Body Fluid Compartments and Ion Regulation PDF

Body fluid compartments and their contents Regulation of ion concentrations in body fluids Dr. Arzu Temizyürek  BODY FLUIDS Body fluids Dilute, watery solutions containing dissolved chemicals inside or outside of the cell We know that about 60-70 % of our body is made up of water. ...

Body fluid compartments and their contents Regulation of ion concentrations in body fluids Dr. Arzu Temizyürek  BODY FLUIDS Body fluids Dilute, watery solutions containing dissolved chemicals inside or outside of the cell We know that about 60-70 % of our body is made up of water.  Factors affecting body fluids Water intake & output Age: - newborn: 80% - elderly: 45% Sex: - adult male: 60% - adult female: 40-50% Obesity Climate Level of physical activity In general, total body water correlates inversely with body fat. Thus, total body water is a higher percentage of body weight when body fat is low and a lower percentage when body fat is high.  Functions of water in the body ▪ Transports nutrients, enzymes, hormones, blood cells, neurotransmitters, etc. ▪ Serves as a liquid medium for chemical reactions ▪ Maintains body temperature, ▪ Helps digestion and excretion ▪ Serves as a solvent for electrolytes  Fluid Compartments Total body water = 42 L 1. Intracellular fluid (ICF) compartment: 2/3 or 28 L in cells 2. Extracellular fluid (ECF) compartment: 1/3 or 14 L Plasma: 3 L Interstitial fluid (IF): 11 L in spaces between cells Other ECF (transcellular fluId: lymph, CSF, humors of the eye, synovial fluid, serous fluid, and gastrointestinal secretions  BODY FLUIDS Intracellular fluid (40%) Extracellular fluid (20%) Fluid within cells Fluid outside cells Interstitial fluid (15%) Blood plasma (5%) (Tissue fluid) is ECF Present in blood between cells and tissues Transcellular fluid outside of the normal compartments (1-2 liters) e.g. Digestive Juices, Mucus, etc. Balance (Intake + metabolic production) - output = 0 ICF and ECF are separated by the cell membranes. Plasma and interstitial fluid are separated by the capillary wall → their ionic composition is similar but protein content is high in plasma  The plasma is the noncellular part of the blood; It exchanges substances continuously with the interstitial fluid through the pores of the capillary membranes. These pores are highly permeable to almost all solutes in the extracellular fluid except the proteins.  Calculation of Intracellular Volume. The intracellular volume cannot be measured directly. However, it can be calculated as Intracellular volume = Total body water – Extracellular volüme Calculation of plasma volüme Plasma Volume = TBV * (1 – hematocrit/100) Calculation of Interstitial Fluid Volume. Interstitial fluid volume cannot be measured directly, but it can be calculated as Interstitial fluid volume = Extracellular fluid volume – Plasma volume Measurement of Blood Volume. Plasma volume Total blood volume= Hematocrit The Ionic Basis of the Resting Membrane Potential Neurons have a selectively permeable membrane During resting conditions membrane is: Permeable to Potassium (K+ channels are open) Impermeable to Sodium (Na+ channels are closed) Diffusion force pushes K+ out (concentration gradient) Electrostatic force pushes K+ in Thus, there is ‘dynamic equilibrium’ with zero net movement of ions The Resting membrane potential is negative  Constituents of Extracellular and Intracellular Fluids Ionic composition of plasma and interstitial fluid is similar The most important difference between these two compartments is the higher concentration of protein in the plasma Because of the Donnan effect, the concentration of positively charged ions (cations) is slightly greater (about 2 % ) in the plasma than in the interstitial fluid.  Osmosis Osmosis is the net diffusion of water across a selectively permeable membrane from a region of high water concentration to one that has a lower water concentration. When a solute is added to pure water, this reduces the concentration of water in the mixture. Thus, the higher the solute concentration in a solution, the lower the water concentration. Further, water diffuses from a region of low solute concentration (high water concentration) to one with a high solute concentration (low water concentration) Tonicity is a physiological term used to describe a solution and how that solution would affect cell volume if the cell were placed in the solution and allowed to come to equilibrium: A) If the cell in the solution does not change size at equilibrium the solution is isotonic. B) If a cell loses water and shrinks at equilibrium, the solution is said to be hypertonic. C) If a cell placed in the solution gains water at equilibrium and swells, we say that the solution is hypotonic to the cell.  Glucose and Other Solutions Administered for Nutritive Purposes Many types of solutions are administered intravenously to provide nutrition and water to people who cannot otherwise take adequate amounts of nutrition. Glucose solutions are widely used, and amino acid and homogenized fat solutions are used to a lesser extent. When these solutions are administered, their concentrations of osmotically active substances are usually adjusted nearly to isotonicity.  If an isotonic saline solution is added to the extracellular fluid compartment, the osmolarity of the extracellular fluid does not change; therefore, no osmosis occurs through the cell membranes. The only effect is an increase in extracellular fluid volume.The sodium and chloride largely remain in the extracellular fluid because the cell membrane is impermeable to the sodium chloride.  If a hypertonic solution is added to the extracellular fluid, the extracellular osmolarity increases and causes osmosis of water out of the cells into the extracellular compartment. Again, almost all the added sodium chloride remains in the extracellular Osmosis compartment, and fluid diffuses from the of water cells into the extracellular space to achieve osmotic equilibrium. The net effect is an increase in extracellular volume (greater than the volume of fluid added), a decrease in intracellular volume, and a rise in osmolarity in both compartments  If a hypotonic solution is added to the extracellular fluid, the osmolarity of the extracellular fluid decreases and some of the extracellular water diffuses into the cells until the intracellular and extracellular compartments have the same osmolarity. Osmosis Both the intracellular and the extracellular of water volumes are increased by the addition of hypotonic fluid, although the intracellular volume increases to a greater extent.  Clinical Abnormalities of Fluid Volume Regulation: Hyponatremia and Hypernatremia The primary measurement that is readily available to the clinician for evaluating a patient’s fluid status is the plasma sodium concentration. Hyponatremia Vomiting Diarrhea Overuse of diuretics Renal diseases Addison Disease impairs the kidneys' ability to reabsorb sodium Excessive secretion of antidiuretic hormone resulting in excessive water reabsorption from the renal tubules  Regulation of Water Intake Thirst mechanism is the driving force for water intake The hypothalamic thirst center osmoreceptors are stimulated by Plasma osmolality of 2–3% Angiotensin II or baroreceptor input Dry mouth Substantial decrease in blood volume or pressure  Regulation of Water Intake Drinking water creates inhibition of the thirst center Inhibitory feedback signals include Relief of dry mouth Activation of stomach and intestinal stretch receptors  Thirst-driving systems are present in the forebrain sCVOs, such as the SFO and OVLT CVO, circumventricular organs OVLT, organum vasculosum of the lamina terminalis SFO, subfornical organ lacking a blood-brain barrier A: Neural pathways responsible for the activation of thirst. Ang II-mediated thirst signals originate from AT1a neurons in the SFO and OVLT,96),115) and clock-driven thirst signals from VP neurons in the SCN.157) These signals are integrated in the MnPO and transmitted to the thalamus.115) B: Neural pathways responsible for the suppression of thirst. Water drinking signals sensed by the oral cavity and/or gastrointestinal tract are relayed to the NTS to activate CCK neurons in the SFO,138) GLP1R neurons in the MnPO,143) and Oxtr neurons and PDYN neurons in the PBN148),149) in order to suppress thirst. Arrowhead lines show neural projections from excitatory neurons and blunt-headed lines show those from inhibitory neurons. Dotted lines indicate hypothetical neural connections. Adcyap, adenylate cyclase-activating polypeptide; AP, area postrema; AT1a, angiotensin receptor 1a; CCK, cholecystokinin; GLP1R, glucagon-like peptide-1 receptor; LH, lateral hypothalamus; MnPO, median preoptic nucleus; NTS, nucleus of the solitary tract; OVLT, organum vasculosum of the lamina terminalis; Oxtr, oxytocin receptor; PBN, parabrachial nucleus; PDYN, prodynorphin; pre-LC, pre-locus coeruleus; PVN, paraventricular nucleus; PVT, paraventricular thalamus; SCN, suprachiasmatic nucleus; SFO, subfornical organ; VP, vasopressin  Water intake control Activation mechanisms of thirst: 1. Increase in [Na] and osmolality in body fluids Thirst-driving systems are present in the forebrain sCVOs, but systemic dehydration is also sensed by peripheral sensing systems Na sensors and osmosensors for water intake control OVLT is the main sensing site of [Na] increases for water intake induction. the Nax signal in the OVLT appears to play a role in controlling water intake behavior. Increases in [Na]co-activate SLC9A4-positive neurons ASIC1a: acid-sensing ion channel 1a SLC9A4: Transmembrane proteins encoded by the family of slc9 genes Nax belongs to the voltage-gated Na channel family Ang II receptor 1a (AT1a) Noda et.al., 2022  Water intake control 2. Angiotensin II The peptide hormone Ang II in the brain induces thirst, salt appetite, and Blood Pressure elevations. the medial prefrontal cortex, Ang II in body fluids is physiologically increased by also participates in the decision- making of water ingestion hypovolemia, dehydration, and Na deficiency Noda et.al., 2022 Water intake control 3. Dipsogenic hormones. Secretin regulate water homeostasis throughout the body and influence the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver Relaxin-3 is involved in water drinking behavior during pregnancy and/or other conditions. Noda et.al., 2022  Inhibitory mechanisms of thirst 1. Na decrease in body fluids Cholecystokinin- dependent modulation of water intake. Ang II-dependent water intake is controlled by CCK through GABAergic neurons B: Stimulation of CCK neurons and whole-cell patch-clamp recording of GABAergic neurons Noda et.al., 2022 with their synaptic connections in the SFO. Inhibitory mechanisms of thirst Feedback regulation through the lateral parabrachial nucleus (LPBN) Water-predicting cues. Estrogen Ghrelin. the negative feedback control of Atrial natriuretic peptide. intake behaviors in order to avoid overconsumption. Noda et.al., 2022  Osmolality Na+ concentration in plasma Plasma volume Stimulates BP (10–15%) Osmoreceptors Inhibits in hypothalamus Negative feedback Baroreceptors inhibits in atrium and Stimulates large vessels Stimulates Posterior pituitary Releases ADH Antidiuretic hormone (ADH) Targets Collecting ducts of kidneys Effects Water reabsorption Results in Osmolality Scant urine Plasma volume Figure 26.6  Regulation of Water Output: Influence of ADH Water reabsorption in collecting ducts is proportional to ADH release  ADH → dilute urine and  volume of body fluids  ADH → concentrated urine and  volume of body fluids Antidiuretic Hormon (ADH OR VASSOPRESSIN)  Dehydration Decreased body water Dehydration can be caused by losing too much fluid, not drinking enough water or fluids, or both Vomiting and diarrhea are common causes  Plasma osmolality Plasma volume* Blood pressure Saliva Osmoreceptors Granular cells in hypothalamus in kidney Renin-angiotensin Dry mouth mechanism Angiotensin II Hypothalamic thirst center Sensation of thirst; person takes a drink Water moistens mouth, throat; stretches stomach, Initial stimulus intestine Physiological response Result Water absorbed Increases, stimulates from GI tract Reduces, inhibits Plasma osmolality (*Minor stimulus) Figure 26.5  Overhydration Excess water in the body Overhydration generally results in low sodium levels in the blood. Brain cells are particularly susceptible to overhydration (as well as dehydration) When overhydration occurs quickly confusion, seizures coma may develop.  Brain cells are particularly susceptible to overhydration (as well as dehydration) When overhydration occurs slowly, brain cells have time to adapt, so few symptoms occur When overhydration occurs quickly confusion, seizures coma may develop. Treatment Regardless of the cause of overhydration, fluid intake usually must be restricted. Causes of Hypernatremia: Water Loss or Excess Sodium Increased plasma sodium concentration Due to either loss of water from the extracellular fluid which concentrates the sodium ions, or excess sodium in the extracellular fluid. When there is primary loss of water from the extracellular fluid, this results in hyperosmotic dehydration.  Causes of Hypernatremia: Lack of antidiuretic hormone the kidneys excrete large amounts of dilute urine (a disorder referred to as diabetes insipidus) In certain types of renal diseases the kidneys cannot respond to antidiuretic hormone, also causing a type of nephrogenic diabetes insipidus. A more common cause of hypernatremia is dehydration caused by water intake that is less than water loss, as can occur with sweating during prolonged, heavy exercise. Causes of Hypernatremia: Hypernatremia can also occur as a result of excessive sodium chloride added to the extracellular fluid. This often results in hyperosmotic overhydration because excess extracellular sodium chloride is usually associated with at least some degree of water retention by the kidneys as well.  Thus, deciding on proper therapy, One should first determine whether the abnormality is caused by a 1. Primary loss or gain of sodium or 2. Primary loss or gain of water. Edema: Excess Fluid in the Tissues Edema refers to the presence of excess fluid in the body tissues. In most instances, edema occurs mainly in the extracellular fluid compartment, but it can involve intracellular fluid as well. The mechanism involves Increased capillary hydrostatic pressure Decreased plasma oncotic pressure Increased capillary permeability Obstruction of the lymphatic system  1. Intracellular Edema Two conditions are especially prone to cause intracellular swelling: (1) Depression of the metabolic systems of the tissues (2) Lack of adequate nutrition to the cells. If the blood flow becomes too low to maintain normal tissue metabolism, the cell membrane ionic pumps become depressed. Na-K pump prevents the cell from swelling  Sometimes this can increase intracellular volume of a tissue area ischemic leg it is usually a prelude to death of the tissue. Intracellular edema can also occur in inflamed tissues. Inflammation usually has a direct effect on the cell membranes to increase their permeability, allowing sodium and other ions to diffuse into the interior of the cell, with subsequent osmosis of water into the cells. 2. Extracellular Edema Extracellular fluid edema occurs when there is excess fluid accumulation in the extracellular spaces. There are two general causes of extracellular edema: (1) abnormal leakage of fluid from the plasma to the interstitial spaces across the capillaries, and (2) failure of the lymphatics to return fluid from the interstitium back into the blood.  Lymphatic Blockage Causes Edema When lymphatic blockage occurs, edema can become especially severe because plasma proteins that leak into the interstitium have no other way to be removed. The rise in protein concentration raises the colloid osmotic pressure of the interstitial fluid, which draws even more fluid out of the capillaries. Thank you