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فیزیولوژی تکمیلی Advanced Physiology (part 5, Acid-base Balance) By: A. Riasi (PhD in Animal Nutrition & Physiology) Animal Sci. Dep. Isfahan University of Technology http://riasi.iut.ac.ir Acid-base balance Three aspects that ECF and ICF are crucial to the whole animal and to its individual cells: The osmotic balance Total fluid volume of the body Acid –base status Acid-base balance If balance is to be maintained, input must equal output Adapted from Animal Physiology by Sherwood et al. 2013 Acid-base balance The balance extremely important in maintaining homeostasis. Some constituents undergo frequent and/or large disturbances. Salt and H2O can be lost to the terrestrial environments to varying degrees through the: Digestive tract (vomiting, diarrhea) Skin (sweating) Lungs (panting) Acid-base balance Hydrogen ions are uncontrollably generated internally (especially during muscle activity) and added to body fluids. If possible, compensatory adjustments must be made for these uncontrolled changes. Acid-base balance Adapted from Animal Physiology by Sherwood et al. 2013 Acid-base balance The composition of the ECF as a whole differs considerably from that of the ICF in all animals. Among the major differences between the ECF and ICF are: Cellular proteins that cannot permeate the plasma membranes to leave the cells. Cellular organic osmolytes (typically higher in the ICF than in the ECF). Na+and K+ and their attendant anions: In most organisms, Na+ is the primary ECF cation, and K+ is the primarily ICF cation. Acid-base balance The majority of the ECF and ICF ions are electrically balanced. In the ECF, Na+ is accompanied primarily by the anion Cl− and to a lesser extent by HCO3− (bicarbonate). In the ICF, K+ is accompanied primarily by the anion PO43−(phosphate) and by the negatively charged proteins trapped within the cell. Acid-base balance The acid-base balance refers to the precise regulation of free hydrogen ion (H+) and hydronium ion (OH-) concentration in the body fluids. Acids A are a special group of hydrogen-containing substances. strong acid has a greater tendency to dissociated in solution than does a weak acid. Acid-base balance Acid-base balance in body fluids Adapted from Animal Physiology by Sherwood et al. 2013 Acid-base balance The normal pH of arterial and venous blood Acidosis exists whenever the blood pH falls below 7.3 Alkalosis occurs when the blood pH is above 7.45 Death can occur if arterial pH falls outside of the range of 6.8-8.0 Acid-base balance Adapted from Animal Physiology by Sherwood et al. 2013 Acid-base balance Fluctuations in hydrogen ion concentration have profound effect on body chemistry. Even small changes in [H+] have dramatic effect on proteins. The most prominent whole body consequences of fluctuations in [H+] are changes in excitability of nerves and muscle cells. Acid-base balance Hydrogen ions are continually being added to body fluids Metabolic activities are main source for H+ in the body fluids Normally, H+ is continually being added to the body fluids by: Carbonic acid formation Inorganic acid produced during the breakdown of nutrients Organic acid resulting from intermediary metabolism Acid-base balance CO2 + H2O H2CO3 CA CO2 + OH- H2O H+ + HCO3- HCO3- H+ + OH- Acid-base balance Sulfuric acid and phosphoric acid are produced in the body. Fatty acids and lactic acid that are produced during intermediary metabolism partially dissociate to yield free H +. In certain disease additional acids may be produced. Acid-base balance Three line of defense against changes in [H+]: Chemical buffer systems Respiratory mechanisms of pH control Excretory mechanisms of pH control Acid-base balance There are four buffer system in the vertebrate body: CO2-HCO3- buffer system The peptide and protein buffer system The hemoglobin buffer system The phosphate buffer system Acid-base balance The Co2-HCO3- buffer system in the ECF. Adapted from Animal Physiology by Sherwood et al. 2013 Acid-base balance The most plentiful buffers on the ICF are the cell proteins. The most important buffering amino acid is histidine. Hemoglobin (Hb) in erythrocytes buffers the H+ generated. The phosphate buffer system consists of an acid phosphate slat (NaH2PO4) and a basic phosphate salt (Na2HPO4). The phosphate system serve as an excellent urinary buffer. Acid-base balance The respiratory system plays an important role in acid-base balance through its ability to alter ventilation Acid-base balance The excretory organs are the third line of defense against changes in [H+] in body fluids. In mammals, the kidneys are the most potent acid-base regulatory mechanism. The kidneys can remove of H+ from any source The kidneys can variably conserve or eliminate HCO3- Acid-base balance The kidneys control the pH of the body fluids by adjusting three interrelated factors: H+ excretion H2CO3- excretion Ammonia secretion Acid-base balance Hydrogen ion excretion by the kidneys The kidneys eliminate H+ derived from sulfuric, phosphoric, lactic, and other acids. Acid-base balance pH Regulation: Excretion Adapted from Animal Physiology by Sherwood et al. 2013 Acid-base balance pH Regulation: Excretion The H+ secretary process begins in the tubular cells with CO2 that has come from three sources: The CO2 diffused from plasma The CO2 diffused from the tubular fluid CO2 that has been metabolically produced within the tubular cells. Acid-base balance The kidneys adjust H+ excretion to compensate for changes in both carbonic and noncarbonic acids. The kidneys regulate plasma [HCO3-] by two mechanisms: Variable reabsorption of the filtered HCO3- back to the plasma. Variable addition of new HCO3- to the plasma. Acid-base balance pH Regulation: Excretion Adapted from Animal Physiology by Sherwood et al. 2013