of the concentration of the dissociated ions in solution ([cation]x[anion]) and the ionic molecule ([CA]).
o The pKa of a solution is the log₁₀1/Ka. Ionic dissociation is an equilibrium reaction. This is physiologically significant because it means that removing reactants from the solution results in a shift of the chemical reaction in favour of reactant (i.e. conjugate base) formation and a decrease in concentration of the product (i.e. cation and anion) in the solution.
o Thus for the bicarbonate reaction, removing CO2, a dissolved gas, from the solution, scavenges H+ ions and bicarbonate to form carbonic acid, increasing the pH of the solution.

Question 6

The 5 physiological buffers

Answer 6

o There are five major physiological buffers of pH in the body. The most important buffer system in extracellular space is the bicarbonate. HCO3- buffer (a gas) when dissolved in water will form hydrogen ions and bicarbonate.
o This reaction is catalysed by the enzyme carbonic anhydrase.
o Inside the cell there are two major physiological buffers hydrogen phosphate (also known as inorganic phosphate) and protons.
o Hydrogen ions are positively charged (they are cations) and are therefore able to displace other cations involved in ionic bonds. Ionic reactions in solution are equilibrium reactions, so excess cations in solution will drive formation of the ionic molecule.
o Bone is a major store of calcium/Ca/Ca2+ cations and phosphate anions. Low/low pH can lead to the formation of dihydrogen phosphate can calcium/Ca/Ca2+ release from bone. This could lead to osteoporosis.
o In plasma the major protein buffer is albumin, while inside the red blood cell haemoglobin/Hb is a major protein buffer

Question 7

Location of buffer systems in the body

Answer 7

o Intracellular fluid
 Phosphate and protein buffer systems
o Extracellular fluid
 Carbonic acid-bicarbonate and protein buffer systems

Question 8

Isohydric principle

Answer 8

o All the buffer systems in the body are linked
 Altering one = impact on all others
 By knowing what happens in the bicarbonate system in the body we can know what is happening in all systems
 Thus usually only assess the HCO3- system

Question 9

Basic forms of acids

Answer 9

o Volatile acids
o Fixed acids

Question 10

Volatile acids

Answer 10

o Can be converted to gas
o Eliminated by lungs
o Most prominent = CO2

Question 11

Fixed acids

Answer 11

o Non-volatile – cannot be made into a gas
o Eliminated via kidneys
o Normal metabolism of proteins and phospholipids results in generation of sulfuric acid

Question 12

Alterations in PaCO2 alter pH CSF

Answer 12

o Respiration is involved in the short-term control of pH in body
o Central chemoreceptors are sensitive to changes in pH
o Increased ventilation, decreased PaCO2, increased pH

Question 13

Ventilation control of pH

Answer 13

o Low pH = acidemia, high pCO2, low HCO3
o High pH = alkalemia, low PCO2, high HCO3

Question 14

Kidneys in long term regulation of pH

Answer 14

o Sixty five percent of water reabsorption takes place in the proximal convoluted tubules. This is driven by the placement of Na/K ATPase pumps on the basolateral membrane of the epithelial cells that line the PCT.
o Inside the epithelial call the carbonic anhydrase catalysed reaction results in CO2 and water forming hydrogen cation and bicarbonate anions.
o The strategic placement of H+ ATPase on the apical membrane of the PCT epithelial cells results in active secretion/pumping of hydrogen cations into the filtrate.
o More hydrogen cations are secreted into the filtrate as a result of secondary active transport via a Na/H antiport/exchanger.
o Strategic placement of bicarbonate/chloride exchangers and Na/HCO3 symporters on the basolateral membrane of the epithelial cells facilitates bicarbonate/HCO3-/HCO3 reabsorption.
o Finally, carbonic anhydrase attached to the microvilli along the apical membrane of the epithelial cells facilitates the formation of CO2 and water in the filtrate.

Question 15

Ammonia as a pH buffer

Answer 15

o Deamination of glutamine leads to the formation of ammonia
o Ammonia allows acid secretion without carbonic anhydrase
o Ammonium is a cation that cannot cross the apical membrane
o Deamination reactions take place in the epithelial cells of the proximal convoluted tubules

Question 16

Anion gap

Answer 16

o The anion gap is a measure of acid-base balance. Electroneutrality means that the sum of all cations in the body equals the sum of all anions in the body (this is intuitively obvious because any ionic molecule has a balance of charge).
o Anion gap is measured from plasma.
o The major cation in plasma is sodium/Na/Na+. Potassium is a minor cation in plasma.
o The major anions in plasma are bicarbonate/HCO3/HCO3- and chloride (Cl-).
o Any difference between the sum of cation and anions can be attributable to unknown cations or unknown anions.
o A large anion gap indicates a large amount of unknown anion and is most frequently an indication of metabolic acidosis.

Question 17

Acidosis

Answer 17

An increase in arterial Pco2 stimulates chemoreceptors that accelerate breathing cycles at the inspiratory centre. This change increases the respiratory rate, encourages CO2 loss at the lungs and decreases arterial Pco2

Question 18

Alkalosis

Answer 18

A decrease in arterial Pco2 inhibits these chemoreceptors. Without stimulation, the rate of respiration decreases, slowing the rate of CO2 loss at the lungs and increasing arterial Pco2.

Question 19

Tubular regulation of acid-base balance

Answer 19

o CO2 combines with water within the tubule cell, forming H2CO3
o H2CO3 is quickly split, forming H+ and bicarbonate ion (HCO3-)
o H+ is secreted into the filtrate
o For each H+ secreted, a HCO3- enters the peritubular capillary blood either via symport with Na+ or via antiport with Cl-
o Secreted H+ combines with HCO3- in the filtrate, forming carbonic acid. HCO3- disappears from the filtrate at the same rate that HCO3- enters the peritubular capillary blood
o The H2CO3 formed in the filtrate dissociates to release CO2 and H2O
o CO2 diffuses into the tubule cells, where it triggers further H+ secretion

Question 20

Acid secretion coupled with phosphate buffer

Answer 20

o CO2 combines with water within the type A intercalated cell, forming H2CO3
o H2CO3 is quickly split forming H+ bicarbonate ion
o H+ is secreted into the filtrate by a H+ ATPase pump
o For each H+ secreted a HCO3- enters the peritubular capillary blood via an antiport carrier in a HCO3-/Cl- exchange process
o Secreted H+ combines with HPO42- in the tubular filtrate forming H2PO4-
o The H2PO4- is excreted in the urine

Question 21

Amino acid metabolism: ammonia secretion PCT

Answer 21

o PCTY cell metabolises glutamine to NH4+ and HCO3-
o The weak acid, NH4+ is secreted into the filtrate, taking the place of H+ on a Na+/H+ antiport carrier
o For each NH4+ secreted, a bicarbonate ion (HCO3-) enters the peritubular capillary blood via a symport carrier
o The NH4+ is excreted in the urine