Maintenance of the effective circulating volume is essential for adequate tissue perfusion and is mainly related to the regulation of sodium balance. In contrast, maintenance of osmolality prevents changes in cell volume and is largely related to the regulation of water balance.
Regulation of extracellular volume
The regulation of extracellular volume is determined by a tight control of the balance of sodium, which is excreted by normal kidneys. Although only a small proportion of total extracellular fluid resides in the arterial circulation it is the fullness of the arterial vascular compartment - or the so-called effective arterial blood volume (EABV) - that is the primary determinant of renal sodium and water excretion. The fullness of the arterial compartment depends on a normal ratio between cardiac output and peripheral arterial resistance. Thus, diminished EABV is initiated by a fall in cardiac output or a fall in peripheral arterial resistance (an increase in the holding capacity of the arterial vascular tree). When the EABV is expanded, this in turn leads to an increase in urinary sodium excretion and vice versa.
Two types of volume receptors sense changes in the EABV:
■ Extrarenal: in the large vessels near the heart
■ Intrarenal: in the afferent renal arteriole, which Controls the renin-angiotensin system via the juxtaglomerular apparatus.
A decreased effective circulating volume leads to activation of these volume receptors, which leads to an increase in sodium (and hence water) reabsorp-tion by the kidney and expansion of the extracellular volume via stimulation of the sympathetic nervous system and activation of the renin-angiotensin system (p. 655). In contrast, atrial natriuretic peptide (ANP), produced by the atria of the heart in response to an increase in blood volume, increases sodium excretion.
Abnormalities of extracellular volume
Increased extracellular volume
Extracellular volume expansion is the result of increased sodium (and hence water) reabsorption or impaired excretion by the kidney.
These depend on the distribution of excess fluid within the extracellular space (i.e. between the interstitial space and intravascular compartment), which in turn depends on venous tone (which determines hydrostatic pressure), capil-lary permeability, oncotic pressure (mainly dependent on serum albumin) and lymphatic drainage. For instance, with hypoalbuminaemia there is a reduction in plasma oncotic pressure and predominantly interstitial volume overload. Cardiac failure leads to expansion of both compartments:
■ Interstitial volume overload- ankle oedema, pulmonary oedema, pleural effusion and ascites.
■ Intravascular volume overload - raised jugular venous pressure, cardio-megaly and a raised arterial pressure in some cases.
This must be differentiated from local causes of oedema (e.g. ankle oedema as a result of venous damage following thrombosis), which do not reflect a disturbance in the control of extracellular volume.
Most causes of extracellular volume expansion are associated with renal sodium chloride retention.
■ Cardiac failure due to a reduction in cardiac output and impaired per-fusion (therefore effective hypovolaemia) of the volume receptors. The increased sympathetic activity generated by stimulation of the volume receptors also leads to release of antidiuretic hormone (ADH) even though plasma osmolality (see later) is unchanged.
■ Cirrhosis. This is through a complex mechanism, but there is vaso-dilatation and hence underperfusion of the volume receptors. Hypo-albuminaemia may also contribute.
■ Nephrotic syndrome. Sodium retention is primarily due to increased sodium reabsorption in the renal collecting tubules directly induced by the renal disease. In addition, in some patients the low plasma oncotic pressure induced by hypoalbuminaemia leads to plasma volume depletion and arterial underfiNing as in cardiac failure and cirrhosis.
■ Sodium retention. This may be as a result of renal impairment, where there is a reduction in renal capacity to excrete sodium, or due to drugs such as mineralocorticoids (aldosterone-like actions), thiazolidinediones (by upregulation of epithelial sodium transporter channel) and non-steroidal anti-inflammatory drugs (NSAIDs). The latter inhibit synthe-sis of vasodilatory prostaglandins in the kidney with an increase in renal vascular resistance and increase in water and sodium reabsorption.
The underlying cause must be treated. The cornerstone of treatment, the diuretics, increase sodium and water excretion in the kidney. There are a number of different classes of diuretic, of which the most potent are the loop diuretics, e.g. furosemide (Table 8.4 and p. 349).
Decreased extracellular volume
This may be the result of loss of sodium and water, plasma or blood.
Volume depletion occurs in haemorrhage, plasma loss in extensive burns, or loss of salt and water from the kidneys, gastrointestinal tract or skin (Table 8.5). Signs of volume depletion occur despite a normal or increased body content of sodium and water in sepsis (due to vasodilatation and increased capillary permeability) and diuretic treatment of oedematous states where mobilization of oedema lags behind a rapid reduction in plasma volume due to diuresis.
Symptoms include thirst, nausea and postural dizziness. Interstitial fluid loss leads to loss of skin elasticity ('turgor'). Loss of circulating volume causes
Table 8.4 The main classes of diuretics in clinical use
Mechanism of action
Reduce Na+ and Cl- reabsorption in ascending limb of loop of Henle
Reduce sodium reabsorption in distal convoluted tubule
Prevent potassium exchange for sodium in distal tubule
|Table 8.5 Causes of extracellular volume depletion|
The diagnosis is usually made clinically. A Central venous line allows the measurement of central venous pressure, which helps in assessing the response to treatment. Plasma urea may be raised because of increased urea reabsorption and, later, prerenal failure (when the creatinine rises as well). This is, however, very non-specific. Urinary sodium is low (<20 mmol/L) if the kidneys are working normally. The urinary sodium can be misleading, however, if the cause of the volume depletion involves the kidneys, e.g. with diuretics or intrinsic renal disease.
The aim of treatment is to replace what has been lost.
■ Haemorrhage involves the loss of whole blood. Immediate treatment is with crystalloid or colloid until packed red cells are available.
■ Loss of plasma, as in burns or severe peritonitis, should be treated with human plasma or a colloid (p. 326).
■ Loss of sodium and water, as in vomiting, diarrhoea or excessive renal losses, is treated with replacement of water and electrolytes. In chronic conditions associated with mild/moderate sodium depletion, e.g. salt-losing bowel or renal disease, oral supplements of sodium chloride or sodium bicarbonate (depending on acid-base balance) may be suffi-cient. Glucose-electrolyte solutions are often used to restore fluid balance in patients with diarrhoeal diseases. This is based on the fact that the presence of glucose stimulates intestinal absorption of salt and water (p. 38).
■ In the acute situation if there have been large losses of sodium and water, patients are usually treated with intravenous sodium chloride 0.9% (Tables 8.3), and replacement is assessed clinically and by measurement of serum electrolytes. Rapid infusion (1000 mL/h) of sodium chloride 0.9% or colloid is given if the patient is hypotensive.
■ Loss of water alone, e.g. diabetes insipidus, only causes extracellular volume depletion in severe cases because the loss is spread evenly over all the compartments of body water. The correct treatment is to give water. If intravenous treatment is required, water is given as glucose 5% (pure water is not given because it would cause osmotic lysis of blood cells).
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2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
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