Ionization of water molecules produces equal amounts of OH – and H + Acids, Bases, and the pH Scale An acid is defined as a molecule that can release protons (H + ) into a solution; it is a “proton donor.” A base is a molecule such as NaOH that can ionize to produce a negatively charged ion (hydroxide, OH – )- a “proton acceptor,” The H + concentration of a solution is usually indicated in pH units on a pH scale that runs from 0 to 14. [H + ] =molar H + concentration. 1

Pure water has a pH of 7 (neutral) 2 Acidic solutions have a pH of less than 7, whereas basic (alkaline) solutions have a pH between 7 and 14. Buffers A buffer is a system of molecules and ions that acts to prevent changes in H + concentration and thus serves to stabilize the pH of a solution. In blood plasma, the pH is stabilized by the following reversible reaction involving the bicarbonate ion (HCO 3 – ) and carbonic acid (H 2 CO3):

3 the net direction of the reaction depends on the concentration of molecules and ions on each side. If an acid (such as lactic acid) should release H + into the solution, for example, the increased concentration of H + would drive the equilibrium to the right and the following reaction would be promoted. In this reaction, H + is taken out of solution. Thus, the H + concentration is prevented from rising (and the pH prevented from falling) by the action of bicarbonate buffer.

4 Blood pH The physiologic pH of blood is 7.40 ± 0.05, which maintained in part by the buffering action of bicarbonate. Bicarbonate serves as the major buffer of the blood. Excessive vomiting that results in loss of gastric acid could cause the concentration of free H + in the blood to fall and the blood pH to rise. In this case, the reaction previously described could be reversed. The dissociation of carbonic acid yields free H +, which helps to prevent an increase in pH.

5 Acidosis and alkalosis are normally prevented by the action of the bicarbonate /carbonic acid buffer pair and by the functions of the lungs and kidneys. Bicarbonate ions and carbonic acid thus act as a buffer system to prevent either decreases or increases in pH, respectively. This buffering action normally maintains the blood pH within the narrow range of 7.35 to 7.45.

6 Body Fluids Intracellular compartment contains approximately 67% of the total body water. Extracellular compartment contains about 33% of the total body water. About 20% of extracellular fluid is contained within in the blood, or blood plasma. The blood:- - Transports O 2 from the lungs to the body cells, and CO 2 from the body cells to the lungs. - Transports nutrients derived from food in the intestine to the body cells. - Transports nutrients between organs (such as glucose from the liver to the brain, or lactic acid from muscles to the liver).

7 - Transports metabolic wastes from the body cells to the liver and kidneys for elimination in the bile and urine, respectively. - Transports hormones from endocrine glands to the cells of their target organs. The remaining 80% of the extracellular fluid makes up the tissue fluid, also called interstitial fluid. The interstitial fluid is formed continuously from blood plasma, and it continuously returns to the blood plasma. Oxygen, nutrients, and regulatory molecules traveling in the blood must first pass into the interstitial fluid before reaching the body cells. Waste products and hormone secretions from the cells must first pass into the interstitial fluid before reaching the blood plasma.

8 The extracellular environment contains interstitial tissue fluid within a matrix of glycoproteins and proteoglycans. Interstitial fluid is derived from blood plasma that filters through the pores (not shown) between the cells of the capillary walls, and delivers nutrients and regulatory molecules to the tissue cells. The extracellular environment is supported by collagen and elastin protein fibers, which also form the basal lamina below epithelial membranes.

9 Extracellular Matrix The cells that compose the organs of our body are embedded within the extracellular material of connective tissues. The extracellular matrix consists of the protein fibers collagen and elastin as well as gel-like ground substance. The ground substance is composed of molecules chemically linked to the extra- cellular protein fibers of collagen and elastin, as well as to the carbohydrates that cover the outside surface of the cell’s plasma membrane. The gel is composed of glycoproteins and proteoglycans (composed primarily of polysaccharides and have a high content of bound water molecules). The collagen and elastin fibers provide structural strength to the matrix.

10 Collagen contributes to the basal lamina (basement membrane) underlying epithelial membranes. The basal lamina helps to wed the epithelium to its underlying connective tissues. “By binding between the carbohydrates on the outside surface of the plasma membrane of the epithelial cells, and the glycoproteins and proteoglycans of the matrix in the connective tissue.” Integrins extend from the cytoskeleton within a cell, through its plasma membrane, and into the extracellular matrix, serve as a glue (or adhesion molecule) between cells and the extracellular matrix. “Integrins physically joining the intracellular to the extracellular compartments.” Certain snake venoms slow blood clotting by blocking integrin-binding sites on blood platelets, preventing them from sticking together.

11 Clinical Application There is an important family of enzymes that can break down extracellular matrix proteins. These enzymes are called matrix metalloproteinases (MMPs) because of their need for a zinc ion cofactor. MMPs are required for tissue remodeling (for example, during embryonic development and wound healing), and for migration of phagocytic cells and other white blood cells during the fight against infection. MMPs are secreted as inactive enzymes and then activated extracellularly. However, they can contribute to disease processes if they are produced or activated inappropriately. For example, cancer cells that become invasive (that metastasize, or spread to different locations) produce active MMPs, which break down the collagen of the basal lamina and allow the cancerous cells to migrate. The destruction of cartilage protein in arthritis may also involve the action of these enzymes, and MMPs have been implicated in the pathogenesis of such neural diseases as multiple sclerosis, Alzheimer’s disease, and others. Therefore, scientists are attempting to develop drugs that may be able to treat these and other diseases by selectively blocking different matrix metalloproteinases.