Human Physiology Introduction and Homeostasis (2024-2025) PDF

Republic of Iraq Ministry of Higher Education And Scientific Research University of Esraa College of Pharmacy Human Physiology Introduction and Homeostasis LEC. SABA NASEER ABBAS 2024-2025 Objectives By the end of this lecture the student should be able to answer the following:...

Republic of Iraq Ministry of Higher Education And Scientific Research University of Esraa College of Pharmacy Human Physiology Introduction and Homeostasis LEC. SABA NASEER ABBAS 2024-2025 Objectives By the end of this lecture the student should be able to answer the following: 1. Describe the basic components of the cell membrane 2. Explain the transport processes through cell membranes. 3. Define diffusion and its types. 4. List the factors that affect the net rate of diffusion. 5. Define osmosis. 6. Explain the active transport of substances through membranes. 7. Give examples on the types of active transport. 8. Explain homeostasis. Physiology: science that describes how the body function and survive in continually changing environments. The levels of structural complexity: 1. CHEMICAL LEVEL -includes all chemical substances (atoms, ions& molecules) necessary for life. 2. CELLULAR LEVEL - cells are the basic structural and functional units of the human body, there are many different types of cells (e.g., muscle, nerve, blood, etc..). 3. TISSUE LEVEL - a tissue is a group of cells that perform a specific function and the basic types of tissues in the human body include epithelial, muscle, nervous and connective tissues and glands. 4. ORGAN LEVEL - an organ consists of 2 or more tissues that perform a particular function (e.g.; heart, liver, stomach) 5. SYSTEM LEVEL - an association of organs that have a common function; there are 11 major systems in the human body, including; digestive, nervous, endocrine, circulatory, respiratory, urinary, reproductive, muscular, lymphatic, skeletal, and integumentary (skin and associated glands). The levels of structural complexity Body Composition In the average young adult male, 18% of the body weight is protein and related substances, 7% mineral and 15% fat. The remaining 60% is water. 1. Cells ◦ CELLS ARE THE LIVING UNITS OF THE BODY ◦ The basic living unit of the body is the cell. Each 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. They all share the same basic characteristics. 2. BODY FLUIDs, The (Internal Environment) ◦ The fluid inside cells is the intracellular fluid (ICF) compartment. ◦ The fluid outside cells is the extracellular fluid (ECF) compartment, which is subdivided into the interstitial fluid and the blood plasma. The volume of total body water is approximately 60% of body weight in men and 50% in women Cell structure Composed of 3 major components: 1. Cell membrane (Plasma membrane) Thin membrane composed mostly of lipids and proteins that separate cell’s contents from its surroundings. ◦ It acts as: 1. Physical barrier. 2. Its proteins selectively control the movement of molecules between intracellular fluid ICF and extracellular fluid ECF. 2. Nucleus ❑ Typically, largest single cell component. ❑ Surrounded by nuclear envelope perforated by nuclear pores. Control center of the cell. ❑ Contains DNA; the genetic material that: ❖Directs protein synthesis. ❖ Serves as genetic draft during cell replication. 3. Cytoplasm it contains different organelles each with different function that help the cells to fulfil its individual function: 1. Cytoskeleton; interconnected system of protein fibres and tubes (microtubules, microfilaments, intermediate filaments)extends throughout the cytosol, gives cell shape, framework, regulates various movements. 2. Cytosol; intracellular fluid (ICF); semiliquid, gel-like mass 3. Organelles; structures suspended in ICF; each has specific role and work in integrated manner. Most cells have 6 organelles types: A. Endoplasmic reticulum (ER); series of membranes that contain protein-and lipid-manufacturing factories (ribosomes; produce proteins) B. Golgi complex; raw proteins are processed, sorted, packaged, and directed to proper destination Fluorescent light micrograph showing their nuclei (purple) and cytoskeletons (yellow and blue) CYTOPLASM C. Lysosomes: contain powerful enzymes that break down organic molecules, vary in size and shape depending on what they are digesting. -Average cell has about 300 lysosomes -Digest extracellular material brought into cell - Remove worn out organelles (Autophagy, Apoptosis) D. Peroxisomes; house oxidative enzymes that degrade toxic wastes produced with cell or toxins that have entered cell (such as alcohol) E. Mitochondria; powerhouse of cell; extract energy from food nutrients and transform it into usable form for cellular activities: Adenosine triphosphate (ATP). -Number varies widely depending on cell’s energy requirements F. Ribosomes; make proteins by translating ribonucleic acid (RNA) into chains of amino acids in sequence controlled by deoxyribonucleic acid(DNA)-exist free in cytosol or attached to rough ER Basic structure of cell membrane 1. lipid bilayer, which is a thin, double-layered film of lipids—each layer only one molecule thick—that is continuous over the entire cell surface. ◦ Interspersed in this lipid film are large globular proteins. ◦ One end of each phospholipid molecule is soluble in water; that is, it is hydrophilic. ◦ The other end is soluble only in fats; that is, it is hydrophobic. ◦ The phosphate end of the phospholipid is hydrophilic, and the fatty acid portion is hydrophobic. 2. Membrane carbohydrates: (glycoproteins, glycolipids) small amount located only at outer surface. 3. Membrane Proteins: attached to or inserted within lipid bilayer. Anatomically, 2 groups: a. Peripheral: attach loosely to other proteins that span the membrane or to lipid bilayer. b. Integral: tightly bound into the phospholipid bilayer. ◦ Transmembrane Proteins are integral proteins that extend all the way through the membrane. Proteins that penetrate the membrane are hydrophobic 4. Some membranes have microvilli, cilia, flagella  Membrane proteins Membrane proteins have many functions: 1. Receptors for hormones: 2. Pumps for transporting: materials across the membrane 3. Ion channels: Create water-filled passageway to enable water-soluble substances that are small enough to enter or pass through membrane without coming into direct contact with hydrophobic lipid interior. o Restricted to ions and water. o May be specific for 1 ion. o May allow ions of similar size & charge to pass. o May be open or gated. 4. Adhesion molecules: for holding cells to extracellular matrix 5. Cell recognition antigens: Recognition of “self-glycoproteins” on surface of membrane structural proteins; maintain shape of cell. General Functions of the cell membrane 1. Physical Isolation. 2. Supporting and hold the cytoplasm. 3. Transport: Helps determine cell’s composition by selectively permitting certain substances to pass between cell and its environment (selective barrier). 4. Structural-participates; in joining of cells to form tissues & organs. 5. Recognition: Plays key role in enabling cell to respond to changes in cell’s environment (The immune response; is the ability to distinguish between self and non-self, every cell in the body carries distinctive molecules that distinguishes it as "self"). Normally the body's defenses do not attack tissues that carry a self-marker. Rather, immune cells coexist peaceably with other body cells in a state known as self-tolerance. Membrane Transport Membrane Permeability: Permeability refers to ability of the membrane to allow substances to enter/leave cell. They could be: 1. Permeable 2. Impermeable 3. or Selectively permeable. Two properties influence whether substance can pass through unassisted: 1. Solubility of particle in lipid (highly lipid-soluble particles dissolve & pass through). 2. Size of particle Terms you should know ❖ Concentration gradient; difference in concentration of substance between two places (sometimes called chemical gradient) ❖ Solution: is a special type of homogeneous mixture composed of two or more substances ❖ Solvent: a substance that dissolves a solute, resulting in a solution. ❖ Solutes: a substance that can be dissolved by a solvent to create a solution Two general types of movement occurs across cell membrane. 1. Passive transport: (Diffusion): which is Passive, does not require input of energy (uses only energy of molecular movement). ◦ Includes: simple diffusion, facilitated diffusion and osmosis. 2. Active transport: requires energy (ATP) to transport substance across. ◦ divided into primary and secondary active transport. ◦ Active transport of Na+ and K+ is one of the major energy-using processes in the body. On the average, it accounts for about 24% of the energy utilized by cells, and in neurons it accounts for 70%. Thus, it accounts for a large part of the basal metabolism. 1. Passive transport (Diffusion) Divided into two subtypes called simple diffusion and facilitated diffusion. A. Simple diffusion: means that kinetic movement of molecules or ions occurs through a membrane opening or through intermolecular spaces without any interaction with carrier proteins in the membrane. ◦ Simple diffusion can occur through the cell membrane by two pathways: 1. Through the interstices of the lipid bilayer if the diffusing substance is lipid soluble. 2. Through watery channels that penetrate all the way through some of the large transport proteins. 1. Passive transport (Diffusion) cont. B. Facilitated diffusion (passive transport) Requires interaction of a carrier protein. The carrier protein aids passage of the molecules or ions through the membrane by binding chemically with them and shuttling them through the membrane in this form. Rate of diffusion is affected by (Fick’s Law of Diffusion 1. Surface area of membrane 2. Magnitude of concentration gradient 3. Molecule size & weight 4. Temperature 5. Thickness of cell membrane 5. Lipid solubility of substance ❖ Ions can also permeate membrane along electrical gradient: Electrical forces; (like charges repel, opposite charges attract). Carrier-Mediated Transport, Co-transport or Assisted Membrane Transport ❖ Large, poorly lipid- soluble molecules, such as proteins, glucose, etc. cannot cross plasma membrane on their own no matter what forces are acting on them, so need the aid of a carrier protein. ❖ Carrier protein spans thickness of plasma membrane ❖ Carrier proteins bind to specific substances and transport them by changing shape. ❖ Carrier mediated Transport, demonstrates 3 properties: 1. Specificity 2. Competition 3. Saturation Two forms of carrier-mediated transport depending on whether energy must be supplied to complete the process: facilitated diffusion (and active transport discussed later) Properties of facilitated diffusion 1. Facilitated diffusion cannot cause net transport of molecules from a low to a high concentration, as this would require input of energy 2. ATP energy not required 3. Transport rate reaches a maximum when all of the protein transporters are being used (saturation) 4. It's very specific it allows cell to select substances taken up 5. Sensitive to inhibitors that react with protein side chains  Passive transport (Diffusion) cont. C. Osmosis (water diffusion) o The most abundant substance that diffuses through the cell membrane is water. o Normally, the amount that diffuses in the two directions is balanced so precisely that zero net movement of water occurs. Therefore, the volume of the cell remains constant. a. Movement of water down its concentration gradient across a selectively permeable membrane (many cell types have aquaporins that allow passage of water) b. Water moves by osmosis to the area of higher solute concentration, i.e. to dilute the area. c. As solute concentration increases, the water concentration decreases correspondingly. d. Osmolarity: measure of a solutions total concentration given in terms of number of ions (osmole/liter),normal osmolarity of body fluids is 300mOsm/L (millosmole/liter). (Osmolarity tendency of a solution to pull water in) osmosis often produces significant volume changes, causing swelling or shrinking; a) If the external solution balances the osmotic pressure of the cytoplasm it is said to be isotonic. b) If the external solution is more dilute than the cytoplasm it is hypotonic c) if the external solution is more concentrated it is hypertonic. Active Transport When a cell membrane moves molecules or ions “uphill” against a concentration gradient (or “uphill” against an electrical or pressure gradient), the process is called active transport. Active transport is divided into two types according to the source of the energy used to cause the transport: 1. Primary active transport: the energy is derived directly from breakdown of adenosine triphosphate (ATP) or of some other high – energy phosphate compound. 2. Secondary active transport: the energy is derived secondarily from energy that has been stored in the form of ionic concentration differences of secondary molecular or ionic substances between the two sides of a cell membrane, created originally by primary active transport. In both instances, transport depends on carrier proteins that penetrate through the cell membrane Properties of Active transport 1. Can transport substances from a low concentration to a high concentration ("uphill" transport) 2. ATP energy required 3. Examples: The Na+ /K+ -ATPase (known as the “sodium pump”), Ca2+ -ATPases (the Ca pump), H+ / K+ -ATPases, H+ -ATPases, multidrug resistance (MDR) transporters 4. Transport rate reaches a maximum when all of the protein transporters are being used (saturation). 5. Very specific, allows cell to select substances taken up 6. Sensitive to inhibitors that react with protein side chains ❑Note: about a third of your basal metabolism is used in active transport of various substances. Sodium -Potassium Pump as an example of Primary Active Transport 1. Most important form of active transport in cells. 2. Maintains concentration gradients of NA+ and K+ across cell membrane. 3. Moves 3 sodium ions from inside cell to ECF. 4. Moves 2 potassium ions from ECF into cell. 5. Net movement =high Na+ concentration in ECF and high K+ concentration in ICF. 6. Transmembrane potential: inside of cell has slight negative charge as compared to outside of cell 7. Difference in charges=a potential. reflects unequal distribution of positive and negative charged ions. Secondary Active Transport Secondary Active Transport: Combines active transport and facilitated diffusion. Examples: Glucose transport across the wall of the gut. Na+ gradient is produced by the Na pump (active transport) The Na+ concentration gradient is used to produce secondary transport of sugars and amino acids (facilitated diffusion) Some sugar and amino acid transporters must bind Na as well as the sugar or amino acid (coupled transport) Both Na+ and the organic molecule must be present at the same time and on the same side of the membrane Since there is more Na outside the cell, sugars and amino acids get transported mainly from the outside to the inside The sugar and amino acid transporters do not use ATP directly, but ATP is required to set up the Na gradient. There are many examples of secondary active transporters Cotransporters (symporters) couple the movement of two or more solutes in the same direction. Examples of Na+ -driven cotransporters include Na+ /glucose uptake in the intestine and Na+ /Cl uptake in the kidney. Exchangers (antiporters) couple the movement of two solutes in the opposite direction. Na+ - driven exchangers include Na+ /Ca+2 and Na+ /H+ exchange, which are important for maintaining low intracellular [Ca+2]and [H+ ], respectively. Homeostasis: describes the state of 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. ◦ E.g: the lungs provide oxygen to the extracellular fluid to replenish the oxygen used by the cells. ◦ the kidneys maintain constant ion concentrations. ◦ the gastrointestinal system provides nutrients