Mon Feb 2 - EXAM #1 - Transport through Smooth Muscle Contraction

Wed Feb 4 - The Heart

                        Mechanical Functions of the Heart

                        Electrical Properties of Cardiac Tissue

                        Chapter 9, pp. 96-106

Fri Feb 6 -      Rhythmic Excitation of the Heart

                        Chapter 10, pp. 107-112

Mon Feb 9 - EKGs - Flow of Current Around the Heart

                        Chapter 11, pp. 114-119

Wed Feb 11 - Analysis of EKGs

                         Chapter 12, pp. 120-133

                        QUIZ #3 - Mechanical Functions of the Heart through EKGs

Fri Feb 13 -   Cardiac Arrhythmias

                        Chapter 13, pp. 134-142

Mon Feb 16 - Circulation

                         Physical Characteristics

                        Chapter 14, pp. 144-151

Wed Feb 18 - Cardiac Output, Venous Return, and Their Regulation

                          Chapter 20, pp. 210-221

                  QUIZ #4 - Analysis of EKGs through Physical Characteristics of Circulation

Fri Feb 20 -     Functions of the Arterial and Venous System

                         Chapter 15, pp. 152-160

                        TERM PAPER OUTLINE DUE

Mon Feb 23 - The Microcirculation and Lymphatic System

                          Chapter 16, pp. 162-174

Wed Feb 25 - Local Control of Blood Flow by Tissues and Humoral Regulation

                          Chapter 17, pp. 175-182

Fri Feb 27 - EXAM #2 - The Heart through Microcirculation & Lymphatic System

Mon Mar 1 - Nervous Regulation of Circulation

                         Chapter 18, pp. 184-193

Wed Mar 3 - Renal Involvement in the Regulation of Blood Pressure

                         Chapter 19, pp. 195-208

                        QUIZ #5 - Cardiac Output through Nervous Regulation of Circulation

Fri Mar 5 -    Special Circulation (Skeletal and Cardiac Muscle)

                        Chapter 21, pp. 223-233

Mon Mar 8 - Cardiac Failure

                         Chapter 22, pp. 235-244

Wed Mar 10 - Congenital Heart Defects

                           Chapter 23, pp. 245-252

Fri Mar 12 - Circulatory Shock

                         Chapter 24, pp. 253-262

   QUIZ #6 - Renal Involvement in the Regulation of Blood Pressure through Congenital Heart Defects

Mon Mar 15 - Pulmonary Ventilation

                         Chapter 37, pp. 432-442

Wed Mar 17 - Pulmonary Circulation, Pulmonary Edema

                          Chapter 38, pp. 444-450

Fri Mar 19 -    EXAM #3 - Local Control of Blood Flow through Circulatory Shock

Mon Mar 22 - SPRING BREAK

Wen Mar 24 - SPRING BREAK

Fri Mar 26 -   SPRING BREAK

Mon Mar 29 - Physical Principles of Gas Exchange

                         Chapter 39, pp. 452-461

Wed Mar 31 - Gas Transport through the Blood and Body Fluids

                        Chapter 40, pp. 463-472

          QUIZ #7 - Pulmonary Ventilation through Physical Principles of Gas Exchange

Fri Apr 2 -     Gas Transport through the Blood and Body Fluids

                        Chapter 40, pp. 463-472

Mon Apr 5       RBCs, Anemia, and Polycythemia

                        Chapter 32, pp. 382-391

Wed Apr 7 -    Regulation of Ventilation

                         Chapter 41, pp. 474-482

Fri Apr 9 - Respiratory Pathophysiology  

                          Chapter 42, pp. 484-492

                         QUIZ #8 - Gas Transport through Regulation of Ventilation

Mon Apr 12 - Special Circumstances for Respiratory Physiology

                          Chapters 43 and 44, pp. 496-502

Wed Apr 14 - The Body Fluid Compartments

                         Chapter 25, pp. 264-278

Fri Apr 16 - KANSAS ACADEMY OF SCIENCES

Mon Apr 19 - Renal Blood Flow and Glomerular Filtration

                        Chapter 26, pp. 279-293

Wed Apr 21 - EXAM #4 - Pulmonary Ventilation through Special Circumstances for Respiratory Physiology

Fri Apr 23 - Renal Blood Flow and Glomerular Filtration

                        Chapter 26, pp. 279-293

Mon Apr 26 - Tubular Reabsorption and Secretion

                         Chapter 27, pp. 295-312

    QUIZ #9 - Body Fluid Compartments through Blood Flow and Glomerular Filtration

Wed Apr 28 - Renal Control of Osmolality

                          Chapter 28, pp. 313-328

Fri Apr 30 -   Renal Regulation of Blood Volume and Extracellular Fluid Volume 

                         Chapter 29, pp. 329-344

Mon May 3 - Regulation of Acid Base Balance

                         Chapter 30, pp. 346-363

Wed May 5 - Diuretics and Kidney Disease

                        Chapter 31, pp. 364-378

Fri May 7 - Diuretics and Kidney Disease

                        QUIZ #10 - Tubular Reabsroption through Diuretics and Kidney Disease

                        Chapter 31, pp. 364-378

                        FINAL DRAFT OF TERM PAPER DUE

FINAL EXAM - MONDAY MAY 10 - 10:10 - 12:00

Body Fluid Compartments through Kidney Disease

DIFFUSION THROUGH THE CELL MEMBRANE

I. Simple Diffusion

      Requires a concentration gradient

       A. Two Types of Simple Diffusion (Fig 4-2, p. 41)

            1. Diffusion through interstices of the lipid bilayer

                a. rate of diffusion dependent upon substances

                   lipid solubility

                        Oxygen, Carbon Dioxide, Nitrogen and

                        Alcohols are very lipid soluble, thus

                        diffuse readily through cell membrane

                        Hydrogen, Sodium, Potassium and other ions

                        are not very lipid soluble, thus do not

                        readily diffuse through the cell membrane

            2. Diffusion through protein channels of cell membrane

                 a. selectively permeable to certain substances

                     mostly as a result of the size and/or charge of the

                     protein channel (Fig 4-4, p. 42)

                              - urea is a larger molecule than water, how does

                                its diffusion through the membrane compare to

water?

                              - does significant amounts of urea pass through the

                                cell membrane?

                 b. many protein channels can be opened or closed by gates

                    (Fig 4-4, p. 42)

II. Gating of Protein Channels

      A. Two principal ways of controlling the opening and closing

            of protein channels

          1. Voltage Gating

               a. potential voltage differences between the inside and

                  outside of the cell determines if the gates of the

                  channel will be open or closed

                    Ex. Inside of the cell is strongly negative, sodium

                         gates will remain closed

                        If the inside of the cell should become less

                         negative, the sodium gates open allowing sodium

                         to rush in (nerve impulse).

          2. Ligand (Chemical) Gating

               a. substance binds to the protein channel causing a

                  conformational change in the protein structure that

                  either opens or closes the gate

                    Ex. Acetylcholine binding to the protein channels

                        located on muscle membranes making the membrane

                        permeable to sodium (muscle contraction).

                    - what is the patch-clamp method and why is it used?

III. Facilitated Diffusion (Carrier-mediated Diffusion)

          a. carrier proteins facilitate the diffusion of substances through

              protein channels

          b. rate of diffusion is determined by rate at which the channel

protein can undergo a conformational change

          c. as a result, facilitated diffusion has a maximum rate at which

              substances can diffuse regardless of diffusing conditions (Vmax)

              (See next section: Factors that Affect Net Rate of Diffusion)

              (Fig 4-6, p. 44)

IV. Factors that Affect Net Rate of Diffusion

          a. Concentration Gradient (4-8a, p. 45)

                    Net Diffusion ∞ (Co - Ci)

          b. Electrical Gradient (4-8b, p. 45)

                    Nernst Equation - the voltage at which no net movement

                                                   of a particular ion occurs for a given

                                                   concentration gradient

                              Electromotive Force (EMF) = + 61 log C₁/C₂

          c. Pressure Gradient (Fig 4-8c, p. 45)

V. Osmosis (Fig 4-9, p. 46)

          a. Defined as: the net movement of water caused by a concentration

              difference of water

          b. Osmotic Pressure

                    - the pressure required to exactly stop osmosis

                              - Fig 4-10, p.46

          c. Importance of Molar Concentration

                    - osmotic pressure is exerted by the NUMBER of particles

                      in solution (solutes) and not by their size

                              - due to large particles moving slower

                                         - k = mv²/2

                                             where k is average kinetic energy

                                                       m is the mass of particles

                                                        v is the velocity particles

                     d. Osmolality

                              - the number of solutes in solution

                              - one mole per kilogram = 1 osmole

                              - Thus, in order to make a 1 osmole solution of glucose

                                (180 grams per mole) would need to add 180 grams of

                                glucose to 1Kg of distilled water

                              - if the chemical in question can dissociate into two ions

                                (NaCl) then the the osmolality is twice the molecular weight

                                         Ex. NaCl has a MW of 58.5 g/Mole

                                         58.5 grams of NaCl in 1 Kg water = 2 Osmoles

                                                   - due to 1 Osmole contribution of Na and 1 Osmole

                                                     contribution of Cl - assumes complete dissociation

                              - a milliosmole is 1/1000 of an osmole

          - How much water diffuses through a red blood cell per second relative to

             its normal cell volume?

          - How much NET diffusion occurs through a red blood cell

          - How does osmolality differ from osmolarity?

V. Active Transport

       Allows for movement of substances uphill against a concentration

       gradient but requires energy derived from ATP.

          A. Two Types of Active Transport

                    1. Primary Active Transport

                              - energy derived directly from the breakdown of a high-energy

                                 phosphate compound (ex. ATP)

                    2. Secondary Active Transport

                              - energy derived from stored (potential) energy source that was

                                 created via the breakdown of a high-energy phosphate cmpd.

                    - Both primary and secondary active transport require carrier proteins\

         B. Sodium-Potassium "Pump" (Fig 4-11, p. 47)

             - a primary active transport mechanism present in all cells of the body

             - allows for the establishment of a negative electrical

               potential inside the cell

             1) How the sodium-potassium pump works

                  a) 3 Na⁺ bind to the inside of the protein channel

                      and 2 K⁺ to the outside of the channel

                  b) causes the activation of an ATPase also located

                     on the protein channel near the Na⁺ binding site

                  c) ATPase splits ATP into ADP + Pi which releases energy

                  d) The energy released is used to bring about a conformational change in the protein channel

                  e) conformational change results in the 3 Na⁺ being

                       moved out of the cell and the 2 K⁺ being moved

                       into the cell

             2) Result of the sodium-potassium pump

                  a) one net positive charge is moved out of the cell

                     causing the interior of the cell to become more

                     negative with respect to the fluid surrounding

                     the cell

          3) Importance of the sodium-potassium pump

                    a) control of cell volume

                              - large number of proteins and organic cmpds in cell

                                 creating an osmotic gradient pulling water into the cell

                              - left unchecked the cell would burst

                              - recall remove 3 Na⁺ from interior and brings into the cell

                                2 K⁺. Net loss of one ion from interior of the cell, water

                                follows

                              - cell swelling activates the sodium-potassium pump

                    b) electrogenic pump

                              - recall remove 3 Na⁺ from interior and brings into the cell

                                2 K⁺. Net loss of one positive ion from interior of the cell,

                                results in the cell interior becoming more negative relative

                                to cell exterior.

     B. Calcium Pump

              1. In most cells the amount of Ca⁺⁺ inside the cell is

                 10,000 times less than that of Ca⁺⁺ surrounding the

                 cell.

              2. This gradient is maintained by the Calcium pumps

                    a) cell membrane bound calcium pumps, pump calcium

                        to the cell exterior

                    B) pump calcium into cytoplasmic organelles

                        (sarcoplasmic reticulum and mitochondria)

          C) Hydrogen Ion Pumps

                    - where in the body do these occur?

                    - what is there function in those parts of the body

          D) Co-transport (Secondary Active Transport)

                    1) Glucose and Amino Acids along with Sodium Ions (4-12, p. 49)

                              - when sodium and glucose bind to their respective binding

                                 sites on the same receptor protein, a conformational change

                                 occurs in which sodium travels down its concentration

                                 gradient providing the energy for glucose to be moved up

                                 its concentration gradient

          E) Counter-transport

                    1) Sodium Counter-transport of Calcium and Hydrogen

                              - same as above except that sodium is moved in a direction

                                opposite that of calcium or hydrogen

                              - in what cells does this occur?

          F) Active Transport through Cellular Sheets

                    - transport through a lining of cells (sheet)

                    - where does this occur?

                    - Fig 4-13, p. 50

PHYSICS OF MEMBRANE POTENTIALS

I. Movements of Ions

    A) Concentration Gradient

        1) substances tend to go from places of higher concentrations

           to places of lower concentrations

    B) Electrical Gradient

        1) unlike charges attract; like charges repel each other

II. Concentration Gradients Across the Cell Membrane (Fig 4-1, p. 41)

     A. Concentration of selected ions inside and outside a

        typical cell at rest.

                                          Concentration (mEq/L)

                  Ion Inside Cell Outside Cell

                  Na⁺ 10 142

                   K⁺ 140 4

                  Cl^- 4 103

       B. Given the above table, what would be the forces working on

          sodium in a typical cell at rest.

             1) Concentration gradient forces

                  there would be a tendency for sodium to diffuse from

                   outside the cell toward the inside

             2) Electrical gradient forces

                    there would be a tendency for sodium to be pulled into

                    the cell

III. The Nernst Potential

       - the potential voltage across a membrane that would prevent net

         diffusion of an ion in either direction

       A. The Nernst Potential for a given ion can be calculated using

            the Nernst Equation

            + 61 mV log₁₀ concentration of a given ion inside the cell

                                     concentration of a the same ion outside the cell

                 When the ion is negative (Cl^-) use + 61 log

                 When the ion is positive (K⁺ or Na⁺) use - 61 log

          Example for Na⁺

                 - 61 mV log₁₀ [10 mEq/L] = 70mV

                                        [142 mEq/L] 

IV. Goldman-Hodgkin-Katz Equation

          - Used to calculate the membrane potential on the inside of the membrane

             when the membrane is permeable to several different ions

                    EMF = - 61 mV log₁₀ C Na(i) + P Na + C K(i) + P K + C Cl(o) + P Cl

                                                       C Na(o) + P Na + C K(o) + P K + C Cl(i) + P Cl

          Where: C = concentration, P = Permeability of the ion

RESTING MEMBRANE POTENTIAL OF NERVES

I. Resting Membrane Potential

    - the membrane potential of a nerve cell when it is not carrying an

      impulse (i.e. resting)

    - Resting membrane potential is usually about -90 mV, that is the

      inside of the nerve cell is 90 mV more negative with respect to

      the fluid surrounding the nerve cell

II. Ion Concentration of Resting Nerve Cells

                                     Concentration (mEq/L)

                 Ion Inside Outside

             Potassium 140 4

             Sodium 14 142

       A) Why this concentration for potassium and sodium?

           1) Sodium-potassium pumps

                - recall pump 3 Na⁺ out for every 2 K⁺ pumped in

           2. The nerve cell membrane is much more permeable to

               K⁺ than to Na⁺, in fact 100X more permeable to K⁺

                - As a result, the K⁺ plays a much larger role in

                  the determination of the membrane resting potential

                     - 61 mV log₁₀ [140 mEq/L] = -94mV

                                             [4 mEq/L]

NERVE ACTION POTENTIALS

I. Nerve action potentials are rapid changes in the membrane potential

   that allows for the transmission of nerve signals (Fig 5-6, p. 56)

II. How Are Nerve Action Potentials Brought About?

      1. A stimulus (neurotransmitter for example) causes the nerve

         membrane to become less negative

      2. at a certain point called threshold (usually between - 70 and

         - 50 mV) a conformational change occurs in the sodium channel

          (Activated State)

      3. this conformational change opens up sodium gates (Fig 5-7, p. 56)

         increasing the permeability of the membrane to sodium by

         500 to 5000 fold (Voltage Gating)

      4. due to the concentration and electrical gradients, sodium comes

         rushing into the cell

      5. the entrance of sodium into the cell causes the inside of the

         cell to become more positive (depolarization) This change

         occurs very rapidly

      6. Once the membrane potential reaches approximates + 35 mV, the

         gates of the sodium channels close (Fig 5-7, p. 62)

      7. Sodium gates will not become activated again until the resting

         membrane potential is nearly back to normal (i.e. must be

         below threshold)

III. How Is The Membrane Potential Returned Back To Resting?

      1. When the membrane potential hits threshold, the potassium

         gates also open but open up much more slowly than do the

         sodium gates (Fig 5-9, p. 57)

      2. The opening of the K⁺ gates allows for the movement of K⁺ out

         of the cell

      3. The decrease in the entry of Na⁺ into the cell and the increase

         of K⁺ out of the cell will make the inside of the cell more

         negative (repolarization)

      4. Not only do the K⁺ gates open slower but also remain open

         longer than do the Na⁺ gates. As a result, the membrane

         potential goes more negative than the resting membrane

         potential (positive afterpotential)

      5. Even though repolarization has taken place and the resting

         membrane potential is back to normal, the ion concentration

         inside the cell is not back to normal.

      6. Sodium-Potassium Pumps work to get the initial concentration

         of these two ions back

IV. Influence of Ion Concentrations on Action Potentials

     A. Hypopolarization

         - occurs when the resting membrane potential moves closer

           to threshold value

         - for example if the resting membrane value is normally - 90mV

           and it becomes less negative and closer to the threshold

           value (-75mV), the membrane is said to be hypopolarized

          1. How does this occur?

               A. a increase in the potassium concentration outside the

                   nerve cell

                       For example

                          - 61 mV + log [140 mEq/L K⁺] = - 75.8mV

                                                   [8 mEq/L K⁺]

                       Recall that the normal Nernst Potential for K⁺

                       was - 94mV. If one finds the difference between

                       the normal Nernst potential and the calculated

                       value, the effect on the membrane potential can

                       be determined

                        - 94mV (normal value) + X = - 75.8mV

                        X = + 18.2mV

                        Recall that normal Resting Membrane Potential was

                        - 90 mV. A increase in potassium surrounding the

                        cell to a value of 8 mEq/L leads to a + 18.2mV

                        change. Thus new resting membrane potential is

                        - 90mV + 18.2mV = - 71.8mV

               B. Hyperpolarization

                    - said to occur when the resting membrane potential

                      becomes even more negative than normal

                    - example is if the normal resting membrane potential

                      where - 90mV then it became more negative, - 110mV

                      the membrane would be hyperpolarized

                    - can result due to a decrease in K⁺ surrounding the

                      cell

IV. Propagation of an Action Potential

     A. All-or-None Principle

         - if the membrane potential does not reach threshold, there

           will be no action potential

         - if the membrane potential does reach threshold, there will

           be an action potential

    B. Direction of Propagation (Fig 5-11, p. 60)

        - an action potential at any point on the membrane will cause

          depolarization of adjacent areas

V. Propagation of an Action Potential: Myelinated v.s. Unmyelinated Axons

     A. Unmyelinated Axons

          - must have ion movements down the entire length of the

            membrane

          - very slow impulse conduction

     B. Myelinated Axons

         - surrounded by multiple layers of membranes consisting of a

           lipid substance called sphingomyelin

         - acts as a very good insulator, preventing the flow of ions

           through the membrane

         - only area where ions can freely flow are at unmyelinated

           areas termed the Nodes of Ranvier

         - myelinated axons use saltatory conduction in which the impulse

           is carried from node to node

         - greatly increases the speed of impulse conduction

VI. Nerve Conduction Velocity

     A. Speed at which an impulse is carried down a nerve depends upon

          1. Myelination

               - myelinated axons conduct nerve impulses much faster

                 than unmyelinated axons

          2. Size

               - larger diameter axons carry impulses much faster than

                 do smaller diameter axons

          3. Examples of the Influence of Myelination and Size

                 - small unmyelinated fibers - 0.5m/sec

                 - large myelinated fibers - 100m/sec

VII. Rhythmicity

      - Self-induced discharge of cells

      - Examples include

          a. heart

          b. smooth muscle - peristalsis

          c. Central Nervous System - rhythmic control of breathing

      A. Processes Necessary for Rhythmicity to Occur

           1. membrane at rest must be more permeable to Na⁺ or Ca⁺⁺

           2. this ensures that the resting membrane potential is

              closer to threshold

           3. once threshold is reached Na⁺ channels open up and Na⁺

              rushes in and an action potential occurs

           4. repolarization occurs slowly due to slow opening and

              closing of K⁺ gates (Fig 5-14, p. 61)

CONTRACTION OF SKELETAL MUSCLE

I. Transmission of a Nerve Impulse to Skeletal Muscle

     - Contraction of skeletal muscle requires a nerve impulse

     A. Neuromuscular Junction (Fig 7-1, p. 81)

          1. Motor end-plate

               - consist of the nerve terminals that invaginate

                 into the muscle fiber

               - the space between the nerve and the muscle membrane

                 is termed the synaptic cleft (Fig 7-1C, p. 81)

               - folds of the muscle membrane are termed subneural

                 synaptic clefts and increase the surface area for

                 neural transmission

     B. Release of Acetylcholine (ACh)

         1. ACh is stored within synaptic vesicles located in the axon

             terminal

         2. as the nerve impulse reaches the nerve terminal, it is thought

that the impulse opens up the gates of Ca⁺⁺ channels (Fig 7-2, p. 81)

         3. Ca⁺⁺ rushes into the axon terminal

         4. Ca⁺⁺ is thought to attract ACh vesicles toward the nerve

            membrane adjacent to the calcium channels

         5. about 300 vesicles fuse to the membrane of the axon terminal

            and release ACh into the synaptic cleft by exocytosis

     C. Effect of ACh on the Skeletal Muscle Membrane

         1. ACh binds to ACh receptors (ligand-gated channels) located

            on the muscle membrane at the subneural clefts (Fig 7-2, p. 81)