Midterm 1 Flashcards
Physiology definition
& emergent properties
Comes from Greek word PHUSIOLOGIA – knowledge of nature
Today’s definition – physiology is the study of the normal functioning of a living organism and its component parts
o Structure and function relationships
o Chemical and physical interactions (ex. the way nt bind to nt receptors)
Emergent properties – living organisms possess; cannot be predicated to exist based only on knowledge of the systems individual parts
o Organized in a way that gives rise to complex life – the whole is greater than the sum of it’s parts
o Properties that are a result of non linear interaction between component parts
Ex. mona lisa from component parts
What defines if something is alive (4)
- Made of one or more cells
a. Cell – basic unit of life - Regulate its internal environment
a. Single cell – intercellular enviro
b. Multicellular – Humans; enviro of cells and collection of cells that make up body - Respond to stimuli
a. “sensory systems” to detect stimuli – Important for survival - Capable of reproduction
a. Self-replication – one cell is able to replicate
i. Viruses cannot self replicate – need a host cell in order to replicate; not actually alive (according to physiology)
Levels or organization
- Biomolecules – lipids, carbs, proteins, nucleic acid and nucleotides
- Cells – smallest units of life capable of carrying out all life processes
- Tissues – group of cells with similar function
- Organs – 2 or more tissues; structural and functional
- Organ systems
- Organisms
- Population of one species
- Includes atoms – responsible for electrical excitability in neurons
Organ systems
Integumentary system – skin; protective; separates the internal from external environment
Musculoskeletal – provides support and body mvmt; skeletal muscles and bone
4 systems exchange material between internal and external enviro
- Respiratory/pulmonary – gases; lungs and airways
- Digestive/gastrointestinal – nutrient and water uptake & waste elimination; stomach, intestines, liver, pancreas
- Urinary/renal – removes excess water and waste material; kidneys and bladder
- Reproductive – produces eggs/sperm; ovaries and uterus and testes
Circulatory/cardiovascular – distributes materials by pumping blood through vessels; heart, blood vessels, blood
Nervous (brain and spinal cord) and endocrine – coordinate body functions
- A continuum more than 2 separate and distinct systems
Immune – anatomically the lymphatic system (not limited to this); specialized cells throughout the body
- Protects the internal enviro
Why is physiology important & exciting
Important:
Leads to treatment of diseases in humans and other organisms
o Pathophysiology – treating diseases
Helps us understand how organisms cope with environmental stressors – helps understand the environment
o Ex. climate change
Foundation of understanding of the philosophical question “What is life?”
o What does it mean to be alive – physio helps define critical processes
Organization:
Fundamental understanding of how life works
Post-genomic era
- Personalized medicine, “$1000 genome” – to know your genome
- You can submit a sample of your cells and they’ll send you the entire sequence of your genome
- Can be used for personalized medicine
- Molecular basis of evolution
- Allowed understanding about molecule basis of evolution
- Structure of individual proteins and how they can be modified with new drugs
Pathway and drug discovery
o Intelligent design drugs
New tech
o Computing, robotics, nanotech
Themes in physio (5)
Structure and function are closely related – particular shape (anatomy) of a protein/cell/organism and how its related to what it does o Organs o Cells (ex. neurons have an axon) o Molecular interactions (ex. protein has a particular structure because it will bind a ligand that will allow it to be part of the signaling pathway)
Information flow coordinates body function
o Electrical/neural signaling throughout the body
o Hormonal communication
Need for energy
o Processing of ATP – metabolism that is dependent on it
Evolution
o Nothing in Biology Makes Sense Except in the Light of Evolution -Theodosius Dobzhansky
o Different processes happening in a similar way in different species – studying other species give us insight to how humans function
Homeostasis and control systems
o Mastering A&P -> study area ->animations ->bioflix-homeostasis
Homeostasis definition
- who named & first mention
- internal parameters that must be maintained
- does not mean
The ability to maintain a relatively constant internal environment even when the external environment is variable.
o 1800’s Claude Bernard called this “la fixite du milieu interieur”. – the constancy of internal enviro
o Word was coined by Walter Canon, 1929
Internal environmental parameters must be maintained within a certain window of acceptable values – respond to fluctuations in external enviro
o Temperature
o pH
o Salinity (concentration of ions and other solutes)
o Oxygen, carbon dioxide
o Nutrients
Homeostasis does not mean “equilibrium” or never changing
Homeodynamics – we observe a dynamic steady state inside vs outside cells
- Ex. Ions are not equal on ECF and ICF but these states must be maintained in order to maintain homeostasis
Requires energy to maintain (ATP)
- not an “equilibrium” - often functions to maintain states of disequilibrium
Control systems
- definition
- pathway
- vary in 3 ways (& what affects intensity)
monitors and adjusts regulated variables at set point; respond to loss of homeostasis
o Requires compensation from external (ex. temp) or internal (ex. ate something) change
Pathway:
- Input signal
- Integrating center
- Output signal
- Response
Long or short distance
1. Local – restricted to one tissue
• Relatively isolated change occurs in a tissue
• Nearby cells sense changes within their vicinity and respond
2. Long distance reflexive control – can be more complex and have input from multiple sources and output that acts on multiple targets
• Endocrine & NS control & neuroendocrine
Vary in speed and specificity
1. Neural – aimed at specific target, fast acting, shorter lived
• Frequency of electrical signals proportional to signal intensity
2. Endocrine – target specificity determined by only receptors, longer to act, tends to last longer
• Will contact almost every cell in body – cells must have a receptor to effect it
• Amount of hormone released proportional to signal intensity
Feedback loops
- sides
- process
2 sides
- Response loop
- Feedback loop – to monitor if compensation was effective; Modulate the response loop
Process
- Stimulus
- Sense or receptor
- Afferent pathway – brings info to brain/integrating center; ex. sensory NS
- Integrating center – ex. brain
- Efferent pathway – acts on target; ex. motor NS
- Target or effector
- Response
Negative feedback
- effects/loop
- properties
- ex. glucose
homeostatic; stabilize variable/cancelling out
Initial stimulus – response – decreased stimulus – response loop shut off
o Error signals act to maintain ‘cruise control’ limits
Properties
- Keeps system near a setpoint
- Response acts to negate the stimulus
- Response can restore homeostasis, but cannot prevent the initial perturbation
Ex. control of glucose – video from mastering A&P Bioflix
o Secretion of insulin – decreases glucose
o Low glucose levels no longer generate signal for insulin to be released – within ideal set of limit
Positive feedback
- effects/loops
- properties
- homeostatic?
- ex. labour
reinforce a stimulus; brings further from set point; some argue not homeostatic
Initial stimulus – response – increases stimulus – feeds into response – feeds into greater response
o An outside factor is required to shut off
Properties
- Brings a system further from a setpoint
- Response acts to reinforce the stimulus – makes error signal stronger
- Requires an outside factor to shut off.
Non-homeostatic? – however, the process of the baby being born is homeostatic and is critical to survival of mother
- Must look at larger context
- Ultimately it is homeostatic
Ex. Labour
o Baby drops in uterus and stretches the cervix – stretching is detected by sensory system
o Hypothalamus secrets oxytocin – contacting uterine muscles cause uterine muscles to contract
o Pushes baby down pushing on cervix more and cycle repeats
o Baby being born stops pos feedback cycle
Feedforward control
allow body to anticipate change; generate response before variable change to prevent severity
o Argued not a loop
o A small stimulus sets off a chain of events aimed at preventing a perturbation.
Requires a complex “program”, or a “reflex”
1. Ex. Mouth watering in anticipation of food is an often-used example
• Psychologists may disagree because of the influence of learning
2. Ex. bag of salt and vinegar chips causes increased salivation when you smell it
o Effects PSNS – salivary glands
3. Ex. Response to exercise
• Respiration, heart rate increase at the beginning of exercise, before changes in O2/CO2
4. Ex. “Fight or flight” activation of sympathetic NS
Ex. Bear in woods – it’s not touching you, but it activates the response nonetheless to prepare your body to survive
- Stimulus was a small visual input – response was a complicated series of events from activation of SNS
Walter Cannon’s Postulates
describe regulated variables and control systems (July 1929) – 4 postulates
1. Nervous system has a key role in regulation of internal environment (often controlling endocrine system – slight bias; most people recognize NS and endocrine as equally important)
o Regulates parameters
2. Some systems of the body are under tonic control
o ‘volume button’ – you can turn it up or down
o Ex. Applies to blood vessel dilation
3. Some systems of the body are under antagonistic control
o 2 opposing factors that balance each other out
o Ex. heart rate – one branch of autonomic NS causes increases and the other causes decease
4. One chemical signal can have different effects in different tissues (communication lecture, ANS lecture)
o ex. epinephrine – blood vessels contract in some areas and contract in other areas (tonic control)
Biomolecules
- organic molecules
- types of biomolecules
Organic molecule that is commonly associated with life
Organic molecule – contains carbon; not technically naturally occurring or healthy
o Exceptions – co2, co, h2co3
Types
- carbohydrates
- nucleic acids/nucleotides/nucleosides
- lipids
- proteins
Carbohydrates
- general chemical formula
- common examples
- properties
- types
CnH2nOn
Common types
o Glucose – C6H12O6 (hexose)
o Ribose – C5H10O5 (pentose)
Properties
1. Hydrophilic (mostly) – water soluble/loving/polar
2. Very abundant
3. Used for:
a) Energy – almost all euk cells can use glucose for energy and can store some form of glucose (monomer or polymer) for energy
• Although most energy is stored as fat
b) Structure
i) Glycosylated proteins – have carbs added to them
o May need to become activated
o May be important for transcription
o May determine localization (ex. moving out of cell membrane)
ii) Glycolipids – carbs attached to lipids
Types – Monosaccharides form disaccharides form polysaccharides
o Monosaccharides – glucose, fructose,
o Disaccharides
ex. Sucrose – glucose + fructose
ex. Maltose – glucose + glucose
o Polysaccharides – most abundant carb; used for structure and energy
ex. Glycogen – storage molecule; polymerized glucose stored in organs (ex. liver)
Nucleotides
- structure
- types
Structure a) 1 or more phosphate group b) 5 carbon sugar c) Nucleobase – carbon-nitrogen ring Structure determines type o Adenine o Cytosine o Guanine o Thymine o Uracil
Types:
a. Adenosine – a neurotransmitter
b. Adenosine triphosphate (ATP) – basic molecule of energy storage in most organisms, including animals; energy is stored in bonds between phosphate
- & Adenosine monophosphate & adenosine diphosphate
c. Cyclic AMP (cAMP) – important signalling molecule within cells
- Adenylyl cyclase (enzyme) – converts ATP to cAMP
d. Guanosine triphosphate (GTP) – energy source in physiological reactions; important in communication pathways (ex. adenylyl cylase pathway)
- & Guanosine monophosphate & guanosine diphosphate
e. Cyclic GMP (cGMP) – important signalling molecule within cells
- Guanylyl cyclase (enzyme) – convert GTP to cGMP
Lipids
- properties (contain)
- structure
- roles
Properties
- Hydrophobic (generally; or have parts that are hydrophobic)
- Contain mostly C and H; a few O, N, P
- Very diverse
Fatty acids
a) Structure
- long, unbranched hydrocarbon chains with 8-28 carbons
- carboxyl (= acidic) functional group
b) Saturated FA – no double bonds; form a straight chain
c) Unsaturated FA – has double bonds; create a ‘kink’
- More double bonds = less likely to be solid at room temp
- Don’t stack as well – pack together more loosely
- More double bonds = greater curl
Roles
a. Structure of cells – define the cell
- Waterproof – separates ECF and ICF
- Pliable
b. Energy source – can be metabolized and converted to ATP
c. Communication – within and between cells
Types of lipids (6)
Glycerides – derivative of FA; glycerol backbone with 1-3 FA
- Types
1. Mono = 1 FA
2. Di = 2 FA
3. Tri = 3 FA - Primary storage product – major component of fat (high = lots of body fat)
Phospholipids – derivative of glyceride - Structure 1. Glycerol backbone 2. 2 FA 3. Phosphate group 4. R group – commonly an amino acid molecule (ex. serine, choline, ethanolamine) The R group: a. Identifies species of phospholipid b. Variable polar group - Amphipathic – has hydrophobic and hydrophilic components 1. FA – nonpolar 2. Phosphate head – polar - Form 3 structures in water 1. Bilayer – cell membrane 2. Liposomes – spherical with aqueous core (bilayer forms sphere) 3. Micelles – difficult to form; not often found in nature; energetically unfavourable
Sphingolipids – analogous to phospholipid in structure
- Contributes to cell membrane formation
- Structure
1. 1 FA
2. Phosphate group
3. R group
4. Sphingosine – instead of glycerol and additional FA
5. Contains nitrogen – usually at bend (be able to recognize by this feature)
Glycolipids – attached carb; contributes to structure, function, localization
see diagrams!
Steroids
- Basic structure – three 6-carbon rings and one 5-carbon ring (17 carbons)
1. Planar/flat molecule – allows protein receptors to recognize and bind
2. Functional R groups – confer different function - Function in: Communication and cell structure
- Examples – same basic structure with ‘décor’
1. Cholesterol – used to make hormones (ex. estrogen, testosterone, cortisol)
Oxylipins – oxygenated metabolites
Eicosanoids – subset of oxylipins
- Structure:
1. Polyunsaturated FA with 20 carbons (fishhook shape)
a. Many are derived from FA arachidonic acid & other unsaturated FA - metabolization of arachidonic is important
- Function
1. Not generally stored – only synthesized as needed
a. Main function is communication between and within cells
i. Inflammation, pain, platelet aggregation
ii. Include prostaglandins and leukotrienes
Protein structure
oligopeptide vs polypeptide
Macromolecules
o Short chain – peptide
o Long chain – protein
Structure of protein:
- Primary structure – sequence of amino acids
a. Linear chain of amino acids – generally
- Oligopeptide – 2-9
- Polypeptide – 10-100 - Secondary – covalent bond angles between amino acids determine secondary structure
a. Secondary structure – created by hyd bonding (cov bonds) between local (adjacent) interactions of amino acids
- A-helix
- B-pleated - Tertiary – 3 dimensional structure of proteins
a. Combine secondary structures
- Formed from chemical interactions between R groups of individual AA (can be cov, ionic, van der waals; depends on AA R group)
b. Pieces can also be removed if not needed on protein
4. Quaternary – interaction of multiple subunits to form active protein; noncovalent interactions Often either fibrous or globular a. Fibrous – not soluble - Ex. collagen – structural protein b. Globular – often soluble - Ex. hemoglobin
Structure of amino acids
- how many
- structure
- properties
- components
Components
a. R group – determines properties (polar/nonpolar/basic/acidic)
b. *20 amino acids encoded by the universal genetic code (debatable – 2 additional may be incorporated)
- 9 of 20 are essential – we need to consume them; our body does not synthesize them
- 11 of 20 are nonessential – we can synthesize them
Varying properties
- Acidic, basic, polar, nonpolar
- Alphabet – analogous to AA and proteins
- Chains can be up to 10,000 AA - Usually a couple hundred or thousand
Structure of amino acid – same basic structure with varying properties Central carbon – 4 bonds are: 1. Carboxyl group (-COOH) 2. Amino group (-NH2) 3. Hydrogen 4. R group – can have varying properties
Functions of proteins
- how many types within mammalian cell
Highly complex
- Determined by the sequence of AA – encoded in genome
- Don’t need to know specific structures of AA – know they have different properties based on structure
Functions of proteins – extremely versatile
o In mammalian cell – between 10,000-15,000 types of protein expressed
o Don’t often do single job (swiss army knife)
Ex. ATPase – uses energy to move; enzyme and transporter
Fibrous vs globular
1. Fibrous – generally insoluble
• Structural (ex. collagen & keratin)
- Globular – generally soluble
Functionally – 7 categories of soluble protein
a. Enzymes – facilitate chemical reactions; without, reactions may not be possible
- Ex. proteases
b. Membrane transporters – sits in membrane and shuttles solute molecule that could otherwise not cross
c. Signal molecules – within and between cells there is communication
- Ex. g-protein – become activated; part of a signalling cascade
d. Receptors – protein that binds something else; does so as part of a communication process
- Ex. hormone receptors – insulin receptors binds insulin and causes reaction
e. Binding proteins – main job is binding something else; sequestering
- Ex. calcium binding protein – binding free calcium inside cells and keep concentration within low
f. Regulatory proteins – many physiological processes occurring; regulatory proteins turns processes on and off
- Ex. DNA binding proteins regulate transcription
g. Immunoglobins – protein binds to antigens
Ligands
- definition
- effects on proteins
- endogenous vs non
- affinity & specificity
- types of effects on proteins (2)
- how types of ligands enact effects (2)
Ligand - molecule that binds to protein site
Protein binding – In order for protein to activate, it must interact/bind to other protein; binding site and activity
- Very specific – shape of binding site is precise
- Ex. insulin receptors bind insulin – insulin is the ligand
Endogenous ligand – occurs naturally in body (ex. hormone, nt)
Nonendogenous – may be a drug/toxin; still a ligand
Affinity
- High = binds strongly
- Low/weak = binds weakly
Types
1. Agonist – ligand that binds to protein site and alters the state of protein resulting in biological response
• Ex. hormone or nt; insulin – all cause response in cell
• Drugs can also be agonist – mimics nt
2. Antagonist – ligand reduces the action of the agonist; binds but causes no biological response; inhibitors/blockers
• Drugs can be antagonist
Agonist and antagonist can both be
1. Competitive – act to block agonist at its normal binding site; binds to it instead
• Acts at the normal binding site
2. Allosteric – block competitive agonist by binding to the protein away from binding site and inactivating the binding site; prevent normal agonist from binding by changing shape of binding site
• Acts at a distant site
Factors that alter protein binding
- isoforms (example)
- activation of proteins (2 methods) & inactive forms
WHAT CAN ATTACH - types of modulators
- physical
- chemical (3)
- saturation
Isoforms – closely related proteins whose function is similar but affinity differs
i. Quaternary structure – subunits acting together; other proteins that are expressed by the body may be similar
ii. Ex. fetal vs adult hemoglobin
Activation
- Cofactors – proteins may need cofactor to function properly; ion or small organic functional group must attach before binding site will activate
- Ex. Mg++ ions binds to slightly alter 3D shape and expose binding site - Protein processing – when proteins are expressed, that may not be the final version
a. Ex. may need to be glycosylated
b. Proteolytic activation – enzymes chop of 1+ portions to activate
- Common in hormones and enzymes
- Inactive forms – ‘pro’ prefix ang/or ‘ogen’ suffix
Types of modulation
i. Changes the ability to bind to a ligand
ii. Changes proteins activity or ability to create response
Physical factors/modulators
- pH, temp – can cause structural changes
- proteins may become denatured – can often not return to normal shape and resume function
Chemical modulation – can be covalent or non; may increase/decrease activity, activate binding site; reversible or irreversible; not necessarily making it ‘functional’
- covalent modulation – can be activating or antagonistic
a. phosphorylation and dephosphorylation – addition or removal of phosphate from protein
- kinases – enzymes, covalently add phosphates
- phosphatases – enzymes, remove phosphate
- phosphorylation may cause activation or inhibition of protein – may allow it to become fully active/activate binding site
Edwin Krebs and Edmond Fisher 1992 Nobel prize – described how important phosphorylation process was in regulating protein activity
a. Described sites proteins are phosphorylated at
- Serine, threonine, and tyrosine AA side chain
- Addition of lipid or carbohydrate
- Presence of agonist or antagonist
a. Antagonist – inhibitors; decrease activity; block binding sites
- Competitive – reversible; degree of inhibition depends on concentrations of ligand vs antagonist and proteins’ affinity for both; Increasing customary ligand can displace competitors
- Irreversible – tightly bound; cannot be displaced
b. Allosteric
Reaction rates can reach a maximum
i. Constant protein concentration – ligand concentration determines response
ii. Saturation – ligands are plentiful but all proteins are active and no binding sites are available
4 functions of cell membrane
- Physical barrier – separates ICF from ECF
- Gateway for exchange – controls mvmts of solutes and regulates concentration in ECF and ICF
a. Semipermeable – allows some to cross, prevents others - Communication – receptors that detect physical and chemical changes and starts cascade response
a. Ex. contracting muscle cells – detect chemical stimuli that cause contraction - Cell structure – some membrane proteins hold cytoskeleton proteins to give cell structure
a. Neurons – have a very specific shape; cell structure is critical to function
b. May also form specialized junctions
- Synapses – specialized
- Tight junctions
Structure of membrane
- mainly
- models that describe
Made of mostly protein and lipid – ration is different for different cell types
o Types or proteins – determines cell’s function
Early model – butter sandwich
a. Layer of fat between 2 bread
- Bread was initially thought to be protein
- Later discovered to be the phosphate head
b. Shortcomings
- Homogenous – not accurate
More recently/accurate – fluid mosaic
a. Proteins are afloat on a sea of lipid
- Shortcomings – not actually afloat
b. Types of proteins
- Peripheral – sitting on surface; afloat
- Integral – anchored within; span the membrane
Types of lipids in cell membrane
- errors in one may cause what
Phospholipids – majority of lipids
o R-groups differ – do not need to be able to distinguish; know they’re different and are distinguished by R-groups
Cholesterol – flat lipids
a. Regulates membrane fluidity – creates more waxy, solidified consistency
- Creates ideal consistency for movements in 37c environment
b. Flat structure – allows it to sit between FA tails
- Slows diffusion of molecules across membrane – fills up space and prevents movement across
Sphingolipids
a. Create lipid rafts – tend to aggregate together; have longer tails than phospholipids
- Some proteins associate only with lipid rafts – leads to areas of specialization on cell membranes
Ex. g-protein coupled receptors
- Have high density of cholesterol relative to phospholipids
b. Ex. sphingomyelin
c. Recent research – errors in lipid raft composition may play role in development of some disease (ex. Alzheimer’s)
Types of proteins within & surrounding cell (3)
- Membrane proteins
- Cytoskeleton
- Extracellular matrix
Membrane proteins
- types (& what kinds of bonds) (how many AA in MSR)
- 4 major functions of membrane proteins
Integral – associated tightly with cells membrane; critical part of cell membrane
a. Transmembrane
- Approx. 20-25 hydrophobic amino acids span hydrophobic middle of cell membrane per MSR
- Ex. 3 MSR (20 AA each); 2 hydrophilic regions
i) Polytopic – transmembrane with more than one MSR
ii) Bitopic – transmembrane with one MSR
b. Monotopic – permanently associated to one side; lipid anchored proteins
May:
i) have strong hydrophobic sections that allow it to tightly associate with lipid portion of bilayer
- No long enough to thread through membrane
ii) be modified by the addition of a FA – FA will protrude into membrane and hold tight
iii) be electrostatic or ionic interaction between protein and phospholipid
- Mediated by Ca2+ where Ca2+ binds to protein and polar head group – anchors
Peripheral – more weakly associated; associates non covalently with integral proteins or polar heads of phospholipids
o Can be removed without disrupting integrity
4 major function of membrane proteins
- Structural – 3 roles in cell membrane:
- Create cell junctions that hold tissues together (ex. gap junctions, tight junctions)
- Connect the membrane to the cytoskeleton – maintains the shape of cell
- Attach to the extracellular matrix – links cytoskeleton fibres to extracellular protein fibres (ex. collagen) - Enzymes – catalyze chemical reactions on external or internal surface
- Receptors – chemical signalling system
- Binding of ligand triggers response
- Play role is vesicular transport - Transporters – move across membranes
- Channels
- Carriers
Cytoskeleton and Extracellular matrix proteins
- how is cytoskeleton attached
- functions of glycosylation in ECF matrix
Cytoskeleton – not a membrane proteins; flexible skeleton of fibrous proteins – give shape and structure
a. Often interacts directly or indirectly with membrane proteins
o Indirectly – Can be attached to a cytoskeleton associated protein to a peripheral protein
o Direct – directly attached to integral protein
Extracellular matrix – membrane proteins and secreted proteins found on ECF side of membrane; forms a husk
- Highly variable glycosylation
a. Functions
- Helps body identify as being part of you (immune)
- Sticky – allows cells to stick together; not loosely aggregated; allows organs to stick together - Contribute to physical strength of cells
Muscular dystrophy
Disease of cytoskeleton
a. Dystrophin – protein that provides link between cytoskeleton and extracellular matrix
- Can be either missing or non-functional in MD
b. Strongly expressed in muscle cells – loss of protein causes muscle to have no physical strength; results in easily damaged muscles
- Repeated damage causes muscle to eventually waste away
- Scar tissue
Diffusion
- definition
- properties
- simple diffusion
- diffusion across membrane
Diffusion – process of moving solutes from high to low concentration
a. Passive – no external energy (ex. ATP); uses kinetic energy of molecules (heat from vibrations of molecules)
o Down the concentration gradient
o Continues until equilibrium – solutes concentration is the same throughout
Simple diffusion – no membrane
o Diffusion is fast
o Net movement is high to low – some will move low to high due to randomness of movement
Semipermeable membrane – allows select solutes to pass
a. Slows movement of permeable solutes due to presence of membrane
- Passive diffusion – net movement is down concentration gradient
b. Does not allow some solutes to pass (rate = 0)
- Their concentration gradient is maintained
- requires transport mechanisms
Factors that affect the rate of diffusion (5)
Fast over short distance & slow over long
- Time to get A to B is ‘distance squared’ relationship – if distance doubles from 1 to 2; time increases 1 to 4 (2^2)
Increases with temp
- Temp = heat energy -> vibrational mvmt increase
Faster for smaller molecules
Slower across membrane
- Even if the membrane is easily permeable – crossing membrane inherently slows
Permeability of membrane
Semipermeability of cell membrane
Molecules able to cross via diffusion
1. Hydrophobic nonpolar – can pass through membrane easily; move through FA tails
• Ex. o2, co2, lipids, steroids, fat soluble molecules
2. Small uncharged polar molecules – water and urea
- Polar – does not like to interact with FA
- Water and urea are exceptions – able to move across
a. Water
o Able to move across for 2 reasons:
Size - water is small relative to bilayer
Uncharged
o Water mainly gets through membrane via aquaporins – controversial in biology
Cannot diffuse across cell membrane – require transport mechanisms
- Large uncharged polar molecules – glucose, proteins, amino acids
- Charged ions – Na+, K+, phosphate
Factors that affects the rate of diffusion across cell membrane (5)
- ex of 2 diff sized molecules within cell
Speed of diffusion is affected by
a. Size – larger will move more slowly
o Ex. glucose vs glycogen (made up of glucose) – glycogen has more inertia & is harder to move
b. Lipid solubility – polar or nonpolar or VERY nonpolar
o Polar – do not like to move at all
o Nonpolar (ex. cholesterol) – moves across membrane
o Very nonpolar (ex. benzene ring) – moves across very quickly
Concentration gradients
a. Large = faster diffusion (10:1 vs 1000:1)
Surface area
a. Larger = more area to diffuse across = more quickly than smaller surface area
b. Can increase surface area by increasing folding – same volume but one will have more surface area
Temp
a. Heating = greater KE (vibrational mvmt increases)
Composition of membrane
a. Simple lipid bilayer vs membrane with many proteins and extracellular matrix
• Simple – easier
• More impediments – slower
b. Types of phospholipids and sphingolipids
c. Presence of cholesterol between FA tails – slows rate of diffusion
Ficks Law of Diffusion
Rate of diffusion is proportional to: surface area x concentration gradient x membrane permeability
o Surface area
o Concentration gradient
o Membrane permeability
Membrane permeability is proportional to: Lipid solubility/molecular size
• Smaller molecular size = greater permeability (inversely related)
• More lipid soluble = greater permeability (directly related)
Liposomal drug delivery
Some drugs have low bioavailability due to poor solubility – doesn’t reach concentrations required to induce physiological effects
o May also be toxic at useful doses and must be targeted to a specific cell type (ex. only cancer cells; concentration needed is toxic to the rest of the body)
Can take advantage of liposomes formed by phospholipids in hydrophilic environment
a. Can target specific cells by modifying phospholipids by adding protein tag
- When liposome binds to cell of interest bind – will deliver drug to that cell
- Ex. targeting insulin receptors – attach a molecule similar to insulin
b. Can glycosylate to keep them from being destroyed by immune system
Uses
- Oil soluble drugs – can be dissolved and stored in bilayer
- Solid or water soluble drugs that will not dissolve otherwise – can be broken down into nanoparticles and stored in aqueous core
- Not as effective as soluble – still able to be delivered
Osmosis
- % in ECF vs ICF
- men vs women
Osmosis – the diffusion of water
60% of body weight is water
a. ICF – 2/3 of body water volume
b. ECF – 1/3 of body fluid volume
- Interstitial fluid – between circulatory system and the cells has 75% of ECF volume
- Plasma – liquid matric of blood within circulatory system has 25% of ECF volume
Men vs women
a. 70kg man – 60% water; 42L of water
b. Women – have less water & more adipose tissue
• Must be taken into account when administering drugs – women will have higher concentrations in their blood than men
States of homeostasis within the body
- states of disequilibrium
- osmotic equilibrium & osmotic pressure
- Chemical disequilibrium – distribution in and out of cells
- Electrical disequilibrium – ions in and out of cells; creates voltage difference
- Osmotic equilibrium
a. Water diffuses down concentration gradient (high to low; low solute to high solute)
• Pure water has the highest concentration – solutes lower the concentration
• Movement of water can cause pressure
b. Ex. u tube – selectively permeable membrane
• 2M and 1M glucose – water moves 1M to 2M
o Volume of water on 2M side increases – not complete equilibrium due to volume
c. Osmotic pressure – the amount of pressure that must be applied to oppose osmosis
Osmolarity
- units
- types
- important because
Describes the number of particles per litre of solution
Units:
Osmol/L or OsM
Milliosmoles/L = mOsM
Comparing osmolarity
a. Isometric/isosmotic – same number of particles
b. Hyperosmotic – solution has high osmolarity (more particles)
c. Hypoosmotic – solution has low
• Will always be hypotonic
Ex. 3 solutions
a. 1M glucose = 1 OsM
b. 2M glucose = 2 OsM
c. 1M NaCl = 2 OsM (NaCl will dissociate into Na+ and Cl-)
Important because – changes of osmolarity of ECF causes redistribution of solutes in cells
- Can influence tonicity (will determine whether cell will shrink/swell)
Osmolarity vs Molarity vs Osmolality
- converting between osmolarity and molarity
Osmolarity differs from molarity
- Molarity – does not take into account that some molecules dissociate into 2 ions (ex. NaCl)
- Osmolarity – takes into account the number of particles
To convert between osmolarity and molarity:
(mol/L) x particles (osmol/mol) = osmol/L
- Osmolality – osmol/kg (often interchangeable with osmolarity)
- Used clinically – 1kg = 1L; a loss of 1kg is equivalent to 1L of water lost
Normal physiological concentrations of salts
ECF ~290 mOsM (concentration of solutes & other things) K+ 5mM Na+ 145mM Cl- 108mM Ca2+ 1mM
ICF ~290 mOsM K+ 150mM Na+ 15mM Cl- 5mM Ca2+ 0.0001mM
Tonicity
- definition
- types
Tonicity – describes solution and how solution effects cell if placed within and allowed to come to equilibrium
Concentration in normal/healthy cells is ~290 mOsM
Hypertonic - cell shrivels
ECF = 360 mOsM (ex. 180mM NaCl)
Isotonic - cells don’t change
ECF = 290 mOsM (ex. 145 mM NaCl)
Hypotonic - cells swell
ECF = 200 mOsM (ex. 100 mM NaCl)
Osmolarity vs tonicity
- functionally non penetrating?
Osmolarity
a. Only describes number of solute molecules in cell
b. Can compare any two solutions
c. Does not always tell is cell shrinks or swells
d. Measures the concentration of penetrating and nonpenetrating solutes
- Penetrating – able to cross membrane; Small polar (ex. water & urea) and nonpolar
- Nonpenetrating – ions and larger polar molecules; don’t diffuse across bilayer
- Functionally nonpenetrating – able to cross membrane/leak out; concentrations are maintained by homeostatic mechanisms
(Ex. Na+, glucose, amino acids)
Tonicity
a. Comparative – whether or not cell changes volume; compares ECF solution to a cell’s ICF solution
b. Always specifically refers effect on cell – whether cell will shrink swell
c. Disregards penetrating solutes – solutes able to cross and don’t influence water movement in/out of cell (affecting hypo/hyper)
- When penetrating and nonpenetrating are present
Ex. initially isosmolar
- P solutes want to establish their own equilibrium – will move into cell
- Hypotonic solution
Rules for tonicity and osmolarity
Normal physiological ICF solutes are functionally non-penetrating (~290 mOsM)
Hypoosmotic solution – always hypotonic
- Hyperosmotic solution – not necessarily hypertonic – solutes in ECF may be penetrating and create hypotonic solution
When determining tonicity with penetrating solutes
a. Disregards concentrations of P solutes – water will ultimately flow to area of higher NP solutes
b. Penetrating solutes – may influence tonicity if establishing
