Body fluid physiology(DR.FERHAN)

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Body fluid physiology:

Body fluid physiology Moderators: Dr G.K. Bhat Dr N.R. Bhat

Introduction…:

Introduction… Total body water – 60% of body weight Varies with age, gender, adiposity. 70 kg man – 600ml/kg or 40 liters. Fetus- high content of water initially but decreases progressively during late gestation and by 3-5yrs age.

Factors Factors affecting body fluidsbody fluids:

Factors Factors affecting body fluids body fluids Water intake & output Age: - infant: 73% - elderly: 45% Sex: - adult male: 60% - adult female: 40-50% Obesity Climate Level of physical activity

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In average young adult male: Body composition % of body weight Body composition 18% Protein, & related substances 15% Fat 7% Mineral 60% Water

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Total body water and its distribution between different compartments

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Adult ICF- 400-450ml/kg ( about 30 liters). ECF- 150-200ml/kg (about 14 liters). Blood volume– 60-65ml/kg and is distributed as 15% arterial and 85% venous. Major components of ECF : - plasma volume- 30-35ml/kg - interstitial fluid 120-165ml/kg -Also includes lymph, cerebrospinal fluid, synovial fluid, aqueous humor, vitreous body, endolymph , perilymph , pleural, pericardial, and peritoneal fluids

Comparison in male and female:

Comparison in male and female

Differences between ECF & ICF:

Differences between ECF & ICF ECF Anions : Cl - (108) HCO 3 - (24) Cations : Na + (142 mmol/L ) K + (4.2) Mg 2+ (0.8) Nutrients : O 2 , glucose, fatty acids, & amino acids. Wastes : CO 2 , Urea, uric acid, excess water, & ions . ICF Anions : Cl - (4) HCO 3 - (10) Phosphate ions Cations : Na + (14) K + (140) Mg 2+ (20) Nutrients : High concentrations of proteins.

Daidaily intake and output of water ml/kg (ml/day)da:

Dai daily intake and output of water ml/kg (ml/day) da Prolonged, heavy exercise Normal ? 200 2100 200 Intake: Fluids ingested (Drinking/in food) From metabolism ? 2300 Total intake 350 650 5000 100 500 350 350 100 100 1400 Output: Insensible – skin Insensible – lungs Sweat Feces Urine 6600 2300 Total output In steady state, water intake = water loss

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Saladin’s Anatomy & Physiology fourth edition McGraw Hill Shift of body fluids through different compartments

Measuring body fluid volumes::

Measuring body fluid volumes: Principle: Indicator-dilution principle Method: Administer a known amount (A) of a substance that will get distributed in a particular body fluid compartment; Determine the final steady state concentration (C) of this indicator in blood; Volume of distribution Vd of the indicator = Amount of indicator injected (A) Concentration in blood after mixing (C)

Indicators used for measuring plasma volume, ECF volume and total body water:

Indicators used for measuring plasma volume, ECF volume and total body water Compartment Criterion Indicators Plasma Substance should not cross capillaries Evans blue dye; radioiodinated fibrinogen; radioiodinated albumin ECF volume Substance should cross capillaries but not cross cell membranes Isotonic solutions of sucrose, inulin, mannitol, NaCl Total body water (TBW) Substance distributes evenly in ICF & ECF Heavy water, tritiated water, aminopyrine , antipyrine

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How would you measure interstitial fluid (ISF) volume? Cannot be measured; it is calculated (estimated).. ISF volume = ECF volume – plasma volume How would you measure intracellular fluid(ICF) volume? Cannot be measured; it is calculated (estimated).. ICF volume = Total body water – ECF volume

Osmosis :

Osmosis Definition… The osmotic pressure exerted by nondiffusible particles in a solution is determined by number of particles and not the type of particles. e.g. 1-mol of glucose or albumin and 0.5-mol of Nacl ( dissociates into 2 ions) should exert the same osmotic pressure. Osmole is the unit used to express osmotic pressure in solutes.

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Osmolality – osmole conc. of a solution expressed in osmole /kg. Osmolarity - osmole conc. expressed in osmole /liter. Mole- is the gram molecular weight of a substance & each mole contains about 6*10 23 molecules. e.g. 1 mol solution of sodium chloride is 58.5gm.

Capillary fluid exchange:

Capillary fluid exchange

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Equivalent- 1mol of an ionized substance divided by its valence. E.g.- Na + = 23gm Ca 2+ : 40/2 = 20gm

Osmolarity of body fluids:

Osmolarity of body fluids Plasma osmolarity is about 280-290mOsm/L. All but about 20mOsm is contributed by sodium ions and their accompanying anions, mainly chloride and bicarbonate ions. Glucose and urea contribute significantly when hyperglycemia or uremia is present. Plasma osmolarity = 2(Na + ) + 0.055(glucose) +0.36(blood urea nitrogen)

Tonicity of fluids:

Tonicity of fluids Term used to describe the osmolarity of a solution relative to plasma. Isotonic Hypotonic Hypertonic RL-278mOsm/l NS-308mOsm/l DNS-585mOsm/l 5D-277mOsm/l

Regulation of Water Intake:

Regulation of Water Intake Low water intake will lead to ↑plasma osmolality Low blood volume or blood pressure activate angiotensin II Both stimuli stimulate hypothalamic thirst center to secrete ADH High plasma osmolality leads to ↓ salivary secretion → thirst → water intake Once wet, the buccal mucosa eliminates the feeling of thirst Stretch receptors in the GI tract act on to inhibit thirst center and avoid excessive water intake and ↓plasma osmolality *

Water intake regulation:

Water intake regulation

Electrolytes in body fluids:

Electrolytes in body fluids Ions form when electrolytes dissolve and dissociate 4 general functions Control osmosis of water between body fluid compartments Help maintain the acid-base balance Carry electrical current Serve as cofactors

ICF differs considerably from ECF :

ICF differs considerably from ECF ECF most abundant cation is Na + , anion is Cl - Sodium Impulse transmission, muscle contraction, fluid and electrolyte balance Chloride Regulating osmotic pressure, forming HCl in gastric acid Controlled indirectly by ADH and processes that affect renal reabsorption of sodium ICF most abundant cation is K + , anion are proteins and phosphates (HPO 4 2- ) Potassium Resting membrane potential , action potentials of nerves and muscles Maintain intracellular volume Regulation of pH Controlled by aldosterone Na + /K + pumps play major role in keeping K + high inside cells and Na + high outside cell

Sodium physiology :

Sodium physiology Most abundant ion in ECF compartment. Critical in determining the extracellular and intracellular osmolality . Distribution b/w plasma and interstitial fluid is roughly 5 or 6 to 1 at equilibrium and distribution equilibrium time is 15 to 20 mins . Renin – angiotensin system plays a role in sodium homeostatsis and renal function. Daily requirements- Infants- 2-3meq/kg/day adults- 1.5meq/kg/day

Sodium regulation:

Sodium regulation

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Potassium The most abundant ion in the ICF Determines intracellular osmolarity Part of the sodium potassium pump Essential for protein synthesis

Fluids and Electrolytes:

Fluids and Electrolytes Potassium Regulation Normally 60% - 80% of potassium is resorbed through renal PCT Additional 10% resorbed through ascending limb loop of Henle . If interstitial K + is low, K + will move from cells to interstitial space CD principal cells reduce K + loss to a minimum Adrenal cortex cells are sensitive to K + level, an increase will lead to aldosterone secretion, which acts on Collecting ducts to increase potassium secretion. High dietary K + intake leads to K + loss in the urine

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Most important transcellular enzyme involved in potassium regulation is the Na + /K + ATPase . Beta-2 adrenergic agents increase the activity of the Na + /K + ATPase by binding to cell surface receptors. Insulin causes more sodium to enter the cell through Na + /H + antiporter , & increase in sodium must removed in exchange for potassium. Daily requirements: infants – 2-3mEq/kg/day adults- 1.0-1.5mEq/kg/day

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The relation between potassium and hydrogen ions in the plasma Saladin’s Anatomy & Physiology fourth edition McGraw Hill

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Potassium balance in the body Costanzo Physiology second edition Saunders

Calcium Ca2+ :

Calcium Ca 2+ Most abundant mineral in body 98% of calcium in adults in skeleton and teeth In body fluids mainly an extracellular cation Contributes to hardness of teeth and bones Plays important roles in blood clotting, neurotransmitter release, muscle contraction, and excitability of nervous and muscle tissue

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Regulated by parathyroid hormone Stimulates osteoclasts to release calcium from bone – resorption Also enhances reabsorption from glomerular filtrate Increases production of calcitriol to increase absorption for GI tract Calcitonin lowers blood calcium levels

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When ionozed calcium cannot be measured, the approximate amount of calcium bound to protein is calculated. Protein boung calcium(%)= 0.8*albumin(g/L)+0.2*globulin(g/L)+3 a correction of 1mg/dl is added to serum calcium for every 1g/dl, that serum albumin is below 4.0g/dl.

Magnesium :

Magnesium In adults, about 54% of total body magnesium is part of bone as magnesium salts Remaining 46% as Mg 2+ in ICF (45%) or ECF (1 %) Second most common intracellular cation (1.3-2.1 mEq /liter in plasma) Cofactor for about 300 enzymes and sodium-potassium pump

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Essential for normal neuromuscular activity, synaptic transmission, and myocardial function Essential for the production and function of ATP, which is fully functional only when chelated to Magnesium. Regarded as a natural physiologic antagonist to calcium.

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Phosphorus Concentrated intracellularly as mon . di and triphosphates Part of the nucleic acids, lipophosphates , ATP, GTP and cAMP Activate many metabolic reactions Help maintain body fluid pH Same hormones governing calcium homeostasis also regulate HPO 4 2- in blood Parathyroid hormone – stimulates resorption of bone by osteoclasts releasing calcium and phosphate but inhibits reabsorption of phosphate ions in kidneys Calcitriol promotes absorption of phosphates and calcium from GI tract

Acid-base balance:

Acid-base balance Major homeostatic challenge is keeping H + concentration (pH) of body fluids at appropriate level 3D shape of proteins sensitive to pH Several mechanisms help maintain pH of arterial blood between 7.35 and 7.45 Buffer systems, exhalation of CO 2 , and kidney excretion of H + / reabsorption of HCO 3 -

Acid-Base Balance:

Acid-Base Balance Blood pH is regulated by three mechanisms Chemical buffers: act immediately Respiratory rate and depth: intermediate speed Renal correction: slow but most potent

Buffer systems :

Buffer systems Act to quickly temporarily bind H + Raise pH but do not remove H + Most consist of weak acid and salt of that acid functioning as weak base Major buffer systems: proteins, carbonic acid/bicarbonate, phosphates

Buffer systems :

Buffer systems Protein buffer system Most abundant buffer in ICF and blood plasma Hemoglobin in RBCs Albumin in blood plasma Free carboxyl group acts like an acid by releasing H + Free amino group acts as a base to combine with H + Side chain groups on 7 of 20 amino acids also can buffer H +

Acid-Base Balance:

Acid-Base Balance Chemical Buffers Ammonia/Ammonium System: NH 3 / NH 4 + NH 3 is generated in tubular cells absorbs H + NH 3 reacts with Cl - NH 3 + H + → NH 4 + + Cl - → NH 4 Cl

Buffer Systems:

Buffer Systems Carbonic acid / bicarbonate buffer system Based on bicarbonate ion (HCO 3 - ) acting as weak base and carbonic acid (H 2 CO 3 ) acting as weak acid HCO 3 - is a significant anion in both ICF and ECF Because CO 2 and H 2 O combine to form this buffer system cannot protect against pH changes due to respiratory problems in which there is an excess or shortage of CO 2 Phosphate buffer system Dihydrogen phosphate (H 2 PO 4 - ) and monohydrogen phosphate (HPO 4 2- ) Phosphates are major anions in ICF and minor ones in ECF Important regulator of pH in cytosol

Exhalation of carbon dioxide :

Exhalation of carbon dioxide Increase in carbon dioxide in body fluids lowers pH of body fluids Because H 2 CO 3 can be eliminated by exhaling CO 2 it is called a volatile acid Changes in the rate and depth of breathing can alter pH of body fluids within minutes Negative feedback loop

Regulation of blood pH by the respiratory system:

Regulation of blood pH by the respiratory system

Kidney excretion of H+ :

Kidney excretion of H + Metabolic reactions produce nonvolatile acids One way to eliminate this huge load is to excrete H + in urine In the proximal convoluted tubule, Na + /H + antiporters secrete H + as they reabsorb Na + Intercalated cells of collecting duct include proton pumps that secrete H + into tubule fluid; reabsorb K + and HCO 3 - Urine can be up to 1000 times more acidic than blood 2 other buffers can combine with H + in collecting duct HPO 4 2- and NH 3

Secretion of H+ by intercalated cells in the collecting duct:

Secretion of H + by intercalated cells in the collecting duct

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