Learning Objectives: Physiology Lecture 1: 1.

Describe the major subdivisions of the body fluids and the approximate percentage of total 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 blood ISF 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 extracellular and intracellular fluids to interpret electrolyte disorders, e.g. hyponatremia. Electrolyte Plasma Interstitial Intracellular meq/L meq/L meq/L Na+ high: high: 145 low: 12 145 K+ low: 4 low: 4 high: 150 ClHCO3 Protein (-) high: 105 med: 25 high: 14 high: 117 med: 27 low: 0 low: 5 med: 12 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 the concentrations 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 the extracellular 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

5. Explain why a change in concentration of NaCl in extracellular fluids reflects a disorder in 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, hypotonic and 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 LF water 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 flux Net 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 potential Electrochemical 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 fluxes Voltage differences across membranes are caused by ions moving at different rates. (as the 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 equation appropriately to calculate equilibrium potentials for Na+, K+, and Cl-, and membrane potentials

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 fibrosis Elevated 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 glands Sweat 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 altered chloride permeability 8. Defective chloride channel means that: 9. Chloride can no longer passively enter the cell from the lumen 10. Positive charge builds up in the cell 11. Sodium can no longer passively enter the cell from the lumen 12. 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

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