Exam 1 PHYSIOLOGY

If cell has extracellular K+ of 14 mM and an intracellular K+ of 140 mM, and membrane only permeable to K+, what would be resting membrane potential?

-60 mV -What would be effect of rushing extracellular K+ from 14 to 1.4 mM in same cell? 60 mV hyperpolarization

Adding Water to ECF

-ECF osmolality would be diluted initially compared to ICF (become hypotonic) -water would enter the ICF (swell the cell) to equilibrate the osmolality between compartments *IV administration of distilled water will cause a patients RBCs to swell and burst/hemolysis which could cause death

Cerebral Edema

-Hyponatremia (water gain/low osmolarity) (loss of sodium, potassium, and chloride/low osmolarity) -confusion, drowsiness, weakness, headache, ataxia, seizures, coma, death

Mechanisms of Solute Transport

-Vesicular transport- movement of large molecules across but not through the cell membrane- endocytosis, exocytosis, organellar vesicular fusion -Passive transport- simple diffusion- move down concentration gradient- under influence of Brownian/thermal motion toward a uniform distribution

Osmolality of Body Compartments

-a rough estimate of ECF osmolality can be obtained by doubling the sodium concentration (Na+) -plasma osmolarity= 2 (plasma (Na+))= 290 mOsm/kg H20 -Plasma (Na+)= 145= osmolality- 290 -ICF concentration roughly K+ and conc of inorganic phosphates and proteins

Action potential vs. Electrogenic potential

-action potential- threshold, active, all or none conduction, all or none (same amplitude, electrical stimulus, polarity inside positive, self-regenerating, propagates, refractory period, no temporal and spatial summation -electrogenic potential- no threshold, passive, decremental conduction, size graded, chemical, mechanical stimulus, polarity inside negative, not self-regenerating, does not propagate, no refractory period, temporal and spatial summation

Ohm's Law

-allows us to predict the amplitude of ion fluxes Voltage (V)= electrical current (I) x Resistance (R) V=IR I=g(V) -predict amplitude of ion fluxes: Iion=gion(Vm-Eion) -The K+ current is described by: Ik=gk(Vm-Ek) -For Na+ current: INa=gNa(Vm-ENa)

Charge

-an electrical potential difference across a cell membrane will cause movement of ions even if there is not a conc gradient

Gated Ion Channels

-are open only a span of time -most gated channels are closed at resting membrane potential -the probability that a gated channel will open is primarily determined by membrane potential, specific ligands or chemicals, and mechanical distortion

The membrane potential of a cell is at K+ equilibrium. The intracellular conc for K+ is 150 mM and extracellular is at 5.5 mM. What is resting potential?

-at equilibrium potential: -90mV

Permeant solutes

-can give rise to temporary, but not permanent, changes in osmotic pressure -therefore, transient changes in cell volume occur in response to changes in extracellular conc. of permeant solutes -ex. adding a permeant solute such as urea or glycerol to ECF will increase ECF osmolality- urea will rapidly penetrate the CM by facilitated diffusion- initial effect is to shrink cells, will gradually equilibrate to normal -sustained changes in cell volume do not occur with a change in extracellular concentration of a permeant solute

Generation of Action Potential

-change in the voltage of the membrane potential that causes it to go from its negative resting state to a positive value for a very brief time -the membrane switches from its state of being highly permeable to K+ ions at rest to being highly permeable to Na+ at peak of AP

Excitability

-changes in membrane potential; the membrane potential will change if an electrical current is passed across the membrane 1. Depolarization- a decrease in potential difference (e.g. a change from -70mV to -40 mV)- decrease in RMP, less negative, increase excitability (Suprathreshold stimulus, threshold stimulus) 2. Hyperpolarization- occurs when polarization across the membrane is increased (e.g. a change from -70 mV to -100 mV)- increase RMP, more negative, decrease excitability (subthreshold stimulus)

Equilibrium potential

-chemical and electrical driving forces in opposite directions, the point at which each equals each other is equilibrium potential -depends upon its conc gradient and valence

Driving forces acting on molecules

-chemical driving force: the net force driving molecules down a conc gradient -electrical driving force: ions, atoms, molecules that have a charge, can be affected by membrane potential which results from unequal distribution of charges across membrane (like charges repel and opposite charges attract); the magnitude of the electrical force depends upon the size of the membrane potential and the charge of the ion (the greater the membrane potential or charge of the ion, the greater the electrical driving force)

Chemical and electrical driving forces acting on K+ in typical cells under resting membrane pot (-70 mv)

-chemical force favors efflux, and electrical force favors influx

Carrier mediated vs. secondary active transport Similarities

-conformational change occurs once solute binds -both mechanisms uses specific carrier proteins -both are saturable -affinity plays a role in both mechanisms

Conductance

-depends on permeability, but it also depends on concentrations -Ohm's law allows us to predict the amplitude of ion fluxes -specifies the relationship between current (flux of charge carrier), electromotive force (force that drives the fluxes), and conductance

Magnitude of electrical force

-depends on size of membrane potential and the charge of the ion -the greater the membrane potential or the charge of the ion, the greater the electrical driving force

Ex. Increase concentration K+ outside cell

-depolarize (less negative), increase excitability

Mechanisms of ECF Dilution

-excessive water intake/water intoxication which will lead to hyponatremia (Serum Na+<135 mEq/L)- infants, elderly, military personnel, marathon runners) -syndrome of inappropriate antidiuretic hormone secretion (SIADH) (too much ADH) -severe head injury or trauma

Counterrtransporters/Antiport/exchanger

-exchange one type of anion for another type of anion or one type of cation for another type of cation -Ex. Na+Ca2+ exchanger- intracellular calcium maintained low by Ca2+-ATPase and the exchanger Cl-HCO3- exchanger- the best studied exchanger in RBCs, helps carry blood CO2 from tissues to lungs Na+H+ exchanger- controls intracellular pH

Generation of Resting Membrane Potential

-flow of ions (K+ and Na+) through leak (non-gated) channels down electrochemical potential gradients generates resting membrane potential -leak channels for K+ are major way to generate resting membrane potential -by convention, membrane potentials are expressed relative to extracellular fluid- that is, negative membrane potentials indicate inside of cell membrane is more negative than outside -Na+K+ATPase pump contributes to about -4mV of RMP

Carrier mediated vs. secondary active transport differences

-for carrier mediated- downhill transport of solute occurs, while secondary active transport- uphill transport of solute -secondary active transport needs the driver solute to expend energy for the uphill transport of solute to occur, while carrier mediated does not require energy to be expended for downhill transport of solute

Channels- Nonseletive Pass/Pores

-gap junctions- in epithelia, endothelia, smooth muscle, cardiac muscle -allow passage of water-soluble molecules up to MW of 1200-1500 -pathway for electrical current flow between cells -synchronized electrical activity of heart and gut -Ion channels- non-gated/leak and gated ion channels

Lipid Solubility

-has the strongest influence on permeability as most substances in the body are hydrophilic and don't cross lipid bilayer easily -partition coefficient= olive oil/water solubility -compounds that are soluble in nonpolar solvents (i.e. olive oil) enter cells more readily than do water soluble substances of similar molecular weight

A 10 fold concentration change in extracellular K+ will change resting membrane potential by about 60mV

-if 100 fold, by 120 mV

Adding Hypertonic Saline (excessive NaCl intake) to ECF

-if hypertonic saline added to ECF, ECF osmolarity would increase greatly initially and fluid would be drawn out of cells and into ECF to lower tonicity of ECF -this would contract the ICF volume (cells would shrink) and increase the ECF volume, as well as increase overall osmolarity -slow infusion to correct- hyponatremia

Adding Isotonic Saline (0.9% NaCl or 250 mM NaCl, common IV solution) to ECF

-if isotonic saline (150 mM or 300mOsm/L NaCl solution) is added to ECF the fluid will stay in the ECF because it is isotonic expanding ECF -IV isotonic solutions help rehydrate individuals suffering from dehydration/may give continued hydration levels

Freshly isolated, normal human RBC's placed in a solution composed of 150 mm NaCl and 75 mm urea. Which of the following statement is true regarding cell volume changes?

-if present, NA+ K+ 2Cl- cotransporters would be activated to bring volume back to normal

Hyperosmotic solution

-if the solution has greater osmotic pressure than the cell -water moves out of cell and shrinks in cell volume (ICF volume decreases) -consequences of dehydration

Hypoosmotic Solution

-if the solution has less osmotic pressure than the cell -water moves into the cell and swell in cell volume (ICF volume increases) -consequences of hypotonic hydration- water gain- if more water than solutes is gained, cells swell

Isoosmotic Solution

-if total osmotic pressure of the solution is equal to that of the cell -no water movement into/out of cell

Electrical driving force

-ions, atoms, or molecules that have a charge, can be affected by membrane potential which results from unequal distribution of charges across the membrane -an electrical driving force across a cell membrane will cause movement of ions even if there is not a conc gradient -the direction of the electrical driving force results in the ion moving toward a region where the opposite charge exists- like charges repel and opposite charges attract -cell membrane usually has more anions on intracellular side -the excess charges on either side of membrane are attracted to the separating membrane because the anions are attracted to cations and vice vers

Non-gated (leak) ion channels

-leak channels always open, allowing the passage of sodium ions (Na+) and potassium ions (K+) across the membrane to maintain the resting potential

Ca2+ ATPase (primary active transport)

-located in cell membrane and organelles -pumps Ca2+ to outside of cell or into cell organelles to maintain low intracellular Ca2+

H+K+ATPase (primary active transport)

-located in parietal cells in gastric glands of GI tract and epithelial cells of renal system -acidify urine and control acid-base balance -basis for secreting HCl in stomach digestive secretions

Driving forces acting on molecules

-molecules will move from an area of higher energy to lower energy -the forces that create this energy will be chemical, electrical, or electrochemical

Na+K+ ATPase (Primary active transport

-most abundant pump in higher organisms, heterodimer of alpha subunit of 100,000 MW and B subunit of 55,000 MW -pumps 3 Na+ out of cell for every 2 K+ pumped in -transporter binds 3 Na+ from cytosol-> phosphorylation by ATP conformational change-> Na+ released, K+ binds-> dephosphorylation, conf change-> K+ released in cytosol -Function: maintain low Na+ and high K+ conc in cell, resting membrane potential, contribute to RMP by -4mV, control cell volume

Goldman-Hodgkin-Katz equation

-most cell membranes not only possess a resting permeability to K+ ions, but also have a degree of permeability to Na+ and Cl- ions (put anion inside over outside) -the membrane potential approaches the equilibrium potential for any ion whose permeability becomes much greater than others

Channels

-only capable of facilitating downhill transport (i.e. net transport transport from a higher to a lower electrochemical gradient) -active site simultaneously accessible from both sides of membrane

Carriers

-only capable of facilitating downhill transport; active sites only accessible from one side at a time

Tonicity of solutions

-only determined by the impermeant solutes -determines steady-state cell volume -more permanent effect -isotonicity: no change in cell volume -hypertonicity: cell shrinkage -hypotonicity: cell swelling

Pumps

-oppose the equilibrating systems to preserve intracellular concentrations of solutes, particularly ions, which are compatible with life -electrochemical potential gradient

Water channels- Aquaporins

-pore diameter larger than water molecules but not as great as solute molecules -found predominantly in RBCs, epithelium of lung, kidney, and intestines

Properties of Protein-Mediated Transport

-reaction rate -saturation -conformation change -specificity/stereospecificity -competitive inhibition

Regulatory Volume increase (RVI)

-response to cell shrinkage- when cells exposed to hypertonic medium, they shrink and undergo RVI -during RVI, NaCl and organic osmolytes enter the cell -the increase in cellular solute concentration increases intracellular osmotic pressure and brings water back into the cell, and cell returns to near its original volume

Regulatory volume decrease (RVD)

-response to swelling- when cells exposed to hypotonic medium, the will swell and undergo RVD -the RVD involves a loss of KCl and organic osmolcytes from the cell -the reduction of cellular KCl and organic osmolcytes decreases intracellular osmotic pressure, water leaves cell and the cell returns to near its original volume

Ex. increase Na+ outside

-slight depolarize (less leak channels for Na), increase excitability slightly

Homeostasis

-steady state balance -negative feedback- stabilizes the system -positive feedback- destabilizes the system

Secondary Active Transport

-stored energy used from maintaining ionic gradients to fuel uphill transport of another solute -most use sodium ions as driver solute and use the energy of sodium gradient to carry out uphill transport

carrier mediated transport (facilitated diffusion)

-substance cannot be transported without aid of specific protein -transport along concentration gradient -monosaccharide or amino acid transport -active site only accessible from one side of membrane at a time -glucose transporters- GLUT 1-5 -amino acid transporters- neutral, basic, acidic AAs

Diffusion potential

-the concentration difference of an ion across a selectively permeable membrane creates a diffusion potential

Diffusion Potential

-the concentration difference of an ion across a selectively permeable membrane creates a diffusion potential -by convention, membrane potentials are expressed relative to the extracellular fluid, that is, negative membrane potentials indicate that the inside of the cell membrane is more negative than the outside

Permeability vs. conductance

-the goldman equation is very useful for caluculating membrane potential and their dependence on conc gradients- however, doesn't directly predict the fluxes of ions in order that we understand the job of the membrane pumpos -Fluxes are measured more easily by conductances than permeabilities- while permeability describes the ease with which an ion can move through the membrane, conductance describes the ability of a given ion species to carry electrical current across the membrane

Chemical driving force

-the net driving force driving molecules down concentration gradient -directly proportional to conc gradient -the greater the gradient, the greater the force -if there is more than one kind of molecule across a cell membrane each molecule has its own conc gradient or chemical driving force

Cotransporters- symports/symporters

-the solute being transported moves in same direction as drive solute (sodium ions) and nearly always in positive direction -go in cell -ex. Na-glucose, Na-AA, Na-K2Cl, NaCl, KCl

Electrochemical driving force

-the total forces acting upon ions across a membrane is a combo of both chemical and electrical forces -the net direction of this force is equal to the sum of both forces -if chem and electrical forces in opposite directions= equilibrium potential

Assuming complete dissociation of all solutes, which of the following solutions would be hyperosmotic relative to 1 mM NaCl?

1 mM CaCl2

Positive Feedback Control

1. Childbirth 2. Control of voltage gate sodium current

Factors influencing diffusion of solutes across a cell membrane

1. Concentration Difference- difference between concentration inside and outside of cell- net flux of a molecule is directly proportional to the size of the chemical driving force -if ion not involved, the net flux is proportional to both the chemical and electrical driving forces 2. Fick's first law of diffusion- the rate of diffusion across a plane is proportional to the concentration gradient across the plane and to the area of the plane 3. membrane thickness- the thinner the membrane, more permeable to molecules 4. temperature- greater the temp, higher the permeability 5. Diffusion coefficient (D) 6. lipid solubility 7. molecular size 8. charge

Treatment of Hyponatremia

1. Osmotherapy- meant to draw water out of brain by improving blood flow in brain as well as reduce swelling and raised intracranial pressure in skull- infusion rate depends on cause of hyponatremia, severity, and whether it is acute or chronic -infuse hypertonic saline (3%) a. Acute hyponatremia (developed in less than 6 hours)- slow IV infusion of 3% saline (50 ml bolus- hypertonic saline), discontinue drugs that may be causing hyponatremia, monitor serum sodium levels hourly b. Chronic hyponatremia (developed in more than 6 hours)- slow IV infusion of 3% saline (100ml bolus- hypertonic saline- may need to repeat), look for intracranial pathologies- brain hemorrhage, neoplasm, monitor serum sodium level hourly * if severe above 120 mEw/L- infusion 3% saline at 15-30 mL/hr plus IV furosemide (diuretic) twice daily

Negative feedback regulation

1. blood glucose 2. BP 3. thermoregulation

1. decrease gK (conductance) 2. increase gNa

1. depolarize, increase excitability 2. depolarize, increase excitability

Total Body Water

1. intracellular fluid- 2/3 total body water, high K+, proteins, inorganic phosphates 2. extracellular fluid- 1/3 total body water- intersitial fluid + plasma, high Na+, Cl-, HCO3-

Gating mechanisms of ion channels

1. membrane potential- some channels only open when the membrane potential changes beyond a certain threshold value, and are called voltage-gated ion channels 2. specific ligands- ligand-gated ion channels cannot open unless they first bind to a specific stimulus or agonist 3. mechanical distortion- mechanosensitive ion channels only open when membrane is mechanically stretched ex. mechanosensitive sodium channels in hair cells

2 pump mechanisms

1. primary active transport- energy derived directly from breakdown of ATP, transport solutes against their electrochemical gradient -intrinsic proteins, active site accessible from only 1 side at a time, against electrochemical gradient, oppose equilibrating systems 2. secondary active transport- energy derived secondarily from energy stored in form of ionic concentration differences between 2 sides of membranes; Na+ gradient considered driver solute

ECF Osmolality roughly

300 mOsm/kg H20

The voltage gated potassium channels associated with action potential is an example of what type of membrane transport?

Facilitated diffusion

The rate of absorption of a drug taken orally found to increase as the dose ingested is increased up to a point where further increases in dose result in no further increases in rate of absorption. Absorption does not appear to result in splitting of ATP. Which process best describes drug absorption?

Facilitated diffusion (downhill)

Fick's first law of diffusion

J=DA(CA-Cb)/deltaX J= flow of solute from region A to region B in the solution D= diffusion coefficient of the solute in a given solvent Ca-CB or deltaC= the difference in solute between regions A and B Delta X= distance between regions A and B (membrane thickness)

Permeability Coefficient (P)

J=PA(deltaC) -includes the membrane thickness, the diffusion coefficient of the solute within the membrane, and the solubility of the solute in the membrane

The resting potential of myelinated neuron fiber is primarily dependent on the concentration gradient of

K+

Some tumor cells have large number Cl- channels on plasma membrane. This makes Cl- permeability higher than that of any other ion and therefore does?

causes membrane potential to be near equilibrium potential for Cl-

during diffusion, when the concentration of molecules on both sides of a membrane is the same, the molecules will

continue to move across the membrane in both directions

In the case of low blood glucose, concentration, the negative feedback is which of the following?

conversion of glycogen to glucose

Diffusion Coefficient (D)

decreases as: -the size of the molecule increases -the temperature of the solution decreases -the viscosity of the solvent increases

Ex. decrease K+ inside

depolarize, increase excitability

During Regulatory volume increase, many cells will decrease

efflux of K+

If a poison such as cyanide stops the cellular production of ATP, which of the following processes will cease?

exit of Na+ from cell

78 year old male gardening on hot day. Man thirsty fatigued, sweating, dizzy, faints.

heat exhaustion- faint, dizzy, excessive sweating, cool, clammy skin, nausea, rapid, weak pulse, muscle cramps

The first physiological change that occurs upon infusing a hypertonic solution IV into an experimental rat will be

increase in extracellular osmolality

Patient with kidney failure, resting membrane potential of muscle cells will become less negative. This is likely due to:

increased K+ conc outside

Drug changes resting membrane potential of intestinal epithelial cells from -60 mV to -50 mV. What change observed?

increased rate of diffusion of sodium into cells

The Na+/H+ transporter in plasma membrane of many cell types

is important for control intracellular pH

During surgery, exposed tissues are moistened with solution to prevent shrinkage or lysis of cells. Which of the following does the solution have to possess relative to cells in the tissue

isotonic

The nernst equation is useful for calculating the

membrane potential due to a single ion at equilibrium

What factor would need to be lower to contribute to greater net flux of solute A compared to B?

membrane thickness

Van't Hoff's Equation

osmotic pressure=(number of ions formed by dissociation of solute molecule) x (molar conc. of solute) x (ideal gas constant) x (absolute temperature) osmotic pressure=nCRT

what would most readily cross lipid bilayer by simple diffusion?

oxygen

Certain tumor cells have plasma membrane Na+ channel activated by acidic extracellular pH. In these cells, if acid added to extracellular medium which of the following would occur?

rate of ATP utilization will increase

Ex. increase Na+ inside

slightly hyperpolarize (more negative), slightly decrease excitability

A cell bathed in a solution that has a greater osmolarity than that of cytosol.

solution is hyperosmotic

Nernst potential

the electrical potential difference (Eion) across the membrane required to oppose the conc force exactly to prevent net diffusion of ion -Nernst equation: Eion (mV)=60/(valence of ion) log (conc ion outside of cell/ conc ion inside of cell)

Why doesn't permeability to Cl- ions significantly contribute to resting membrane potential?

the equilibrium potential for Cl- in typical cell is -85 mV. The resting membrane potential (-86 mV) is almost identical to Ecl. Therefore, there would be essentially no net flux of Cl- ions across cell membrane to contribute to RMP

Molecular size

the smaller the molecule, the faster it penetrates

Rate of solute conc will increase if decrease in

thickness of the membrane

Heat stroke

throbbing headache, no sweating, red, hot, dry skin, nausea, rapid, strong pulse, may lose consciousness

Electrochemical equilibrium

when chemical and electrical gradients are equal and opposite, there is no net force on ion, no net movement, and ion is in electrochemical equilibrium across membrane