Cell Membrane PDF

# Cell Membrane Dr. Dalia El Agamy ## Physiology of the Cell - The human body is formed of different systems, e.g., cardiovascular, respiratory, and digestive systems. - Systems are formed of a group of organs of complementary function. - Organs are made up of different tissues of complementary fu...

# Cell Membrane Dr. Dalia El Agamy ## Physiology of the Cell - The human body is formed of different systems, e.g., cardiovascular, respiratory, and digestive systems. - Systems are formed of a group of organs of complementary function. - Organs are made up of different tissues of complementary function. - Tissues are made up of cells which are the smallest structural units in the body - The functions of different parts of the body are well coordinated to maintain the health of the individual. ## Structure of the Cell 1. A mass of protoplasm: which consists of. - Cytoplasm. - Cell organelles. - Nucleus. 2. Cell membrane. ## Cell Structure A diagram of a human cell is shown, labeled with: - Lysosome - Rough endoplasmic reticulum - Nucleus - Nucleolus - Mitochondrion - Golgi apparatus - Centriole - Cytoplasm - Ribosomes - Vacuole - Cell membrane **Figure 1**: The structure and components of human cell. Adopted from [1] ## The Cell Membrane - The cell membrane, also known as the plasma membrane, is a double layer of lipids and proteins that surrounds a cell and separates the cytoplasm from its surrounding environment. ### Function 1. Protects the cell from its surroundings. 2. Controls the movement of substances in and out of cells and organelles. It is selectively permeable to ions and organic molecules. 3. Contains receptors for chemical substances that stimulate or inhibit the cell functions. ### Structure - The cell membrane is a lipid bilayer with embedded proteins and small amount of carbohydrates: 1. Lipids: - The lipids in the cell membrane are polar, mostly a mixture of phospholipids and cholesterol. - Phospholipids are arranged in bilayer with the hydrophilic head of the phospholipid molecule arranged on the inner and outer surfaces of the cell membrane and the hydrophobic non-polar tail inside. - Cholesterol is responsible for toughness of the cell membrane and solidity of the cell membrane is directly proportional with cholesterol/phospholipid ratio. 2. Proteins: - Proteins are embedded in the phospholipid bilayer. Some are combined with lipids (lipoproteins) and some are combined with carbohydrates (glycoproteins). - **Types:** - Peripheral proteins: appear on the outer surface of the membrane. - Internal proteins: appear on the inner surface of the membrane. - Transmembrane or integral proteins: occupy the whole thickness of the membrane and appear on both outer and inner surfaces. - **Functions:** - **Membrane receptors:** relay signals between the cell and the external environment. - **Transport proteins:** for transport of water and ions either through active or passive transport. - **Membrane enzymes:** catalyze reactions on inner and outer surface of the membrane. - **Adhesion molecules:** that give the cell its label of identity. So that the cell can identify each other and interact, e.g., proteins involved in the immune response. - **Structural proteins:** that give the membrane its integrity. 3. Carbohydrates - Small in amount, less than 10% of the cell membrane mass. - They are either combined with lipids (glycolipids) or with proteins (glycoproteins). - Glycolipids and glycoproteins are present on the outer surface of the cell membrane. - **Functions:** - Attach cells to each other. - Act as a receptor substance. - Some enter in the immune reaction. - Give most of the cells -ve surface charge which affects interaction of regulatory molecules with the membrane A diagram is shown of the membrane labeled with: - Protein channel - Carbohydrate chains - Proteins - Lipid bilayer **Figure 2**: Structure of the cell membrane. Adopted from [2] ## Transport Across Cell Membrane - The cell membrane is described as partially permeable or semi-permeable. - It mostly consists of phospholipids, which are composed of hydrophobic (water hating) tails and hydrophilic (water loving) heads. This tail prevents water soluble, polar ions and molecules to pass in and out of the cell. - Those ions and molecules restricted by the phospholipids pass in and out of the cell via membrane proteins. ## Methods of Transport of Molecules Across the Cell Membrane ### A. Passive Transport - Transmembrane proteins create a water-filled pore through which ions can pass by diffusion down a concentration gradient. - It requires NO energy. - **Types of passive transport:** 1. **Simple diffusion:** - It is the movement of molecules across the cell membrane down its concentration and electric gradient. - It requires no energy. - ***Factors affecting rate of diffusion:*** - **Concentration gradient of the substance:** - The rate of diffusion is DIRECTLY proportionate to the concentration gradient of the substance across the cell membrane. - **The molecular weight of the substance:** - The rate of diffusion is INVERSELY proportionate to the molecular weight of the substance. - **The solubility of the substance in the medium:** - The rate of diffusion is DIRECTLY proportionate to the solubility of the substance in the medium. - **Surface area of the cell membrane:** - The rate of diffusion is DIRECTLY proportionate to the surface area of the cell membrane. - **Distance though which the substance must diffuse:** - The rate of diffusion is INVERSELY proportionate to the thickness of the cell membrane. - **The temperature of the medium:** - The rate of diffusion is DIRECTLY proportionate to the temperature of the medium. 2. **Facilitated Diffusion:** - It is the movement of molecules across the cell membrane down its concentration and electric gradient. - It requires no energy - It is concerned for transport of substances that have larger molecular diameter than the channels pore and insoluble in lipid, e.g., glucose and amino acids. - It requires carrier protein. A diagram is shown of facilitated diffusion labeled with: - Carrier protein - Solute **Figure 5**: Facilitated Diffusion. Carrier protein. Adopted from [5] - **Characteristics of the carrier protein:** - **Specificity:** the carrier is specific to the substance bound to it. - **Saturation:** increased concentration of the substance to be transported beyond a certain extent → no more carriers will be available for the transport process. - **Competition:** similar substances compete for the same carrier and the transport of the substance depends on its relative concentration to the other substances and affinity of the carrier. 3. **Osmosis:** - Movement of a solvent (such as water) through a semipermeable membrane (as the cell membrane) into a solution of higher solute concentration that tends to equalize the concentration of solute on the two sides of the membrane. A diagram is shown of osmosis labeled with: - Semipermeable membrane **Figure 6**: Osmosis. Adopted from [6] - **Osmotic pressure:** the pressure needed to prevent movement of the solvent (such as water) across the semipermeable membrane caused by different osmolarity. - The osmotic pressure of a solution depends on number of particles in the solution rather than the type of particles. ### B. Active Transport - Occurs against concentration and electrical gradient. - Requires energy. - Requires carrier protein. - Requires ATPase enzyme for breaking down of ATP to release energy. - **Mechanism:** The receptor of the carrier protein binds to the specific substance →activation of ATPase enzyme → break down of ATP and release of energy that is required for the transport. - **Types of active transport:** according to the source of energy: 1. **Primary active transport:** - The source of energy is the breakdown of ATP. - **Examples:** - **Active Na+ - K+ pump:** - It transports 3 Na+ out and 2 K+ into the cell. - It is an electrogenic pump. - It contains Na+ - K+ ATPase enzyme. - **H+ - K+ pump** - Present in the gastric mucosa for HCl secretion. - **Ca²+ pump:** - Present in the cardiac and skeletal muscles. A diagram is shown of active transport labeled with: - ATP - Active transport **Figure 7**: Active transport. Adopted from [7] 2. **Secondary active transport:** - The carrier protein couples the movement of an ion (typically Na+ or H+) down its electrochemical gradient to the movement of another molecule or ion against a concentration/electrochemical gradient. - Thus, energy stored in the electrochemical gradient of an ion (driving ion) is used to drive the transport of another solute against a concentration or electrochemical gradient. - The free energy needed to perform active transport is provided by the concentration gradient of the driving ion. - **Examples:** - **Na+/glucose cotransporter:** - It utilizes the Na+ electrochemical gradient to drive the transport of glucose into the cell against the concentration gradient. ## Type of carriers (Transport Proteins) 1. **Uniport:** - Transport 1 substance in one direction. - Example: Ca2+ pump. 2. **Symport:** - Transport 2 substances simultaneously in the same direction. - Example: Na+/glucose cotransporter. 3. **Antiport:** - Transports one substance in one direction and another substance in the opposite direction. - Example: Na+ - K+ pump. A diagram is shown of different types of carriers labeled with: - **Uniporter** - **Symporter** - **Antiporter** **Figure 8**: Types of carriers. Adopted from [8] ### C. Endocytosis and Exocytosis The primary mechanisms by which cells import and export macromolecules. Requires energy (Active transport). ### Mechanism 1. **Exocytosis:** The process by which a cell expels molecules and other objects that are too large to pass through the cellular membrane, e.g., enzymes, hormones, and proteins. Macromolecules inside the cells are surrounded by the vesicle → the vesicle moves to the edge of the cell and tethers itself to the cellular membrane → breakdown of the fusion area. It then pushes its molecular contents out through the cellular membrane. 2. **Endocytosis:** The process by which a cell takes in molecules and other objects that are too large to pass through the cellular membrane, e.g. nutrients, bacteria and other pathogens. The cell engulfs molecules or proteins near the surface of the cellular membrane. It can create receptor pockets to which specific types of molecules are attracted. Once the molecule is surrounded by the cellular membrane, the area is pinched off to create a vesicle inside the cell that holds the molecule. Endocytosis may be receptor-mediated, or spontaneous (non-receptor mediated. - In endocytosis, if the substance taken is dissolved and non-visible under the microscope e.g., water, then, the process is called pinocytosis (cell drinking). Whereas, if the substance taken is large and visible under the microscope, e.g., bacteria and cellular debris, the process is called phagocytosis (cell eating). A diagram is shown of exocytosis and endocytosis labeled with: - Plasma membrane - Endocytic visicle forming - Exocytic visicle leaving cytoplasm **Figure 9**: Exocytosis and endocytosis. Adopted from [9] # General Physiology Dr. Dalia El Agamy ## General Physiology General physiology represents the general concepts and principals that are basic to the function of all systems in the body. ### Composition of the human body - The body of a normal young adult male is composed of: - **Water:** represents about 60% of the total body weight. - **Proteins:** represents about 18% of the total body weight. - **Fats:** represents about 15% of the total body weight. - **Minerals:** represents about 7% of the total body weight. A diagram is shown of the composition of a human, labeled with: - Water 42 kg - Fat 10.5 kg - Protein 12.6 kg - Glycogen - Calcium - Phosphorous - Mg Cl Fe Zn - Potassium - Sodium Cu - other **Figure 10**: Composition of the human body. Adopted from [10]. ## Body Fluids - **Total body water (TBW)** represents about 60% of the total body weight. ### Body Fluid Compartments - Total body water is distributed among the following compartments: 1. **Intracellular fluid (ICF):** the fluid inside the cells. Represents 40% of the total body weight. 2. **Extracellular fluid (ECF):** the fluid outside the cells. It represents 20% of the total body weight. - The extracellular fluid is distributed into the following compartments: - **Interstitial fluid (ISF):** the fluid in the interstitial spaces bathing the cells. It represents 15% of the total body weight. - **Plasma:** the fluid portion of the blood that is present inside the circulatory system. It represents 5% of the total body weight. - **Transcellular fluid:** the fluid present within epithelial-lined spaces. - Organs: Gall bladder, stomach, intestine, and urinary bladder. - Peritoneal, pleural, pericardial cavities. - Cerebrospinal fluid. - Intraocular fluid. - Synovial fluid (joint spaces). A diagram is shown of the body fluid compartments labeled with: - Intracellular fluid (ICF) - Plasma - Interstitial fluid (ISF) ### Physiological Variations in the Total Body Water - Different physiological factors can affect the percentage of the total body water: 1. **Age:** total body water as a percent of total body weight is greater in infants and young children than adults (75% of the total body weight). It reaches adult level at puberty (60-65% in men and 50-55% in women) and lesser content at old age. 2. **Sex:** total body water as a percent of total body weight is lesser in females than males of the same age because of the high fat content. 3. **Fat content:** obese people have lesser total body water as a percent of total body weight because fat is relatively free of water. A diagram is shown of the body water compartments labeled with: - Total body water (60%) - Intracellular water (40%) - Extracellular water (20%) - Interstisial water (13-14%) - Plasma (5%) - Transcellular water (1-2%) ### Importance of Water in the Body - It constitutes not less than 40% of the total body weight. - Water acts as a solvent, so it is important for: - **Nutrition:** nutritive materials are dissolved in water. - **Digestion:** digestive enzymes are hydrolytic (need water to break down chemical bonds). - **Absorption:** it acts as a vehicle for the nutritive materials to be absorbed. - **Excretion:** it acts as a vehicle for the waste products to be excreted from the body. - **Osmolarity:** it is a property of fluids only. Important for regulating the flow of water between fluid compartments in the body. - **Mobility of ions, molecules, and particles** - **Formation of ions:** e.g., Na+, K+, Cl, and HCO3 which is important for membrane polarization and excitability. - Water has ionizing property (dissociation into H⁺ and OH) which is important for: - **Regulation of pH of body fluids.** - **Formation of hydrochloric acid (HCI) in the stomach.** - **Reabsorption of HCO3- at the kidney during acidosis.** - **Electron transport in biological oxidation inside mitochondria.** - Water is essential for all sensations except tactile sensation, e.g., vision, hearing, taste, smell, and equilibrium sensation. - **Regulation of body temperature:** water is important in body temperature regulation because it has high specific heat value, high latent heat of evaporation, high latent heat of solidification, and high heat conductivity. - Water makes tissue pliable and flexible, thus preventing cracking and easy fracture of the tissue. - **Loss of total body water:** - More than 1% of the total body weight → thirst sensation. - More than 5% of the total body weight → dehydration. - More than 20% of the total body weight → Death. ### lonic Composition of the Different Fluid Compartments: - **Sodium (Na+)** is the principal cation and **chloride (CI)** is an important anion in the ECF. - **Potassium (K+)** is the principal cation in ICF, and phosphate and sulphates predominate in ICF. - **Proteins** contribute significantly to the anion content in the ICF. But in ECF it is largely confined to plasma. - The difference in composition between ICF and ECF depend on two main mechanisms: - **The integrity of the cell membrane** → inability of large molecules to pass freely through cell membranes. - **Sufficient supply of energy** which will be required for the active transport of substances across the cell membrane. ## Routes of Water Loss - Water balance occurs by matching the daily water input/output to and from the body. - The primary means of water intake is by consumption of food and fluids. ### Water loss from the body can be classified into: 1. **Sensible water loss:** loss that can be perceived or recognized by senses [ you know you've lost it!] and can be measured. Example: water loss occurring by urine, stool, and sweat 2. **Insensible water loss:** can neither be perceived [ you don't know that you've lost it or how much you have lost!] nor measured directly. Example: water evaporated from skin and respiratory tract. - A reduction of the central circulating blood volume, e.g., due to hypovolemia accompanying dehydration, if uncompensated, results in a fall in cardiac output and blood pressure. - Interstitial fluid provides a reservoir from which the vascular volume can be maintained during periods of hemorrhage or loss of vascular fluid. Among the possible compensatory mechanisms is the body's ability to mobilize water from the extravascular to the intravascular space. # Homeostasis Dr. Dalia El Agamy ## Homeostasis - **Definition:** it is the process of keeping the internal environmental conditions constant. - **The internal environment:** is the extracellular fluid that contains the ions and nutrients needed by the cells for maintenance of cellular life. All cells live in the same environment. - The composition of ECF is the same all over the body due to: - **Rapid exchange of water and solutes between plasma and interstitial fluid.** - **Rapid circulation of blood in the circulatory system.** - **Very short distance between the cell and capillary wall (50 micrometers)** → any substance can diffuse rapidly from the capillary to cell within few seconds. ## Control of Homeostasis - There are many control systems in the body which serve for maintenance of homeostasis. 1. **Nervous System:** - Rapid control mechanism through nerve impulses that travel along nerves. - **Example:** regulation of arterial blood pressure: - If the arterial blood pressure was increased → inhibition of vasomotor center in the medulla oblongata → (vasodilation of blood vessels and inhibition of cardiac properties) → decreased blood pressure toward normal and vice versa. 2. **Endocrine System:** - Slower regulatory mechanism through secretion of hormones from different endocrine glands. - **Example:** regulation of blood glucose level: - If blood glucose level was increased → stimulation of insulin hormone secretion (increased glucose entry into the cells and increased tissue utilization of glucose) → decreased blood glucose toward normal level and vice versa. 3. **Chemical Mechanism:** - **Example:** maintenance of constant O2 concentration in ECF - The oxygen buffering function of hemoglobin: at the lungs (in which there is high O2 tension) → the affinity of hemoglobin O2 increases → hemoglobin binds to O2. - While at the tissues (where O2 tension is low) → the affinity of hemoglobin to O2 decreases → hemoglobin releases O2 to tissues. - This depends on the chemical properties of hemoglobin. ## Feedback Control of the Homeostatic Mechanisms - Feedback control means the control of certain function by the resultant effect of this function. ### Types: 1. **Negative feedback control:** - The resultant effect of a function inhibits that function. - The response is negative to the initiating stimulus. - **Examples:** - **Regulation of CO2 concentration in arterial blood.** - increased CO2 concentration in arterial blood → increased pulmonary ventilation → washout of CO2 from the body → decreased CO2 toward normal level. And vice versa. - **Regulation of arterial blood pressure.** - increased arterial blood pressure → inhibition of vasomotor center (inhibition of the heart and vasodilation of blood vessels) → decreased ABP toward normal level. And vice versa. - **Regulation of blood glucose level:** - increased blood glucose level above normal → stimulation of insulin secretion (increased glucose entry and utilization by the tissues) → decreased blood glucose toward normal level. And vice versa. 2. **Positive feedback control:** - The resultant effect of a function stimulates that function. - The response is positive to the initiating stimulus. - **Examples:** - **Parturition:** - Stretch of uterine cervix → reflex uterine contraction → descend of the baby's head into the cervix → more stretch of the uterine cervix → more uterine contraction → continuation of the process until the baby is borne. - **Death cycles:** - In abnormal conditions, when positive feedback mechanisms are initiated, vicious cycles occur that lead finally to death. - Examples: heart failure and heat stroke cycles. A diagram is shown of the death cycles labeled with: - Weakness of the heart - Coronary blood flow - Cardiac output - Arterial blood pressure - More heat production - Rise of blood temperature - Stimulate metabolic rate **a) Heart Failure** **a) Heat Stroke** - Negative feedback control mechanisms leads to stability of the internal environment. - Positive feedback control mechanisms lead to instability and they operate in the body to complete certain function.