RENAL

LECTURE 12

Acid-Base Regulation
 Acids and Bases-Their Definitions and Meanings

Acids
• Molecules containing hydrogen atoms that can release hydrogen ions in solutions are referred to
as acids.
• i.e. any substance that adds H+ to a solution.

Examples:
• Hydrochloric acid (HCl), which ionizes in water to form hydrogen ions (H+) and chloride ions (Cl-)
• Carbonic acid (H2CO3) ionizes in water to form H+ and bicarbonate ions HCO3-
 Acid-Base Regulation

• Regulation of hydrogen ion (H+) is essential in order to achieve homeostasis.

• The kidneys play a key role in regulating H+ removal from the body.

• Also multiple acid-base buffering mechanisms involving the blood, cells, and lungs that are
essential in maintaining normal H+ concentrations in both the ECF and ICF.
 Acids and Bases-Their Definitions and Meanings
Bases
• A base is an ion or a molecule that can accept an H+
• i.e. any substance that removes H+ from solution.

Examples:
• HCO3- is a base because it can combine with H+ to form H2CO3
• Body proteins function as bases as some of their amino acids have a nett negative charge and
take up H+

• Alkalosis refers to excess removal of H+ from the body fluids

• Acidosis is the excess addition of H+ to body fluids
pH and H+ Concentration of Body Fluids
Regulation of pH (Acid-Base Balance)
 Regulation of pH (Acid-Base Balance)

• Regulation of acid-base balance involves regulation of [H+] in the body fluids

pH
↑
input [ H+ ] output
Metabolic in body Urine - kidneys
production fluids Respiratory removal of CO 2
of acids ↓

buffers
 Regulation of pH of Body Fluids

• Regulation of acid-base balance involves the regulation of [H +] in body fluids. More acids than
base are produced during metabolism and homeostatic mechanisms for pH control are concerned
with acid disposal.
• Body fluid pH regulated within a very narrow range of between 7.35 and 7.4.
• Acidosis or alkalosis occurs if pH falls out of this range and can lead to death. (pH 6.8 and 8).
• Carbonic acid formation – main source of H+ ions.
 Regulation of H+ concentration in the body fluids: Buffers,
Lungs, and Kidneys
Three primary systems regulate the H+ concentration in the body fluids to prevent acidosis or
alkalosis:

1. The chemical acid-base buffer systems of the body fluids, which immediately combine with acid
or base to prevent excessive changes in H+ concentration – quick acting, respond immediately.

2. The respiratory center, which regulates the removal of CO2 (and, therefore, H2CO3) from the
extracellular fluid. Respond within hours.

3. The kidneys, which can excrete either acid or alkaline into urine, filter acids and regulate HCO3-
in body fluids thereby readjusting the extracellular fluid H+ concentration toward normal during
acidosis or alkalosis. Slow response, within days, but most powerful.
1. Blood and Body Fluid Buffers

• Chemical buffering mechanism serves as a first line of defense against a change in pH.
• Extracellular and intracellular buffers instantly take up excess H+ when acids are liberated or
release H+ when bases (alkali) are liberated.
• Principal buffers in the blood are the bicarbonate/ carbonic acid (HCO3-/ H2CO3) buffer, the
phosphate (HPO4-/ H2PO4-) buffers, the erythrocyte haemoglobin buffer system and the plasma
proteins.
• In the ICF, the phosphate buffer system and intracellular proteins are most important.

• The bicarbonate carbonic acid buffer system is of special importance in the ECF because it is the
only buffer system whose components are regulated. The lungs regulate H2CO3 while the kidneys
regulate HCO3-. It is through this system that the final adjustment of the pH of body fluids takes
place and is also the main buffer used by the kidneys to buffer H+ ions secreted by the tubules.
2. Respiratory Control of Acid-Base Balance

• The respiratory system regulates pH by adjusting the concentration of H2CO3 in the body fluids.

• A fall in pH of the ECF stimulates hyperventilation which blows off much alveolar CO2, lowers
blood [H2CO3] and therefore raises pH towards normal.

• Conversely, a rise in pH above normal inhibits respiration and the resulting hypoventilation
causes CO2 retention, [H2CO3] rises and the pH drops towards normal.

• This is regarding a second line of defense of pH because it takes a few hours to take effect.
3. Renal Regulation of Acid-Base Balance

• The kidneys regulate extracellular fluid H+ concentration through three fundamental mechanisms:

(1) secretion of H+ → Acid

(2) reabsorption of filtered HCO3- → Base
(3) production of new HCO3-

Role of Kidneys
• During acidosis, acid is secreted and base retained or increased to increase pH.
• During alkalosis, base is excreted to decrease pH.

Other factors that increase H+ secretion include

• Hypokalemia
• Aldosterone
 Disturbances in Acid-Base Balance

• An increase in pH of the ECF above 7,45 is called alkalosis and a fall below 7,35 is known as
acidosis.

• Changes in pH may be due to respiratory disorders or they may be due to non-respiratory causes
referred to as metabolic disorders. When respiratory disorders alter pH, the kidneys try to
restore normal pH by a process called renal compensation.

• If the respiratory system is involved in restoring pH, it is called respiratory compensation.

 Simple Acid-Base Disorders

Respiratory Acidosis
• Arise from pulmonary hypoventilation due to emphysema, airway obstruction, injury to the
thoracic cage, neuromuscular disorders that affect the respiratory muscles and the depression of
the respiratory centre by certain drugs.

Responses
• Hypoventilation causes CO2 retention in the blood leading to a rise in Pco2 and increased H2CO3
and a fall in pH. High intracellular Pco2 causes increased renal secretion of H+ and increased HCO3-
generation and reabsorption. The final blood picture is a pH towards normal, and raised HCO 3-
 Simple Acid-Base Disorders

Respiratory Alkalosis
• Results from hyperventilation due to over-breathing or salicylate poisoning.

• Hyperventilation decreases arterial Pco2 and lowers [H2CO3] concentration in the ECF and a rise in
pH.

• The low intracellular Pco2 decreases H+ secretion and decreased HCO3- reabsorption by the
tubules leading to increased HCO3- loss in the urine. The final picture is low plasma [HCO3-] and a
lower pH.
 Simple Acid-Base Disorders

Metabolic Acidosis
• Metabolic acidosis is commonly due to accumulation of acids other than carbonic acid
• In diabetes mellitus there may be overproduction of keto acids or lactic acid (in shock), methanol
poisoning causes acidosis through forming formic acid, chronic renal failure leading to failure of
proximal tubules to reabsorbing HCO3- or an abnormal loss of HCO3- by the gut during severe
diarrhea.

Respiratory response:
• A ↓pH and ↑CO2 → stimulates hyperventilation and so more CO2 is blown off, decreasing Pco2

Renal response:
• Increased excretion of H+ → which will decrease urine pH
• Increased reabsorption of HCO3-