Exam 1 outline
Exam 1 outline BISC276010
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Chapter 1 Physiology – the study of the normal functioning of a living organism and its component parts, including all its chemical and physical processes “Knowledge of nature” – Aristotle used this to describe the functioning of all living organisms Hippocrates – father of medicine; “healing power of nature” o The field then became closely associated with medicine th 16 century Europe – physiology became the study of vital functions of the human body A few decades ago, we thought that we would find the key to the secret of life by sequencing the human genome (all the genetic information contained in the DNA of a species) o One gene may code for many proteins o Living organisms are much more than the simple sum of their parts Physiology is an integrative science o Complex systems possess emergent properties – properties that cannot be predicted to exist based only on knowledge of the system’s individual components Emergent properties result from complex, nonlinear interactions of the different components Example: emotion, intelligence, etc Human Genome Project Proteomics – study of proteins in living organisms o Knowing that a protein is made in a particular cell does not always tell us the significance of that protein to the cell, the tissue, or the functioning organism The integration of function across many levels of organization is a special focus of physiology o At the level of the organism, physiology is closely tied to anatomy (structure) Cells – smallest unit of structure capable of carrying out all life processes Cell membrane/plasma membrane – lipid protein barrier which separates cells from their external environment Tissues – collections of cells that carry out related functions Organs – structural and functional units made of tissues Organ systems – groups of organs that integrate their functions Organ systems: Circulatory (cardiovascular) – heart, blood vessels, blood; transport of materials between all cells of the body Digestive (gastrointestinal) – stomach, intestine, liver, pancreas; conversion of food into particles that can be transported into the body, elimination of some wastes Endocrine – thyroid gland, adrenal gland, ovaries, testes; coordination of body function through synthesis and release of regulatory molecules Immune – thymus, spleen, lymph nodes; defense against foreign invaders Integumentary – skin; protection from external environment Musculoskeletal – skeletal muscles, bone; support and movement Nervous – brain, spinal cord; coordination of body function through electrical signals and release of regulatory molecules Reproductive – ovaries, uterus, testes; perpetuation of the species Respiratory (pulmonary) – lungs, airways; exchange of oxygen and carbon dioxide between the internal and external environments Urinary (renal) – kidneys, bladder; maintenance of water and solutes in the internal environment, waste removal Respiratory, digestive, urinary, and reproductive all exchange materials between internal and external environments 4 other systems extend throughout the body Immune tissues are closely associated with the circulatory system The function of a physiological system is the “why” – what is the adaptive significance? o The production of highly concentrated urine by the kidney allows the body to conserve water – does not tell how the kidney accomplishes that task o Thinking in terms of adaptive significance is the teleological approach to science The mechanism of a physiological system is the “how” – examines process o “Oxygen binds to hemoglobin molecules in the red blood cells” o This answer explains exactly how oxygen transport occurs, but says nothing about the significance of oxygen transport Applying concepts of integrated functions and mechanisms is the underlying principle in translational research – uses the insights and results gained from basic biomedical research on mechanisms to develop treatments and strategies for preventing human diseases Themes of Physiology Theme 1: Structure and function are closely related o The integration extends across all levels of organization, from molecular level to the body o Molecular interactions – a molecule’s function depends on its structure and shape; a small change to structure or shape has significant effects on function Example – the change in one amino acid of the hemoglobin protein; this change converts normal hemoglobin to sickle cell Mechanical properties – compliance (ability to stretch), elastance, strength, flexibility, and fluidity o Compartmentation – division of space into separate compartments which allow a cell, tissue, or organ to specialize and isolate functions Theme 2: Living Organisms Need Energy o Growth, reproduction, movement, and homeostasis require the continuous input of energy Theme 3: Information Flow Coordinates Body Functions o Information flow ranges from the transfer of information stored in DNA from generation to generation to the flow of information within the body of a single organism o Information flow between cells takes form of chemical or electrical signals Local communication – information goes from one cell to its neighbors Longdistance communication – from one part of the body to another When chemical signals reach their target cells, they must transfer their information from outside the cell to the inside of the cell o Signal molecules cannot enter the cell and must pass their message across the cell membrane Theme 4: Homeostasis Maintains Internal Stability Homeostasis – relatively stable internal environment – Claude Bernard o Body temperature, heart rate, blood pressure o “It is the constancy of the internal environment that is the condition for a free and independent life” o Walter B. Cannon proposed variables that are under homeostatic control Environmental factors that affect cells: osmolarity, temperature, and pH “Materials for cell needs” – nutrients, water, sodium, calcium, other inorganic ions, oxygen, as well as internal secretions (hormones and other chemicals) having general and continuous effects o Homeo – meaning like or similar rather than same o State of maintaining a similar condition o Failure to maintain homeostasis of the critical variables – pathological condition Disease – when the problem arises from internal failure of some normal physiological process (growth of tumors, autoimmune diseases, premature death of cells) and when the originate from an outside source (toxic chemicals physical trauma, bacteria, viruses) o The body attempts to compensate if homeostasis is disturbed Success – homeostasis is restored Failure – illness or disease o Pathophysiology – study of body functions in a disease state o Diabetes mellitus – metabolic disorder characterized by abnormally high blood glucose concentrations Extracellular fluid (ECF) – watery internal environment that surrounds the cells o Serves as transition between external environment and ICF Intracellular fluid (ICF) – inside cells The law of mass balance – if the amount of a substance in the body is to remain constant, any gain must be offset by an equal loss To maintain mass balance, excrete the material or convert the substance to a different substance through metabolism Mass flow applies to the entry, production, and removal of substances and also to the movement of substances from one compartment in the body to another Clearance – the rate at which the substance disappears from the blood o Kidney and liver are 2 primary organs that clear solutes from the body Homeostasis – stability of internal environment (ECF) which is easy to monitor by taking a blood sample o Blood separates into 2 parts: plasma (fluid) and heavier blood cells o Dynamic steady state o Equilibrium implies that the composition of the body compartments is identical Sodium and chloride are more concentrated in ECF than ICF Potassium is most concentrated in ICF o Not at equilibrium Regulated variables are kept within their acceptable range All control systems have 3 components: o Input signal o Controller/integrating center – integrates incoming information and initiates an appropriate response o Output signal – creates a response Local control – simplest form of control; relatively isolated change occurs in a tissue; nearby cell/group of cells senses the change in their immediate vicinity and responds, usually by releasing a chemical o Example: oxygen decreases in a tissue; cells of the blood vessels secrete chemical signal; signal molecule diffuses to muscles nearby, telling them to relax, which widens the blood vessel, increases blood flow into the tissue Reflex control – requires long distance communication; long distance pathway that uses the nervous system, endocrine system, or both Response loop of reflex control – input signal, integrating center (integrate the signal), and output signal o Stimulus (change that occurs when the regulated variable moves out of its desirable range) sensor (monitors environment for the variable) input signal (neural: chemical and electrical; endocrine: no input pathway) integrating center (evaluates information from sensor & initiates output signal; neural: central nervous system; endocrine: in endocrine cell) output signal (efferent; electrical and/or chemical signal that travels to a target; nervous system: electrical and chemical signals transmitted by efferent neuron; endocrine: through blood) target (effector; cell/tissue that carries out response; neural: muscle, endocrine/exocrine glands, adipose tissue; endocrine: cells with proper receptor for the hormone) response (cellular response; systemic response) o All sensors have a threshold – minimum stimulus needed to set the reflex response in motion o Endocrine reflexes that are not associated with the nervous system do not use sensory receptors to initiate pathway; endocrine cells act as sensor and integrating center for the reflex o If successful, response brings regulated variable back to normal o Integrating centers – usually part of nervous system or endocrine system o Output signals – chemical, electrical, or both o Targets – can be any cell of the body o Antagonistic control – 2 different hormones, for example, have opposing effects on a single target Comparing endocrine and neural control 1. Specificity – each neuron has specific target cell; endocrine is more general, chemical messenger is released into the blood and can be reached by every cell, multiple tissues in the body can respond to a hormone simultaneously 2. Nature of the signal – nervous system uses electrical and chemical signals, electrical signals travel long distances through neurons, releasing chemical signals (neurotransmitters) that diffuse across the small gap between the neuron and its target; endocrine uses only chemical signals, hormones secreted into blood by endocrine glands or cells a. Neurohormone pathway – hybrid; neuron creates electrical signal, but chemical released by neuron is a neurohormone that goes into the blood 3. Speed – neural reflexes are much faster than endocrine reflexes 4. Duration of action – neural usually very short, if longer they’re mediated by neuromodulators; endocrine responses last longer 5. Coding for stimulus intensity – neural signals’ magnitude are identical in strength, cannot reflect stimulus intensity, frequency increases; endocrine intensity = amount of hormone released Feedback loop – response feeds back to influence the input portion of the pathway For most reflexes, feedback loops are homeostatic Negative feedback – pathway in which the response opposes or removes the signal; stabilize the regulated variable; aid maintaining homeostasis o Can restore normal state, but cannot prevent initial disturbance Positive feedback – the response reinforces the stimulus, sending the variable farther from the set point; requires event outside the loop to stop the response o Example: hormonal contractions during childbirth; baby puts pressure on cervix; sensory signals from cervix to brain release oxytocin (causes uterus to contract); pushes baby harder against cervix; increased stretch causes more oxytocin release; causes more contraction; continues until baby is born, releasing stretch, stopping positive feedback loop Feedforward control – anticipatory responses; salivation reflex Biorhythms – regulated variables that change predictably and create repeating patterns or cycles of change o Timing coincides with predictable environmental change o Create anticipatory response to a predictable environmental variable o Digestive system shuts down in anticipation of going to bed o Acclimatization – adaptation of physiological processes to a given set of environmental conditions o Acclimation – if process takes place in a lab Crossover study – each individual acts as experimental subject and as control; reduce variability; the response to the treatment can be compared with his or her own control value Placebo effect Nocebo effect – if you warn people that a drug they are taking may have adverse side effects, those people will report a higher incidence of the side effects than a similar group of people who were not warned Blind study – subjects don’t know whether they’re receiving placebo or treatment Doubleblind study – 3 party only knows which group gets what Doubleblind crossover study – the control group in the first half of the experiment becomes the experimental group in the second half and vice versa; no one involved knows who is taking the active treatment Longitudinal studies – carried out of a long period of time Prospective study – looking forward Crosssectional study – survey a population for the prevalence of a disease or condition; this data identifies trends to be investigated further; example: whether age group is associated with developing the condition being surveyed Retrospective study – match groups of people who all have a particular disease to a similar but healthy control group; goal is to determine whether development of the disease can be associated with a particular variable Metaanalysis – combines all the data from a group of similar studies and extracts trends Types of graphs Bar graph – when IV are distinct entities Histogram – shows distribution of one variable over a range Line graph – IV is a continuous phenomenon Scatter plots – shows relationship between 2 variables Chapter 6 Human body is composed of 75 trillion cells 2 forms of communication: electrical signals and chemical signals Electrical signals – changes in a cell’s membrane potential Chemical signals – molecules secreted by cells into the extracellular fluid; responsible for communication within the body Targets – cells that respond to electrical or chemical signals 4 methods of celltocell communication 1. Gap junctions – local communication; simplest form; protein channels that create cytoplasmic bridges between adjacent cells o Forms from the union of proteins (connexins) on 2 adjacent cells; creates a channel that can open and close; when open, connected cells function like a single cell with multiple nuclei o Amino acids, ATP, cyclic AMP diffuse o Electrical signals pass directly from cell to cell 2. Contactdependent signals – local communication; surface molecules on one cell membrane binds to a membrane protein of another cell o Occurs in immune system o Cell adhesion molecules (CAM) – act as receptors; linked to cytoskeleton and to intracellular enzymes 3. Chemicals that diffuse through extracellular fluid – local communication 4. Combination of chemical and electrical signals carried by nerve cells & chemical signals transported in the blood – longdistance communication Paracrine signal – chemical that acts on cells in the immediate vicinity of the cell that secreted the signal; range is restricted to adjacent cells o Example: histamine (released from damaged cells) Autocrine signal – chemical signal that acts on the cell that secreted it o Both reach their target cells by diffusing through the interstitial fluid o Both are local communication Long distance communication Endocrine system communicates using hormones – chemical signals that are secreted into the blood and distributed all over the body by circulation; only target cells with receptors for the hormone respond to the signal Nervous system uses chemical and electrical signals o Electrical signal travels along a neuron until it reaches the end where it’s translated into a chemical signal (neurocrine) secreted by the neuron o Neurotransmitters – neurocrine diffusing across a small gap to the target cell o Neuromodulator – neurocrine acts more slowly as an autocrine or paracrine signal o Neurohormone – neurocrine released by neurons diffuses into the blood for distribution Similarities between neurohormones and classic hormones make the 2 systems a functional continuum Cytokines – a variety of regulatory peptides that modulate immune responses o Control cell development, cell differentiation, and the immune response Development and differentiation – cytokines function as autocrine or paracrine signals Stress and inflammation – cytokines may act of distant targets; transported through the circulation o They act on a broader spectrum of target cells; not produced by specialized cells the way hormones are; they are made on demand o Signal pathways for cytokines are different than for hormones o Erythropoietin – controls synthesis of red blood cells; considered a hormone but functionally fits definition of cytokine Types of signal molecules: hormones, neurohormones, neurotransmitters, cytokines, paracrines, autocrines Signal pathways Receptor proteins – chemical signals bind here o A cell can respond to a chemical signal only if the cell has the appropriate receptor proteins for that signal o Targetcell receptor proteins may be in the nucleus, cytosol, or on the cell membrane as integral proteins o Whether a chemical signal binds to this receptor depends on whether signal molecule is lipophilic or lipophobic Lipophilic signal molecules – diffuse through the phospholipid bilayer of cell membrane (intracellular); bind to cytosolic or nuclear receptors; activation turns on a gene, nucleus makes mRNA, synthesize new proteins; slow process; could also turn off gene activity; example: hormones Lipophobic signal molecules – unable to diffuse through cell membrane; remain in extracellular fluid and bind to receptor proteins on cell membrane; response time for pathways linked to membrane receptor protein is very rapid Membrane receptors: receptorchannel (ligand binding opens or closes the channel and alters ion flow across the membrane); receptorenzymes, G proteincoupled receptors, and integrin receptors (information from signal molecule must be passed across membrane to initiate intracellular response) Signal transduction – transmission of information from one side of a membrane to the other using membrane proteins Ligand – signal molecule that binds to a protein receptor; first messenger because it brings information to the target cell (example: insulin, cytokines, and growth factors) Ligandreceptor binding activates the receptor The receptor in turn activates one or more intracellular signal molecules Last signal molecule in the pathway initiates synthesis of target proteins or modifies existing target proteins to create a response Signal transduction – extracellular signal molecule (first messenger) activates a membrane receptor that alters intracellular molecules (second messenger system) to create a response o Transducer – a device that converts a signal from one form into a different form Membrane proteins act as transducers – convert message of extracellular signals into intracellular messenger molecules that trigger a response Signal Transduction Pathway 1. Extracellular signal molecule (first messenger) binds to and activates a membrane receptor o Membrane receptors and associated proteins usually either activate protein kinases (enzymes that transfer a phosphate group from ATP to a protein) or activate amplifier enzymes that create intracellular second messengers 2. Activated membrane receptor turns on associated proteins and starts intracellular cascade of second messengers o Second messengers: alter gating of ion channels (creates electrical signals by altering cell’s membrane potential); increase intracellular calcium (Ca binding to proteins changes their function, creating cellular response); change enzyme activity, especially of protein kinases or protein phosphatases (enzymes that remove a phosphate group) which changes configuration and creates response 3. The last second messenger in the cascade acts on intracellular targets to create a response o Proteins modified by calcium binding and phosphorylation control: metabolic enzymes, moto proteins for muscle contraction and cytoskeletal movement, proteins that regulate gene activity and protein synthesis, membrane transport and receptor proteins Signaling cascade starts when a stimulus converts the receptor to an active form which converts and inactive molecule to active… until the final step a substrate is converted into a product o Example: blood clotting Signal amplification – original signal is amplified; turns one signal molecule into multiple second messenger molecules o Receptorligand complex turns on an amplifier enzyme o Small amount of ligand creates a large effect Receptorenzymes – have 2 regions: on extracellular side of cell membrane and on cytoplasmic side o Ligand binding to the receptor activates the enzyme o Enzymes are either protein kinases (example: tyrosine kinase) or guanylyl cyclase (the amplifier enzyme that converts GTP to cyclic GMP) G Proteincoupled receptors (GPCR) – membranespanning proteins that cross phospholipid bilayer 7 times; cytoplasmic tail is linked to 3part membrane transducer molecule (G protein) o Types of ligands that bind to GPCR include hormones, growth factors, olfactory molecules, visual pigments, and neurotransmitters o G proteins bind guanosine nucleotides o Inactive G proteins are bound to GDP; exchanging GDP to GTP activates G protein o Activated G proteins either: open an ion channel in the membrane, or alter enzyme activity on the cytoplasmic side of the membrane o 2 most common amplifier enzymes for GPCR are adenylyl cyclase and phospholipase C G proteincoupled adenylyl cyclasecAMP system – signal transduction system for many protein hormones; adenylyl cyclase is the amplifier enzyme that converts ATP to second messenger molecule cAMP; cAMP activates protein kinase A (PKA) which phosphorylates other intracellular proteins as part of signal cascade Some GPCR are linked to phospholipase C (PLC) – amplifier enzyme; converts a membrane phospholipid into 2 lipidderived second messenger molecules: diacylglycerol and inositol triphosphate o Diacylglycerol (DAG) – nonpolar diglyceride that remains in lipid portion of membrane; interacts with PKC (phosphorylates cytosolic proteins that continue the signal cascade) o Inositol triphosphate (IP 3 – water soluble messenger molecule that leaves membrane and enters cytoplasm; binds to calcium channel on ER, allowing Ca to diffuse out of ER into cytosol Integrins – membranespanning proteins; mediate blood clotting, wound repair, cell adhesion, recognition in immune response, cell movement during development o Integrin receptors in extracellular side bind to proteins of extracellular matrix or ligands such as antibodies and molecules involved in blood clotting o Integrins attach to cytoskeleton via anchor proteins Simplest receptors are ligandgated ion channels – mostly neurotransmitter receptors Receptorchannel – most rapid intracellular response; alters cell’s permeability to an ion; creates electrical signal that alters voltagesensitive proteins o Example: acetylcholinegated monovalent cation channel of skeletal muscle; acetylcholine released from adjacent neuron binds to acetylcholine receptor and opens the channel; Na enters cell, K leaves cell o Cascade of intracellular events results in muscle contraction Some ligandgated ion channels are controlled by intracellular second messengers; other ion channels open or close in response to extracellular signals, but signal ligand does not bind to channel protein; it binds to a GPCR that is linked to ion channel Calcium ions – signal molecules Most versatile ionic messengers Enters cell through voltagegated Ca2+ channels or ligandgated or mechanically gated channels; can be released from second messengers like IP3 Stored in ER Release of Ca into cytosol creates a Ca signal; calcium ions combine with cytoplasmic calciumbinding proteins to bring about calciumdependent results: o Ca binds to protein calmodulin; alters enzyme or transporter activity or gating of ion channels o Ca binds to regulatory proteins and alters movement of contractile cytoskeletal proteins (microtubules) Example: protein troponin initiates muscle contraction o Binds to proteins to trigger exocytosis of secretory vesicles Example: release of insulin in response to calcium signal o Binds to ion channels to alter gating state Example: Ca activated K channel in nerve cells o Entry into fertilized egg initiates development of embryo Gases – signal molecules Shortacting paracrine/autocrine signal molecules that act close to where they are produced Endothelialderived relaxing factor (EDRF) – diffuses from endothelium into adjacent smooth muscle cells causing muscle to relax and dilate the blood vessel; EDRF is NO Nitric oxide (NO) – diffuses into target cells where it binds to a receptor that activates the cytosolic form of guanylyl cyclase and causes formation of second messenger cGMP o Relaxes blood vessels, acts as neurotransmitter & neuromodulator Carbon monoxide (CO) – toxic effects; activates guanylyl cyclase and cGMP; targets smooth muscle and neural tissue Hydrogen sulfide (H2S) – relax blood vessels; example: garlic Lipids – paracrine signals Orphan receptors – receptors that have no known ligand Eicosandoids – lipid derived paracrine signals; derived from arachidonic acid o Arachidonic acid – produced from membrane phospholipids by the action of phospholipase A2 (PLA2); it may act directly as second messenger, altering ion channel activity and intracellular enzymes; may be converted to a paracrine which diffuses out of cell and combines with receptors of neighboring cells Leukotrienes – produced by enzyme lipoxygenase on arachidonic acid; secreted by WBC; play role in asthma Prostanoids – produced by enzyme cyclooxygenase (COX) on arachidonic acid; includes prostaglandins and thromboxanes; act on platelets, kidney, bone, sleep, inflammation, pain, fever o Nonsteroidal antiinflammatory drugs (NSAIDs) – ibuprofen; inhibit COX enzymes and decrease prostaglandin synthesis Sphingolipids – regulate inflammation; like eicosanoids, they combine with GPCR in membranes of target cells For most signal molecules, the target cell response depends on its receptor or its associated intracellular pathways, not on the ligand. Neurohormone epinephrine dilates blood vessels in skeletal muscle but constricts blood vessels in the intestine o Receptors come in related forms called isoforms o When epinephrine binds to alpha receptors in intestinal blood vessels, signal pathways begin and cause vessels to constrict o When it binds to beta receptors on skeletal muscle blood vessels, associated signal transduction pathways cause vessel to dilate o Response depends on receptor isoform and its signal transduction pathway, not on the ligand Different ligand molecules with similar structures may be able to bind to same receptor o Example: fightorflight; neurotransmitter norepinephrine and neurohormone epinephrine (adrenaline); both molecules bind to adrenergic receptors; they also compete for a single receptor; both neurocrines bind to alpha (higher affinity for norepinephrine) and beta (higher affinity for epinephrine) Agonists – ligands that turn receptors on; principle of competing agonists to design drugs that are longeracting and more resistant to enzymatic degradation o Example: birth control pills; agonists of naturally occurring estrogens but have chemical groups added to protect them from breakdown and extend their active life Antagonists – ligands that block receptor activity A cell’s ability to respond to a chemical signal can be limited by the number of receptors for that signal Flexibility of a cell to create and destroy receptors permits a cell to vary its responses to chemical signals depending on conditions and needs Increased signal level creates an enhanced response Downregulation – decrease in receptor number; cell removes receptors from membrane through endocytosis Desensitization – quicker and more easily reversible way to decrease cell response o Binding a chemical modulator to receptor protein o Result is diminished response of target cell, even though concentration of signal molecule remains high o Downregulation and desensitization explain development of drug tolerance – response to a given dose decreases despite continuous exposure Upregulation – used when ligand concentration decreases; target cell inserts more receptors into its membrane; more receptors make target cell more responsive to whatever neurotransmitters (for example) are present o Mechanism that allows cells to vary their responsiveness to growth factors and other signal molecules Receptor activity can be stopped: extracellular ligand can be degraded by enzymes in extracellular space; other chemical messengers can be removed from extracellular fluid through transport into neighboring cells; endocytosis of receptorligand complex Diseases can be caused by alterations in receptors or by problems with G proteins or second messenger pathways Properties of homeostatic control systems 1. Nervous system has a role in preserving the “fitness” (conditions that are compatible with normal function) of the internal environment a. Nervous system coordinates and integrates blood volume/osmolarity/pressure and body temperature 2. Some systems of the body are under tonic control a. A response that is always on but can increase or decrease 3. Some systems are under antagonistic control a. When a factor shifts homeostatic state in one direction, another factor will have an opposing effect 4. One chemical signal can have different effects in different tissues Chapter 3 Compartments separate biochemical processes that might conflict Barriers between them can make it difficult to move needed materials from one to another Body cavities – lined with tissue membranes Cranial – contains brain; primary control center Thoracic – bounded by spine and ribs with diaphragm as the floor; contains heart (in pericardial sac) and lungs (in pleural sacs) Abdominopelvic – abdomen and pelvis; peritoneum lines abdomen (stomach, intestines, liver, pancreas, gallbladder, spleen); pelvis is reproductive organs, urinary bladder, terminal portion of large intestine Lumen – interior of any hollow organ o Example: blood vessels are filled with fluid blood o For some organs (example digestive tract) lumen is an extension of external environment Extracellular fluid (ECF) – outside the cells o Plasma – fluid portion of blood o Interstitial fluid – surrounds most cells of the body Intracellular fluid (ICF) – within the cells Dividing wall between ECF and ICF is cell membrane – thin layer of lipids that separated the aqueous fluids of interior and outside Membrane – tissue or phospholipidprotein boundary layer Functions of cell membrane 1. Physical isolation barrier 2. Regulation of exchange with the environment – controls entry of ions and nutrients, elimination of wastes, release of products 3. Communication between the cell and its environment – proteins enable cell to respond to molecules/changes in external environment 4. Structural support – proteins hold the cytoskeleton Protein to lipid ratio varies depending on the source of the membrane o More metabolically active a membrane is, more proteins Fluid mosaic model by G. L. Nicolson in 1972 – membrane proteins could move laterally Phospholipids arranged in a bilayer – heads out, tails in Types of lipids – phospholipids (glycerol backbone with 2 fatty acid chains extending to one side and a phosphate group to the other), sphingolipids (fatty acid tails, heads are either phospholipids or glycolipids; longer than phospholipids), and cholesterol (mostly hydrophobic, insert themselves between hydrophilic heads of phospholipids) Micelles – small droplets with single layer of phospholipids; interior is filled with hydrophobic fatty acid tails Liposomes – larger spheres with bilayer phospholipid walls; hollow center Membrane proteins Integral proteins – tightly bound to membrane; transmembrane and lipidanchored proteins o Transmembrane proteins – “membranespanning”; important ones have 7 transmembrane segments; amino acids in protein chain are nonpolar; noncovalent interactions with lipid tails o Lipidanchored proteins – some are covalently bound to lipid tails that insert themselves into the bilayer; others are only on surface held by GPI anchor (membrane lipid and sugarphosphate chain) Found in association with sphingolipids, leading to lipid rafts Peripheral proteins – attached to membrane proteins by noncovalent interactions; enzymes and some structural binding proteins that anchor the cytoskeleton to the membrane Ability of cytoskeleton to restrict the movement of integral proteins allows cells to develop polarity – different faces of the cell have different proteins/properties Glycocalyx – membrane carbohydrates are found on external surface of cell and form this protective layer Differentiation – cells specialize; only selected genes activate The cell Cell membrane – outer boundary; controls movement in and out Nucleus – controls internal workings of cell and interaction with other cells Surrounded by dilute salt solution of ECF Cytoplasm – consists of fluid portion (cytosol, semigelatinous fluid separated from ECF), insoluble particles (inclusions), insoluble protein fibers (form cytoskeleton), membranebound organelles (mitochondria…) o Inclusions – don’t have boundary membranes; direct contact with cytosol; ribosomes o Protein fibers – actin fibers/microfilaments (thinnest), muscle contraction; intermediate filaments (keratin, neurofilament; somewhat larger), protective barrier of skin; microtubules made of protein tubulin (movement of cilia, flagella, and chromosomes; intracellular transport of organelles; cytoskeleton Microtubules – centrosome (organizing center, assembles tubulin monomers into microtubules); centriole (cylindrical bundle of 27 microtubules, arranged in 9 triplets); cilia; flagella Cytoskeleton – flexible; some protein fibers are permanent, but most are synthesized or disassembled according to cell’s needs; functions: cell shape, internal organization, intracellular transport, assembly of cells into tissues, movement o Motor proteins – convert stored energy into directed movement Myosins – bind to actin fibers; muscle contraction Kinesins – assist movement of vesicles along microtubules Dyneins – assist movement of vesicles along microtubules; associate with microtubule bundles of cilia and flagella Organelles Mitochondria – double wall; inside inner membrane is mitochondrial matrix which contains enzymes, ribosomes, granules, and its own DNA; inner matrix is surrounded by a membrane that folds called cristae; intermembrane space lies between outer and inner mitochondrial membranes and plays role in ATP production; can replicate themselves by budding Endoplasmic reticulum (ER) – network of interconnected membrane tubes with 3 major functions: synthesis, storage, transport o RER – protein synthesis; proteins are assembled on ribosomes attached to cytoplasmic side of RER o SER – lacks attached ribosomes; main site for synthesis of fatty acids, steroids, and lipids Golgi apparatus – hollow curved sacs called cisternae, stacked on top of one another; receives proteins made on RER, modifies them, and packages them into the vesicles Vesicles o Secretory vesicles – contain proteins that will be released o Storage vesicles – contents never leave the cytoplasm Lysosomes – act as digestive system of cell Peroxisomes – smaller than lysosomes; degrade longchain fatty acids and potentially toxic foreign molecules; generate hydrogen peroxide, which they convert to oxygen and water using catalase Nucleus Nuclear envelope – 2 membrane structure; both membranes have pores Nuclear pore complexes – large protein complexes with a central channel; where communication between nucleus and cytosol occurs Chromatin – composed of DNA and associated proteins Nucleoli – contain the genes and proteins that control the synthesis of RNA for ribosomes Tissues Cells in tissues are held together by cell junctions Histology – the study of tissue structure and function Tissue is described by the shape and size of the cells, arrangement of cells, the way cells are connected to one another, and amount of extracellular material present Types of tissues – epithelial, connective, muscle, neural Extracellular matrix – extracellular material that is synthesized and secreted by the cells of a tissue; some diseases are due to overproduction/disruption of matrix o Consists of proteoglycans and insoluble protein fibers (collagen, fibronectin, laminin) o Attachments between extracellular matrix and proteins are ways cells communicate with their external environment Cell adhesion molecules (CAMs) – membranespanning proteins responsible for cell junctions and for transient cell adhesions; cell adhesion helps white blood cells escape from circulation and move to infected tissues Stronger cell junctions – communicating junctions (gap junctions), occluding junctions (tight junctions), anchoring junctions o Gap junctions – simplest; allow direct and rapid communication through cytoplasmic bridges; channels open and close; allow chemical and electrical signals o Tight junctions – restrict movement of materials between the cells they link; cell membranes partly fuse with proteins claudins and occludins, making a barrier; barrier properties are dynamic; various degrees of “leakiness” “Bloodbrain barrier” – prevents harmful substances in blood from reaching ECF of brain Like a brick wall o Anchoring junctions – attach cells to each other or to matrix Cadherins – cellcell anchoring junction in vertebrates, connect across intercellular space Integrins – cellmatrix junction; membrane proteins that can also bind to signal molecules in environment, transfer information across cell membrane Contribute to mechanical strength of tissue (buttons/zippers) Protein linkage is very strong Like a picket fence – spaces allow materials to pass from side to side Paracellular pathway – movement between cells Cellcell anchoring junctions take form of adherens junctions (link actin fibers together) or desmosomes (strongest; attach to intermediate filaments of cytoskeleton) Cellmatrix anchoring junctions Hemidesmosomes – strong junctions that anchor intermediate fibers of the cytoskeleton to fibrous matrix proteins Focal adhesions – tie intracellular actin fibers to different matrix proteins Loss of normal cell junctions – diseases and metastasis Epithelial tissues – protect internal environment of body and regulate exchange of materials between internal and external environments o Consists of one or more layers of cells with thin layer of extracellular matrix (basal lamina/basement membrane) lying between the cells; protein filaments hold epithelial cells to the underlying cell layers Types of epithelial tissue: o Sheets of tissue that lie on the surface of the body or that line the inside of tubes and hollow organs 2 types of layering – simple and stratified 3 shapes – squamous (flat), cuboidal, and columnar o Exchange epithelia – thin cells; allow gases to pass rapidly; lines blood vessels and lungs; simple squamous epithelium; endothelium o Transporting epithelia – actively and selectively regulate exchange of nongaseous materials between internal and external environments; line digestive system and kidney; absorption/secretion; tight junction Shape – thicker than exchange; act as barrier and entry point; one cell thick (simple epithelium); cuboidal/columnar cells Membrane modification – apical membrane: surface that faces the lumen, has microvilli that increase surface area available for transport; basolateral membrane: surface that faces extracellular fluid may also have folds that increase surface area Cell junctions – tight junctions; material must move into a cell on one side and out on the other Cell organelles – properties differ depending on where in the body the epithelia are located o Ciliated epithelia – nontransporting tissue; line respiratory system and female reproductive tract; surface facing lumen is covered with cilia, moving fluid and particles across surface of tissue o Protective epithelia – prevent exchange; protect areas subject to mechanical/chemical stresses; stratified tissues; constantly being replaced o Secretory epithelia – cells that produce a substance and then secrete it into extracellular space; group up to form a gland Exocrine glands – release secretions to external environment through ducts Serous secretions – watery, tears, sweat, digestive enzyme solutions Mucous secretions – sticky, contain glycoproteins and proteoglycans o Goblet cells – produce mucus Endocrine glands – ductless; secretions are hormones; released into body’s extracellular compartment; enter blood for distribution to other parts of the body Pancreas, thyroid, gonads, pituitary glands Connective tissues – provide structural support and physical barrier; extensive extracellular matrix containing widely scattered cells that secrete and modify the matrix; includes blood o Extracellular matrix is a ground substance of proteoglycans and water in which insoluble protein fibers are arranged; consistency is highly variable (example: blood to bone) o Cells – fixed: responsible for local maintenance, tissue repair, energy storage; mobile: responsible for defense o Matrix fibers Collagen – most abundant protein in the body; flexible, not elastic; very strong Elastin – coiled, wavy protein; returns to original length after being stretched Fibrillin – straight fibers; combines with elastin to form filaments and sheets of elastic fibers; important in lungs, blood vessels, and skin Fibronectin – connects cells to extracellular matrix; play role in wound healing and blood clotting Types of connective tissue: o Loose connective tissue – elastic; underlie skin and provide support for small glands o Dense connective tissue – provide strength or flexibility; collagen fibers are dominant Tendons – attach skeletal muscles to bones; lack elastic fibers, cannot stretch Ligaments – connect one bone to another; also contain elastic fibers o Supporting connective tissue – dense ground substance that contains closely packed fibers Cartilage – solid, flexible, lack of blood supply Bone – calcified, strong, rigid o Adipose tissue – made up of adipocytes (fat cells) White fat – single large lipid droplet Brown fat – multiple lipid droplets o Blood – characterized by water extracellular matrix called plasma Plasma – dilute solution of ions and dissolved organic molecules Muscle tissue – excitable tissue (ability to generate and propagate electrical signals called action potentials); has external lamina; has ability to contract and produce force and movement o Cardiac muscle in heart o Smooth muscle – makes up most internal organs o Skeletal muscle – most attach to bones and are responsible for gross movement of the body Neural tissue – excitable tissue; has external lamina o Neurons – carry information in the form of chemical and electrical signals from one part of the body to another; concentrated in the brain and spinal chord o Glial cells – support cells for neurons Necrosis – cells die from physical trauma, toxins, or lack of oxygen when their blood supply is cut off; these cells swell, organelles deteriorate, then rupture o Red area of skin surrounding a scab Apoptosis – programmed cell death; do not disrupt neighbors when they die; cell shrinks, then breaks into blebs Totipotent – these cells have the ability to develop into any and all types of specialized cells; has the potential to become a functioning organism Pluripotent – can develop into many different cell types but not all cell types o Can be replaced by new cells created from stem cells – less specialized cells that retain the ability to divide Multipotent – undifferentiated stem cells in a tissue that retain the ability to divide and develop into the cell types of that tissue; bone marrow One goal of stem cell research is to find a source of pluripotent or multipotent stem cells that could be grown in the laboratory Plasticity – ability to specialize into a cell of a type different from the type for which they were destined Organs – groups of tissues that carry out related functions Example: skin Chapter 8 Nervous system – network of billions of nerve cells to form the rapid control system of the body Neurons – carry electrical signals rapidly; have one long thin extension (process) o Neurotransmitters – neurons release this chemical signal in most pathways to communicate with neighboring cells o Linked by gap junctions Emergent properties Central nervous system (CNS) – brain and spinal cord; integrating center for neural reflexes; integrate information that arrives from the sensory division of the PNS and determine whether a response is needed Peripheral nervous system (PNS) – sensory (afferent) neurons and efferent neurons o If a response is needed, CNS sends output signals that travel through efferent neurons to their targets Efferent neurons subdivide into somatic motor division (controls skeletal muscles) and autonomic division (controls smooth and cardiac muscles, exocrine glands, some endocrine glands, and some types of adipose tissue Autonomic division is also called visceral nervous system – controls contraction and secretion in various internal organs Autonomic neurons sympathetic and parasympathetic Enteric nervous system – digestive tract CNS can initiate activity without sensory input Neuron – long processes that extend outward from the nerve cell body o Processes are classified as dendrites (receive incoming signals) or axons (carry outgoing information) o Classified by the number of processes that originate from cell body Multipolar – many dendrites and branched axons; lack long extensions Pseudounipolar – cell body located off one side of one long process, the axon Bipolar – single axon and single dendrite Anaxonic – lack identifiable axon but have numerous branched dendrites o Classified by functions Sensory (afferent) – carry information about temperature, pressure, light from sensory receptors to the CNS Peripheral sensory neurons are pseudounipolar; cell body is out of the direct path of signals passing along the axon Interneurons – lie entirely within the CNS Efferent (somatic motor and autonomic) – enlarged axon terminals Nerves – long axons of afferent and efferent peripheral neurons are bundled with connective tissue into cordlike fibers o Sensory nerves – carry afferent signals o Motor nerves – carry efferent signals o Mixed nerves – carry signals in both directions Dendrites – branched processes that receive incoming information o Function in PNS is to receive incoming information and transfer it to an integrating region within the neuron o Function in CNS – can function as independent compartments sending signals back and forth with other neurons in the brain Axon terminal – contains mitochondria and membranebound vesicles filled with neurocrine molecules Axon – transmit outgoing electrical signals from integrating center of the neuron to the end of the axon o At the distal end, electrical signal is usually translated into chemical message by secretion of a neurotransmitter/modulator/hormone o Convey chemical and electrical signals Slow axonal transport – moves material by axoplasmic (cytoplasmic) flow from cell body to axon terminal Fast axonal transport – moves organelles at faster rates o Neuron uses stationary microtubules as tracks along which transported vesicles and mitochondria “walk” with the aid of attached footlike motor proteins o Forward – anterograde; moves synaptic and secretory vesicles and mitochondria from cell body to axon terminal o Backward – retrograde; returns old cellular components from the axon terminal to cell body for recycling Synapse – region where axon terminal meets target cell; presynaptic vs postsynaptic Glial cells – communicate with and provide important biochemical support to neurons o PNS: Schwann cells and satellite cells
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