physiology - bs

8/13/2019 Physiology - BS

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Compartmentalization of Fluids

1. Describe the major subdivisions of the body fluids and theapproximate percentage of total body water, sodium and potassium in

each compartment.

TBW (total body water) = Body weight x .6ECF = 2/3 TBW

ICF = 1/3 TBW

Isotonic saline = 0.9% = 0.9 gms NaCl/100 ml


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= 9 gms NaCl/liter

(9 gms NaCl/L) (58 gms/mole NaCl) = 0.155 M NaCl

155 mM NaCl1M NaCl dissociates into 1.87 Osm

(not into 2 Osm because a small fraction is undissociated in solution asNaCl)

155 mM x 1.87 is ~ 290 mOsm

2. Be able to use the normal concentrations of Na+, K+, Cl-, and

HCO3- in extracellular and intracellular fluids to interpret electrolyte

disorders.-Hyponeutremia: lots of water, not any food-Cholera:

3. Explain why fixed negative charges on plasma proteins leads to a

difference in the concentrations of anions in plasma water vsinterstitial fluid.

- Because Plasma proteins are very negative (average 14 meq/L), butcant cross capillary epithelium, they force cations


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4. Explain why a change in total amount of NaCl in the bodyprimarily affects the extracellular fluid volume rather than extracellular

osmolality when water/drinking is not limiting.

- Water follows ions and will maintain osmolality across themembrane. So a sodium pump deficiency (i.e. dysfunctional CFTR)results in deficiency.

5. Explain why a change in concentration of NaCl in extracellular

fluids reflects a disorder in water intake or output rather than sodiumintake or output.

If there is elevated NaCl intake, thirst will accompany and the [NaCl]

will normalize.

Someone would have to drink lots of fluids without salt/food fluids tolower [NaCl] - this happens with alcoholics who don't eat food/salt

sometimes.Since water movement will equilibrate osmolality between ICF and ECF

elevated or depressed [NaCl] indicates either not enough (person inthe desert question) or too much fluid (beer).

Finally, I didn't give you enough info to address the "why" but basicallyit pertains to the thirst response or access to water.


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6. Demonstrate the ability to predict how infusions of: isotonic

saline, water, hypotonic and hypertonic fluid affect ICF and ECFvolume and osmolality.

- See problem set

Cinitialx Vinitial(+/-) Cchange X Vchange = Cfinal X Vfinal


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Ionic Equilibria and Membrane Potential

1. Distinguish between net flux and unidirectional flux

JABor JBA are unidirectional fluxes

Net flux: Sum of unidirectional flux

Unidirectional fluxes exist when Net Flux is zero

2. Define: electrochemical potential, electrochemical equilibrium,equilibrium potential difference, membrane potential, conductance

Electrochemical Potential: Chemical potential (dependent onconcentration) + Electrical potential (dependent on charge of electrical

field)Electrochemical Equilibrium: When the net forces of concentration

differences and voltage differences are of equal magnitude, but ofopposite direction

Equilibrium Potential: The voltage difference that prevents themovement of an ion down a concentration gradient


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-Ion specific

- Nernst Equation

RT/ F = 25 for ln, 60 for log

Membrane Potential:Weighted average of the equilibrium potential

of all the ions across a membrane

- Chord Conductance equation

Conductance: The rate of travel of an ion across a membrane

The total conductance (g) of the membrane for any ion is equal to thenumber of channels (N) times the single channel conductance (),

times the probability that the channel is open (Po):

g = NPo

3. Describe how voltage differences across membranes are generatedby ion fluxes

- Ions moving at different rates cause voltage differences

4.Write the Nernst equation and the chord conductance equation, and

use each equation appropriately to calculate equilibrium potentials forNa+, K+, and Cl-, and membrane potentials

5. List the major clinical symptoms of cystic fibrosis:

- Mechanism: defect in CFTR (Cystic Fibrosis TransmembraneConductance Regulator)

Sweat: Salty SweatPancreas: Decrease Pancreatic Enzymes

Lungs: Thick, dehydrated mucosal lining Pseudimonas Aeruginosa

infection


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6. Describe the mechanism of sweat production in sweat glands- Primary sweat is secreted by Acinar cells in secretory coil of duct

(bottom of sweat gland)- ion reabsorption in epithelial cells of resportive duct reduces

osmolality of sweat Cl-absorbed through CFTR pulls NA+through channels (to

maintain electrical equilibrium.7. Explain the relationship between elevated sweat NaCl in cysticfibrosis and altered chloride permeability

- CFTR deficiency reduces chloride permeability in the membrane.


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Membrane Transport Mechanisms

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

ion pumps: Activeion channels: passive-carrier mediated

facilitated diffusion transporters: passive-carrier mediatedsodium-solute cotransporters: Active

2. Define:CFTR:Cystice Fibrosis Transmembrane Conductance Regulator: Cl

passive ligand-gated transport protein channelGating: mechanism for controlling activation of channel in membrane(ligand vs voltage gating)cardiac glycosides: ouabain and digitalis: stabilizes E2-P transition

state of NA,K-ATPase end result is Ca buildup in cytoplasm increased muscle contraction

symport: Na transport down gradient coupled to brings molecule intocell

Na, glucose symporterAntiport: Na transport down gradient coupled to extruding moleculefrom cell (ex/ Na, H antiporter on apical face of epithelium)

Electrogenic:contributes to the membrane potential Ex/ Na,K ATPase

IsotonicHypertonic

Hypotonictranscellular pathway: Passes through cell, through apical and

basolateral membranesparacellular pathway: Passes through tight junction

apicalbasolateralbrush border:microvilli coated surface apical membrane of

intestinesamiloride: Sodium channel inhibitor (also Na/antiporter)

CF treatmentFurosemide:inhibits Na,K,2Cl-symporterDIDS: Inhibits Cl,HCO3

-antiporter

3. What is the most common mutation in CFTR and what are theconsequences of that mutation for CFTR function?

- delta508 loss of phenylalanine


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AA deletion causes CFTR to get stuck in ER, never reachesmembrane

4. Explain how the activity of Na,K-ATPase can generate a membranepotential.

- The difference in stoichiometry of Na/K transport (3 + out, 2+ in)contributes to a negative membrane potential inside the cell

5. List two mechanisms whereby transport of small molecules or ionsis regulated in animal cells.1) Modification of transcription and translation rates

2) Posttranslational modification: phosphorylation

Ex/ CFTR3) Insertion into and removal from the plasma membrane- Recruitment of GLUT4 (glucose channel) to membrane due to insulin

4) Reversible binding of regulatory molecules

Ex/ Lingand gated

6. Describe three mechanisms that are used by animal cells tomaintain a constant intracellular volume in response to changes in

extracellular osmolarity.1) Hypotonic medium: Cell activates K channels (Cl follows) which

move down their gradient-Bring water with them, shrinking cell

2) Hypertonic medium: Cell activates Na channels (Cl follows) whichmoves into the cell

- Water follows and cell swells3) Na,K-ATPase

7. Explain the mechanism whereby Vibrio cholerae causes symptoms

of cholera and how oral rehydration therapy for cholera works.

In this disease the bacterium Vibrio cholerae invades the GI tract andsecretes a protein toxin called cholera toxin. The toxin inhibits theNa/H antiporter in intestinal villus cells and activates chloride effluxthrough chloride channels in the crypt cells. The net reduction of NaCl

absorption and increase in Cl- secretion leads to diarrhea and loss of

fluids and electrolytes.

Oral Rehydration therapy:Uses a sugar, salt solution to create a

glucose chemical gradient that pulls sodium into the cell through theNa,Glucose-symporter. It gives the body time to fight the infection


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8. Describe the mechanism of electrolyte and water secretion by

secretory epithelia and explain how mutations in CFTR affect thismechanism to cause symptoms of cystic fibrosis.

- See answer in Ionic Equilibria


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Acid Base Homeostasis: Maintaining Homeostasis + Acid-Base Balance

I. Maintaining Homeostasis Objectives

1. Use the normal value range of the constituents in Table 1 in interpretation of simpleclinical scenarios

a.b. Simple clinical scenarios (see question 3)

2. Define feedback regulation and its importance in homeostasisa. Feedback regulation= controller. Aka, a mechanism that uses the results of a

process to regulate the rate at which the process occurs

i. InputPlantOutputController

ii. Input example: brain senses thirst, vasopressin releasediii. Plant: kidneys, where vasopressin acts (In general, a plant accepts an

input and makes it an output)

iv. Output: low volume high osmolality urine produced NOTE: For thislecture, ECF constituents= output

v. Controller: kidneys, which no longer stimulated NOTE: For this lecture,nervous and hormonal systems that act on a plant to regain

homeostasis

b. Importance to homeostasis: feedback control is responsible for specific normalranges of ions, amongst other important functions in the body that keep us alive

3. Define the main organ systems responsible for rapidand for longterm homeostaticregulation of each of the following: plasma sodium/volume, plasma potassium, plasma

pH, plasma osmolality (For efficacy, I have combined objective 1 in here, regarding

simple clinical scenarios)

a. Rapid response in homeostasis (this fuses with the next lecture on acids andbases)

i. ECF buffering: bicarbonate, proteins, etc. (fastest)ii. IF buffering: bone, protein, organic and inorganic phosphates (2ndfastest)

b. Long term homeostasisi. Respiratory compensation (in minutes, not seconds, so its not really

long term, but its not the mere seconds of the previous two)

ii. Renal adjustment: takes days to reach full efficacy


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Molecule

& in ECF

Which organ

systems at work

Homeostatic Regulation Pathway What Clinical

Scenario is

this?/ Range

Na+ Cardiovascular

system (to sense

changes), renal,brain (thirst

response)

Atria stretch receptors release atrial natriuretic

peptideinhibit renal Na+ and volume

reabsorptionincreased output (slow)

ORDietary Na+ sensed in GI tractfactors

releasedincrease urine Na+ excretion (fast)

Hypernatremia

>146 mM

Na+ Cardiovascular

system (to sense

changes), renal,

brain (thirst

response)

Cardiovascular stretch receptors and

baroreceptors sense decreased Na+

Hyponatremia

5 mM

K+ Muscle and renal Increased renal K+ reabsorption and transfer of

K+ out of muscle ICF into the ECF (slow)

Hypokalemia


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Acid-Base Balance Objectives

1. Learn the various buffers in the body that are important in responding to acid-basechanges, and learn the relative speed of each group of buffers

a.

Fastest (seconds): ECF buffersi. HCO3-, via HCL+ NaHCO3NaCl + H2CO3H2O + CO2ii. Plasma proteins

iii. Inorganic phosphateiv. Amino acids, etc.

b. 2ndfastest (seconds to minutes): ICF buffersi. bone- up to 40% of the acid load

ii. proteinsiii. organic and inorganic phosphates

c. 3rdfastest (minutes to hours): Respiration ratei. controlled by nerves that sense pH and CO2

d. 4thfastest (hours to days): Renal adjustmenti. started in minutes but full effectiveness is not until several days

ii. due to renal gene expression change2. Write the Henderson-Hasselbach equation:

there it is.

3. Explain the unique role of the CO2- HCO3- system in regulating body fluid pH

a. CO2 + H2O H2CO3 HCO3-+ H+

b. why is this is a good bufferi. [HCO3-] is in great quantity

ii. CO2and HCO3- are well regulated by respiration and renal systems

iii. CO2is volatile, so it readily leaves the body

iv. HCO3- is easily removed via renal system or absorbed back

c. Conclusion: pH can be quickly and easily be regulated using the above buffer system

4. Learn the changes in blood pH, [HCO3-], and Pco2 that occur in the followinguncompensated acid-base disturbances: metabolic acidosis, metabolic alkalosis,

respiratory acidosis, respiratory alkalosis

a. Acidosis and alkalosis: interplay of respiratory and renal (metabolic) regulationof CO2and HCO3-

b. This is different from acidemia and alkalemia, which is the term describing thepH in blood and does not describe whether respiration or metabolism resultedin the academia or alkalemia


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c.d. Patterns to help remember this stuff

i. metabolic acidosis/alkalosis is compensated via respiration regulation,and vice versa

ii. if [HCO3-] is disturbed, it is compensated by PCO2, and vice versa5. Explain how the kidney compensates for acid-base disturbances induced by the

respiratory system, and how the respiratory system compensates for metabolic

disturbances

a. Respiratory acidosis- caused by hypoventilation or lung diseases that decreaserespiration rate

i. Kidneys secrete and excrete H+b. Respiratory alkalosis-caused by hyperventilation, hypoxia, pain, or hysteria

i. Kidney will attempt to hold onto HCO3c. Metabolic acidosis- caused by diarrhea, diabetes, renal failure

i. Lungs will reduce pCO2breath fasterd. Metabolic alkalosis- caused by ingestion of strong base or loss of acid (vomiting)

i. Reduced breathing

Disorder pH [H+] primary

disturbance

compensatory response

metabolic acidosis plasma[HCO3-] PCO2, respiratory

metabolic alkalosis plasma[HCO3-] PCO2, respiratory

respiratory acidosis PCO2 [HCO3-], renal production

respiratory alkalosis PCO2 [HCO3-], renal loss

physiology - bs

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