Chapter 9: Regulation of Hydrogen Ion Balance Flashcards Preview

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What value of protons in ECF is essential for proteins exposed to ECF to function properly?

It is essential for body to regulate the concentration of free protons in the ECF to a value close to 40nM (pH 7.4) in order for proteins exposed to the ECF to function properly

this regulation is acid-base balance
(matching excretion of acid/base equivalents to input and regulating ratio of weak acids to their conjugate bases in buffer systems)


Describe some routes for entry of acids or bases.

(1) processing of ingested food, (2) secretions of the gastrointestinal (GI) tract, and (3) de novo generation of acids
and bases from metabolism of stored fat and glycogen.


Acids and bases that enter the body must be excreted at the same rate to maintain
balance. There is often a lag between input and output, allowing a transient
accumulation of acid or base. What prevents large changes in pH when these transient accumulations occur?

buffer system

(=weak acid, its conjugate base, and free protons)


In a buffer system how is free aqueous concentration of protons determined?
Give equation.

by ratio of concentrations of conjugate base to weak acid

[H]= K [acid]/[base]
pH=pK + log [base/acid]

p 165


Describe how a system is different with/without buffers.

If we added strong
acid (eg, hydrochloric acid) to water that contained no buffers, the concentration of free protons would equal the concentration of the acid. If we had 10 mmol/L acid, we would have 10 mmol/L protons (ie, pH 2 blood). However, if the same
amount of acid is added to a buffer system, most of the protons combine with the conjugate base, resulting in only a small rise in concentration of free protons.


What are the important buffers in the ECF?

phosphate and albumin


What is the important buffer in RBC? Why?


important bc changes in plasma pH lead to uptake or release of protons from RBC


What is the most important buffer system in the body?

CO2-bicarbonate buffer system

their ratio is regulated
ratio of weak acid to conj base sets pH so this system regulates pH.


Describe CO2 as an acid.

CO2 is not a weak acid but it acts like a weak acid in the buffer system bc when it combines w water it releases protons.

CO2 is called a volatile acid bc it can evaporate
(all other acids; sulfuric, lactic...are fixed acids)


Would a change in PCO2 reflect a response to addition or loss of hydrogen ions? Why/why not?

no... change in PCO2 would reflect activity of respiratory system


If there is excess input of fixed acid, the body cannot convert this acid to CO2 and excrete
it through the lungs. Why?

every proton derived from a fixed acid that combines with bicarbonate to form CO2 removes that bicarbonate and lowers its concentration. Although the CO2 is simply exhaled, the deficit in bicarbonate
remains. A continuous input of fixed acid would soon reduce the bicarbonate concentration
to zero. Thus, an input of fixed acid must be balanced by renal output


What is the end result of sulfur-or phosphorus- containing amino acids and those with cationic side chains metabolized to CO2, water and urea?

end result is fixed acid

(metabolism of dietary protein)


Describe the fruit juice paradox.

metabolism of citrus fruit can alkalinize the blood

complete oxidation of the protonated form of an organic acid (citrus acid) to CO2 and water is acid-base neutral

but the complete oxidation of the base form adds bicarbonate to the body

One can think of this as taking a
hydrogen ion from the body fluids to protonate the base, converting it to the acid,
and then oxidizing the acid.
Before oxidation, the mixture is
acidic, but on complete oxidation to CO2 and water, the result is addition of base


When we generate bicarbonate and protons from CO2 and water in a given medium, say in blood or cell, is the result always acidification or alkalization?

Why? Where do bicarb and protons go from GI tract?

acidication bc concentration of protons rises

cells of the GI tract separate the protons from the bicarbonate. They transport protons out of the cell into one medium
(eg, the lumen of the GI tract), and bicarbonate into another (the interstitium bathing the basolateral surface). Therefore, the lumen becomes acidified and the surroundings (and therefore the blood leaving the tissue) becomes alkalinized (see
Figure 9–1 p 170

In other regions of the GI tract the cells reverse the direction of these processes, ie, they transport bicarbonate into the lumen (alkalinizing it) and protons
into the surroundings. Thus, different regions of the GI acidify and alkalinize the blood. Normally, the sum of GI tract secretions is nearly acid-base neutral


What does the anaerobic metabolism of carbohydrate produce?

When will the effects of this be greatest?

a fixed acid (lactic acid)

In conditions of poor tissue perfusion, this can be a
major acidifying factor


Describe renal processing of acids and bases in the proximal tubule and distal nephron.

early part (mostly PT) kidneys reabsorb enormous filtered load of bicarb from plasma

distal nephron (mostly collecting tubules) kidneys secrete either protons or bicarb to balance the net input into the body

proximal tubule: reabsorb most filtered bicarb (about 80%), produce and secrete ammoninum

TAL: reabsorb second largest fraction of filtered bicarb (normally about 10-15%)

distal convoluted tubule and collecting duct:

reabsorb virtually all remaining filtered bicarb as well as any secreted bicarb (type A intercalated cells)
produce titrable acid (type A intercalated cells)
secrete bicarb (type B intercalated cells)


What do type A and type B intercalated cells do?

reabsorb virtually all remaining filtered bicarb as well as any secreted bicarb (type A intercalated cells)

produce titrable acid (type A intercalated cells)

secrete bicarb (type B intercalated cells)


Describe how bicarb is reabsorbed.

enormous amount of H ion secretion occurs in PT with additional secretion in the TAL and collecting duct system

(collecting duct cells that secrete hydrogen ions are type A intercalated cells, not principal cells)


How does the process of H ion secretion achieve bicarbonate reabsorption?

once in the tubular lumen, the secreted H ion combines w a filtered bicarb to form water and carbon dioxide which diffuse into the cell

the CO2 and water that is now within the cell combines to form bicarbonate and hydrogen ion

Thus, no net change
in plasma bicarbonate concentration has occurred as all bicarbonate filtered has
combined with secreted hydrogen ion and subsequently ended up first inside the
cell and then in plasma.



What happens to the H ion secreted into the lumen (participating in bicarb reabsorption)? Is it excreted?

not excreted in the urine. It has been incorporated into water. Any secreted hydrogen ion that combines with bicarbonate in the lumen to cause bicarbonate
reabsorption does not contribute to the urinary excretion of hydrogen ions but
only to the conservation of bicarbonate.


How is H secreted into the lumen?

actively secreted by a N-H antiporter in the PT lumen

also a primary active H-ATPase exists in all the hydorgen-ion secreting distal tubular segments


What receptors are present in type A intercalated cells? What do they do?

type A intercalated cells of collecting-duct system...

in addition to their primary active H-ATPase, possess a primary active H-K-ATPase, which moves H ions into the lumen and K into the cell both actively

(the luminal
membrane H-K-ATPase also mediates active potassium reabsorption by these cells
and contributes to potassium homeostasis)


Describe the basolateral transporters for bicarb.

Cl-HCO3 antiporters or Na-HCO3 symporters -PT
(dep on tubular segment)

(both cases transport is passive bc HCO3 is moving down its conc. gradient.


Summarize the tubular segments in which bicarb is reabsorbed.

Through its secretion of hydrogen ions, the proximal tubule reabsorbs 80–90%
of the filtered bicarbonate. The thick ascending limb of Henle’s loop reabsorbs
another 10%, and almost all the remaining bicarbonate is normally reabsorbed by the distal convoluted tubule and collecting-duct system (except for alkalotic
individuals, who will excrete some of the bicarbonate;


How does the kidney balance input and output of bicarb.

excrete enough bicarb in urine to match input

1) allow some filtered bicarb to pass through urine
2) secrete bicarb via type B intercalated cells

type B intercalated cells (found only in cortical collecting duct) do secrete bicarb


Explain the disappearance of excess plasma bicarbonate and the appearance of bicarbonate in the urine, with resulting acidification of the plasma and
alkalinization of the urine and maintenance of bicarbonate balance.

H-ATPase pump is located in
the basolateral membrane, and the Cl-HCO3 antiporter is in the luminal membrane.
Accordingly, bicarbonate moves into the tubular lumen, whereas hydrogen ion is actively transported out of the cell across the basolateral membrane and enters the blood, where it can combine with a bicarbonate ion.


Summarize the process by which kidney replaces lost bicarb.

(Start in the cells with CO2 and water.)

Hydrogen ions and bicarbonate are produced from carbon dioxide and water within cells. Hydrogen ions are secreted and combine with the conjugate
base of buffers in the tubular lumen other than bicarbonate, thereby generating the
acid form of the buffer. The acid form of that buffer is excreted in the urine. The process of producing and secreting hydrogen ions generated new bicarbonate that goes into the blood and replaces the bicarbonate lost when the acid load entered the body. The key is generation of new bicarbonate to replace the bicarbonate that
was lost. If we just reabsorb filtered bicarbonate, nothing is changed. We must
generate new bicarbonate.


Identical transport process of hydrogen ion secretion
can also achieve acid excretion and addition of new bicarbonate to the blood. How can the same process produce these two different end results?

The answers lies in the fate of the hydrogen ion once it is in
the lumen. If the secreted hydrogen ion combines with bicarbonate, then we are
simply replacing bicarbonate that would have left the body. In contrast, if the secreted
hydrogen ion combines with a non-bicarbonate buffer in the lumen (or, to an extremely small degree, remains free in solution), the hydrogen ion is excreted.
The bicarbonate produced in the cell and transported across the basolateral membrane
is new bicarbonate, not a replacement for existing bicarbonate.

so renal contribution of a new bicarbonate to the blood is accompanied by the excretion of an equivalent amount of buffered H ion in the urine


What is the most important filtered buffer?

Most important synthesized buffer?

most important filtered buffer- phosphate

most important synthesized buffer- ammonia


Write the equation for monovalent dihydrogen phosphate.

H2PO4- H+ +HPO42-
(monovalent dihydrogen phosphate is a weak acid and divalent monohydrogen phosphate is its conjugate base)

at normal pH of plasma 7.4, of the glomerular filtrate, we find that about 80% of the phosphate is the base (divalent) form and 20% is the acid (monovalent) form