Lectured on: August 29, 2013 Lectured by: Dra.

Felices Emerita Pascual - Perez RENAL PHYSIOLOGY Topic: THE BODY FLUIDS COMPARTMENTS : ECF & ICF Maintenance of a relatively constant volume and a stable composition of the body fluids is essential for homeostasis Water Balance to maintain a steady state, water intake must equal water excretion. Average INTAKE per day 2300 mL

2100 mL from ingested food and beverages 200 mL from metabolism Average OUTPUT per day 2300 mL 100 mL feces (4%) 100 mL sweat (8%) 700 mL insensible losses via skin and lungs (25%) 1400 mL urine (60%) BALANCE CONCEPTS Balance is necessary, in the long-term, to maintain life. Fluid Loss = Fluid Intake Electrolyte Loss = Electrolyte Intake Fluid Intake: regulated by thirst mechanism, habits Electrolyte intake: governed by dietary habits Fluid Output: regulated mainly by kidneys Electrolyte output: regulated mainly by kidneys BODY FLUIDS COMPARTMENTS TOTAL BODY WATER IN RELATION TO BODY WEIGHT: EFFECTS OF GENDER, BODY BUILD AND AGE

Transcellular fluid compartment a specialized type of ECF 1-2 liter Synovial fuid Peritoneal fluid Pericardial fluid CSF (cerebrospinal fluid)

BODY FLUID COMPARTMENTS ECF 20% of body weight = 14 L (++) Na+, Cl- and Bicarbonate ions Has small amount of Potassium, Calcium, Magnesium phosphate and organic acids Proteins: Plasma > ISF ICF 40% of total body weight = 28 L Only small amount of Na+ and Clions and almost no Calcium Large amount of K+ and PO4- ions. Moderate quantities of Mg++ and Sulfate ions Proteins -4x greater than ECF

FLUID BALANCE (ml/day) 70 kg Adult

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REGULATION OF FLUID EXCHANGE AND OSMOTIC EQUILIBRIUM b/w ICF & ECF The distribution of fluids between ECF and ICF is determined mainly by the osmotic effect of smaller solutes. Sp. NaCl and other electrolyte acting across the cell membrane Involves semi-permeable cell membrane Permeability: Water >>> NaCl Thus water moves very rapidly across the membrane so that the ICF remains isotonic with the ECF. CONTROL OF BODY FLUID DISTRIBUTION Distribution across cell membranes determined by osmotic forces (mainly from electrolytes) Distribution across capillaries determined by hydrostatic and colloid osmotic forces. BASIC PRINCIPLES OF OSMOSIS AND OSMOTIC PRESSURE BLOOD VOLUME Both ECF & ICF Average blood volume = 5 L (7 % of body weight) 60% plasma, 40% RBC Hematocrit Fraction of the blood composed of RBC Men 0.40 Females 0.36 Anemia low levels Polycythemia excessive production COMPUTATION OF BODY WATER (for a 70 kg man) Total Body Water (TBW) = 60% or 0.6 x Body weight (BW) B. 42L ECF =20% or 0.2 x BW 13L Plasma 1/3 of ECF 3.5L MEASUREMENT OF BLOOD VOLUME Total Volume = Plasma volume 1-Hematocrit An average 70 kg man: Total blood volume = 3.5 L / 1-0.40 = 5.8 L Blood volume = 7% of body weight Hct in male = .40 Osmole - refers to the number of osmotically active particles in a solution. 1 osmole is equal to 1 molecule of solute 1 mole of Glucose L = 1 osmole L 1 mole of NaCl L = 2 osmoles L 1 mole of Na2SO4 L = Osmoles L 1 milliosmole = 1 1000 osmole ICF =40% or 0.4 x BW 28L Pure water Osmosis Net diffusion of water across a selectively permeable membrane from a region of high water concentration that has a lower water concentration. - The higher the solute concentration the lower the water concentration. Rate of osmosis Rate of diffusion of water WHAT IS THE DIRECTION OF OSMOSIS? A.

ISF of ECF 10.5L

C.

* * *
With solute

* * *

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OSMOLARITY AND OSMOLALITY Osmolality Osmolal concentration of solution OSmoles per kg of water (osm/kg H2O) Osmolarity Osmoles per literof solution (osm/L) OSMOLARITY Fluid Osmolarity: ECF: Na and Cl ions ICF: 50% due to K+ Corrected osmolarity is 282 mosm/L RELATION BETWEEN OSMOTIC PRESSURE AND OSMOLARITY Osmotic pressure of a solution is directly proportional to the concentration of osmotically active substances regardless of the size of the solute/

OSMOLARITY OF A 0.9% NaCl SOLUTION

OSMOLARITY Plasma mosm/L 301.8* 282 mosm/L 5443 ISF 300.8 281 mosm/L 5423 ICF 300.8 281 mosm/L 5423

Which has a higher osmotic pressure? Albumin, Glucose, NaCl OSMOTIC PRESSURE : VAN HOFFS LAW

Total mosm/L Corrected** Total osm. Pressure at 37C

*Slightly higher in plasma due to osmotic effects of plasma proteins **Correction factor (osmotic coefficient) for NaCl is 0.93 EFFECTS OF DIFFERENT CONCENTRATION OF IMPERMEANT SOLUTES IN ECF ON CELL VOLUME

PRINCIPLES OF OSMOTIC EQUILIBRIUM

Tonicity of solution, refers to whether solution will cause a change in a cell volume; depends on concentration of impermeant solute . Isosmotic solution has same osmolarity as body fluids CALCULATION OF THE OSMOLARITY AND OSMOTIC PRESSURE OF A SOLUTION What is the osmotic pressure of a -.9% NaCl solution? Is this isotonic, hypotonic or hypertonic? Hyperosmotic higher osmolarity than body fluids Hyposmotic lower osmolarity than body fluids Osmolarity of solution refers to solution with higher or lower osmolarity compared with Normal ECF without regard for whether it can permeate the cell membrane.

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REVIEW: WHATS THE EFFECT OF SOLUTIONS OF CARYING TONICITY ON RBC?

WHAT ARE THE CHANGES IN THE FF VARIABLES AFTER GIVING 2.0 L OF WATER I.V.? ECF Volume? Increase ECF Osmolarity? Decrease ICF Volume? Increase ICF Osmolarity? Decrease

280 mOsm/L QUESTIONS:

200 mOsm/L

360 mOsm/L

What is the osmolarity of a 5% glucose solution? (MW is 180 g/mol) Is the solution hyperosmotic, hypo-osmotic or isosmotic? What is a hypo-osmotic solution? OSMOLARITY OF A 5% GLUCOSE SOLUTION

REMEMBER!!! Water moves rapidly across cell membranes, thus osmolarities between ECF & ICF remain almost equal. Cell membrane are almost impermeable to many solutes therefore the number of osmoles in ECF or ICF generally are constant unless solutes. WHAT ARE THE CHANGES IN THE FF VARIABLES AFTER GIVING 2L OF 3% NaCl I.V.? ECF Volume? Increase > 2.0 L ECF Osmolarity? Increase ICF Volume? Decrease ICF Osmolarity? Increase

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SUMMARY

ABNORMALITIES OF BODY FLUID VOLUME REGULATION ABN Hyponatremic Dehydration Cause Diarrhea, vomiting, adrenal insuff; overuse of diuretics, Addisons Excess ADH, bronchogenic tumor Lack ADH, Diabetes insipidus, excessive sweating Cushingsm primary aldosteronism Plasma Na+ Conc ECF Vol ICF Vol

Hyponatremic overhydration Hypernatremic dehydration

Hypernatremic overhydration

HYPO/HYPER OSMOTIC REFERS TO PLASMA Na+ CONCENTRATION EDEMA Presence of excess fluid in the body tissues.

INTRACELLULAR EDEMA Depression of tissue metabolic systems (e.g. hypothyroidism) Inadequate tissue nutrition (e.g. ischemia) Inflammation of tissues (increased cell membrane permeability)

EXTRACELLULAR EDEMA ABNORMALITIES OF ECF FLUID Na+ CONCENTRATION Causes of increased interstitial fluid volume Increased Capillary Filtration Failure of lymphatics to return interstitial fluid to circulation

3 Factors that can increase capillary filtration 1. Increased capillary hydrostatic pressure (Pc) 2. Decreased plasma colloid osmotic pressure 3. Increased capillary filtration coefficient (permeability) (Kf) DETERMINANTS OF CAPILLARY FILTRATION ECF solute is 90% due to NaCl, hence an indicator of plasma osmolarity. CONSEQUENCES OF HYPONATREMIA AND HYPERNATREMIA Water moves in and out of cells cells swell or shrink This has profound effects on the brain. Neurologic function is altered Rapid shrinking can tear vessels and cause hemorrhage Rapid swelling can cause herniation because the skull is rigid, the brain cannot increase its volume by more than 10% without being forced down the neck (herniation).

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CAUSES OF INCREASED CAPILLARY FILTRATION

NORMAL FILTRATION FILT = Kf x Net Filt Pressure = 6.6 x ( 17.3 - (-3) - 28 +8) = 6.6 x ( + 0.3) = 1.89 ml/min FILT = 2722 ml/day Where does all of this fluid (and protein in it) go? FUNCTION OF LYMPHATICS LOW TISSUE COMPLIANCE AND NEGATIVE INTERSTITIAL FLUID HYDROSTATIC PRESSURE

NEGATIVE PRESSURE SUCKS. (If negative IFPr, IF volume does NOT change much if +3 fluid start to accumulate), because tissue became highly compliant,

Lymphatic Failure = Edema

INCREASED LYMPH FLOW

CAUSES OF ECF EDEMA Lymphatic blockage Infection Cancer Surgery Congenital absence of lymphatics SAFETY FACTORS AGAINST EDEMA Low compliance of interstitium when = 3 mmHg interstitial fluid pressure is negative Increased lymph flow = 7 mmHg Washdown of interstitial protein = 7 mmHg at high lymph flow rates TOTAL SAFETY FACTORY = 17 mmHg

Lymph Flow

EFFECT OF INTERSTITIAL FLUID PRESSURE ON LYMPH FLOW

Increases lymph flow 10-50x

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PITTING VS NON PITTING EDEMA Thumbprint - When the thumb press against the tissue area, it pushes the fluid away from the area. When tissue cell swells instead of interstitium, fluid do not move away from the area. WASHDOWN OF INTERSTITIAL PROTEINS

CONDITIONS CAUSING EDEMA 1. High capillary hydrostatic pressure Excess fluid retention by kidneys acute or chronic kidney failure glomerulonephritis mineralocorticoid excess Decreased arteriolar resistance vasodilator drugs autonomic insufficiency Increased venous pressure congestive heart failure high output heart failure (e.g. anemia) -venous obstruction venous valve failure cirrhosis 2. Decreased plasma proteins (low oncotic pressure) Loss of proteins burns, wounds nephrosis gastroenteropathy Failure to produce proteins - malnutrition (kwashiorkor) - cirrhosis - analbuminemia 3. Increased capillary permeability Immune reactions (histamine) Toxins Burns Prolonged ischemia Vitamin deficiency (e.g. vitamin C) Pre-eclampsia and eclampsia in Pregnancy 4. Blockage of lymphatics Cancer Surgery Infections (e.g. filaria nematodes) FLUIDS IN THE POTENTIAL SPACES OF THE BODY Pleural, peritoneal, pericardial, synovial cavities Fluid is exchanged between the capillaries and the potential spaces Lymphatic vessels drain protein from the potential spaces Effusion Edema fluid in the potential spaces Abdominal cavity ascites Normal Interstitial hydrostatic pressure of Pleural cavity (-) 7 to (-) 8 mmHg Pericardial cavity (-) 5 to (-) 6 mmHg Joint spaces (-3) to (-) 5 mmHg

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