Kidney and sodium

You get most of the sodium you need in your diet. If you take in too much, your kidneys get rid of the extra sodium in your urine. Normally, your body keeps your sodium levels in a very narrow range. If your sodium blood levels are too high or too low, it may mean that you have a kidney problem, dehydration, or another type of medical condition. 

Recent findings from chemical analysis studies of laboratory animals, as well as noninvasive quantitative Na+ MRI (Na-MRI) studies in patients, have shown that remarkable amounts of Na+ are stored in muscle and in skin without commensurate water retention

Controlling blood volume

The total amount of sodium in the body affects the amount of fluid in blood (blood volume) and around cells. The body continually monitors blood volume and sodium concentration.

When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal.

When blood volume or sodium concentration becomes too low, the sensors trigger mechanisms to increase blood volume. These mechanisms include the following:

• The kidneys stimulate the adrenal glands to secrete the hormone aldosterone. Aldosterone causes the kidneys to retain sodium and to excrete potassium. When sodium is retained, less urine is produced, eventually causing blood volume to increase.

• The pituitary gland secretes vasopressin (sometimes called antidiuretic hormone). Vasopressin causes the kidneys to conserve water.

Proximal tubules :

The main role of the proximal tubule is reabsorption of water and fi ltered electrolytes, glucose and amino acids, including: • 60 – 80% of water • 60 – 70% of fi ltered sodium (via the Na/K - ATPase) • 90% of potassium • 90% of bicarbonate

Loop of Henle:

  The main role of the loop of Henle is to generate an interstitial sodium gradient between the cortex (low concentration Na + ) and inner regions of the medulla (high concentration Na + ). This concentration gradient is generated by virtue of the fact that the ascending limb of the loop of Henle is impermeable to water. Twenty to 40% of sodium is reabsorbed from the tubular space into the interstitium in the loop of Henle by the NaK2Cl co - transporter and around 10% of fi ltered water. This generates a high concentration of Na + in the interstitium but water is unable to follow, due to the impermeable ascending limb. The high interstitial Na + concentration provides a gradient which allows urine to be concentrated as it fl ows through the collecting tubules (the permeability of which is controlled by ADH). The NaK2Cl co - transporter is inhibited by loop diuretics, the effect of which is to reduce sodium reabsorption, and hence the concentration gradient generated, so that a more dilute urine is produced. In addition to sodium transport, the majority of magnesium is also absorbed in the ascending limb of the loop. At the end of the loop of Henle, as it arrives back up in the cortex, lie the cells of the macula densa. These cells sense luminal sodium concentration and are involved in controlling the release of renin, and hence systemic blood pressure (see below). 

Distal tubule:

  The distal tubule plays a role in fi ne tuning the fi nal urine sodium concentration (and hence determines how dilute or concentrated it will be). Around 5% of sodium is reabsorbed here via the NaCl co - transporter, which is inhibited by thiazide diuretics. 

Collecting duct:

  A further 2% of sodium is reabsorbed by the aldosterone - sensitive sodium channels found within the distal convoluted tubule and the collecting duct

Renin -angiotensin-aldosterone ( RAA) pathway (Figure E ) :

Renin is released from the juxtoglomerular apparatus of the kidney in response to reduced renal perfusion or low sodium delivery to the distal part of the loop of Henle. Renin coverts angiotensinogen (made in liver) to angiotensin I. This is converted to angiotensin II by angiotensin - converting enzyme (ACE), found principally in the pulmonary vasculature. Angiotensin II is a potent vasoconstrictor and will thus increase TPR and MAP. It also causes the release of aldosterone from the adrenal cortex, which acts on the distal tubule to cause retention of sodium, and thus water, expanding volume and increasing venous return, CO and MAP. 

What would you expect the urine sodium to be in a patient with ATN ?

 In ATN there is dysfunction and death of tubular cells. The normal function of these cells is to pump sodium out of the tubular lumen (urine) and into the interstitium (in order to generate an osmotic gradient within the medulla). If the tubular cells are damaged or dead, they cannot move sodium appropriately, so there is an increased concentration of sodium in the urine (Figure 1.4 ). Typical results for pre - renal failure versus ATN are shown in Table 1.1 .

Dietary salt should be restricted to 6 g per day. This equates to 2.4 g of sodium per day (1 g sodium = 2.5 g of salt)

 Urate and cystine stone formation is inhibited by alkylinising the urine. Aim for a urine pH > 6.5 (give oral sodium bicarbonate)

 How would you manage this patient? The main management of SIADH is to restrict fl uid intake to 0.5 – 1 L per day. This is usually in the form of normal saline, if IV fl uids are used (NB: normal (0.9%) saline contains approximately 150 mmol/L of Na). Occasionally hypertonic saline is given but this requires careful management to avoid a rapid increase in sodium levels. The aim is to bring the sodium up by no more than 5 mmol/day. Severe cases may require the use of demeclocycline, an agent which causes nephrogenic diabetes insipidus, i.e. it makes the collecting tubules insensitive to the actions of ADH. 

Mild hyponatraemia is common and usually asymptomatic. If the sodium falls to around 120 mmol/L then there is often restlessness, irritability and confusion. Sodium levels of <110 mmol/L lead to progressive coma and seizures. • Hyponatraemia occurs if there is too little sodium, too much water or both. • When assessing the cause of hyponatraemia, it is important to establish the volume status of the patient. • If the patient is hypovolaemic then hyponatraemia may be caused by diuretics, hypoadrenalism, salt -wasting nephropathy (see Table 23.1). • If the patient is euvolaemic or fl uid overloaded then hyponatraemia may be due to SIADH, chronic renal failure, LVF, cirrhosis or nephrotic syndrome (see Table 23.1). • In SIADH, typical fi ndings are: Na <125 mmol/L patient is normovolaemic urinary Na >20 mmol/L plasma osmo <260 mosmol/kg urinary osmo >500 mosmol/kg. • Syndrome of inappropriate antidiuretic hormone may be caused by intracranial pathology such as head injury or infection, pulmonary pathologies including pneumonia, malignancies and drugs (particularly chlorpropamide and chlorpromazine). • Treatment of SIADH is with fl uid restriction. The aim should be to bring the sodium up slowly in order to avoid central pontine myelinolysis. 

Although urine electrolytes (e.g. measurement of urine sodium) can help to distinguish between pre - renal ARF (low urine sodium) and established ATN (high urine sodium due to death/dysfunction of tubular cells and therefore lack of pump activity moving sodium out of the urinary space), in practice by the time the result has returned, the diagnosis is clinically obvious.

Mild hyponatraemia is common and usually asymptomatic. If the sodium falls to around 120 mmol/L then there is often restlessness, irritability and confusion. Sodium levels of < 110 mmol/L lead to progressive coma and seizures. Serum sodium should be corrected gradually (usually with fl uid restriction) as rapid correction can result in central pontine myelinolysis (CPM). When assessing the cause of hyponatraemia, it is important to establish the volume status of the patient. If the patient is hypovolaemic then hyponatraemia may be caused by diuretics or hypoadrenalism (Addison ’ s disease).

a,b,c. Secondary causes of hypertension are shown in case 15 , Box 15.1 . Addison ’ s disease is usually associated with hypotension due to excess renal sodium loss, which results in hyponatraemia and intravascular volume depletion.