Why would a buffer be important to homeostasis? | Socratic
A buffer is a special solution that stops massive changes in pH levels. It can be also defined as the quantity of strong acid or base that must. Does not homeostasis entail stability in the face of change?. Buffering is important in living systems as a means of maintaining a fairly constant internal environment, also known as homeostasis. Small molecules such as Related Sciencing Articles What Is the Goal of Homeostasis?.
This can be very serious, because many of the chemical reactions that occur in the body, especially those involving proteins, are pH-dependent. Ideally, the pH of the blood should be maintained at 7. If the pH drops below 6. Fortunately, we have buffers in the blood to protect against large changes in pH.
This external fluid, in turn, exchanges chemicals with the blood being pumped throughout the body. A dominant mode of exchange between these fluids cellular fluid, external fluid, and blood is diffusion through membrane channels, due to a concentration gradient associated with the contents of the fluids. Recall your experience with concentration gradients in the "Membranes, Proteins, and Dialysis" experiment.
Hence, the chemical composition of the blood and therefore of the external fluid is extremely important for the cell. As mentioned above, maintaining the proper pH is critical for the chemical reactions that occur in the body. In order to maintain the proper chemical composition inside the cells, the chemical composition of the fluids outside the cells must be kept relatively constant.
This constancy is known in biology as homeostasis. Figure 2 This is a schematic diagram showing the flow of species across membranes between the cells, the extracellular fluid, and the blood in the capillaries. The body has a wide array of mechanisms to maintain homeostasis in the blood and extracellular fluid.
The most important way that the pH of the blood is kept relatively constant is by buffers dissolved in the blood. Other organs help enhance the homeostatic function of the buffers. The kidneys help remove excess chemicals from the blood, as discussed in the Kidney Dialysis tutorial. Acidosis that results from failure of the kidneys to perform this excretory function is known as metabolic acidosis. However, excretion by the kidneys is a relatively slow process, and may take too long to prevent acute acidosis resulting from a sudden decrease in pH e.
The lungs provide a faster way to help control the pH of the blood. The increased-breathing response to exercise helps to counteract the pH-lowering effects of exercise by removing CO2, a component of the principal pH buffer in the blood. Acidosis that results from failure of the lungs to eliminate CO2 as fast as it is produced is known as respiratory acidosis.
A Quantitative View The kidneys and the lungs work together to help maintain a blood pH of 7. Therefore, to understand how these organs help control the pH of the blood, we must first discuss how buffers work in solution.
Acid-base buffers confer resistance to a change in the pH of a solution when hydrogen ions protons or hydroxide ions are added or removed. An acid-base buffer typically consists of a weak acid, and its conjugate base salt see Equations in the blue box, below.
Buffers work because the concentrations of the weak acid and its salt are large compared to the amount of protons or hydroxide ions added or removed. When protons are added to the solution from an external source, some of the base component of the buffer is converted to the weak-acid component thus using up most of the protons added ; when hydroxide ions are added to the solution or, equivalently, protons are removed from the solution; see Equations in the blue box, belowprotons are dissociated from some of the weak-acid molecules of the buffer, converting them to the base of the buffer and thus replenishing most of the protons removed.
However, the change in acid and base concentrations is small relative to the amounts of these species present in solution. Hence, the ratio of acid to base changes only slightly. The Carbonic-Acid-Bicarbonate Buffer in the Blood By far the most important buffer for maintaining acid-base balance in the blood is the carbonic-acid-bicarbonate buffer.
The simultaneous equilibrium reactions of interest are. Hence, the conjugate base of an acid is the species formed after the acid loses a proton; the base can then gain another proton to return to the acid. In solution, these two species the acid and its conjugate base exist in equilibrium.
Recall from this and earlier experiments in Chem and the definition of pH: When an acid is placed in water, free protons are generated according to the general reaction shown in Equation 3. HA and A- are generic symbols for an acid and its deprotonated form, the conjugate base. Hence, the equilibrium is often written as Equation 4, where H2O is the base: Equilibrium Constant for an Acid-Base Reaction Using the Law of Mass Action, we can also define an equilibrium constant for the acid dissociation equilibrium reaction in Equation 4.
This equilibrium constant, known as Ka, is defined by Equation 7: To more clearly show the two equilibrium reactions in the carbonic-acid-bicarbonate buffer, Equation 1 is rewritten to show the direct involvement of water: Carbonic acid H2CO3 is the acid and water is the base.
Carbonic acid also dissociates rapidly to produce water and carbon dioxide, as shown in the equilibrium on the right of Equation This second process is not an acid-base reaction, but it is important to the blood's buffering capacity, as we can see from Equation 11, below. Notice that Equation 11 is in a similar form to the Henderson-Hasselbach equation presented in the introduction to the Experiment Equation 16 in the lab manual. Equation 11 does not meet the strict definition of a Henderson-Hasselbach equation, because this equation takes into account a non-acid-base reaction i.
However, the relationship shown in Equation 11 is frequently referred to as the Henderson-Hasselbach equation for the buffer in physiological applications. In Equation 11, pK is equal to the negative log of the equilibrium constant, K, for the buffer Equation It follows that the formula for Ka is.
Why would a buffer be important to homeostasis?
Solving for the equilibrium concentration of carbonic acid gives. As shown in Equation 11, the pH of the buffered solution i. This optimal buffering occurs when the pH is within approximately 1 pH unit from the pK value for the buffering system, i. However, the normal blood pH of 7. The lungs remove excess CO2 from the blood helping to raise the pH via shifts in the equilibria in Equation 10and the kidneys remove excess HCO3- from the body helping to lower the pH.
Acid–base homeostasis - Wikipedia
The lungs' removal of CO2 from the blood is somewhat impeded during exercise when the heart rate is very rapid; the blood is pumped through the capillaries very quickly, and so there is little time in the lungs for carbon dioxide to be exchanged for oxygen. Insulin resistance in metabolic tissues such as skeletal muscle, adipose tissue, and the liver accelerates the utilization of lipids as an energy substrate instead of glucose. Excess lipolysis caused by impaired glucose metabolism leads to free fatty acids in circulation, which facilitate hepatic gluconeogenesis by the oxidation of fatty acids resulting in large quantities of ketone bodies.
This further accelerates proton overloads, leading to the metabolic ketoacidosis found in diabetic patients. Such acidic conditions prevent the activity of metabolic enzymes such as phosphofructokinase and further accelerate the progression of pathological conditions [ 33 — 35 ]. Acidic conditions can also result in physical fatigue of diabetic patients.
Therefore, maintaining normal pH is important for physiological homeostasis. It has been suggested that loss of function of MCTs causes a change of body fluid pH. Several point mutations of the MCT gene have been shown to affect both specificity and transport activity. The spontaneously occurring mutation of arginine to threonine in domain 8 of MCT1 resulted in reduced transport activity [ 36 ].
In addition, it has been shown that subjects who have mutations in MCT1 cDNA have drastically lower transport rates and a delayed decline of blood lactate after exercise [ 3738 ]. Healthy subjects feel severe chest pain and muscle cramping after strenuous exercise, along with a defect in lactate efflux from muscle. Furthermore, many amino acid differences that are not attributable to polymorphisms are found in MCT1 obtained from muscle tissues in these subjects [ 3739 ]; thus, mutations in MCT1 are related to physical fatigue and exercise performance.
MCT dysfunction may lead to metabolic disorder. Indeed, lower level expression of MCT1 and MCT4 is found in the skeletal muscle of obese rats compared to normal rats [ 40 ]. In addition, the activity of lactate transport in muscle is also decreased by both denervation and aging [ 4142 ].
A significant negative correlation between the level of circulating lactate and degree of insulin sensitivity is found in humans [ 43 ], suggesting that lower lactic acid disposal caused by reduction of MCT function is associated with insulin resistance. Interstitial Fluid pH and Disease Development Body fluid acidosis could also contribute to the development of metabolic diseases. The buffering capacity is relatively high in the cytosol and blood but low in the interstitial fluid due to limited buffering factors such as proteins [ 4546 ].
Therefore, interstitial fluid pH in metabolic tissues easily changes Figure 1 and may contribute to the onset of insulin resistance.
We have shown the inhibitory effect of extracellular pH on the insulin signaling pathway in the L6 rat myotube. The phosphorylation level and binding affinity to insulin of insulin receptors were significantly diminished in media with low pH [ 47 ].
In addition, the levels of Akt phosphorylation, a downstream of the insulin receptor, are also decreased in low pH media, along with a reduction in glucose uptake. These in vitro observations support the hypothesis that lower extracellular pH may cause insulin resistance in skeletal muscle cells.
Other studies [ 48 — 50 ] have suggested a close correlation between organic acid production and insulin sensitivity in both type 2 diabetes patients and healthy subjects.
In a cross-sectional study of over 1, subjects [ 48 ], it has been demonstrated that body weight and waist circumference have a negative correlation with both insulin sensitivity and urine pH. Patients with metabolic syndrome have also reported a significantly lower pH of 24 h urine compared to the normal subjects and a negative correlation between the mean 24 h urine pH and the number of metabolic syndrome abnormalities [ 4950 ].
It has been suggested that lower levels of serum bicarbonate and higher levels of anion gap resulting from metabolic acidosis are associated with lower insulin sensitivity [ 51 ].
Hyperlactacidemia is found in patients with obesity and type 2 diabetes [ 43 ], which supports the strong relationship between acidic condition and insulin sensitivity. Even in healthy subjects, acids level could be an independent risk factor for the development of type 2 diabetes [ 52 ]. Insulin resistance is one of the major symptoms of metabolic disorders and is frequently associated with hypertension, high blood glucose levels, visceral obesity, and dyslipidemia.
Insulin resistance also causes type 2 diabetes and plays a key role in developing cancer and cardiovascular disease. Thus, pH abnormalities can cause abnormal metabolic regulation in a predisease state. We recently found an observation that the interstitial pH around the hippocampus, an important region for memory [ 53 ], is lower in diabetic OLETF rats 26 weeks of age than in normal Wistar rats [ 54 ].
The insulin action is required for neuronal survival within the central nervous system [ 56 ]. Therefore, we indicate that maintenance of the interstitial fluid pH within the normal range or the recovery of the interstitial pH to the normal range could be one of the most important factors in developing molecular and cellular therapies for metabolic brain disorders.
Physical exercise and appropriate diet contribute to pH homeostasis. Habitual exercise adaptively accelerates the entry of fatty acids both from the plasma into the muscle cell and from the cytosol into the mitochondria, while also enhancing Krebs cycle function in the resting state.
Their actions are caused by elevation of activity and expression of related enzymes in skeletal muscles [ 59 — 61 ]. In addition, circulating and intramuscular buffering capacities are improved via habitual exercise increasing proteins, amino acids, and phosphate [ 62 — 64 ].
Peripheral circulation is also improved through vasodilation caused as a physiological adaptation to exercise [ 65 ], which further facilitates the proton washout. In particular there is evidence suggesting that excretion of protons from the cytosol to the extracellular space or into circulation via transporters located on the plasma membrane contributes to the prevention of intracellular acidosis.
It has been reported that exercise training increases the MCT1 and MCT4 levels in the skeletal and cardiac muscle of humans and animals [ 66 — 68 ]. Although the regulation of MCT expression levels is not clearly understood, it has been suggested that protein kinases A and B are involved in the regulation of MCT expression [ 69 ] as an adaptation mechanism, which may be mediated by an increase in lactate movement across the membrane.
In addition, our recent study has reported that MCT1 content in erythrocyte membranes is elevated by exercise training in rats [ 7071 ]. A proportion of the lactate released from skeletal muscles into the plasma is taken up by erythrocytes.
The mature erythrocytes generate ATP only through the glycolytic pathway, since they have no mitochondrial machinery. Thus, erythrocytes cannot utilize lactate produced as a respiratory fuel and this necessitates the release of lactate into the plasma via MCT1 [ 72 ]. However, one of the most important roles of erythrocytes is to distribute released monocarboxylates by taking up monocarboxylates, since erythrocytes produce much less lactate than other tissues.
Based on the results of our in vitro study, the skeletal muscle may be entirely dependent on MCT1-mediated lactate uptake by erythrocytes to maintain pH homeostasis [ 71 ].
In addition, there is a high correlation between the athletic performance of horses and their erythrocyte lactate concentrations after racing [ 73 ]. Therefore, efficient proton transport via MCTs induced by habitual exercise may contribute to the improvement of insulin sensitivity and muscle fatigue caused by lowered pH.
It is well known that adequate diet is important for controlling pathological conditions in patients with metabolic disorders. In addition, intervention studies in humans have reported that several bioactive factors included in foods such as antioxidants [ 74 — 77 ] and n-3 unsaturated fatty acids [ 7879 ] improve energy metabolism. The effects of these nutrients are only beneficial when administered in combination. In contrast to the successful application of dietary approaches or combined nutrients [ 85 — 87 ], various types of intervention studies using single nutrients have failed to clarify their beneficial action on cardiovascular risk and insulin resistance [ 8889 ].
Therefore, administration of multiple nutrients is considered more effective when compared to administration of a single bioactive factor. Propolis, a natural product derived from the plant resins collected by honeybees, contains various types of compounds including polyphenols, phenolic aldehydes, sesquiterpene quinones, coumarins, amino acids, steroids, and inorganic compounds [ 90 ] and has been reported to reduce the metabolic defects caused by abnormal blood glucose and insulin in young 18 weeks of age OLETF rats [ 42 ] characterized by hyperphagia, obesity, decreased glucose infusion rate in a euglycemic clamp at 16—18 weeks of age, hyperinsulinemia around 25 weeks of age responding to an intravenous glucose infusion, and developing type 2 diabetes [ 9192 ].
Thus, our study indicates that propolis has a beneficial and preventive action on type 2 diabetes mellitus at early stages developing insulin resistance. Further, we have obtained evidence that intake of propolis elevates the pH of ascites and metabolic tissues compared with normal diet, indicating that dietary propolis diminishes production of organic acids or increases buffering capacity in those tissues.