1. Fluid, Electrolyte, and Acid - Base Homeostasis

2. Fluid Compartments
Body Fluids are separated by semi-permeable membranes into various physiological (functional) compartments
Two Compartment Model
Intracellular = Cytoplasmic (inside cells)
Extracellular (outside cells)
The Two Compartment Model is useful clinically for understanding the distribution of many drugs in the body

3. Fluid Compartments Three Compartment Model
[1] Intracellular = Cytoplasmic (inside cells)
[Extracellular compartment is subdivided into:]
[2] Interstitial = Intercellular = Lymph (between the cells in the tissues)
[3] Plasma (fluid portion of the blood)
The Three Compartment Model is more useful for understanding physiological processes
Other models with more compartments can sometimes be useful, e.g., consider lymph in the lymph vessels, CSF, ocular fluids, synovial and serous fluids as separate compartments

4. Fluid Compartments Total Body Water (TBW) - 42L, 60% of body weight
Intracellular Fluid (ICF) - 28L, 67% of TBW
Extracellular Fluid (ECF) - 14L, 33% of TBW
Interstitial Fluid - 11L, 80% ECF
Plasma - 3L, 20% of ECF

5. Fluid Balance Fluid balance
When in balance, adequate water is present and is distributed among the various compartments according to the body’s needs
Many things are freely exchanged between fluid compartments, especially water
Fluid movements by:
bulk flow (i.e., blood & lymph circulation)
diffusion & osmosis – in most regions

6. Water
General
Largest single chemical component of the body: 45-75% of body mass
Fat (adipose tissue) is essentially water free, so there is relatively more or less water in the body depending on % fat composition
Water is the solvent for most biological molecules within the body
Water also participates in a variety of biochemical reactions, both anabolic and catabolic

7. Water Water balance Sources for 2500 mL - average daily intake
Metabolic Water
Preformed Water
Ingested Foods
Ingested Liquids
Balance achieved if daily output also = 2500 mL
GI tract
Lungs
Skin
evaporation
perspiration
Kidneys

8. Regulating Fluid Intake - Thirst
Recall the role of the Renin-Angiotensin System in regulating thirst along with the Autonomic NS reflexes diagramed below

9. Regulating Fluid Intake - Thirst Quenching
Wetting the oral mucosa (temporary)
Stretching of the stomach
Decreased blood/body fluid osmolarity = increased hydration (dilution) of the blood is the most important

10. Regulation of Fluid Output
Hormonal control
AntiDiuretic Hormone (ADH) [neurohypophysis]
Aldosterone [adrenal cortex]
Atrial Natriuretic Peptide (ANP) [heart atrial walls]
Physiologic fluid imbalances
Dehydration:  blood pressure,  GFR
Overhydration:  blood pressure,  GFR
Hyperventilation - water loss through lungs
Vomiting & Diarrhea - excessive water loss
Fever - heavy perspiration
Burns - initial fluid loss; may persist in severe burns
Hemorrhage – if blood loss is severe

11. Concentrations of Solutes
Non-electrolytes
molecules formed by only covalent bonds
do not form charged ions in solution
Electrolytes
Molecules formed with some ionic bonds;
Disassociate into cations (+) & anions (-) in solutions (acids, bases, salts)
4 important physiological functions in the body
essential minerals in certain biochemical reactions
control osmosis = control the movement of water between compartments
maintain acid-base balance
conduct electrical currents (depolarization events)

12. Distribution of H2O & Electrolytes
Recall Starling’s Law of the Capillaries which explains fluid and solute movements

13. Distribution of Electrolytes

14. Cations and Anions in Body Fluids
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15. Distribution of Major Electrolytes
Na+ and CL- predominate in extracellular fluids (interstitial fluid and plasma) but are very low in the intracellular fluid (cytoplasm)
K+ and HPO42- predominate in intracellular fluid (cytoplasm) but are in very low concentration in the extracellular fluids (interstitial fluid and plasma)
At body fluid pH, proteins [P-] act as anions; total protein concentration [P-] is relatively high, the second most important “anion,” in the cytoplasm, [P-] is intermediate in blood plasma, but [P-] is very low in the interstitial fluid

16. Distribution of Minor Electrolytes
HCO3- is in intermediate concentrations in all fluids, a bit lower in the intracellular fluid (cytoplasm); it is an important pH buffer in the extracellular comparments
Ca++ is in low concentration in all fluid compartments, but it must be tightly regulated, as small shifts in Ca++ concentration in any compartment have serious effects
Mg++ is in low concentration in all fluid compartments, but Mg++ is a bit higher in the intracellular fluid (cytoplasm), where it is a component of many cellular enzymes

17. Electrolyte Balance Aldosterone  [Na+] [Cl-] [H2O]  [K+]
Atrial Natriuretic Peptide (opposite effect)
Antidiuretic Hormone  [H2O] ( [solutes])
Parathyroid Hormone  [Ca++]  [HPO4-]
Calcitonin (opposite effect)
Female sex hormones  [H2O]

18. Electrolytes Sodium (Na+) - 136-142 mEq/liter Most abundant cation
major ECF cation (90% of cations present)
determines osmolarity of ECF
Regulation
Aldosterone
ADH
ANP
Homeostatic imbalances
Hyponatremia - muscle weakness, coma
Hypernatremia - coma

19. Electrolytes Chloride (Cl-) - 95-103 mEq/liter Major ECF anion
helps balance osmotic potential and electrostatic equilibrium between fluid compartments
plasma membranes tend to be leaky to Cl- anions
Regulation: aldosterone
Homeostatic imbalances
Hypochloremia - results in muscle spasms, coma [usually occurs with hyponatremia] often due to prolonged vomiting
elevated sweat chloride diagnostic of Cystic Fibrosis

20. Electrolytes Potassium (K+) Major ICF cation
intracellular mEq/liter
plasma mEq/liter
Very important role in resting membrane potential (RMP) and in action potentials
Regulation:
Direct Effect: excretion by kidney tubule
Aldosterone
Homeostatic imbalances
Hypokalemia - vomiting, death
Hyperkalemia - irritability, cardiac fibrillation, death

21. Electrolytes Calcium (Ca2+) Most abundant ion in body Regulation:
plasma mEq/liter
most stored in bone (98%)
Regulation:
Parathyroid Hormone (PTH) -  blood Ca2+
Calcitonin (CT) -  blood Ca2+
Homeostatic imbalances:
Hypocalcemia - muscle cramps, convulsions
Hypercalcemia - vomiting, cardiovascular symptoms, coma; prolonged  abnormal calcium deposition, e.g., stone formation

22. Electrolytes Phosphate (H2PO4-, HPO42-, PO43-)
Important ICF anions; plasma mEq/liter
most (85%) is stored in bone as calcium salts
also combined with lipids, proteins, carbohydrates, nucleic acids (DNA and RNA), and high energy phosphate transport compound
important acid-base buffer in body fluids
Regulation - regulated in an inverse relationship with Ca2+ by PTH and Calcitonin
Homeostatic imbalances
Phosphate concentrations shift oppositely from calcium concentrations and symptoms are usually due to the related calcium excess or deficit

23. Electrolytes Magnesium (Mg2+)
2nd most abundant intracellular electrolyte, mEq/liter in plasma
more than half is stored in bone, most of the rest in ICF (cytoplasm)
important enzyme cofactor; involved in neuromuscular activity, nerve transmission in CNS, and myocardial functioning
Excretion of Mg2+ caused by hypercalcemia, hypermagnesemia
Homeostatic imbalance
Hypomagnesemia - vomiting, cardiac arrhythmias
Hypermagnesemia - nausea, vomiting

24. Acid–Base Balance

25. Terms
Acid
Any substance that can yield a hydrogen ion (H+) or hydronium ion when dissolved in water
Release of proton or H+
Base
Substance that can yield hydroxyl ions (OH-)
Accept protons or H+

26. Terms pH Negative log of the hydrogen ion concentration
Represents the hydrogen concentration

27. Acid-Base Imbalances Acidosis Alkalosis High blood [H+]
Low blood pH, <7.35
Alkalosis
Low blood [H+]
High blood pH, >7.45
Note: Normal pH is

28. Terms
Buffer
Combination of a weak acid and /or a weak base and its salt
What does it do?
Resists changes in pH
Effectiveness depends on
pK of buffering system
pH of environment in which it is placed

29. Acid-Base Balance Normal metabolism produces H+ (acidity)
Three Homeostatic mechanisms:
Buffer systems - instantaneous; temporary
Exhalation of CO2 - operates within minutes; cannot completely correct serious imbalances
Kidney excretion - can completely correct any imbalance (eventually)
Buffer Systems
Consists of a weak acid and the salt of that acid which functions as a weak base
Strong acids dissociate more rapidly and easily than weak acids

30. Acid–Base Balance Buffer System Consists of a combination of
A weak acid
And the anion released by its dissociation
The anion functions as a weak base
In solution, molecules of weak acid exist in equilibrium with its dissociation products
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31. Acid–Base Balance Buffers Are dissolved compounds that stabilize pH
By providing or removing H+
Weak acids
Can donate H+
Weak bases
Can absorb H+
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32. Acid–Base Balance Three Major Buffer Systems Protein buffer systems:
Help regulate pH in ECF and ICF
Interact extensively with other buffer systems
Carbonic acid–bicarbonate buffer system:
Most important in ECF
Phosphate buffer system:
Buffers pH of ICF and urine
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33. Acid–Base Balance Protein Buffer Systems Depend on amino acids
Respond to pH changes by accepting or releasing H+
If pH rises
Carboxyl group of amino acid dissociates
Acting as weak acid, releasing a hydrogen ion
Carboxyl group becomes carboxylate ion
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34. Acid–Base Balance Protein Buffer Systems At normal pH (7.35–7.45)
Carboxyl groups of most amino acids have already given up their H+
If pH drops
Carboxylate ion and amino group act as weak bases
Accept H+
Form carboxyl group and amino ion
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35. Acid–Base Balance
The Role of Amino Acids in Protein Buffer Systems.
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36. Acid–Base Balance The Hemoglobin Buffer System
CO2 diffuses across RBC membrane
No transport mechanism required
As carbonic acid dissociates
Bicarbonate ions diffuse into plasma
In exchange for chloride ions (chloride shift)
Hydrogen ions are buffered by hemoglobin molecules
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37. Acid–Base Balance The Hemoglobin Buffer System
Is the only intracellular buffer system with an immediate effect on ECF pH
Helps prevent major changes in pH when plasma PCO2 is rising or falling
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38. Oxygen Dissociation Curve
Curve B: Normal curve
Curve A: Increased affinity for hgb, so oxygen keep close
Curve C: Decreased affinity for hgb, so oxygen released to tissues

39. Bohr Effect
It all about oxygen affinity!

40. Acid–Base Balance Carbonic Acid–Bicarbonate Buffer System
Carbon Dioxide
Most body cells constantly generate carbon dioxide
Most carbon dioxide is converted to carbonic acid, which dissociates into H+ and a bicarbonate ion
Is formed by carbonic acid and its dissociation products
Prevents changes in pH caused by organic acids and fixed acids in ECF
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41. Acid–Base Balance Carbonic Acid–Bicarbonate Buffer System
Cannot protect ECF from changes in pH that result from elevated or depressed levels of CO2
Functions only when respiratory system and respiratory control centers are working normally
Ability to buffer acids is limited by availability of bicarbonate ions
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42. Acid–Base Balance Phosphate Buffer System
Consists of anion H2PO4- (a weak acid)
Works like the carbonic acid–bicarbonate buffer system
Is important in buffering pH of ICF
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43. Acid–Base Balance Maintenance of Acid–Base Balance
Requires balancing H+ gains and losses
Coordinates actions of buffer systems with
Respiratory mechanisms
Renal mechanisms
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44. Acid–Base Balance Respiratory and Renal Mechanisms
Support buffer systems by
Secreting or absorbing H+
Controlling excretion of acids and bases
Generating additional buffers
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45. Acid–Base Balance Respiratory Compensation
Is a change in respiratory rate
That helps stabilize pH of ECF
Occurs whenever body pH moves outside normal limits
Directly affects carbonic acid–bicarbonate buffer system
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46. Acid–Base Balance Respiratory Compensation
Increasing or decreasing the rate of respiration alters pH by lowering or raising the PCO2
When PCO2 rises
pH falls
Addition of CO2 drives buffer system to the right
When PCO2 falls
pH rises
Removal of CO2 drives buffer system to the left
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47. Acid–Base Balance Renal Compensation
Is a change in rates of H+ and HCO3- secretion or reabsorption by kidneys in response to changes in plasma pH
The body normally generates enough organic and fixed acids each day to add 100 mEq of H+ to ECF
Kidneys assist lungs by eliminating any CO2 that
Enters renal tubules during filtration
Diffuses into tubular fluid en route to renal pelvis
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48. Acid–Base Balance Hydrogen Ions Are secreted into tubular fluid along
Proximal convoluted tubule (PCT)
Distal convoluted tubule (DCT)
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49. Acid–Base Balance Buffers in Urine
The ability to eliminate large numbers of H+ in a normal volume of urine depends on the presence of buffers in urine:
Carbonic acid–bicarbonate buffer system
Phosphate buffer system
Ammonia buffer system
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50. Acid–Base Balance Major Buffers in Urine
Glomerular filtration provides components of
Carbonic acid–bicarbonate buffer system
Phosphate buffer system
Tubule cells of PCT
Generate ammonia
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51. Acid–Base Balance Renal Responses to Acidosis Secretion of H+
Activity of buffers in tubular fluid
Removal of CO2
Reabsorption of NaHCO3
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52. Acid–Base Balance Renal Responses to Alkalosis
Rate of secretion at kidneys declines
Tubule cells do not reclaim bicarbonates in tubular fluid
Collecting system transports HCO3- into tubular fluid while releasing strong acid (HCl) into peritubular fluid
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53. Acid–Base Balance Disturbances
Disorders:
Circulating buffers
Respiratory performance
Renal function
Cardiovascular conditions:
Heart failure
Hypotension
Conditions affecting the CNS:
Neural damage or disease that affects respiratory and cardiovascular reflexes
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54. Acid–Base Balance Disturbances
Figure 27–11a Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH.
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55. Acid–Base Balance Disturbances
Figure 27–11b Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH.
Copyright © 2009 Pearson Education, Inc., publishing as Pearson Benjamin Cummings