Cell Physiology Lecture 5 Capillary fluid balance Fluid compartments

1. Cell Physiology – Lecture 5Capillary fluid balanceFluid compartments swood@umhs-sk-physiology.org 2011

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3. Water transport across capillaries Water can cross capillary membranes via: the intercellular gaps between the endothelial cells (typical gap = 7nm; H2O = 0.12nm) pores in the endothelial cells special areas where the cytoplasm is so thinned out that it produces deficiencies known as fenestrations. diffusion across the lipid cell membranes of the endothelial cells (Kp is low, 10-6, BUT total surface area = 6300 m2; thickness = 1 mm) 3

4. 4 Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org). http://emedicine.medscape.com/article/244631-overview Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org).Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org). http://emedicine.medscape.com/article/244631-overview Schematic drawing of the glomerular barrier. Podo = podocytes; GBM = glomerular basement membrane; Endo = fenestrated endothelial cells; ESL = endothelial cell surface layer (often referred to as the glycocalyx). Primary urine is formed through the filtration of plasma fluid across the glomerular barrier (arrows); in humans, the glomerular filtration rate (GFR) is 125 mL/min. The plasma flow rate (Qp) is close to 700 mL/min, with the filtration fraction being 20%. The concentration of albumin in serum is 40 g/L, while the estimated concentration of albumin in primary urine is 4 mg/L, or 0.1% of its concentration in plasma. Reproduced from Haraldsson et al, Physiol Rev 88: 451-487, 2008, and by permission of the American Physiological Society (www.the-aps.org).

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7. 7 Glomerular capillaries have a reflection coefficient close to 1 as normally no protein crosses into the glomerular filtrate. In contrast, hepatic sinusoids have a low reflection coefficient as they are quite permeable to protein. This is advantageous because albumin is produced in hepatocytes and can relatively freely pass from these cells into the blood in the sinusoids. The predominant pathway for albumin and other proteins to enter the circulation is via the lymph. [edit] Approximated values Following are approximated values for the variables in the equation for both arterioles and venules: Location Pc (mmHg) [2] Pi (mmHg) [2] spc (mmHg) [2] spi (mmHg) [2] arteriolar end of capillary +35 -2 +28 +0.1 venular end of capillary +15 -2 +28 +3Glomerular capillaries have a reflection coefficient close to 1 as normally no protein crosses into the glomerular filtrate. In contrast, hepatic sinusoids have a low reflection coefficient as they are quite permeable to protein. This is advantageous because albumin is produced in hepatocytes and can relatively freely pass from these cells into the blood in the sinusoids. The predominant pathway for albumin and other proteins to enter the circulation is via the lymph. [edit] Approximated values Following are approximated values for the variables in the equation for both arterioles and venules: Location Pc (mmHg) [2] Pi (mmHg) [2] spc (mmHg) [2] spi (mmHg) [2] arteriolar end of capillary +35 -2 +28 +0.1 venular end of capillary +15 -2 +28 +3

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13. 13 Angioedema may be caused by an allergic reaction. During the reaction, histamine and other chemicals are released into the bloodstream. The body releases histamine when the immune system detects a foreign substance called an allergen. Often the cause of angioedema is never found. The following items may cause angioedema. Animal dander (scales of shed skin) Medications (drug allergy), such as antibiotics (penicillin and sulfa drugs) and blood pressure medicines (ACE inhibitors) Exposure to water, sunlight, cold or heat Foods (such as berries, shellfish, fish, nuts, eggs, milk, and others) Insect bites Pollen Hives and angioedema may also occur after infections or with other illness (including autoimmune disorders such as lupus and leukemia and lymphoma). A form of angioedema runs in families and has different triggers, complications, and treatments. This is called hereditary angioedema, and it is not discussed here. Angioedema may be caused by an allergic reaction. During the reaction, histamine and other chemicals are released into the bloodstream. The body releases histamine when the immune system detects a foreign substance called an allergen. Often the cause of angioedema is never found. The following items may cause angioedema. Animal dander (scales of shed skin) Medications (drug allergy), such as antibiotics (penicillin and sulfa drugs) and blood pressure medicines (ACE inhibitors) Exposure to water, sunlight, cold or heat Foods (such as berries, shellfish, fish, nuts, eggs, milk, and others) Insect bites Pollen Hives and angioedema may also occur after infections or with other illness (including autoimmune disorders such as lupus and leukemia and lymphoma). A form of angioedema runs in families and has different triggers, complications, and treatments. This is called hereditary angioedema, and it is not discussed here.

14. 14 Elephantiasis, or Lymphatic Filariasis, is a rare disorder of the lymphatic system caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi, and B. timori, all of which are transmitted by mosquitos. Inflammation of the lymphatic vessels causes extreme enlargement of the affected area, most commonly a limb or parts of the head and torso. It occurs most commonly in tropical regions and particularly in parts of Africa. Elephantiasis, or Lymphatic Filariasis, is a rare disorder of the lymphatic system caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi, and B. timori, all of which are transmitted by mosquitos. Inflammation of the lymphatic vessels causes extreme enlargement of the affected area, most commonly a limb or parts of the head and torso. It occurs most commonly in tropical regions and particularly in parts of Africa.

15. Body Fluids Volumes Concentrations Amounts 15 Learning Objectives: Body Fluids 1.  Given the body weight, estimate the a) total body water, b) extracellular fluid volume, c) intracellular fluid volume,d) blood volume, ande) plasma volume.  2. Identify normal extracellular fluid (plasma) osmolarity and concentrations of Na+, K+, Cl-, HCO3-, proteins, creatinine, and urea, and contrast these values with those for intracellular fluids. 3.  Given the composition and osmolality of a fluid, identify it as hypertonic, isotonic, or hypotonic. Predict the change in transcellular fluid exchange that would be caused by placing a red blood cell in solutions with varying tonicities. Learning Objectives: Body Fluids 1.  Given the body weight, estimate the a) total body water, b) extracellular fluid volume, c) intracellular fluid volume,d) blood volume, ande) plasma volume.  2. Identify normal extracellular fluid (plasma) osmolarity and concentrations of Na+, K+, Cl-, HCO3-, proteins, creatinine, and urea, and contrast these values with those for intracellular fluids. 3.  Given the composition and osmolality of a fluid, identify it as hypertonic, isotonic, or hypotonic. Predict the change in transcellular fluid exchange that would be caused by placing a red blood cell in solutions with varying tonicities.

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17. Concentration = amount/volume e.g., g/L or mol/L Problem: What amount of NaCl is present in 10 L of a NaCl solution with a concentration of 5g/L ?

18. Concentration = amount/volume e.g., g/L or mol/L Problem: you add 10 g of NaCl to 2 L of water. What is the concentration?

19. Concentration = amount/volume e.g., g/L or mol/L Problem: A physician injects 10 g of a chemical into a patient’s vein. The chemical has properties that “traps” it in the circulatory system. A blood sample is taken 5 minutes later (after complete mixing has occurred) and the concentration is measured at 1 g/L. What is the patient’s blood volume?

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21. USMLE practice problem A 30-year-old woman, weight 100 kg) is given 0.1 g inulin intravenously. One hour later, the plasma inulin concentration is 1 mg/100ml. Which of the following is the extracellular fluid volume of the woman? 8 L 10 L 12 L 14 L 16 L 21

22. Body Fluids Osmosis Osmotic Pressure (?) From thermodynamics, the chemical potential of water is related to the activity of water and the hydrostatic pressure. When solute is increased the activity of water is decreased so that at equilibrium (across a semi-permeable membrane) the hydrostatic pressure of the solution with higher solute is increased.From thermodynamics, the chemical potential of water is related to the activity of water and the hydrostatic pressure. When solute is increased the activity of water is decreased so that at equilibrium (across a semi-permeable membrane) the hydrostatic pressure of the solution with higher solute is increased.

23. Learning Objectives Define osmolarity (and osmolality) Use the van’t Hoff equation to calculate the osmotic pressure of a solution Contrast the terms “isotonic” and “isosmotic” Describe the “reflection coefficient” for solutes

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25. Cells from a single population are suspended in solutions X and Y, and cell volume measurements are made. The graph shows the volume of cells in solution X (solid curve) and solution Y (dashed curve). The results indicate that solution Y, with respect to X, is which of the following? (A) Hypertonic (B) Hypotonic (C) Isosmotic (D) Isotonic The correct answer is B. The dashed curve is shifted to the right along the x-axis, indicating an increase in volume of the cells. The volume of the cells is greater in solution Y because of cellular swelling as water flows into the relatively hypertonic cells from the relatively hypotonic solution (osmosis). If solution Y were relatively hypertonic (choice A), the cells would shrink as water flowed out of the cells into the solution, and curve Y would be left-shifted with respect to curve X. If solution Y were isoosmotic (choice C) with solution X, there would be no volume change and the two distributions would be identical. Another way of saying this is that the two solutions are isotonic (choice D) with respect to each other. The correct answer is B. The dashed curve is shifted to the right along the x-axis, indicating an increase in volume of the cells. The volume of the cells is greater in solution Y because of cellular swelling as water flows into the relatively hypertonic cells from the relatively hypotonic solution (osmosis). If solution Y were relatively hypertonic (choice A), the cells would shrink as water flowed out of the cells into the solution, and curve Y would be left-shifted with respect to curve X. If solution Y were isoosmotic (choice C) with solution X, there would be no volume change and the two distributions would be identical. Another way of saying this is that the two solutions are isotonic (choice D) with respect to each other.

26. Osmolarity Osmolarity = concentration of osmotically active particles Osmolarity = g x concentration, mol/L g = particles per mole , Osm/mol Osm = g x C = Osm/mol x mol/L = Osm/L

27. examples 2 mmol/L urea Osmolarity = g x C = 1 mOsm/mmol x 2 mmol/L = 2 mOsm/L 1 mmol/L NaCl (g = 1.85)) (NaCl not completely dissociated) Osmolarity = 1.85 mOsm/mmol x 1 mmol/L = 1.85 mOsm/L NOT isosmotic

28. Osmotic Pressure (revised) Osmosis is the flow of water from an area of low solute concentration to an area of high solute concentration Particles in solution exert pressure against semipermeable membranes (so water exerts less pressure) Number of particles, not mass of particles, determines how much pressure is exerted

29. Osmotic pressure ? = g C ? RT (van't Hoff equation) ? = reflection coefficient ( 0 to 1) ? = difficulty for given solute to penetrate membrane ? = 0 for freely permeable (e.g., urea) ? = 1 for impermeable (e.g., serum albumin) If ? = 0, ? = 0

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31. Osmotic Pressure

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35. Measuring volumes in different body compartments Dilution technique 35

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38. USMLE practice problem A 30-year-old woman, weight 100 kg) is given 0.1 g inulin intravenously. One hour later, the plasma inulin concentration is 1 mg/100ml. Which of the following is the extracellular fluid volume of the woman? 8 L 10 L 12 L 14 L 16 L 38 Answer = 10 L Solution: Amt = VC Amt. injected = 0.1 g = 100 mg Amt after equilibrium also = 0.1 g = 100 100mg g = VC 100 mg = V x 1mg/100 ml or 10 mg/L 100 mg = V x 10 mg/L V = 100 mg/10 mg/L = 10 L Answer = 10 L Solution: Amt = VC Amt. injected = 0.1 g = 100 mg Amt after equilibrium also = 0.1 g = 100 100mg g = VC 100 mg = V x 1mg/100 ml or 10 mg/L 100 mg = V x 10 mg/L V = 100 mg/10 mg/L = 10 L

39. Blood volume = plasma vol. + RBC vol. 39

40. Blood volume Blood volume can be determined by measurement of plasma volume and hematocrit. Hematocrit (Hct) = RCV/BV BV = PV/(1-Hct) (hct expressed as fraction (45% = 0.45) 40

41. Tps (new problem) A 100kg patient is admitted to the ER after an auto accident. BP is 80/50. radial pulse cannot be felt. Femoral pulse is weak. CBC shows a Hb of 15 and hct of 40%. Plasma volume is 1.8 L. What is the patient’s predicted blood volume? 41

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