Functional Organization of the Human Body and Control of the Internal Environment PDF

‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Functional Organization of the Human Body and Control of the “Internal Environment” PHYSIOLOGY I LEC 1 1 ...

‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Functional Organization of the Human Body and Control of the “Internal Environment” PHYSIOLOGY I LEC 1 1  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Physiology is the science that seeks to explain the physical and chemical mechanisms that are responsible for the origin, development, and progression of life. In Human Physiology we attempts to explain the specific characteristics and mechanisms of the human body that make it a living being. CELLS ARE THE LIVING UNITS OF THE BODY The basic living unit of the body is the cell. Each tissue or organ is an aggregate of many different cells held together by intercellular supporting structures. Each type of cell is specially adapted to perform one or a few particular functions. For example, the red blood cells, numbering about 25 trillion in each person, transport oxygen from the lungs to the tissues. The many cells of the body often differ markedly from one another but all have certain basic characteristics that are alike. Almost all cells also have the ability to reproduce additional cells of their own type. Fortunately, when cells of a particular type are destroyed, the remaining cells of this type usually generate new cells until the supply is replenished. EXTRACELLULAR FLUID THE “INTERNAL ENVIRONMENT” About 50% to 70% of the adult human body is fluid, mainly a water solution of ions and other substances. Although most of this fluid is inside the cells and is called intracellular fluid, about one-third is in the spaces outside the cells and is called extracellular fluid. In the extracellular fluid are the ions and nutrients needed by the cells to maintain life. Thus, all cells live in essentially the same environment the extracellular fluid. For this reason, the extracellular fluid is also called the internal environment of the body. Cells are capable of living and performing their special functions as long as the proper concentrations of oxygen, glucose, different ions, amino acids, fatty substances, and other constituents are available in this internal environment. Differences in Extracellular and Intracellular Fluids. The extracellular fluid contains large amounts of sodium, chloride, and bicarbonate ions plus nutrients for the cells, such as oxygen, glucose, 2  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ fatty acids, and amino acids. It also contains carbon dioxide that is being transported from the cells to the lungs to be excreted, plus other cellular waste products that are being transported to the kidneys for excretion. The intracellular fluid contains large amounts of potassium, magnesium, and phosphate ions instead of the sodium and chloride ions found in the extracellular fluid. HOMEOSTASIS-- MAINTENANCE OF A NEARLY CONSTANT INTERNAL ENVIRONMENT The term homeostasis means the maintenance of nearly constant conditions in the internal environment Essentially, all organs and tissues of the body perform functions that help maintain these relatively constant conditions. For example, the lungs provide oxygen to the extracellular fluid to replenish the oxygen used by the cells, the kidneys maintain constant ion concentrations, and the gastrointestinal system provides nutrients while eliminating waste from the body. EXTRACELLULAR FLUID TRANSPORT AND MIXING SYSTEM THE BLOOD CIRCULATORY SYSTEM. Extracellular fluid is transported through the body in two stages. The first stage is movement of blood through the body in the blood vessels. The second is movement of fluid between the blood capillaries and the intercellular spaces between the tissue cells. As blood passes through blood capillaries, continual exchange of extracellular fluid occurs between the plasma portion of the blood and the interstitial fluid that fills the intercellular spaces. This process is shown in Figure 1-2. The capillary walls are permeable to most molecules in the blood plasma, with the exception of plasma proteins, which are too large to pass through capillaries readily. Therefore, large amounts of fluid and its dissolved constituents diffuse back and forth between the blood and the tissue spaces, as shown by the arrows in Figure 1-2. This process of diffusion is caused by kinetic motion of the molecules in the plasma and the interstitial fluid. That is, the fluid and dissolved molecules are continually moving and bouncing in all directions in the plasma and fluid in the intercellular spaces, as well as through capillary pores. 3  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ ORIGIN OF NUTRIENTS IN THE EXTRACELLULAR FLUID Respiratory System. Figure 1-1 shows that each time blood passes through the body, it also flows through the lungs. The blood picks up oxygen in alveoli, thus acquiring the oxygen needed by cells. The membrane between the alveoli and the lumen of the pulmonary capillaries, the alveolar membrane, is 4  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ only 0.4 to 2.0 micrometers thick, and oxygen rapidly diffuses by molecular motion through this membrane into the blood. Gastrointestinal Tract. A large portion of the blood pumped by the heart also passes through the walls of the gastrointestinal tract. Here different dissolved nutrients, including carbohydrates, fatty acids, and amino acids, are absorbed from ingested food into the extracellular fluid of the blood. Liver and Other Organs That Perform Primarily Metabolic Functions. Not all substances absorbed from the gastrointestinal tract can be used in their absorbed form by the cells. The liver changes the chemical compositions of many of these substances to more usable forms, and other tissues of the body fat cells, gastrointestinal mucosa, kidneys, and endocrine glands help modify the absorbed substances or store them until they are needed. Musculoskeletal System. How does the musculoskeletal system contribute to homeostasis? The answer is obvious and simple. Were it not for the muscles, the body could not move to obtain the foods required for nutrition. The musculoskeletal system also provides motility for protection against adverse surroundings, without which the entire body, along with its homeostatic mechanisms, could be destroyed. REMOVAL OF METABOLIC END PRODUCTS Removal of Carbon Dioxide by the Lungs. At the same time that blood picks up oxygen in the lungs, carbon dioxide is released from the blood into lung alveoli; the respiratory movement of air into and out of the lungs carries carbon dioxide to the atmosphere. Carbon dioxide is the most abundant of all the metabolism products. Kidneys. Passage of blood through the kidneys removes most of the other substances from the plasma besides carbon dioxide that are not needed by cells. These substances include different end products of cellular metabolism, such as urea and uric acid; they also include excesses of ions and water from the food that accumulates in the extracellular fluid. The kidneys perform their function first by filtering large quantities of plasma through the glomerular capillaries into the tubules and then reabsorbing into the blood substances needed by the body, such as glucose, amino acids, appropriate amounts of water, and many of the 5  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ ions. Most of the other substances that are not needed by the body, especially metabolic waste products such as urea and creatinine, are reabsorbed poorly and pass through the renal tubules into the urine. REGULATION OF BODY FUNCTIONS Nervous System. The nervous system is composed of three major parts 1-the sensory input portion, 2-the central nervous system (or integrative portion), and 3-the motor output portion. Sensory receptors detect the state of the body and its surroundings. For example, receptors in the skin alert us whenever an object touches the skin. The central nervous system is composed of the brain and spinal cord. The brain stores information, generates thoughts, creates ambition, and determines reactions that the body performs in response to the sensations. Appropriate signals are then transmitted through the motor output portion of the nervous system to carry out one’s desires. An important segment of the nervous system is called the autonomic system. It operates at a subconscious level and controls many functions of internal organs, including the level of pumping activity by the heart, movements of the gastrointestinal tract, and secretion by many of the body’s glands. Hormone Systems. Located in the body are endocrine glands, organs and tissues that secrete chemical substances called hormones. Hormones are transported in the extracellular fluid to other parts of the body to help regulate cellular function. For example, thyroid hormone increases the rates of most chemical reactions in all cells, thus helping set the tempo of bodily activity. Insulin controls glucose metabolism, adrenocortical hormones control sodium and potassium ions and protein metabolism, and parathyroid hormone controls bone calcium and phosphate. Thus, the hormones provide a regulatory system that complements the nervous system. The nervous system controls many muscular and secretory activities of the body, whereas the hormonal system regulates many metabolic functions. The nervous and hormonal systems normally work together in a coordinated manner to control essentially all the organ systems of the body. 6  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ The Cell and Its Functions ORGANIZATION OF THE CELL A typical cell, as seen by the light microscope, is shown in Figure 2-1. Its two major parts are the nucleus and the cytoplasm. The nucleus is separated from the cytoplasm by a nuclear membrane, and the cytoplasm is separated from the surrounding fluids by a cell membrane, also called the plasma membrane. The different substances that make up the cell are collectively called protoplasm. Protoplasm is composed mainly of five basic substances—water, electrolytes, proteins, lipids, and carbohydrates. CELL STRUCTURE The cell contains highly organized physical structures called intracellular organelles, which are critical for cell function. For example, without one of the organelles, the mitochondria, more than 95% of the cell’s energy release from nutrients would cease immediately. The most important organelles and other structures of the cell are shown in Figure 2-2. 7  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Cell membrane The cell membrane is a thin semi-permeable membrane that surrounds the cytoplasm of a cell, enclosing its contents. Its function is to protect the integrity of the interior of the cell by allowing certain substances into the cell, while keeping other substances out. It also serves as a base of attachment for the cytoskeleton in some organisms and the cell wall in others. Thus the cell membrane also serves to help support the cell and help maintain its shape. The cell membrane is primarily composed of a mix of proteins and lipids. While lipids help to give membranes their flexibility, proteins monitor and maintain the cell's chemical climate and assist in the transfer of molecules across the membrane. Phospholipids are a major component of cell membranes. They form a lipid bilayer in which their hydrophillic (attracted to water) head areas spontaneously arrange to face the aqueous cytosol and the extracellular fluid, while their hydrophobic (repelled by water) tail areas face away from the cytosol and extracellular fluid. The lipid bilayer is semi- permeable, allowing only certain molecules to diffuse across the membrane. 8  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ There are many different proteins embedded in the membrane. They exist as separate globular units and many pass through the membrane (integral proteins), whereas others (peripheral proteins) stud the inside and outside of the membrane. Some are cell adhesion molecules that anchor cells to their neighbors or to basal laminas. There are proteins that function as pumps, actively transporting ions across the membrane. Other proteins function as carriers, transporting substances down electrochemical gradients by facilitated diffusion. Still others are ion channels, which, when activated, permit the passage of ions into or out of the cell. Proteins in another group function as receptors that bind neurotransmitters and hormones, initiating physiologic changes inside the cell. Proteins also function as enzymes, catalyzing reactions at the surfaces of the membrane. In addition, some glycoproteins function in antibody processing and distinguishing self from non self. Underlying most cells is a thin, fuzzy layer plus some fibrils that collectively make up the basement membrane or, more properly, the basal lamina. The basal lamina and, more generally, the extracellular matrix are made up of many proteins that hold cells together, regulate their development, and determine their growth. Cell Adhesion Molecules Cells are attached to the basal lamina and to each other by Cell adhesion molecules (CAMs). These adhesion proteins have attracted great attention in recent years because they are important in embryonic development and formation of the nervous system and other tissues; in holding tissues together in adults; in inflammation and wound healing; and in the metastasis of tumors. Many pass through the cell membrane and are anchored to the cytoskeleton inside the cell. Some bind to like molecules on other cells (homophilic binding), whereas others bind to other molecules (heterophilic binding). Many bind to laminins, a family of large cross-shaped molecules with multiple receptor domains in the extracellular matrix. Intercellular Connections Two types of junctions form between the cells that make up tissues: junctions that fasten the cells to one another and to surrounding tissues, 9  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ and junctions that permits transfer of ions and other molecules from one cell to another. The types of junctions that tie cells together and endow tissues with strength and stability, include the 1- Tight junction, which is also known as the zonula occludens, tight junctions between epithelial cells are also essential for transport of ions across epithelia. 2- The desmosome and zonula adherens) hold cells together, and the hemidesmosome attach cells to their basal laminas. 3-Gap Junctions At gap junctions, the intercellular space narrows from 25 nm to 3 nm, and hexagonal arrays of protein unit's connexons in the membrane of each cell are lined up with one another. 10  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Ribosomes and the Rough (Granular) Endoplasmic Reticulum. Attached to the outer surfaces of many parts of the endoplasmic reticulum are large numbers of minute granular particles called ribosomes. Where these particles are present, the reticulum is called the rough (granular) endoplasmic reticulum. The ribosomes are composed of a mixture of RNA and proteins; they function to synthesize new protein molecules in the cell. Smooth (Agranular) Endoplasmic Reticulum. Part of the endoplasmic reticulum has no attached ribosomes. This part is called the smooth, or agranular, endoplasmic reticulum. The smooth reticulum functions for the synthesis of lipid substances and for other processes of the cells promoted by intrareticular enzymes. Golgi apparatus The Golgi apparatus, shown in Figure 2-5, is closely related to the endoplasmic reticulum. It has membranes similar to those of the smooth endoplasmic reticulum. This apparatus is prominent in secretory cells, where it is located on the side of the cell from which secretory substances are extruded. The Golgi apparatus functions in association with the endoplasmic reticulum. In this way, substances entrapped in the endoplasmic reticulum (ER) vesicles are transported from the endoplasmic reticulum to the Golgi apparatus. The transported substances are then processed in the Golgi apparatus to form lysosomes, secretory vesicles, and other cytoplasmic components. 11  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Lysosomes. Are vesicular organelles that form by breaking off from the Golgi apparatus; they then disperse throughout the cytoplasm. The lysosomes provide an intracellular digestive system that allows the cell to digest the following: (1) Damaged cellular structures; (2) Food particles that have been ingested by the cell; and (3) Unwanted matter such as bacteria. They are surrounded by typical lipid bilayer membranes and are filled with large numbers of small granules, which are protein aggregates of as many as 40 different hydrolase (digestive) enzymes. A hydrolytic enzyme is capable of splitting an organic compound into two or more parts by combining hydrogen from a water molecule with one part of the compound and combining the hydroxyl portion of the water molecule with the other part of the compound. Peroxisomes Peroxisomes are physically similar to lysosomes, but they are different in two important ways. First, they are believed to be formed by self-replication (or perhaps by budding off from the smooth endoplasmic reticulum) rather than from the Golgi apparatus. Second, they contain oxidases rather than hydrolases. 12  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Cytoskeleton All cells have a cytoskeleton, a system of fibers that not only maintains the structure of the cell but also permits it to change shape and move. The cytoskeleton is made up primarily of microtubules, intermediate filaments, and microfilaments, along with proteins that anchor them and tie them together. In addition, proteins and organelles move along microtubules and microfilaments from one part of the cell to another propelled by molecular motors. Mitochondria The mitochondria, shown in Figure 2-7, are called the powerhouses of the cell. Without them, cells would be unable to extract enough energy from the nutrients, and essentially all cellular functions would cease. Mitochondria are present in all areas of each cell’s cytoplasm; the mitochondria are concentrated in those portions of the cell responsible for the major share of its energy metabolism. The basic structure of the mitochondrion, shown in Figure 2-7, is composed mainly of two lipid bilayer protein membranes, an outer membrane and an inner membrane. 13  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Many infoldings of the inner membrane form shelves or tubules called cristae onto which oxidative enzymes are attached. The cristae provide a large surface area for chemical reactions to occur. In addition, the inner cavity of the mitochondrion is filled with a matrix that contains large quantities of dissolved enzymes necessary for extracting energy from nutrients. These enzymes operate in association with oxidative enzymes on the cristae to cause oxidation of nutrients, thereby forming carbon dioxide and water and, at the same time, releasing energy. The liberated energy is used to synthesize a high-energy substance called adenosine triphosphate (ATP). ATP is then transported out of the mitochondrion and diffuses throughout the cell to release its own energy wherever it is needed for performing cellular functions. Mitochondria are self-replicative, which means that one mitochondrion can form a second one, a third one, and so on whenever the cell needs increased amounts of ATP. Indeed, the mitochondria contain DNA similar to that found in the cell nucleus. FUNCTIONAL SYSTEMS OF THE CELL ENDOCYTOSIS—INGESTION BY THE CELL If a cell is to live and grow and reproduce, it must obtain nutrients and other substances from the surrounding fluids. Most substances pass through the cell membrane by the processes of diffusion and active transport. Diffusion involves simple movement through the membrane caused by the random motion of the molecules of the substance. Substances move through cell membrane pores or, in the case of lipid-soluble substances, through the lipid matrix of the membrane. Active transport involves actually carrying a substance through the membrane by a physical protein structure that penetrates all the way through the membrane. These active transport mechanisms are so important to cell function. Very large particles enter the cell by a specialized function of the cell membrane called endocytosis. The principal forms of endocytosis are pinocytosis and phagocytosis. Pinocytosis means ingestion of minute particles that form vesicles of extracellular fluid and particulate constituents inside the cell cytoplasm. 14  ‫جامعة كلكامش‬ ‫محمد محسن‬.‫د‬ Physiology ‫كلية الصيدله‬ Phagocytosis means ingestion of large particles, such as bacteria, whole cells, or portions of degenerating tissue. Phagocytosis occurs in the following steps: 1. The cell membrane receptors attach to the surface ligands of the particle. 2. The edges of the membrane around the points of attachment evaginate outward within a fraction of a second to surround the entire particle; then, progressively attach to the particle ligands. All this occurs suddenly in a zipper-like manner to form a closed phagocytic vesicle. 15