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102 Cards in this Set
- Front
- Back
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Types of Physiological Subdiciplines
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Cellular and Molecular Phys
-genetics, metabolism, organelles Systems Phys -function of organs Organismal Phys -whole animal Ecological Phys -animal and it's environment Integrative Phys -multiple levels of organization |
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Levels of Study in Physiology
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Reductionism
Emergence |
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Reductionism
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understanding a system by studying the function of it's parts
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Emergence
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The whole is more than the sum of its parts
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Homeostasis
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maintenance of internal consistency
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Genotype
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genetic makeup
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Phenotype
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morphology, physiology, and behavior
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Allometric Scaling
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Body size influences physiological pattern
metabolic rate over body mass line of unity between the two |
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Strategies for coping with changing conditions
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Conformers
Regulators |
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Conformer
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allows internal conditions to change with external conditions
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Types of Physiological Subdiciplines
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Cellular and Molecular Phys
-genetics, metabolism, organelles Systems Phys -function of organs Organismal Phys -whole animal Ecological Phys -animal and it's environment Integrative Phys -multiple levels of organization |
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Levels of Study in Physiology
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Reductionism
Emergence |
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Reductionism
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understanding a system by studying the function of it's parts
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Emergence
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The whole is more than the sum of its parts
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Homeostasis
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maintenance of internal consistency
involves continuous maintenance nervous system and endocrine systems accomplish the communication via nerve impulse and hormones |
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Strategies for Coping with Changing Conditions
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Conformers
Regulators |
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Conformers
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Allow internal conditions to change with external conditions
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Regulators
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Maintain relatively constant internal condition regardless of external condition
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Homeostatic Control Mechanisms
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Nervous-- quick
Endocrine-- slow |
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Components of Control Mechanism
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Receptor (sensor)
Control Center Effector |
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Receptor
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Monitors the environment
Responds to Stimuli (changes in controlled variables Receptor--Afferent Pathway--Control Center |
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Control Center
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Determines the set point at which the variable is maintained
Receives input from receptor Determines appropriate response Control Center-- Effernet pathway-- Effector |
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Effector
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Receives output form control center
Provides the means to respond Response acts to reduce or enhance the stimulus (feedback) Involved after control center is elicited by afferen signal sent to control center to effernt signal which elicites the effector which wich effects feedback and returns the variable to homeostatic level |
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Negative Feedback Loop
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Response reduces or shuts off the original stimulus
eg stress hormones (endocrine system) regulation of body temp regulation of blood volume by ADH (also endocrine system response) |
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Negative Feedback Loop Examples
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Stim of risen body temp-- receptors in the skin-- to the afferent pathway-- to control center-- to effernt pathway-- sweat glads triggered-- body temp is reduced-- stim ends
Body temp is lowered-- efferent pathway sends stim to control center-- afferent pathway sends signal to skin-- triggers shakes or goose bups-- body temp is risen-- end of stim |
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Positive Feedback Loop
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Response enhances or exaggerates the original stim
May exhibit a cascade or amplifying effect Usually controls: enhancement of labor contractions via oxcytocin or platlet plug formation and blood clotting |
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Phenotypic Plasticity
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single genotype generates more than one phenotype DEPENDING upon environmental stimulus
*PHENOTYPE is a product of genotype and its interaction with the environment eg Daphnia look at figure 1.1 can be reversible or irreversible |
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Irreversible Phenotypic Plasticity
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Polyophenism-- developmental plasticity
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Reversible Phenotypic Plasticity
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Acclimation-- under laboratory conditions
Acclimatization-- under natural environment |
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Natural Coping Under Phentoypic Plasticity
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Diversity in anatomic and physiological strategies animals use to cope with their environment
2 Types of questions : Proximate Cause and Ultimate Cause eg: giraffe heart size and log neck apposed to desert rodent renal tubule size |
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Proximate Cause
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How did certain phenotypes develop?
eg for Daphnia-- to protect them from predator |
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Ultimate Cause
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Why are these changes helpful?
eg for Daphnia-- to become immune to predator via phenotypic changes |
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Basis for Evolution and Natural Selection
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Darwin did not discover evolution
he came up with notion of a mechanism for evolution (natural selection) Alfred Russel Wallace and Darwin came up with the idea.. BASIC IDEA:There is evolution; traits in population change in time ~ change can occur enough for speciation (new formed species) |
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Fundamental Principles of Evolution
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Traits are heritable
Variation among individuals for specific traits (They are heritable) Some versions of those traits are more adaptive (more fitness) than others eg Giraffe hearts Combine these three pieces together and you get changes in populations; changes in frequency of traits -Add to random changes int riats (i.e. genteic mutations) and you get large changes in traits of a population --Environmental changes, thus adaptive traits might no longer be adaptive over time |
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Genetic Drift
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Not all differences are adaptable
RANDOM changes in the frequency of genotypes over time Independent of adaptive evolution Most common in SMALL populations --eg forest fires resulting in founder effect This can cause a founder effect |
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Founder Effect
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Survival without genetic or evolutionary dominance, they just happened through genetic drift
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Evolutionary Relationships
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Common evolutionary ancestor
Despite diversity in animal form and function, there are similarities The more closely related, the more shared featrues Understanding evolution is necessary to understand physiological diversity |
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Cellular Physiology
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Modern phys is much about the interactions of molecules and cells as it is about the interactions of organs in organisms
Necessary to understand the structure and characteristics of cells to be able to understand organs, organ systems, and organisms |
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Cellular Physiology Functions
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Cell is the smallest structural functioning living unit
Organismal functions depend on individual and collective cell functions Biochem activities of cells are dictated by their specific subcellular structures --structure dictates function |
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Cellular Physiology Cell Functions
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Cells for task s essential to survival to maintain homeostasis based on INTRACELLULAR functions
Cells need to generate energy from nutrient molecules to sustain life Energy is generated intracellularly via the cytosol and mitochondria |
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Cellular Physiology Cell Organelles
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Organelles and cytoskeleton participate in many tasks contributing to homeostasis
Understand the function of plasma membrane --membrane transport and membrane potential-- vital to maintaining homeostasis in various cell types Disturbances causes issues-- eg K abnormalities in cardiac cells How do adaptations on a cellular level allow organs to perform tasks --emphasize protein synthesis modification and trafficking |
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Cells
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2 MAJOR TYPES
Prokaryotes -bacteria, cyanobacterial -small 1-10 microns -primitive, simple structure Eukaryotes -fungi, plants, animals - larger, 10X larger than prokaryotes -complicated structure - lots of intracellular compartments |
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Eukaryotic Cells
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Plasma membrane
-- phospholipid bilayer -- outer boundary Cytosol/Cytoplasm -- inside of cells -- filled with protein fillaments -- filled with organells Nucleus -- control center Intracellular membranes form distinct compartments, like rooms in a house, concentrate specific characteristic set of proteins with biochem funtion, segregate biochem reactions that could be hazardous to one another. --- allows cells to be bigger, and accomplish a wide range of functions |
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Generalized Cell
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All cells have common structures and functions
LOOK AT Life of a Cell: http://multimedia.mcb.harvard.edu/ |
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Cytosol
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space between membrane and orgnanells
50% of cell volume site of protein synthesis, much of intermediary metabolism Gelatinous(high concentration of soluble filamentous proteins Small molecules diffuse easily EG of cytosolic proteins enzymes required for glycolysis: glucose-6-phosphate dehydrogenase Synthesis of cytosolic protein... peptide chain completed and released! |
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Mitochondria
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Site of ATP sythesis
-- oxidative phosphorylation 2 compartments -- matrix -- inter-membrane space some proteins synthesized here on their own ribosomes It has it's own genomes b/c evolved from bacterium |
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Endoplasmic Reticulum
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Extensive membrane network
Defines a continuous internal space (ER lumen) Rough ER Smooth ER Most proteins translocated to ER get glycosylated |
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Rough Endoplasmic Reticulum
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ribosomes associated on surface
major function: biosythesis of membrane and secreted proteins close to nucleus |
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Smooth Endoplasmic Reticulum
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no associated ribosomes
major function: lipid biosythesis most cells have very small SER Liver cells ahve a lot: site of drug detoxification and glycogen breakdown --eg cytochrome P450 enzyme |
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Protein Glycosylation in ER
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1.Carbohydrate (sugar) molecules are linked to amino acid in protein
2. Carried out by enzymes that reside in ER FUNCTION of glycosylation Increase resistance to proteases some protein-protein interactions are dependent After translocation into the ER all proteins move on to the Golgi |
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Golgi Apparatus
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series of distinct compartments
disk-like shaped ER-- to Golgi-- Cis Golgi-- Medial Golgi-- Trans Golgi-- Plasma Membrane FUNCTION of GOLGI protein maturation and sorting it packages protein for movement Some proteins are removed/ added Each reaction occurs in specific compartment... cis, medial, trans so glycosylation can be used to determine the progress of proteins through ER/ Golgi -- some enzymes subclasses get unique modifications ---eg: protein that function in lysosome (only) get manno-6-phosphate In Golgi there are enzymes that chop proteins |
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Protein Maturation in Golgi: II Proteolytic Processing
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Some proteins are sythesized as inactive precursor proteins, that need to be proteolytically cleaved to become mature (active) cleavage can occur in Golgi
EG: peptide hormones: including insulin, and some growth factors In accordance to diabetes: Insulin is a protein secreted to decrease or regulate blood glucose levels and golgi stores it away for later use Probly also in Golgi-- if insulin is not broken down, glucose levels go through the roof and casue damage to blood vessels |
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Protein Sorting in Golgi
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Golgi is like a clearing house; proteins with differnt destinations are segregated and sent to final location
Sorting is accomplished via special sorting sequences Possible destinations: 1. Golgi Retenation: Golgi-resident proteins (proteases, glycosylation enzymes) have a Golgi Retention Signal eg: some stay in Cis, some move to Medial, some move to Trans Other possible destinations: 2. Plasma Membranes/ Constitutive Secretion-- default pathway. no special sorting info requiredother than signal peptide. Soluble proteins get secreted, integral membrane proteins go to plasma membrane 3. Specialized Secretory Vesicles (i.e. regulated secretion or exocytosis) Only occurs in some cells (neurons). Proteins have undefined signal. They get sorted, concentrated, sroted in specialized secretory vesicles. When cell is stimulated, vesicles fuse with dock protiens on plasma membrane and get released. 4. Lysosome: proteins that receive mannose-6-phosphatein Golgi go to the Lysosome. |
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Lysosome
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Small membrane-bounded vesicles
Contain hydrolytic enzymes to digest macromolecules (i.e. proteases, nuclease, lipases, phosphotases, ect) FUNCTION: to breakdown macromolecules and recycle components to use in the cell. Inside of lysosome is acidic!! pH approx. 5.0 due to ion pump that hydrolyzes ATP and pumps H into lysosome Macromolecules get delivered to Lysosome via endocytosis. |
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Lysosomal Enzyme Sorting form Golgi to Lysosome
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*Lysosomal proteins receive specific modification: Mannose-6-phosphate
1. In Golgi, proteins containing mannose-6-phosphate get packaged into clathrin-coated vesicles ---- cathrin forms a basket-like coat on surface of Trans-Golgi membrane and promotes vesicle formation. Coat also contains adaptins (look at figure p 19) 2. Mannose-6-phosphate receptor binds lysosomal protein in Golgi and binds clathrin coat via adaptation. This allows (mannose-6-phosphate-protein-receptor-clathrin) complex to accumulate in a bud and pinch off into a vesicle 3. Coat comes off vesicle and fuses with endosome and delivers content --- endosome is preexisting compartment with low pH like the lysosome 4. Low pH in endosome casues mannose-6-phosphate& receptor complex to fall apart. phosphate on protein is removed by phosphatase in Lysosome 5. Mannose-6-phosphate receptor is recycled back to Golgi via transport vesicle 6. Sorted protein stays in endosome, endosome matures to become a Lysosome |
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Lysosomal Storage Disease
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1.Disruption of lysosome sorting can occur in several ways
--Drug tunicamycin blocks addition of N-linked sugars to newly synthesized proteins, preventing attachment of mannos-6-phosphate recognition marker -- Compounds that elevate pH prevent enzymes from dissociating from receptor and block recycling back to TGN so proteins pass through TGN unrecognized 2. Tay-Sachs results from mutated gene that encodes lysosomal enzyme (HEX A); unable to degrade substance that contains certain specific sugar linkages. Overcrowding of these sugar linkages causes cell death. |
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Cell Signaling and Endocrine Regulation
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-Nucleus & Plasma Membrane
-Membrane Transport - Cellular Communication - Endocrine Regulation |
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Membrane Structure
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Phospholipid Bilayer
Within the bilayer, there are integral proteins, peripheral proteins, cholesterol, glycoproteins (with sugar that is connected/ resides on them), and channel proteins |
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Membrane Transport
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Cells have to transport molecules across the membrane
3 types: Passive Diffusion Facilitated Diffusion Active Transport Distinguished by direction of transport, nature of carriers and role of energy |
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Cellular Communication
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communication between cells
Signaling cell sends a signal (usually a chemical) and target cell receives the signal and responds to it |
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Types of Cell Signaling
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DIRECT
Signaling cell and target cell connected by gap jusnctions Signal passed directly from one cell to another INDIRECT signaling cell releases chemical messenger chemical messenger carried in extracellular fluid (some secreted into environment) chemical messenger binds to a receptor on the target cell activation of signal transduction pathway response in target cell |
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Indirect Signaling over Short Distances
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Paracrine
Chemical messenger diffuses to nearby cell Autocrine Chemical messenger diffuses back to signaling cell --eg of Autocrine is a T-cell. this is also a part of a positive-feedback loop memorize at table 3.1 |
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Indirect Signaling over Long Distances
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Endocrine System
Chemical messenger (hormone) transported by circulatory system Nervous System Electrical signal travels along neuron and chemical messenger (NT) released memorize at table 3.1 |
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Direct Signaling
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Gap Junctions
Specialized protein complexes creates an aqueous pore between adjacent cells Movement of ions between cells Changes in membrane potential (via electrical signal)(eg heart block-- block in electrical signal between cells) Chemicla messenger can travel through the gap junction (eg cAMP) Opening and closing of gap junction can be regulated |
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Steps Involved in Indirect Signaling
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3 Steps:
--Release of chemical messenger from signaling cell (gland) --Transport messenger through extracellular environment to target cell --Communication of signal to target cell Systems for indirect signaling have similarities and differences |
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Glands
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Exocrine Gland
-- excrete substance into center of gland (into environment) Endocrine Gland -- secretory cells release hormone into blood stream and the hormone only binds to target cell |
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Chemical Messengers
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6 Classes of Chemical Messengers:
-Peptides -Steroids -Amines -Lipids -Purines -Gasses Structure of chemical messenger (especially hydrophilic vs hydrophobic) affects signaling mechanism memorize table 3.2 |
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Peptide/Protein Hormones
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2-200 amino acids long
Synthesized in RER --often larger preprohormones Stored in vesicles --prohormones Secretes by exocytosis --hormones Hydrophilic --soluble in aqueous solutions -- travel to target cell dissolved in extracellular fluid Binds to transmembrane receptor --signal transduction RAPID EFFECT ON TARGET CELL eg insulin |
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Transmembrane Receptor
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eg: G-protein
stretches across cell membrane the ligand binding domain is in the extracellular fluid. The transmembrane domain is in the phospholipid bilayer. The inracellular domain is contained in the cytoplasm |
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Steroid Hormones Types
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Derived from cholesterol
Synthesized in SER or Mitochondria Steroids are a 4 ring structure 3 Classes of Hormones Mineralocorticoids -- Electrolyte Balance Glucocorticoides --Stress Hormones (eg: chortosol) Reproductive Hormones --Regulate sex-specific characteristics (eg: testosterone, estrogen, oxcytocin |
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Steroid Hormones
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Hydrophobic
Can diffuse through plasma membrane so they ONLY bind inside of cell No carrier protein is needed but if bound, must dissociate before entering cell Cannot be stored in the cell Must be synthesized on demand Tranported to target cell by carrier proteins -eg. albumin Bind to intracellular or transmembrane receptors Slow effect on target cell (gene transcription) ---- stress hormone cortisol has rapid non-genomic effects |
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Amine Hormones
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Chemical possessing amine group (NH2)
-- eg: ACh, Catecholamines(dopamine, norepinephrine, epinephrine) serotonin, melatonin, histamine thyroid hormones -- sometimes called biogenic amines Some true hormones, some NT, some both Most hydrophilic -- thyroid hormones are hydrophobic Diverse effects |
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Other Chemical Messengers
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Eicosanoids
-most act as paracrines -hydrophobic -often involved in inflammation and pain. eg: arachidonic acid these need a protein for transport Other examples 1st Prosaglandin-- inflammation 2nd Prostocycline-- thins blood 3rd Thromboxanes-- promotes clotting |
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COX inhibitors
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Cycloogenase exists in 2 forms (COX-1 and COX-2)
Aspirin irreversibly inhibits COX-1 -- know the downstream effect |
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COX Inhibitors (COX-1 and COX-2 Effects)
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Cycloogenase Exists in 2 forms- COX-1 and COX-2
Aspirin irreversibly Inhibits COX-1 and weakens COX-2 - Reduces Prostaglandis (anti-inflammatory) via COX-2 -Reduces Thromboxanes (less platelet aggregation= thinned blood) via COX-1 -Reduces Prostacyclins (removes inhibition of clotting= increased bleeding) via COX-1 --normally inhibits platelet plug formation( notice homeostatic antagonism between TX and PG) --can lead to GI bleeding after chronic ingenstion NSAIDS such as aspirin, acetaminophen, ibuprofen- directly target cycloogenase SO drug companies now generate a compound that ONLY inhibits COX-2 (anti-inflammatory) *celecoxib (Celebrex) *rofecoxib (Vioxx)-- but was withdrawn in 2004 by Merck after cardiovascular risks found associated with it |
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Gases are Chemical Messengers
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Most act as paracrines (nearby cells)
eg: nitirc oxide (NO) and carbon monoxide (CO) |
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Purines are Chemical Messengers
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Function as neuromodulators and paracrines
eg: adenosine, AMP, ATP, GTP |
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Communication to the Target Cell (Overview)
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Hormones made from plentiful precursors wit easy synthesis
When possible, one generates many diff hormones with similar starting product -steriodal ring makes <1,000 diff major and minor steroid hormones --- progesterone, major, gives rise to minor ones with anti-anxiety effects Endocrine glands conserve resources so require fancy receptor that can differentiate among similar hormones ------ imagine estrogen receptor mistaking it for testosterone |
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Receptors on Target Cell (Communication to the Target Cell)
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Hydrophilic messengers bind to transmembrane receptor
Hydrophobic messengers bind to intracellular receptor |
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Ligands to Target Cell (Communication to the Target Cell)
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chemical messenger can bind to specific receptor
receptor changes shape when ligand binds |
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Ligand-Receptor Interactions
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Very specific
Only correctly shapes ligand can bind to receptor Ligand mimics -Agonist- Active receptor -Antagonist- block receptor -Many ligand mimics act as drug or poisons (beta blockers, Ca++ channel blockers, ect) |
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Ligand-Receptor Binding
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L+R=LR
Formation of LR causes response More free L or R will increase the response --- Law of Mass Action Receptors are saturated at high L -- response is maximal [L][R]/[LR]=KD KD tells you how likely binding is to occur smaller the KD, steeper slope, more affinity to bind (shown in Skatchard graph) BUT HIS SLIDES show it as %of receptors bound over the concentration of messenger (Ligand?) |
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Changes in Number of Receptors
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Number if receptors affects L-R complexes
-More receptors= more LR complexes= higher response Target cells alter respons numbers -DOWN Regulation -- target cell decreases the number of receptors --often due to high concentration ligand UP Regulation --target cell increases the number of receptors |
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Inactivation of Ligand-Receptor Complexes
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Diffusion
Endocytosis Enzyme Digestion -eg ACh esterase is an enzyme that digests extracellular ACh in synapse |
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Signal Transduction Pathway
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When hormone binds to receptor they cause a variety of changes within the cell
-Chenges mediated by intracellular signal transduction pathway |
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Interaction Among Transduction Pathways
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Cells have receptors for different ligands
Diff Ligands activate diff transduction pathways Response of the cell depends upon the complex interaction of signaling pathways --often involving a negative-feedback loop |
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Endocrine System
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Endocrine System- cells, tissues, organs- secrete and respond to circulating chemical messenger molecules
Controls FUNCTIONS -salt and water balance -bp -stress response -cellular metabolism -growth and development -sexual maturation and desire |
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Organ System of Endocrine System
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Pineal Gland
Hypothalamus Pituitary Gland Thyroid Gland Parathyroid Gland (on dorsal aspect of thyroid) Thymus Adrenal Gland Pancreas Ovary/ Testis |
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Several Ways the Brain Controls Endocrine System
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Anterior Pituitary hormone system
Posterior Pituitary hormone system Autonomic nervous system |
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Posterior Pituitary-Hypothalamus Relationship
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It's a downgrowth of hypothalamic tissue
Neurohormones are produced in cell body of hypothal and sent down axons to the post pituitary gland. -Following AP in neuron, hormone is released form axon terminal in posterior pituitary into the blood FIGURE page 19 |
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Anterior Pituitary- Hypothalamus Relationship
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Aka Hypophyseal portal system (ant pit called hypophysis)
When stimulated, hypothal releases homones into primary capillary plexus from axon Hypothalamis hormones travel through the portal veins into ant pit and stimulate or inhibit the release of hormones from the ant pit Ant pit hormones are secreted into secondary capillary plexus Anterior Pit releases tropic hormones (eg. ACh) that cause the release of another hormone Third order endocrine pathway FIGURE page 20 |
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ANS control of Endocrine System
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ANS can also control the release of hormones
EG: Sympathetic NS controls the release of epinephrine from the adrenal gland |
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Regulation of Blood Glucose
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Precisely controlled
-blood glucose too high=osmotic balance of blood disturbed -blood glucose too low= brain cannot function properly Hormones -Insulin lowers blood glucose levels -Glucagon raises blood glucose levels Insulin and glucagon are secreted by pancreas --direct feedback loop --pancreas also receives neural and hormonal signals FIGURE 3.33 page 22 |
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Additivity
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When hormones cause same response in target cell
Hormones do not use the same signaling pathway --EG: glucagon, epinephrine, and cortisol all raise blood glucose levels by different mechanisms Response of target cell to combos of these hormones is ADDITIVE |
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Synergism
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When hormones enhance the effect of other hormones
Response of target cell to combos of these hormones is more than additive |
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Evolution of Cell Signaling
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Chemical messengers, receptors, and cell signaling mechanisms of animals share many similarities
*Suggest a common ancestor |
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Vertebrate Hormones
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Evolutionary change in the way tissues respond to hormones, rather than a change in the hormone molecule
Some hormones have same effect in diff animals -EG: HGH increases growth rate in fish; estrogen from pregnant mares can be used in post menopausal women Some hormones have diff effet in diff animals -EG: prolactin- stim milk production in mammals, inhibits metamophosis and promotes growth in amphibians, and regulates water balance in fish |
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Stress Response
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adaptive and maladaptive components to stress response
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Homeostatic Control Mechanisms
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Involve continuos monitoring and regulation of many factors
Nervous and Endocrine system accomplish communication Stress is a short-term physical stressor that disturbs homeostasis |
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What is Stress?
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stimulus (stressor) that is recognized by the brain (stress perception) which activates fight/flight response (stress response)
Acute Stress: minutes to hours Chronic Stress: weeks/months/years |
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Fight-or-Flight Response
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Mobilization of energy
Increased cardiovascular tone Suppression of digestion Sharpening of cognition |
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HPA Axis
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Hypothalamus--releases factor to-- Anterior Pituitary-- releases ACTH through blood-- to Adrenal Gland--- releases cortisol
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