chapter 15 fluid and acid-base balance - the …biology/classes/255/chapter15.pdffluid balance water...

Chapter 15Chapter 15

Fluid and AcidFluid and Acid--Base BalanceBase Balance

V. Pag. 559-589

VI. Pag. 547-577

Fluid BalanceWater constitutes ~60% of body weight.

All cells and tissues are surrounded by an aqueous environment. Most biochemical reactions inside the cell occurs in the cytosol.

Body systemsmaintain homeostasis

Homeostasis

Cells make up body systems

Fluid balance is critical for maintaining bodyhomeostasis

Fluid BalanceDisruption of normal fluid balance can disrupt cell function

No net movement of water

Water tends to move in causing cell swelling

Water tends to move out of cellcausing cell shrinking

Water Distribution

In the human organism, water is distributed between:

1) The intracellular fluid(~62%)

2) The extracellular fluid that consist of plasma(6.6%) and interstitial fluid (26.4%)Slide 30

VesselsHeart(pump)

Tissues

Cells

Circulating plasma(20% of extracellular fluid)

Interstitial fluid(80% of extracellular fluid)

Figure 10.21Page 364

Ionic Composition of Body Compartments


Barriers regulating body fluid composition in human body:

1) Capillary wall

2) Cell membrane

Fluid Balance

Fluid balance is maintained by regulating:

1) Extracellular fluid volume. Effect on blood pressure

2) Osmolarity: measure of solutes dissolved in aqueous medium. Effect on cell volume

Slide 30

VesselsHeart(pump)

Tissues

Cells




Fluid BalanceDisruption of normal fluid balance can disrupt cell function



Water tends to move out of cellcausing cell shrinking

Regulation of Extracellular Fluid Volume is Important

in the Regulation of Blood PressureReduction in EC volume causes a fall in blood pressure

Short term regulation of blood pressure:

1) Baroreceptor reflex , and

2) Fluid shift between plasma and intestinal fluid

Long term regulation of blood pressure:

1) Control of Na+ ions filtration and reabsorption by the renin-angiotensin-aldosterone system

Parasympatheticstimulation Heart Heart

rateCardiacoutput

Bloodpressure

Sympatheticstimulation Heart

Heartrate

Contractilestrengthof heart

Strokevolume

Cardiacoutput

Cardiacoutput

Bloodpressure

Bloodpressure

Bloodpressure

Total peripheralresistance

Strokevolume

VenousreturnVeins Vasoconstriction

VasoconstrictionArterioles

Baroreceptor Reflex

Baroreceptor Reflex

Slide 54

Figure 10.41 Page 384

Consequences

Compensations

11 mm Hg(ultrafiltration) Interstitial fluid

From arteriole To venule

-9 mm Hg(reabsorption)

Initial lymphaticvessel

Blood capillary (See next slide)

Fluid Shift Between Plasma and Interstitial Fluid

Long Term Control of Blood Pressure: Na+ Control

1) Regulation of Na+ filtration in glomerulus by GFR2) Regulation of Na+ reabsorption by the renin-angiotensin-

aldosterone system

Long Term Control of Blood Pressure: Na+ Control

Decreased blood pressure or Na+ load

Decreased Na+

filtration rate

Decreased blood pressure or Na+

load

Increased renin production and insertion of Na+ channels in luminal membrane and Na+/K+

ATPase in basolateral membrane

Juxtaglomerular ApparatusMacula dense cells can detect changes in flow rate and

release vasoactive substances (vasoconstrictors and vasodilators) that alter capillary blood flow.

Granular cells sense changes in pressure and release renin.

Sese chages in blood pressure, NaCl volume.Secrete renin

Sense changes in flow rate.

Secrete vasoactive Substances (endothelin)

Regulation of GFR by Baroreceptor Reflex and Sympathetic Activity

The idea here is toincrease blood volume when drop in blood pressure occurs

Slide 17

Short-termadjustment for

Arterial blood pressure

Long-termadjustment for

Arterialblood pressure

Detection by aorticarch and carotid sinusbaroreceptors

Cardiacoutput

Totalperipheralresistance

Sympathetic activity

Generalizedarteriolar vasoconstriction

Afferent arteriolarvasoconstriction

Glomerular capillaryblood pressure

GFR

Urine volume

Conservation of fluid and salt



Notice that sympathetic nerve activation reduce filtration coefficient (and GFR) by stimulating contraction of podocytes

Renin-Angiotensin-Aldosterone Regulates Na+ Reabsorption

Aldosterone acting on distal/collecting tubules, drives the insertion of new Na+ channels and Na+/K+ ATPases in tubular cells

Slide 23


NaCl / ECF volume /


Liver Kidney Lungs Adrenalcortex Kidney

H2Oconserved

Na+ (and CI–)osmotically holdmore H2O in ECF

Na+ (and CI–)conserved

Na+ reabsorptionby kidney tubules( CI–

reabsorptionfollows passively)

Vasopressin Thirst Arteriolarvasoconstriction

H2O reabsorptionby kidney tubules

Fluid intake

ReninAngiotensin-convertingenzyme

Angiotensinogen Angiotensin I Angiotensin II Aldosterone

Aldosterone FunctionAldosterone stimulates Na+ reabsorption by promoting

the insertion of new Na+ channels in the luminal membrane and additional Na+/K+ ATPase carriers in the

basolateral membrane

© Brooks/Cole - Thomson Learning

Other Functions of the Renin-Angiotensin-Aldosterone System

Slide 23


NaCl / ECF volume /



H2Oconserved







Fluid intake



Water conservation

Arteriolar vasoconstriction

Water/fluid intake

Fluid Balance

Fluid balance is maintained by regulating:

1) Extracellular fluid volume. Effect on blood pressure

2) Osmolarity: measure of solutes dissolved in aqueous medium. Effect on cell volume: hypertonic and hypotonic extracellular fluid

Slide 30

VesselsHeart(pump)

Tissues

Cells




Osmolarity-Induced Changes in Cell Volume



Water tends to move out of cell. Cell shrinking


Between plasma andinterstitial fluid, differences in osmolarity are due tounequal distribution of plasma proteins

Between interstitial fluidand intracellular fluid differences in osmolarity are due to differences inionic composition

Regulation of Osmolarity in Human Body

Osmolarity can be regulated by:

1) Water intake (angiotensin-thirst)

2) Water output (vasopressin effect on kidneys)

Slide 30

VesselsHeart(pump)

Tissues

Cells




Vasopressin Release Controls Water Secretion and Osmolarity

Fromproximaltubule

Filtrate has concentrationof 100 mosm/liter as itenters distal andcollecting tubules

In the face of water deficit: vasopressin stimulates water movement out of distal/collecting tubules

Collectingtubule

Loop ofHenle

Medulla

Cortex

Distal tubule

Concentration ofurine may be upto 1,200 mosm/literas it leavescollecting tubule

= permeability to H2Oincreased by vasopressin

= passive diffusion of H2O

= active transport of NaCl

= portions of tubule impermeable to H2O

*

*

*

*

Figure 15.4Page 569

ECF volume

Arterialblood pressureOsmolarity

Hypothalamicosmoreceptors(dominant factorcontrolling thirst andvasopressin secretion)

Left atrial volume receptors(important only in large changes in plasmavolume/arterial pressure)

Hypothalamic neurons

Thirst Vasopressin

Arteriolarvasoconstriction

H2O intake H2O permeabilityof distal and collecting tubules

H2O reabsorption

Urine output

Plasma osmolarity Plasma volume

Angiotensin Regulates Thirst AND Water Intake

Slide 23


NaCl / ECF volume /



H2Oconserved







Fluid intake



Vasopressing and Angiotensin Also Regulate Total Peripheral Resistance

Slide 23


Total peripheral resistance

Arteriolar radius

Blood viscosity

Number ofred blood cells

Concentrationof plasma proteins

Local (intrinsic) control

Extrinsic control

Myogenic responses to stretch Vasopressin

Heat, cold application(therapeutic use) Angiotensin II

Histamine release(involved with injuriesand allergic responses)

Epinephrine and norepinephrine

Local metabolic changes in O2, CO2, other metabolites

Sympathetic activity(exerts generalizedvasoconstrictor effect)

Major factors affecting arteriolar radius

Acid-Base BalanceRegulation of free H+ in body fluids

Acids are substances that generate free H+ in solution Ex: H2CO3 HCl

Bases are substances that accept free H+ in solutionEx: HCO3

- NaOH

Acids Release H+ in SolutionStrong Acid versus Weak Acid

Strong acids undergo complete dissociation in solution

Weak acids undergo incomplete dissociation in solution. At certain point, the amount of dissociated ions and whole molecule reach an equilibrium

Concentration of each component in the reaction is regulated by the law of mass action and dissociation constant Khttp://www.chembio.uoguelph.ca/educmat/chm19104/chemtoons/chemtoons4.htm

http://www.chembio.uoguelph.ca/educmat/chm19104/chemtoons/chemtoons4.htm

pH

Acids are substances that generate free H+ in solution

How do we quantify the amount of H+ present in a solution?

pH is a number that allow us to quantify the amount of H+ in solution:

pH= log 1/[H+]

pH ScaleSince pH is inversely proportional to the H+

concentration, an acidic solution will have a low pH and a basic solution will have a high pH

Notice that a pH = 7 is considered a neutral pH.

Pure water have a pH = 7

Physiologically, a pH = 7.4 is considered normal and correspond to the average pH of blood

pH Values For Some Substances and Body Fluids

Physiological Changes Induced By H+

Fluctuations

Blood pH = 7.4Acidosis pH < 7.35Alkalosis pH > 7.45

Death may occur if 6.8 < Blood pH <8

Physiological Changes Induced By pH Changes

1) Increased H+ (acidosis) depresses nerve activity, whereas decreased H+ causes overexcitability of the nervous system

2) Changes in H+ concentration can modify protein structure and change enzymatic activity

3) Increased H+ results in lower K+

secretion in kidneys

K+ and H+ SecretionBasolateral pump can use K+ or H+ for Na+ reabsorption.

If body fluids become acidic then kidneys will secrete more H+ and leave K+ in blood…Not good!

H+

H+

H+H+

Sources of H+ in Human Body

1) Carbonic acid formation (H2CO3)

2) Inorganic acids produced during nutrients degradation(Sulfuric and phosphoric acid formation)

3) Organic acids produced during cell metabolism(Lactic acid, Fatty acids)

How Does The Human Body Avoid Dramatic Changes in [H+]

1) Chemical buffers

2) Respiration

3) Renal function

How Does The Human Body Avoid Dramatic Changes in [H+]:Role of Chemical Buffers

A Chemical buffer is a mix of a weak acid and its salt that can minimize pH changes when strong acids or bases are added.

Effect of law of mass action.Addition of a one component will shift equilibrium and partially compensate for changes in pH.




Chemical Buffers in Human Body

Carbonic acid-bicarbonate buffer (H2CO3/HCO3

-)is the most important system that control blood pH

Protein Buffer (Intracellular buffer)

Hemoglobin buffer

Phosphate buffer (Intracellular buffer)

Carbonic Acid-Bicarbonate BufferUse to buffer extracellular fluid and changes in pH caused by fluctuations of H+ non related to

CO2 formation

HCO3- + H+ H2CO3

The Henderson-Hasselbalch Equation describes the relationship between H+ and the other members of the

bufferCO2 + H2O H2CO3 HCO3

- + H+

pH = pK + log ([HCO3- ]/ [CO2])

pH = 7.4 (normal pH)pK is a constant, for H2CO3 = 6.1

[HCO3- ]/ [CO2] = 20/1 (normal)

[HCO3- ] is regulated by the kidneys

[CO2] is regulated by lungs

Protein BufferProteins contain acidic or basic groups that can give up or take up H+. These groups can be used to buffer H+

changes in the intracellular fluid

Hemoglobin BufferUse to buffer H+ generated from carbonic acid

Hb + H+ HHb

Phosphate BufferUse to buffer urine and intracellular fluids

Na2HPO4 + H+ NaH2PO4 + Na+

(basic phosphate salt) (acid phosphate salt)


Regulation of pH by Respiration

CO2 + H2O H2CO3 HCO3- + H+

Effect of CO2 on ventilation


Chemical buffers (can regulate plasma pH instantly)

Respiration (is involved in the minute-to-minute regulation of plasma pH, but can not fully compensate for charges in pH)

Renal function (is involved in the long term regulation of pH- from hours to days)


Notice that chemical buffers just mask any excess of H+

(H+ ions do not disappear but are converted into something else)

The respiratory and renal systems are the only systems that actually can eliminate H+

from the body

Kidneys Control pH by Adjusting:1) H+ excretion

(H+ filtration is very low)2) HCO3

- filtration-reabsorption 3) NH3 secretion

HCO3-

H+

HCO3-

NH3

HCO3-

CO2H+

Kidneys Regulate pHMore Effectively Than the Lungs

(Lungs only regulate CO2. Beside regulating HCO3

-, kidneys regulate H+ formed as a result of metabolic activity: lactic & fatty acids formation)

Notice there is no H+ reabsorption in kidneys. There isonly HCO3

-

reabsorption

Kidneys Control pH by Adjusting:1) H+ excretion

(H+ enter kidneys by secretion resulting in a very acid urine, there is very little filtration WHY?)

Basolateral pump can use K+ or H+ for Na+

reabsorption. If body fluids become acidic then kidneys will secrete more H+

H+ in urine is buffered by phosphate buffers and NH3

H+

H+ excretion is influenced by:1) [H+] in plasma

2) [CO2] in plasma

HCO3-

HCO3-

H+

HCO3-

CO2H+

The ability of the kidneys to regulate H+ and CO2independently allows regulation of free H+

produced as a result of respiratory and/or metabolic activity. There is no neuronal/hormonal control

HCO3- Regulation

1) Kidneys regulate HCO3- by variable reabsorption of

filtered HCO3-

2) Or variable addition of new HCO3- to plasma

Kidneys Control pH by Adjusting:1) Kidneys regulate HCO3

- by variable reabsorption of filtered HCO3

-

HCO3- is filtered

but can not cross the luminal membrane. Notice however that HCO3

- can cross the basolateral membrane

There is a indirect reabsorption of filtered HCO3

-

HCO3- Regulation

2) Variable addition of HCO3- to plasma

(Buffering of H+ with phosphate allows release of new HCO3

- from peritubular capillaries)

Difference Between New and Reabsorbed HCO3

-

Notice differential permeability of luminal and basolateral membrane of tubular cells to HCO3

-

Luminal membrane is impermeable to HCO3

-

Basolateral membrane is permeable to HCO3

-

How Do the Kidneys Buffer Secreted H+?

1) Phosphate Buffer (Na2HPO4) 2) NH3 secretion

Na2HPO4

H+

H+Na2HPO4 + H+ NaH2PO4 + Na+

Why Is The Kidney Excreting Na2HPO4Continuously?

(Chapter 14)

Carrier saturation limits transport of a substance in tubules- tubular maximum

If concentration of substance in tubules goes above tubular maximumexcretion will take place-renal threshold

Kidneys regulate Na2HPO4plasma levels

[Glucose] 125 mg

[Na2HPO4] 300 mg

How Do the Kidneys Buffer Secreted H+?

1) Phosphate Buffer (Na2HPO4) 2) NH3 secretion

H+

H+

NH3 + H+ NH4+

Notice:NH3 is formed and released into the lumen by tubular cells

NH4+ is impermeable to luminal

membranesNH3

NH3

Acid-Base Imbalances Arise From:1) Respiratory Disturbance2) Metabolic Disturbance

HCO3-

HCO3-

H+

HCO3-

CO2H+

Respiratory disturbance may cause:Respiratory acidosis (too much CO2)Respiratory alkalosis (too little CO2

Metabolic disturbance may cause:Metabolic acidosis (too little HCO3

-)Metabolic alkalosis (to much HCO3

-)

Acid-Base Imbalance

Notice: kidneys control HCO3-

and H+ by regulating the creation of new HCO3

- or the reabsorbtion of filtered HCO3

-

During respiratory acidosis (+CO2) kidneys conserve more HCO3

- and add more new HCO3

- while secreting more H+

During respiratory alkalosis (-CO2) kidneys conserve more H+ and excrete more HCO3

-

Acid-Base ImbalanceRespiratory

AcidosisRespiratory

AlkalosisMetabolicAcidosis

MetabolicAlkalosis

Too much CO2, hypoventilation

Too little CO2, hyperventilation

Fall in HCO3- Increase in HCO3

-

Cause: Lung disease

Depression of respiratory centerRespiratory motor

dysfunction

AnxietyAspirin

poisoningHigh altitude

DiarrheaDiabetes mellitus

Strenuous exercise

Renal failure

VomitingIngestion of

alkaline compounds

Compensation:Chemical buffers

Kidneys(notice that

damaged lungs can not regulate CO2)

Chemical buffersLungs

Kidneys


Kidneys


Kidneys

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