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    Learning Objectives: Physiology

    Lecture 1:

    1. Describe the major subdivisions of the body fluids and the approximate percentage oftotal body water, sodium and potassium in each compartment.

    Intracellular fluid (ICF) fluid in cells. Separated from ECF by plasma membrane

    Extracellular fluid (ECF) surrounds the cells, composed of :

    Interstitial fluid (fluid in extracellular spaces between cells)

    Plasma: liquid component of bloodISF and plasma separated by capillary vascular endothelium that

    prevents RBCs and plasma proteins from crossing into ISF

    Luminal Fluid: input and output of body, separated from ECF by epithelium

    TBW: 0.6 x body weight

    ICF: 2/3 of TBW, .4 x body weight

    ECF: 1/3 of TB, 0.2 x body weight

    ISF: of ECF, or .15 x BW

    Plasma: ECF, or 0.05 of BW

    Blood volume = plasma volume times 100%/hematocrit

    Ionic composition

    Inside cell: Na-low, K-high, Cl- low, proteins- high,

    Outside cell: Na- high, K-low, Cl- high, proteins - low

    2. Be able to use the normal concentrations of Na+, K+, Cl-, and HCO3- in extracellularand intracellular fluids to interpret electrolyte disorders, e.g. hyponatremia.

    Electrolyte Plasma

    meq/L

    Interstitial

    meq/L

    Intracellular

    meq/L

    Na+ high:

    145

    high: 145 low: 12

    K+ low: 4 low: 4 high: 150

    Cl- high:

    105

    high: 117 low: 5

    HCO3 - med: 25 med: 27 med: 12

    Protein (-) high: 14 low: 0 high: 54

    -Na and Cl are high in ECF and control 80% of osmolality

    -K high in ICF and control 75% osmolality

    -HCO3- twice as much in ECF

    3. Explain why fixed negative charges on plasma proteins leads to a difference in theconcentrations of anions in plasma water vs interstitial fluid.

    Proteins cant move across the membrane, so the electronic potential is uneven, thus

    ions that can cross the membrane must move to compensate for this charge difference,and in doing so will causes a change in concentration. Proteins tend to be negatively

    charged, so the Cl is lower in plasma than in interstitial fluid

    4. Explain why a change in total amount of NaCl in the body primarily affects theextracellular fluid volume rather than extracellular osmolality when water/drinking is

    not limiting.

    Increase in extracellular NaCl will cause water to diffuse from ICF and water intake to

    balance the ECF. Sodium pump keeps NA in the ECF And ECF becomes hypertonic and

    water is replenished through water increasing the volume but keeping osmolality

    equal

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    5. Explain why a change in concentration of NaCl in extracellular fluids reflects a disorderin water intake or output rather than sodium intake or output.

    Salts do not cross membrane to adjust for changes in salt concentration, thus water

    will move and water intake/output is more important factor for regulation

    When water is gained/lost, NaCl cannot follow without transport and ECF osmolality

    will change

    6. Demonstrate the ability to predict how infusions of: isotonic saline, water, hypotonicand hypertonic fluid affect ICF and ECF volume and osmolality.Hypotonic fluid: water enters LF ECF, water redistributes b/n ECF and ICF to

    maintain equal osmolality (water goes into ICF)

    -ECF vol increases, ECF osmolality decrease, IFC vol incr, ICF osm decreases

    Hypertonic fluid: solutes enter LFwater moves from ICF to ECF

    -ECF vol inc, ECF osm incr, ICF vol dec, ICF osm inc

    Isotonic fluid: no movement of H20

    -ECF vol inc, no change to ECF osm, ICF vol, or ICF osm

    Isotonic fluid loss: throw up, diarrhea

    -ECF vol decreases, no change to ECF osm, ICF vol or ICF osm

    Lecture 2:

    1. Distinguish between net flux and unidirectional fluxNet flux: overall movement of ions that changes their end concentrations

    Unidirectional flux: temporary changes in ion concentration due to ions random

    movement

    Net fluxes move system towards equilibrium, unidirectional fluxes occur randomly

    during equilibrium

    2. Define:Electrochemical potential: total potential energy across membrane, measure of driving

    forces on the ions: 2 sources: electrical potential and chemical potentialElectrochemical equilibrium: state where electrical and chemical driving forces on ions

    are balanced, no net flux across membrane

    Equilibrium potential difference: voltage necessary to prevent any single ion species

    from flowing down its concentrations across a membrane

    Membrane potential: difference in electrical potential between the inside and the

    outside of the cell (Vm = Vinterior Vexterior)

    Conductance: permeability of a membrane to a specific ion, each ion will have its own

    conductance value based on how easily those ions can movement through membrane

    3. Describe how voltage differences across membranes are generated by ion fluxesVoltage differences across membranes are caused by ions moving at different rates. (asthe ions catch up, the voltage difference dissipates to zero)

    Voltage differences attracts an ion across the membrane. SO if a negative voltage is

    generated on one side of the membrane, positive ions will move to that side to bing

    system back to equilibrium

    4. Write the Nernst equation and the chord conductance equation, and use each equationappropriately to calculate equilibrium potentials for Na+, K+, and Cl-, and membrane

    potentials

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    Nernst: purpose is to calculate equilibrium potential for a

    single ion species ata given concentration difference

    Chord: purpose: determine cells resting

    membrane potential based on each of its ions equilibrium potentials

    5. List the major clinical symptoms of cystic fibrosisElevated Na and Cl I n sweat , heat prostration

    Abnormal mucus that causes COPD and pancreatic insufficiency

    Abnormal secretion of digestive enzymes

    Pseudomonas lung infection colonization and infection of airways and lung

    parenchyma

    6. Describe the mechanism of sweat production in sweat glandsSweat is secreted by acinar cells in secretory coil at bottom of the gland. NaCl is

    resorbed by the ductal epithelium by ion channels and pumped into interstitium by

    active transport

    7. Explain the relationship between elevated sweat NaCl in cystic fibrosis and alteredchloride permeability

    8. Defective chloride channel means that:9. Chloride can no longer passively enter the cell from the lumen10.Positive charge builds up in the cell11.Sodium can no longer passively enter the cell from the lumen12.Salt is not reabsorbed and sweat becomes salty.

    Lecture 3:

    1. Categorize the following as either active transport or passive carrier-mediated transport:

    ion pumps, ion channels, facilitated diffusion transporters, sodium-solute cotransporters

    2. Define: CFTR, gating, cardiac glycosides, symport, antiport, electrogenic, isotonic,hypertonic, hypotonic, transcellular pathway, paracellular pathway, apical, basolateral, brush

    border, amiloride, furosemide, DIDS,

    3. What is the most common mutation in CFTR and what are the consequences of that

    mutation for CFTR function?

    4. Explain how the activity of Na-K-ATPase can generate a membrane potential.

    5. List two mechanisms whereby transport of small molecules or ions is regulated in animal

    cells.

    6. Describe three mechanisms that are used by animal cells to maintain a constant

    intracellular volume in response to changes in extracellular osmolarity.

    7. Explain the mechanism whereby Vibrio cholerae causes symptoms of cholera and how

    oral rehydration therapy for cholera works.8. Describe the mechanism of electrolyte and water secretion by secretory epithelia and

    explain how mutations in CFTR affect this mechanism to cause symptoms of cystic fibrosis.

    Lecture 4a

    1. Use the normal value range of the constituents in Table 1 in interpretation of simple clinical

    scenarios

    2. Define feedback regulation and its importance in homeostasis

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    3. Define the main organ systems responsible for rapid and for long term homeostatic

    regulation of each of the following: plasma sodium/volume, plasma potassium, plasma pH,

    plasma osmolality.

    Lecture 4B:

    1. Learn the various buffers in the body that are important in responding to acid-base

    changes, and learn the relative speed of each group of buffers.

    2. Write the Henderson - Hasselbalch equation.3. Explain the unique role of the CO2 - HCO3- system in regulating body fluid pH.

    4. Learn the changes in blood pH, [HCO3-], and PCO2 that occur in the following

    uncompensated acid-base disturbances: metabolic acidosis, metabolic alkalosis, respiratory

    acidosis, respiratory

    alkalosis.

    5. Explain how the kidney compensates for acid-base disturbances induced by the respiratory

    system, and how the respiratory system compensates for metabolic disturbances