Physio 5

1. Body Fluids and Transport

2. WaterWater
 Body fluid is composed primarily of waterBody fluid is composed primarily of water
 Water is theWater is the solventsolvent in which all solutes in the body arein which all solutes in the body are
either dissolved or suspendedeither dissolved or suspended
 An average male has 60-63% of his body weight asAn average male has 60-63% of his body weight as
waterwater
 An average female has 45-52%, due to extra body fatAn average female has 45-52%, due to extra body fat
 Infants are 80% water, and this decreases as a childInfants are 80% water, and this decreases as a child
grows until about age 8.grows until about age 8.

3. Key concepts involving waterKey concepts involving water
 Body water is contained in two major bodyBody water is contained in two major body
compartmentscompartments (intracellular fluid compartment and(intracellular fluid compartment and
extracellular fluid compartment)extracellular fluid compartment)
 Fluid balance is maintained when input and output areFluid balance is maintained when input and output are
equalequal
 TheThe primary source of intakeprimary source of intake is water ingestion (eatingis water ingestion (eating
and drinking)and drinking)
 In addition, digestion and metabolism of carbohydrates,In addition, digestion and metabolism of carbohydrates,
proteins, and fats provides another source of intakeproteins, and fats provides another source of intake

4. Key concepts involving waterKey concepts involving water

5. CompartmentsCompartments
 Intracellular fluid (ICF) represents theIntracellular fluid (ICF) represents the fluidfluid
inside the cells and is the largestinside the cells and is the largest compartmentcompartment
(2/3 of body water)(2/3 of body water)
 Extracellular fluid (ECF) represents the fluidExtracellular fluid (ECF) represents the fluid
outside the cells and is 1/3 of total.outside the cells and is 1/3 of total.
 ECF is further divided intoECF is further divided into interstitialinterstitial (ISF) and(ISF) and
is theis the plasma.plasma.

6. ECF divisionsECF divisions
 ISF occupies the space between cells andISF occupies the space between cells and
consists of 15% of total body fluid or ¾ of ECFconsists of 15% of total body fluid or ¾ of ECF
 Plasma is the fluid portion of the blood and isPlasma is the fluid portion of the blood and is
5% of total body fluid or ¼ of ECF5% of total body fluid or ¼ of ECF

7. BODY FLUIDS
ICF ECF
40% TBW 20% TBW
P IS
Distribution of Body Fluids
60-kg man
TBW = 0.6 x 60 kg = 36 L
ICF = 0.4 x 60 kg
= 24 L
ECF
= 12 L
3L 9L

8. Movement of molecule across cell
membrane

9.  The movement of molecules and ions both
between cell organelles and the cytosol and
between cytosol and extracellular fluid depends
on the properties of these membranes
 Impermeable membrane - membrane though which
nothing can pass
 Freely permeable membrane - any substance can pass
through it
 Selectively permeable membrane - permits free passage of
some materials and restricts passage of others
Membrane Transport

10. Simple Diffusion
 The movement of molecules from one location
to another as a result of their random thermal
motion is known as diffusion
 Net movement of particles from area of high
concentration to area of low concentration

11. Membrane Permeability
 Diffusion through lipid bilayer
 Nonpolar, hydrophobic substances diffuse much
more rapidly across plasma membrane
 Diffusion of Ions through channel proteins
 water and charged hydrophilic solutes diffuse
through channel proteins; these are lipid insoluble
substances
 Cells control permeability by regulating number
of channel proteins

12. Major characteristics of diffusion
pathways
Through lipid
Bilayer
Through protein
Channels
Use of integral
membrane protein
No Yes
Typical molecules
using pathway
Nonpolar Ions
Chemical
specificity
No Yes

13. Electric Forces and Ion Movement
 Separation of electric charge across plasma
membrane known as membrane potential
 The direction of ion flux across membranes
depend on:
Concentration difference
Electrical difference
 These two driving forces known as
electrochemical gardient

14. Osmosis
 The net diffusion of water across a membrane is
called osmosis
 Most plasma membrane have permeability to
water.
 A group of membrane protein known as
aquaporins form channel through which water
can diffuse

15. SolutesSolutes
 Substances dissolved in a solution (sugar in your tea)Substances dissolved in a solution (sugar in your tea)
 The addition of solute to water lowers theThe addition of solute to water lowers the
concentration of water in the solutionconcentration of water in the solution
The greater the solute concentration the lower the waterThe greater the solute concentration the lower the water
concentrationconcentration
 It does not depend on chemical natureIt does not depend on chemical nature
 A molecule that ionizes in solution decreases the waterA molecule that ionizes in solution decreases the water
concentration in proportion to the number of ionconcentration in proportion to the number of ion
formed.formed.

16. Osmolarity
 The total concentration of a solution is known
as osmolarity.
 It determine the water concentration in the
solution. Higher osmolarity lower water
concentration.
 Osmotic pressure is the pressure that must be
applied to the solution to prevent net flow of
water.

17.  Isotonic : A solution containing 300 mOsmol/L
of non penetrating solutes,

18. SolutesSolutes
 Substances dissolved in a solution (sugar in your tea)Substances dissolved in a solution (sugar in your tea)
 These may be electrolytes or non-electrolytesThese may be electrolytes or non-electrolytes
 ElectrolytesElectrolytes have anhave an electrical chargeelectrical charge when they arewhen they are
dissolved in waterdissolved in water
 Electrolytes that have aElectrolytes that have a positive chargepositive charge are calledare called
cationscations
 Electrolytes withElectrolytes with negative charge are anionsnegative charge are anions

19. Diffusion Summary
 Diffusion is the movement of molecule from
one location to another by random thermal
motion
The net flux between the two compartments
always proceed from higher to lower
concentration
Diffusion equilibirum is reached when the two
concentration become equal

20.  Nonpolar molecule diffuse rapidly than do polar or
ionized molecules
 Mineral ions diffuse across membranes by passing
through ion channels formed by integral proteins
Diffusion of ions across membrane depends on both
concentration difference and the membrane potential.
The flux of ions across a membrane can be altered by
opening and closing ion channels
Diffusion Summary

21. Osmosis Summary
 Water crosses membranes by (1) diffusion
through lipid by layer and (2) diffusing through
protein channels in the membrane
 Osmosis is the diffusion of water from higher
water concentration to lower water
concentration. Osmolarity total solute
concentration in the solution. The higher
osmolarity of a solution the lower the water
concentration.

22.  Osmosis across membrane permeable to water
but impermeable to solute leads to increase
volume in the compartment that initially had
higher osmolarity.
 Application to a solution of sufficient pressure
will prevent the osmotic flow of water into the
solution from the compartment of pure water.
This pressure is osmotic pressure.
Osmosis Summary

24. Osmolality
 1 osmol solute dissolved in each kg of water

25. Permeable to water,
Not permeable to solutes
Presence of a membrane
Impermeable to solute
That leads to the volume
Changes associated with
Osmosis.

26. Osmotic Pressure
 The greater the osmolarity, the greater its
osmotic pressure.
 The lower the water concentration, the higher
the osmotic pressure.

27. Tonicity
 Describes the behavior of a cell when it is placed
in a solution
 Depends not only on the number of particles in
solution, but also on the NATURE of the solute

28. Tonicity
 Describes the behavior of a cell when it is placed
in a solution
 Depends not only on the number of particles in
solution, but also on the NATURE of the solute

29. Water diffuses inWater diffuses out

30. -osmotic vs. -tonic
 Example: 1L solution containing 300 mOsm of
non-penetrating NaCl and 100 mOsm of urea,
which can cross the membrane would have a
total osmolarity of 400 mOsm and would be
hyperosmotic. However, it would be an isotonic
solution producing no change in the equilibrium
volume of cells immersed in it.

31. Therapies Based on Two Basic
Principles
 Water moves rapidly across cell membranes:
Osmolarities of ICF and ECF remain almost
exactly equal
 Cell membranes are almost completely
impermeable to many solutes: the number of
osmoles in the ECF or ICF remains constant
unless solutes are added or lost from the ECF
compartment

32. Transport, the big picture
fig 4-15

33. Facilitated diffusion (properties)
Passive, carrier mediated
Examples: glucose into most cells (not luminal membrane
of kidney or intestine), urea, some amino acids
Kinetics:
shows: passive shows: carrier mediated

34. Non-mediated vs. mediated transport
fig 4-9

35. Primary active transport (Na+
/K+
ATPase pump)
3 Na+
’s out, 2 K+
’s in, 1 ATP hydrolyzed
fig 4-11

36. Primary active transport (Na+
/K+
ATPase pump)
3 Na+
’s out, 2 K+
’s in, 1 ATP hydrolyzed
fig 4-11

37. Primary active transport kinetics
shows active transport shows carrier mediated

38. Effect of Na+
/K+
ATPase pump
fig 4-12

39. Secondary active transport
fig 4-13

40. Secondary active transport properties
Active (energy from ion gradient, usually Na+
)
Carrier mediated
Can be cotransport (symport) or countertransport (antiport)
Examples (many):
Na+
/amino acids, Na+
/glucose (luminal membrane kidney,
GI tract), *Na+
/H+
kidney, *Ca++
/3Na+
muscle,
*Cl-
/HCO3
-
red cell. (* = countertransport)
Kinetics
see primary active transport graphs

41. Sodium Reabsorption: Primary ActiveSodium Reabsorption: Primary Active
TransportTransport
 SodiumSodium reabsorption is almost always byreabsorption is almost always by active transportactive transport
 NaNa++
enters the tubule cells at the luminal membraneenters the tubule cells at the luminal membrane
 Is actively transported out of the tubules by aIs actively transported out of the tubules by a
NaNa++
-K-K++
ATPase pumpATPase pump
 From there it moves to peritubular capillaries due to:From there it moves to peritubular capillaries due to:
 Low hydrostatic pressureLow hydrostatic pressure
 High osmotic pressure of the bloodHigh osmotic pressure of the blood
 NaNa++
reabsorption provides the energy and the means for reabsorbingreabsorption provides the energy and the means for reabsorbing
most other solutesmost other solutes

42. Electrolytes-SodiumElectrolytes-Sodium
 MajorMajor cation in ECFcation in ECF (positively charged)(positively charged)
 Responsible forResponsible for 90-9590-95% of extracellular osmotic% of extracellular osmotic
pressurepressure
 Regulated byRegulated by aldosterone and the kidneysaldosterone and the kidneys
 Increases sodium reabsorption in DCT of nephronIncreases sodium reabsorption in DCT of nephron
 Also regulates K+ (secretion)Also regulates K+ (secretion)
 Normal serum concentration in ECF rangesNormal serum concentration in ECF ranges
from 135-146 mEq/Lfrom 135-146 mEq/L

43. Sodium FunctionsSodium Functions
 Sodium maintains ECF osmolality, ECF volume,Sodium maintains ECF osmolality, ECF volume,
andand influences water distributioninfluences water distribution (where salt(where salt
goes water follows)goes water follows)
 It affects the concentration, secretion, andIt affects the concentration, secretion, and
adsorption of potassium and chloride ions, andadsorption of potassium and chloride ions, and
can combine with bicarbonate ions and chloridecan combine with bicarbonate ions and chloride
ions to help regulate acid/base balanceions to help regulate acid/base balance
 It also help aid the impulse transmission ofIt also help aid the impulse transmission of
nerve and muscle fibersnerve and muscle fibers

44. Sodium Recycling: Recycling andSodium Recycling: Recycling and
ExcretionExcretion
 Ascending loop of HenleAscending loop of Henle
 HH22O impermeableO impermeable
 NaNa++
Active TransportActive Transport
 To ECFTo ECF
 GradientGradient
 Diffuses to bloodDiffuses to blood
 Collecting Duct:Collecting Duct:
 Aldosterone regulatesAldosterone regulates
 NaNa++
recycled or excretedrecycled or excreted

45.  Aldosterone: steroid H from adrenal cortexAldosterone: steroid H from adrenal cortex
 Stimulates NaStimulates Na++
uptake (& Kuptake (& K++
secretion)secretion)
 ↑↑ channel synthesischannel synthesis
Mechanism of NaMechanism of Na++
Selective Reabsorption inSelective Reabsorption in
Collecting DuctCollecting Duct

46. Mechanism of NaMechanism of Na++
Selective Reabsorption inSelective Reabsorption in
Collecting DuctCollecting Duct
Figure 20-12: Aldosterone action in principal cells

47. ImbalancesImbalances
 HyponatremiaHyponatremia (less than 130 mEq/L)-low sodium(less than 130 mEq/L)-low sodium
level-may cause seizures, headache, tachycardia,level-may cause seizures, headache, tachycardia,
hypotension, cramps, muscle twitching, irritability,hypotension, cramps, muscle twitching, irritability,
decreased body temp, nausea, vomiting, and possibledecreased body temp, nausea, vomiting, and possible
coma (polyuria due to diabetes insipidis may be onecoma (polyuria due to diabetes insipidis may be one
cause),cause),
 HypernatremiaHypernatremia (more than 150 mEq/L) -high sodium(more than 150 mEq/L) -high sodium
level-usually indicates water deficit in ECF-symptomslevel-usually indicates water deficit in ECF-symptoms
include thirst, tachycardia, dry sticky tongue,include thirst, tachycardia, dry sticky tongue,
disorientation, hallucination, lethargy, seizures, coma,disorientation, hallucination, lethargy, seizures, coma,
hypotension, agitation, low feverhypotension, agitation, low fever

48. Artial Natruretic Peptide: Regulates NaArtial Natruretic Peptide: Regulates Na++
& H2O& H2O
ExcretionExcretion
 Hormone from myocardial cellsHormone from myocardial cells
 Stimulates: hypothalamus, kidney, adrenal, &Stimulates: hypothalamus, kidney, adrenal, &
medullamedulla

49. Artial Natruretic Peptide: Regulates NaArtial Natruretic Peptide: Regulates Na++
& H& H22OO
ExcretionExcretion
Figure 20-15: Atrial natriuretic peptide

50. Potassium Balance:Potassium Balance:
Critical for Excitable Heart & Nervous TissuesCritical for Excitable Heart & Nervous Tissues
 Hypokalemia – low [KHypokalemia – low [K++
] in ECF, Hyperkalemia] in ECF, Hyperkalemia
- high [K- high [K++
]]
 Reabsorbed in Ascending Loop, secreted inReabsorbed in Ascending Loop, secreted in
Collecting ductCollecting duct

51. Potassium Balance:Potassium Balance:
Critical for Excitable Heart & Nervous TissuesCritical for Excitable Heart & Nervous Tissues
Figure 20-4: Osmolarity changes as fluid flows through the nephron

52. Potassium Balance:Potassium Balance:
Critical for Excitable Heart & Nervous TissuesCritical for Excitable Heart & Nervous Tissues
Figure 20-12: Aldosterone action in principal cells

53.  Thirst & "salt craving", or avoidance behaviorThirst & "salt craving", or avoidance behavior
 Integrated circulatory & excretory reflexesIntegrated circulatory & excretory reflexes
Response to Dehydration & OsmolarityResponse to Dehydration & Osmolarity
ImbalanceImbalance

54. Response to Dehydration & OsmolarityResponse to Dehydration & Osmolarity
ImbalanceImbalance

55.  Acidosis:Acidosis: ↓↓ plasma pHplasma pH
 Protein damageProtein damage
 CNS depressionCNS depression
 Alkalosis:Alkalosis: ↑↑ plasma pHplasma pH
 HyperexcitabilityHyperexcitability
 CNS & heartCNS & heart
 Buffers: HCOBuffers: HCO33
--
& proteins& proteins
 HH++
input: diet & metabolicinput: diet & metabolic
 HH++
output: lungs & kidneyoutput: lungs & kidney
Acid/Base Homeostasis: OverviewAcid/Base Homeostasis: Overview

56. Acid/Base BalanceAcid/Base Balance
 Homeostasis of hydrogen ion contentHomeostasis of hydrogen ion content
 Body fluids are classified as either acids or basesBody fluids are classified as either acids or bases
depending on H ion concentrationdepending on H ion concentration
 Acid is an H donorAcid is an H donor and elevates the hydrogen ionand elevates the hydrogen ion
content of the solution to which it is addedcontent of the solution to which it is added
 Base is an H acceptorBase is an H acceptor and can bind hydrogen ionsand can bind hydrogen ions
 Concentration is expressed asConcentration is expressed as pHpH
 Normal pH of blood is 7.35-7.45Normal pH of blood is 7.35-7.45 (alkaline)(alkaline)
 pH below 6.8 or above 7.8 is incompatible with lifepH below 6.8 or above 7.8 is incompatible with life

57. AcidsAcids
 During the process of cellular metabolism acids areDuring the process of cellular metabolism acids are
continually being formed and excess hydrogen ionscontinually being formed and excess hydrogen ions
must be eliminatedmust be eliminated
 There are two types of acids formed: volatile acids areThere are two types of acids formed: volatile acids are
excreted by the lungs and nonvolatile acids are excretedexcreted by the lungs and nonvolatile acids are excreted
by the kidneyby the kidney
 Volatile acids can be excreted from the body as gas.Volatile acids can be excreted from the body as gas.
Carbonic acid produced by the hydration of carbonCarbonic acid produced by the hydration of carbon
dioxidedioxide is a volatile acidis a volatile acid
 Normally carbon dioxide is excreted by the lungs as fastNormally carbon dioxide is excreted by the lungs as fast
as metabolism produces it, so carbonic acid isas metabolism produces it, so carbonic acid is notnot
allowed to accumulateallowed to accumulate and alter pHand alter pH

58. Non-volatile acidsNon-volatile acids
 Cannot be eliminated by the lungs and must beCannot be eliminated by the lungs and must be
eliminated by the kidneyseliminated by the kidneys
 All metabolic acids except carbolic are non-All metabolic acids except carbolic are non-
volatile acidsvolatile acids
 These include sulfuric acid, phosphoric acid,These include sulfuric acid, phosphoric acid,
lactic acid, ketoacids like acetoacetic acid andlactic acid, ketoacids like acetoacetic acid and
beta hydroxybutyric acid, and small amounts ofbeta hydroxybutyric acid, and small amounts of
other inorganic and organic acidsother inorganic and organic acids

59. Regulation of pHRegulation of pH
 Three methods control pHThree methods control pH
 1.1. chemical buffers-whenchemical buffers-when Hydrogen is removedHydrogen is removed
a buffer replaces ita buffer replaces it
 2.2. regulation of carbon dioxideregulation of carbon dioxide by respiratoryby respiratory
systemsystem
 3.3. regulation of plasma bicarbonateregulation of plasma bicarbonate
concentration by the kidneys-slower, secondconcentration by the kidneys-slower, second
line of defenseline of defense

60. Chemical buffersChemical buffers
 These areThese are the first line of defensethe first line of defense againstagainst
changes in pHchanges in pH
 Act within a fraction of a second forAct within a fraction of a second for immediateimmediate
defensedefense against H+ shiftagainst H+ shift
 These are a mixture of 2 or more chemicals thatThese are a mixture of 2 or more chemicals that
minimize changes in pHminimize changes in pH
 Convert strong acids into weak acids and strongConvert strong acids into weak acids and strong
bases into weak basesbases into weak bases

61. Buffers continuedBuffers continued
 Carbonic acid-bicarbonate system isCarbonic acid-bicarbonate system is most importantmost important
extracellular bufferextracellular buffer because it can be regulated by bothbecause it can be regulated by both
lungs and kidneyslungs and kidneys
 Carbonic acid/bicarbonate ratio is usually 1:20Carbonic acid/bicarbonate ratio is usually 1:20
 COCO22 + H+ H22O↔HO↔H22 COCO33 ↔H↔H++
+ HCO+ HCO33
--
 Phosphates act as a buffer like the bicarbonate systemPhosphates act as a buffer like the bicarbonate system
does and protein buffers are the most abundant buffersdoes and protein buffers are the most abundant buffers
in body cells and bloodin body cells and blood

62. Regulation of pH through kidneysRegulation of pH through kidneys
 Tubular secretion of H+ from convoluted tubules andTubular secretion of H+ from convoluted tubules and
collecting ducts so extra is excreted in urinecollecting ducts so extra is excreted in urine
 Helps regulate sulfuric acid and phosphoric acid, andHelps regulate sulfuric acid and phosphoric acid, and
other organic acids in body fluids as a result ofother organic acids in body fluids as a result of
metabolismmetabolism
 Diets high in protein generate more acid, so kidneysDiets high in protein generate more acid, so kidneys
respond by secreting more hydrogen ion. (Atkins Diet)respond by secreting more hydrogen ion. (Atkins Diet)
 In urine, hydrogen ion is buffered by phosphate andIn urine, hydrogen ion is buffered by phosphate and
ammoniaammonia

63. Acid/Base Homeostasis: OverviewAcid/Base Homeostasis: Overview
Figure 20-18: Hydrogen balance in the body

64.  HH++
& NH& NH44
++
secreted into lumen and excretedsecreted into lumen and excreted
 HCOHCO33
--
is reabsorbedis reabsorbed
Kidney Hydrogen Ion Balancing: ProximalKidney Hydrogen Ion Balancing: Proximal
TubuleTubule

65. Kidney Hydrogen Ion Balancing: Proximal TubuleKidney Hydrogen Ion Balancing: Proximal Tubule
Figure 20-21: Proximal tubule secretion and reabsorption of filtered HCO3
-

66.  Type A Intercalated cells excrete HType A Intercalated cells excrete H++
absorb HCOabsorb HCO33
--
 Type B intercalated cells absorb HType B intercalated cells absorb H++
secrete HCOsecrete HCO33
--
Kidney Hydrogen Ion Balancing: CollectingKidney Hydrogen Ion Balancing: Collecting
DuctDuct

67. Kidney Hydrogen Ion Balancing: CollectingKidney Hydrogen Ion Balancing: Collecting
DuctDuct
Figure 20-22: Role of the intercalated cell in acidosis and alkalosis

68. AmmoniaAmmonia
 Ammonia (NH3) is a weak base produced inAmmonia (NH3) is a weak base produced in
cells of renal tubule by removal of amine groupcells of renal tubule by removal of amine group
from some amino acidsfrom some amino acids (deamination)(deamination)
 It diffuses into the tubule and accepts hydrogenIt diffuses into the tubule and accepts hydrogen
ions to become NH4+ which is trapped in theions to become NH4+ which is trapped in the
tubule and excretedtubule and excreted

69. SummarySummary
 Electrolyte balance depends on integration of circulatory,Electrolyte balance depends on integration of circulatory,
excretory and behavioral physiologyexcretory and behavioral physiology
 Water recycling and ECF/plasma balance depends onWater recycling and ECF/plasma balance depends on
descending loop of Henle and vasopressin regulateddescending loop of Henle and vasopressin regulated
collecting duct for conservationcollecting duct for conservation
 Osmolarity depends on aldosterone and angiotensin pathwayOsmolarity depends on aldosterone and angiotensin pathway
to regulate CNS & endocrine responsesto regulate CNS & endocrine responses
 Along with respiration, proximal tubule and collecting ductAlong with respiration, proximal tubule and collecting duct
cells reabsorb or excrete Hcells reabsorb or excrete H++
& HCO& HCO33
--
to balance pHto balance pH