Total body water and its distribution in the body compartments. The ...

Total body water andits distribution in the bodycompartments.The main functions of water inthe human organism.WaterLargest single chemical component of the body:45-75% of body massFat (adipose tissue) is essentially water free, sothere is relatively more or less waterin the body depending on % fat compositionWater is the solvent for most biologicalmolecules within the bodyWater also participates in a variety ofbiochemical reactions, both anabolic andcatabolic

Fluid Compartments• Total Body Water (TBW) - 42L,60% of body weight– Intracellular Fluid (ICF) -28L, 67% of TBW– Extracellular Fluid (ECF) -14L, 33% of TBW• Interstitial Fluid - 11L,80% ECF• Plasma - 3L, 20% ofECFWater balance– Sources for 2500 ml- average dailyintake• Metabolic Water• Preformed Water– Ingested Foods– Ingested Liquids– Balance achieved ifdaily output also =2500 ml• GI tract• Lungs• Skin– evaporation– perspiration• Kidneys

Water Movement Between the ICF and ECFOsmolality – the concentrations of solutes in water– solutes will influence the movement of water across membranesH 2Oπ = iRTcAquaporins- water channel proteins in membranesNet filtration (Starling hypothesis)H 2O= forces favoring filtration – forces opposing filtrationAs fluid flows through capillary it looses water and create greater osmoticreturn of water as it flows toward veinule end of capillaryForces favoring filtration- Capillary hydrostatic pressure (blood pressure)- Interstitial oncotic pressure (water-pulling)Forces favoring reabsorptionfiltrationH 2O- Plasma oncotic pressure (water-pulling)reabsorption- Interstitial hydrostatic pressureOncotic pressure…Colloid osmotic pressure• is formed by colloid particles dissolved in solution• in plasma the major part forms proteins 65-85 g/lElectrophoretic separation of plasma proteins(directly proportional to size and charge)Albumin60%α 1globulin α1-antitrypsin, α1-acid glycoproteinα 2globulin haptoglobin, α2-macroglobulin,α2-antiplasmin, ceruloplasmin4% 7%β globulintransferin, complement, LDL10%fibrinogenγ globulin = ImunoglobulinsIgA, IgD, IgE, IgG and IgMMr 67x10 3 Mr150x10 3Mr340x10 35% 14%

Water Movement Between the ICF and ECFOsmotic Equilibrium

Plasma Osmolarity - Measures ECF Osmolarity• Plasma is clinically accessible• Dominated by [Na + ] and the associated anions• Under normal conditions, ECF osmolarity can be roughly estimatedas:P OSM = 2 [Na + ] p……..270-300 mOsm{ P OSM = 2[Na + ] + 2[K + ] + [Urea] + [Glucose] }EdemaAccumulation of fluid within theinterstitial spaces• Causes:– Increase in hydrostatic pressure (blood pressure / hypertension)– Losses or diminished production of plasma albumin (hypoproteinemia…decrease in oncotic pressure /malnutrition (at insufficient supply of proteins…abdominal edema/ insufficient production of proteins at cirrhosis/ largelosses of proteins by kidney at nephrotic syndrome/)- Increases in capillary permeability (at anaphylaxis, allergicreaction (release of histamin), inflammation)- Lymph obstruction – elephantitus, flibitus- Decreased resorption due to raised systemic venouspressure – edema due to heart failure

EdemaRegulating Fluid IntakeThirstThirst Quenching1. 2.Wetting the oral mucosa(temporary)Stretching of the stomachDecreased blood/bodyfluid osmolarity =increased hydration(dilution) of the blood isthe most important

Regulation of Fluid Output• Hormonal control– Antidiuretic hormone (ADH) [neurohypophysis]– Aldosterone [adrenal cortex]– Atrial natriuretic peptide (ANP) [heart atrial walls]• Physiologic fluid imbalances– Dehydration: ↓ blood pressure, ↓ GFR– Overhydration: ↑ blood pressure, ↑ GFR– Hyperventilation - water loss through lungs– Vomiting & Diarrhea - excessive water loss– Fever - heavy perspiration– exudating Burns, contusion - fluid loss– Hemorrhage – if blood loss is severe

Atrial natriuretic peptide (ANP) is a 28-amino acid peptide that is synthesized, stored, andreleased by atrial myocytes in response to atrial distension- elevated levels of ANP are found during hypervolemic states (elevated blood volume) andcongestive heart failureA second natriuretic peptide (brain-type natriuretic peptide; BNP) is a 32-amino acid peptide thatis synthesized within the ventricles (as well as in the brain where it was first identified). LikeANP, BNP is released by the same mechanisms that release ANP, and it has similarphysiological actions, BNP serves as sensitive, diagnostic markers for heart failure inpatients

Regulation of Fluid OutputOsm V PBADHFactors affectingADH release

Urine osmolarity regulation by ADHADHHuman angiotensinogenis 118 amino acids longPathway of RAAS

Principal cells & aldosteroneAtrial natriuretic peptide28-amino acid peptide

Distribution of SolutesInterstitial fluid is essentially anultrafiltrate of plasma, water andelectrolytes move freely withinthis compartment and between itand the intravascular fluid.Intravascular fluid has almost thesame composition as interstitialfluid except for its higher proteinlevel.Electrolyte BalanceElectrolytes have 4 important physiological functions in the body• essential minerals in certain biochemical reactions• control osmosis = control the movement of water betweencompartments• maintain acid-base balance• conduct electrical currents (depolarization events)Regulators:Aldosterone ↑ [Na + ] [Cl - ] [H 2 O] ↓ [K + ]Atrial Natriuretic Peptide (opposite effect)Antidiuretic Hormone ↑ [H 2 O] (↓ [solutes])Parathyroid Hormone ↑ [Ca ++ ] ↓ [HPO 4- ]Calcitonin (opposite effect)Female sex hormones ↑ [H 2 O]

Electrolytes• Sodium (Na + ) - 136-146 mmol/liter– Most abundant cation• major ECF cation (90% of cations present)• determines osmolarity of ECF– Regulation• Aldosterone•ADH•ANP– Homeostatic imbalances• Hyponatremia• HypernatremiaHypertonic Alterations - Related to sodium gain or water loss• Hypernatremia– Serum sodium >146 mmol/L– Water movement from the ICF to the ECF• Intracellular dehydration– Manifestations:• Convulsions, pulmonary edema, tachycardia, etc.• Water deficit-Dehydration- Renal free water clearance- Manifestations:– Tachycardia, weak pulses– Elevated hematocrit and serum sodium level

Hypotonic Alterations - Related to Hyponatremia or free water excess• Hyponatremia- Serum sodium level

Electrolytes• Potassium (K + )– Major ICF cation, concentration maintained by the Na + /K + pump• intracellular 120-125 mmol/L• plasma 3.5-5.0 mmol/L– Very important role in resting membrane potential (RMP) and inaction potentials = essential for transmission and conduction of nerveimpulses, normal cardiac rhythms, and skeletal and smooth musclecontraction• Changes in pH affect K + balance– Hydrogen ions accumulate in the ICF during states of acidosis. K +shifts out to maintain a balance of cations across the membrane.• Aldosterone, insulin, and catecholamines influence serum potassiumlevels• Homeostatic imbalances• Hypokalemia• Hyperkalemia• Hypokalemia- Potassium level 5.5 mmol/L- Caused by increased intake, shift of K+ from ICF, decreased renal excretion,insulin deficiency, or cell trauma- Mild attacks- Hypopolarized membrane, causing neuromuscular irritability, Tingling of lipsand fingers, restlessness, intestinal cramping, and diarrhea- Severe attacks- The cell is not able to repolarize, resulting in muscle weakness, loss ormuscle tone

Electrolytes• Calcium (Ca 2+ )– Most abundant ion in body• plasma 2.3-2.6 mmol/L• most stored in bone (98%) as hydroxyapatite- Necessary for structure of bones and teeth, blood clotting, hormonesecretion, and cell receptor function- Regulation:• Parathyroid Hormone (PTH) - ↑ blood Ca 2+• Calcitonin (CT) - ↓ blood Ca 2+– Homeostatic imbalances:• Hypocalcemia - muscle cramps, convulsions• Hypercalcemia - vomiting, cardiovascular symptoms, coma;prolonged abnormal calcium deposition, e.g., stoneformationElectrolytes• Phosphate (H 2 PO 4- , HPO 42-, PO 43-)– Important ICF anions; plasma 1.7-2.6 mmol/L• most (85%) is stored in bone as calcium salts• also combined with lipids, proteins, carbohydrates, nucleic acids (DNAand RNA), and high energy phosphate transport compound• important acid-base buffer in body fluids– Regulation - regulated in an inverse relationship with Ca 2+ by PTH andcalcitonin and Vitamin D (If the concentration of one increases, that of the otherdecreases)– Parathyroid hormone (PTH) - Increases plasma calcium levels– Vitamin D = Fat-soluble steroid - Increases calcium absorption from the GI tract– Calcitonin - Decreases plasma calcium levels– Homeostatic imbalances• Phosphate concentrations shift oppositely from calcium concentrationsand symptoms are usually due to the related calcium excess or deficit

Hypophosphatemia and Hyperphosphatemia• Hypophosphatemia– Osteomalacia (soft bones)– Muscle weakness– Bleeding disorders (platelet impairment)– Anemia– Leukocyte alterations• Hyperphosphatemia– High phosphate levels are related to the low calcium levels- Increased neuromuscular excitability (partial depolarization)- Muscle crampsElectrolytes• Magnesium (Mg 2+ )– 2 nd most abundant intracellular electrolyte, 0.8-1.3 mmol/L in plasma• more than half is stored in bone, most of the rest in ICF(cytoplasm)• important enzyme cofactor; involved in neuromuscular activity,nerve transmission in CNS, and myocardial functioning– Homeostatic imbalance• Hypomagnesemia - Associated with hypocalcemia andhypokalemia, Neuromuscular irritability,Tetany, Convulsions,Hyperactive reflexes vomiting, cardiac arrhythmias• Hypermagnesemia - Muscle weakness, Hypotension,Respiratory depression, Lethargy, drowsiness, Bradycardia

Acid-Base Balance• Normal metabolism produces H + (acidity)• Three Homeostatic mechanisms:– Buffer systems - instantaneous; temporary– Exhalation of CO 2 - operates within minutes; cannotcompletely correct serious imbalances– Kidney excretion - can completely correct any imbalance(eventually)• Buffer Systems– Consists of a weak acid and the salt of that acid whichfunctions as a weak baseAcid-Base Balance• Carbonic Acid - Bicarbonate Buffer– A weak base (carbonic anhydrase)H + + HCO 3- ⇔ H 2 CO 3 ⇔ H 2 O + CO 2• Phosphate BufferNaOH + NaH 2 PO 4 ⇔ H 2 O + Na 2 HPO 4HCl + Na 2 HPO 4 ⇔ NaCl + NaH 2 PO 4• Protein Buffer (resp. hemoglobin & albumin)Most abundant buffer in body cells and plasmaAmino acids have amine group (protonacceptor = weak base) and a carboxyl group(proton donor = weak acid)

Acid-Base Balance• CNS and peripheralchemoreceptors controlchanges in blood pH• Increased [H + ] causesimmediate hyperventilationand later increased renalsecretion of [H + ] and [NH 4+ ]• Decreased [H + ] causesimmediate hypoventilationand later decreased renalsecretion of [H + ] and [NH 4+ ]Acid-Base Imbalances• Acidosis– High blood [H + ]– Low blood pH, 7.45• Acid-Base imbalances may be due to problems with ventilation or due to avariety of metabolic problems– Respiratory Acidosis (pCO 2> 45 mm Hg)– Respiratory Alkalosis (pCO 2< 35 mm Hg)– Metabolic Acidosis (HCO 3-< 23 mmol/l)– Metabolic Alkalosis (HCO 3-> 26 mmol/l)• Compensation: the physiological response to an acid-base imbalancebegins with adjustments by the system less involved

Causes of Acid-Base Imbalances• Respiratory Acidosis– Chronic Obstructive Pulmonary Diseases e.g., emphysema,pulmonary fibrosis– Pneumonia• Respiratory Alkalosis– Hysteria– Fever– AsthmaCauses of Acid-Base Imbalances• Metabolic Acidosis– Diabetic ketoacidosis, Lactic acidosis– Salicylate poisoning (children)– Methanol, ethylene glycol poisoning– Renal failure– Diarrhea• Metabolic Alkalosis– Prolonged vomiting– Diuretic therapy– Hyperadrenocortical disease– Exogenous base (antacids, bicarbonate IV, citrate toxicity aftermassive blood transfusions)

Metabolic AcidosisMetabolic Alkalosis

Respiratory AcidosisRespiratory Alkalosis