1. Fluid & Electrolyte Balance
Part 4: Regulation & Maintenance

2. Fluid In a lean adult….. That’s a lot of fluid!
Females have 55% body mass as fluids
Males have 60% body mass as fluids.
That’s a lot of fluid!

3. Fluid Compartments Two fluid compartments where fluids are present!
Intracellular Fluid Compartment: Contains the fluid within the cells – composes 2/3 of the body fluid!
Intracellular fluid (ICF) aka Cytosol: The bodily fluid actually located inside cells.
Extracellular Fluid Compartment: Contains the fluid not inside body cells – the other 1/3 of body fluid!
Interstitial Compartment: Contains the fluid between cells.
Intravascular Compartments: Contains the fluid within the blood vessels.
Extracellular Fluid (ECF): The fluid outside of body cells, including interstitial fluid, plasma, etc.
Interstitial Fluid: Occupies the microscopic spaces between tissue – 80% of ECF.
Intravascular Fluid aka Plasma: The liquid portion of the blood – 20% of the ECF.

4. Fluid Compartments
Barriers exist between the intracellular fluid, interstitial fluid, & blood plasma.
Plasma Membranes of the Body Cells
Blood Vessel Walls (except for capillaries with thin walls designed to allow leakage)

5. Fluid Balance
Fluid Balance: The presence of the required amount of water & solutes, in correct proportions, in the all compartments.
Water: 45-75% of body mass, dependent on age & gender.
Electrolytes: The solid inorganic compounds within the solute that dissociate into ions.
Fluid Balance is maintained by the kidneys via filtration, reabsorption, diffusion, & osmosis.

6. Water Gain
Preformed Water: Water ingested via food & liquids – roughly 2300 mL.
Metabolic Water: Water produced as a by-product of cellular respiration, depending on the level of aerobic cellular respiration. The more ATP used, the more water is produced – roughly 200 mL per day.
Thirst Center: The area in the hypothalamus that controls the urge to drink – triggered by an increase in osmolarity, Angiotensin II, and a drop in blood pressure.
Thirst also triggered by neurons in the mouth detecting dryness due to decreased salivary production, or baroreceptors detecting low blood pressure in the heart and blood vessels.

7. Water Loss Water Loss is controlled via variations in urine volume.
Sodium reabsorption is adjusted proportionately to the amount of water excreted.
ADH is used to minimize water loss by stimulating the collecting tubules to retain more water, causing the sodium levels to become imbalanced.
ADH is inhibited if the blood volume & pressure are too high or osmolarity is too low to encourage water output.

8. Water Loss
Dehydration: Occurs when the rate of water loss is greater than the rate of water gain.
Causes reduced blood volume, lowered blood pressure, and increased osmolarity of bodily fluids.
Can be triggered by thirst not occurring quickly enough, fluid access being restricted, excessive heat, etc.
The body compensates by decreasing saliva production, decreasing the amount of water excreted by the kidneys, and the triggering of ADH to control water output.

9. Water Loss
Total body fluid volume is determined mainly by the extent of urinary salt excretion.
Extracellular fluid contains two main ions – Sodium ions (Na+) and Chloride ions (Cl-).
Excretion rates must be varied to maintain homeostasis.
Fluid osmolarity is regulated via water loss.
Increases in NaCl would lead to increase in plasma Na+ & Cl- which increases osmolarity.
Water moves from intercellular fluid to interstitial fluid then into blood plasma to increase blood volume.
Renal sodiom & chloride reabsorption and loss via urine is regulated via Angiotensin II, Aldosterone, & Atrial Natriuetic Peptide (ANP).

10. Factors Regulating Body Water Balance
Thirst Center in Hypothalamus:
Mechanism: Triggers sensation of thirst & desire to drink.
Results: Water gained if thirst is quenched.
Angiotensin II:
Mechanism: Stimulates secretion of aldosterone.
Results: Reduces the loss of water in urine.
Aldosterone:
Mechanism: Increase water reabsorption via osmosis – promotes urinary reabsorption of sodium & chloride.

11. Factors Regulating Body Water Balance
Atrial Natriuretic Peptide:
Mechanism: Promotes natriuresis (elevated urinary excretion of sodium, chloride, & water).
Results: Increases the loss of water in urine.
Antidiuretic Hormone:
Mechanism: Promotes reabsorption of water in collecting ducts of kidneys.
Results: Reduces the loss of water in urine.

12. Movement of Water
Increased Osmolarity of Interstitial Fluid: Causes fluid to draw out of cells & into interstitial fluid – causes cells to shrink.
Decreased Osmolarity of Interstitial Fluid: Causes the cells to swell & potentially lyse.

13. Movement of Water
Water Intoxication: Occurs when the person consumes water faster than the kidneys can excrete it.
Causes excess levels of body water, which causes the cells to swell to dangerous sizes.
Can cause cell lysing and tissue death.

14. Movement of Water Loss of Na+ and body water is dangerous!
Can be caused by blood loss, excessive sweating, vomiting, or diarrhea leading to body water loss – if this is replaced by plain water it can cause problems!
Hyponatremia: Na+ concentration in plasma & interstitial fluid to fall below normal, leading to osmolarity falling. Water moves from the interstitial fluid to the intercellular fluid to correct this, causing cells to swell & lyse.
Can lead to convulsions, coma, & possibly death.
Simply add electrolytes – even just a small amount of table salt. Electrolyte drinks are critical when these symptoms are present!

15. Electrolytes & Body Fluids
Ions form when electrolytes dissolve & dissociate – these serve 4 main functions.
Control the osmosis of water between fluid compartments.
Maintain the acid-base balance necessary for normal cellular activity.
Ions carry electrical currents that allow the production of action potentials & graded potentials.
Several ions are cofactors needed for optimal activity of enzymes.

16. Electrolytes & Body Fluids
Milliequivalents: The unit for measuring concentration of ions.
Measured as milliequivalents per liter (mEq/liter).
Tells us the concentration of cations & anions in a given volume of solution.
For ions with a single positive or negative charge, the mEq is equal to one thousandth of its molecular weight.
E.g. Na+, K+, Cl-.
For ions with two positive or negative charges, the mEq/liter is twice the number of mml/liter.
E.g. Ca+2 (calcium) & HPO4-2 (phosphate).

17. Electrolytes & Body Fluids
Major Cations: Sodium, Potassium, Calcium, Magnesium.
Major Anions: Chloride, Bicarbonate, Phosphate.
Intracellular Fluid: K+ is the most abundant cation, while HPO4-2 is the most abundant anion.
Extracellular Fluid: Na+ is the most abundant cation, while Cl- is the most abundant anion.

18. Electrolytes & Body Fluids
Why are electrolytes important?
They are chemically active & participate in all metabolism.
They determine the electrical potential across cell membranes.
They strongly affect the osmolarity of body fluids & the body’s water content & distribution.

19. Ions
Sodium: The main ion responsible for resting membrane potential in cells – normal range for blood plasma concentration Is mEq/liter.
Principle cation of the ECF.
Important in determining total body water & its concentration among fluid compartments.
Accounts for half the osmolarity of extracellular fluids.
Primary homeostatic concern is adequate renal excretion of the excess.
Aldosterone increases renal reabsorption of sodium.
Hyponatremia: Blood plasma sodium concentration below 135 mEq/liter – stops the release of ADH, permitting greater excretion of water in urine to restore the sodium in ECF.
Hypernatremia: Blood plasma sodium concentration above 149 mEq/liter – triggers Atrial Natriuretic Peptide release to increase sodium excretion by the kidneys.

20. Ions
Potassium: Greatest contributor to intracellular osmosis & cell volume – normal concentration is 3.5 – 5.0 mEq/liter.
Most abundant cation in the ICF.
Promotes resting membrane potentials & action potentials of nerve & muscle cells.
Acts as a cofactor for protein synthesis & some other metabolic processes.
Helps regulate pH of body fluid by “exchanging” itself for hydrogen when moving through cells.
90% of potasssium ions are filtered by the glomerulus & reabsorbed by the PCT – the rest is secreted in urine.
Aldosterone is used to control potassium levels in the blood plasma.
Hyperkalemia: K+ concentrations in the blood plasma above normal – triggers aldosterone to be secreted, which causes increase excretion of K+ in the urine. Can cause death via ventricular fibrillation.
Hypokalemia: K+ concentrations in the blood plasma below normal – prevents aldosterone secretion to minimize K+ excretion in the urine.

21. Ions
Chloride: Provide a major contribution to the osmolarity of the ECF – normal concentration is 95 – 105 mEq/liter.
Most abundant anion in the ECF.
Needed for the formation of stomach acid H+CL-.
Involved in chloride shift mechanism that accompanies carbon dioxide loading & unloading in the red blood cells & plasma.
Homeostasis achieved via sodium balance.
Chloride secretion follows sodium’s excretion.
Chloride ions easily move between the fluid compartments due to plasma membranes typically containing Cl- leakage channels & antiporters.
Hyperchloremia: Blood plasma concentration of chloride above normal.
Hypochloremia aka Hypochloraemia: Blood plasma concentration of chloride below normal ranges – rarely occurs as the only problem. Often due to vomiting if accompanied by metabolic alkalosis (decreased blood pH).

22. Ions
Calcium: Plays countless roles in the body – normal blood plasma concentration is 4.5 – 5.5 mEq/liter.
Most abundant mineral in the body.
98% of calcium in the body stored in bone.
Combines with phosphates to form mineral salts.
Mainly an extracellular cation.
Makes bones & teeth hard.
Plays important roles in blood clotting, neurotransmitter release, maintenance of muscle tone, & the excitability of nervous & muscle tissue.
Calcium concentration in blood plasma regulated via parathyroid hormone (PTH) & calcitriol (vitamin D – to help absorb calcium from food).
If concentrations drop, PTH secretion is stimulated, allowing bone to be broken down and its calcium reabsorbed.
Hypercalcemia: An elevated calcium level in the blood, causing increased urinary excretion – can be asymptomatic, but often is a sign of serious disease.
Hypocalcemia: An abnormally low concentration of calcium in the blood plasma – typically triggers the kidneys to reabsorb calcium instead of excreting it.

23. Ions
Phosphates: A critical component to several systems – normal blood plasma concentration is 1.7 – 2.5 mEq/liter.
Needed to synthesize ATP, other nucleotide phosphates, nucleic acids, & phospholipids.
85% of phosphates in adults are calcium phosphate salts – a structural component of bones & teeth.
15% of phosphates are ionized.
3 Important Phosphate Ions: Dihydrogen phosphate (H2PO4-), orthophosphate (PO4-3 ), & monohydrogen phosphate (HPO4-2).
HPO4-2 Is the most prevalent form – acts as an important buffer of H+ in body fluids & urine.
Regulated by PTH - stimulates the release of phosphates & calcium into the blood stream – inhibits reabsorption of phosphate & stimulates the reabsorption of calcium in the kidneys to lower blood phosphate levels.
Regulated by calcitriol (promotes the absorption of phosphates & calcium in the digestive tract).

24. Ions
Magnesium: One of those components needed for everything – normal blood plasma concentration is 1.3 – 2.1 mEq/liter.
Second-most common intracellular cation.
54% of magnesium in adults is part of the bone matrix as magnesium salts.
46% if magnesium in adults is ions in the ECF & ICF.
Cofactor for enzymes that metabolize proteins & carbohydrates & the sodium-potassium pumps.
Needed for normal neuromuscular activity, synapse transmission & myocardial functioning.
Controls the secretion of the parathyroid hormones.
Blood plasma levels regulated by the rate at which it is excreted in the urine.
Hypermagnesemia: An increase in magnesium concentration due to renal failure, increased in take of Mg+, increases in extracellular fluid volume, decreases
Hypomagnesemia: A lowered amount of Mg+, typically due to either an inadequate intake or an excessive loss through urine or feces.

25. Ions
Bicarbonate: An important metabolic component – normal concentrations from 2.2 – 2.6 mEq/liter.
Second most prevalent extracelular ion.
HCO3- concentration increases as blood flows through the systemic capillaries.
CO2 combines with H2O, forming carbonic acid.
Carbonic acid dissociates into hydrogen & bicarbonate ions.
Bicarbonate decreases as CO2 is exhaled.
Kidneys mainly responsible for regulating bicarbonate concentration.
Intercalated cells in renal tubules form bicarbonate & release it into the blood stream when levels are low, or excrete the excess if levels are high.

26. Acid-Base Balance
Acid-Base Balance: The major homeostatic challenge responsible for keeping pH (H+ concentration) of body fluids at the correct level.
This is vital for normal cellular function.
Remember: Blood pH is normally !
Any excess H+, which is a normal metabolic waste, must be removed from the body.
Buffer Systems: Act quickly to temporarily bind H+ to raise pH, but they don’t remove H+ from the body.
Exhalation of CO2: Increases the rate & depth of breathing to cause more CO2 to be exhaled – this reduces the carbonic acid in the blood to raise pH and reduce H+ levels.
Kidney Excretion of H+: Urination eliminates acids other than carbonic acid – slowest mechanism for pH change, but only method of removing acids.

27. Buffer Systems
Buffer System: Consists of a weak acid & its salt (that functions as a weak base).
Acid: A chemical that releases H+ into a solution.
Base: Chemical that accepts H+.
Buffer: Any mechanism that resists changes in pH by rapidly converting a strong acid or base into a weak acid or base.
Strong acids lower pH more than weak acids due to their readily releasing H+.
Strong bases raise pH more than weak bases do.
3 Main Buffer Systems:
Protein Buffer System
Carbonic Acid-Bicarbonate Bugger System
Phosphate Buffer System

28. Protein Buffer Systems
Protein Buffer System: Most abundant buffer in intracellular fluid & blood plasma – can buffer acids or bases.
Proteins are composed of amino acids with one carboxyl group (-COOH), which is a functional component of the buffer, & one amino group (NH2).
The free carboxyl group at one end of a protein acts like an acid by releasing H+ when pH rises.
When it dissociates, the H+ can react with excess OH- in the solution to form water.
NH2 groups can act as a base by combining with H+ when pH falls.

29. Carbonic Acid-Bicarbonate Buffer System
Carbonic Acid-Bicarbonate Buffer System: Includes bicarbonate ions acting as a weak base, and carbonic acid acting as a weak acid.
Excessive H+ would cause bicarbonate ions to function as a weak base, removing excess H+.
The carbonic acid dissociates into water & carbon dioxide, and the CO2 is exhaled from the lungs.
If there is a deficiency of H+ then carbonic acid can function as a weak base to relase more H+.

30. Phosphate Buffer System
Phosphate Buffer System: Works similarly to the carbonic acid-bicarbonate buffer system.
Dihydrogen phosphate (H2PO4-) and monohydrogen phosphate (HPO42-) work as the major components.
Phosphates are major anions in intracellular fluid & minor anions in extracellular fluid.
Combining a strong base, such as OH- with a weak acid such as dihydrogen phosphate yields monohydrogen phosphate (a weak base).
Monohydrogen phosphate ions can act as a weak base to buffer H+ released by strong acids (such as hydrochloric acid (HCL)).
Dihydrogen phosphate forms in the presence of excess H+ in the kidney tubules that then combines with monohydrogen phosphate – the H+ then passes into the urine.
The concentration of phosphates is higher in intracellular fluid, causing the buffer system to regulate within the cells.

31. Exhalation of Carbon Dioxide
Breathing helps maintain the pH of body fluid by exhaling CO2.
Exhaling CO2 removes carbonic acid from the system, which raises the blood pH.
This is why carbonic acid is called a volatile acid (an acid produced from carbon dioxide).
An increase in ventilation causes more CO2 to be exhaled, resulting in H+ concentration falling & blood pH raising.
Decreases in ventilation causes less CO2 to be exhaled, resulting in H+ concentration rising & blood pH falling.

32. Renal Regulation
Nonvolatile Acids: An acid produced from a source other than carbon dioxide, such as metabolic reactions.
H+ secretion in the urine is the only way to get rid of these acids.
Cells in the PTC & collecting ducts secrete H+ ions into the tubular fluid.
Intercalated cells have apical membranes containing proton pumps (H+ ATPases) that secrete H+ into the tubular fluid.
Bicarbonate ions inside the reneal intercalated cells cross the basolateral membrane by Cl-/HCO3- antiporters, then diffuse into peritubular capillaries.
Some intercallated cells have proton pumps in the basolateral memrbanes and Cl-/HCO3- antiporters in the apical membranes – these secrete bicarbonate ions & reabsorb hydrogen.
Intercallated cells regulate pH by excreting excess bicarbonate ions when pH is too high and H+ when pH is too low.

33. Mechanisms Maintaining Fluid pH
Buffer Systems: Mostly consist of a weak acid & that acid’s salt, which functions as a weak base – prevents drastic changes in pH.
Proteins: Most abundant buffers in body cells & blood – histidine & cysteine (amino acids) contribute most of the buttering along with hemoglobin.
Carbonic Acid-Bicarbonate Phosphates: Important regulator of blood pH – most abundant buffer in ECF – important ion intracellular fluid & urine.
Exhalation of CO2: Increase exhalation raises pH while decreased exhalation lowers pH.
Kidneys: Renal tubules secrete H+ into the urine & reabsorb HCO3 so it is not lost.

34. Acid-Base Imbalances
Acidosis (Acidemia): Occurs when the blood pH falls below 7.35, resulting in H+ diffusing into the cells and driving out potassium.
Depresses the central nervous system by inhibiting synaptic transmission.
Symptoms include confusion, disorientation, & coma (if pH falls below 7).
Alkalosis (Alkalemia): Occurs when the blood pH rises higher than 7.45, resulting in H+ diffusing out of the cells while potassium diffuses in.
Lowers the potassium concentration in the ECF.
Over-excites the central & peripheral nervous systems, causing nervousness, muscle spasms, convulsions, and sometimes even death.

35. Acid-Base Imbalances
Respiratory Acidosis & Alkalosis: Result from changes in the partial pressure of CO2 in the blood – compensated for by the kidneys.
Metabolic Acidosis & Alkalosis: Result from changes in the concentration of HCO3 in the blood – compensated for by the lungs.

36. Acid-Base Imbalances
Compensation: The response to an acid-base imbalance that seeks to normalize arterial blood pH.
Respiratory Compensation: Seeks to correct altered pH dye to metabolic causes via hyperventillation & hypoventillation.
Used to counter the effects of metabolic acidosis & metabolic alkalosis by elevating the bicarbonate concentration & pH of the urine.
Renal Compensation: A change in the secretion of hydrogen & reabsorption of bicarbonate ions by the kidney tubules that counters altered pH due to respiratory causes.
Used to counter the effects of respiratory acidosis & respiratory alkalosis.
Simple Version: If the lungs caused it, the kidneys try to fix it. If the kidneys caused it, the lungs try to fix it.

37. Acid-Base Imbalances
Respiratory Acidosis: Increased PCO2 (above 45 mmHg) and decreased pH (below 7.35) if no compensation occurs.
Common Causes: Hypoventilation due to emphysema, pulmonary edema, respiratory trauma, airway obstruction, or dysfunction of the respiratory muscles.
Compensatory Mechanisms: Renal – kidneys increase the excretion of H+ & increase the reabsorption of HCO-3.
If compensation completes, pH will be normal but PCO2 will be high.

38. Acid-Base Imbalances
Respiratory Alkalosis: Decreased PCO2 (below 35 mmHg) & increased pH (above 7.45) if no compensation occurs.
Common Causes: Hyperventilation due to oxygen deficiency, pulmonary disease, cerebrovascular accident (CVA), or severe anxiety.
Compensatory Mechanisms: Renal – kidneys decrease the excretion of H+ & decrease the reabsorption of HCO-3.
If compensation is complete, pH will be normal but PCO2 will be low.

39. Acid-Base Imbalances
Metabolic Acidosis: Decreased HCO3 (below 22 mEq/liter) & decreased pH (below 7.35) if no compensation occurs.
Common Causes: Loss of bicarbonate in the ions due to diarrhea, accumulation of acid (ketosis) or renal dysfunction.
Compensatory Mechanisms: Respiratory – hyperventilation occurs to increase the loss of CO2.
If compensation completes, pH will be normal but HCO-3 will be low.

40. Acid-Base Imbalances
Metabolic Alkalosis: Increased HCO3 (above 26 mEq/liter) & increased pH (above 7.45) if no compensation occurs.
Common Causes: Loss of acid due to vomiting, gastric suctioning, use of certain diuretics or excessive intake of alkaline drugs.
Compensatory Mechanisms: Respiratory – hypoventillation, which slows down the loss of CO2.
If compensation completes, pH will be normal but HCO-3 will be high.