Acid-Base Balance Dr Taha Sadig Ahmed. At the end of the acid-base balance course, the students should be able to: 1.understand the need for precise regulation.

Acid-BaseBalanceDr Taha Sadig Ahmed

At the end of the acid-base balance course, the students should be able to:

1. understand the need for precise regulation of hydrogen ion concentration

2. relate temporal changes in hydrogen ion concentration with three defense systems, body fluids, lungs and kidney

3. define a buffer system

4. relate the bicarbonate buffer system and [CO2] to pH

5. identify the lungs in control of [CO2]

6. relate the long term changes in hydrogen ion

concentration with the kidney

7.differentiate between normal and abnormal pH

8.identify clinical causes of acid-base disturbances

9. identify the characteristics of primary acid-base

disturbances

About 80 mEq of H+ ions are ingested daily or produced by

mtabolic processes ; and without buffering, these would produce

large changes in body fluid [H+] shifting blood to the acidic

side .

Therefore , to prevent pathological changes , body systems

should strive to maintain hydrogen ion homeostasis ( keeping [H+]

nearly within controlled limits ) =7.35-7.45

And resist this natural tendency to produce acidosis

Why is H+ homeostasis important ? Because all enzymes are

affected by the [H+], which affects almost all body functions.

That is why , the blood [H+] is kept in a tight range around the

normal concentration of 0.00004 mEq/liter = 0.00004 mmol/liter.

pH (power of hydrogen)As the [H+] is very small, the term pH is used for practical purposes . pH is the negative logarithm of hydrogen ion concentration (– log [H+] ) expressed in eq/liter.

pH = log 1 = – log [H+] [H+]

Normal pH = – log [0.00000004] = 7.4

pH 7 is neutral, above 7 is alkaline and below is

acidic.

7.4 is the pH for arterial blood.

Venous blood pH is 7.35, because in venous

blood there is more CO2 to make carbonic acid.

If the pH falls below 7.4, the person is in

acidosis, while if more than 7.4, alkalosis.

However, the limits of pH that a

person can live more than a few hours

are 6.8 – 8.0 (10 – 160 nEq/liter).

When disturbances result from a

primary change in ECF [HCO3-], they are

called metabolic disorders.

Decreases in [HCO3-] are called metabolic

acidosis, while conversely , increase in [HCO3-]

metabolic alkalosis.

An increase in PCO2 is called respiratory

acidosis and a decrease PCO2 a respiratory

alkalosis.

(Paco2 is arterial Pco2)

Acidosis occurs when the HCO3-:PCO2 ratio falls,

if HCO3- falls; then metabolic.

• About 80 mEq of H+ ions are made or ingested daily, and

without buffering, these would produce large changes in body

fluid [H+].

•These 3 systems work on differing time scales

•(1) Blood & body fluid buffers can immediately bind to

excess acid or base . react in a fraction of a second and tie

up acids or bases until a balance can be made.

•(2) Lungs control removal of CO2 .act within a few minutes.

•These two lines of defense ( blood buffer & lung ) are

relatively short-term and keep the [H+] close to normal

until the kidneys can remove excess acid or base.

(3) Kidneys can secrete acid or alkaline urine

although relatively slow ( if compared to blood buffers &

lung ) taking hours to days they are the most powerful

of the 3 systems.

Body fluid ( & Blood ) buffersThe definition of a buffer is any substance that can reversibly bind H+ ions.

Buffer + H+ H Buffer ( 2 way road)

H buffer is now a weak acid ( why called acid? Because it has Hbound to it ) , which can remain as it is, or dissociate back.

If [H+] is high the reaction moves to the right, so that the buffers takes up & consumes the excess H+

Buffer + H+ H Buffer

Conversely, if [H+] is low, H+ is released from buffer H Buffer Buffer + H+

Therefore, buffers decrease changes in [H+].

Excess

Bicarbonate Buffer System

Quantitatively, this is by far the most important buffering

system. It consists of a weak acid (H2CO3) and a salt (NaHCO3).

H2CO3 is made by: H2O + CO2 H2CO3

H2CO3 weakly ionizes to HCO3- + H+. The bicarbonate salt in

the ECF completely ionizes to form HCO3- & Na+.

Putting both together we have:

H2O + CO2 H2CO3 H+ + HCO3-

H2CO3 weakly ionizes to HCO3- + H+.

CA=carbonic anhydrase enzyme is the catalyst for this reaction ; & without CA this reaction is very slow .

H2O + CO2 H2CO3 H+ + HCO3-

+ Na+

Bicarbonate Buffer System

Quantitatively, this is by far the most important buffering

system. It consists of a weak acid (H2CO3) and a salt (NaHCO3).

H2CO3 is made by: H2O + CO2 H2CO3

H2CO3 weakly ionizes to HCO3- + H+. The bicarbonate salt in

the ECF completely ionizes to form HCO3- & Na+.

Putting both together we have:

H2O + CO2 H2CO3 H+ + HCO3-

H2CO3 weakly ionizes to HCO3- + H+.

CA=carbonic anhydrase enzyme is the catalyst for this reaction ; & without CA this reaction is very slow .

CA enzyme is found in (1) RBCs, (2) alveoli & (3) renal tubular cells .

Due to the weak dissociation of H2CO3, [H+] is low .

•However, when HCl ( strong acid) is added, to the

bicarbonate solution, then the increased [H+] from

HCl are buffered by HCO3-.

H+ + HCO3- H2CO3 H2O + CO2

More H2CO3 is formed, and then H2O & CO2 are made.

From a strong acid, a weak acid is made which dissociates and is lost

as water and CO2 which is blown off.

•The opposite takes place if a strong alkali is added, like NaOH.

NaOH + H2CO3 NaHCO3 + H2O

In this situation, the strong base (NaOH) is replaced by a weak

base (NaHCO3). Also the [H2CO3] falls as it is combining with

NaOH. This results in more H2O & CO2 being used to replace the H2CO3:

H2O + CO2 H2CO3 H+ + HCO3-

+ + NaOH Na+

•Therefore, CO2 would decrease, but this inhibits respiration,

so less is expired. The increase in HCO3- is removed by the

kidneys.

Phosphate Buffer systemThis is important as an intracellular and renal tubular

fluid buffer. The components of this system are H2PO4-

and HPO42-.

HCl + Na2HPO4 NaH2PO4 + NaCl

Therefore, a strong acid, HCl, is replaced by a weak

acid, NaH2PO4, so the decrease in pH is minimized.

Protein buffer system•These are found in high concentrations inside cells. Intracellular pH does change when extracellular pH changes.

• H+ & HCO3- are not very permeable through the

membrane, though CO2 is highly permeable. In the

RBCs, hemoglobin is also a buffer.

H+ + Hb HHb

Of the total buffering capacity of body fluids, 60 – 70 %

is in the cells, but as the permeability of H+ & HCO3- are

poor, it delays the effectiveness of these intra-cellular proteins to buffer acid-base disturbances in the ECF

Respiratory effects in acid-base balance

If there is an increase in the ECF PCO2, by decreased

ventilation or increased metabolism, pH falls, and vice versa.

Therefore, by changing the PCO2, the lungs can regulate

the [H+] in the ECF.

PCO2 in the ECF is about 40 mm Hg (1.2 mol/liter).

The [H+] also affects alveolar ventilation, where a low pH can increase the rate 4-5 times, and a high pH can decrease the rate. Therefore, the respiratory system acts as a negative feedback controller of [H+], either being stimulated or depressed:

[H+] Alveolar ventilation

-ve PCO2

The efficiency of the respiratory control system is not 100 %, so if [H+] increased from pH 7.4 to 7.0, the lungs can return this value to 7.2 – 7.3 in 3-12 minutes.

Renal control systemThe kidneys can secrete either acidic or basic urine, to alter ECF pH. The overall mechanism is that the kidneys continuously filter a large number of HCO3

- ions into

the tubules. If they are excreted into the urine, this removes base from the blood. Many H+ ions are secreted into the lumen, thus removing acid from the blood. If more H+ ions are secreted than HCO3

- ions filtered, then ECF will have a

net loss of acid, and vice versa. Each day, the body makes about 80 mEq of non-volatile acids from protein metabolism.

Non-volatileacids , unlike H2CO3, cannot be excreted

by the lungs, only by the kidneys.

Also the kidneys must prevent loss of HCO3- in the

urine. 4320 mEq of HCO3- is filtered daily (24mEq/liter x

180 liters/day), and almost all is reabsorbed.

The filtered HCO3- ion has to combine with a secreted

H+ ion to make H2CO3 before it can be reabsorbed.

Therefore 4320 mEq of secreted H+ ions are needed only for bicarbonate reabsorption.

•Then non-volatile acids add 80 mEq, for a total of 4400 mEq of H+ ions secreted into the tubular fluid daily.

•If there is an alkalosis in the body, the kidneys will not reabsorb all the bicarbonate, and the loss of one HCO3

-

ion is similar to adding one H+ ion to the ECF.

Therefore, the kidneys regulate ECF [H+] in 3 ways (all are done through the same mechanism):1. secretion of H+ ions2. reabsorption of filtered bicarbonate ions3. production of new bicarbonate ions

H+ ion secretion & HCO3- ion reabsorption by

renal tubules

H+ secretion and HCO3- reabsorption occur along the

whole tubule, except the descending and ascending

thin limbs of the loop of Henle.

80 – 90 % of HCO3- reabsorption and H+ secretion

takes place in the proximal tubule, the rest in the thick

ascending limb of the loop of Henle, distal tubule and

collecting duct.

Hydrogen ion secretion

Epithelial cells of the proximal tubule, thick ascending limb of the loop of Henle and distal tubule secrete H+ by Na+/H+ counter-transport.

This is secondary active transport, where the energy is derived from Na+ going down its electro-chemical gradient, helped by the Na+/K+ ATPase pump on the basolateral membrane.

More than 90 % of HCO3- is reabsorbed this way, requiring

3900 mEq of H+ to be secreted daily.

H+ inside the cell is made from H2O and CO2, making H2CO3

using carbonic anhydrase

The HCO3- ion made in the cell goes down its concentration

gradient onto the renal interstitial fluid and into the capillary blood. Therefore, the net effect is that for every H+ ion secreted

into the tubular lumen, one HCO3- ion enters the blood.

The HCO3- ion made in the cell goes down its

concentration gradient onto the renal interstitial fluid and into the capillary blood. Therefore, the net effect is that for every H+ ion secreted into the tubular lumen, one HCO3

- ion

enters the blood.

Bicarbonate ion reabsorption

HCO3- ions have low membrane permeability on the luminal

side of renal tubular cells, and cannot be directly reabsorbed.

Therefore, they combine with H+ to form H2CO3, which

dissociates to CO2 and H2O. The CO2 easily moves across the tubular membrane and in

the cell it combines with H2O, with the help of carbonic

anhydrase, to make H2CO3.

This again dissociates in the cell to H+ & HCO3-. The HCO3

-

ion diffuses through the basolateral membrane to the capillary blood.

Therefore, the reabsorption of HCO3- ions occurs, though

these ions are not the same ones that were filtered into the tubules.

As mentioned, the rate of H+ ions secreted into the

tubular fluid is 4400 mEq/day, and the rate of HCO3- ion

filtration is 4320 mEq/day.

The amounts of these two ions entering the tubules are almost equal, therefore, it is said that these ions titrate each other.

The titration is not exact, as the non-volatile acids have to be removed.

In metabolic alkalosis, there are more HCO3- than H+ ions

in the urine, so the HCO3- cannot be reabsorbed and are

excreted.

In acidosis, the opposite is true, where HCO3- ions are

reabsorbed, and excess H+ ions are lost in the urine.

Here they are buffered by phosphate and ammonia and are excreted as salts.

Active secretion of H+ ions in late distal tubules &

collecting ducts

From the late distal tubules onwards, the tubular

epithelia secrete H+ ions by H+ ATPase, which lies on the

luminal membrane.

This is different from the mechanism in the proximal

tubule and the loop of Henle. This primary active

transport occurs in specialized cells called intercalated

cells. Although the late distal tubule and collecting duct

only make up 5 % of the total H+ ions secreted,

the [H+] can be concentrated here up to 900 fold. In

comparison, the proximal tubule can only concentrate the

[H+] 3 or 4 fold. The minimum pH secreted from the

kidneys can be 4.5.

Excess H+ ions combine with phosphate & ammonia,

making new bicarbonate

When H+ ions are secreted in excess of HCO3- ions

filtered, only some H+ ions can be in the ionic form, as pH

4.5 (0.03 mEq/liter) is the lower limit of urine.

Therefore, for each liter of urine, only 0.03 mEq of H+

ions can be secreted. But, a minimum of 80 mEq of non

volatile acids have to be secreted daily.

So, 2, 666.6 l of urine would have to be excreted daily if

H+ ions were free.

This is done by combining the H+ ions with phosphate

and ammonia buffers.

The phosphate buffer system is made of HPO42- and

H2PO4-.

They have poor reabsorption, and are concentrated in the tubular fluid. H+ ions enter the tubule by H+/Na+ counter transporter and combine with HCO3

- ions.

But if all HCO3- ions are reabsorbed, then H+ ions bind to

HPO42-, to finally make a sodium salt, carrying excess

hydrogen (NaH2PO4).

One major difference here is that the HCO3- ion made in the

tubular cell and which enters the capillary blood causes a net gain in HCO3

- ions by the blood.

When H+ ions are buffered by HCO3- ions then that HCO3

-

ion represents only a replacement of the ion reabsorbed. So whenever a H+ ion is buffered by a buffer other than bicarbonate, a new HCO3

- is added to the blood. Only a small

amount of phosphate is available for buffering …

Ammonia (NH3) buffer system

Quantitatively, NH3 and ammonium ion (NH4+) is an

important buffer. The ion is made from glutamine and for each molecule metabolized, 2 new HCO3

- ions are made

which are reabsorbed by the blood. A decrease in ECF pH stimulates glutamine metabolism, and more NH4

+ and

HCO3- ions and vice versa.

Regulation of tubular H+ ion secretion

In alkalosis, the kidneys must reduce H+ ion

secretion, so less HCO3- ions will be reabsorbed, and

vice versa for acidosis, except here more H+ ions

which get buffered with ammonia will make new

HCO3- ions.

In acidosis, 2 stimuli are needed for increasing

tubular H+ ion secretion:

1. increased PCO2 in the ECF, causing increased PCO2 in

the tubular cells, which increase [H+] and therefore

H+ ion secretion

2. decreased pH (or increased [H+]) in the ECF,

causing the same as above

In alkalosis, the opposite occurs. Whether acidosis

is due to metabolic or respiratory reasons, the

kidneys reabsorb all the HCO3- ions, and make new

HCO3- ions by titration of NH4

+.

In metabolic acidosis, there is primarily a

decrease in filtration of HCO3- ions, while in

respiratory acidosis, there is excess H+ ion secretion

due to increased PCO2 in the ECF.

Compensatory mechanisms

In respiratory acidosis, there is a compensatory

response to increase plasma HCO3- ions by making

new HCO3- in the kidney.

In metabolic acidosis, the response is an increase in ventilation, and renal compensation to make new HCO3

- in the kidney.

In respiratory alkalosis, the response to the primary reduction in PCO2 is to increase renal

excretion of HCO3- ions.

In metabolic alkalosis, the response is a decrease

in ventilation, which increases PCO2 and also an

increased renal excretion of HCO3- ions.

Respiratory Adjustments

Metabolic Acidosis

Metabolic Alkalosis

Respiratory Rate Tidal Volume Ventilation Rate of CO2 removal Rate of H2CO3

formation

Rate of H+ generation from CO2

Renal Adjustments

Respiratory Acidosis

Respiratory Alkalosis

HCO3-

reabsorption

H+ secretion

Ammonia synthesis

Factors causing respiratory acidosis:(1) respiratory center damage

(2) obstructive airways diseases (asthma, COPD),

pneumonia, fibrosis

Factors causing respiratory alkalosis:(1) Hyperventilation ( of any cause )

(2) acute stay at high altitude

Factors causing Metabolic Acidosis Diabetic keto-acidosis ( fats converted to acetoacetic and

keto acids)

Renal failure (reduced GFR reduces ammonium &

phosphate excretion)

Severe diarrhea (loss of NaHCO3)

ingesting/infusing acids

lactic acidosis

Factors causing Metabolic Alkalosis

Hyperaldosteronism (Na+ is reabsorbed in

exchange with H+ ions)

vomiting

overdose of antacids used in gastric/peptic ulcers

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