Which hormone uses extracellular membrane receptors?

8.1 Water balance and fluid spaces

Lothar Thomas

8.1.1 Water and electrolyte balance

The hydrogen change describes the balance between the uptake and excretion of water. The cell membrane separates the intracellular space (IZR) and extracellular space (EZR) and is freely permeable to water, but not to electrolytes. Due to the free movement of water between IZR and EZR, the osmolality, defined as the ratio of electrolytes to free water, is kept constant and constant.

Changes in the homeostasis of water in the organism are divided into hypo- and hyperosmolar disorders, depending on whether there is an excess or a lack of water in relation to the dissolved substances (solutes). Depending on gender, age and body fat, the water content is 55–65% of body weight and the distribution between IZR and EZR is 2: 1. In the EZR, 80% of the water is in the interstitial space and 20% is intravascular (circulating blood volume).

In the EZR is Na+ the dominant cation and its concentration in the plasma reflect the osmolality. In the IZR, K+ the most important cation. The different distribution pattern of the cations is caused by the energy- and oxygen-dependent Na+-K+-Maintain the pump of the cell membrane. If there is a lack of energy or oxygen, the Na+-K+Insufficient pump, the ion gradients collapse, primarily intracellularly, resulting in cellular edema / 1 /.

In order to maintain the osmotic equilibrium (isotonicity) and the homeostasis of the volume (isovolemia) of the fluid spaces, the organism maintains a balanced balance of import and export of water and electrolytes. It is regulated by:

  • The kidneys, which maintain a constant plasma osmolality in the narrow range of 275–290 mmol / kg through excretion or reabsorption of water free of solute. The regulating hormone is arginine vasopressin.
  • The thirst mechanism stimulated by intravascular hypovolemia and hyperosmolality. Thirst is the primary defense mechanism against excessive fluid loss.

The water and electrolyte homeostasis is regulated by sensors and neurohumoral mechanisms with effector hormones that function via negative feedback (Tab. 8.1-1 - Neurohormonal mechanisms with a regulatory effect on volume homeostasis).

8.1.2 Diagnosing disorders of the water and electrolyte balance

The disturbances in the electrolyte and water balance are based on complex processes. An integrative analysis is therefore necessary. It consists of the history, medical examination and laboratory results.

Important laboratory tests and their informative value are shown in Tab. 8.1-2 - Laboratory tests in the event of disturbances in the electrolyte and water balance.

Examinations and findings for two clinical questions are shown in Table 8.1-3 - Assessment of pathological laboratory findings of the electrolyte and water balance.

8.1.3 Osmotic balance

The total body water is the determinant of the osmolality of the fluid compartments of the organism.

The maintenance of the osmotic homeostasis is regulated by a change in the renal excretion of free, i.e. osmotically unbound water / 2 /. The antidiuretic hormone (ADH) arginine vasopressin plays a central role in the regulation of free water. Important stimuli for the release of ADH are:

  • Increase in plasma osmolality; Even fluctuations below 2% are registered by the osmoreceptors located in the anterolateral hypothalamus and lead to a change in the concentration of ADH in the plasma. The stimulation of ADH release begins at a plasma osmolality of ≥ 280 mmol / kg and is a maximum of 290 mmol / kg. ADH causes increased reabsorption of water in the kidneys (antidiuresis). An increase in plasma osmolality to ≥ 295 mmol / kg triggers a feeling of thirst via the mediation of the osmoreceptors.
  • Changes in effective arterial blood volume reported to the anterolateral hypothalamus by baroreceptors in the right atrium and lungs. Total body water

The proportion of total body water is up to 94% in the fetus, 75% in the newborn and 60% in the one year old. Between the 1st and 2nd year of age and during puberty, the proportion of body water again shows two short-term increases and then levels off at 60% in the adult man and 50% in the woman / 2 /.

The homeostasis of water is maintained in temperate climates by drinking 1.5 liters of water per day. In addition, there are about 600 ml from the metabolism of food and 300 ml of oxidation water. The controlled water loss of around 1 l / day occurs through the kidneys, the uncontrolled (insensitive) water loss occurs through the respiratory tract (0.3 l), stool (0.1 l) and sweat (0.1 l). The renal excretion of water is regulated by the kidneys in such a way that the osmolality of the plasma remains constant within narrow limits.

8.1.4 Liquid spaces

The total body water is distributed between the EZR and the IZR.


The tonicity, also known as effective osmolality, is the concentration of dissolved substances that exerts an osmotic force on the cell membrane, so that, depending on the gradient, there is a displacement of water out of or into the cell. These are not freely permeable substances such as Na+, K+ or glucose. Low molecular weight organic substances such as urea, ethanol, methanol or ethylene glycol permeate the cell membrane unhindered like water and thus do not exert any osmotic forces or water displacements. Extracellular space (EZR)

The EZR comprises all water outside the cells, that is about 45% of the total body water. The plasma, the interstitial fluid, the lymph, the water of the dense tissue, e.g. connective tissue and bones and the transcellular fluid / 2 / are counted for the EZR.


Blood plasma contains 93% water and 7% solid components, mainly proteins and lipids. The essential cation is Na+, the essential anions are Cl and HCO3. Since the plasma proteins do not permeate intact endothelium, they are decisive for the osmotic pressure on the capillary membrane. The colloid osmotic pressure in the plasma, for which 80% albumin is responsible, is 28 mmHg. Plasma makes up 7.5% of total body water.

Interstitial fluid

The interstitial fluid is created by the filtration of plasma through the vessel wall. This is well permeable to water, electrolytes and low molecular weight substances. 25–50% of the circulating proteins are filtered off into the interstitium every day, about 80% of the fibrinogen is intravascular. The height and direction of the plasma flow through the capillaries is determined by the Starling forces. In certain diseases such as heart failure and liver cirrhosis, changes in Starling's forces can lead to the formation of edema. The interstitial fluid makes up 20% of the total body water.

Transcellular fluid

These are the fluids secreted by organs such as saliva, pancreatic juice, bile and intestinal secretions, which make up 2.5% of the total body water.

Water in connective tissue and bones

It is water that is bound in a collagen matrix. The proportion of total body water is 15%. Intracellular space (IZR)

The IZR contains 55% of the adult body water. The Na+-K+Pump, the intracellular Na+ after extracellular and extracellular K+ Pumps intracellularly in a ratio of 3: 2, maintains a balance of ions. The intracellular Na+-Concentration is 10 mmol / l and the extracellular 140 mmol / l. The concentration of Mg2+ is about 13 mmol / l intracellularly and only 1.5 mmol / l extracellularly. Intracellular are Cl and HCO3 lower than extracellular, the phosphate and sulphate concentration is intracellular but higher / 2 /.

The tendency of the cell to swell when the colloid osmotic pressure rises due to anionic macromolecules that are constantly occurring in the metabolism is counteracted by ion pumps in the plasma membrane that transport equivalent quantities of anions to the outside. Changes in liquid volumes

For the understanding of disorders of the Na+- and water balance, it is important to know the relationships listed below / 3 /.

Extracellular Fluid Volume (EZFV)

The EZFV is directly from the whole body Na+ dependent, as well+ and its anions are confined to the extracellular fluid, where the essential osmotically active substances are. Expansion or contraction of the FCFV activate regulatory systems with the aim of achieving a good balance between exogenous uptake and excretion of Na+ to manufacture. The effector is the kidney that has the Na+- and water excretion resets the FCFV in accordance with the stimuli of the regulatory systems.

Changes to the Na+-Concentration of the FCFV

The Na+-Concentration and thus the osmolality of the EZFV is regulated by the circulating blood volume. Volume sensors located in the carotid sinus, the auricles and the afferent arterioles of the kidneys report negative feedback (Fig. 8.1-1 - Physiology of water and volume homeostasis in the event of dehydration).

The result of any change in blood volume is a change in renal excretion of Na+by:

  • Activation of the sympathetic nervous system.
  • Activation of the renin-angiotensin-aldosterone system.
  • An increase or inhibition of the release of natriuretic peptides.
  • Influencing the arginine-vasopressin system.

The measured variable of the concerted working systems is the osmolality in the plasma. To maintain normal osmolality, the mechanisms mentioned adjust the intra- and extracellular water volume to the osmotically active substances. In order to keep the osmolality of the FCFV and thus the tonicity constant within narrow limits, the organism can absorb an unlimited amount of water when thirsty or excrete 15–20 l / 24 h of free water when exposed to water.

Changes in total body Na+

The FCFV is dependent on the amount of Na+ determined in the body, not by its concentration. An increase or decrease in the total body water changes the Na+-Concentration, but this says nothing about the FCF, as the water balance between IZR and FCR changes regardless of the size of the FCF. As a result, hypo- or hypernatremia occurs with a reduced, normal or increased FCFV. Reduction of the FCFV

A reduction in the EZVF above 5% causes a reversible reduction in renal blood flow. That causes:

  • The drop in glomerular filtration rate (GFR).
  • The increased secretion of arginine vasopressin.
  • Activation of the renin-angiotensin-aldosterone system.
  • An increase in the renal filtration fraction. It is the ratio of the GFR and the renal plasma flow (RPF) of a substance. Renal Filtratin Fraction = GFR / RPF.

A decrease in GFR causes the renal filtration fraction to increase. This results in:

  • Decreased urine volume and high osmolality in the urine.
  • A na+-Concentration above 20 mmol / l and a K+-Value above 40 mmol / l in the urine.
  • A disproportionate increase in serum urea in relation to creatinine. Normally the ratio urea-N (mg / dl) / creatinine (mg / dl) = 10, if the volume is reduced by more than 20 (conversion: urea × 0.357 = urea-N).
  • An increase in HCO3 in the urine to over 20 mmol / l due to the exchange of H+ against Na+.
  • An increase in uric acid in the serum due to a reduced excretion in the urine.
  • An increase in serum calcium, e.g. if there is hyperparathyroidism or bone metastases.
  • The intensification of hyperkalemia in a poorly controlled diabetic as less glucose is eliminated renally. Enlargement of the FCFV

Volume overload of over 5% manifests itself in edema, anasarca, pleural exudate and ascites and is common in the critically ill. It leads to an increase in body weight, heart rate and arterial blood pressure.

Which cause against regulatory mechanisms:

  • An increase in the volume of urine and the concentration of Na+ (over 20 mmol / l).
  • The increase in renal K+Excretion (over 40 mmol / l) and hypokalaemia despite suppression of the renin-angiotensin-aldosterone system, caused by volume expansion.
  • A hypouricemia; less uric acid is reabsorbed in the proximal tubule and more is secreted distally.

8.1.5 Volume homeostasis

The homeostasis of the volume is essentially determined by the filling of the arterial circulation. The effective arterial blood volume is registered by baroreceptors in the right atrium of the heart, in the lungs and in the aortic arch. It depends on the balance between vasoconstrictors and vasodilators (Tab. 8.1-1 - Neurohormonal mechanisms with a regulatory effect on volume homeostasis).

If the balance is disturbed, the distribution of water and electrolytes changes. This results in / 2 /:

  • Inadequate filling of the arterial circulation due to vasodilation or cardiac insufficiency, compensatory vasoconstriction with retention of Na+ and water due to activation of the sympathetic nervous system, the renin-angiotensin-aldosterone system and an increased release of ADH.
  • If the arterial vascular system is too full, due to volume expansion or tachycardia, vasodilation with increased excretion of water and Na+. It is induced by atrial natriuretic peptides, the kallikrein-kinin system and endothelial factors such as prostaglandins and NO. Regulators of the homeostasis of electrolytes and water

Essential regulators of homeostasis of electrolytes and water are:

  • The renin-angiotensin-aldosterone system.
  • The atrial natriuretic peptides.
  • The ADH thirst mechanism.

Renin-Angiotensin-Aldosterone System (RAAS)

A change in the secretion of renin takes place depending on the water and Na+-Admission. The secretion of renin is inhibited when NaCl is absorbed and stimulated when water is absorbed, thus preserving the blood volume in the event of salt and water loss, which can be changed by sweating, diarrhea or vomiting. The concentration of the aldosterone effector increases rapidly as a result of a decrease in blood volume or decreased renal perfusion.

Another powerful stimulator of aldosterone synthesis is a K+- Increase in plasma, resulting in increased aldosterone-induced renal K+-Excretion. The RAAS thus prevents hyperkalemia in the case of increased K+- Ingestion with food or according to K+-Released by strong muscle activity.

In chronic heart failure and liver cirrhosis, hyperaldosteronism occurs with retention of Na+and water and a volume expansion. In chronic heart failure, hyperaldosteronism is based on reduced renal perfusion and in liver cirrhosis on a reduced hepatogenic metabolism of aldosterone. See also Chapter 31 - Mineralocorticoid Hypertension.

Natriuretic peptides

This family consists of three structurally similar peptides, the atrial natriuretic peptide (ANP), the brain type (BNP) and the C type of natriuretic peptides. ANP and BNP are released when heart muscle cells stretch, CNP is formed by many organs. The primary function of ANP and BNP is to regulate blood volume and pressure. At high volume or increased pressure, they are released into the circulation. In their target organs, the kidneys and peripheral arteries, they activate the natriuretic peptide receptor A (NPR-A), which increases the intracellular concentration of cyclic guanosine monophosphate. The consequences are natriuresis, diuresis, vasodilation and lowering of blood pressure. The effect on the kidneys is as follows: on the glomerula, ANP and BNP cause dilation on the afferent arterioles and vasoconstriction on the efferent arteries. Thus the GFR is increased. In the collecting pipes, ANP and BNP lead to a reduced reabsorption of Na+ and thus the Na+-Excretion increased. The natriuretic effect of ANP and BNP is in two stages.

The Na+-Excretion is increased by:

  • A short-term increase in GFR, coupled with an antagonistic effect against RAAS-mediated Na+-Reabsorption in the proximal tubule.
  • Long-term inhibition of the reabsorption of Na+ in the ascending part of Henle’s loop and the collecting pipes.

ANP and BNP also suppress the release of renin and endothelin, an additional effect that regulates vascular tone.

ADH thirst mechanism

Thirst is triggered by intravascular hypovolemia and low blood pressure to maintain water homeostasis and is not osmotic. The increased secretion of arginine vasopressin in chronic heart failure with Na+-Retention for increased retention of water and hyponatremia.

The hyponatremia is rarely due to polydipsia, caused by an increased feeling of thirst. In patients with chronic heart failure and hyponatremia, the hypoosmolality of the plasma should inhibit arginine-vasopressin secretion.However, this is not the case; on the contrary, persistently increased concentrations of arginine vasopressin are measured. See also Article 8.5 - Osmolality).

8.1.6 Renal regulation of water and sodium excretion

The kidney filters about 150 liters of isotonic glomerular filtrate (GFR) daily. To maintain the water balance, the kidneys can produce both maximally diluted and maximally concentrated urine.

Conceptually, renal water regulation is divided into the following steps / 5 /:

  • Two thirds of the GFR is isotonically reabsorbed in the proximal tubule. In the case of arterial volume depletion, an increase to 80% is possible.
  • In the descending part of Henle’s loop, water is reabsorbed, while salts remain in the tubule and the osmolality can rise to 1,200 mmol / kg.
  • The ascending part of Henle’s loop and the distal tubule are relatively waterproof. Only salts are reabsorbed, which is why these nephron segments are also called dilution segments. The osmolality of the tubular fluid can drop below 50 mmol / kg.
  • In the collecting tube, the reabsorption of water is modulated by the antidiuretic hormone arginine vasopressin. If the tonicity in the ECR is too low, the secretion of vasopressin is inhibited and diluted urine is excreted. With increased tonicity, the secretion of vasopressin is increased, the water permeability of the collecting tube is increased and concentrated urine is excreted. Since water withdrawal is a function of arginine-vasopressin secretion, the osmolality in the urine can vary from less than 100 to 1,200 mmol / kg.

See also Fig. 8.1-2 - Renal tubular treatment of water and electrolytes. Determinants of maximum urine concentration and urine dilution

The delivery of GFR to the dilution segments depends on the volume, the composition of the GFR and the proximal tubular function. This results in a reduced formation of free water from:

  • A reduction in GFR due to volume depletion, heart failure, liver cirrhosis and nephrotic syndrome.
  • The reduction in salt transport in the dilution segments. This means that minimal osmolality is not achieved and the formation of free water is limited. This is the case with interstitial kidney disease or treatment with thiazides and loop diuretics.
  • The maintenance of a corticomedullary concentration gradient in the interstitium of the kidneys. The concentration gradient begins with isotonicity at the corticomedullary border and rises to 1,200 mmol / kg in the tip of the papilla. This interstitial osmotic gradient is responsible for the reabsorption of water from the collecting pipes into the great circulation. The development of the gradient depends on the vasopressin effect on the collecting tubes. In the case of interstitial kidney disease, treatment with loop diuretics, inadequate protein nutrition (reduced amount of urea), osmotic diuresis and all conditions with increased urine flow, the build-up of a normal interstitial osmotic gradient is disturbed.