Outline of pathophysiology : electrolyte water balance

2021-04-28 02:24 PM

The main stimulus of water intake is thirst, which occurs when the effective osmotic pressure increases or the extracellular volume or blood pressure decreases.


Water is essential for the human body; all biological and chemical processes of cells and organizations are closely related to the properties of water. The body cannot grow and survive without water. Dehydration or disturbance in the distribution of water between areas of the body can lead to death if not corrected in time.

Water distribution

Water accounts for about 50% of the body weight in women and 60% of the body weight in men. This difference is due to the proportion of adipose tissue in women is higher than in men. This means that increasing the fat content will decrease the percentage of water in the body. The proportion of water also changes with the course of life: In children, water accounts for 75% of the body weight, the elderly only 50%. Water in the body is divided into two main areas: Intracellular water accounts for 55 - 75%, extracellular: 25-45%. The extracellular area includes water in the lumen (plasma) and extracellular matrix at a rate of one third.

Table: Water distribution among regions and organizations.


ml / kg weight

% body water

Intracellular water



Extracellular water

Water of plasma, interstitial fluid

In association

In bone

Cerebrospinal fluid excreted fluid

















Water balance

Normal plasma osmolality (ALTT) is between 275-290mOsm / kg. In equilibrium, the amount of water imported and exported is in balance. Abnormalities in this balance will lead to a decrease or increase in blood sodium. In a normal person, there is mandatory dehydration through urine, faeces, evaporation through the skin and respiration. Dehydration due to evaporation through the skin and respiration contributes to the regulation of body temperature. Renal dehydration is associated with a minimum daily excretion of 600mOsm. Know that the maximum urine osmolality is 1200mOsm / kg, so the minimum urine osmosis is 500ml per day.

Table: Bilan water of human body for 24 hours.

Enter / 24 hours

Export / 24h

Drinking water: 1000- 1500ml

Urine: 1000-1500ml

Water in feed: 700ml

Water through skin and respiration: 900ml

Endogenous water (due to oxidation): 300ml

Water in feces: 100ml

Total: 2000-2500ml

Total: 2000-2500ml

Enter: The primary stimulus of water intake is thirst, which occurs when the effective osmotic pressure increases or the extracellular volume or blood pressure decreases. Usually, water intake is higher than physiological need.

Export: Excretion of water is subtly regulated. The main determinant of renal water excretion is arginine-vasopressin (AVP or ADH), a polypeptide synthesized by the hypothalamus and secreted by the posterior pituitary gland. The binding of AVP to the receptor V2 of the collecting cell membrane activates adenyl cyclase and leads to water-based passive reabsorption following the osmotic gradient. AVP secretion is stimulated by hypertonia. Given that the main extracellular solutes are sodium salts, the effective osmotic pressure is determined primarily by the sodium concentration in the plasma. An increase or decrease in tonicity will be detected by osmotic receptors in the hypothalamus as a corresponding decrease or increase in cell volume, indicating an increase or decrease in AVP secretion.

The basic principles of water movement in the body

The basic principle of osmosis

Osmosis is the pure diffusion of water from high to low concentration. A soluble substance added to the water reduces the water in the mixture. The solute concentration increases, the water concentration decreases and vice versa. In the body, the movement of water back and forth between membranes obeys the Donnan balance, which means that water will go from where there is a low ALTT to a place with a higher ALTT.

The exchange between the intercellular and the cell

The intercellular is the buffer area between the lumen and the cell, so large fluctuations from the lumen do not have a direct effect on the cell area. The cell membrane separating these two regions does not allow free ions to diffuse back and forth, so the electrolyte composition between these two regions is completely different. Na + has a very high concentration in the intercellular space, which can be diffused through the cell but is actively pumped out by the cell at the energy cost of ATP. Likewise, the concentration of K + in the cell is 30 times that of the intercellular.

Thus, the electrolyte composition of the two sides is very different, but the total amount of them is equal, so the osmotic pressure (ALTT) of the two sides is still equal. If ALTT is different, the water will exchange to restore balance to ALTT. For example, if you put 4g of NaCl into the body, 3g will enter the intercellular and that will increase ALTT in the intercellular. Na + and Cl- cannot enter the cell, so the water in the cell will go to the intercellular to balance ALTT. When there are disorders of water transport through the cell membrane, damage or disturbance of cell membrane activity will lead to various pathological conditions such as cell dehydration, cytostasis ...

The exchange between the intercellular and the lumen

A capillary wall is a membrane separating the intercellular space from the lumen. This membrane has tiny holes that allow electrolyte water and molecules less than 68,000 in molecular weight to diffuse freely. Therefore, the protein in the lumen is normally higher than in the intercellular fluid and the electrolyte content is similar. In fact, the electrolyte composition between them is slightly different because the protein is negatively charged, so it pushes some anions to the intercellular (Cl-, HCO3-) and attracts some cations (Na +, Ca ++). However, when Donnan's equilibrium was established, the total electrolytes between the two regions were still equal. Therefore, the two sides are equal. When there is an imbalance in the volume of water and electrolytes between these two regions, there will be an exchange of both water and electrolytes to re-establish balance.

The role of hydrostatic pressure (Ptt) and ALTT in water exchange between two regions: Hydrostatic pressure created by the contractile force of the heart. As far from the heart, this pressure gradually decreases, until the capillary Ptt is 40mmHg, in the middle of the capillary is 28mmHg and in the posterior capillary Ptt is 16mm the protein in the lumen (mainly alb) produces a colloidal ALTT (Pk) with value 28mmHg that tended to draw water from the intercellular into the lumen. In the normal state of the body, the hydrostatic pressure at the capillary tip is greater than the colloidal pressure, so it pushes the water out of the lumen to diffuse into the tissues. In the posterior capillary, Ptt is less than Pk, so water will be pulled back into the lumen again. The balance between these two pressures results in equal amounts of water entering and exiting the capillaries (Starling Equilibrium). When the upper imbalance or capillary permeability increases with protein, this balance is disrupted.

Water balance regulation

Osmotic conditioning

To protect cells from changes in ALTT and changes in cell volume and also because the intracellular and extracellular regions do not have the same osmotic gradient, the body must regulate the osmotic pressure. in the extracellular region. The normal plasma osmolality is 275-290mOsm / kg. The reason that ALTT is maintained between this normal value is due to the extremely sensitive mechanism of the osmotic receptors in the hypothalamus capable of detecting a tonal change of even as small as 1-2% for timely correction. time. These osmotic receptors are activated when there is an increase in tonicity (ineffective osmols such as urea or glucose do not play a role in thirst stimulation). The average permeability threshold for thirst stimulants is about 295mOsm / kg, but it varies from person to person.

Increased ALTT stimulates the release of ADH in the posterior pituitary and stimulates the thirst centre in the hypothalamus and causes a feeling of thirst. An increase in water reabsorption in the distal and manifold under the effect of ADH, along with an increase in thirst, normalizes osmotic pressure and increases extracellular volume.

Conversely, a decrease in ALTT inhibits ADH secretion leading to increased water excretion.

In fact, ADH deficiency in urine excretion will increase from 15-20l with 40-80mosmol / kg of water per day. The maximum excretion of ADH will reduce urinary excretion to 0.5l with 800-1400 mmol/kg water per day.

So ALTT change will be firstly regulated by water composition adjustment.

Volumetric conditioning

Volume regulation via renal pressure receptors (via the RAA system: renin-angiotensin-aldosterone):

A determined extracellular volume required to maintain circulation and metabolism in the body is independent of osmolality (correlation rate). Pressure receptors in the glomerular apparatus are important receptors for extracellular volume. When the local pressure is reduced, it releases renin into the bloodstream. Renin will convert Angiotensinogen produced by the liver to Angiotensin I. Then Angiotensin I will be converted to Angiotensin II by the action of ACE (Angiotensin-converting enzyme) and effective:

Increases blood pressure.

Stimulating thirst causes drinking water.

Adrenal stimulation increases Aldosterone secretion.

Aldosterone’s increase sodium reabsorption in the distal tubule and lead to an increase in extracellular ALTT. This in turn stimulates the pituitary to increase ADH secretion and the hypothalamus causes a feeling of thirst.

Volume regulation through pressure receptors in the atria:

In 1986, Ackermann discovered that the atrial muscle cells can synthesize a peptide that increases urinary sodium excretion called ANP (atrial sodium uretic peptide) when the atrium is straining or increasing central venous pressure. or after eating (due to increased sodium burden). ANP is found to work today:

Increased renal tubular excretion of sodium.

Diuretic due to inhibition of ADH and Aldosterone secretion.

Reduced blood pressure (due to a decrease in the sensitivity of vascular smooth muscle to vasoconstrictors).

Increases glomerular filtration rate.

In addition to these two major stimulation mechanisms in 1988 Schrier further discovered that there are pressure receptors in the body of the thoracic and carotid sinuses. It may also stimulate increased secretion of ADH via nerve mechanisms. However, the sensitivity of these receptors is much lower than that of the osmotic receptors. Effective circulatory (arterial) volumetric changes, vomiting, pain, stress, hypoglycaemia, pregnancy and some drugs can be stimulated via pressure detectors of the carotid sinuses.

On the other hand, after an increase in salt burden S.Valdes also found a Digoxin-like that inhibits Na + - K + - ATPase and increases urinary sodium excretion.

Thus the change in extracellular volume will be regulated primarily through the adjustment of sodium content.

Mechanism of renal Macula-Densa reverse control:

This is an inverted control mechanism in the kidneys to regulate the speed

Glomerular filtration, ensuring circulation volume for the body.

The parietal apparatus has Macula-Densa cells at the end of the distal tube. When blood pressure increases, glomerular hydrostatic pressure increases, thereby increasing glomerular filtration rate and increasing urine flow in the renal tubules. This increases renin release and leads to increased Angiotensin II in the kidneys. Angiotensin II constricts the incoming artery thereby reducing the filtration pressure and, in turn, the rate of glomerular filtration.

Summary: Reduction of extracellular volume reduces plasma volume and decreases blood pressure. Reduced blood pressure is caused by decreased blood return to the heart and reduced cardiac flow. It stimulates pressure receptors in the carotid sinuses and the aorta to increase the activation of the sympathetic nervous system and the RAA system. This is intended to maintain average BP and perfusion through the brain and coronary vessels. In contrast to the cardiovascular response, the renal response aims to reset the extracellular volume by reducing the glomerular filtration rate (GFR) but increasing renal tubular sodium reabsorption due to increased sympathetic tone that induces stimulation. spasm of incoming vessels. The proximal tubular salt reabsorption is due to the mechanism of increased Angiotensin II release and the hemodynamic change in the peritubular capillaries (decreased Ptt and increased Pk). Increased sodium reabsorption in the manifold is an important factor in renal adaptation to extracellular volume reduction.

Impairment of osmolality and volume

Significance of the RAA system in hypertension

Especially in the case of increased renal vascular tone and renal artery stenosis will increase renin release with the end result of increased vascular resistance and increased plasma volume due to the effect of Angiotensin II and Aldosterone.

Hyperaldosteronism syndrome

Primary hyperaldosteronism syndrome (Conn's syndrome):

Reason. Pathology of the adrenal cortex such as adenoma that produces aldosterone, primary overproduction or cancer

Consequences: Hypernatremia, hyponatremia, increased blood volume with increased tonicity, increased potassium, decreased blood potassium, metabolic alkalosis due to increased proton excretion, non-oedema, decreased plasma renin activity.

Secondary hyperaldosteronism syndrome:

Causes: Cirrhosis of the liver (decreased Aldosterone degradation), kidney failure, heart failure ..., increased renin in adrenal tumours or Bartter syndrome.

Consequences: increased plasma renin activity, increased tonicity, oedema, decreased blood potassium. Normal or slightly increased plasma sodium concentrations.

Aldosterone deficiency


Primary adrenocortical insufficiency (Addison's disease).

Secondary adrenocortical insufficiency (deficiency of ACTH from the pituitary gland).

Consequences: decreased volume, decreased Na + blood, decreased Cl- blood, increased K + blood, increased Mg ++ and acidosis.

DI: diabetes insipidus


Central diabetes insipidus (CDI: central DI). Due to abnormality in the hypothalamus reduces ADH secretion.

Renal pale diabetes (RDI: laconic DI). Because the receptor of the tubular cells is less sensitive to ADH

Manifestations: polyuria and hypotonic urine.

Distinguishing CDI and RDI: Give orally 10 µg of Desmopressin. Post-stimulant osmolality will increase at least over 50% in the CDI and unchanged in the RDI.



oedema is the normal excess water retention during the perforation of the cell, the accumulation of water in natural cavities such as the pleura, pericardium, and peritoneum.

The main mechanisms of oedema

Increased extracellular osmotic pressure: The extracellular osmotic pressure is largely determined by sodium, so sodium retention plays an important role in oedema because water is later trapped in the passive tissues according to sodium.

Sodium retention can result from a decrease in glomerular filtration rate, either from an increase in tubular reabsorption, or both. But regardless of the disease mechanism, sodium retention will cause extracellular fluid retention, increasing extracellular water volume. The excess extracellular fluid will be distributed in the intercellular (causing oedema) and distributed in plasma (causing stagnation in the venous system).

Hydrostatic hypertension: This pressure is determined by blood pressure; it has the effect of repelling water from the lumen of the cell to the level of the capillary. All the causes affecting the contractile force of the heart muscle and all the causes that interfere with blood circulation can increase the hydrostatic pressure, disrupt the Starling balance, causing water to back up in the intercellular causing oedema. However, this is not the only mechanism because pure hydrostatic pressure increases without causing oedema.

Reducing colloidal osmotic pressure: Colloidal pressure is undertaken by plasma proteins (80% is albumin), which holds and absorbs water into the lumen as opposed to hydrostatic pressure.

When there is a decrease in blood Protides such as decreased supply, decreased synthesis or excessive loss in urine, ... will reduce the osmotic pressure of the blood colloid, the water does not return to the vessel, the intercellular accumulation causes swelling. It should be noted that there is no strong correlation between the hypovolemia level with the onset or severity of symptom oedema.

Increased vascular permeability to proteins: The vascular wall is seen as a semi-permeable membrane that normally does not allow proteins with a molecular weight of more than 68,000 Da to pass. Organizational hypoxia, anaerobic metabolism, local inflammation, allergies, ... all cause vasodilation, increased vascular permeability. As a result, blood proteins escape into the interstitial tissue, increasing the colloidal pressure in the interstitial tissue, causing it to become oedema.

Interference with Lymph Circulation: In Starling equilibrium, the amount of water that is actually expelled from the endothelium by hydrostatic pressure is more than the amount of water drawn back by colloidal pressure. The excess water is pushed out in that space back into the general circulation through the lymphatic pathways. Each day, white blood vessels lead to about 2-4 litres of fluid.

There is also a small amount of protein released from the capillaries that will also return to the blood this way. Therefore, when the lymphatic circulation is hindered the amount of fluid and that protein is deposited in the interstitial tissue causing oedema.

Oedema by obstructing lymph circulation is usually local oedema. For example curettage of axillary lymph nodes in breast cancer treatment of arm oedema. Oedema in the scrotum and legs found in helminthiasis caused only by the development of parasites that cause obstruction of the lymphatic vessels of the lower extremities.

Favourable factors: Mechanical stress in tissues also plays an important role in the appearance and distribution of oedema. The looser the organization, the easier it is to appear oedema and to appear at the earliest.

The mechanism is due to the loose organization not creating enough of the mechanical pressure needed to balance a state of oedema. Therefore, oedema often appears early on the eyelids, at the pelvic crest, on the anterior tibial plateau, ...

In summary, oedema can manifest as systemic or local, may be joined by one or more of the above mechanisms, have mechanisms that act as a trigger, have mechanisms that play an auxiliary role, they often interact. Mutual influence forms a pathological spiral. For example, cardiac oedema affects the functioning of the liver and kidneys, leading to the mechanisms found in these two types of oedema.


Electrolyte distribution

In an adult about 70kg, sodium accounts for about 4200 mmol, respectively 60mmol / kg and divided as follows:

Intracellular compartment: 80 mmol = 2%.

Bone: 1700 mmol = 40%.

Intercellular compartment: 340 mmol = 8%.

Extracellular space: 2100 mmol = 50%.

Distribution in the extracellular:

Table: Concentrations of ions in the intracellular and extracellular fluids.


Sodium is the main ion of extracellular fluid, which determines the extracellular volume. Serum sodium is between 138-143 mEq / l or mmol / l. It accounts for 95% of the extracellular cations, so it is directly related to water metabolism.

Potassium is the main cation of intracellular fluid. Intracellular potassium accounts for 98% of the total potassium content of the body, so the serum potassium is very low from 3.5 to 4.5 mEq / l or mmol / l. It is involved in maintaining intracellular fluid tonicity and osmotic balance between the intracellular and extracellular. Potassium is essential for cell life, especially for the functioning of cell membranes. In clinical practice, the electrocardiogram can reflect well blood potassium status.

Other cations all have an important role: for example, Ca ++, Mg ++ are involved in nerve conduction and cell potential ...


Cl- is the most important extracellular anion, serum Cl- from 95-105mEq / l. Bicarbonate: Its value is between 22-28 mEq / l or mmol / l.

Protein: Values ​​of 65-75g / l corresponds to 15-20 mEq / l in the anion column.

Other plasma anions are generally not quantified. These are organic acids (6 mEq / l), phosphates (2 mEq / l), sulfates (1 mEq / l). In the anion-cationic equilibrium, it occupies an average value of 9-10 mEq / l. Physiologically, the anion-cation balance is calculated as 150-155 mEq / l. In the case of anion gap, the so-called anion gap (AG: anion gap) is very common in metabolic acidosis and is calculated as:

Under normal conditions: (cation = anion).

Na + + K + + Ca ++ + Mg ++ = Cl -   + HCO3 - + Protid + 10 + AG

The anion gap is inferred by:

AG = (Na + + K + + Ca ++ + Mg ++ ) - (Cl -   + HCO3 -   + Protid + 10)

Or a simple formula to calculate: AG = [Na + - (Cl - + HCO3 - )]

Therefore, loss or stagnation of electrolytes causes pathological upheavals. Na + cation is the main osmotic force of the extracellular matrix, K + is the main osmotic force of the intracellular. Because these two cations have the same osmotic effect, when the extracellular Na + decreases, water will enter the cell and vice versa. Therefore, the changes in extracellular sodium concentration are the cause and also the only symptom that tells us the changes in water balance in the intracellular region.




↑ Na+

← H2O →


Figure: Movement of water according to sodium ion concentration.

Na + and Cl- are the most important ions in the extracellular matrix, accounting for 80% of the ions in a liter of fluid. Therefore, electrolyte loss is mainly and first is loss of Na + and Cl-.

Electrolyte balance

Sodium is entered into the body as a dry salt. The real requirement for salt is about 1g per day but usually people eat more, about 6 g (or 110 mEq / 24g). Sodium requirements can be 3-4 times higher than normal requirements in hot climates.

Sodium is filtered through the glomerulus and reabsorbed up to 60-70% through the proximal tubule depending on charge neutralization and is osmosis. In the distal tubule and the loop of Henle, Aldosterone and ANP will be responsible for sodium excretion or reabsorption according to the body's current needs 25-30% reabsorption in the loop of Henle by the co-capillary factor. Na + K + 2Cl- (apical co- transporter), 5% reabsorption in the distal tubule by the sensitive co-transporter Thiazide Na + Cl-

Potassium requirement is about 3 g or 50-100 mEq / 24g. Potassium is mainly excreted in urine (80-90%). Note: do not enter the body still output about 30-50 mEq / 24g through urine.

Electrolyte balance conditioning



Figure: Relationship between osmotic regulation and volume regulation.


In short, the regulation of volume (water) and the tonicity (electrolyte) is closely related. Changes in tonicity (weakness or hypertonia) alter absorption (water, electrolytes) and thus affect volume. Conversely, changes in volume alter absorption and excretion to maintain tonicity. It should be noted that the absorption and excretion of electrolytes occur more slowly than the absorption and excretion of water, so when drinking a lot of water, there is an immediate increase in the urinary tract, but when eating more salt, there is a feeling of thirst and oliguria first when excess salt excretion takes effect.


Glucide metabolism: Potassium is necessary for glycogen formation, so when glycogen degradation will increase blood potassium.

Protide metabolism: Protide anabolism reduces and catabolism causes hyperkalaemia.

Adrenal cortex: Corticosteroids increase urinary potassium thereby reducing the potassium of blood and cells.

Acid-base balance: alkalosis causes decreased, acidosis causes hyperkalaemia.


Renal excretion of potassium has no threshold, so excretion persists despite a decrease in serum potassium.

Gastrointestinal excretion can be from 5-10 mEq / L increased to 100 mEq / L in case of diarrhoea.

Subcutaneous potassium excretion is negligible but may be increased in stressful cases, with increased adrenocortical function.


Pathophysiology of cardiogenic shock

Urine formation: Reabsorbed glomerular filtration

Air in and out of the lungs: pressure causes the movement of air

Mechanism of urine concentration: osmotic pressure changes in different segments of the renal tubule

Absorption and excretion of potassium through the kidneys

Prothrombin activation: initiates blood clotting

Pulmonary capillary dynamics: capillary fluid exchange and pulmonary interstitial fluid dynamics

Graphical analysis of high-volume heart failure

Calculate the glomerular filtration rate (GFR): the forces that cause the filtration process

Estimated renal plasma flow: PAH clearance

Nephron: The functional unit of the kidney

Reduced sodium chloride, dilates arterioles, increases Renin release.

Ammonia buffering system: excretes excess H + and creates new HCO3

Red blood cells: differentiation and synthesis

Concentrated urine formation: urea contributes to increased osmotic pressure in the renal medullary

Extracellular fluid distribution between interstitial space and blood vessels

The proximal tubule reabsorption: active and passive reabsorption

Origin of lymphocytes: the body's resistance to infection

The endocrine regulates tubular reabsorption

Acidosis causes a decrease in HCO3- / H + in renal tubular fluid: compensation mechanism of the kidney

Sodium channel blockers: decrease the reabsorption of sodium in the manifold

Physiological anatomy of the kidneys and urinary system

Self-regulation of glomerular filtration rate and renal blood flow

Pathophysiology of fever

The kidneys excrete sodium and fluid: feedback regulates body fluids and arterial pressure