Acid-base chemistry

pKa

-Acid dissociation constants vary widely and often are small numbers. It is convenient to convert Ka to a logarithmic form, defining pKa -inversely proportional to acid strength

ammonia buffer system

-Another important but more complex buffer system that facilitates the excretion of H+ and generation of new HCO3- -Renal tubular cells are able to use the amino acid glutamine to synthesize ammonia (NH3) and secrete it into the tubular fluid -Hydrogen ions then combine with the ammonia NH3 to form ammonium ions (NH4+). -The ammonium ions (NH4+) combine with Cl- ions that are present in the tubular fluid to form ammonium chloride (NH4Cl), which is then excreted in the urine -Under normal conditions, the amount of H+ ion eliminated by the ammonia buffer system is about 50% of the acid excreted and generation of new bicarbonate HCO3- -However, with chronic acidosis, it can become the dominant mechanism for H+ excretion and new HCO3- generation

The hydrogen/bicarbonate exchange system regulates pH through the secretion of excess H+ and reabsorption of bicarbonate (HCO3- ) by the renal tubules

-Bicarbonate is freely filtered in the glomerulus and reabsorbed or reclaimed in the tubules -Each HCO3- that is reclaimed requires the secretion of a H+ ion, a process that is tightly coupled with sodium ( Na+ ) reabsorption

transcellular hydrogen/potassium exchange system provides another important system for regulation of acid-base balance

-Both H+ and potassium (K+ ) are positively charged, and both ions move freely between the ICF (intracellular fluid) and ECF (extracellular fluid) compartments -When excess H+ is present in the ECF, it moves into the ICF in exchange for K+, and when excess K+ is present in the ECF, it moves into the ICF in exchange for H+. -Thus, alterations in potassium levels can affect acid-base balance, and changes in acid-base balance can influence potassium levels

The pH of body fluids is regulated by three major mechanisms

-Chemical buffer systems in body fluids, which immediately combine with excess acids or bases to prevent large changes in pH. -The lungs, which control the elimination of CO2 -The kidneys, which eliminate H+ and both reabsorb and generate bicarbonate HCO3- .

Another mechanism that the kidney uses in controlling HCO3- loss is the chloride/bicarbonate anion exchange that occurs in association with Na+ reabsorption

-Chloride is absorbed along with sodium ion Na+ throughout the tubules -In situations of volume depletion due to vomiting, the kidney is forced to substitute HCO3- for the chloride anion (Cl- ) anion, thereby increasing its absorption of bicarbonate ion (HCO3-).

Carbon dioxide, which is the end product of aerobic metabolism, is transported in the circulation as a

-Dissolved gas -Bicarbonate (HCO3- ion) -CO2 bound to hemoglobin.

Bone represents an additional source of acid-base buffering

-Excess H+ ions can be exchanged for Na+ and K+ on the bone surface. -Dissolution of bone minerals with release of compounds (i.e. sodium bicarbonate (NaHCO3) and calcium carbonate (CaCO3)) into the ECF can be used for buffering excess acids -It has been estimated that as much as 40% of buffering of an acute acid load takes place in bone -The role of bone buffers is even greater in the presence of chronic acidosis -The consequences of bone buffering include demineralization of bone and predisposition to development of kidney stones due to increased urinary excretion of calcium -Persons with chronic kidney disease are at particular risk for reduction in bone calcium due to acid retention

The respiratory system provides for the elimination of CO2 into the air and plays a major role in acid-base regulation

-Increased pulmonary ventilation increases CO2 elimination, producing a decrease in arterial pCO2 -Decreased ventilation decreases CO2 elimination, producing an increase in arterial pCO2 -Chemoreceptors in the brain stem and the peripheral chemoreceptors in the carotid and aortic bodies sense changes in the pCO2 and pH of the blood and alter the ventilatory rate. -The respiratory control of pH is rapid, occurring within minutes, and is maximal within 12 to 24 hours -Although the respiratory response is rapid, it does not completely return the pH to normal and is only about 50% to 75% effective as a buffer system

Base excess or deficit is a measure of the bicarbonate HCO3- excess or deficit

-It describes the amount of a fixed acid or base that must be added to a blood sample to achieve a pH of 7.4 -A base excess indicates metabolic alkalosis, and a base deficit indicates metabolic acidosis

Proteins are the largest buffer system in the body

-Proteins are amphoteric, meaning that they can function either as acids or bases. -They contain many ionizable groups that can release or bind H+. -protein buffers are largely located within cells, and H+ ions and CO2 diffuse across cell membranes for buffering by intracellular proteins

in red blood cells the enzyme carbonic anhydrase (CA) catalyzes its conversion to carbonic acid (H2CO3).

-The (carbonic acid) H2CO3, in turn, dissociates into hydrogen (H+) and bicarbonate (HCO3-) ions -The H+ combines with hemoglobin and the bicarbonate anions (HCO3- ) diffuse into the plasma and participates in acid-base regulation

Laboratory tests are used to measure serum electrolytes, CO2 content, and bicarbonate HCO3-.

-These measurements are determined by adding a strong acid to a blood sample and measuring the amount of CO2 that is produced -More than 70% of the CO2 in the blood is in the form of bicarbonate. -The serum bicarbonate is then determined from the total CO2 content of the blood.

equilibrium constant (Ka)

-also called the ionization constant or acid dissociation constant -The higher the acid dissociation constant, the more an acid is ionized and the greater is its strength

the kidneys

-eliminate hydrogen ions (H+) combined with urinary buffers and anions in the urine -add new bicarbonate HCO3- to the extracellular fluid, to replace the HCO3- consumed in buffering strong acids

The concentration of hydrogen anion (H+ ) in the body fluids is ______ compared with other ions.

-low -ex. the sodium ion (Na+ ) is present at a concentration approximately 3.5 million times more than that of the H+. -Because it is cumbersome to work with such a small number, the H+ concentration is commonly expressed in terms of the pH.

pKb

-the negative base-10 logarithm of the base dissociation constant (Kb) of a solution -used to determine the strength of a base or alkaline solution pKb = -log10Kb -The lower the pKb value, the stronger the base!!

bicarbonate buffer system

-the principal ECF buffer -uses Carbonic acid (H2CO3) as its weak acid -uses a bicarbonate salt such as sodium bicarbonate (NaHCO3) as its weak base -replaces the weak carbonic acid (H2CO3 ) for a strong acid such as hydrochloric acid -replaces the weak bicarbonate base for a strong base such as sodium hydroxide -particularly efficient system because its components can be readily added or removed from the body -Metabolism provides an ample supply of CO2, which can replace any carbonic acid (H2CO3 ) that is lost when excess base is added, and CO2 can be readily eliminated when excess acid is added -the kidney can conserve or form new bicarbonate ion (HCO3- ) when excess acid is added, and it can excrete HCO3- when excess base is added

an acid with a low Ka is a

-weak acid -ex.acetic acid, lactic acid, carbonic acid, ammonium ion

The three major buffer systems that protect the pH of body fluids

1) The bicarbonate buffer system 2) The transcellular hydrogen-potassium exchange system. 3) The body proteins -Bone provides an additional buffering of body acids

pKw of water at 25 C

14

ECF pH

7.35-7.45

dissolved CO2 and bicarbonate (HCO3- ) account for approximately ____% of the CO2 that is transported in the extracellular fluid

77%

Arterial blood gases provide a means of assessing the respiratory component of acid-base balance

Arterial blood gases are used because venous blood gases are highly variable, depending on metabolic demands of the various tissues that empty into the vein from where the sample is being drawn

Body metabolism results in a continuous production of carbon dioxide (CO2).

As CO2 is formed during the metabolic process, it diffuses into the tissue spaces and then into the circulation

carbon dioxide measurements are commonly used when calculating pH

Because it is almost impossible to measure carbonic acid (H2CO3)

Both reabsorption of HCO3- and excretion of acid are accomplished through H+ secretion as the urine filtrate moves through the tubular structure of the kidney

The potassium/hydrogen exchange system in the collecting tubules functions in H+ secretion, by substituting the reabsorption of potassium (K+ ) for excretion of H+

The kidneys play a critical role in maintaining acid-base balance

They accomplish this through: -The reabsorption of bicarbonate (HCO3- ) -Regulation of H+ secretion -Generation of new HCO3- -cannot adjust the pH within minutes, as respiratory mechanisms can, but they continue to function for days until the pH has returned to normal or the near-normal range

Base

a compound that can accept or combine with H+ ex. bicarbonate ion (HCO3-) is a base because it can combine with H+ to form carbonic acid (H2CO3).

pH is inversely related to the H+ concentration

a low pH indicates a high concentration of H+ and a high pH a low concentration of H+

The major source of bases is the metabolism of

amino acids (aspartate and glutamate) and certain organic anions (e.g., citrate, lactate, acetate).

Laboratory tests that are used in assessing acid-base balance include

arterial blood gases and serum electrolytes, base excess or deficit, and anion gap

The movement of (bicarbonate) HCO3- into the plasma is made possible by a special transport system on the red blood cell membrane in which

bicarbonate (HCO3- ) ions are exchanged for chloride ions (Cl-)

The most important base is

bicarbonate ion HCO3- (weak base)

The remaining CO2 in the red blood cells combines with hemoglobin to form

carbaminohemoglobin (HbCO2) (this is a reversible reaction characterized by a loose bond, so that CO2 can be easily released in the alveolar capillaries and exhaled from the lung)

The most important acid is

carbonic acid (H2CO3) (a weak acid, derived from carbon dioxide (CO2)

The difference between the two types of acids arises because

carbonic acid (H2CO3) is in equilibrium with dissolved carbon dioxide (CO2 ), which is volatile and leaves the body by way of the lungs.

The reaction that generates carbonic acid (H2CO3 ) from CO2 and water is catalyzed by an enzyme called

carbonic anhydrase (present in large quantities in red blood cells, renal tubular cells, and other tissues in the body)

The moment - by - moment regulation of pH depends on

chemical buffer systems (These buffer systems are immediately available to combine with excess acids or bases and prevent large changes in pH from occurring during the time it takes for the respiratory and renal mechanisms to become effective)

what maintains the normal blood pH

chemical buffers, the respiratory system, and the kidneys

acid

compound that can dissociate and release a hydrogen ion (H+) ex. hydrochloric acid (HCl) dissociates in water to form Hydrogen (H+ ) and Chloride (Cl-) ions.

the respiratory system

disposes of carbon dioxide (CO2).

A milli equivalent or mEq is derived by

dividing the concentration in millimol or mmol by the valency of the ion involved.

The metabolism of dietary proteins and other substances results in the generation of nonvolatile acids and bases

ex. the metabolism of sulfur-containing amino acids (e.g.,methonine and cysteine) results in the production of sulfuric acid; of arginine and lysine, hydrochloric acid; and of nucleic acids, phosphoric acid

the metabolic activities of the body require precise regulation of acid-base balance as reflected in the pH of the

extracellular fluid (ECF)

strong acids are buffered in the body by chemical buffer bases such as

extracellular fluid (ECF) bicarbonate (HCO3-).

Elements in the same group of the periodic table

have the same valency

A strong acid has a

high Ka and a low pKa.

The valency of an element is related to

how many electrons are in the outer shell.

strong acids

hydrochloric acid (HCl), sulfuric acid (H2SO4), phosphoric acid (H3PO4), nitric acid (HNO3)

Incomplete oxidation of fats results in the production of

ketoacids

Incomplete oxidation of glucose results in the formation of

lactic acid

A weak acid has a

low Ka and a high pKa.

Milli equivalents and milli moles are units used to describe

molecular or ionic grades of concentration

membrane excitability, enzyme systems, and chemical reactions all depend on the

pH being regulated within a narrow physiologic range to function in an optimal way

pH represents the negative logarithm log10 of the H+ concentration expressed in (milli equivalent) mEq / liter, i.e. moles/liter

pH= -log[H+] concentration ex. If the H+ concentration is 0.0000001M, then: pH= -log[0.0000001] = -log [1 X 10 -7] = - (-7) = 7

On a mixed diet, pH is threatened by the production of strong acids (sulfuric, hydrochloric, and phosphoric) mainly as the result of

protein metabolism

Carbon dioxide in excess of that which can be carried in the plasma moves into the

red blood cells

Henderson-Hasselbalch equation

shows that the pH of a solution is determined by the pKa of the acid and the ratio of the concentrations of conjugate base to acid

Alkalosis

tends to decrease H+ elimination and increase K+ elimination, with a resultant decrease in serum potassium levels.

Acidosis

tends to increase H+ elimination and decrease K+ elimination, with a resultant increase in serum potassium levels

what contributes to the pH of the blood

the carbonic acid (H2CO3) formed from hydration of dissolved CO2

Although useful in determining whether acidosis or alkalosis is present, the pH measurements of the blood provide little information about

the cause of an acid-base disorder

Acids are continuously generated as by-products of metabolic processes

these acids fall into two groups: -Volatile (Carbonic Acid (H2CO3)) -Nonvolatile or fixed acids (e.g., sulfuric, hydrochloric, and phosphoric acid).

nonvolatile or fixed acids are not eliminated by the lungs

they are buffered by body proteins or extracellular buffers, such as bicarbonate (HCO3-) and then eliminated by the kidney

A small portion (about 10%) of the CO2 that is produced by body cells is transported in the dissolved state to

to the lungs and then exhaled

Albumin and plasma globulins are the major protein buffers in the

vascular compartment

Most of the body's acids and bases are

weak

Although CO2 is a gas and not an acid, a small percentage of the gas combines with water to form

weak carbonic (H2CO3 ) acid