Lecture1 a gen physiology

Introduction to GENERAL PHYSIOLOGY and CELL PHYSIOLOGY Lecture No. 1

General Physiology Objectives: This presentation features the basic physiologic concepts you need to explain scientific basis of disease with emphasis on specific cause-and-effect mechanisms. Through these basic concepts you should be able to apply scientific information to the clinical reasoning process.

What is General Physiology? It is a branch of biological science which deals with the study of how the human body functions. All cells, tissues and organs perform their functions in concert with each other as smoothly operating systems. Knowledge of the mechanisms in which these systems work have been obtained experimentally through applications of the scientific method.

Let’s start with Homeostasis! Homeostasis is the process by which an organism maintains the composition of the extracellular fluid (ECF) and intracellular fluid (ICF) in a steady-state condition. ECF consists of the blood plasma and interstitial fluid. The composition of the ECF is maintained by the cardiovascular, pulmonary, renal, gastrointestinal, endocrine, and nervous systems acting in coordinated fashion. ICF’s composition is maintained by the cell membrane, which mediates the transport of material between between the ICF and ECF by diffusion, osmosis, and active transport.

How does homoestasis take place?

Blood Calcium levels Blood levels of calcium are held constant at set point by hormones. Normal value of calcium: 9-11 mg% Parathyroid hormone or parathormone is one hormone that helps raise the blood calcium concentration. Thyrocalcitonin – acts to reduce the blood level of calcium and to inhibit bone resorption. It also promotes the excretion of phosphate, sodium and calcium by decreasing their reabsorption in kidney tubules.

Temperature Control In homeostasis, the critical concept describing the body’s response to any deviation from some particular setpoint (such as temperature rising when exercising), which results the activation of mechanisms to oppose that deviation (return temperature toward normal), is known as negative feedback. In this kind of homeostasis, the setpoint is analogous to the house thermostat setting that operates to regulate the temperature in the house. The sequence that best reflects how the body maintains homeostasis (example, during a fever): 1. sensor activated 2. integrating center process 3. effector activated 4. negative feedback loops activated 5. return to setpoint

Homeostasis & Feedback Control Homeostasis refers to the dynamic constancy of the internal environment Homeostasis is maintained by mechanisms that act through negative feedback loops. A negative feedback loop requires a sensor that can detect a change in the environment and an effector that can be activated by the sensor The effector acts to cause changes in the internal environment that compensates the initial deviations that were detected by the sensor.

Negative Feedback Neurons in the hypothalamus secrete thyroid releasing hormone (TRH) which stimulates cells in the anterior pituitary to secrete TSH TSH binds to receptors on epithelial cells in the thyroid gland, stimulating synthesis and secretion of thyroid hormones, which affect probably all cells of the body When blood concentrations of thyroid hormones increase above a certain threshold, TRH secreting neurons in the hypothalamus as inhibited and stop secreting TRH. This is an example of “negative feedback ”

What is the Donnan Equilibrium? When two solutions containing charged particles (ions) are separated by a membrane that is permeable to some of the ions and not to others, a Donnan equilibrium will be established. A Donnan equilibrium is an example of an electrochemical equilibrium, because the electrical and chemical energies on either side of the membrane are equal and opposite to each other.

What are some of the apparatus used in Physiology? Kymograph

MRI & Spirometer Magnetic Resonance Imaging (MRI) – the new technique of visualizing the brain creates excellent images by detecting emitted radio wave signals released from stimulated protons aligned in the tissues. Positron-Emission Tomography (PET) – a computerized radiographic technique used to examine the metabolic activity of various body structures. Computed Tomography (CT Scan) – visualizes how the brain utilizes complex manipulation of x-ray absorption data obtained from tissues of different densities. Spirometer – used to measure and record the volume of inhaled and exhaled air, used to assess pulmonary function.

Coulter Counter, Oscilloscope & Ergograph Coulter Counter is a trademark for an electric device that rapidly identifies, sorts, and counts the various kinds of cells present in a small specimen of blood. Oscilloscope – used in cardiography, used to display graphic representation of beam of electrons on the screen. Ergograph – a device used to measure contraction of specific muscles or muscle groups.

HEMODIALYSIS MACHINE Hemodialysis is a procedure in which impurities or wastes are removed from the blood, used in treating renal failure and various toxic conditions. The patient’s blood is shunted from the body through a machine for diffusion and ultrafiltration and then returned to the patient’s blood circulation.

Audiometer, Tuning Fork & Rubber mallet Audiometer an electric device used to test the sensitivity of the sense of hearing. Tuning fork – a small metal instrument consisting of a stem and two prongs that produces a constant pitch when either prong is struck. It is used in auditory tests of nerve function and of air and bone conduction. Rubber hammer or mallet – used in patelllar reflex or in ankle jerk reflex

The Cell The cell is the basic unit of structure and function in the body. Many of the functions of cells are performed by particular subcellular structures called organelles. The human body contains about 100 trillion cells, each of which is a living structure. Several hundred basic types of cells exist in the body, Yet despite the difference between cells, they will have some functions in common, like their ability to live, grow and reproduce. Some show characteristics of metabolism, irritability and even movement or locomotion . Each is specially adapted to perform one particular function

Functions of organelles Mitochondria as the powerhouse of the cell, have membranes folded into cristae with matrix material involved in ATP production (energy).

Golgi complex The important role of the Golgi complex is to make certain the plasma membrane proteins reach their destination. The orientation of the protein is maintained so that the region destined to project outside the cell ends up in that place. In order to do this, it must be placed so that it faces inside the vesicle.

Secretory Pathway in a Cell 1.Nuclear membrane 2. Nuclear pore 3. rER 4. sER 5. Ribosomes attached to rER 6. Macromolecules 7. Transport vesicles 8. Golgi apparatus 9. Cis face of Golgi 10. Trans face of Golgi 11. Cisternae of Golgi apparatus

Endoplasmic reticulum rER – consists of flattened sacks of cisternae studded with ribosomes for the synthesis of proteins destined for secretion sER - consists of an anastomosing network of interconnected citernae and tubules. It functions in glycogen breakdown, synthesis of cholesterol and phospholipids and serves to detoxify drugs and poisons

Lysosomes Lysosomes are membrane- bounded organelles containing hydrolytic enzymes. They have several functions in cell physiology. They degrade phagocytized foreign materials, lipid aggregates and glycogen granules, responsible also in tissue degradation during regression, and are abundant in macrophages and in leukocytes.

Microfilaments This is a flourescence digital image of a fibroblast showing actin cytoskeletal network .

Microfilaments Microfilaments are actin-rich filamentous structures. In muscle cells, they provide a dynamic framework for the cell permitting extensions of pseudopodia, endocytosis of extracellular materials, and cell motility They are especially abundant in muscle cells where they are essential component of the thin filaments. Intermediate filaments are fibrous structures consisting of several proteins including desmin, vimentin, and keratin.

Microtubules are cytoskeletal elements in certain forms of cell movement and is an essential component of the mitotic spindle, centrioles, basal bodies, cilia, and flagella. They attach to chromosomes at the kinetochore and are essential for mitotic separation of chromosomes.

The Nucleus This is found in all cells except in mature rbc’s and blood platelets. Functions: - Contains chromosomes which consist of genes (bearers of hereditary characteristics) - Concerned with the growth and reproduction of cells Parts: Nuclear envelope, nuclear pores, chromatin materials, nucleolus, nuclear sap or karyoplasm Heterochromatin – forms the condensed or coiled parts of the chromosomes (metabolically inert) Euchromatin – forms the dispersed or extended parts of the chromosomes (metabolically active)

The Genetic Code The genetic code is based on the structure of DNA and is expressed through the structure and function of RNA. DNA and RNA are composed of subunits called nucleotides, and together these molecules are known as nucleic acids. The genetic code is based on the sequences of DNA nucleotides, which serve to direct the synthesis of RNA molecules. It is through the RNA-directed synthesis of proteins that the genetic code is expressed.

Nucleotides Nucleotides are the repeating units of nucleic acids. They are made up of nitrogenous base (pyrimidine and purine), pentose sugar and phosphate group .

Ribosomal RNA (rRNA) In the cytoplasm, rRNA and protein combine to form a nucleoprotein called a ribosome. The ribosome serves as the site and carries the enzymes necessary for protein synthesis

Types of RNA RNA: tRNA, mRNA, rRNA tRNa is characterized by bending on itself to form a cloverleaf structure that twists further into an upside down “L” shape. In order for a gene to be expressed, it first must be used as a guide, or template, in the production of a complementary strand of mRNA. This mRNA is then itself used as a guide to produce a particular type of protein whose sequence of amino acids is determined by the sequence of base triplets (codons) in the mRNA

Translation and Transcription Translation is best defined as the synthesis of specific proteins from the mRNA base sequence code Transcription is the synthesis of RNA molecules from DNA

History of the Plasma Membrane 1665: Robert Hooke 1895: Charles Overton - composed of lipids 1900-1920’s: must be a phospholipid 1925: E. Gorter and G. Grendel - phospholipid bilayer 1935: J.R. Danielli and H. Davson – proteins also part, proposed the Sandwich Model 1950’s: J.D. Robertson – proposed the Unit Membrane Model 1972: S.J. Singer and G.L. Nicolson – proposed Fluid Mosaic Model

Plasma Membrane is made of Phospholipids Gorter + Grendel Red Blood Cells analyzed Enough for Phospholipid bilayer Polar heads face out and Nonpolar tails face in Does not explain why some nonlipids are permeable

Plasma Membrane Models Sandwich Model (Danielli + Davson) 2 layers of globular proteins with phospholipid inside to make a layer and then join 2 layers together to make a channel for molecules to pass Unit Membrane Model (Robertson) Outer layer of protein with phospholipid bilayer inside, believed all cells same composition, does not explain how some molecules pass through or the use of proteins with nonpolar parts, used transmission electron microscopy Fluid Mosaic Model (Singer + Nicolson) Phospholipid bilayer with proteins partially or fully imbedded, electron micrographs of freeze-fractured membrane

Which membrane model is correct? 1) Rapidly freeze specimen 2) Use special knife to cut membrane in half 3) Apply a carbon + platinum coating to the surface 4) Use scanning electron microscope to see the surface According to the electron micrograph which membrane model is correct? Why? Fluid-Mosaic Model

Fluid-Mosaic Model Fluid – the plasma membrane is the consistency of olive oil at body temperature, due to unsaturated phospholipids. (cells differ in the amount of unsaturated to saturated fatty acid tails) Most of the lipids and some proteins drift laterally on either side. Phospholipids do not switch from one layer to the next. Cholesterol affects fluidity: at body temperature it lessens fluidity by restraining the movement of phospholipids, at colder temperatures it adds fluidity by not allowing phospholipids to pack close together. Mosaic – membrane proteins form a collage that differs on either side of the membrane and from cell to cell (greater than 50 types of proteins), proteins span the membrane with hydrophilic portions facing out and hydrophobic portions facing in. Provides the functions of the membrane

Structure of the Plasma Membrane

Structure of the Plasma Membrane Phospholipid bilayer Phospholipid Hydrophilic head Hydrophobic tails Cholesterol Proteins Transmembrane/ Intrinsic/Integral Peripheral/Extrinsic Cytoskeletal filaments Carbohydrate chain Glycoproteins Glycolipids

Proteins of the Plasma Membrane Provide 6 Membrane Functions: 1) Transport Proteins 2) Receptor Proteins 3) Enzymatic Proteins 4) Cell Recognition Proteins 5) Attachment Proteins 6) Intercellular Junction Proteins

1) Transport Proteins Channel Proteins – channel for lipid insoluble molecules and ions to pass freely through Carrier Proteins – bind to a substance and carry it across membrane, change shape in process

2) Receptor Proteins – Bind to chemical messengers (Ex. hormones) which sends a message into the cell causing cellular reaction

3) Enzymatic Proteins – Carry out enzymatic reactions right at the membrane when a substrate binds to the active site

4) Cell Recognition Proteins – Glycoproteins (and glycolipids) on extracellular surface serve as ID tags (which species, type of cell, individual). Carbohydrates are short branched chains of less than 15 sugars

5) Attachment Proteins Attach to cytoskeleton (to maintain cell shape and stabilize proteins) and/or the extracellular matrix (integrins connect to both). Extracellular Matrix – protein fibers and carbohydrates secreted by cells and fills the spaces between cells and supports cells in a tissue. Extracellular matrix can influence activity inside the cell and coordinate the behavior of all the cells in a tissue.

6) Intercellular Junction Proteins – Bind cells together Tight junctions Gap junctions

Materials must move in and out of the cell through the plasma membrane. Some materials move between the phospholipids. Some materials move through the proteins. How do materials move into and out of the cell?

Plasma Membrane Transport Molecules move across the plasma membrane by: Passive Transport Active Transport

What are three types of passive transport? Diffusion Facilitated Diffusion Osmosis Passive Transport ATP energy is not needed to move the molecules through.

Passive Transport 1: Diffusion Molecules can move directly through the phospholipids of the plasma membrane This is called … DIFFUSION

What is Diffusion? Diffusion is the net movement of molecules from a high concentration to a low concentration until equally distributed. Diffusion rate is related to temperature, pressure, state of matter, size of concentration gradient, and surface area of membrane. http://www.biologycorner.com/resources/diffusion-animated.gif

What molecules pass through the plasma membrane by diffusion ? Gases (oxygen, carbon dioxide) Water molecules (rate slow due to polarity) Lipids (steroid hormones) Lipid soluble molecules (hydrocarbons, alcohols, some vitamins) Small noncharged molecules (NH 3 )

Why is diffusion important to cells and humans? Cell respiration Alveoli of lungs Capillaries Red Blood Cells Medications: time-release capsules

Passive Transport 2 : Facilitated Diffusion Molecules can move through the plasma membrane with the aid of transport proteins This is called … FACILITATED DIFFUSION

What is Facilitated Diffusion? Facilitated diffusion is the net movement of molecules from a high concentration to a low concentration with the aid of channel or carrier proteins .

What molecules move through the plasma membrane by facilitated diffusion? Ions (Na + , K + , Cl - ) Sugars (Glucose) Amino Acids Small water soluble molecules Water (faster rate)

How do molecules move through the plasma membrane by facilitated diffusion? Channel and Carrier proteins are specific: Channel Proteins allow ions, small solutes, and water to pass Carrier Proteins move glucose and amino acids Facilitated diffusion is rate limited, by the number of proteins channels/carriers present in the membrane.

Specific Types of Facilitated Diffusion Counter Transport – the transport of two substances at the same time in opposite directions, without ATP. Protein carriers are called Antiports . Co-transport – the transport of two substances at the same time in the same direction, without ATP. Protein carriers are called Symports . Gated Channels – receptors combined with channel proteins. When a chemical messenger binds to a receptor, a gate opens to allow ions to flow through the channel.

Why is facilitated diffusion important to cells and humans? Cells obtain food for cell respiration Neurons communicate Small intestine cells transport food to bloodstream Muscle cells contract

Passive Transport 3: Osmosis Water Molecules can move directly through the phospholipids of the plasma membrane This is called … OSMOSIS

What is Osmosis ? Osmosis is the diffusion of water through a semipermeable membrane. Water molecules bound to solutes cannot pass due to size, only unbound molecules. Free water molecules collide, bump into the membrane, and pass through.

Osmosis in action What will happen in the U-tube if water freely moves through the membrane but glucose can not pass? Water moves from side with high concentration of water to side with lower concentration of water. Movement stops when osmotic pressure equals hydrostatic pressure.

Why is osmosis important to cells and humans? Cells remove water produced by cell respiration. Large intestine cells transport water to bloodstream Kidney cells form urine

Osmosis and Tonicity Tonicity refers to the total solute concentration of the solution outside the cell. What are the three types of tonicity? Isotonic Hypotonic Hypertonic

Isotonic Solutions that have the same concentration of solutes as the suspended cell. What will happen to a cell placed in an Isotonic solution? The cell will have no net movement of water and will stay the same size. Ex. Blood plasma has high concentration of albumin molecules to make it isotonic to tissues.

Hypotonic Solutions that have a lower solute concentration than the suspended cell. What will happen to a cell placed in a Hypotonic solution? The cell will gain water and swell. If the cell bursts, then we call this lysis. (Red blood cells = hemolysis) In plant cells with rigid cell walls, this creates turgor pressure.

Hypertonic Solutions that have a higher solute concentration than a suspended cell. What will happen to a cell placed in a Hypertonic solution? The cell will lose water and shrink. (Red blood cells = crenation) In plant cells, the central vacuole will shrink and the plasma membrane will pull away from the cell wall causing the cytoplasm to shrink called plasmolysis.

Review: Passive Transport Diffusion – O 2 moves in and CO 2 moves out during cell respiration Facilitated Diffusion – glucose and amino acids enter cell for cell respiration Osmosis – cell removal or addition of water

Review Tonicity What will happen to a red blood cell in a hypertonic solution? What will happen to a red blood cell in an isotonic solution? What will happen to a red blood cell in a hypotonic solution?

1) Active Transport 2) Exocytosis 3) Endocytosis Phagocytosis Pinocytosis Receptor-Mediated endocytosis What are three types of Active transport? Active Transport ATP energy is required to move the molecules through.

Active Transport Molecules move from areas of low concentration to areas of high concentration with the aid of ATP energy. Requires protein carriers called Pumps.

The Importance of Active Transport Bring in essential molecules: ions, amino acids, glucose, nucleotides Rid cell of unwanted molecules (Ex. sodium from urine in kidneys) Maintain internal conditions different from the environment Regulate the volume of cells by controlling osmotic potential Control cellular pH Re-establish concentration gradients to run facilitated diffusion. (Ex. Sodium-Potassium pump and Proton pumps)

The Sodium-Potassium Pump 3 Sodium ions move out of the cell and then 2 Potassium ions move into the cell. Driven by the splitting of ATP to provide energy and conformational change to proteins by adding and then taking away a phosphate group. Used to establish an electrochemical gradient across neuron cell membranes. http://www.biologie.uni-hamburg.de/b-online/library/biology107/bi107vc/fa99/terry/images/ATPpumA.gif

The Role of the Na +- K + Pump The most essential role of this ion pump is to maintain the volume of cells . The cytosol contains many negatively charged proteins and small molecular weight solutes. These bind ions. If the ion pumps were not active in expelling more cations than they took into calls, then water would diffuse into cells, eventually causing them to swell to bursting. The Na + -K + pump also establishes gradients of Na + across the plasma membrane since it expels 3 Na + for every 2 K + taken in. Since these ion gradient contribute to the resting membrane potential, the Na + -K + pump is electrogenic.

Active Transport 2 : Exocytosis Movement of large molecules bound in vesicles out of the cell with the aid of ATP energy. Vesicle fuses with the plasma membrane to eject macromolecules. Ex. Proteins, polysaccharides, polynucleotides, whole cells, hormones, mucus, neurotransmitters, waste

Active Transport 3 : Endocytosis Movement of large molecules into the cell by engulfing them in vesicles, using ATP energy. Three types of Endocytosis: Phagocytosis Pinocytosis Receptor-mediated endocytosis

Phagocytosis “ Cellular Eating” – engulfing large molecules, whole cells, bacteria Ex. Macrophages ingesting bacteria or worn out red blood cells. Ex. Unicellular organisms engulfing food particles.

Pinocytosis “ Cellular Drinking” – engulfing liquids and small molecules dissolved in liquids; unspecific what enters. Ex. Intestinal cells, Kidney cells, Plant root cells

Receptor-Mediated Endocytosis Movement of very specific molecules into the cell with the use of vesicles coated with the protein clathrin. Coated pits are specific locations coated with clathrin and receptors. When specific molecules (ligands) bind to the receptors, then this stimulates the molecules to be engulfed into a coated vesicle. Ex. Uptake of cholesterol (LDL) by animal cells

Types of Endocytosis What is phagocytosis? What is pinocytosis? What is receptor-mediated endocytosis?

SURFACE TENSION IS THE TENDENCY FOR A LIQUID TO CONTRACT AS A CONSEQUENCE OF ITS POSSESION OF FREE ENERGY, SINCE APPROACH TO EQUILIBRIUM IS ALWAYS ACCOMPANIED BY A DIMINUTION OF FREE ENERGY . We’ve all played with it- water drops being added one at a time, until that one drop breaks the surface and the water spills out.

IT IS HARD TO BELIEVE THAT H-BONDS AND SURFACE TENSION ARE ENOUGH TO KEEP THE VOLUME OF WATER THAT IS IN THESE BEADS STUCK TO THE PLANT

What are biologic activities which can be best explained in terms of surface tension? Phenomena : - the spherical form of a falling dro of water - a soap bubble floating in the air - a globule of mercury resting on flat surface Applications in the Body : - phagocytosis or ameboid motion - absorption of metabolites/nutrients - transport of blood

DIALYSIS is the separation of the more diffusible from the less diffusible

Types of Cell Junctions In Animal Cells: Tight Junctions Desmosomes Gap Junctions In Plant Cells: Plasmodesmata

Tight Junctions Transmembrane Proteins of opposite cells attach in a tight zipper-like fashion No leakage Ex. Intestine, Kidneys, Epithelium of skin

Desmosomes Cytoplasmic plaques of two cells bind with the aid of intermediate filaments of keratin Allows for stretching Ex. Stomach, Bladder, Heart

Gap Junctions Channel proteins of opposite cells join together providing channels for ions, sugars, amino acids, and other small molecules to pass. Allows communication between cells. Ex. Heart muscle, animal embryos

Plasmodesmata Channels between the cell walls of plant cells that are lined with the plasma membranes of adjacent cells and smooth ER runs through. Allows for the exchange of cytosol between adjacent cells; moving water, small solutes, sugar, and amino acids. Ex. Xylem and Phloem in Plants

Types of Cell Junctions What is the difference between a plasmodesmata, tight junction, gap junction, and desmosome?

What are the factors which influence diffusion? Temperature Molecular weight Shape and size of molecules Solubility of gas in the medium Presence or absence of lectrical charge of diffusing solute Ability of diffusing solute to dissolve in lipids

Events During an Action Potential Depolarization – cell goes from inside negative (-) to inside positive(+). Sodium channels open so sodium diffusively floods in (-70mV toward 58mV) Repolarization – Na channels close and K channels open (returns to inside negative). K follows its diffusive gradient and K diffuses out of the cell Hyperpolarization – “undershoot” of resting potential )-75mV Refractory period – time before another action potential can “fire”

Next Meeting Quiz on Cell Physiology Membrane Transport Mechanisms Action Potential Assignment: Read on Blood Physiology

Lecture1 a gen physiology

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