1. Introduction and Body Fluid Compartments Vivek Bhalla, MD Division of Nephrology Stanford University School of Medicine August 28th, 2015

2. Anatomy of the Renal Block PhysiologyPathophysiologyUrology Body Fluids -1Glomerular Diseases – 3Histology Lab GFR, Clearance -1Acute Kidney Injury – 1Malignancy – 1 Sodium / Diuretics – 2Chronic Kidney Disease – 3 Potassium – 2Renal Lab -2 Acid – 2Transplant Pathology-1 Water – 2Vascular Diseases – 1/2 Steady State - 1Plumbing- 1/2

3. The Roles of the Kidneys Control the volume and composition of the body compartments i.e. keep us in chemical balanceControl the volume and composition of the body compartments i.e. keep us in chemical balance Remove organic waste productsRemove organic waste products Make necessary hormonesMake necessary hormones –(our own personal Lance Armstrong)

4. Learning Objectives (3) Memorize (unfortunately) the concentrations of the principal ions in the extracellular and intracellular fluid.Memorize (unfortunately) the concentrations of the principal ions in the extracellular and intracellular fluid. Know the difference between intracellular fluid, extracellular fluid, plasma, and interstitial fluid, and how to estimate the volume of each of these compartments in a patient.Know the difference between intracellular fluid, extracellular fluid, plasma, and interstitial fluid, and how to estimate the volume of each of these compartments in a patient. Understand the composition of two common intravenous fluids used in medicine – 5% Dextrose (“D5W”) and 0.9% Sodium Chloride (“Normal Saline”)Understand the composition of two common intravenous fluids used in medicine – 5% Dextrose (“D5W”) and 0.9% Sodium Chloride (“Normal Saline”)

5. “le milieu intérieur” The fixity of the milieu supposes a perfection of the organism such that the external variations are at each instant compensated for and equilibrated.... All of the vital mechanisms, however varied they may be, have always one goal, to maintain the uniformity of the conditions of life in the internal environment.... The stability of the internal environment is the condition for the free and independent life. Claude Bernard The fluid surrounding our cells Extracellular Fluid (ECF)

6. The Roles of the Kidneys Control the volume and composition of the body compartments i.e. keep us in chemical balanceControl the volume and composition of the body compartments i.e. keep us in chemical balance Remove organic waste productsRemove organic waste products Make necessary hormonesMake necessary hormones –(our own personal Lance Armstrong) Internal milieu

7. Cells Environment ECF = Water in the Fish Tank ECF = Water in the Fish Tank

11. How the kidney regulates the volume and ionic composition of the extracellular fluid (the fish tank) Learning Objective (Renal Physiology)

12. Example The plasma K + concentration is 6.5 mEq/L (normal 4.5 mEq/L) Approach #1: What are the common causes of a high plasma K + concentration? Approach #2: How does my body regulate the plasma K + concentration? Common causes are those which frequently affect the regulatory machinery. How? Not What? (Renal Physiology)

13. Basic Body Compartments Intracellular Fluid Extracellular Fluid

14. Bacteria…..Not Us! Intracellular Fluid Extracellular Fluid 100 mOsm < 10 mOsm

15. Our Body Composition…Our Fish Tank Intracellular Fluid Extracellular Fluid 290 mOsm 140 meq/L Na+ 4.5 meq/L K+ 40 neq/L H+

16. Total body water (TBW) – all the fluid in and out of cells Intracellular fluid - inside cells; 2/3 rd of TBW Extracellular fluid - outside cells; 1/3 rd of TBW Plasma - in blood vessels, about 1/4 th of ECF Interstitial - between cells Definitions…Need to Memorize

17. Definitions Extracellular Fluid Intracellular Fluid Interstitial FluidPlasma

18. Blood Rough Estimates – 70 kg, person Extracellular Fluid Intracellular Fluid Interstitial FluidPlasma 28 Liters 11 L 14 L 3 L Total Body Water = 60% of total body weight = 42 L

19. Total body water (TBW) – all the fluid in and out of cells Intracellular fluid - inside cells; 2/3 rd of TBW Extracellular fluid - outside cells; 1/3 rd of TBW Plasma - in blood vessels, about 1/4 th of ECF Interstitial - between cells Let’s Repeat That 70 kg * 60% = 42L 42 L* 2/3 = 28L 42 L* 1/3 = 14 L 14 L* ~1/4 = 3L 14 L – 3L= 11L

20. Body Compartments…Let’s Repeat That

21. Composition of Body Compartments

22. Pop Quiz The [Na + ] outside the cell is approximately… 1. 150 mEq/L 2. 100 mEq/L 3. 50 mEq/L 4. 10 mEq/L

23. Our Body Composition…Our Fish Tank Intracellular Fluid Extracellular Fluid 290 mOsm 140 meq/L Na+ 4.5 meq/L K+ 40 neq/L H+ Na+ K+ Na+-K+ ATPase pump

24. If you infuse a saline solution (salt in water) into a person’s vein (intravenous infusion), where does the Na + go? 1.Into the vascular (plasma) space 2.Into the vascular and interstitial spaces 3.Throughout the body water (vascular space plus interstitial space plus cells) Pop Quiz

25. mmole = 1/1000 of a mole of ions or molecules mEq = 1/1000 of a mole of charge so 1 mmole of Na + is the same as 1 mEq of Na + but 1 mmole of Ca ++ is the same as 2 mEq of Ca + + mosmole = 1/1000 of a mole of particles in solution so 1 mmole/liter of glucose gives a 1 mosmolar solution but 1 mmole/liter of NaCl gives a 2 mosmolar solution ? a glucose solution of 5mmoles/liter is how many mEq/liter? Zero….glucose has no charge Definitions…Need to Memorize

26. Calculate the osmolality of a 5% dextrose solution… 5% dextrose is: 5 grams / 100 milliliters = 50 grams / liter 50 grams/liter divided by 180 grams/mole: = 0.278 moles/liter = 278 millmoles/liter = 278 mOsm Why do we use a dextrose solution of 5 grams/100 ml? Example # 1

27. You can’t infuse pure water (the red cells would blow up) 280 mOsm inside the cell start with 280 mOsm in the plasma but rapidly infuse pure water and the plasma osmolality goes down in the vein where the water is infused <200 mOsm in the plasma

28. Add sugar…

29. If you infuse 5% dextrose intravenously, the sugar will be metabolized (remember biochemistry). Where will the water go? 1.into the vascular space 2.into the vascular and interstitial spaces 3.throughout the body water (vascular space plus interstitial space plus cells) Pop Quiz

30. Example # 2 Calculate the NaCl concentration in grams per liter (g/L) required to get an osmolality of 290 milliosmoles per liter (mOsm/L)… We want: 290 mOsm/L Since each NaCl breaks up into 2 ions in solution, then we will need: 145 mmol/L After a small correction (technicality), the answer is: ~ 155 mmol/L 0.155 moles/liter * 58.5 grams/mole :~ 9.0 g/L = 0.9 grams/100 mL = 0.9% saline = “Normal Saline”

31. If you infuse 1 liter of “normal” saline intravenously, the ECF volume will… 1.increase by about 2 liters 2.increase by about 1 liter 3.increase by about 1/3 liter 4.decrease by about 1 liter Pop Quiz

32. If you infuse 1 liter of 5% dextrose in H2O intravenously, the ECF volume will… 1.increase by about 2 liters 2.increase by about 1 liter 3.increase by about 1/3 liter 4.decrease by about 1 liter But…

33. Rough Estimates – 70 kg, person Extracellular Fluid Intracellular Fluid Interstitial FluidPlasma 28 Liters 11 L 14 L 3 L Total Body Water = 60% of total body weight = 42 L Blood

34. Body Compartments

35. Most of the body water is? 1.Outside the cells 2.Inside the cells Pop Quiz

36. The standard 70 kg genderless teaching person contains about… 1. 20 liters of extracellular fluid 2. 15 liters of extracellular fluid 3. 10 liters of extracellular fluid Pop Quiz

37. Quantitative But Not Precise Renal Physiology

38. A 70 kg patient has a plasma [Na + ] of 165 mEq/L. About how much water must you give to bring the [Na + ] down to 150 mEq/L? 1.7 liters 2.4 liters 3.1.5 liters Pop Quiz

39. Why Does this Stuff Matter? Need to be Quantitative but not Precise

40. Don’t Memorize This!

41. Take Home Points (3) Memorize (unfortunately) the concentrations of the principle ions in the extracellular and intracellular fluid.Memorize (unfortunately) the concentrations of the principle ions in the extracellular and intracellular fluid. Know the difference between intracellular fluid, extracellular fluid, plasma, and interstitial fluid, and how to estimate the volume of each of these compartments in a patient.Know the difference between intracellular fluid, extracellular fluid, plasma, and interstitial fluid, and how to estimate the volume of each of these compartments in a patient. Understand the composition of two common intravenous fluids used in medicine – 5% Dextrose (“D5W”) and 0.9% Sodium Chloride (“Normal Saline”)Understand the composition of two common intravenous fluids used in medicine – 5% Dextrose (“D5W”) and 0.9% Sodium Chloride (“Normal Saline”)