1 Chapter 2 Normal Water, Electrolytes, and Acid-base Balance Professor A. S. Alhomida Disclaimer The texts, tables, figures and images contained in this.

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1

Chapter 2Normal Water, Electrolytes, and

Acid-base BalanceProfessor A. S. Alhomida

Chapter 2Normal Water, Electrolytes, and

Acid-base BalanceProfessor A. S. Alhomida

Disclaimer

The texts, tables, figures and images contained in this course presentation (BCH 376) are not my own, they can be found on:

• References supplied• Atlases or• The web

King Saud University

College of Science

Department of Biochemistry

2

Total body water(60 – 70%)

36 – 49 Liter

Intracellular Fluid )ICF((50% )35 L

Extracellular Fluid )ECF((20% )14 L

Interstitial Tissue Fluid )ITF((15% )11 L

Plasma; Intravascular )Fluid )IVF((5% )3 L

3

Darrow’s semipermealbe membrane

(Cell membrane)

Darrow’s permealbe membrane

(Capillary membrane)

ABC

35 L 11 L 3 L

A = Plasma; B = Tissue Fluid; A + B = Extracellular Fluid (ECF); C = Intracellular Fluid (ICF)

Figure 2. Showing distribution of body water in three compartments

ICF ECF

Capillary and Cell Membrane

4

Colloid Osmotic Pressure

ECF

Interstitial

Pla

sma

Capillary Membrane

Capillary membrane freely permeable to water and electrolytes, but not to large molecules such as proteins (albumin)

The albumin on the plasma side gives rise to a colloid osmotic pressure gradient favouring movement of water into the plasma

This is balanced out by the hydrostatic pressure difference

H2O

H2O120/80

H2O

H2O

5

Cell Membrane

ICF

Cell Membrane

Na+

K+

Interstitial

H2O

H2O

Cell membrane is freely permeable to H20, but Na and K are pumped across this membrane to maintain a gradient

[K+] =4 [K+] =150

Na+= 144Na+= 10

6

Body Fluid

1. Intracellular )within the cell( Fluid )ICF(• All fluids inside cells of body• About 40% of total body weight

2. Extracellular Fluid )ECF(• All fluids outside cells• About 20% of total body weight• Subcompartments

• Interstitial fluid (between cells) and plasma; lymph, CSF, synovial fluid

7

Body Fluid Compartments

8

Body Fluid Compartments

9

Normal Daily Inputs and Outputs: Water

Input mL Output mL

Drink 1500 Urine 1500

Food 750 Faeces 100

Metabolic 350 Lungs 400

. Skin 600

Total 2600 Total 2600

10

Movement of Fluid

1. Movement of Fluid and Solutes • They are allowed by membrane permeability,

pressures, active and passive transport

2. Diffusion• Movement of molecules from area of higher

concentration to area of low concentration• Membrane must be permeable, requires no energy,

most efficient

11

Movement of Fluid, Cont’d

1. Facilitated Diffusion• Molecules move from area of high concentration to

low concentration, but combines with another substance to facilitate movement or increase speed of diffusion, example:

• Glucose combined with insulin increases rate of diffusion across cell membrane

12

Movement of Fluid, Cont’d

1. Osmosis• Process by which only water molecule move

through a selectively permeable membrane• Membrane must be impermeable to solute

• Concentration gradient must exist

13

Movement of Fluids, Cont’d

3. Active Transport• Cell must use extra energy to transport a substance

across the cell membrane and uphill or against the concentration gradient

14

Osmosis

1. Osmotic Pressure• Describes movement of water (force) • Osmolality measures osmotic force of solute per unit of

weight of solvent (amount of solute in solution)• The more solute the higher the osmolality

2. Unit• Measured in millimoles, measured by number of dissolved

particles per kilogram

15

Osmosis, Cont’d

1. Osmolarity • Measures total millimoles of solute per unit of total

volume of solution

2. Osmolality and Osmolarity • They are used interchangably, but osmolality is usually

performed on plasma and urine

3. Fluid of High Osmolality • They tend to pull water across a membrane to reduce the

ratio of solute to solvent

16

Osmosis, Cont’d

1. Normal value: 275-295 mmol/kg

2. Na+, glucose, and urea are major determinants with Na+ as primary

3. Kidneys are mainly responsible for maintaining this narrow range

17

Water Content Regulation

1. Content Regulated • Total volume of water in body remains constant

2. Kidneys • Primary regulator of water excretion

3. Regulation Processes• Osmosis• Osmolality• Baroreceptors• Learned behavior

18

Water Content Regulation, Cont’d

1. Sources of Water• Ingestion• Cellular metabolism

2. Routes of Water Loss• Urine• Evaporation

• Perspiration

• Respiratory passages• Feces

19

Extracellular Fluid Osmolality

1. Osmolality• Adding or removing water from a solution changes this

2. Increased Osmolality• Triggers thirst and ADH secretion

3. Decreased Osmolality• Inhibits thirst and ADH secretion

20

Hormonal Regulation of Blood Osmolality

21

Regulation of ECF Volume

• Mechanisms1. Neural

2. Renin-angiotensin-aldosterone

3. Atrial natriuretic hormone (ANH)

4. Antidiuretic hormone (ADH)

22

Regulation of ECF Volume, Cont’d

• Increased ECF Results in:1. Decreased aldosterone secretion

2. Decreased ADH secretion

3. Decreased sympathetic stimulation

4. Increased ANH secretion

23

Regulation of ECF Volume, Cont’d

• Decreased ECF results in:1. Increased aldosterone secretion

2. Increased ADH secretion

3. Increased sympathetic stimulation

4. Decreased ANH secretion

24

Hormonal Regulation of Blood Volume Increase

25

Hormonal Regulation of Blood Volume Decrease

26

Regulation of ECF Volume

27

Regulation of ICF and ECF

28

Regulation of ECF Electrolytes

• Electrolytes1. Molecules or ions with an electrical charge

• Water ingestion adds electrolytes to body

• Kidneys, liver, skin, lungs remove from body

2. Concentration changes only when growing, gaining or losing weight

29

Regulation of ECF Electrolytes, Cont’d

1. Sodium Ions• Dominant ECF cations• Responsible for 90-95% of osmotic pressure• Regulation of Na+ ions

• Kidneys major route of excretion• Small quantities lost in sweat

• Terms• Hypernatremia• Hyponatremia

30

Mechanisms Regulating Blood Sodium

31

Mechanisms Regulating Blood Sodium

32

Abnormal Plasma Levels of Sodium Ions

33

Regulation of Chloride and Magnesium Ions

2. Chloride Ions• Predominant anions in ECF

3. Magnesium Ions• Capacity of kidney to reabsorb is limited• Excess lost in urine• Decreased extracellular magnesium results in

greater degree of reabsorption

34

Regulation of Blood Magnesium

35

Abnormal Plasma Levels of Magnesium Ions

36

Regulation of Potassium Ions

4. Potassium Ions• Maintained in narrow range• Affect resting membrane potentials• Aldosterone increases amount secreted• Terms

• Hyperkalemia

• Hypokalemia

37

Potassium Ion Regulation in ECF

38

Abnormal Concentrations of Potassium Ions

39

Regulation of Calcium Ions

5. Calcium Ions• Regulated Within Narrow Range

• Elevated extracellular levels prevent membrane depolarization

• Decreased levels lead to spontaneous action potential generation

• Terms• Hypocalcemia• Hypercalcemia

40

Regulation of Calcium Ions, Cont’d

• PTH • Increases Ca2+ extracellular levels• Decreases extracellular phosphate levels

• Vitamin D • Stimulates Ca2+ uptake in intestines

• Calcitonin • Decreases extracellular Ca2+ levels

41

Regulation of Calcium Ions, Cont’d

42

Regulation of Phosphate Ions

5. Phosphate Ions• Under normal conditions

• Reabsorption of phosphate occurs at maximum rate in the nephron

• An increase in plasma phosphate • Increases amount of phosphate in nephron beyond that

which can be reabsorbed; excess is lost in urine

43

Regulation of Blood Phosphate Ions

44

Abnormal Plasma Levels of Phosphate Ions

45

Acids, Bases and Buffers

1. Acids• Release H+ into solution

2. Bases• Remove H+ from solution

3. Acids and Bases• Grouped as strong or weak

46

4. Buffers• Resist changes in pH

• When H+ added, buffer removes• When H+ removed, buffer replaces

5. Types of Buffer Systems• Carbonic acid and bicarbonate• Protein• Phosphate

Acids, Bases and Buffers, Cont’d

47

Regulation of ECF pHRegulation of ECF pH

• Buffering MechanismsBuffering Mechanisms1. Chemical buffers in ECF, ICF and bone

• Phosphate• Proteins• Bicarbonate and CO2 system• Hemoglobin

2. Lungs3. Kidneys

48

Carbonic Acid–Bicarbonate Carbonic Acid–Bicarbonate BufferBuffer

1. Operates in both the lung and the kidney

2. The greater the partial pressure of carbon dioxide, the more carbonic acid is formed

• At a pH of 7.4, the ratio of bicarbonate to carbonic acid is 20:1

• Bicarbonate and carbonic acid can increase or decrease, but the ratio must be maintained

49

3. If the amount of bicarbonate decreases, the pH decreases, causing a state of acidosis

4. If the amount of bicarbonate increases, the pH increases, causing a state of alkalosis

Carbonic Acid–Bicarbonate Carbonic Acid–Bicarbonate Buffer, Cont’dBuffer, Cont’d

50

5. The pH can be returned to normal if the ratio of bicarbonate to carbonic acid is maintained

• This type of pH adjustment is referred to as compensation• Respiratory compensation• Renal compensation

Carbonic Acid–Bicarbonate Carbonic Acid–Bicarbonate Buffer, Cont’dBuffer, Cont’d

51

6. The respiratory system compensates by increasing or decreasing ventilation

7. The renal system compensates by producing acidic or alkaline urine

Carbonic Acid–Bicarbonate Carbonic Acid–Bicarbonate Buffer, Cont’dBuffer, Cont’d

52

Other Buffering SystemsOther Buffering Systems

1. Protein Buffering• Proteins have negative charges, so they can serve as

buffers for H+

2. Renal Buffering• Secretion of H+ in the urine and reabsorption of HCO3

3. Cellular Ion Exchange• Exchange of K+ for H+ in acidosis and alkalosis

53

Regulation of Acid-base BalanceRegulation of Acid-base Balance

54

Regulation of Acid-base Balance, Cont’d

55

Buffer Systems

56

Transport of HCO3- and O2

• CO2 is transported by the blood in three forms

1. Dissolved CO2 in the plasma (7%)

2. Bound to Hb (23 %)

3. As HCO3- in the blood

(70%)

57

1. CO2 diffuses into RBC, where carbonic anhydrase catalyzes a reversible reaction that converts CO2 into HCO3

-

2. H2CO3 forms first but quickly dissociates to HCO3

- and H+

3. HCO3- diffuses out of the RBC

and into the blood plasma 4. H+ attaches to Hb and other

proteins, resulting in only a slight change in the pH

5. The process is reversed in the lungs

Transport of HCO3- and O2,

Cont’d

58

Transport of HCO3- and O2,

Cont’d

• In Lungs1. Hb-H+ binds to O2 to form Hb-

O2 and releases H+ which reacts with HCO3

- to form H2CO3

2. Hb-O2 is transported into tissues

3. H2CO3 dissociates to CO2 and H2O

4. CO2 is eliminated in the expired air

59

Transport of HCO3- and O2,

Cont’d

• In Tissues1. CO2 from metabolic reactions is hydrated to H2CO3

which dissociates to H+ and HCO3-

2. Hb-O2 releases O2 and binds to H+ to form Hb-H+ which is transported to lungs

3. HCO3- is transported to lungs

60

Respiratory Regulation ofECF pH

1. Respiratory Regulation of pH • It is achieved through carbonic acid/bicarbonate

buffer system• As carbon dioxide levels increase, pH decreases

• As carbon dioxide levels decrease, pH increases

• Carbon dioxide levels and pH affect respiratory centers• Hypoventilation increases blood carbon dioxide levels• Hyperventilation decreases blood carbon dioxide levels

61

Respiratory Regulation of ECF pH, Cont’d

62

Mechanisms of Renal Regulation of ECF pH

• Renal Buffer Blood pH by: Urinary Excretion of H+ (Urinary Acidification):

1. Mechanism of Renal Tubular Reabsorption of HCO3

-

2. Mechanism of Renal Excretion of Titratable Acid• Excretion of H+ (as H2O)

• Excretion of H+ (as H2PO4-)

3. Mechanism of Renal Excretion of NH4+

63

Mechanism of Renal Reabsorption of HCO3

-

1. Secretion of H+ into filtrate and reabsorption of HCO3

- into ECF • Cause extracellular pH to increase

• HCO3- in filtrate reabsorbed

2. Rate of H+ secretion increases as • Body fluid pH decreases or

• Aldosterone levels increase

3. Secretion of H+ inhibited • When urine pH falls below 4.5

64

Mechanism of Renal Reabsortion of HCO3

-

65

Mechanism of Renal Excretion of Titratable Acid and NH4

+

66

THE ENDTHE END

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