[Clinical thinking and decision making in daily practice. An old man with hyponatremia].
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Addison Disease↗
Biomedical subjects
M L Halperin
Publications and source records attributed to M L Halperin.
Severe hypokalaemia in a Chinese male.
A 34-year-old Chinese man developed acute, severe, generalized muscle weakness while mountain climbing. In the Emergency Department that morning, the most striking abnormalities were flaccid paralysis of both upper and lower limbs and a plasma potassium (K+) concentration (P(K)) of 1.7 mmol/l. To explain the basis for this constellation of findings, an imaginary consultation was sought with Professor McCance, the legendary integrative physiologist. Using both a deductive and a quantitative analysis, he illustrated that a simple story of an acute shift of K+ into cells was not sufficient to explain the patient's hypokalaemia. The clue he used to suspect a large total body deficit of K+ was a higher than expected rate of K(+) excretion on the initial spot urine (higher than expected ratio of K+: creatinine in the urine). This interpretation was supported by the fact that the patient needed a large supplement of K(+) to raise his P(K) to just under 3 mmol/l. It was only after more detailed studies based on urine chemistry that an accurate diagnosis and effective treatment could be instituted. The final question was why one of the hallmarks of the diagnosis of hyperaldosteronism (hypertension) was absent, yet hypokalaemia was so severe.
Acute Disease↗
Severe degree of hyperglycaemia: insights from integrative physiology.
We illustrate how the application of principles of integrative physiology at the bedside can reveal novel insights that have been largely overlooked to this day. In this didactic exercise, modern-day physicians seek an imaginary medical consultation with Professor Sir Hans Krebs because of an unusual finding in his area of expertise: a very severe degree of hyperglycaemia. Although Professor Krebs is restricted to data prior to World War II, this does not prevent him from making novel discoveries. First, he illustrates how an occult factor, rapid absorption of glucose from the intestinal tract, was a critical feature in explaining the basis of the severe degree of hyperglycaemia without obvious ketoacidosis in a 16-year-old patient with type 1 diabetes mellitus in poor control. Second, by examining simple principles of renal and gastrointestinal physiology in a quantitative fashion, Professor Krebs speculates as to how cerebral oedema might occur before therapy in a patient with a severe degree of hyperglycaemia. We hope that readers and educators will appreciate the value of applying principles of integrative physiology in a quantitative fashion at the bedside.
Adolescent↗
Hyponatraemia and hyperglycaemia during laproscopic surgery.
The aim of this masterclass is to develop a rational plan of therapy to deal with a severe degree of hyponatraemia (90 mmol/l) and hyperglycaemia (100 mmol/l) that occurred 100 min after the start of laproscopic surgery in a young woman. The lavage fluid used in this procedure was 10% dextrose.H(2)O in water (505 mmol glucose/l). To focus attention on specific issues, three questions are posed to the reader, as they were to a panel of 59 modern-day experts. Two imaginary consultants from the past were asked the same (and additional) questions. Their responses were restricted to knowledge available before the molecular era, to show the power of integrative physiology at the bedside. An analysis of intracellular events was helpful in answering the first question: 'Is an infusion of hypertonic saline required to treat her acute hyponatremia?' Similarly, a quantitative analysis of changes in the composition of the extracellular fluid compartment was helpful in answering the second question: 'Is an infusion of isotonic saline required to treat her hypotension?' A metabolic analysis was used to answer the third question, 'Should insulin be administered?'
Adult↗
Acute hyponatraemia and 'ecstasy': insights from a quantitative and integrative analysis.
A 20-year-old woman attended a 'rave party' where she took the drug 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). She had used this drug previously without serious adverse effects. On this occasion, while both she and her friends drank a large quantity of water, only she became seriously ill. The initial manifestation was an altered sensorium; several hours later she had a grand mal seizure. In the Emergency Department, the most striking features were the severe degree of hyponatraemia (112 mmol/l) and cerebral oedema. To explain the basis for this life-threatening clinical presentation, an imaginary consultation was sought with Professor McCance. Using both a deductive and a quantitative analysis that involved several medical subspecialties, he illustrated that a simple story of water ingestion and vasopressin release was not sufficient to explain her hyponatraemia. It was only after events in her gastrointestinal tract were analysed that a plausible hypothesis could be constructed.
Adult↗
Lesson of the week: Acute hyponatraemia in children admitted to hospital: retrospective analysis of factors contributing to its development and resolution.
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Child↗
Tonicity balance, and not electrolyte-free water calculations, more accurately guides therapy for acute changes in natremia.
The usual way to decide why hyponatremia or hypernatremia has developed and to plan goals for its therapy is to analyze events in electrolyte-free water (EFW) terms. We shall demonstrate that an EFW balance does not supply this information. Rather, one must calculate mass balances for water and sodium plus potassium separately (a tonicity balance) to understand the basis for the change in natremia and the proper goals for its therapy. These points are illustrated with a clinical example.
Adolescent↗
The approach to a patient with acute polyuria and hypernatremia: a need for the physiology of McCance at the bedside.
We present a case to illustrate the importance of emphasizing elementary physiology to deduce the basis for the acute onset of polyuria and hypernatremia. An imaginary consultation with Professor McCance is utilized to illustrate how a clinician-physiologist would have explained why these abnormalities developed and how they should have been treated. His approach began with a consideration of the most impressive abnormality. His analysis relied heavily on deductions and the anticipation of the expected responses to a stimulus in quantitative terms. The goals of therapy became evident after he performed mass balance calculations. Professor McCance would not understand why modern clinicians abandoned this form of analysis.
Adult↗
A patient with partial central diabetes insipidus: clarifying pathophysiology and designing treatment.
Studies were undertaken in a 32-year-old man who developed polyuria (4 L/d) a few days after a basal skull fracture; the condition persisted 1 year after the accident. The other major features were thirst, a plasma sodium of 143 mmol/L, 24-hour urine osmolality of 221 mOsm/kg H(2)O, and levels of vasopressin in plasma that were less than 0.5 pg/mL on 20 separate occasions. The 24-hour urine volume implied that the diagnosis was partial rather than complete central diabetes insipidus; however, several random urine samples had a much higher osmolality. An infusion of hypertonic saline led to the release of vasopressin and the excretion of concentrated urine. We propose that the basis for the lesion may be the transection of some, but not all, of the fibers connecting the osmostat and vasopressin release center. This partial transection could permit vasopressin to be secreted in response to a larger rise in plasma sodium concentration. This pathophysiologic analysis provided the basis for therapy to minimize the degree of polyuria.
Adult↗
Citric acid ingestion: a life-threatening cause of metabolic acidosis.
We present a case that illustrates the acute (<6 hours) metabolic and hemodynamic effects of the ingestion of a massive oral citric acid load. The principal findings included metabolic acidosis accompanied by an increase in the plasma anion gap that was not caused by L -lactic acidosis, hyperkalemia, and the abrupt onset of hypotension. A unique feature was a dramatic clinical improvement when ionized calcium was infused. The case illustrates the importance of considering the properties of the conjugate base (anion) of the added acid because, in this instance, the citrate anion had a unique and life-threatening consequence (lower ionized calcium level) that was rapidly reversible.
Acid-Base Equilibrium↗
Possible mechanisms to explain the absence of hyperkalaemia in Addison's disease.
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Addison Disease↗
Hypokalaemia and paralysis.
It is not uncommon for patients to present to the emergency room with severe weakness and a markedly low plasma potassium concentration. We attempted to identify useful clues to the diagnosis of hypokalaemic periodic paralysis (HPP), because its acute treatment aims are unique. We retrospectively reviewed charts over a 10-year period: HPP was the initial diagnosis in 97 patients. Mean patient age was 29+/-1.1 and the male:female ratio was 77:20. When the final diagnosis was HPP (n=73), the acid-base state was normal, the urine K(+) concentration was low, and the transtubular K(+) concentration gradient (TTKG) was <3. In patients with thyrotoxic periodic paralysis (TPP) (n=39), hypokalaemia was very commonly accompanied by hypophosphataemia (1.9+/-0.1 mg/dl). A clinical diagnosis of sporadic periodic paralysis (SPP) was made if hyperthyroidism and a family history of HPP were both absent (n=29). One subgroup of patients with HPP had a severe degree of hypernatraemia (167+/-5.0 mmol/l, n=3). There were only two patients with familial periodic paralysis (FPP). In 24 patients, the initial diagnosis was HPP, but subsequent studies failed to confirm this diagnosis. Each of these patients had an acid-base disorder, a high rate of renal K(+) excretion in the presence of hypokalaemia, and a TTKG of close to 7. With respect to therapy, much less K(+) was given to patients with HPP, yet 1:3 subsequently had a plasma K(+) concentration that eventually exceeded 5.0 mmol/l. Using plasma acid-base status, phosphate and K(+) excretion parameters allows a presumptive diagnosis of HPP with more confidence in the emergency room.
Acid-Base Equilibrium↗
A method to estimate urinary electrolyte excretion in patients at risk for developing cerebral salt wasting.
OBJECT: Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting. METHODS: A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent. CONCLUSIONS: Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.
Adolescent↗
[A new concept to explain dysnatremia: the tonicity balance of entries and exits].
Plasma sodium concentration, or natremia, results from three main factors: exchangeable sodium (Na+), exchangeable potassium (K+) and total body water (H2O). Its alterations often imply a change in cell volume. Understanding dysnatremias is essential for the treatment and prevention of hydromineral disorders. Extra-cellular fluid tonomoles consist almost exclusively of Na+ salts. Their dilution is the tonicity. K+ is an essential tonomole for intra-cellular fluid tonicity. The balance between intra and extracellular tonicities depends on water movements and is responsible for changes in intra- and extracellular fluid volumes. Cell volume is therefore depending on the tonicity balance. A change in body tonicity (which is not osmolality) can be correctly and rapidly appreciated by measuring the (Na+ + K+) and H2O balances. Clinical cases emphasize the misleadings resulting from the free-water clearance calculation or the only measurements of urinary losses. They also demonstrate that tonicity balance provides indications for therapy whereas analyses based upon electrolyte-free water do not. Intakes should be quantified with the same care than losses. The units used must be coherent to allow a quick and easy understanding at the bedside. Tonicity balance should be taught and Na+ + K+ and H2O balances should be routinely utilized by practitioners, dieticians and nurses in the concerned pediatrics, in particular intensive care, internal medicine, nephrology, pediatry and anesthesiology.
Adolescent↗
Integrative physiology of basal water permeability in the distal nephron: implications for the syndrome of inappropriate secretion of antidiuretic hormone.
Patients who drink more electrolyte-free water than they can excrete may develop hyponatremia. A subgroup of hyponatremic patients has a reduced excretion of electrolyte-free water and a low rate of excretion of solutes even though vasopressin is not detected in their plasma. Basal water permeability in the distal nephron, by permitting a limited volume of electrolyte-free water to be reabsorbed, offers a way to help explain these findings. Basal water permeability will also be considered from the perspective of integrative physiology in evolutionary and developmental biology settings. Its possible clinical importance will be explored in patients with chronic hyponatremia who have a low distal volume delivery. These patients may develop osmotic demyelination if a large solute load leads to a very rapid excretion of electrolyte-free water.
Capillary Permeability↗
Treatment of acute hyponatremia: ensuring the excretion of a predictable amount of electrolyte-free water.
BACKGROUND: Hypertonic saline is the recommended therapy to shrink swollen brain cells in patients with acute hyponatremia accompanied by seizures. OBJECTIVES: In the absence of hypertonic saline, hypertonic mannitol will shrink the cell volume. Because mannitol is excreted rapidly, our aim was to ensure that it would be excreted with electrolyte-free water (EFW) and to evaluate the renal mechanisms responsible for EFW excretion. DESIGN: A randomized, prospective, placebo-controlled study in rats was carried out in a research laboratory. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: The control group of rats (n = 6) was administered hypotonic saline, a loop diuretic, vasopressin, and glucose by the intraperitoneal route; in the experimental group (n = 6), glucose was replaced with mannitol. Plasma electrolytes were measured at 0 and 210 mins, and balances for water, sodium, and potassium were obtained from 0 to 90 mins and from 90 to 210 mins. MEASUREMENTS AND MAIN RESULTS: Virtually 100% of the administered mannitol was excreted within 210 mins, and half was excreted in the first 90 mins. The urine contained EFW only in the mannitol group because of a larger volume in the first 90 mins (EFW, 3.7 mL) and to a lower excretion of NaCl in the next 120 mins (EFW, 3.5 mL). CONCLUSIONS: The combined use of mannitol and a loop diuretic caused the excretion of a predictable volume of EFW because the urine was iso-osmotic to plasma and contained all the administered mannitol. The calculated decrease in intracellular fluid volume was equivalent when mannitol was retained or excreted.
Acute Disease↗
Integrative physiology of splanchnic glutamine and ammonium metabolism.
The substrates for hepatic ureagenesis are equimolar amounts of ammonium and aspartate. The study design mimics conditions in which the liver receives more NH(+)(4) than aspartate precursors (very low-protein diet). Fasted dogs, fitted acutely with transhepatic catheters, were infused with a tracer amount of (15)NH(4)Cl. From arteriovenous differences, the major NH(+)(4) precursor for hepatic ureagenesis was via deamidation of glutamine in the portal drainage system (rather than in the liver), because there was a 1:1 stoichiometry between glutamine disappearance and NH(+)(4) appearance, and the amide (but not the amine) nitrogen of glutamine supplied the (15)N added to the portal venous NH(+)(4) pool. The liver extracted all this NH(+)(4) from glutamine deamidation plus an additional amount in a single pass, suggesting that there was an activator of hepatic ureagenesis. The other major source of nitrogen extracted by the liver was [(14)N]alanine. Because alanine was not produced in the portal venous system, we speculate that it was derived ultimately from proteins in peripheral tissues.
Acid-Base Equilibrium↗