Pharmacy Lecture 2 (General Physiology) PDF

Lecture 2 General Physiology Dr. Mohamed Shebl Amer PhD in Human Physiology, Leeds Uni, UK Faculty of Medicine 2024-2025 Cell Structure and Functions The Cell The cell is the basic structural and functional unit of th...

Lecture 2 General Physiology Dr. Mohamed Shebl Amer PhD in Human Physiology, Leeds Uni, UK Faculty of Medicine 2024-2025 Cell Structure and Functions The Cell The cell is the basic structural and functional unit of the body. It produces many different functions. The functions of any organ are the sum of functions of cells composing it. It consists of three principal parts: Plasma membrane. Cytoplasm and organelles. Nucleus.  Cell Membrane Definition: It is a thin elastic semipermeable membrane that surrounds the cell cytoplasm. Characters: Very thin (75-100 Ao). Elastic. Semipermeable (have selective permeability). Flexible. Fluidity. 1. Selective barrier (selective permeability) that allows some substance to pass and prevent others. 2. Protects the cytoplasmic mass and keep internal environment of the cell. 3. Regulates the transport of substances into and out of the cell. 4. Contains protein receptors for hormones and transmitters. 5. Contains numerous regulated ion channels. 6. Links adjacent cell together and to extracellular matrix. 7. Generates the membrane potential in excitable cells (nerves and muscles).  Composition of the Cell Membrane Composition: It has certain common features as: 1. 55% proteins 2. 42% lipids 3. 3% carbohydrate A) Cell Membrane  Form a continuous layer all through the cell membrane. There are 3 types of lipids in the cell membrane: 1. Phospholipids bilayer 2. Dissolved cholesterol 3. Glycolipid (1) Phospholipids bilayer membrane:  Composed of phospholipid molecules.  One end (phosphate end) is soluble in water (hydrophilic).  The other end (fatty acid portion) is soluble only in fats (hydrophobic). Functions:  It responsible for selective permeability of the cell membrane (It prevents the passage of H20 and H20 soluble molecules but allows the passage of lipid soluble molecules).  Responsible for fluidity of the membrane Present only on the inner side of the cell membrane in between the heads of the phospholipid where it is dissolved in the lipid bilayer. Function of membrane cholesterol: 1. Responsible for toughness and solidity of the cell membrane. 2. Share in selective permeability and fluidity of the membrane like phospholipid bilayer. (3) Glycolipids Some carbohydrates molecules are attached loosely to the outer surface of membrane attached to phosphate group called glycolipids. (2) Cell Membrane Proteins: 1- Integral proteins: Protrude all the way through the membrane. Function: 1. Structural channels (or pores): water-soluble substances (ions). 2. Carrier proteins for transporting substances that cannot penetrate. 3. Active transport: opposite to the natural direction of diffusion. 4. Receptors for water-soluble chemicals. 5. Function as enzymes facilitating the biochemical reactions at the cell surface. 2- Peripheral proteins: Attached only to one surface of the membrane and do not penetrate. Function: 1. Act mainly as enzymes. 2. Controllers of transport of substances through the cell membrane. (3) Membrane Carbohydrates: They are present mainly in the form of glycolipid and glycoprotein. They are present on outer surface of cell membrane forming a thin layer (coat) called glycocalyx. Functions of glycolipids and glycoproteins: 1. They act as markers that facilitate Cell-Cell recognition. 2. Stabilizer of membrane structure. 3. Enter in immune reaction that distinguish self from non self. 4. They contribute to cell adhesion by interacting with other cells. 5. Receptors for hormones and other neurotransmitters. 6. Antigens like those of ABO system on RBCs. 7. Function as enzymes facilitating the biochemical reactions at the cell surface. Cytoplasm and Organelles Cytoplasm: It is the aqueous content of the cell. Organelles: They are sub-cellular structures within the cytoplasm. Nucleus: It is a large spheroid body. It is the largest organelle within the cell. It contains the genetic material (DNA). Cytoplasm and Organelles (continued) Cytoplasm Cytoplasm: It is a jelly-like matrix within the cell where cell- organelles are suspended. It contains a highly organized structure with microtubules and microfilaments (mainly Actin that functions as cytoskeleton. Lysosomes Lysosomes are responsible for: 1. Digestion: Because they contain digestive enzymes for digestion of nutrients and harmful molecules. 2. Autophagy: It is the process that destroys worn-out (old) organelles, so that they can be continuously replaced. 3. Apoptosis (programmed cell death): Lysosomes release digestive enzymes into the cell so, a naturally programmed cell death is started that is called apoptosis. Mitochondria Mitochondria are the sites for energy production of all cells (ATP molecules production); except, in mature RBCs. They contain their own DNA and can reproduce themselves. Ribosomes Ribosomes are essential for Protein synthesis in the cell. Proteins produced according to genetic information contained in mRNA. Ribosomes are located both in the cytoplasm and on the surface of endoplasmic reticulum. Endoplasmic Reticulum (ER) ER is two types: 1. Granular (rough) ER: a) It carries ribosomes on it’s surface, in cells active in protein synthesis. b) Proteins enter ER are modified for secretion. 2. A granular (smooth) ER: a) It provides a site for steroid hormone production and inactivation. b) Storage of Ca2+ (calcium) ions. Golgi Complex It is hollow, flattened sacks- like organelle with cisternae. It modifies proteins and separates them according to their final destination. Cell Nucleus Most cells have a single nucleus. Some cells such as Red Blood Cells (RBCs) contain no nucleus. Enclosed by inner and outer membrane called the nuclear envelope. Functions of the nucleus: 1. It contains the genetic material (DNA). 2. It controls all cellular functions by regulating gene expression.  Chromosomes: They are found in the nucleus. They made of DNA. They contain instructions for characteristics. Somatic cell contain 46 chromosomes. Germ cell (sperms and ova) contain 23 chromosomes. Nucleolus It constitutes 25% of the nuclear volume. It composed of proteins and RNA. It is the center for production of ribosomes  Transport of substances across cell membrane 1) Passive transport: a) Diffusion: Simple diffusion and Facilitated diffusion b) Osmosis c) Filtration d) Solvent drag 2) Active transport: a) Primary active b) Secondary active 3) Vesicular transport: a) Exocytosis b) Endocytosis  (1) Passive transport Along concentration, electrical or pressure gradients. A) Diffusion: Definition: passive transport of molecules from areas of higher concentration to areas of lower concentration with no need for energy. Diffusion includes simple diffusion and facilitated diffusion. 1. Simple diffusion: Small molecular weight molecules are transported due to their random movement such as transport of gases at RBCs and at the capillaries of the lungs with no need for energy or carriers. ∆ 𝐶x A 𝑥 𝑇 J = 𝐷𝑥 Factors affecting the rate of diffusion (J): 𝑑 𝑥 ( 𝑚𝑤)  Directly proportional to the concentration gradient (∆ C).  Directly proportional to cross-sectional area (A).  Directly proportional to the temperature (T).  Inversely proportional to the distance (d) to be travelled (thickness).  Inversely proportional to the molecular weight of transported molecules (√mw). 2) Facilitated diffusion: Definition: The only difference between it and simple diffusion is the molecular size of the transported substance. if the molecular size is too large to be transported by simple diffusion, then the only way to carry this substance is through a carrier without any need for energy consumption such as glucose and most of the amino acids transport at the intestine and renal epithelium. Mechanism: The molecule to be transported is attached to a specific receptor site on the carrier, then a conformational changes occur in the carrier molecule that enables it to drive the molecule to its destiny. b) Osmosis: Definition: is the diffusion of water or any other solvent molecules through a semipermeable membrane (i.e. membrane permeable to solvent but not to the solute) from a solution containing lower concentration of solutes towards the solution containing higher concentration of solutes. Osmotic pressure: Definition: is the minimum pressure which when applied on the side of higher solute concentration prevents the osmosis. 29 C) Filtration Definition: It is the movement of the fluid molecules through a semipermeable membrane by the force of the hydrostatic pressure of that fluid. Mechanism: Fluid is forced through a porous membrane by difference in hydrostatic pressure (from high pressure side to low pressure side and takes with it small molecules that can pass through the pore of this membrane. Examples: filtration of tissue fluid at capillaries and interstitial fluid formation (ISF). 30 D) Solvent drag Definition: Diffusion of a solute following the diffusion of its solvent through a semipermeable membrane. Mechanism: In this type of transport, when solvent is separated from a solution by a semipermeable membrane. The solvent flows in one direction and drags some molecules of the solute with it. Example: tubular reabsorption of water increases urea concentration in tubular fluid leading to increase urea reabsorption.  (2) Active transport Definition: transport against the chemical and/or electrical gradient and involves expenditure of energy. A) Primary active transport: Energy is derived directly from the breakdown of ATP. 1. Sodium–potassium (Na+– K+) pump: Present in all the cells of the body. Pumping 3 Na+ outside and draw 2 K+ inward into the cell Functions of Na+–K+ pump: 1. Controlling the cell volume. 2. Electrogenic activity: Na+–K+ pump: creates the electrical potential across the cell membrane. This is basic requirement in nerves and muscles to regain resting membrane potential "RMP" and transmit the signals. B) Secondary active transport: Energy is derived secondarily or indirectly from the movement of another molecule along its concentration gradient. Examples of secondary active transport: 1. Co-transport (Symport): Such as the sodium-glucose co-transporter in the luminal border of the intestine that allows glucose to enter the cells against its concentration gradient along with Na+ ions that moves down its concentration gradient. 2. Counter-transport (Antiport): Such as the sodium-calcium exchanger in the cardiac cells that allows Ca+2 ions to be transported outside the cells against its concentration gradient where Na+ ions moves down its concentration gradient to inside the cells. Types of carrier protein system: 1) Uniport: the carrier proteins transport only one type of molecules. 2) Symport: The transport of one substance is linked with the transfer of another substance in the same direction. 3) Antiport: carrier proteins exchange one substance for another in the opposite direction. The symports and antiports are together known as co- transport. Figure 10: Types of carrier protein system: A) Uniport, B) Symport, C) Antiport  (3) Vesicular transport Definition: it is an export or import process of material from vesicles targeted to the cell membrane dependent on Ca2+ ions. A) Exocytosis: Transport of proteins to the cell membrane in vesicles → the area of fusion between vesicle and cell membrane then breaks down → leaving the contents of the vesicle outside → the cell membrane intact. B) Endocytosis: The reverse of exocytosis. Types of endocytosis: 1) Phagocytosis (cell eating) 2) Pinocytosis (cell drinking) Intercellular direct connections: Cells are physically joined by specialized types of junctions: 1) Desmosomes: 20 nm apart and have a dense accumulation of protein at the cytoplasmic surface of each membrane and between them. Function: Hold adjacent cells firmly together in areas that are subject to considerable stretching, such as in the stomach, bladder and skin. 2) Tight junctions: no extracellular space between them. Function: Most epithelial cells are joined by tight junctions. 3) Gap junctions: protein channels linking the cytosols of adjacent cells with 2- 4 nm apart to allows specific proteins from the 2 membranes to join forming small, protein lined channels linking the 2 cells. Function: a) Gap junctions connect cardiac muscle cells and smooth-muscle cells. b) Play a very important role in the transmission of electrical activity between the cells. 37 Chemical Communication : Occurs through a release of chemical messenger from one cell that combines with specific receptors on another cell to achieve the desired response. It is the most common type of transmission in the body. It includes the following mechanisms: 1. Autocrine transmission (Self signaling): The cell secretes chemical messenger that binds to receptors and acts on the same cells ( as interferon, growth factors). 2. Paracrine transmission: the chemical messenger affects nearby cells such as GIT hormones & renin hormone in the kidney. 3. Endocrine transmission : The chemical transmission are hormones that released from endocrine glands that diffuse to the blood then pass to target remote organs. 38 Neural (Synaptic transmission): The nerve cell endings contain neurotransmitter as Acetylcholine (Ach) that diffuses and crosses the synaptic cleft to bind to specific receptors on the postsynaptic membrane of a muscle membrane. 39 Electrical Communication : Communication occurs via gap junctions that are present between cells in some tissues. Direct flow of electrical ions to neighboring cells as in cardiac muscle.  Thank You Faculty of Medicine 2024 - 2025