Disturbances of Plasma Sodium PDF

# Disturbances of Plasma Sodium ## Dr Damian Griffin Consultant Chemical Pathologist ## Basis for investigating disturbances of plasma sodium - Plasma sodium is primarily a surrogate marker of plasma osmolality. - Are the key regulatory systems working as expected? - Osmoregulation - Ef...

# Disturbances of Plasma Sodium ## Dr Damian Griffin Consultant Chemical Pathologist ## Basis for investigating disturbances of plasma sodium - Plasma sodium is primarily a surrogate marker of plasma osmolality. - Are the key regulatory systems working as expected? - Osmoregulation - Effective circulating volume regulation - The correlation of plasma sodium and osmolality and the regulatory responses to disturbances in plasma sodium usually enable us to elucidate the cause of the disturbance. ## Sodium and Osmolality - Our bodies primarily regulate osmolality, not sodium. - It would therefore make sense for us to monitor plasma osmolality rather than plasma sodium. - However, we don’t routinely measure osmolality, as analytical methods for osmolality are not easily automated. - Sodium is the major extracellular contributor to osmolality, and under most circumstances, it correlates with osmolality. - Sodium is relatively easy to measure, so we use it as a surrogate marker for plasma osmolality. - In the assessment of hyponatraemia, it is important to be on the lookout for situations in which the normal correlation between sodium and osmolality is disturbed. ## Osmoregulation - This regulatory system is governed by osmoreceptors in the hypothalamus that respond to changes in plasma osmolality. - The responses to hyperosmolality are: - Thirst which regulates free water intake. - Secretion of the antidiuretic hormone, arginine vasopressin, via the posterior pituitary gland, which regulates water excretion by the kidneys. - It is important to note that even though osmoregulation is a response to changes in plasma osmolality, these changes are almost entirely mediated by changes in water balance, not salt balance. ## Diagram of Osmoregulation A diagram of Osmoregulation is included. ## Effective Circulating Volume Regulatory System - Effective circulating volume (ECV) is not a quantitatively measurable entity but refers to the rate of perfusion of the capillary circulation. - ECV is maintained by varying vascular resistance, cardiac output, as well as renal sodium, and water excretion. - The body senses changes in ECV through volume receptors (aka baroreceptors, stretch receptors) in the cardiopulmonary circulation, the carotid sinuses and the aortic arch, and the afferent glomerular arterioles in the kidney. - The response to changes in ECV is primarily through the sympathetic nervous system, angiotensin II generation, regulation of renal Na+ excretion. ## Diagram of ECV Regulation A diagram of ECV Regulation is included. ## Hypernatraemia - Hypernatraemia represents both extracellular and intracellular hyperosmolality. - The increase in plasma osmolality induced by the rise in plasma Na+ creates an osmotic gradient that results in water movement out of the cells and into the extracellular fluid. - Hypernatraemia is almost exclusively due to an impairment of the osmoregulatory system. - However, understanding the effective circulating volume regulatory system helps us interpret what is happening. ## Case 1 - 60-year-old woman, living alone, found unconscious. She had a stroke one or two days earlier. - On admission: - Pulse rate 80/min, blood pressure 140/80, considered to be dehydrated. A table of plasma and urine values is included. ## Diagram of Osmoregulation in Case 1 A diagram of Osmoregulation, with relevant values highlighted in red, is included. <start_of_image> - Thirst and drink value is highlighted in yellow. ## Diagram of ECV Regulation in Case 1 A diagram of ECV regulation, with relevant values highlighted in red, is included. ## Case 2 - 56-year-old man who sustained a fracture of the base of the skull following a motor vehicle accident. - During his first day in the hospital, a negative fluid balance of 5-6 liters was recorded. A table of plasma and urine values is included. ## Diagram of Osmoregulation in Case 2 A diagram of Osmoregulation, with relevant values highlighted in red, is included. - Thirst and drink value is highlighted in yellow. ## Diagram of ECV Regulation in Case 2 A diagram of ECV regulation, with relevant values highlighted in red, is included. ## Hyponatraemia - Hyponatraemia is a more challenging diagnostic conundrum than hypernatraemia for a number of reasons. - It doesn’t always reflect hypo-osmolality. - Hypo-osmolality can reflect a problem in the regulation of osmolality, effective circulating volume, or both! ## Case 3 - A 42-year-old man was admitted with acute pancreatitis. - His blood sample resembled a strawberry milkshake. - Found to be profoundly hyponatraemic with a normal plasma osmolality! A table of plasma and lipids values is included ## Hyponatraemia with a normal plasma osmolality - This is termed ‘pseudohyponatraemia’ and is due to a known analytical problem. - As an offshoot, however, it can alert the doctor to the possibility of other defects unrelated to body water and blood pressure regulation ## Pseudohyponatraemia (an analytical error!) A diagram of a normal plasma sample, with 94% H2O solution and 6% protein and lipoprotein is included. - Plasma is a mixture of solids (protein and lipid) and a water solution. - Electrolytes (Na+, K+, Cl–,  HCO3–) are essentially confined to the water phase and are excluded from the solid phase. - However, in standard analytical methods for Na+, the concentration in a fixed volume of total plasma (not just the water phase) is measured. - Thus, when we measure plasma [Na⁺] as 140 mmol/L, the actual Na in the water phase is more like 140 x 100/94 = 149 mmol/L. - This error has been recognised for years. - Even though it is the electrolyte concentration in plasma water that is physiological, it is tacitly assumed that the volume fraction of water is sufficiently constant that this difference could be ignored. ## Pseudohyponatraemia - High Content of Solids A diagram of 'High content of solids' plasma sample, with 88% H2O solution and 12% protein and lipoprotein is included. - Problematic when pathophysiological conditions are present that alter the plasma water volume, such as hypertriglyceridaemia or hyperproteinemia (e.g. multiple myeloma). - In this setting, the error becomes more marked. - If the true Na⁺ is 149 mmol/L plasma water as before, standard methods would give a result of 149 x 88/100 or 131 mmol/L. - The term pseudohyponatraemia is used to describe this error in calculation. ## Pseudohyponatraemia - How to Pick up on this error <start_of_image> - There are two common ways of picking up on this error. - Measure plasma osmolality. - This provides a direct measure of osmoles per kg of water. - A normal osmolality in the presence of hyponatraemia is suggestive of pseudohyponatraemia - Measure the solids - Total protein. - Triglycerides as a marker of raised lipoproteins. ## Case 4 - A 14-year-old diabetic presented in semi-coma. - His glucose was 41 mmol/l. - He was noted to have hyponatraemia with an increased plasma osmolality. A table of plasma and glucose value is included. ## Hyponatraemia with hyperosmolality - This combination informs us that while the patient is hyperosmolar, the osmotically active constituent present in excess is not sodium. - In health, plasma electrolytes, glucose, and urea are the main determinants of plasma osmolality. - In disease, homeostatic mechanisms prioritise on maintaining a normal osmolality, sometimes at the expense of specific electrolytes. - One needs to look for high concentrations of other osmotically active constituents (e.g. glucose, urea, alcohol, ethanol, ethylene glycol). - Sometimes referred to as ‘appropriate hyponatraemia’. ## Diagram of Osmoregulation in Case 4 A diagram of Osmoregulation, with relevant values highlighted in red, is included. - Hyponatraemia is highlighted in the middle. ## Case 5 - A 40-year-old man with a history of schizophrenia presented with mild confusion, nausea and vomiting. - His family reported that he had been drinking excessive amounts of water (up to 20 liters/day). - Hyponatraemia with hypotonicity with a very dilute urine. A table of plasma and urine values is included ## Diagram of Osmoregulation in Case 5 A diagram of Osmoregulation, with values highlighted in red, is included. - Thirst, drink water, and urine osmolality value are highlighted in red. ## Case 6 - A 40-year-old woman presented with vomiting due to bowel obstruction. - She appeared ‘dehydrated’, had a pulse rate of 105/min, and postural hypotension. - Note: Vomit is hypotonic. A table of plasma and urine values is included. ## Diagram of ECV Regulation in Case 6 A diagram of ECV regulation, with relevant values highlighted in red, is included. - Blood pressure is highlighted in red. ## Diagram of Osmoregulation in Case 6 A diagram of Osmoregulation, with values highlighted in red, is included. - ADH secretion is highlighted in red. - Urine osmolality value is highlighted in blue (U.Osm 725?). ## Diagram of Osmoregulation in Case 6 - Alternative A diagram of Osmoregulation, with values highlighted in red, is included. - This diagram shows a different scenario where osmoreceptor stimulation is increased. - Urine osmolality value is highlighted in blue (U.Osm 725). ## Case 7 - 67-year-old woman with bronchiectasis (damaged, permanently enlarged bronchial tree) admitted to hospital with a two-week history of a productive cough with green sputum. - Over the previous week, she had become confused, and disorientated. - Blood pressure was 150/80 mmHg. - Neither clinically volume depleted nor oedematous . - Bilateral widespread coarse crepitations in the lungs. A table of plasma, lipids, and urine values is included. ## Diagram of ECV Regulation in Case 7 A diagram of ECV regulation, with relevant values highlighted in red, is included. - Cortisol and urinary Na+ value are highlighted in blue. - Bladder pressure is highlighted in red. ## Diagram of Osmoregulation in Case 7 A diagram of Osmoregulation, with values highlighted in red, is included. - ADH secretion is highlighted in red. - Urine osmolality value is highlighted in blue (Urine Osmol 560 mosm/kg). ## Causes of Inappropriate ADH Secretion - Ectopic Production - Bronchogenic carcinoma. - Islet cell tumours of the pancreas. - Lymphoma. - Pulmonary disorders - Pneumonia. - Tuberculosis. - Pneumothorax. - Positive pressure ventilation. - Neurological disorders - Encephalitis. - Meningitis. - Head injury. - Acute intermittent porphyria.