Integrative Physiology Ch. 6 - Communication, Integration, and Homeostasis
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show | ~75 trillion
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Two basic types of physiological signals | show 🗑
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Electrical signals | show 🗑
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show | Molecules secreted by cells into the ECF
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_____ signals are responsible for most communication within the body | show 🗑
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show | Targets for short, are the cells that receive the electrical or chemical signals
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Four basic methods of cell-to-cell communication: | show 🗑
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Four basic methods of cell-to-cell communication: gap junctions | show 🗑
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Four basic methods of cell-to-cell communication: contact-dependent signals | show 🗑
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show | Communication by chemicals that diffuse through the ECF
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Four basic methods of cell-to-cell communication: long-distance communication | show 🗑
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Connexins | show 🗑
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show | The united connexins create a protein channel called a connexon that can open or close.
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Syncytium | show 🗑
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What kind of molecules flow through connexons when they’re open? | show 🗑
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The only means by which electrical signals can pass directly from cell to cell | show 🗑
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Are all gap junctions the same? | show 🗑
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Where does contact-dependent signaling commonly occur? | show 🗑
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CAMs | show 🗑
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Local communication is accomplished by _____ and _____ signaling | show 🗑
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show | A chemical that acts on cells in the immediate vicinity of the cell that secreted the signal.
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show | If a chemical acts on the cell that secreted it, it’s an autocrine signal (acts on itself)
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show | …diffusing through the interstitial fluid. Distance is a limiting factor for diffusion so the effective range of paracrine signals is restricted to adjacent cells
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Example of paracrine signaling | show 🗑
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Which cells in the body can release paracrine signals? | show 🗑
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Most long-distance communication between cells is the responsibility of… | show 🗑
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The endocrine system communicates by using… | show 🗑
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Hormones | show 🗑
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How does the nervous system communicate? | show 🗑
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What are the electrical-turned-chemical signals released from neurons called? | show 🗑
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Neurotransmitter | show 🗑
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Neuromodulator | show 🗑
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Neurohormone | show 🗑
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The similarities between the neurohormones from the nervous system and classic hormones from the endocrine system cause… | show 🗑
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show | A large and diverse family of regulators produced throughout the body. They are small cell-signaling proteins and can be proteins, peptides, or glycoproteins.
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show | Cell development, cell differentiation, and the immune response
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show | Cytokines act on a broader spectrum of target cells. Also they’re not produced by specialized cells the way hormones are (all nucleated cells can produce cytokines in response to stimuli), and they are made on demand
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show | They’re made in advance and stored in the endocrine cell until needed
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Receptor proteins | show 🗑
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show | A cell cannot respond to a chemical signal if the cell lacks the appropriate receptor proteins for that signal
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Ligand | show 🗑
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The ligand is known as the _____ because… | show 🗑
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show | The ligand-receptor binding activates the receptor
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What does the receptor do after being activated? | show 🗑
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show | The last signal molecule in the pathway initiates synthesis of target proteins or modifies existing target proteins to create a response
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show | Signal molecules –(binds to)-> Receptor protein –(activates)-> Intracellular signal molecules –(alters)-> Target proteins –(create)-> Response
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Chemical signals fall into two broad categories based on their lipid solubility: | show 🗑
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show | In the nucleus, cytosol, or cell membrane as integral proteins
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Lipophilic signal molecules | show 🗑
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show | Unable to diffuse through membrane, instead they remain in the EFC and bind to receptor proteins on the cell membrane. A very rapid response time, within milliseconds to minutes.
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show | Receptor-channels, receptor-enzymes, G protein-coupled receptors, integrin receptors
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Signal transduction | show 🗑
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show | The extracellular signal molecule (ligand) is the first messenger; the intracellular molecules form a *second messenger system*
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Transducer | show 🗑
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Signal amplification | show 🗑
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Amplifier enzyme | show 🗑
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Signal transduction pathway pattern: (1) | show 🗑
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show | The activated receptor turns on its associated proteins which may be protein kinases (which transfer phosphates from ATP to proteins) or amplifier enzymes (which create ICF second messengers)
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show | Second messengers alter the gating of channels (opening or closing them, affecting the cell’s membrane potential) then increase intracellular calcium which will bind to proteins and change their function, creating cellular response
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Signal transduction pathway pattern: (4) | show 🗑
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Signal transduction pathway pattern: (5) | show 🗑
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Signaling cascade | show 🗑
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show | Adenylyl cyclase, guanylyl cyclase, and phospholipase C
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show | Ca^2+, cAMP, cGMP, IP_3, DAG
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show | Have two regions: receptor region on the ECF side, and enzyme region on ICF side. Enzyme region may be on a different protein than the receptor. The enzyme will be either a protein kinase (e.g. tyrosine kinase) or guanylyl cyclase
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show | Converts GTP to cGMP. Found in membrane cytosol. Activated by receptor-enzyme nitric oxide (NO)
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show | …the hormone insulin as well as many growth factors and cytokines. Note: the insulin receptor protein has intrinsic tyrosine kinase activity. Most cytokines don’t have intrinsic enzyme activity and instead activate cytosolic enzymes
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show | A cytosolic enzyme called Janus family tyrosine kinase, abbreviated JAK kinase
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show | Large membrane-spanning proteins that cross the bilayer 7 times. The cytoplasmic tail is linked to the G protein
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show | A 3-part membrane transducer molecule. When inactive they’re bound to guanosine diphosphate (GDP). Exchanging GDP for GTP activates the G protein.
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show | (1) open an ion channel in the membrane, or (2) alter enzyme activity on the cytoplasmic side of the membrane
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show | Amplifier enzymes
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show | Adenylyl cyclase and phospholipase C
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show | The types of ligands that bind to the G protein-coupled receptors include hormones, growth factors, olfactory molecules, visual pigments, and neurotransmitters
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show | Converts ATP to cAMP. Found in membrane. Activated by G protein-coupled receptor.
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show | Converts membrane phospholipids to IP3 and DAG. Found in membrane. Activated by G protein-coupled receptor
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The G protein-coupled adenylyl cyclase-cAMP system: (1) | show 🗑
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The G protein-coupled adenylyl cyclase-cAMP system: (2) | show 🗑
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The G protein-coupled adenylyl cyclase-cAMP system: (3) | show 🗑
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The G protein-coupled adenylyl cyclase-cAMP system: (4) | show 🗑
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show | Protein kinase A phosphorylates other proteins, leading ultimately to a cellular response
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The G protein-coupled phospholipase C system summary | show 🗑
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show | A nonpolar diglyceride that remains in the membrane and interacts with protein kinase C (PK-C), a Ca^2+-activated enzyme on the cytoplasmic face of the cell membrane. PK-C phosphorylates cytosolic proteins for signal cascade
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Inositol triphosphate (IP_3) | show 🗑
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The G protein-coupled phospholipase C system: (1) | show 🗑
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show | G protein activates PL-C, an amplifier enzyme
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The G protein-coupled phospholipase C system: (3) | show 🗑
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The G protein-coupled phospholipase C system: (4) | show 🗑
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The G protein-coupled phospholipase C system: (5) | show 🗑
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show | Membrane-spanning integrins have receptors on the ECF side binding either to proteins of the matrix or to ligands such as antibodies or blood clotting molecules.
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Integrin receptors: ICF | show 🗑
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show | Blood clotting is defective in individuals who lack integrin receptors on their platelets
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The simplest receptors are… (also, where are they found?) | show 🗑
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show | When a ligand binds to the receptor-channel protein, a channel gate opens or closes, altering the cell’s permeability to an ion. The membrane potential is rapidly effected, creating an electrical signal
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Acetylcholine-gated cation channel of the skeletal muscle | show 🗑
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How does calcium enter the cytosol | show 🗑
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Where are most calcium ions stored, and how does it get there? | show 🗑
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Effects of calcium ions entering the cytoplasm: (1) | show 🗑
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Effects of calcium ions entering the cytoplasm: (2) | show 🗑
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show | They bind to regulatory proteins to trigger exocytosis of secretory vesicles.
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Effects of calcium ions entering the cytoplasm: (4) | show 🗑
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show | Entry into a fertilized egg initiates development of the embryo
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show | Soluble gases are short-acting paracrine/autocrine signal molecules that act close to where they’re produced
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The best known gaseous signal molecules | show 🗑
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Half-life | show 🗑
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show | In endothelial tissues NO is produced by nitric oxide synthase (NOS): arginine + O2 –(NOS)-> NO + citrulline. The NO diffuses into target cells where, through a cascade, ultimately relaxes blood vessels.
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NO in the brain | show 🗑
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Carbon monoxide (CO) as a signal | show 🗑
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Hydrogen sulfide (H2S) as a signal | show 🗑
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show | Receptors with no known ligand
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show | Lipid-derived paracrine signals. They are all derived from arachidonic acid, a 20-carbon fatty acid. They ultimately act on their target’s G protein-coupled receptors
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The synthesis process network that produces arachidonic acid is known as the… | show 🗑
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Arachidonic acid cascade | show 🗑
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show | Leukotrienes and prostanoids. These lipid-soluble molecules can diffuse out of the cell and combine with G protein coupled-receptors on neighboring cells to exert their action
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Leukotrienes | show 🗑
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show | Produced when the enzyme cyclooxygenase (COX) acts on arachidonic acid. Prostanoids include prostaglandins and thromboxanes which signal a huge assortment of actions, e.g. prostaglandins play a role in inflammation
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show | They inhibit COX enzymes and decrease prostaglandin synthesis. Prostaglandins play a role in inflammation and inflammation causes pain due to a release of chemicals that stimulate nerve endings
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Another example (other than eicosanoids) of lipid signal molecules | show 🗑
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For most signal molecules, the target cell response is determined by… | show 🗑
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show | …the same receptor’s binding site. This can result in competition
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Example of specificity and competition with binding site receptors | show 🗑
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When a ligand binds with a receptor, one of two events follows: | show 🗑
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Agonists | show 🗑
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Antagonists | show 🗑
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Note: what does “endogenous” mean? | show 🗑
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Example of a pharmacologically synthesized agonist | show 🗑
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show | When epinephrine binds to the alpha receptor, e.g. in the intestinal tract blood vessels, the blood vessels constrict. When epinephrine binds to the beta-2 receptor, e.g. in skeletal muscle blood vessels, blood vessels dilate
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What happens when a signal molecule is present in the body in abnormally high concentrations for a sustained period of time? | show 🗑
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show | A decrease in receptor number. The cell can physically remove receptors from the membrane through endocytosis
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show | A faster method of decreasing cell response than down-regulation. It is achieved by binding a chemical modulator to the receptor protein. E.g. phosphorylating beta receptors
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Desensitization diminishes the target cell’s response regardless of… | show 🗑
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show | A condition in which the response to a given dose decreases despite continuous exposure to the drug; it occurs due to down-regulation and desensitization
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show | The insertion of more receptors into the membrane. E.g. if a neuron is damaged and can’t release normal amounts of neurotransmitter, the target cell may up-regulate its receptors
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How does a cell terminate a response from a Ca^2+ signal? | show 🗑
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show | One way is by degrading the ligands with enzymes in the ECF. Another is by transporting the messengers into neighboring cells
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show | By endocytosis of the receptor-ligand complex. Once in the cytoplasm the ligands are removed and the receptors return to the membrane via exocytosis
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Disease caused by toxin: Bordetella pertussis | show 🗑
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Homeostasis is a continuous process that uses a _____ to monitor key functions, which are often called _____ | show 🗑
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In its simplest form, any control system has three basic parts: | show 🗑
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The input signal of the physiological control system | show 🗑
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show | The integrating center (often neurons or endocrine cells) – it evaluates information coming from the sensor and initiates a response that is designed to bring the regulated variable back into the desired range
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show | The effector: muscles or other tissues controlled by the integrating center
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Cannon’s postulates describing regulated variables and control systems | show 🗑
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show | Fitness = compatible with normal function. Nervous system regulates blood volume, pressure, osmolarity, body temp., etc.
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Cannon’s postulates describing regulated variables and control systems: (2) | show 🗑
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show | There are agents in the body that are constantly moderated sending opposing signals to them, e.g. parasympathetic and sympathetic pathways
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Cannon’s postulates describing regulated variables and control systems: (4) | show 🗑
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Local control | show 🗑
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show | Respond to changes that are widespread throughout the body, i.e. *systemic*. This is a long-distance pathway
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show | The nervous and endocrine systems. Cytokines are also involved
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A reflex pathway can be broken down into two parts: | show 🗑
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Three components of the reflex loop and their steps. I.e. Steps of a reflex | show 🗑
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Stimulus/sensor -> afferent pathway | show 🗑
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show | Evaluates the incoming signal, compares it with the *setpoint* (desired value) and decides on an appropriate response.
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show | The output signal, or efferent pathway, is initiated by the integrating center. This is the electrical or chemical signal that’s sent to the effector (AKA target). The effector carries out the appropriate response to normalize the situation
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Sensory receptors vs. receptor molecules | show 🗑
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show | Receptors located in, or closely linked to, the brain
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show | Receptors residing elsewhere in the body
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show | All sensory receptors have a threshold, a minimum stimulus that must be achieved to set the reflex response in motion
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Do endocrine reflexes that are not associated with the nervous system have sensory receptors? | show 🗑
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In endocrine reflexes, what’s the integrating center? | show 🗑
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show | Central nervous system (brain/spinal cord)
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Two levels of response for any reflex control pathway | show 🗑
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Factors that influence an individual’s setpoint for a given variable | show 🗑
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show | The adaptation of physiological processes to a given set of environmental conditions if it occurs naturally
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Acclimation | show 🗑
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Feedback loop | show 🗑
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show | Negative (keeps system near setpoint); positive
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show | …the sensitivity of the system. If not very sensitive, the regulated variable will oscillate around the setpoint. Some sensors in physiological systems are more sensitive than others
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show | The response reinforces the stimulus rather than decreasing it (like negative feedback loops)
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show | Hormonal control of uterine contractions during childbirth. The baby drops and puts pressure on cervix. Oxytocin is released causing uterus to contract, putting more pressure on cervix causing oxytocin release
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show | Reflexes that enable the body to predict that a change is about to occur and start the response loop in anticipation of the change
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show | Salivation, initiated by the sight, smell, or even thought of food
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show | Daily biological rhythm. Humans have many circadian rhythms including blood pressure, body temperature, and metabolic processes. E.g. you feel cold at night due to the circadian rhythm-controlled thermoregulatory reflex
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Are cortisol concentrations in the body constant? | show 🗑
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While neural and endocrine reflexes can be relatively simple, _____ can be very complex | show 🗑
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Specificity of reflex pathways: neural vs. endocrine | show 🗑
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show | Neural reflexes are much faster than endocrine pathways, with electrical signals reaching speeds of up to 120 m/sec.
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REVIEW AND MEMORIZE DIAGRAM ON PAGE 207 | show 🗑
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Duration of action of reflex pathways | show 🗑
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Stimulus intensity of reflex pathways | show 🗑
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Knee-jerk response | show 🗑
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show | REVIEW AND MEMORIZE TABLE ON PAGE 209
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show | Gap junctions, contact-dependent signals, local communication, long-distance communication
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Type of junctions between contractile cardiac cells | show 🗑
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Contact-dependent signals | show 🗑
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show | Autocrine and paracrine
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How far away between paracrine signaling? What’s the limit (distance) for communication? | show 🗑
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Long distance communication is accomplished by… | show 🗑
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show | The gland that secretes the hormone is filled with them, so secretion into the blood occurs down their concentration gradient.
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Nervous communication does not require… | show 🗑
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show | Molecules that are secreted by neurons across a small gap to the target cells neurotransmitters are made in relatively LOW quantities
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show | Large: it’s more of a brute force method of communication than neural communication
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show | Endocrine: secreted from gland rather than through duct. What is secreted is a hormone
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show | Lipophilic = hydrophobic; lipophobic = hydrophilic (i.e. hydrophilic hormones need to use surface receptors to enter cells)
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cAMP is a… | show 🗑
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Explain how the G protein is exactly activated by the coupled receptor. How does that work? | show 🗑
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show | GTP is hydrolyzed to GDP; the G protein then reassociates with the remainder of the dissociated G protein (beta and gamma)
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Recap: parts of the G-protein | show 🗑
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G protein may work in a different pathway, not cAMP but… | show 🗑
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show | …epinephrine
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Major adrenergic receptors. What type of receptor are they? | show 🗑
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How do adrenergic receptors lead to vasoconstriction (thus increasing blood pressure)? Use an alpha-1-adrenergic receptor an example. | show 🗑
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An agonist to an adrenergic receptor would… (Example of an agonist?) | show 🗑
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show | On smooth muscle cells
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show | Beta-1 adrenergic receptors
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Catecholamine storm after heart attack | show 🗑
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show | G protein-couple receptor kinase
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Give detailed explanation of the process of down-regulation | show 🗑
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Sorting endosome – How does it determine whether or not to recycle the G protein-coupled receptor? | show 🗑
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Chronic beta-blocker therapy results in… | show 🗑
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show | Carotid artery which senses the bp change and sends a signal to the brain which decides the proper response. The brain will either initiate a reflex response or there can be a local change and a local response.
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How to shut off a positive feedback loop? | show 🗑
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show | E.g. for ovulation, wherein you want a powerful surge of response
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