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PHYSIO ● PHYSIOLOGY Water and Electrolytes Homeostasis (Renal 2) TRANS 6 R MODULE 11 oberto A. Razo II, M.D. March 04, 2023 LECTURE OUTLINE I BODY FLUID COMPARTMENTS A. Fluid Compartments II ELECTROLYTES A. Electrolyte Concentration III MOVEMENT OF WATER A. Between Compartments B. Between ICF and ECF IV Osmosis: Balance Between Water and Solutes A. Distribution of Water and Solutes V Clinical Application of Water Regulation A. Water Loss B. Sodium C. Edema D. Causes of Edema E. Blood Loss VI Clinical Application of Water Intake LECTURE OBJECTIVES 1. Discuss the different body fluid compartments 2. Characterize the components of the body fluid compartments 3. Discuss the blood compartment as a unique fluid compartment 4. Describe the electric concentration of the fluid compartments 5. Discuss the effect of electrolyte concentration on fluid distribution 6. Discuss the clinical correlation of physiologic principles of water regulation. I. BODY FLUID COMPARTMENTS TOTAL BODY WATER (TBW) ● Can be estimated by multiplying a factor to Body Weight (BW) ● Example: 70kg Male ○ TBW = 42L ● Age increases: ○ TBW decreases ○ Fat increases Table 1. Total Body Water Males Females 60% of Body Weight 50% of Body Weight A. Fluid Compartments 1. Blood Compartment ● Separated from the space around it via the blood vessel wall and capillary membrane ● Plasma ○ Non-cellular portion of the blood compartment ○ Contains materials such as protein ○ Cellular Compartment: Includes the RBCs and WBCs BLOOD COMPARTMENT Plasma CAPILLARY MEMBRANE Interstitial Fluid Transcellular Fluid CELL MEMBRANE Intracellular Fluid Figure 1. Physiologic Fluid Compartments where Total Body Water along with electrolytes and other solutes is distributed. Guyton and Hall Textbook of Medical Physiology (14th ed) p. 306. 2. Capillary Membrane ● Site of exchange of fluids, electrolytes, and other components in the blood between the blood compartment and the adjacent interstitial fluid compartment 3. Interstitial Fluid Compartment ● Contains fluid and other solutes that exist outside the blood compartment and various cells in the body. ● Along with plasma, is part of the compartment called “extracellular fluid space.” 4. Cell Membrane ● Separates interstitial fluid and intracellular fluid compartment. 5. Transcellular Compartment ● A special compartment ● Describes the fluid contained in the: ○ Synovium, ○ Peritoneum, ○ Pericardial space, ○ Intraocular spaces, and ○ Cerebrospinal fluid 6. Intracellular Fluid ● Describes the fluid that is contained within the cells of our body such as the adipocytes, hepatocytes, and myocytes ● 40% of the total body weight ○ In a 70 kg male → estimated to be 28 L ● 2⁄3 of total body fluid ● Small variance between cells ○ Each cell’s fluid content is separated from other cells via its own cell membrane ○ Total fluid inside a cell is clumped in a physiological compartment since there is a small variance in the components of the said fluid in each of the individual cells. ○ A systemic change in electrolyte balance will have a homogeneous effect in every cell of the body (with some exceptions) Group 7A, 8A, 9A, & 10A | Water and Electrolytes Homeostasis (Renal 2) 1
7. Extracellular Fluid ● 20% of body weight ○ In a 70 kg male → estimated to be 14 L ● Includes plasma and interstitial fluid ● Almost the same composition and concentration of solutes in different regions of the body ● Protein concentration: Higher in plasma than in interstitial fluid 8. Blood compartment (cont.) ● Completely different compartment compared to ICF and ECF ○ Due to its enclosure between blood vessel wall and capillaries ○ Contains ICF from blood cells and ECF from plasma ● At capillary level, there is noticeable exchange of material between blood compartment and the interstitial space through the capillary membrane ● Important in circulation and its dynamics ○ Blood compartment is important in maintaining adequate circulation and distribution of nutrients and oxygen in the body ■ Regulation and hemodynamics involve aspects of this compartment ○ Depletion of contents in blood compartment → collapse in circulation and hemodynamics ○ Blood volume is 7% of body weight ■ In a 70 kg male → estimated to be 5 L ■ 60% plasma ● In a 5 L blood compartment, 3 L is plasma ■ 40% RBC ● In a 5 L blood compartment, 2 L is plasma II. ELECTROLYTES Table 2. Summary of cations and anions inside and outside the cell Extracellular Intracellular ● Sodium: most predominant extracellular cation ● Chloride: most common extracellular anion ● Bicarbonate ● Calcium ● Potassium: most predominant intracellular cation ● Organic Anions + phosphates: predominant intracellular anion ● Protein: significant in maintaining a negative charge (-) inside the cell ● Magnesium Figure 2. Concentrations of major cations and anions of the intracellular and extracellular fluids. Guyton and Hall Textbook of Medical Physiology (14th ed) p.307. Figure 3. Non-electrolytes of the plasma. Guyton and Hall Textbook of Medical Physiology (14th ed) p. 307. ● Non-electrolytes ○ Exert electrical charges because of their structures ○ Contribute to osmotic gradient forces. ○ Can cause enough solute concentration to draw water towards those of higher osmotic gradient. A. ELECTROLYTE CONCENTRATION ● Solutes particularly electrolytes have slightly different concentrations in the plasma and in the interstitial space Cations Na + ,Ca 2+ , K + , Mg 2+ Concentration is slightly higher in the plasma than the interstitial space Anions Cl - , HCO3 - , HPO4 - , H2PO4 - , SO4 - Have a slightly lower concentration in the plasma than the interstitial space. Group 7A, 8A, 9A, & 10A | Water and Electrolytes Homeostasis (Renal 2) 2
Figure 4. Osmolar Substances in Extracellular and Intracellular Fluids. Guyton and Hall Textbook of Medical Physiology (14th ed) p. 308. 1. Donnan Effect ● The effect of negatively-charged molecules in the plasma in which they attract positively-charged cations and repel negatively-charged anions ○ Attracts (+) charged cations and repels (-) charged anions ○ Explains why cations have a slightly increased concentration in the plasma while anions have a decreased concentration in the plasma. 2. Osmolarity ● Total osmolarity takes into account all the effects of all solutes in each space ● Equilibrium = 280 Figure 5. Body Fluid Measurement Doc Razo’s video lecture. ● Some body fluids are only indirectly measured ○ Two volumes are taken, and one is subtracted from the other ○ Eg. Intracellular fluid, interstitial fluid III. MOVEMENT OF WATER 1. Osmolality ● The drive of movement of water in the body. ● Osmoles of solute or the amount of solute per kilogram of solvent. ○ In the body the most significant solvent is water REMEMBER: Water moves in between compartments, and compartments are separated by semi-permeable membranes– solutes do not. General Rule: water moves from one compartment to another freely between the semi-permeable membrane; while solutes inside the compartment remain there unless affected by certain processes like active transport or facilitated diffusion. “WHERE SODIUM GOES, WATER FOLLOWS” ● The concentration of solutes in one compartment creates an osmotic gradient that attracts water. ○ When the compartment has a higher osmolality than the other compartment, water from the compartment with the lower osmolality will move towards the compartment with the higher osmolality. ● Sodium is the most predominant extracellular solute ○ Water is bound to get dragged by sodium A. BETWEEN COMPARTMENTS 1. Osmosis ● Governs water shifts in between compartments 1 2 Isotonic Hypotonic Hypertonic Iso-osmotic Hyperosmotic Hypo-osmotic ● Water shift: compartment with low solute concentration → compartment with a higher solute concentration, over a semi-permeable membrane ● 2 solutions are compared in terms of their solute concentration as to whether they are isotonic, hypotonic, or hypertonic. Table 3. Osmolality 1 Solute Concentration Statement A = B Solution A is isotonic to Solution B A < B Solution A is hypotonic to Solution B A > B Solution A is hypertonic to Solution B It is not about the absolute amount of solute but rather the concentration of the solute within a given solvent– its osmolality. A solution can be isotonic to another solution, but the behavior of the solute influences the final shifts in the fluids. Table 4. Osmolality 2 Solution A: Glucose + Water Solution A is placed beside Solution B, over a semi-permeable membrane, the osmolality of solutions A and be are the same. 1 Both solutions are isotonic, however, the semi-permeable membrane is permeable to a certain amount of glucose. 2 Some of the glucose molecules from Solution A will transfer to Solution B. Net effect: Solution A would be hypo-osmotic to Solution B. ● Movement of the solute and solvent would cause solution A to be less concentrated, in terms of solute concentration, than Solution B. General Rule: Isoosmotic, Hyperosmotic, and Hypo-osmotic solutions take into consideration the movement of solute and solvent. ● Compared to the Isotonic, Hypotonic, and Hypertonic which only refers to the concentration of the solute between Solutions A and B Group 7A, 8A, 9A, & 10A | Water and Electrolytes Homeostasis (Renal 2) 3
B. BETWEEN ICF AND ECF Figure 6. Effects of Adding Different Solutions. Doc Razo’s video lecture. NORMAL STATE Predominantly fluid is found in the intracellular fluid space than the extracellular fluid space A. ADD ISOTONIC NaCl If an Isotonic NaCl solution is added in the vascular space and infused in the blood compartment, since the blood compartment is part of the extracellular fluid, then the net volume of the extracellular fluid space increases. ● Ex. 0.9% Isotonic NaCl Solution ● Since the solution is isotonic, the osmolarity of the extracellular space does not change that much. ● The net movement of water is negated, and the extra fluid that was infused remains in the extracellular fluid space. B. ADD HYPERTONIC NaCl If a Hypertonic Solution is added in the blood ● ↑ volume ● ↑ osmolality of the space since it has more solute. ● Since ECF space has more solute, water from the ICF space will shift towards the hypertonic ECF space, causing the net volume of the ICF to contract. ● Since free fluid now moves towards the ECF, the solutes remain in the ICF, causing the net concentration of these solutes to increase inside the ICF space. C. ADD HYPOTONIC NaCL If a Hypotonic NaCl solution is added in the blood compartment ● Ex. 0.3% Hypotonic NaCl solution ● Then the volume will be increased since it is found in the blood. ● The tonicity of the solution is lower than that of the body, the net osmolarity of the extracellular space decreases. ● Since the hypotonic solution is infused, water will move from the extracellular fluid space to the intracellular fluid space. ○ The extracellular fluid space has been diluted, making it less concentrated. ○ Increase in the volume of the fluid found in the intracellular fluid space. Figure 7. What happens when a 3% hypertonic NaCl solution is added to the ECF. Doc Razo’s video lecture. ● The concentration of the solutes of the body in equilibrium is 280. ● When you infuse a 3% NaCl solution that is 2 liters in the blood compartment, that goes to the ECF. TABLE 1 The first table in figure 7 represents the volume and the concentration of the ECF and the ICF before the 3% hypertonic solution of NaCl is added, therefore in equilibrium. 2 The second table shows the immediate effects after the infusion. ● The volume of the extracellular fluid space will increase by 2 liters (from 14 to 16 L) ● The concentration of solutes will increase (from 280 to 373) because it’s a hypertonic saline solution. ● There is still no movement yet in the intracellular fluid space (still 28 L). 3 The third table shows the later effects as equilibrium is reached. ● Since this is a hypertonic saline solution and the ECF is now more concentrated, fluid from the ICF will now move towards the ECF, causing a drop in the volume of the ICF (from 28 to 24.98 L). ● And since water moved from the ICF to the ECF, the volume of water in the ECF increased (from 16 to 19L). ● The concentration of the ICF and ECF are equal, so equilibrium is reached. ● Basically, for the net effect to be seen fully, you need to allow for equilibrium. IV. OSMOSIS: BALANCE BETWEEN WATER AND SOLUTES ● Osmosis is important in predicting the movement of water and the change in osmolality between compartments. ○ This is what governs the balance between solutes such as sodium and water. ● In real life, water and solutes, particularly sodium, come in via oral intake (in the food we eat). ● In special circumstances such as when one is confined, they may come in via intravenous fluid or via intravascular access. Group 7A, 8A, 9A, & 10A | Water and Electrolytes Homeostasis (Renal 2) 4
A. DISTRIBUTION OF WATER AND SOLUTES BLOOD ➜ INTERSTITIAL SPACE ➜ ICF ● When the fluids, water, solutes, etc. get around the body, they usually go first from the blood and into the interstitial space. ○ The blood compartment and the interstitial space are separated by the capillaries. ● Then they go from the interstitial space to the intracellular fluid. ○ The interstitial space is invariably in contact with the intracellular space. ○ They are separated by the cell membrane. ● Special cases of distribution happen in terms of the cells located directly in the blood such as the RBCs and WBCs. NOTE: In any of the intakes, the blood compartment will ultimately become affected and this will be important in the clinical application of hemodynamics or the control and management of the circulatory capacity and blood pressure. V. CLINICAL APPLICATION OF WATER REGULATION A. WATER LOSS ● Everyday we lose water voluntarily and involuntarily ● In normal individuals we lose water in various sites such as in the skin, lungs, sweat, feces, and urine Table 5. Water Loss in the Different Parts of the Body PART AMOUNT OF WATER LOSS SKIN 350 ml/day LUNGS 350 ml/day SWEAT 100 ml/day FECES 100 ml/day URINE 1400 ml/day Source: Dr. Roberto Razo II's Lecture Video Part 3 1. Skin ● The insensible losses from the skin are water which the skin cannot hold onto that evaporates in the air 2. Lungs ● The air we breathe, in and out, carries water with it 3. Sweat ● Sweat can release as low as 100 ml/day, but in extreme temperatures and during extraneous activities, expect to lose more than 100 ml/day. 4. Feces ● In cases of diarrhea and loose stools, we may lose more than 100 ml/day of water in feces which may be dangerous as it can lead to dehydration. This may need rehydration strategies such as intravenous fluid infusion or oral rehydration solution to replenish lost fluids 5. Urine ● Urine output can be as little as 500 ml to as much as 1500 ml/day with an average of almost 1.5 liters/day. ● Average intake: ~2100 ml/day ● In cold climates, there is a decrease in atmospheric vapor pressure thus having greater water loss in your breath as compared to hot climates. This may be the reason why we can see our breath visibly when we breathe in and out. ● In hot climates, we tend to lose water in the form of sweat. B. SODIUM Table 6. Clinical Application on Sodium ABNORMALITY CAUSE PLASMA NA+ CONC. ECF VOLUME ICF VOLUME HypoNa+ Dehydration AI, Diuretics, Diarrhea, Vomiting ↓ ↓ ↑ HypoNa+ Overhydration Excess ADH, bronchogenic tumors ↓ ↑ ↑ HyperNa+ Dehydration DI, sweating ↑ ↓ ↓ HyperNa+ Overhydration Cushing’s Disease, Primary Aldosteronism ↑ ↑ ↓ Source: Dr. Roberto Razo II's Lecture Video Part 3 RECALL: Where sodium goes, water follows ● Sodium regulation is closely knit with water regulation ● Hyponatremia and hypernatremia pertain to sodium concentration in the serum or blood compartment lower and higher than normal, respectively ● Overhydration and Dehydration is the status of water contained inside the body or total body water. ○ Overhydration - means we have excess water ○ Dehydration - means we lack water 1. Hyponatremia with Dehydration ● Happens in conditions that promote actual salt (NaCl) loss ○ Because of this salt loss, water is dragged over with it ● Usually happens in the urine and GI tract ● Clinical Correlation: Adrenal insufficiency, use of diuretics, diarrhea and vomiting ● Actual sodium loss: ○ ↓ plasma Na+ concentration = ○ ↓ extracellular fluid volume (ECF Volume), which is part of the blood compartment = ○ ↑ intracellular fluid volume (ICF Volume) WHY ICF VOLUME INCREASES: Sodium loss would make the ECF space more hypotonic than the ICF volume. Thus, the water in ECF would come into the ICF since there was no solute change in it as compared to ECF where there is loss of electrolytes 2. Hyponatremia with Overhydration ● Conditions when there is dilution of the solutes in the blood compartment. ● Basically, water retention ● Excess antidiuretic hormone → water reabsorption in the kidneys ● Causes: ○ Excess ADH ○ Bronchogenic tumors (secretes ADH) ● Because of the retention of water the blood compartment becomes diluted and ○ ↓ sodium concentration in the plasma ● Water goes to the interstitial space ○ ↑ ECF volume increases ○ Because of this the blood compartment and the ECF space becomes relatively hypotonic compared to the intracellular fluid space ● This would lead to the water coming in to the intracellular fluid space Group 7A, 8A, 9A, & 10A | Water and Electrolytes Homeostasis (Renal 2) 5