Human Physiology Silverthorn 7e Chapter 5 Membrane Dynamics
Osmolarity
# of osmotically active particles (ions or intact molecules)/Liter of solution Expresses number of particles Must take two things into consideration: Penetrating solutes (glucose) Non-penetrating solutes (sodium, potassium, chloride) dissolve in solution but don't cross membrane
3 ways to enter a cell
(1) Cross lipid bi-layer (2) Passive Transport (3) Active Transport
Transport Proteins pg139
ABC and SLC
Simple diffusion
Diffusion directly across the phopholipid bilayer of a membrane
Carrier-Mediated Transport
Facilitated Diffusion and Active Transport
Table 5.6 Rules for Diffusion of Uncharged Molecules pg135
Know this table for exam
Diffusion
Movement from high to low concentration
Isotonic Saline
Normal Saline
Figure 5.17 Transporter saturation and competition (c) pg146
Saturation
Hypokalemic
Someone can possible have a heart attack with this situation, they are treated with a hypertonic solution
Figure 5.14 The Sodium-potassium Pump pg143
When going against a gradient ATP used
Apical Membrane
contains sodium glucose transporter on surface
Transporting epithelia are polarized
microvilli always face the lumen
"tonic"
tells what cells will do at the end of the solution
Membrane Proteins have 4 major functions
(1) Structural (2) Enzymes (3) Receptors (4) Transport Proteins
Rules for predicting tonicity
(1)Cell has higher concentration of nonpenetrating solutes than solutoin--water moves into cell--swells. Solution hypotonic (2)Cell has lower concentration of nonpenetrating solutes than solution--water moves out--shrinks. Solution hypertonic (3)Concentration of nonpenetrating solutes are same in cell and solution--no water movement--Solution isotonic
Transepithelial Absorption of Glucose
1. Na+ glucose sumporter brings glucose into cell against its gradient using energy stored in the Na+ concentration gradient. 2.GLUT transporter transfers glucose to ECF by facilitated diffusion 3. Na+-K+-ATPase pumps Na+ out of the cell, keeping ICF na+ concentration low. Ouabain (medication) blocks sodium potassium pump)
Extracellular Fluid (ECF)
1/3 of the total body water volume. Consists of Interstitial fluid and blood plasma Concentration of Na+, Cl-, and HCO3-
Percent Total body water Fig 5.1 Body Fluid Compartments Compartment Volumes for "Standard" 70kg man
28L Intracellular Fluid (2/3 of total body water volume) 14L Extracellular Fluid (1/3 of total body water volume) Plasma (25%) and Interstitial Fluid (75%)
Carrier-Medicated Transport pg140
3 different forms Uniport Symport Antiport (one in and one out)
Normal Person Homeostatic Concentration in body
300mOsM
What is a person's total blood water volume?
42L
Hypertonic
5mM potassium given to someone who is hyperkalemic
Concentration gradient
A difference in the concentration of a substance between two places. Also known as a chemical gradient. The larger the concentration gradient, the faster diffusion takes place.
If you have a 1 M solution of sodium chloride, how much is found to be dissociated in water? pg126
About 1.8 osmolarity of sodium chloride ions are found dissociated (not all) when added to water 1.8 X 6.023-10^-23 (Avogadro's Number)
The body is mostly water, we see a greater variation of water content in humans according to what factors?
Age-- decreases as people grow older than 60. Infants have more water content than adults Sex-- Women have less water per kilogram of body mass than men because women have more adipose tissue.
What does tonicity compare?
Always compares a solution and a cell. Used to describe only the solution--for example "Solution A is hypotonic to red blood cells."
Epithelial Transport Mechanism
Apical Membrane (Mucosal membrane) Basal Membrane (serousal membrane) Paracellular Transport (Through junctions between adjacent cells) Transcellular Transport (through cells themselves and transcytosis with vesicular transport)
Table 5.2 Comparing Osmolarities pg.127
Be able to tell how a solution relates to another solution.
Electricity Review
Because they are opposite charge (positive and negative) to separate them requires energy.
How does water move?
By traversing water filled ion channels and special water channels created by protein aquaporin (AQP)
All Living cells have a membrane potential
Can be measured with pipette and voltmeter
Caveolae
Can participate in signalling Important in uptake of viruses In two different forms of multiple sclerosis we have abnormal caveolae
Cell membranes are selectively permeable
Cell membrane restriction Whether or not a substance enters a cell depends on the properties of a cell membrane and those of the substance.
Hypercholesteremia
Cells fail to take up LDLs and person has a-lot of cholesterol in their blood.
Chemical disequilibrium
Chemical differences between inside and outside of cell. Some solutes more concentrated in one of the two body compartments. Energy is required to return solutes to the compartment they left (example Sodium-potassium pump)
Figure 5.16 Sodium-glucose cotransport pg145
Chemical gradients carry energy to promote events. From high sodium to low sodium High sodium binds to high affinity site for glucose Glucose binding changes carrier conformation so that binding sites now face the ICF Na+ released into cytosol
Figure 5.17 Transporter saturation and competition (d) pg146
Competition
How is Osmolarity a colligative property?
Depends strictly on the number of particles per liter of solution.
Fick's Law of Diffusion
Diffusion rate increases when surface area, the concentration gradient, or the membrane permeability increase.
Primary Active Transport
Direct Transport uses ATP
Homeostasis
Does not equal equilibrium It is disequilibrium
Osmotic equilibrium and the two disequilibria are in what type of state?
Dynamic Steady State
Receptor Mediated Endocytosis
Dynemin pinches the top off of the vesicle during endocytosis to allow for the vessicle to move around freely. Vessicle loses its clatherin. Vessicle can travel through the cells using ravs and SNAIREs Ligands released Vessicles return to surface of cell fuse with cell membrane for exocytosis and recycling of receptors Ligands either got to lysozomes or to golgi apparatus
Secretion
ECF back to lumen inside/out
Figure 5.23 Membrane Potential (a) pg154
ECF has a slight excess of cations (+) ICF has a slight excess of anions (-)
TRUE or FALSE Material moving into and out of the ICF does not need to cross the cell membrane.
FALSE Must cross the cell membrane.
TRUE OR FALSE Without water, life as we know it is able to exist.
FALSE No, life cannot exist without water.
Osmotic equilibrium
Fluid concentrations equal on both sides (ICF and ECF) Due to the free movement of water.
Intracellular Fluid (ICF)
Fluid within the cells 2/3 of the total body water volume. Concentration of K+ ions
Osmotic Pressure Figure 5.2 pg126
Force that moves the water that is applied to exactly oppose osmosis Can be measured using a chamber If you have non-penetrating solutes, water can move across the membrane.
Glucose Transporters
GLUT
Fluids
Gases--compressible Liquids-not compressible
Atherosclerosis
Hardening of arteries
What are the two distinct fluid compartments of the body?
ICF-intracellular fluid--CELLS ECF-extra cellular fluid--FLUID THAT SURROUNDS THE CELLS
Permeable
If a membrane allows a substance to pass through it, the membrane is said to be permeable to that substance.
Impermeable
If a membrane does now allow a substance to pass, the membrane is said to be impermeable to that substance.
Transcytosis across lumen of the intestine
In our intestine we are making IgA that binds to things we do not want in our bodies.
Secondary Active Transport
Indirect Uses potential energy of another molecules uses downhill gradient from one ion or molecule to power the uphill movement
Phagocytosis
Integrins C3bi
The body compartments are in a state of chemical disequilibrium. The cell membrane is a selectively permeable barrier between the ECF and ICF.
Intracellular fluid Interstitial Fluid- High level of Na+ and Cl- Interstitial Fluid-high level of Na+ and Cl- Plasma- High level Na+, Cl-, and proteins
What purpose does the Extracellular Fluid have?
It is the buffer between the cells and the environment outside the body.
Table 5.5 Intravenous Solutions
Know whether they are receiving isotonic or hypotonic solutions, based on non penetrating or penetrating
Where does the interstitial fluid (IF) lie?
Lies between the circulatory system and the cells. Between the tissues.
What are the factors affecting the rate of diffusion through a cell membrane?
Lipid solubility Molecular size Concentration gradient Membrane surface area Composition of lipid layer
Figure 5.11 The Structure of Channel Proteins pg 141
Lipophillic outside and a polar core that allows for movement of ions
Figure 5.15 Mechanism of the Na+-K+-ATPase pg144
Loads on low concentration side See Abigail's recording
LDLs
Low Density Lipoproteins bind to cholesterols
Absorption
Lumen to ECF outside/in
Molarity
Moles/Liter Moles of dissolved solute per liter of solution Expresses concentration
Bulk Flow
Most general form of biological transport of fluids within a compartment. Presure gradient--flow of fluid from regions of higher pressure to regions of lower pressure.
Cell Membrane Enables separation of Electrical Charge in the Body
Movement of K+ ions out of the cell according to chemical gradient Negative ions cannot follow because the membrane is impermeable to anions Electrical gradient established Electrochemical gradient- combination of electrical and concentration gradient Equilibrium potential Eion is the membrane potential that oppposes the concentration gradient (caluculated using Nernst equation)
Osmosis
Movement of water across a membrane in response to a solute concentration gradient Fluids can be liquid or gas, but not ions, not polar or large proteins (these are not permeable) Permeability depends on lipids and proteins
Tonicity
Of a solution, describes the volume change of a cell at equilibrium. Same osmolarity on both sides of membranes allows for retaining of tension Depends on the concentration of the nonpenetrating solutes.
Hyperosmotic solution
One solution has a higher osmolarity (contains more particles per unit volume, more concentrated) than the other solution. One side is higher (hyperosmotic) than the other (hyposmotic)
Hyposmotic Solution
One solution has fewer osmoles per unit volume it is considered this. Always hypotonic
What can move across membranes by simple diffusion?
Only lipids, steroids, and small lipophilic molecules. (non-polar molecules that are lipid soluble (lipophilic) can dissolve in the central lipid core of a membrane. Excepetion is water (although polar) which can diffuse slowly across some phopholipid membranes because of its small size.
How do we establish resting membrane potential?
Overall body is electrically neutral Chemical disequilibrium between ICF (net negative) and ECF (net positive)
Nonpenetrating solutes
Particles that cannot cross the cell membrane Most important in physiology NaCl (functionally nonpenetrating)
Vesicular Transport for Thursday
Phagocytosis Endocytosis Caveolae Exocytosis
Probenicid Medication
Prevents the re-absorption of Uric Acid Flushed out in Uric acid Note: Uric acid pump is competable, saturable, and specific
Active Transport pg133
Requires the input of energy from some outside source, such as the high energy phosphate bond of ATP.
All living cells have a membrane potential
Resting Membrane potential difference (membrane potential) Resting is the steady state Potential energy stored in the electrochemical gradient Difference in electric charges inside and outside of the cell There are two forces competing the concentration gradient pushing potassium out because more inside than outside - but then the positive environment on the outside pushes potassium back in because there are more positive outside.
Figure 5.24 Measuring Membrane Potential pg157 ****Must know this for exam*****
Resting membrane potential of a Cell -70 mV Polarized to start Hyperpolarize- moving farther away from zero Depolarize-moving closer to zero Repolarization- back to resting Leak channels maintain membrane potential.
Figure 5.22 Transcytosis across the capillary endothelium pg153
Review in book
Figure 5.16 Sodium-Glucose Cotransport pg 145
SGLT-Sodium Glucose Transporter
What are the two properties of a molecule that influence its movement across cell membranes?
Size and lipid solubility.
Figure 5.6 Diffusion Experiment
Small substances diffuse more rapidly than large substances
Penetrating solutes
Solute particles (ions or molecules) that can enter the cell by crossing the cell membrane.
Table 5.3 Tonicity of Solutions
Solution is hypotonic-water wants to move into the cell "swells" Solution is Isotonic-Cell doesn't change Solution is hypertonic-water wants to move out cell "shrinks"
Functions of Membrane Proteins
Structural proteins Enzymes Membrane receptor proteins Transporters Channel proteins Carrier proteins
TRUE or FALSE Body is mostly water
TRUE
TRUE or FALSE Everything that enters or leaves most cells passes through the ECF (extracellular fluid).
TRUE
TRUE or FALSE In osmosis, water moves to dilute the more concentrated solution. Once concentrations are equal, net movement of water stops.
TRUE
TRUE or FALSE Ions move in response to combined electrical and concentration gradients, or electrochemical gradients.
TRUE
TRUE or FALSE Membranes with high cholesterol content are less permeable to water than those with low cholesterol content, presumably because the lipid-soluble cholesterol molecules fill spaces between fatty acid tails of the lipid bilayer and thus exclude water.
TRUE
TRUE or FALSE The ECF and ICF are in osmotic equilibrium but in chemical and electrical disequilibrium.
TRUE
TRUE or FALSE The lipid and protein composition of a give cell membrane determines which molecules will enter the cell and which will leave.
TRUE
TRUE or FALSE Tonicity depends on the concentration of nonpenetrating solutes only.
TRUE
TRUE or FALSE Very large lipophobic molecules cannot be transported on proteins and must enter and leave cells in vesicle.
TRUE
TRUE OR FALSE Most water movement across membranes takes place through protein channels.
TRUE Example: Cells insert special water channel proteins into the phospholipid bilayer in parts of the kidney which would otherwise be impermeable to water.
TRUE or FALSE Number of particles determines movement of water
TRUE The important factor for osmosis is the number of osmotically active particles in a given volume of solution, not the number of molecules. Because some molecules dissociate into ions when they dissolve in a solution, the number of particles in solution is not always the same as the number of molecules.
TRUE or FALSE The body is in a state of osmotic equilibrium
TRUE Water is able to move freely between cells and ECF, distributing itself until concentrations are equal throughout the body.
If Ouabain blocks sodium potassium ATPase, what effect will it have on the glucose on the lumen?
The concentration of the glucose would increase because there would be no gradient (Na+ concentration gradient engery) for it to use to move in, thereby increasing the concentration of the glucose in the lumen, since it is not moving in.
Electrical disequilibrium
The ionic imbalance that results from the ICF being slightly negative relative to ECF being slightly positive. Changes in this disequilibrium creates electrical signals Body as a whole electrically neutral
Substances moving between the plasma and interstitial fluid must cross what?
The leaky exchange epithelium of the capillary wall.
What is blood plasma?
The liquid matrix of blood found inside the circulatory system.
Osmolarity
The number of osmotically active particles (ions or intact molecules) per liter of solution.
What are the two subcompartments of the extracellular fluid (ECF)?
The plasma and the interstitial fluid (IF).
Why can't osmolarity be used to predict tonicity?
The tonicity of a solution depends not only on its concentration (osmolarity) but also on the nature of the solutes in the solution.
In the end what happens to the volume of the cells
The volume increases due to NaCl being a hypotonic solution
Why do smaller molecules and ions such as Na+ and Cl- have the same concentrations in plasma and interstitial fluid?
They are small enough to pass freely between the endothelial cells.
Why are proteins and other large anions concentrated in the plasma?
They cannot cross the leaky exchange epithelium of blood vessels, so they are mostly absent from the interstitial fluid.
TRUE or FALSE If a membrane is permeable only to water and not to any solutes, water will move by osmosis from a less concentrated (hyposmotic) solution into a more concentrated (hyperosmotic) solution.
True
True or False Chemically gated channels are normally open
True
True or False Normally gated channels are closed or inactive
True
True or False Urea is penetrating
True
True or False Men have a higher percentage of water in their bodies than females
True Females have less water and more adipose
True or False A carrier protein can move only 1,000 to 1,000,000 molecules per second, in contrast to tens of millions of ions per second that move through a channel protein
True pg141
True or False NaCl is a nonpenetrating
True, NaCl is the most important non-penetrating solute in physiology.
Isosmotic Solution
Two solutions contain the same number of solute particles per unit volume.
Hypotonic
Unusually to give to a patient because cells will break at the end of the solution. Used in lab to rupture red blood cells to count white blood cells Glucose is a penetrating solute making an IV solution of D5W hypotonic. Water will move into the cell where the ions are.
Transcellular transport of glucose
Uses membrane proteins
Protein mediated transport
Vast majority of solutes cross membranes with the help of membrane proteins because the majority of molecules in the body are either lipophobic or electrically charged and therefore cannot cross membranes by simple diffusion.
What is essentially the only molecule that moves freely between cells and the extracellular fluid?
Water
Channels
Water Channel-Aquaporin allows for osmosis to happen Ion Channels Open Channels Gated Channels Chemically gated Voltage-gated Mechanically gated (pressure sensitive)
Questions: Mother brings baby to ER because has been vomiting and diarrhea for 2 days. After weighing the baby they find that the baby has lost 2lbs. What percentage has the baby lost?
We can use the solute over volume concentration formula. 2/2.2=0.91kg of water or 0.91 L Look at example of pages 130 and 131
Since osmolarity alone does not tell you what happens to a cell when placed ina solution, what does Tonicity tell you?
What happens to cell volume at equilibrium when the cell is placed in the solution
Why is it important to allow for variability of body water content when prescribing drugs?
Women and older people have less body water and will therefore have a higher concentration of the dug in the plasma
If a woman is given a lipid soluble drug and gave a man the same, would the dosage need to be different
Yes, women will store in adipose
Facilitated diffusion
a form of passive transport does not require energy example: Osmosis A mediated transport that is passive and that moves molecules down their concentration gradient, net transport stops when concentrations are equal on both sides of the membrane.
Basolateral Membrane
contains sodium potassium ATPase
mOsM (see pg126)
milliosmoles per Liter
Passive Transport (know all of the processes in the video)
no energy required uses kinetic energy inherent in molecules and the potential energy stored in concentration gradients
Figure 535 Transport across membranes
oxygen and carbon dioxide move easily across the membrane large molecules, polar molecules do not move easily across the membrane
Dynamic equilibrium
state in diffusion where concentration has equalized throughout the system but molecules continue to move.
Active transport
transport against concentration gradients requires energy from cell (ATP) or outside source Example Sodium Potassium Transportation