Physiology Class Notes
7/8, 13, & 15

Professor Carl Spirito (Spirit o) / 1^st of 5 professors to teach us

Goal is to teach basic mechanisms R/T principles of chem./physics

We are responsible for Guyton topics not covered in class, so use lecture as a guide to what’s important and use lecture as a supplement to the text

LIBRARY reserve – copies of old exams

He will give us handouts of overhead material

Substances move across cell membrane (from 1 compartment to another) in aqueous medium through

• cell membrane
• cell sheets (layers)
• cap membrane

via: diffusion- solutes move from an area of inc conc to an area of lower conc, until eventually a uniform distribution of particles occurs. NET movement is what is considered. The solute particles move in random directions in straight lines, by simple molecular motion. Velocity determined by T, molec wt

Molecules bounce off wall and keep moving.

Probability—after particles move left to right then some will move right to left and eventually they will move in both directions. This is representative of a dynamic stable equilibrium(no further net movt occurring)

A static equilibrium is where no movement occurs at all, which theoretically occurs at 0K

Diffusion rates vary according to size

• 1u size water cube 2/10 sec, 1mm size cube 50 hrs, 1 cm cube 200days

diffusion works great over tiny distances but is inefficient over large areas, such as in multicellular animals. This is why resp, CV, renal and other systems evolved so substrates could move to needed areas over large distances.

Ficks law describes diffusion in terms of proportionality- and looks at proportionality of movement in one direction as well as movement in another direction. It considers back flow which is considered in NET movement

Flux/flow prop to T, x sec area, conc gradient, 1/chg x – these are conditions

of the solution; and to 1/molecular weight which is related to molecule size

inc T = inc motion

larger particles move slower than small ones

Now add a membrane with slits, like a lipid bilayer membrane

Diffusion is affected by adding a lipid membrane and listed below are the things which determine--- molecule passage through the membrane

• solubility of molecule in water or lipid- oxygen is very sol in lipid and moderately sol in water.
• size of molecule
• particle can bounce off area where there is not a pore- think of x sec area – dec flow
• see Guyton for other determinants

Mechanisms in cell membrane evolved to allow for polar molecules like proteins, AA, ions,

See hand outs – they are very helpful

Channels for diffusion – PASSIVE protein – particles move via simple diffusion

• water channels
• lipid channels
• charged water channels
• gated water channels

Water and u shaped tube drawing – water will move from an area of high conc (no solute) to an area of less conc (solute mixed with water), thus causing a shift in the once even fluid level on both sides of the u ( as long as membrane does not let particles thru – just water). Think of how gravity affects the level of the u where the water and solute are. There are 2 opposing forces

• the osmotic force of water moving to the side of the u with solute in it
• the gravitational force pressing down on the side of the u with the water and solute in it
• once the gravitational force causes the water to stop crossing over to the side with the solute in it a dynamic equilibrium has been established, thus no further NET diffusion will occur
• can measure the force of the gravity to get an idea of osmotic force
• can attach a device with an expandable volume to give a measure of osmotic pressure, or use a manometer to obtain a linear measurement by observing the height of a column in mmHg or cm H2O, 1.4 cm H2O per 1mmHg
• can put a heavy liquid on top of the water solute side and see how much of it is required to hold the level steady

Osmosis deals with diffusion of water

• diffusion of water is quick
• osmotic balance with in cells usually attained quickly compared to solute balance
• osmotic pressure is directly proportional to solute

Tonicity- deals with what solution is

• hypotonic – has lower osmotic pressure than it’s reference solution which could be blood, CSF, etc-
• hypotonic soln has lesser tendency to draw water toward it, since it has a lower conc of solute, therefore cell will swell
• if soln outside of cell is hypertonic (it has high osmotic pressure, because it has a lot of solute particles), then water will move out of cell and the cell will shrink
• hypotonic soln has a lower conc of particles so water will move away toward where more solute is and where less water is

When thinking of tonicity, visualize water as the solute being dissolved, and the concepts of tonicity will be more clear.

Facilated diffusion

• substance cant move across memb
• driving force for movt is diffusional force
• no active mechanism – its a passive mech
• depends on amt of solute
• fd is specific for substrate
• tends to be unidirectional
• no requirement for external energy
• affinity for carrier to carry substrate in
• ie insulin involved with inc affinity for carrier protein to bring more glucose into cell

Active Transport –

• Moves substrate across cell membrane against conc gradient and using

Metabolic energy to push substance against conc gradient

- carrier protein forms complex with substrate to be carried and complex

and which conformational change à substrate moves through cell

membrane

• once substrate is on other side of cm it has to be released into an area

where the conc grad of itself is high and release is not automatic

• this is time for active transport to kick in – ATP in cell interacts with carrier to

supply energy via a strong phosphate bond dissociation, and substrate is

then released.

• then the carrier protein flips back to its original state – eg Na-K pump
• Na-K pump exists in q cell and uses 20% of the metabolic energy
• Na+ predominately in the ECF – net + chg, opp cause some K to enter
• K is predominately in the ICS - net neg chg – opp attract so Na enters the cell and also the concentration gradient is in the right amt for Na to leak in
• The size of the Na just barely allows it to pass in through the passive pores and it does so slowly
• Scenario – if there were no Na pump the cells would burst because water would follow Na into the cell and eventually the cell would rupture
• Binding sites where 2 K attach on outside and # na attach on inside and are flipped toward the right destination – thus Na is moved from low to high conc
• Thus cell equilibrium is maintained

Mechanisms to maintain cell equilibrium –

• passive diffusion
• facilitated diffusion
• active transport
• AT vs facil diffusion – these two mechanisms are:
• Co – transport – which is dependant on having Na Na leak in

concentration gradient utilized to do movement, which itself was derived from ATP process.

• Na goes with conc grad and glucose tags along for the ride
• Na conc grad is utilized( in ECF to ICF) and Na conc grad depends on Na-K pump which depends on energy – so Na goes into cell and brings glucose with it, then Na is moved back out of the cell via active transport.
• Counter transport – as Na moves in to the cell, another substrate moves out of the cell (by the occurrence of Na being carried in) But now the Na needs to be brought back out of the cell by AT, therefore active and passive transport mechanisms are utilized

• See picture – both ECF’s have same conc grad of substrate
• A has inc conc and cell had dec conc so subs enters passively but has to exit on the B side via active transport, against an already high conc gradient

Think of concentration gradient in A&B , in cells and how substrate moves thru to each area and which mechanisms enable substrate to move in

Think of levels of substrate in each compartment and it’s relationship to its concentration gradient.

Body fluid compartments - ICF - RBC=2L + 25L

ECF- plasma = 3L + 11LHow does food get from GI to plasma ECF & ICF

Fluid out via kidney renal tubule & plasma

A little water is synthesized from oxidation but most is obtained through diet and is lost through feces, sweat, exhalation. EQUILIBRIUM is evident by seeing 3L in and 3L out

Measuring fluid volume - via appropriately sized tracers ( about 1/10 mole) and circulate them through the body compartments via cell membrane (they must be able to fit through the pores). Now take blood sample and measure cpmc of tracers present. Looking for volume so – moles of tracer / ml or L

When measuring ECF be sure to choose a molecule that will fit into a capillary but not into the cell.

Fluids contain

Plasma – moderate protein – 90%

ECF – high levels of Na, Cl,

low K, contains 60% lower protein(1/4)that of plasma

Is a virtual space where a matrix exists its not sloshy like plasma, and its

A proteoglypex, has collagen, not alot of volume, its a pathway or a link from what happens in cells and plasma

ICF- high K, Ph, Mg

Low Na, Cl

Very high protein – protein comprises 97% of mass of ICF, therefore it has the highest protein content of all 3 areas

Capillary flow can be conceptualized to understand substance and H2O flow across a membrane

• Capillary wall single layer of endothelial sheet surrounded by a loose basement

Membrane, and there is no smooth muscle because its a passive tube

• Between capillaries are intracellular clefts which are large pores – lots of things pass except for large proteins, under normal physiological conditions
• O2 & CO2 dissolve as they move through the lipid bilayer
• From cap to cell and from cell to cap is usually in balance, if its out of balance & pathos
• What exits capillary and is not returned is usually eventually returned by the lymphatic into the circulation, ie proteins
• Lymph is controlled by muscular movt which messages the lymph vs
• Think of lymph as an extension of the ECF
• There is no concentration gradient in lymph, because they are not porous?????????
• If lymph is ineffective in returning protein to circulation then protein builds up in ECF & edema can occur but this isnt the main reason for edema

Forces in the system

• diffusion – passive – hydrophilic and lipophilic - the exchanges are small and accounts for 10%ov movement across the capillary wall
• Bulk flow is always moving out of capillary as long as COP is higher than ECF pressure, this pressure is driven by hydrostatic pr or BP. Ions, H2O, nutrients, AA, and very small proteins move out of capillary via bulk flow. Bulk flow accounts for 90% of movt across the cap memb
• Oncotic pressure (COP) – is caused by the large proteins that are trapped in the capillary. Water is drawn to the proteins and thus moves into the capillary from the ECF (not from lymph as the lymph vs have one way valves. Small substrates move in along with the water depending on their concentration gradient inside and outside the capillary wall. ie O2,CO2,Na, Cl, K

When thinking about oncotic pressure – think of it like that things that cant move are classified as the solute, and things that can move are classified as solvents-ions, small particles

Net movement – means there is movement to one side of the cell membrane more than to the other. Measuring it can give the gross numbers

Ions move in RT concentration gradient of particle and charge

Osmotic pressure is a force = to the force causing water to move

Tonicity is a comparative measure – X fluid compared to Y fluid. Plasma is generally referenced if no other fluid is mentioned.

In discussing ICF vs ECF, RBCs are a subdivision of ICS, and plasma is a subdivision of ECF

Fluid volume is measured with in the different spaces with tracer molecules , which will be restored to one compartment

Tracer X, the cell membrane determines total body volume is being measured, but if the tracer is constricted to the vascular space due to the intracellular clefts in the capillary, then only the vasc space can be measured.

The capillary wall is an example of fluid and solute movement. The single cell layer with clefts allow a diameter molecule the width of 200 Na atom to fit thru which is big. Egs are AA, water, small plasma proteins.

Hydrophobic – water thru pores &  thru cell wall – sm. Charged ions, Na, Cl, K

Lipophilic – Inc solubility – resp gasses so there is no barrier to CO2 and O2

Diffusion is regulated by concentration difference of substances on both side of the cap wall and each ion has its own concentration gradient. Think it as a ratio 3 Na 1 K

1Na 3K see pic 1

Know the different forces – diffusion, bulk, COP

Diffusion moves 10% of stuff

There is 50-75 microns across a cell, the net exchange occurs slowly unless the concentration gradient is vast

FORCE - Bulk flow moves 90% of the substances and water driven by diffusion, from hydrostatic pressure, from one area the other. Cap BP cap bp 10

The cap BP at the beginning is higher than the ECFs COP. Water, solutes, ions, AA, glucose, proteins are pushed – there is no discrimination sas to what's pushed through the clefts as long the stuff fits through.

Contrast this to specific types of diffusion. AT, gated and carrier proteins

FORCE – Oncotic pressure (COP) – OP due to the presence of substances which don’t pass through the wall. COP causes movement of substrate from ECF to capillary. Water and what ever else fits will move into the capillary. The solvent is thought of as any substance which is drawn to the protein, which could be water, glucose, Na ect

see pic 2

Think of what forces move what stuff in what direction.

There are 4 times as much proteins in the plasma than in the ECF which usually keeps water from building up in the ECF, but smaller proteins move out in the ECF and draw water to them but this excess water is removed by the lymphatic are returned to the vasc space.

See pic 3

plasma is considered to be continuous with the ECF, when comparing the non protein content of each plasma & ECF, because other than the protein the composition is the almost the same.

The lymph moves proteins to the thoracic duct which drains into the thoracic system

The net positive fluid dump into the circ system returns that fluid back to the caps, he change in volume is balanced by the lymph.

Pic 4

FORCES ARTERIAL VENOUS

CAP BEGINS CAP ENDS

Outward Forces (out of cap)

HYDROSTATIC PR 30mmHg 10mmHg

ONCOTIC PR 5 mmHg 5mmHg

ECF FLD PR 6mmHg 6mmHg

___ ___

41 mmHg 21mmHg

Inward Forces (into cap)

ONCOTIC PR 28mmHg 21MMhg

So, 41-28=23mmHg – the net oncotic force is 23 in, because there is > protein in the capillary than in the ECF, so water is drawn to the protein in the capillary.

21-28= a difference of 7, which shows a net inward force of 7

@ 90% of stuff moved out is reabsorbed and the rest 10% is what forms the lymphatic flow.

?????????????????? net force outward force at the arterial end of the cap is out 13, ar a + 13 net in force. Tendency is for the fluid to move out at arterial end and back in in the venous end.

Pic 5 at any given temp there is movement in both directions (of fluid)

Neg ECF fluid pr – the physical pressure is negative in the ECF. There is very little fluid in there. Oncotic pressure moves water out of the capillary into the ECF.

99½% of plasma doesn’t leave capillary during flowing through it, and ½ of 1 % of plasma moves out, mixes with ECF and moves back in. This system works over the long haul.

A typical capillary is 11mm long, and there is a limited for the exchange to occur. 1/200^th of Na, K, water, etc actually leaves the capillary and contributes to the mixing, so the exchanges occur in tiny increments over continuous time.

Think of diffusion and conc gradient, and how the flow is between the capillary to the tissue and back to the cap again.

Edema – bulk force Hydrostatic pressure of 30, and if BP is up, the blood flow will be inc and more fluid will be forced out of blood vessel into tissue. à which inc fld in ECF. Cardiac problems, venous clots can cause an inc in hydrostatic pressures locally or systemically

Oncotic force – suddenly dec protein in blood from say burns, dec nut, renal ds, and others can change the oncotic balance and < fluid enters caps and > fluid stays behind in the tissues, esp if the proteins leak into the ECF.

Inc pouricity fo intra cellular clefts of caps will cause larger proteins to enter ECF and this will change oncotic balance and fluid stays in tissue

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