Cellular Physiology - Key Concept Slides.pdf

Anatomy, Physiology, & Pathophysiology - Definitions Anatomy is the branch of biology concerned with the study of the structure of organisms and their parts. Physiology is the science that is concerned with the function of the living organism and its parts, and of the physical and chemical process...

Anatomy, Physiology, & Pathophysiology - Definitions Anatomy is the branch of biology concerned with the study of the structure of organisms and their parts. Physiology is the science that is concerned with the function of the living organism and its parts, and of the physical and chemical processes involved. Pathophysiology is the science of disordered physiological processes associated with disease or injury. Cellular Physiology: Organization The Human Body - A Complex Society of Differentiated Cells Cells: the basic structural and functional unit (~ 100 trillion) Tissues: (muscles, epithelial, nervous) Organs: (kidney, heart, liver, pancreas) Organ systems: (cardiovascular, urinary) Cellular Physiology: Organization Hormone: A chemical messenger produced by one cell that circulates in the blood and acts on another cell. Paracrine: A chemical messenger produced by one cell that acts on a close by target cell and the chemical signal is broken down too quickly to be carried to other parts of the body. Autocrine: A chemical messenger produced by a cell that acts on that same cell.  BODY FLUID COMPOSITION Body Water Content – 57% (40 L) Infants – 65-70% Dehydration Kg % % Vol W t. Total Body Weight 70 10 0 Lean Body Mass 55 79 Total Body Water 40 57 100 Intracellular Fluid 25 36 63 Volume Extracellular Fluid 15 21 37 Volume Interstitial Fluid 11.5 16 28 Volume Plasma Volume 3.5 5 9 BODY MASS INDEX (BMI): The measurement of choice for many healthcare professionals studying obesity. BMI uses a mathematical formula that takes into account both a person’s height and weight. BMI equals a person's weight in kilograms divided by height in meters squared. BMI=kg/m2 BMI Categories: Underweight = ICF CM CM CM ECF ICF ECF ICF ECF ICF H2O H2O H2O H2O H2O H2O NET water movement Water movement NET water movement down osmotic gradient but no NET down osmotic gradient ECF to ICF ICF to ECF movement Organization of the Cell  Cell Membranes & Solute Movement Diffusion Equilibrium: if solute and water are freely permeable across a membrane then solute concentration and volume will become equal in the two compartments.  Cell Membranes & Solute Movement Cell Membrane: can limit the ability of solutes to move between the intracellular and extracellular compartments Fick’s First Law: describes the movement of solutes across a cell membrane  Cell Membranes & Solute Movement Lipids: 1) barrier to water and water-soluble substances 2) organized in a bilayer of phospholipid molecules CO2 N2 O2 ions glucose H2O halothane hydrophilic “head” hydrophobic FA “tail” Body Fluid Distribution: Reflection Coefficient Reflection Coefficient (s) – The measure of the permeability of a solute through a given membrane. s = 1 solute is completely reflected – impermeable s = 0 solute is not reflected at all – highly permeable s = 0.5 then the membrane is moderately permeable to the solute  Body Fluid Distribution: Na-K Pump Na-K Pump – maintains cell volume at normal levels under isosmotic conditions. Ø Cells would swell and burst if Na-K Pump were absent Ø Proteins and organic compounds trapped inside of cell (anionic) Ø Cations collect and water moves into cell Ø Na-K Pump is 3 Na+ out for 2 K+ in Ø Works because cell membrane is far less permeable to Na+ * An increase in cell size (15%) is sensed and Na-K pump is activated  Body Fluid Distribution: Tonicity Isotonic no net movement of fluid into or out of a red blood cell Hypotonic lower tonicity causing net movement of fluid into a red blood cell Hypertonic higher tonicity causing net movement of fluid out of a red blood cell Isosmotic equal concentration of osmotically active particles across a semipermeable membrane  Osmolarity versus Tonicity 0.15 M 0.3 M 0.3 M 0.3 M 0.1 M Molarity NaCl NaCl Urea CaCl2 CaCl2 Osmolarity 0.3 Osm 0.6 Osm 0.3 Osm 0.9 Osm 0.3 Osm NaCl NaCl Urea CaCl2 CaCl2 Isosmotic Hyperosmotic Isosmotic Hyperosmotic Isosmotic Tonicity Isotonic Hypertonic Hypotonic Hypertonic Isotonic Cell remains Cell Shrinks Cell swells Cell Shrinks Cell the same size and lyses remains the same size  Cell Membrane Transport Diffusion Active Transport occurs down a occurs against a concentration gradient concentration gradient no mediator or involves involves a “carrier” a “channel” or requires ENERGY “carrier” no additional energy  Cell Membrane Transport: Pumps Pumps are enzymes that utilize energy to move ions or solutes across membranes at relatively moderate rates. Energy: Adenosine triphosphate (ATP) or light Establish gradients between membrane-bound compartments  Cell Membrane Transport: ATP Pumps Ø Cardiac Glycosides - strengthen heartbeat by inhibiting cardiac Na/K ATPase isoform Glycosides (eg. digoxin) inhibit the Na/K ATPase… increase intracellular Na+ decrease Na+ gradient decrease Na+/Ca2+ counter-transport increase intracellular Ca2+ Digoxin has been a cornerstone for the treatment of heart failure for decades and is the only oral inotropic support agent currently used in clinical practice.  Cell Membrane Transport: Carriers Carriers are enzyme-like proteins that provide passive pathways for solutes to move across membranes down their concentration gradients. Energy: Ion gradients Cell Membrane Transport: Membrane Carriers  Cell Membrane Transport: Channels Channels are ion selective pores that open and close transiently in a regulated manner. Ion movement is driven by the electrical and chemical gradients. Channel activity is used to produce signals in excitable cells.  Excitable Cells: Membrane Potential Electrical Potential Difference – Ø The electrical potential difference between the inside and outside of cells is called the trans-membrane potential (Em). Ø Transmembrane potential is also known as “resting potential” or “membrane potential”. Ø Living cells in the normal resting state have an Em that is negative with respect to the outside and voltage differences range from -10 mV to -100 mV. Excitable Cells: Ion Concentration Gradients Ø Ion Concentration Gradients – Ø Most cells have relatively high intracellular concentrations of potassium (K+) and anionic proteins (Pr-) and relatively low intracellular concentrations of sodium (Na+) and chloride (Cl-). Ø The extracellular fluid contains relatively high concentrations of Na+ and Cl- and very little K+ and virtually no Pr-. Ø The membrane is slightly permeable to K+, Na+ and Cl- but impermeable to Pr-.  Excitable Cells: Diffusion Potential Factors Determining Diffusion Potential: Membrane Permeable to Different Ions Ø Electrical charge of an ion ØPermeability of membrane to an ion ØIon concentration difference across membrane  Excitable Cells: Membrane Potential Overview - Transmembrane Potential 1. All cells studied so far have a transmembrane potential that is negative inside with respect to the outside. 2. Transmembrane potential difference depends on the ion concentration gradients and relative ion permeability. 3. Physiological changes in membrane permeability to ions regulate transmembrane potential. 4. Na-K ATPase pump utilizes metabolic energy to maintain transmembrane potential. 5. The number of ions required to change transmembrane potential is so small that no concentration changes occur.  Excitable Cells: Membrane Potential Membrane permeability of one or more ions controls the transmembrane potential. Depolarize – membrane potential (Em) becomes more positive (increases). Hyperpolarize - membrane potential (Em) becomes more negative (decreases). Overshoot - membrane potential (Em) is 0 mv to positive mV. Repolarization - membrane potential (Em) moves towards resting membrane potential.  Excitable Cells: Graded Potential Graded potentials refer to a change in amplitude of membrane potential that is proportional to the intensity of the stimulus. Local response results from a local increase in membrane conductance to Na+ that produces a greater depolarization than achieved by the passive, electronic properties of the membrane alone. The amplitude will decay and remain local if it does not exceed threshold. Excitable Cells 1. Neurons 2. Skeletal Muscle 3. Cardiac Muscle 4. Smooth Muscle Action potentials are closely associated with cell function. Excitable Cells: Action Potential  Excitable Cells: Currents Inward Current - flow of positive charge into the cell. Inward currents depolarize the membrane potential (Em). Outward Current - flow of positive charge out of the cell. Outward currents hyperpolarize the membrane potential (Em).  Excitable Cells: Action Potential Depolarizing phase of an action potential is produced, once threshold is reached, by a rapid increase in gNa+. Overshoot of the action potential is due to the fact that gNa+ now exceeds K+ such that Em approaches ENa. Repolarizing phase of an action potential is due to inactivation of gNa+ to normal levels and the increase in gK+ which causes Em to go toward EK. Hyperpolarizing afterpotential is caused by the prevailing gK+ that causes Em to remain somewhat hyperpolarized. Excitable Cells: Action Potential Excitable Cells: Electronic vs. Action Potential Electronic Potential Action Potential Initiated by subthreshold depolarization or Initiated by depolarization to or above hyperpolarization threshold Passive process, dependent on resistive and Active process, dependent on gating of voltage- capacitive membrane properties dependent ion channels Graded response All-or none response Amplitude decreases with distance along Amplitude remains constant with distance membrane along membrane Velocity of conduction is constant; faster than Velocity of conduction is constant; slower than action potentials electronic potentials  Excitable Cells: Action Potential Local circuit current flow is the continued spread of depolarization to adjacent regions of the membrane as threshold is reached. vThreshold – Increases Na+ permeability Refractory region assures that the action potentials will move away from each other and travel in opposite directions. Excitable Cells: Nerve Fibers  Excitable Cells: Nerve Fibers Axon Diameter and Myelination Determine the Speed of Action Potential Propagation Unmyelinated nerve fiber conduction velocity is proportional of the diameter of the fiber. Myelinated nerve fiber conduction velocity is proportional to the diameter, resistance of the myelin sheath and internodal length. This allows for much smaller diameter nerve fibers. Mammalian muscle nerve contains 1000, 10µm diameter myelinated fibers. Nerve diameter is 1 mm. If unmyelinated diameter would have to be 1.5 inches to conduct at the same velocity. Axon Diameter and Functional Properties Functional Large Diameter Small Diameter Property Axon Axon Conduction Fast Slow Velocity Action Potential Low High Threshold Excitability High Low  Excitable Cells: Action Potential Refractory Periods Absolute refractory period is the period of time after the action potential during which another action potential cannot be elicited, no matter how strong the stimulus. Relative refractory period is the period of time after an action potential during which it is more difficult to elicit a second action potential. Neurons can fire action potentials at frequencies up to 500 Hz. Normal frequencies rarely exceed 20Hz. Refractory period assures that each action potential constitutes a distinct signal.  Cell Membrane Transport: Epithelial Transport Epithelial Transport: Ø Epithelia are cellular barriers between the body and external world or body fluid compartments. Ø Epithelial cells are vital in the regulation of body fluid homeostasis, absorption of nutrients and excretions of waste products. Ø The specific functions of an epithelial barrier are based on cell structure, contacts between epithelial cells and the nature and position of epithelial cell membrane channels and transporters. Cell Membrane Transport: Epithelial Transport Intrinsic and Extrinsic Mechanisms of Trans-epithelial Na+ Transport – Na+ transport is regulated in both directions according to the requirements of the organism to excrete or retain salt and maintain body fluid and electrolyte homeostasis.  Cell Membrane Transport: Epithelial Transport Trans-Epithelial Water Transport – Epithelial water transport is driven by osmotic forces. Water can be secreted or absorbed. The direction of water transport can vary in different regions of a tubule or duct. Epithelial Water Transport Properties – 1) High Water Permeability Epithelia – Kf always high and not regulated All leaky epithelia: renal proximal tubule, descending limb of the loop of Henle, small intestine and gall bladder. 2) Low Water Permeability Epithelia – Kf extremely low and in-sensitive to ADH Only example is ascending limb of the loop of Henle. 3) Regulated Water Permeable Epithelia - Kf sensitive to ADH Renal collecting ducts and urinary bladder Excitable Cells: Muscle Types Excitable Cells: Skeletal Muscle  Excitable Cells: Skeletal Muscle Isometric contraction is a muscle contraction without motion. The following measurements of tension can be made as a function of preset length (or preload): Passive tension is the tension developed by simply stretching a muscle to different lengths. Total tension is the tension developed when a muscle is stimulated to contract at different preloads. It is the sum of the active tension developed by the cross-bridge cycling in the sarcomeres and the passive tension caused by stretching the muscle. Active tension is determined by subtracting the passive tension from the total tension. It represents the active force developed during cross-bridge cycling. The active tension developed is proportional to the number of cross-bridges that cycle. Active tension is maximal when there is maximal overlap of thick and thin filaments and maximal possible cross-bridges. When the muscle is stretched to longer lengths, the number of possible cross-bridges is reduced, and active tension is reduced.  Excitable Cells: Pacemaker Potential Pacemaker Potentials: occur at regular frequencies and determine rate of contraction: Heart & Gut: Frequency is modulated by parasymapthetic & sympathetic activity as well as hormones Excitable Cells: Smooth Muscle