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Define physiology
- Study of the logic of life
- No longer just FUNCTION - understand how/why life works
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Define "Teleological"
- Using purpose as a means of explanation
- Ie, we breathe to oxygenate our bodies
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Define "Mechanistic"
- Using cause and effect as a means of explanation
- Ie, concentration gradients are created in capillary beds and drive exchange
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Define the key relationship for Quantity in mathematical terms
- Quantity = Concentration x Volume
- Volume can be exchanged for Flow
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Define the key relationship for Flow in mathematical terms
- Flow = Force x Conductance
- Flow = Force / Resistance
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Define Homeostasis
- The property of an open system (organism) to regulate its internal environment to maintain a stable, constant condition
- Accomplished by adjusting multiple dynamic equilibriums which are controlled by interrelated control mechanisms
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Relative ion concentrations of:
Plasma
- Positive > Negative
- Na+ > Cl- >> K+
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Relative ion concentrations of:
Interstitial fluid
- Positive > Negative
- Na+ > Cl- >> K+
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Relative ion concentrations of:
Intracellular fluid
- Negative > Positive
- K+ > Cl- > Na+
- Note: there are many negatively charged proteins
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How large is the volume of plasma?
3L
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How large is the volume of the ISF?
12L
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Name the organs used to maintain the ISF
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How large is the volume of the intracellular fluid?
25L
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How is water lost?
- Urine
- Insensible water
- Feces
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How is water obtained?
- Drink
- Water content in food
- Oxidative metabolism
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How much water is typically lost in a day?
2.5L
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Describe the point of this experiment:
- Osmolarity acts as a regulator of homeostasis
- The increased amount of fluid into the system dropped osmolarity of the blood
- This triggered increased renal filtration to re-establish proper levels
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What constitues the plasma membrane?
- A lipid bilayer (hydrophobic in, hydrophilic out)
- Proteins
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What is the fluid mosiac model?
- Describes the motility/fluidity of the membrane
- Proteins and lipids are free to diffuse around
- Membrane can buckle and expand
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How does the PM act as a barrier?
It is semipermeable based on molecule: size, polarity, and solubility
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What are the PM's functions?
- Barrier
- Cell Adhesion
- Bearer of self-identity markers/transport proteins
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What are the two types of membrane proteins?
- Extrinsic (perepheral)
- Intrinsic (integral)
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What are the types of integral proteins?
- Carrier - must change shape to permit passage
- Channel - always open
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What are the types of unassisted membrane transport?
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What are the types of assisted membrane transport?
- Carrier-mediated transport
- Active transport
- Vesicle transport
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What is diffusion?
- Spreading of molecules based solely on their thermal energy
- Move from high => low concentration
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What is the difference between Brownian motion and diffusion?
- Diffusion only occurs down a concentration gradient (until uniformly dispersed)
- BM describes the actual motion - when gradient is abolished, movement still occurs
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Factors that affect diffusion
- Concentration gradient
- Lipid solubility of molecule
- Membrane surface area
- Molecular weight of molecule
- Membrane thickness
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How can membrane channels be selective?
Residues within the "ion filter" portion selectively filter the correct ion
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What is the difference between diffusion and carrier-mediated transport?
- Carrier-mediated requires conformational change of protein
- Carrier-mediated may require energy input
- Carrier-mediated reaches a saturation point (speed of which protein can change shape maxed)
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What factors affect speed of carrier-mediated transport?
- Specificity
- Saturation
- Competition
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What are the types of active transport?
- Primary - require direct use of ATP
- Secondary - driven by ion concentration gradient established by a primary pump
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Does facilitated diffusion require energy input?
No
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What are the types of vesicular transport?
- Endocytosis
- Pinocytosis
- Receptor-mediated
- Phagocytosis
- Exocytosis
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Which cells have a membrane potential?
ALL cells
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How is a membrane potential established?
Differences in charge are sequestered to opposite sides of the PM
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What is the resting membrane potential?
- The separation of charge across the PM in all cells
- Nerves maintain this when they are not firing an action potential
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What controls the membrane potential?
Ion channels
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Approximate size of things:
Pores' existance was postulated long before they were discovered (due to size)
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Describe the "ionic hypothesis"
- The membrane potential is determined by the intracellular K+
- Julius Bernstein
- Used squid axon
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Describe the "sodium theory"
- Membrane potential in nerves is based both on intracellular K+ and extracellular Na+
- Hodgkin & Huxley
- Had better instruments - could see action potential better
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What was incorrect about the "ionic hypothesis"?
- Stated an AP was generated to due breakdown of membrane potential
- Did not account for Na+
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What is the Nernst equation?
- Em = ~(60/z) log10 [K+]outside / [K+]inside (mV)
- For 1 ion
- z = charge
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What does the Nernst equation describe?
- At equilibrium, the force exerted by ion concentration is balanced by force exerted by charge
- Chemical vs Electrical
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What is the Goldman-Hodgkin-Katz Constant Field Equation?
- It accounts for numerous ions permeating the PM
- Can simplify to Nernst when permeability of one ion >> other
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Define the relative permeabilities of ions during an AP
- At rest, K >> Na
- At peak AP, NA >> K
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What is a patch clamp?
Allows researcher to analyze (hopefully) a single ion channel in a membrane
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Define depolarization
The abolishment of a membrane potential
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Define repolarization
The re-establishment of a membrane potential
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Define hypopolarization
The further reduce (more negative) the membrane potential
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Define hyperpolarization
To increase (make less negative) the membrane potential
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How to local anesthetics work?
- As a weak base, they can cross membrane in uncharged state
- Inside cell, the charged form can bind to voltage gated Na+ channels
- Prevent generation of an AP
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What are the 3 major channels used in axons?
- Leaky K+
- Voltage gated Na+
- Voltage gated K+
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What is crenation?
The wrinkling of a cell (ie, RBC) due to a high salt solution
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How can water pass across PM?
- By osmosis across bilipid layer (slow)
- Thru aquaporins (fast)
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Describe the structure of aquaporins
- 6 transmembrane segments that associate into an hourglass shape
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What are the two branches of aquaporins?
- Orthodox - extremely selective to water
- Cocktail set - homologs; will let similar molecules pass
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Define osmosis
- The net diffusion of water down its concentration gradient
- Thru a selectively permeable membrane impermeable to the SOLUTE
- Moves from low => high SOLUTE CONCENTRATION
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When does osmosis reach equalibrium?
When osmotic pressure = hydrostatic pressure
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Define Osmolarity
- Measure of a solution's total solute concentration
- Expressed in Osmoles/L
- A colligative property
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What is a colligative property?
- One that depends solely on the number of particles, not the nature of them
- Ie, Osmolarity
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What is the normal osmolarity of body fluids?
290-300 mOsm
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What is the van't Hoff limiting law?
- π = RTΦic
- Calculates osmotic pressure
- "i" is the number of moeities the molecule dissolves into
- "c" (molarity) can also be substituted for "m" (molality)
- Φ is the osmotic coefficient
- Closer to ideal the more dilute a solution is
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What is the osmotic coefficient (Φ) for some solutions?
- Ideal = 1
- Monovalent = 0.9-0.95
- Multivalent < 0.9
- Mono-/disaccharides ~ 1 (a little over)
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Determining net flow of water
- Jv(net) = Kf (deltaP –σdeltaπ)
- σ is the reflection coefficient
- Kf is the filtration coefficient
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What is the reflection coefficient (σ)?
- σ = 1 - P(solute)/P(water)
- Describes the permeability of the solute
- σ = 1, impermeable
- σ = 0, permeable
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What factors affect Kf?
- Related to the size of the membrane
- Related to relative conductivity of water thru the membrane
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Why do body cells not normally experience volume changes?
The concentration of nonpenetrating solutes in the ECF is carefully regulated to match the osmolarity of the ISF
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Define tonicity
The effect nonpenetrating solutes in a solution have on cell volume
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Describe the difference between tonicity and osmolarity
- Osmolarity has units to describe concentration in each compartment
- Tonicity is merely the relative concentration between two compartments
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Define Isotonic
Equal solute concentrations between compartments
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Define Hypertonic
[Solutes in ECF] > [Solutes in cell]
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Define Hypotonic
[Solutes in ECF] < [Solutes in cell]
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What is the isotonic condition for RBCs?
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Can proteins penetrate capillaries?
NO
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What is the mechanistic reason for molecule exchange in capillary beds?
- Net blood pressure entering causes solutes to cross into tissues
- Net osmotic pressure exiting causes the reverse
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What makes the capillary beds ideal for exchange?
- Maximized surface area
- Velocity of blood flow is relatively slow
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How to pass a capillary
- Water soluble molecules can diffuse thru water-filled gaps
- Lipid soluble can diffuse across endothelial PM
- Proteins CANNOT diffuse across
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What drives the osmotic pressure in capillaries?
- Proteins
- Since all other solutes have a σ~0, and proteins are σ~1, only the proteins affect osmotic pressure
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What is the Starling equation?
- Describes how net pressure on either end of the capillary beds drives molecule transport
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