III. Metabolism of water and its disturbances

1 Terms

homeostasis   equilibrium of internal environment maintained by organisms regulation mechanisms
dehydratation  decreased overall volume of liquids of organism
dehydratation (isotonic1, hypotonic2, hypertonic3)

 

 decreased volume of somtaic liquids whereas these liquids are equally osmotic active1 as plasma (less osmotic active2, more osmotic active3)
hyper-hydration = over-hydration

(isotonic1, hypotonic2, hypertonic3)

 

 increased volume of bodily liquids of organism (over-hydration can be iso, hypo or hyper  tonic – osmotic equally1, less2 or more3 active than plasma)
hypervolemia  increased volume of circulating liquids (blood)
hypovolémie  decreased volume of circulating  liquids (blood)
polyuria  increased volume of urine over 24 hour than normal, usually more than 3 litres. We recognise pressure polyuria (increased filtration pressure at glomeruli) and osmotic polyuria (when osmotic active substance enters proximal tubules  – e.g. glucose in patients with diabetes mellitus) and water (insufficiency of ADH)
anuria  absence of normal urine creation with volume of secondary urine  less than 100 ml per 24 hours
oligurie  decreased volume of urine to less than 500 ml per 24 hours
nonoliguria  output of urine more than 400 ml per 24 hours in patients with acute or chronic azotemia (= renal failure)
osmolality  summation of all osmotic active particles concentration (molecules and ions) in a solution; expresses total count of particles (independent to their size or electric charge) dissolved in 1 kg of solvent
osmolarita  expresses total amount of particles dissolved in 1 dm3 (litre) of solution, osmotic pressure is proportional to osmolarity (normal osmotic pressure of plasma: 275 – 300 mmol/l)
osmotický tlak  osmotic pressure is pressure caused by outflow of solvent through a semipermeabile membrane to the space in which solution contains higher concentration of dissolved particles; in human this phenomenon is very important in kidneys during water resorption
oncotic pressure = colloid osmotic pressure  colloid osmotic pressure of proteins is a part of osmotic pressure
polydipsia  abnormal excessive thirst; often because of increased plasma osmolarity
free water  solute free water without ions
SIADH  syndrome of inappropriate secretion of Anti-Diuretic Hormone (ADH) causes retention of free water in body, decrease of body liquids osmolarity and oliguria
diabetes insipidus  deficiency or ineffectiveness of ADH causing polyuria and  plasma concentration

2 Physiology of somatic liquids

Life is based on processes going in water so when we are talking about inner environment we talk mainly about somatic liquids. Water has many function for organism:

  • preserving inner environment (homeostasis)
  • space for chemical reactions (hydrolytic and all others)
  • maintaining circulating volume and perfusion
  • transporting substances: nutrients, emissions and information molecules
  • firmness and elasticity of the skin and mucosa
  • termoregulation

Change of water volume influences volume and function of all cells of body, ions concentration and its functions. Regulation of water metabolism is very soft a and reacts even to small changes of volume and quality (osmolarity, natrium concentration). Volumes of liquids can be influenced by malfunction of various organs (cardiovascular system, kidneys, gastrointestinal tract) or functions (termoregulation) and contrarily. Regulation of body fluids is a part of stress reaction too. Disturbance of reactivity can lead to life threatening conditions or even to death.

2.1 Amount and sorting of water

Quantity of water in body depends on age, sex, weight, hydration of organism and on ratio of lipid tissue (the more bigger is part of lipid tissue of body the less contain of water organism  proportionally has). Overall volume of water in adult 75 kg weighting man is 42 l (60% of body weight) of total body fluid TBF. There is only 53 % of water in women because even non-obese women have higher percentage of lipid tissue than men. Maximal percentage of water in organism is during infancy (80% – 85%) and childhood (75%). In elder body fluid decreases to over 50%.

Water can be divided to two main compartments (spaces) – extracellular and intracellular.

Extracellular fluid (ECF) comprises 20% of total body weight of adult man (14 l of water).  Extracellular fluid can be divided to intravasal (blood plasma) and interstitial (tissue) fluid. Don’t forget these fluids out of cells but separated to other parts of ECF to so called third space by some kind of barrier: liquor, intra-articular, intra-ocular fluid.

            Intracellular fluid (ICT) comprises 40% of body weight of adult man so two thirds of his total body fluid (TBF).

2.2 Composition of somatic liquids

Volume and composition of every body fluids are maintained almost in constant range during physiological conditions. Intracellular (ICT) and extracellular (ECT) fluids have different proportion of ions and proteins but they are in electrochemic equilibrium.

For more see fblt.cz or biophysics – Donnans equilibrium = Gibbs-Donnan effect, Nernst equation, semipermeability, membrane potential).

They form osmotic pressure and pH of the inner environment. Osmolarity of ECF is maintained  in the range of 280 ± 2 mmol/l  and  pH je 7,4 ± 0,04.

Ions Extracellular fluid (mmol/l) Intracellular fuid (mmol/l)
Na+ 138 -148 10
K+ 4 – 5 140 -160
Cl 103 2 – 4
HCO3 28,3 10
Ca 2+ 2,25 – 2,75 0,0001

 

           

 

 

 

Tab.3.1: Concentration of the most important ions of extra and intra –cellular fluid

 

Extracellular fluid contains great amount of sodium and chloride ions and relative big amount of HCO3 ions. Nutrients and oxygen are dissolved in ECF and they diffuse from capillaries to cells and waste products are washed away from tissues through it. This is the way how water influences maintaining the homeostasis – stability of inner space (inner environment) balance (we have to encourage that inner space stability should be understood as dynamic and in every moment changing processes).

Plasma is a part of ECF. The most important difference of plasma from another parts is high concentration of proteins, it is important to mention that oncotic pressure is osmotic pressure of proteins.

            Intracellular fluid contains about four times more proteins than blood plasma, there is big number of potassium and phosphate ions but on contrary less natrium and chloride ions. There is very low concentration of calcium ions and its level is maintained by pumping them to endoplasmic or sarcoplasmic reticulum, mitochondria and out of the cell. +vapnik jako signal. a fce?

Pressure caused by migration lower concentration solution solvent to the more concentrated solution is called osmotic pressure. This pressure is proportional to ammount of ions present in the solution. Osmotic pressures of both sides of membrane are in equilibrium in normal state, because intracellular fluid is isotonic according to extracellular fluid. Proteins manifest in the same way and this osmotic pressure is called oncotic pressure, this pressure  is so part of osmotic pressure.

Osmotic gradient between the cell and interstitial space is generated just by those substances which can not move freely through cell membranes (e.g. sodium, glucose etc.). Osmotic gradient induces creation of force imbibing water from the space of lower osmolar activity. If is higher osmolarity in extracellular space, water flows from the cell which is reduces its volume and wrinkles itself. In the contrary when extracellular osmolarity lowers cell expands and swells. Urea crosses freely cell membrane so when it’s the level of osmolarity in plasma rises concentration in cells ascends too and so gradient doesn’t changes, water shift is absent. Manifestation of osmolarity changes depends on the rate and time, extreme violation of homeostasis then shows as central nervous system disturbance symptoms because its cells are the most sensitive to change of volume.

2.3 Regulation mechanisms

Osmolarity of body fluids is monitored by hypothalamus receptors. These are cells very sensitive to change of their volume connected to change in osmolarity of inner environment. After 2% rise of osmolarity they mediate rise in secretion of ADH, a hormone helping to maintain water in body (solute free water) so causing decrease in osmolarity. If the overall osmolarity is increased by increase of urea concentration then there is no higher secretion of ADH.

 

 

 

 

 

 

 

Obr.3.1: Schéma tří prostorů tělesných tekutin a pohybů komponent, které ovlivňují osmolaritu séra: voda i močovina procházejí volně přes cévní stěnu i membránu buněk, glukóza a sodík přecházejí volně do intersticia, ale do buněk se nedostanou (sodík jedině sodným kanálem nebo pomocí Na+/K+ pumpy, glukóza za pomoci inzulinu, glukózových transportérů SGLT či facilitátorů transportu GLUT). Bílkoviny se fyziologicky  nefiltrují ani přes cévní stěnu. (Schéma podle A. Kazdy)

3 Water metabolism control disturbances

3.1 Water intake and loss

Water intake and loss is in equilibrium in physiologic state. There should be change of 1,5 l per 24 hours. Organism losses water through urine, perspiration, respiration and by gastrointestinal tract (stool). 300 ml of water per day is created during chemical transformation of substances. Losses should be substituted by drinking.

Dehydratation can be caused by insufficient intake or by excessive loss (perspiration, vomiting, diarrhoea), hyperhydration in opposite circumstances. Dehydratation endangers especially old people (decreased thirst sensation, worsen regulation of water metabolism or unability to access water during immobilisation) and infants containing 1400 ml of water in tissues and turnover of 700 ml per day. There only small misbalance of intake and loss can lead to develop dehydration.

3.2 Water intake and loss control

Metabolism of water dependant on intake and loss is controlled by homeostatic mechanisms influencing osmolarity and volue at most. Intake of water is regulated by the thirst sensation. Losses are dependant on more factors: water evaporates during respiration, sweating and is excreted by stool and urine. Regulation is allowed only by urine creation through renal concentration mechanisms.

3.2.1 Thirst

Thirst: caused by increase of body fluids osmolarity and is one o the most common symptoms of water loss (is induced when the water loss equals about 2% of body weight). It is provoked by dryness of mouth too. Thirst centre is located in the anterior hypothalamus. It contains osmoreceptros (cells sensitive to osmolarity changes) which change their volume according to osmolarity of extracellular fluid. They reduce their volume in higher osmolarity of ECF. Irritation of these cells induces thirst sensation and ADH secretion.

Thirst sensation evokes:

  • higher osmolaruty of extracellular fluid (higher level of glucose, proteins or ions etc.)
  • relative hyperosmolarity (because of free water loss)
  • severe hypokalemia (significantly lowers ability of kidneys to concentrate urine, leads to polyuria and polydipsia)
  • lowered blood volume (activation of stress reaction induces sympathetic tonus and so secretion of ADH which is causing thirst sensation)
  • dry mouth for example after longer speech (unknown mechanism not connected to volume of somatic liquids), over-spiced food

3.2.1.1 Malfunction of thirst sensation

Polydipsia is increased or often repeated sensation of thirst. It developes during somatic fluids losses (decreased circulating volume) or when ECF is hypoosmolar. Sometimes schizophrenia can lead to psychogenic (= primary) polydipsia when the fluid intake is enormous too. Lowered thirst sensation evolves in elderly (the most probably as a consequence of decreased receptors sensitivity), often as a consequence of the stroke. Another theory considers lowered thirst sensation as a defensive mechanism against hypoosmolarity worsening, this hypoosmolarity can be induced by increased level of basal ADH secretion and decreased ability of kidneys to concentrate urine.

3.2.2 Renal concentration mechanisms

Water reabsorbtion is controlled especially by hormones (ADH and aldosterone).

3.2.2.1 Antidiuretic  hormone

ADH (= antidiuretic  hormone =  vasopresin), this hormone is created in hypothalamus and then is shifted to posterior lobe of hypophysis by axonal transport. It acts at distal and collecting tubules where connects to receptors and allows the reabsorbtion of free water. This mechanism requires evolved osmotic gradient at renal marrow, because presence of ADH leads to aquaporine expression on the tubular cells surface , those pores allow resorption of water at distal tubule and collecting duct, this resorption magnitude is on the basis of mentioned osmotic gradient. Beside this ADH controls resorption of urea from collecting duct and so the increasing of osmotic concentration of urea in kidneys marrow. AntiDiuretic Hormone is vasoconstrictor and thus is called vasopressin.

Sekretion of ADH rises during

  • irritation of osmoreceptor at hypothalamus by increase of ECFs osmolarity
  • activation of sympathetic nervous system by irritation of stretch receptors of great veins, cardial atrias and carotic sinuses (irritation develops after decrease of circulating fluids volume or decrease of pressure)
  • stress situations (activation of stress respond, by pain, trauma, surgical procedure, etc.)
  • nicotine

Secretion of ADH is inhibited by alcohol

Obr.3.2: Regulace osmolarity a množství vody v organismu prostřednictvím antidiuretického hormonu (ADH): osmoreceptory v hypotalamu monitorují změnu osmolarity a při jejím zvýšení zvýší pocit žízně a sekreci ADH. ADH zvýší resorpci volné vody v ledvinných tubulech a tím změní osmolaritu plazmy. Osmolarita plazmy a ostatních tekutin v těle úzce souvisí. Sekrece ADH se zvyšuje také přímo při aktivaci sympatiku.

3.2.2.2 Aldosterone

Mineralocorticoid aldosterone is a hormone produced by adrenal cortex participating on the resorption of water indirectly by its connection to receptors which induces backward resorption of sodium at distal and collecting ducts. Water is then resorbed passively and chloride ions are resorbed too according to electrochemic gradient.

Aldosterone is flooded out as a reaction to decreased perfusion through kidneys. Decreased perfusion induces Renin secretion from juxtaglomerular apparatus of kidneys where sensor cells are situated (baroreceptors monitoring blood flow and chemoreceptors reacting to sodium and chloride concentrations in tubular fluid). Renin is enzyme splitting plasmatic protein angiotensinogen to angiotensin I and this one is then transformed to Angiotensin II mostly at lungs (with help of pneumocites of the 2nd type). Angiotensin II induces aldosterone secretion at adrenal cortex. This is so called Renin – Anngiotensin – Aldosterone (RAAS). Aldosterone augments resorption of sodium and water, so raised circulating volume increases even renal perfusion and thanks to this increases glomerular filtration too (in addition angiotensin helps to glomerular filtration by its vasoconstrictive effect aimed especially to efferent ducts) leading to raise of primary urine volume present for resorption at distal and collecting duct. Beside this aldosterone induces potassium secretion by kidneys, with this potassion hydrogen is secreted too.

Aldosterone level raises when concentration of chloride and potassium in plasma is low (activation is administered by activated chemoreceptors of juxtaglomelural apparatus). Aldosterone is one of the stress hormones and is outflows to circulation when sypathetic part of vegetative nervous system is activated. Secretion of aldosterone as a part of stress respond is activated through two pathways: centralisation of circulation caused by sympathetic activation lowers perfusion of kidneys and activates baroreceptors. Nevertheless sympathetic activation leads directly to renin secretion too.

 

Obr.3.3: Regulace hypovolémie prostřednictvím aldosteronu: snížené prokrvení ledvin nebo nízká koncentrace sodíku zvýší sekreci reninu, renin aktivuje angiotenzinogen, vzniká angiotenzin I (v plicích se změní na angiotenzin II), který zvýší sekreci aldosteronu z kůry nadledvin. Aldosteron resorbuje v tubulech sodík, s nímž jde pasivně voda a vylučuje draslík. Následuje změna intravazálního objemu a tlaku, která změní prokrvení ledvin a cyklus se uzavírá.

Aldosterone secretion is secondary influenced by plasmatic concentration of potassium, its high concentration induces aldosterone secretion at suprarenal gland and so induces potassium secretion by kidneys.

3.2.2.3 Atrial natriuretic factor

Only one hormone called atrial natriuretic factor (ANF) directly causes excretion of water in organism. It is released mostly at right atrium of heart when the the higher volume of circulating fluid or raised venous return alone influences myocardial cells by increased pressure. ANF presence leads to excretion of sodium and following water at distal and collecting duct of kidneys. Beside that ANF causes vasodilatation and lowers secretion of hormones participating on fluid retention, thus it protects heart against increased volume overload.


Tab.3.2: Přehled řízení metabolismu vody

 

3.2.3 Disorders of water metabolism control

3.2.3.1 Disorders of ADH secretion

Syndrome of inappropriate antidiuretic hormone is consequence of increased ADH secretion.

There are various causes of its higher concentration. The most common manifestation among the malignant diseases is ectopic synthesis and release of ADH by cells of small cell lung cancer but it is not solely tumor marker, secretion from bronchi after long term irritation by inflammation is described. Secretion of ADH is often complication of cerebral oedema,  clinical idiopathic form is described when we are not able to confirm cause of higher level of this hormone. Typical symptoms are caused by raised production of ADH at the tissue of olfactory neuroblastoma in childhood.

Thanks to knowledge of mankind about hormones action we can deduce consequences:

  • rapid raise of weight (because of water retention)
  • oliguria (water retention again)
  • urine is not concentrated and its specific gravity and osmolarity is raised
  • osmolarity of plasma decreases and ions concentration too (hyponatremia caused by dilution)
  • volume of cells of CNS expands because of hypotonic fluid entering those cells according to concentration gradient, intracellular swelling of brain evolves and signs of water intoxication manifest (headache, vomiting, vertigo, disorientation, cramps and coma)
  • hypervolemia is not so severe as during increased aldosterone secretion and so does not lead to excessive change of blood pressure (water invades interstitial space and mostly to cells).