STUDY - Technical - New Dacian's Medicine
Fluid
and Electrolyte Imbalances (4)
Translation Draft
I've reached hypernatremia.
I've reached hypernatremia.
From an etiological point
of view, hypernatremia is defined as a plasma concentration of
Na+ greater than 145 mmol/ l. because Na+ and the anions
accompanying it are the majority effective osmoli of the FEC,
hypernatremia is a state of hyperosmolarity. As a result of a
fixed number of particles in fic, maintaining osmotic balance in
hypernatremia causes the FIC volume to decrease.
Hypernatremia can be determined by the primary gain of Na+ or water scarcity. The two components of an adequate response to hypernatremia are the increased intake of water stimulated by thirst and the excretion of a minimum volume of maximum concentrated urine, reflecting the secretion of AVP in response to osmotic stimuli. In practice, most cases of hypernatremia result from water loss.
Since water is distributed by fic and FEC in ratio 2:1, a loss of a certain amount of water without solvents will result in a doubling of the contraction of the FIC compartment compared to the FEC compartment. For example, we consider three scenarios: the loss of one liter of water, one liter of NaCl isotone solution and one liter of NaCl hypotone solution. if one litre of water is lost, the FIC volume will decrease by 667 ml, while the FEC volume will decrease by only 333 ml. Due to the fact that Na+ is largely limited to fEC, this compartment will decrease by 1 l if the lost fluid is isoosmic. One litre of NaCl hypotone solution is equivalent to 500 ml of water (one third in FEC, two thirds in FIC) plus 500 ml of saline isotonic solution (also in FEC). So the loss of 1 l of hypotonic saline solution decreases the fEC and FIC volumes by 667 ml and 333 ml respectively.
The degree of osmolarity is generally average, unless the mechanism of thirst is abnormal or access to water is limited. The latter occurs in infants, mentally handicapped patients, patients with impaired mental status, postoperative states and patients intubated in intensive care units. Rarely, the impairment of thirst may be due to primary hypodipsia.
This usually occurs as a result of damage to hypothalamic osmoreceptors that control thirst and tends to associate with abnormal osmotic regulation of AVP secretion. Primary hypodipsia can be given by a variety of pathological changes including granulomatous disease, vascular occlusion and tumors. A subgroup of hypodipsic hyponatremia refers to essential hypernatremia, which does not respond to the forcing of water intake. This appears to be due to a specific defect in the osmoreceptors, which causes the nonosmotic regulation of the release of AVP.
Thus, the hemodynamic effects of water loading lead to AVP suppression and diluted urine excretion. The source of water loss is both renal and extrarenal. Extrarenal water loss may be caused by evaporation from the skin and respiratory tract (insensitive losses) or loss to the gastrointestinal tract. Insensitive losses are increased in the case of fever, exercise, exposure to high temperatures, severe burns and in mechanically ventilated patients. In addition, the Na+ concentration of perspiration decreases with deep perspiration, thus increasing the loss of solvent-free water.
Diarrhea is the most common gastrointestinal cause of hypernatremia. Specifically, osmotic diarrhoea (induced by lactulose, sorbitol or carbohydrate malabsorption) and viral gastroenteritis cause water loss that exceeds na+ and K+ losses. In contrast, secretory diarrhoea (e.g. cholera, carcinoid, VIP-man) has a fecal osmolarity (twice the sum of Na+ and K+ concentrations) similar to plasma and is accompanied by decreased FEC volume and normal plasma na+ concentration or hyponatremia.
Renal water loss is the most common cause of hypernatremia and is caused by medication, osmotic diuresis or insipid diabetes. Anse diuretics interfere with the countercurrent mechanism and produce an isoosmotic diuresis. This causes a decrease in the interstitial medullary tonicity and an impairment of the ability of the kidney to concentrate.
The presence of non-resorbit organic solvents in the tubular lumen of the nephron affects the osmotic reabsorption of water. This leads to excess water loss compared to Na+ and K+, known as osmotic diuresis. the most common cause of osmotic diuresis is hyperglycaemia and glycosuria in poorly controlled diabetes mellitus.
Intravenous administration of mannitol and increased endogenous production of urea (protein-rich diet) may also cause osmotic diuresis. Hypernatremia secondary to neosmotic urinary water loss is commonly given by: 1. central insipid or neurogenic diabetes characterized by impaired aVP secretion, or 2. nephrogen insipid diabetes resulting from resistance of the target organ (kidney) to the action of AVP. The most common cause of central insipid diabetes (DIC) is the destruction of neurohypophysis.
This may occur as a result of trauma, neurosurgery, granulomatous disease, neoplasm, stroke or infection. In many cases, DIC is idiopathic and can occasionally be hereditary. The familial form of this disease is inherited autosomal dominant and has been attributed to the mutation of the propresophyzine gene (precursor of AVP). Insipid nephrogen diabetes (DIN) can also be inherited or acquired. Congenital DIN is a recessive (X-linked) disorder caused by mutations in the V2 receptor gene.
There may also be autosomal mutations of the acondensin gene 2. This encodes the proteins of water channels whose membrane insertion is stimulated by AVP. The causes of sporadic DIN are numerous and include drugs (especially lithium), hypercalcemia, hypopotasemia and situations in which medullary hypertonicity is affected (e.g. papillary necrosis or osmotic diuresis). Pregnant women, in the second or third trimester of pregnancy, por develop DIN as a result of excessive development of vasopressin by the placenta. In the end, quite rarely, a primary gain of Na+ can cause hypernatremia. For example, inadequate administration of NaCl or NaHCO3 hypertone solution or salt replacement in the infant formula may cause this complication.
In terms of clinical manifestations, as a consequence of hypertonicity, water comes out of cells, leading to a decrease in FIC volume. A decrease in brain cell volume is associated with an increased risk of subarachnoid or intracerebral hemorrhage. Therefore, major symptoms of hypernatremia are neurological and include altered mental status, weakness, neuromuscular irritability, neurological focal deficits and occasionally coma or seizures. Patients may also complain of polyuria or thirst. For unknown reasons, polydipsic patients with DIC prefer very cold water.
These signs and symptoms of volume deplation are often present in patients with excessive sweating, diarrhoea or osmotic diuresis. The mortality rate associated with the plasma concentration of Na+ greater than 180 mmol/ l is very high. As with hyponatremia, the severity of clinical manifestations is related to the rapidity and size of the increase in plasma Na+. Chronic hypernatremia is generally less symptomatic as a result of adaptive mechanisms of cell volume preservation. Brain cells initially increase their concentration of Na+ and K+ salts later, followed by the accumulation of organic osmolites such as inositol. This helps bring the cerebral FIC volume back to normal.
It's time for diagnostic introductions. A complete anamnesis and a thorough physical examination often provide the key to the underlying cause of hypernatremia. Relevant symptoms and signs include the absence or presence of thirst, diaphoresis, diarrhoea, polyuria and manifestations of decreased FIC volume. Anamnesis should include a list of recent and current medicines, and a physical examination is incomplete without neurological and mental status evaluation. Measuring urinary volume and osmolarity are essential for assessing hyperosmolarity.
The appropriate renal response to hypernatremia is the excretion of a minimum volume (500 ml/ day) of maximum concentrated urine (urinary osmolarity greater than 800 mosm/ kg). These findings suggest renal or extrarenal water loss or administration of hypertone saline solutions. The presence of a primary excess of Na+ can be confirmed by the expansion of the FEC volume and natrium (urinary concentration of Na+ greater than 100 mmoli/ l). Many causes of hypernatremia are associated with polyuria and submaximal urinary osmolarity.
The product between urinary volume and osmolarity, i.e. the rate of excretion of solvents is useful in determining the causes of polyuria. To maintain a balance, the total excretion of solvents must be equal to the production of solvents. As described above, individuals on a normal diet generate about 600 mosm per day. So, the daily excretion of solvents greater than 750 mosm defines an osmotic diuresis. This can be confirmed by measurements of glucose and urinary urea.
In general, both DIC and DIN have polyuria with hypotonic urine (urinary osmolarity is less than 250 mosm/ kg). The degree of hypernatremia is normally average, unless thirst disorders are associated. Anamnesis and objective examination, as well as relevant laboratory data, can often exclude causes of acquired DIN. DIC and DIN are generally distinguished by the administration of Avp analogue desmopressin after careful water restriction. Urinary osmolarity should increase by at least 50 percent in DIC and will not change in DIN. Unfortunately, diagnosis is often difficult due to partial defects of secretion and action of AVP.
Therapeutic purposes are to stop continuous water loss by treating the underlying causes and correcting water deficiency. The FIC volume should be restored in hypovolemic patients. In hypernatremy due to water loss, the total amount of water of the body is about 40-50% of the dry weight in men and women respectively. As with hyponatremia, rapid correction of hypernatremia is potentially dangerous.
In this case, a rapid decrease in osmolarity may cause a rapid entry of water into cells that have exhibited a continuous phenomenon of osmotic adaptation. This would cause bloating of brain cells and increase the risk of seizures or permanent neurological impairment. So the water scarcity needs to be slowly corrected in 48-72 hours. When calculating the water replacement rate, continuous water losses should be entered into the equation and the plasma concentration of Na+ should be reduced by 0,5 mmol/ l/ hour, but not more than 12 mmol/ l within the first 24 hours.
The safest way to manage water is per bone or through a nasogastric probe (or any other feeding probe). Alternative 5% dextrose solution in water or saline hypotone solution may be administered intravenously. The most appropriate treatment of DIC is the administration of intranasal desmopressin. Other alternatives used to reduce urinary eliminations include a hyposodized diet in combination with low doses of thiazid diuretics. In some patients with partial ICD, medicines that stimulate AVP secretion or increase its action in the kidney are also useful. These drugs include chlorpromazine, clofibrate, carbamazepine and nonsteroidal anti-inflammatory drugs (NSAIDs).
The concentration defect in DIN can be reversible by treating the underlying conditions or by removing the drugs that caused the defect. Symptomatic polyuria in DIN can be treated with a hyposodized diet and thiazid diuretics, as described above. These measures result in an average volemic doutthat leads to an increase in proximal reabsorption of salt and water and a decrease in the transport of AVP to its place of action, which is the collector duct. By affecting the synthesis of renal prostaglandins, NSAID potentiates the action of AVP and thus increases urinary osmolarity and decreases urinary volume. Amidride may be useful in some patients with DIN who require lithium administration. The nephrotoxicity of lithium requires that the drug be absorbed into the cells of the collector duct via the amyloride-sensitive Na+ channel.
No more posting. We'll move on to the potassium-related introductions.
Hypernatremia can be determined by the primary gain of Na+ or water scarcity. The two components of an adequate response to hypernatremia are the increased intake of water stimulated by thirst and the excretion of a minimum volume of maximum concentrated urine, reflecting the secretion of AVP in response to osmotic stimuli. In practice, most cases of hypernatremia result from water loss.
Since water is distributed by fic and FEC in ratio 2:1, a loss of a certain amount of water without solvents will result in a doubling of the contraction of the FIC compartment compared to the FEC compartment. For example, we consider three scenarios: the loss of one liter of water, one liter of NaCl isotone solution and one liter of NaCl hypotone solution. if one litre of water is lost, the FIC volume will decrease by 667 ml, while the FEC volume will decrease by only 333 ml. Due to the fact that Na+ is largely limited to fEC, this compartment will decrease by 1 l if the lost fluid is isoosmic. One litre of NaCl hypotone solution is equivalent to 500 ml of water (one third in FEC, two thirds in FIC) plus 500 ml of saline isotonic solution (also in FEC). So the loss of 1 l of hypotonic saline solution decreases the fEC and FIC volumes by 667 ml and 333 ml respectively.
The degree of osmolarity is generally average, unless the mechanism of thirst is abnormal or access to water is limited. The latter occurs in infants, mentally handicapped patients, patients with impaired mental status, postoperative states and patients intubated in intensive care units. Rarely, the impairment of thirst may be due to primary hypodipsia.
This usually occurs as a result of damage to hypothalamic osmoreceptors that control thirst and tends to associate with abnormal osmotic regulation of AVP secretion. Primary hypodipsia can be given by a variety of pathological changes including granulomatous disease, vascular occlusion and tumors. A subgroup of hypodipsic hyponatremia refers to essential hypernatremia, which does not respond to the forcing of water intake. This appears to be due to a specific defect in the osmoreceptors, which causes the nonosmotic regulation of the release of AVP.
Thus, the hemodynamic effects of water loading lead to AVP suppression and diluted urine excretion. The source of water loss is both renal and extrarenal. Extrarenal water loss may be caused by evaporation from the skin and respiratory tract (insensitive losses) or loss to the gastrointestinal tract. Insensitive losses are increased in the case of fever, exercise, exposure to high temperatures, severe burns and in mechanically ventilated patients. In addition, the Na+ concentration of perspiration decreases with deep perspiration, thus increasing the loss of solvent-free water.
Diarrhea is the most common gastrointestinal cause of hypernatremia. Specifically, osmotic diarrhoea (induced by lactulose, sorbitol or carbohydrate malabsorption) and viral gastroenteritis cause water loss that exceeds na+ and K+ losses. In contrast, secretory diarrhoea (e.g. cholera, carcinoid, VIP-man) has a fecal osmolarity (twice the sum of Na+ and K+ concentrations) similar to plasma and is accompanied by decreased FEC volume and normal plasma na+ concentration or hyponatremia.
Renal water loss is the most common cause of hypernatremia and is caused by medication, osmotic diuresis or insipid diabetes. Anse diuretics interfere with the countercurrent mechanism and produce an isoosmotic diuresis. This causes a decrease in the interstitial medullary tonicity and an impairment of the ability of the kidney to concentrate.
The presence of non-resorbit organic solvents in the tubular lumen of the nephron affects the osmotic reabsorption of water. This leads to excess water loss compared to Na+ and K+, known as osmotic diuresis. the most common cause of osmotic diuresis is hyperglycaemia and glycosuria in poorly controlled diabetes mellitus.
Intravenous administration of mannitol and increased endogenous production of urea (protein-rich diet) may also cause osmotic diuresis. Hypernatremia secondary to neosmotic urinary water loss is commonly given by: 1. central insipid or neurogenic diabetes characterized by impaired aVP secretion, or 2. nephrogen insipid diabetes resulting from resistance of the target organ (kidney) to the action of AVP. The most common cause of central insipid diabetes (DIC) is the destruction of neurohypophysis.
This may occur as a result of trauma, neurosurgery, granulomatous disease, neoplasm, stroke or infection. In many cases, DIC is idiopathic and can occasionally be hereditary. The familial form of this disease is inherited autosomal dominant and has been attributed to the mutation of the propresophyzine gene (precursor of AVP). Insipid nephrogen diabetes (DIN) can also be inherited or acquired. Congenital DIN is a recessive (X-linked) disorder caused by mutations in the V2 receptor gene.
There may also be autosomal mutations of the acondensin gene 2. This encodes the proteins of water channels whose membrane insertion is stimulated by AVP. The causes of sporadic DIN are numerous and include drugs (especially lithium), hypercalcemia, hypopotasemia and situations in which medullary hypertonicity is affected (e.g. papillary necrosis or osmotic diuresis). Pregnant women, in the second or third trimester of pregnancy, por develop DIN as a result of excessive development of vasopressin by the placenta. In the end, quite rarely, a primary gain of Na+ can cause hypernatremia. For example, inadequate administration of NaCl or NaHCO3 hypertone solution or salt replacement in the infant formula may cause this complication.
In terms of clinical manifestations, as a consequence of hypertonicity, water comes out of cells, leading to a decrease in FIC volume. A decrease in brain cell volume is associated with an increased risk of subarachnoid or intracerebral hemorrhage. Therefore, major symptoms of hypernatremia are neurological and include altered mental status, weakness, neuromuscular irritability, neurological focal deficits and occasionally coma or seizures. Patients may also complain of polyuria or thirst. For unknown reasons, polydipsic patients with DIC prefer very cold water.
These signs and symptoms of volume deplation are often present in patients with excessive sweating, diarrhoea or osmotic diuresis. The mortality rate associated with the plasma concentration of Na+ greater than 180 mmol/ l is very high. As with hyponatremia, the severity of clinical manifestations is related to the rapidity and size of the increase in plasma Na+. Chronic hypernatremia is generally less symptomatic as a result of adaptive mechanisms of cell volume preservation. Brain cells initially increase their concentration of Na+ and K+ salts later, followed by the accumulation of organic osmolites such as inositol. This helps bring the cerebral FIC volume back to normal.
It's time for diagnostic introductions. A complete anamnesis and a thorough physical examination often provide the key to the underlying cause of hypernatremia. Relevant symptoms and signs include the absence or presence of thirst, diaphoresis, diarrhoea, polyuria and manifestations of decreased FIC volume. Anamnesis should include a list of recent and current medicines, and a physical examination is incomplete without neurological and mental status evaluation. Measuring urinary volume and osmolarity are essential for assessing hyperosmolarity.
The appropriate renal response to hypernatremia is the excretion of a minimum volume (500 ml/ day) of maximum concentrated urine (urinary osmolarity greater than 800 mosm/ kg). These findings suggest renal or extrarenal water loss or administration of hypertone saline solutions. The presence of a primary excess of Na+ can be confirmed by the expansion of the FEC volume and natrium (urinary concentration of Na+ greater than 100 mmoli/ l). Many causes of hypernatremia are associated with polyuria and submaximal urinary osmolarity.
The product between urinary volume and osmolarity, i.e. the rate of excretion of solvents is useful in determining the causes of polyuria. To maintain a balance, the total excretion of solvents must be equal to the production of solvents. As described above, individuals on a normal diet generate about 600 mosm per day. So, the daily excretion of solvents greater than 750 mosm defines an osmotic diuresis. This can be confirmed by measurements of glucose and urinary urea.
In general, both DIC and DIN have polyuria with hypotonic urine (urinary osmolarity is less than 250 mosm/ kg). The degree of hypernatremia is normally average, unless thirst disorders are associated. Anamnesis and objective examination, as well as relevant laboratory data, can often exclude causes of acquired DIN. DIC and DIN are generally distinguished by the administration of Avp analogue desmopressin after careful water restriction. Urinary osmolarity should increase by at least 50 percent in DIC and will not change in DIN. Unfortunately, diagnosis is often difficult due to partial defects of secretion and action of AVP.
Therapeutic purposes are to stop continuous water loss by treating the underlying causes and correcting water deficiency. The FIC volume should be restored in hypovolemic patients. In hypernatremy due to water loss, the total amount of water of the body is about 40-50% of the dry weight in men and women respectively. As with hyponatremia, rapid correction of hypernatremia is potentially dangerous.
In this case, a rapid decrease in osmolarity may cause a rapid entry of water into cells that have exhibited a continuous phenomenon of osmotic adaptation. This would cause bloating of brain cells and increase the risk of seizures or permanent neurological impairment. So the water scarcity needs to be slowly corrected in 48-72 hours. When calculating the water replacement rate, continuous water losses should be entered into the equation and the plasma concentration of Na+ should be reduced by 0,5 mmol/ l/ hour, but not more than 12 mmol/ l within the first 24 hours.
The safest way to manage water is per bone or through a nasogastric probe (or any other feeding probe). Alternative 5% dextrose solution in water or saline hypotone solution may be administered intravenously. The most appropriate treatment of DIC is the administration of intranasal desmopressin. Other alternatives used to reduce urinary eliminations include a hyposodized diet in combination with low doses of thiazid diuretics. In some patients with partial ICD, medicines that stimulate AVP secretion or increase its action in the kidney are also useful. These drugs include chlorpromazine, clofibrate, carbamazepine and nonsteroidal anti-inflammatory drugs (NSAIDs).
The concentration defect in DIN can be reversible by treating the underlying conditions or by removing the drugs that caused the defect. Symptomatic polyuria in DIN can be treated with a hyposodized diet and thiazid diuretics, as described above. These measures result in an average volemic doutthat leads to an increase in proximal reabsorption of salt and water and a decrease in the transport of AVP to its place of action, which is the collector duct. By affecting the synthesis of renal prostaglandins, NSAID potentiates the action of AVP and thus increases urinary osmolarity and decreases urinary volume. Amidride may be useful in some patients with DIN who require lithium administration. The nephrotoxicity of lithium requires that the drug be absorbed into the cells of the collector duct via the amyloride-sensitive Na+ channel.
No more posting. We'll move on to the potassium-related introductions.
Have a good day!
Dorin, Merticaru