Body Fluids and Transport

WaterWater

Body fluid is composed primarily of waterBody fluid is composed primarily of water Water is the Water is the solvent solvent in which all solutes in in which all solutes in

the body are either dissolved or the body are either dissolved or suspendedsuspended

An average male has 60-63% of his body An average male has 60-63% of his body weight as waterweight as water

An average female has 45-52%, due to An average female has 45-52%, due to extra body fatextra body fat

Infants are 80% water, and this decreases Infants are 80% water, and this decreases as a child grows until about age 8.as a child grows until about age 8.

Key concepts involving Key concepts involving waterwater

Body water is contained in two major body Body water is contained in two major body compartments compartments (intracellular fluid (intracellular fluid compartment and extracellular fluid compartment and extracellular fluid compartment)compartment)

Fluid balance is maintained when input and Fluid balance is maintained when input and output are equaloutput are equal

The The primary source of intakeprimary source of intake is water is water ingestion (eating and drinking) ingestion (eating and drinking)

In addition, digestion and metabolism of In addition, digestion and metabolism of carbohydrates, proteins, and fats provides carbohydrates, proteins, and fats provides another source of intake another source of intake

Key concepts involving Key concepts involving waterwater

CompartmentsCompartments

Intracellular fluid (ICF) represents Intracellular fluid (ICF) represents the the fluid inside the cells and is the fluid inside the cells and is the largestlargest compartment (2/3 of body compartment (2/3 of body water)water)

Extracellular fluid (ECF) represents Extracellular fluid (ECF) represents the fluid outside the cells and is 1/3 the fluid outside the cells and is 1/3 of total.of total.

ECF is further divided into ECF is further divided into interstitialinterstitial (ISF) and is the (ISF) and is the plasma. plasma.

ECF divisionsECF divisions

ISF occupies the space between ISF occupies the space between cells and consists of 15% of total cells and consists of 15% of total body fluid or ¾ of ECFbody fluid or ¾ of ECF

Plasma is the fluid portion of the Plasma is the fluid portion of the blood and is 5% of total body fluid or blood and is 5% of total body fluid or ¼ of ECF¼ of ECF

BODY FLUIDS

ICF ECF

40% TBW 20% TBW

P IS

Distribution of Body Fluids

60-kg manTBW = 0.6 x 60 kg = 36 L

ICF = 0.4 x 60 kg = 24 L

ECF = 12 L

3L 9L

Movement of molecule across cell membrane

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

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

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

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

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 differenceElectrical difference These two driving forces known as

electrochemical gardient

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

SolutesSolutes

Substances dissolved in a solution (sugar Substances dissolved in a solution (sugar in your tea)in your tea)

The addition of solute to water lowers the The addition of solute to water lowers the concentration of water in the solutionconcentration of water in the solution

The greater the solute concentration the The greater the solute concentration the lower the water concentrationlower the water concentration

It does not depend on chemical natureIt does not depend on chemical nature A molecule that ionizes in solution A molecule that ionizes in solution

decreases the water concentration in decreases the water concentration in proportion to the number of ion formed. proportion to the number of ion formed.

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.

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

SolutesSolutes

Substances dissolved in a solution (sugar Substances dissolved in a solution (sugar in your tea)in your tea)

These may be electrolytes or non-These may be electrolytes or non-electrolyteselectrolytes

ElectrolytesElectrolytes have an have an electrical chargeelectrical charge when they are dissolved in water when they are dissolved in water

Electrolytes that have a Electrolytes that have a positive chargepositive charge are called are called cations cations

Electrolytes with Electrolytes with negative charge are negative charge are anionsanions

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

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

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.

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

Osmolality

1 osmol solute dissolved in each kg of water

Permeable to water,Not permeable to solutes

Presence of a membraneImpermeable to soluteThat leads to the volumeChanges associated withOsmosis.

Osmotic Pressure

The greater the osmolarity, the greater its osmotic pressure.

The lower the water concentration, the higher the osmotic pressure.

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

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

Water diffuses inWater diffuses out

-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.

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

Transport, the big picture

fig 4-15

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

Non-mediated vs. mediated transport

fig 4-9

Primary active transport (Na+/K+ ATPase pump)3 Na+’s out, 2 K+’s in, 1 ATP hydrolyzed

fig 4-11

Primary active transport (Na+/K+ ATPase pump)3 Na+’s out, 2 K+’s in, 1 ATP hydrolyzed

fig 4-11

Primary active transport kinetics

shows active transport shows carrier mediated

Effect of Na+/K+ ATPase pump

fig 4-12

Secondary active transport

fig 4-13

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)

Kineticssee primary active transport graphs

Sodium Reabsorption: Primary Active Sodium Reabsorption: Primary Active TransportTransport

Sodium Sodium reabsorption is almost always by reabsorption is almost always by active active transporttransport NaNa++ enters the tubule cells at the luminal enters the tubule cells at the luminal

membranemembrane Is actively transported out of the tubules by a Is actively transported out of the tubules by a

NaNa++-K-K++ ATPase pump ATPase 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 reabsorption provides the energy and the means for reabsorbing most other solutesfor reabsorbing most other solutes

Electrolytes-SodiumElectrolytes-Sodium Major Major cation in ECFcation in ECF (positively charged)(positively charged) Responsible for Responsible for 90-9590-95% of extracellular % of extracellular

osmotic pressureosmotic pressure Regulated by Regulated by aldosterone and the aldosterone and the

kidneyskidneys Increases sodium reabsorption in DCT of Increases sodium reabsorption in DCT of

nephronnephron Also regulates K+ (secretion)Also regulates K+ (secretion)

Normal serum concentration in ECF Normal serum concentration in ECF ranges from 135-146 mEq/Lranges from 135-146 mEq/L

Sodium FunctionsSodium Functions

Sodium maintains ECF osmolality, ECF Sodium maintains ECF osmolality, ECF volume, and volume, and influences water influences water distributiondistribution (where salt goes water (where salt goes water follows)follows)

It affects the concentration, secretion, It affects the concentration, secretion, and adsorption of potassium and and adsorption of potassium and chloride ions, and can combine with chloride ions, and can combine with bicarbonate ions and chloride ions to bicarbonate ions and chloride ions to help regulate acid/base balancehelp regulate acid/base balance

It also help aid the impulse It also help aid the impulse transmission of nerve and muscle fiberstransmission of nerve and muscle fibers

Sodium Recycling: Sodium Recycling: Recycling and ExcretionRecycling and Excretion

Ascending loop of HenleAscending loop of Henle HH22O impermeableO impermeable NaNa++ Active Transport Active Transport

To ECF To ECF GradientGradient Diffuses to bloodDiffuses to blood

Collecting Duct:Collecting Duct: Aldosterone regulatesAldosterone regulates NaNa++ recycled or excreted recycled or excreted

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 Selective Reabsorption in Collecting DuctReabsorption in Collecting Duct

Mechanism of NaMechanism of Na++ Selective Selective Reabsorption in Collecting DuctReabsorption in Collecting Duct

Figure 20-12: Aldosterone action in principal cells

ImbalancesImbalances Hyponatremia Hyponatremia (less than 130 mEq/L)-low (less than 130 mEq/L)-low

sodium level-may cause seizures, headache, sodium level-may cause seizures, headache, tachycardia, hypotension, cramps, muscle tachycardia, hypotension, cramps, muscle twitching, irritability, decreased body temp, twitching, irritability, decreased body temp, nausea, vomiting, and possible coma nausea, vomiting, and possible coma (polyuria due to diabetes insipidis may be (polyuria due to diabetes insipidis may be one cause), one cause),

HypernatremiaHypernatremia (more than 150 mEq/L) -high (more than 150 mEq/L) -high sodium level-usually indicates water deficit in sodium level-usually indicates water deficit in ECF-symptoms include thirst, tachycardia, ECF-symptoms include thirst, tachycardia, dry sticky tongue, disorientation, dry sticky tongue, disorientation, hallucination, lethargy, seizures, coma, hallucination, lethargy, seizures, coma, hypotension, agitation, low feverhypotension, agitation, low fever

Artial Natruretic Peptide: Regulates Artial Natruretic Peptide: Regulates NaNa++ & H2O Excretion & H2O Excretion

Hormone from myocardial cellsHormone from myocardial cells Stimulates: hypothalamus, kidney, Stimulates: hypothalamus, kidney,

adrenal, & medullaadrenal, & medulla

Artial Natruretic Peptide: Regulates Artial Natruretic Peptide: Regulates NaNa++ & H & H22O ExcretionO Excretion

Figure 20-15: Atrial natriuretic peptide

Potassium Balance: Potassium Balance: Critical for Excitable Heart & Critical for Excitable Heart &

Nervous TissuesNervous Tissues

Hypokalemia – low [KHypokalemia – low [K++] in ECF, ] in ECF, Hyperkalemia - high [KHyperkalemia - high [K++] ]

Reabsorbed in Ascending Loop, Reabsorbed in Ascending Loop, secreted in Collecting ductsecreted in Collecting duct

Potassium Balance: Potassium Balance: Critical for Excitable Heart & Critical for Excitable Heart &

Nervous TissuesNervous Tissues

Figure 20-4: Osmolarity changes as fluid flows through the nephron

Potassium Balance: Potassium Balance: Critical for Excitable Heart & Critical for Excitable Heart &

Nervous TissuesNervous Tissues

Figure 20-12: Aldosterone action in principal cells

Thirst & "salt craving", or avoidance behaviorThirst & "salt craving", or avoidance behavior Integrated circulatory & excretory reflexesIntegrated circulatory & excretory reflexes

Response to Dehydration & Response to Dehydration & Osmolarity ImbalanceOsmolarity Imbalance

Response to Dehydration & Response to Dehydration & Osmolarity ImbalanceOsmolarity Imbalance

Acidosis: Acidosis: plasma pH plasma pH Protein damageProtein damage CNS depressionCNS depression

Alkalosis: Alkalosis: plasma pH plasma pH HyperexcitabilityHyperexcitability CNS & heartCNS & heart

Buffers: HCOBuffers: HCO33-- & proteins & proteins

HH++ input: diet & metabolic input: diet & metabolic HH++ output: lungs & kidney output: lungs & kidney

Acid/Base Homeostasis: OverviewAcid/Base Homeostasis: Overview

Acid/Base BalanceAcid/Base Balance

Homeostasis of hydrogen ion contentHomeostasis of hydrogen ion content Body fluids are classified as either acids or Body fluids are classified as either acids or

bases depending on H ion concentrationbases depending on H ion concentration Acid is an H donor Acid is an H donor and elevates the and elevates the

hydrogen ion content of the solution to hydrogen ion content of the solution to which it is addedwhich it is added

Base is an H acceptor Base is an H acceptor and can bind and can bind hydrogen ionshydrogen ions

Concentration is expressed as Concentration is expressed as pHpH Normal pH of blood is 7.35-7.45 Normal pH of blood is 7.35-7.45 (alkaline)(alkaline) pH below 6.8 or above 7.8 is incompatible pH below 6.8 or above 7.8 is incompatible

with lifewith life

AcidsAcids

During the process of cellular metabolism During the process of cellular metabolism acids are continually being formed and acids are continually being formed and excess hydrogen ions must be eliminated excess hydrogen ions must be eliminated

There are two types of acids formed: volatile There are two types of acids formed: volatile acids are excreted by the lungs and acids are excreted by the lungs and nonvolatile acids are excreted by the kidneynonvolatile acids are excreted by the kidney

Volatile acids can be excreted from the body Volatile acids can be excreted from the body as gas. as gas. Carbonic acid produced by the Carbonic acid produced by the hydration of carbon dioxide hydration of carbon dioxide is a volatile acid is a volatile acid

Normally carbon dioxide is excreted by the Normally carbon dioxide is excreted by the lungs as fast as metabolism produces it, so lungs as fast as metabolism produces it, so carbonic acid is carbonic acid is not allowed to accumulatenot allowed to accumulate and alter pHand alter pH

Non-volatile acidsNon-volatile acids

Cannot be eliminated by the lungs and Cannot be eliminated by the lungs and must be eliminated by the kidneys must be eliminated by the kidneys

All metabolic acids except carbolic are All metabolic acids except carbolic are non-volatile acidsnon-volatile acids

These include sulfuric acid, These include sulfuric acid, phosphoric acid, lactic acid, ketoacids phosphoric acid, lactic acid, ketoacids like acetoacetic acid and beta like acetoacetic acid and beta hydroxybutyric acid, and small hydroxybutyric acid, and small amounts of other inorganic and amounts of other inorganic and organic acidsorganic acids

Regulation of pHRegulation of pH

Three methods control pHThree methods control pH 1. 1. chemical buffers-whenchemical buffers-when Hydrogen Hydrogen

is removed a buffer replaces itis removed a buffer replaces it 2. 2. regulation of carbon dioxideregulation of carbon dioxide by by

respiratory systemrespiratory system 3. 3. regulation of plasma bicarbonateregulation of plasma bicarbonate

concentration by the kidneys-concentration by the kidneys-slower, second line of defenseslower, second line of defense

Chemical buffersChemical buffers

These are These are the first line of defensethe first line of defense against changes in pHagainst changes in pH

Act within a fraction of a second for Act within a fraction of a second for immediate defenseimmediate defense against H+ shiftagainst H+ shift

These are a mixture of 2 or more These are a mixture of 2 or more chemicals that minimize changes in chemicals that minimize changes in pHpH

Convert strong acids into weak acids Convert strong acids into weak acids and strong bases into weak basesand strong bases into weak bases

Buffers continuedBuffers continued

Carbonic acid-bicarbonate system is Carbonic acid-bicarbonate system is most most important extracellular bufferimportant extracellular buffer because it because it can be regulated by both lungs and kidneyscan be regulated by both lungs and kidneys

Carbonic acid/bicarbonate ratio is usually Carbonic acid/bicarbonate ratio is usually 1:201:20

COCO2 2 + H+ H22O↔HO↔H2 2 COCO 3 3 ↔H↔H+ + + HCO+ HCO33--

Phosphates act as a buffer like the Phosphates act as a buffer like the bicarbonate system does and protein bicarbonate system does and protein buffers are the most abundant buffers in buffers are the most abundant buffers in body cells and bloodbody cells and blood

Regulation of pH through kidneysRegulation of pH through kidneys

Tubular secretion of H+ from convoluted Tubular secretion of H+ from convoluted tubules and collecting ducts so extra is tubules and collecting ducts so extra is excreted in urineexcreted in urine

Helps regulate sulfuric acid and Helps regulate sulfuric acid and phosphoric acid, and other organic acids phosphoric acid, and other organic acids in body fluids as a result of metabolismin body fluids as a result of metabolism

Diets high in protein generate more acid, Diets high in protein generate more acid, so kidneys respond by secreting more so kidneys respond by secreting more hydrogen ion. (Atkins Diet)hydrogen ion. (Atkins Diet)

In urine, hydrogen ion is buffered by In urine, hydrogen ion is buffered by phosphate and ammoniaphosphate and ammonia

Acid/Base Homeostasis: OverviewAcid/Base Homeostasis: Overview

Figure 20-18: Hydrogen balance in the body

HH+ + & NH& NH44++ secreted into lumen and excreted secreted into lumen and excreted

HCOHCO33- - is reabsorbed is reabsorbed

Kidney Hydrogen Ion Balancing: Kidney Hydrogen Ion Balancing: Proximal TubuleProximal Tubule

Kidney Hydrogen Ion Balancing: Kidney Hydrogen Ion Balancing: Proximal TubuleProximal Tubule

Figure 20-21: Proximal tubule secretion and reabsorption of filtered HCO3-

Type A Intercalated cells excrete HType A Intercalated cells excrete H++ absorb HCO absorb HCO33--

Type B intercalated cells absorb HType B intercalated cells absorb H++ secrete HCO secrete HCO33--

Kidney Hydrogen Ion Balancing: Kidney Hydrogen Ion Balancing: Collecting DuctCollecting Duct

Kidney Hydrogen Ion Balancing: Kidney Hydrogen Ion Balancing: Collecting DuctCollecting Duct

Figure 20-22: Role of the intercalated cell in acidosis and alkalosis

AmmoniaAmmonia

Ammonia (NH3) is a weak base Ammonia (NH3) is a weak base produced in cells of renal tubule by produced in cells of renal tubule by removal of amine group from some removal of amine group from some amino acids amino acids (deamination)(deamination)

It diffuses into the tubule and It diffuses into the tubule and accepts hydrogen ions to become accepts hydrogen ions to become NH4+ which is trapped in the tubule NH4+ which is trapped in the tubule and excretedand excreted

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 on Water recycling and ECF/plasma balance depends on descending loop of Henle and vasopressin regulated descending loop of Henle and vasopressin regulated collecting duct for conservationcollecting duct for conservation

Osmolarity depends on aldosterone and angiotensin pathway Osmolarity depends on aldosterone and angiotensin pathway to regulate CNS & endocrine responsesto regulate CNS & endocrine responses

Along with respiration, proximal tubule and collecting duct Along with respiration, proximal tubule and collecting duct cells reabsorb or excrete Hcells reabsorb or excrete H++ & HCO & HCO33

-- to balance pH to balance pH