L1 Water Metabolism PDF - Al Azhar University 2023/2024

# AL AZHAR UNIVERSITY ## Faculty of Medicine for Girls ### Year II - Semester III ### Academic year: 2023 / 2024 ## Module Name: Renal ### Course code: IMP-07-20318 ### Credit hours: 5 Hr. ## BIOCHEMISTRY DEPARTMENT # Water metabolism ### Prof. Dr. WAFAA M.E ABDELFATTAH ### [email protected]...

# AL AZHAR UNIVERSITY ## Faculty of Medicine for Girls ### Year II - Semester III ### Academic year: 2023 / 2024 ## Module Name: Renal ### Course code: IMP-07-20318 ### Credit hours: 5 Hr. ## BIOCHEMISTRY DEPARTMENT # Water metabolism ### Prof. Dr. WAFAA M.E ABDELFATTAH ### [email protected] ## By the end of the chapter the student should be able to: - Describe the functions and the properties of water that account for its surface tension - Define pH and its clinical importance, viscosity, absorption, adsorption osmotic pressure and surface tension. - Discuss Acid - base balance and clinical abnormalities of the blood pH (Acidosis & Alkalosis) - Summarize regulation of blood pH - Explain blood buffers ## Water metabolism - Water is the predominant chemical component of living organisms. The daily normal allowance for normal adult (60 Kg) is about 1800-2500 ml/day. - Water is a neutral substance, which means it has a pH of 7. ## Regulation of water balance Regulation of water balance depends upon: - Hypothalamic mechanisms that control thirst. - Antidiuretic hormone (ADH). - Retention or excretion of water by the kidneys. ## Functions of Water - It is an essential constituent of a living cell. No living cell can resist drying. - By its solvent action it forms a great number of crystalloidal and colloidal solutions and thus serves as a universal medium in which the intracellular and extracellular chemical reactions take place. Probably no chemical reaction inside the body can take place without water. - **Crystalloidal solution** = True solution: The size of solute particles is less than 1nm (nm=nanometer= 10-9 meter). - **Colloidal solution**: The size of solute particles is between 1- 200 nm. - It Acts as a Medium for Various Physical Processes such as osmosis, diffusion, filtration - **Hydrolysis**: hydrolysis is an important chemical process involved in digestion and metabolism. In this process the H and OH ions of water are introduced into bigger molecules and the latter are broken down into smaller units. ## Functions of Water "cont." - **Dehydration and Condensation**: In these processes water molecule is removed. This takes place in certain synthetic processes in which bigger particles are formed by the union of smaller ones e.g. glyco-gen from glucose. This action is the reverse of hydrolysis. - **Ionizing Medium**: Water is a very good ionizing medium. The dielectric constant of water being very high, oppositely charged ions can coexist in water without much interference. - Water has a slight propensity to dissociate into hydroxide ions and protons. So it plays an important role in maintenance of intracellular and extracellular pH. $H_2O \iff H^+ + OH^-$ - Water is important for absorption of food material from the intestine, reabsorption from kidney tubules, the transport of the various food stuffs from place to place, the drainage and excretion of the end products of metabolism and for the manufac-ture of various secretions, such as, digestive juices, etc., - **Heat Regulation**: Body temperature is regulated by water. - **Lubricant Action**: Water acts as a lubricant to prevent friction and drying. In joints, pleura, peritoneum, conjunctiva, etc., the aqueous solution is practically free from fats and acts as a lubricant against rubbing and drying. - **Mechanical Action**: The cerebrospinal fluid which contains nearly 99% water acts as a great mechanical buffer preventing injury to the nervous system. ## PH - **Definition of pH**: pH is the negative logarithm of the hydrogen ion concentration. $pH = -log [H^+]$ - (The square brackets around the H+ mean "concentration"). - **pH symbol**: p = power, H= Hydrogen. - **Example**: Water is neutral solution because on ionization it gives equal amounts of H+ and OH - ions =10-7=7. - Low pH values correspond to high concentrations of H - High pH values correspond to low concentrations of H+ ## PH scale: The pH scale is from 1 to 14 ## Clinical importance of pH: The normal pH of human blood is about 7.3-7.4: - If the blood pH falls below 7.3 the condition is called acidosis. - If the blood pH rises above 7.4 the condition is called alkalosis. - Both acidosis and alkalosis are fatal conditions because changes of the blood pH affect different enzyme activities (each enzyme has an optimum pH to act maximally). ## Acid base balance - Acid - base balance is important for keeping hydrogen ion (H+) balance under control. - Organs responsible for control of acid base are healthy kidney and lungs. - The normal ratio of Na bicarbonate (NaHCO3) and & carbonic acid (H2CO3) is 20 to 1 (HCO3-= Bicarbonate, H2CO3= Carbonic acid, NaHCO3= Sodium bicarbonate) - Any alteration in the concentration of one of the two components of this buffer is immediately compensated by alteration in the other to maintain the ratio constant. - Disturbances in this ratio will lead change in pH which results in either acidosis or alkalosis. - The body cells can tolerate only a narrow range of pH. ## Clinical abnormalities of the blood pH ### (A) Acidosis: It is the decrease of the blood pH below 7.3. #### Types of acidosis are: - **Respiratory acidosis:** It is due to of CO2 levels due to: - Failure of the lung to excrete CO2 as in severe bronchial asthma, emphysema, pneumonia and asphyxia. - Depression of the respiratory centers. - Breathing air with excessCO2. - **Metabolic acidosis:** It is due to the decrease of HCO3- as a result of of the bicarbonate buffer in the following conditions. - Severe muscle exercise with excess lactic acid production. - Ketoacidosis in the uncontrolled diabetes mellitus. - Increase of protein in diet with in sulfuric and phosphoric acids. - Failure of the kidney to excrete acids from the body (renal acidosis). - Vomiting with severe diarrhea with excessive loss of the alkaline intestinal and pancreatic juices. ### (B) Alkalosis: It is the of blood pH above 7.4 #### Types of alkalosis are: - **RESPIRATORY ALKALOSIS**: CO2 LEVEL IS DECREASED AS IN CASES OF HYPERVENTILATION E.E.G., IN HIGH ALTITUDE AND IN HIGH FEVER. - **METABOLIC ALKALOSIS**: DUE TO THE INCREASE OF HCO3- CAUSED BY EXCESSIVE VOMITING WITH LOSS OF HCL, AND DIET WITH OF THE NUMBER OF SALTS. ## Regulation of blood pH - Systems responsible for regulation of blood pH are: - Buffers. - Kidneys - Respiratory system. ## Buffers - Normal metabolism generates CO2, metabolic acids (e.g., lactic acid and ketone bodies) and inorganic acids (e.g., sulfuric acid). - The major source of acids is CO2 which reacts with water to produce carbonic acid. - To maintain the pH of the body in a range compatible with life, the body has buffers. - **Buffering is the process by which a strong acid (or base) is replaced by a weaker one, with reduction in the number of free H+ and therefore the change in pH after addition of acid.** ## Buffer "cont." - **Definition of Buffers**: solutions which resist any change in the pH when a moderate amount of an acid or alkali are added to it. - **Composition of buffers**: Buffers are formed of: - **1-Mixture of weak acid and its salt with strong base**: e.g., carbonic acid (weak acid) and its salt (sodium or potassium bicarbonate) and acetic acid and sodium acetate. - **2-Mixture of weak base and its salt with strong acid**, e.g., ammonium hydroxide (weak base) and its salt (ammonium chloride). ## Examples of buffer systems: - **1. Carbonic acid /Bicarbonate buffer system**: Na bicarbonate buffer (H2CO3/NaHCO3), mainly in the extracellular fluid (ECF),it is composed of carbonic acid (weak acid) and Na bicarbonate (its salt of strong base). - **2. Phosphate buffer**: The components of phosphate buffer system are: Na dihydrogen phosphate (NaH2PO4) / Na monohydrogen phosphate (Na2HPO4) - **3. Protein buffers**: It includes: - Amino acid buffers. - Hemoglobin and oxyhemoglobin buffer KHb /Hb in RBCs. - Plasma protein buffers. ## Blood buffers - Blood buffer systems are present in: - **1. Intracellular fluids (ICF) and RBCs:** They include: - Phosphate buffer system. - Protein buffer system - **2. Plasma and extracellular fluids (ECF):** ECF buffer systems include: - Carbonic acid / bicarbonate buffer system. - Protein buffer system. ## Mechanism of buffer action: - Any buffer is formed of two parts, basic part and acidic part: - If a strong acid is added it will react with the basic part of the buffer & minimizes change of pH. - If a strong base is added it will react with the acidic part and minimizes the change of the pH. ## Respiratory regulation of pH - Accumulation of CO2 $H_2CO_3$ $H^+$ ion concentration of blood pH respiratory acidosis stimulation of respiratory center increase rate of respiration elimination of CO2 Buffering of blood pH. $CO_2 + H_2O \iff H_2CO_3 \iff H^+ + HCO_3^-$ - De in blood pH respiratory alkalosis inhibition of respiratory center in rate and depth of respiration accumulation of CO2 formation of carbonic acid buffering of blood. ## Renal regulation of pH - Kidneys have several powerful mechanisms to control pH & acid-base balance by the excretion of excess acids or bases. - **Mechanisms by which kidney regulate PH are:** - Excretion of hydrogen(H+) and potassium in tubules (acidification of urine) in response to acidosis. - Reabsorption of bicarbonate (HCO3-) in response to acidosis and excrete it in response to alkalosis. - Production of ammonia and excretion of ammonium ions (NH4+). ## a. Excretion of hydrogen - Occurs in proximal, distal and collecting tubules by the following mechanism. - CO2 combines with H2O to form H2CO3. - H2CO3 dissociate to bicarbonate (HCO3- and H+). - H+ secreted in exchange for Nat. - Net production of HCO3- and net excretion of H+ ## Na – H exchange - This means exchange of sodium with hydrogen against concentration gradient by ATP hydrolysis. - In kidney H+ ions are extruded into the tubular fluid in exchange for Na+ ions during acidosis but this is inhibited in alkalosis. ## B. Production of ammonia and excretion of ammonium ions. - Ammonia is released in renal tubular cells by the action of glutaminase enzyme on glutamine. - Ammonia is a gas and diffuses readily across the cell membrane into the tubular lumen where it forms ammonium ions which now cannot cross cell membrane and thus trapped in tubular urine and excreted with anions like phosphate, chloride, or sulfate. ## C. Reabsorption of filtered bicarbonate - Bicarbonate reabsorption takes place almost entirely in the proximal convoluted tubules. The excreted hydrogen ion reacts with filtered bicarbonate to form carbonic acid (H2CO3) which is dissociated to CO2and H2O. Carbon dioxide diffuses back and again forms H2CO3 which is again converted to bicarbonate. Normally about 90% of filtered bicarbonate is reclaimed in proximal tubule, and extent of its reclamation parallels sodium reabsorption. ## Mcq - Important buffer system of extracellular fluid is? - Bicarbonate/carbonic acid - Disodium hydrogen phosphate/sodiumdihydrogen phosphate - Plasma proteins - Organic Phosphate ## References - Lippincoott's illustrated review (7th Edition), Lippincott, 2017, Philadelphia. - Harper's illustrated biochemistry,31 th Edition, by Mc Graw Hill, 2018, New York. - Medical biochemistry for second year medical students, by members of biochemistry department under supervision of Professor Hoda Elkholy, biochemistry department, Faculty of medicine for Girls, Al Azhar University, 2023