Bicarbonate buffer system

The bicarbonate buffer system is an acid-base homeostatic mechanism involving the balance of carbonic acid (H2CO3), bicarbonate ion (HCO
3
), and carbon dioxide (CO2) in order to maintain pH in the blood and duodenum, among other tissues, to support proper metabolic function.[1] Catalyzed by carbonic anhydrase, carbon dioxide (CO2) reacts with water (H2O) to form carbonic acid (H2CO3), which in turn rapidly dissociates to form a bicarbonate ion (HCO
3
) and a hydrogen ion (H+) as shown in the following reaction:[2][3][4]

As with any buffer system, the pH is balanced by the presence of both a weak acid (for example, H2CO3) and its conjugate base (for example, HCO
3
) so that any excess acid or base introduced to the system is neutralized.

Failure of this system to function properly results in acid-base imbalance, such as acidemia (pH<7.35) and alkalemia (pH>7.45) in the blood.[5]

2325 Carbon Dioxide Transport
Carbon dioxide, a by-product of cellular respiration, is dissolved in the blood, where it is taken up by red blood cells and converted to carbonic acid by carbonic anhydrase. Most of the carbonic acid then dissociates to bicarbonate and hydrogen ions.

In systemic acid–base balance

In tissue, cellular respiration produces carbon dioxide as a waste product; as one of the primary roles of the cardiovascular system, most of this CO2 is rapidly removed from the tissues by its hydration to bicarbonate ion.[6] The bicarbonate ion present in the blood plasma is transported to the lungs, where it is dehydrated back into CO2 and released during exhalation. These hydration and dehydration conversions of CO2 and H2CO3, which are normally very slow, are facilitated by carbonic anhydrase in both the blood and duodenum.[7] While in the blood, bicarbonate ion serves to neutralize acid introduced to the blood through other metabolic processes (e.g. lactic acid, ketone bodies); likewise, any bases (e.g. urea from the catabolism of proteins) are neutralized by carbonic acid (H2CO3).[8]

Regulation

As calculated by the Henderson–Hasselbalch equation, in order to maintain a normal pH of 7.4 in the blood (whereby the pKa of carbonic acid is 6.1 at physiological temperature), a 20:1 bicarbonate to carbonic acid must constantly be maintained; this homeostasis is mainly mediated by pH sensors in the medulla oblongata of the brain and probably in the kidneys, linked via negative feedback loops to effectors in the respiratory and renal systems.[9] In the blood of most animals, the bicarbonate buffer system is coupled to the lungs via respiratory compensation, the process by which the rate of breathing changes to compensate for changes in the blood concentration of CO2.[10] By Le Chatelier's principle, the release of CO2 from the lungs pushes the reaction above to the left, causing carbonic anhydrase to form CO2 until all excess acid is removed. Bicarbonate concentration is also further regulated by renal compensation, the process by which the kidneys regulate the concentration of bicarbonate ions by secreting H+ ions into the urine while, at the same time, reabsorbing HCO
3
ions into the blood plasma, or vice versa, depending on whether the plasma pH is falling or rising, respectively.[11]

Henderson–Hasselbalch equation

A modified version of the Henderson–Hasselbalch equation can be used to relate the pH of blood to constituents of the bicarbonate buffer system:[12]

where:

When describing arterial blood gas, the Henderson–Hasselbalch equation is usually quoted in terms of pCO2, the partial pressure of carbon dioxide, rather than H2CO3. However, these quantities are related by the equation:[12]

where:

Taken together, the following equation can be used to relate the pH of blood to the concentration of bicarbonate and the partial pressure of carbon dioxide:[12]

where:

  • pH is the acidity in the blood
  • [HCO
    3
    ] is the concentration of bicarbonate in the blood, in mmol/L
  • pCO2 is the partial pressure of carbon dioxide in the blood, in mmHg

Derivation of the Kassirer–Bleich approximation

The Henderson–Hasselbalch equation, which is derived from the law of mass action, can be modified with respect to the bicarbonate buffer system to yield a simpler equation that provides a quick approximation of the H+ or HCO
3
concentration without the need to calculate logarithms:[7]

Since the partial pressure of carbon dioxide is much easier to obtain from measurement than carbonic acid, the Henry's law solubility constant – which relates the partial pressure of a gas to its solubility – for CO2 in plasma is used in lieu of the carbonic acid concentration. After rearranging the equation and applying Henry's law, the equation becomes:[13]

where K’ is the dissociation constant from the pKa of carbonic acid, 6.1, which is equal to 800nmol/L (since K’ = 10−pKa = 10−(6.1) ≈ 8.00X10−07mol/L = 800nmol/L).

By multiplying K’ (expressed as nmol/L) and 0.03 (800 X 0.03 = 24) and rearranging with respect to HCO
3
, the equation is simplified to:

In other tissues

The bicarbonate buffer system plays a vital role in other tissues as well. In the human stomach and duodenum, the bicarbonate buffer system serves to both neutralize gastric acid and stabilize the intracellular pH of epithelial cells via the secretion of bicarbonate ion into the gastric mucosa.[1] In patients with duodenal ulcers, Helicobacter pylori eradication can restore mucosal bicarbonate secretion, and reduce the risk of ulcer recurrence.[14]

References

  1. ^ a b Krieg, Brian J.; Taghavi, Seyed Mohammad; Amidon, Gordon L.; Amidon, Gregory E. (2014-11-01). "In Vivo Predictive Dissolution: Transport Analysis of the CO2, Bicarbonate In Vivo Buffer System". Journal of Pharmaceutical Sciences. 103 (11): 3473–3490. doi:10.1002/jps.24108. ISSN 1520-6017. PMID 25212721.
  2. ^ Oxtoby, David W.; Gillis, Pat (2015). "Acid-base equilibria". Principles of Modern Chemistry (8 ed.). Boston, MA: Cengage Learning. pp. 611–753. ISBN 978-1305079113.
  3. ^ Widmaier, Eric; Raff, Hershel; Strang, Kevin (2014). "The kidneys and regulation of water and inorganic ions". Vander's Human Physiology (13 ed.). New York, NY: McGraw-Hill. pp. 446–489. ISBN 978-0073378305.
  4. ^ Meldrum, N. U.; Roughton, F. J. W. (1933-12-05). "Carbonic anhydrase. Its preparation and properties". The Journal of Physiology. 80 (2): 113–142. doi:10.1113/jphysiol.1933.sp003077. ISSN 0022-3751. PMC 1394121. PMID 16994489.
  5. ^ Rhoades, Rodney A.; Bell, David R. (2012). Medical physiology : principles for clinical medicine (4th ed., International ed.). Philadelphia, Pa.: Lippincott Williams & Wilkins. ISBN 9781451110395.
  6. ^ al.], David Sadava ... [et; Bell, David R. (2014). Life : The Science of Biology (10th ed.). Sunderland, MA: Sinauer Associates. ISBN 9781429298643.
  7. ^ a b Bear, R. A.; Dyck, R. F. (1979-01-20). "Clinical approach to the diagnosis of acid-base disorders". Canadian Medical Association Journal. 120 (2): 173–182. ISSN 0008-4409. PMC 1818841. PMID 761145.
  8. ^ Nelson, David L.; Cox, Michael M.; Lehninger, Albert L (2008). Lehninger Principles of Biochemistry (5th ed.). New York: W.H. Freeman. ISBN 9781429212427.
  9. ^ Johnson, Leonard R., ed. (2003). Essential medical physiology (3rd ed.). Amsterdam: Elsevier Academic Press. ISBN 9780123875846.
  10. ^ Heinemann, Henry O.; Goldring, Roberta M. (1974). "Bicarbonate and the regulation of ventilation". The American Journal of Medicine. 57 (3): 361–370. doi:10.1016/0002-9343(74)90131-4.
  11. ^ Koeppen, Bruce M. (2009-12-01). "The kidney and acid-base regulation". Advances in Physiology Education. 33 (4): 275–281. doi:10.1152/advan.00054.2009. ISSN 1043-4046. PMID 19948674.
  12. ^ a b c page 556, section "Estimating plasma pH" in: Bray, John J. (1999). Lecture notes on human physiology. Malden, Mass.: Blackwell Science. ISBN 978-0-86542-775-4.
  13. ^ Kamens, Donald R.; Wears, Robert L.; Trimble, Cleve (1979-11-01). "Circumventing the Henderson-Hasselbalch equation". Journal of the American College of Emergency Physicians. 8 (11): 462–466. doi:10.1016/S0361-1124(79)80061-1.
  14. ^ Hogan, DL; Rapier, RC; Dreilinger, A; Koss, MA; Basuk, PM; Weinstein, WM; Nyberg, LM; Isenberg, JI (1996). "Duodenal bicarbonate secretion: Eradication of Helicobacter pylori and duodenal structure and function in humans". Gastroenterology. 110 (3): 705–716. doi:10.1053/gast.1996.v110.pm8608879.

External links

  • Essentials of Human Physiology by Thomas M. Nosek. Section 7/7ch12/7ch12p17.
Acid–base homeostasis

Acid–base homeostasis is the homeostatic regulation of the pH of the body's extracellular fluid (ECF). The proper balance between the acids and bases (i.e. the pH) in the ECF is crucial for the normal physiology of the body, and cellular metabolism. The pH of the intracellular fluid and the extracellular fluid need to be maintained at a constant level.Many extracellular proteins such as the plasma proteins and membrane proteins of the body's cells are very sensitive for their three dimensional structures to the extracellular pH. Stringent mechanisms therefore exist to maintain the pH within very narrow limits. Outside the acceptable range of pH, proteins are denatured (i.e. their 3-D structure is disrupted), causing enzymes and ion channels (among others) to malfunction.

In humans and many other animals, acid–base homeostasis is maintained by multiple mechanisms involved in three lines of defence:

The first line of defence are the various chemical buffers which minimize pH changes that would otherwise occur in their absence. They do not correct pH deviations, but only serve to reduce the extent of the change that would otherwise occur. These buffers include the bicarbonate buffer system, the phosphate buffer system, and the protein buffer system.The second line of defence of the pH of the ECF consists of controlling of the carbonic acid concentration in the ECF. This is achieved by changes in the rate and depth of breathing (i.e. by hyperventilation or hypoventilation), which blows off or retains carbon dioxide (and thus carbonic acid) in the blood plasma.The third line of defence is the renal system, which can add or remove bicarbonate ions to or from the ECF. The bicarbonate is derived from metabolic carbon dioxide which is enzymatically converted to carbonic acid in the renal tubular cells. The carbonic acid spontaneously dissociates into hydrogen ions and bicarbonate ions. When the pH in the ECF tends to fall (i.e. become more acidic) the hydrogen ions are excreted into the urine, while the bicarbonate ions are secreted into the blood plasma, causing the plasma pH to rise (correcting the initial fall). The converse happens if the pH in the ECF tends to rise: the bicarbonate ions are then excreted into the urine and the hydrogen ions into the blood plasma.Physiological corrective measures make up the second and third lines of defence. This is because they operate by making changes to the buffers, each of which consists of two components: a weak acid and its conjugate base. It is the ratio concentration of the weak acid to its conjugate base that determines the pH of the solution. Thus, by manipulating firstly the concentration of the weak acid, and secondly that of its conjugate base, the pH of the extracellular fluid (ECF) can be adjusted very accurately to the correct value. The bicarbonate buffer, consisting of a mixture of carbonic acid (H2CO3) and a bicarbonate (HCO−3) salt in solution, is the most abundant buffer in the extracellular fluid, and it is also the buffer whose acid to base ratio can be changed very easily and rapidly.An acid–base imbalance is known as acidaemia when the acidity is high, or alkalaemia when the acidity is low.

Carbonic acid

Not to be confused with carbolic acid, an antiquated name for phenol.Carbonic acid is a chemical compound with the chemical formula H2CO3 (equivalently OC(OH)2). It is also a name sometimes given to solutions of carbon dioxide in water (carbonated water), because such solutions contain small amounts of H2CO3. In physiology, carbonic acid is described as volatile acid or respiratory acid, because it is the only acid excreted as a gas by the lungs. It plays an important role in the bicarbonate buffer system to maintain acid–base homeostasis.

Carbonic acid, which is a weak acid, forms two kinds of salts: the carbonates and the bicarbonates. In geology, carbonic acid causes limestone to dissolve, producing calcium bicarbonate, which leads to many limestone features such as stalactites and stalagmites.

It was long believed that carbonic acid could not exist as a pure compound. However, in 1991 it was reported that NASA scientists had succeeded in making solid H2CO3 samples.

Carboxylic acid

A carboxylic acid is an organic compound that contains a carboxyl group (C(=O)OH). The general formula of a carboxylic acid is R–COOH, with R referring to the rest of the (possibly quite large) molecule. Carboxylic acids occur widely. Important examples include the amino acids (which make up proteins) and acetic acid (which is part of vinegar). Deprotonation of a carboxyl group gives a carboxylate anion. Important carboxylate salts are soaps.

Homeostasis

In biology, homeostasis is the state of steady internal physical and chemical conditions maintained by living systems. This dynamic state of equilibrium is the condition of optimal functioning for the organism and includes many variables, such as body temperature and fluid balance, being kept within certain pre-set limits (homeostatic range). Other variables include the pH of extracellular fluid, the concentrations of sodium, potassium and calcium ions, as well as that of the blood sugar level, and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life.

Homeostasis is brought about by a natural resistance to change in the optimal conditions, and equilibrium is maintained by many regulatory mechanisms. All homeostatic control mechanisms have at least three interdependent components for the variable being regulated: a receptor, a control centre, and an effector. The receptor is the sensing component that monitors and responds to changes in the environment, either external or internal. Receptors include thermoreceptors, and mechanoreceptors. Control centres include the respiratory centre, and the renin–angiotensin system. An effector is the target acted on, to bring about the change back to the normal state. At the cellular level, receptors include nuclear receptors that bring about changes in gene expression through up-regulation or down-regulation, and act in negative feedback mechanisms. An example of this is in the control of bile acids in the liver.Some centers, such as the renin–angiotensin system, control more than one variable. When the receptor senses a stimulus, it reacts by sending action potentials to a control center. The control center sets the maintenance range—the acceptable upper and lower limits—for the particular variable, such as temperature. The control center responds to the signal by determining an appropriate response and sending signals to an effector, which can be one or more muscles, an organ, or a gland. When the signal is received and acted on, negative feedback is provided to the receptor that stops the need for further signaling.

Rubottom oxidation

The Rubottom oxidation is a useful, high-yielding chemical reaction between silyl enol ethers and peroxyacids to give the corresponding α-hydroxy carbonyl product. The mechanism of the reaction was proposed in its original disclosure by A.G. Brook with further evidence later supplied by George M. Rubottom. After a Prilezhaev-type oxidation of the silyl enol ether with the peroxyacid to form the siloxy oxirane intermediate, acid-catalyzed ring-opening yields an oxocarbenium ion. This intermediate then participates in a 1,4-silyl migration (Brook rearrangement) to give an α-siloxy carbonyl derivative that can be readily converted to the α-hydroxy carbonyl compound in the presence of acid, base, or a fluoride source.

Urine

Urine is a liquid by-product of metabolism in humans and in many animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excreted from the body through the urethra.

The cellular metabolism generates many by-products which are rich in nitrogen and must be cleared from the bloodstream, such as urea, uric acid, and creatinine. These by-products are expelled from the body during urination, which is the primary method for excreting water-soluble chemicals from the body. A urinalysis can detect nitrogenous wastes of the mammalian body.

Urine has a role in the earth's nitrogen cycle. In balanced ecosystems urine fertilizes the soil and thus helps plants to grow. Therefore, urine can be used as a fertilizer. Some animals use it to mark their territories. Historically, aged or fermented urine (known as lant) was also used for gunpowder production, household cleaning, tanning of leather and dyeing of textiles.

Human urine and feces are collectively referred to as human waste or human excreta, and are managed with a sanitation system. Livestock urine and feces also require proper management if the livestock population density is high.

Renal function
Hormones
Acid-base balance
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