Clinical application of Advanced Instrument osmometer
Description
Tilmicosin is a broad-spectrum semi-synthetic bactericidal macrolide antibiotic synthesized from Tylosin. It has an antibacterial spectrum that is predominantly effective against Mycoplasma, Pasteurella and Haemophilus spp. and various Gram-positive organisms such as Corynebacterium spp. It is believed to affect bacterial protein synthesis through binding to 50S ribosomal subunits. Cross-resistance between tilmicosin and other macrolide antibiotics has been observed. Following oral administration, tilmicosin is excreted mainly via the bile into the faeces, with a small proportion being excreted via the urine.
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Solute characteristics
When multiple solutes are added to a solvent, the liquid undergoes a variety of changes from the original liquid. The presence of one or more solutes in the solvent will alter the interaction between the molecules in the solvent and reduce the space of motion between them. Therefore, the ability to convert from liquid to solid (or liquid to gas) will also change. These changes, we collectively refer to the colligative properties of the solute, which are determined by the total number of particles of the solute present in the solution. For a simple chemical such as urea, the effect is related to the total moles of urea in the solution: for a chemical compound that can be decomposed, such as sodium chloride, both sodium and chlorine will The dependency feature works. Therefore, in theory, the effect we get in sodium chloride solution is twice as large as that obtained in urea (but if the decomposition is not complete, the effect should be twice as large), and these The actual quality of the particles is irrelevant to this. The effect produced by a small molecule and a large molecule can be the same. Table 1 lists the four basic changes in the presence of solutes in solution. Any change in one of these properties can be used to measure the total molar concentration of the solute dissolved in any solution. For example, when the freezing point depression property is applied, if the freezing point is lowered by 0.93 ° C, it is found that 0.5 mol of total solute is present in the solution.
Table 1: Dependent characteristics
Osmotic pressure
Osmotic pressure refers to the pressure of a semipermeable membrane that resists the passage of a solvent through a solvent that allows only the passage of solvent without allowing the solute to pass. When such a semipermeable membrane is present, its natural tendency is for the solvent to pass through the semipermeable membrane to achieve equilibrium of the solute molecules on either side of the membrane. In order to prevent the movement of this solvent, a pressure is required (see Figure 1). Conversely, we can assume that it is this pressure that drives the solvent through the semipermeable membrane. One mole of solute is present in one liter of solvent to produce an osmole. The measurement of the osmotic concentration is usually expressed in terms of volume osmolarity or osmolality. The volume osmolality refers to the number of moles of solute per liter of solution. Since the volume of the solution varies with the amount of added solute, temperature and pressure, the volumetric osmolality is difficult to measure. The osmolality refers to the number of millimoles of solute particles present per kg of solvent. Since the amount of solvent is constant under constant temperature and pressure, the weight osmolality is easily evaluated and thus becomes a commonly used term. Technically, the weight osmolality should be measured by penetration, but the measurement of osmotic pressure is not so easy. Since the osmotic pressure is proportional to the total molar concentration of the solute, there is a positive correlation between osmotic pressure and freezing point depression or vapor pressure depression. Therefore, the measurement of other dependency characteristics is usually expressed in terms of weight osmolality, although it is technically not precise enough.
Figure 1. Osmotic pressure is due to the difference in particle concentration on both sides of a semi-permeable membrane, which allows the passage of water molecules (rather than particulate matter), the size of which is irrelevant. In this case, the movement of water molecules from left to right stops when the particles on both sides reach equilibrium.
The relationship between the number of characteristics and the specific gravity
The specific gravity and the refractive index are indicators of the solid content of a solution compared to water. The specific gravity refers to the comparison of the weight of a solution with the weight of water, while the refractive index is a description of a solution compared to water. The ability to refract light. If the molecular weight and refractive index of all solutes are similar, then these measures are directly proportional to their osmotic pressure or other dependence properties. In normal urine, the main solute is the relatively constant concentration of metabolites urea and creatinine, and its specific gravity is closely related to the refractive index and the osmolality of the weight. If there is a macromolecular substance, the relationship between the three will be divergent. An increase in the concentration of glucose or protein in the urine increases the proportion of urine in a proportional manner. The specific gravity and refractive index of blood are closely related to its protein concentration. In many laboratories, the refractive index is usually used to measure the concentration of total protein to deduct the relationship between protein and electrolyte. These measured parameters of serum are insensitive to changes in the total molar concentration of solute, and only with the weight osmolality. Show a little related.
Relationship between ionic strength and dependence characteristics
A newer technique for estimating total solute concentration is the urine test strip method, which reacts to changes in urine ionic strength. The main substances in the ionization of urine are electrolytes (sodium and potassium), while some metabolites such as urea and creatinine and some abnormal substances such as glucose and protein are uncharged. Therefore, these substances cannot be measured by this method. In normal urine, the relationship between the weight osmolality and specific gravity and ionic strength is extremely close. However, under pathological conditions, since the ionic strength is not directly proportional to the change in total solute concentration, an estimate of the osmolality provided by these experiments is usually inaccurate. In addition, the test strip changes the pH (with The proportion of the report is inversely proportional to the change in protein concentration (proportional to the reported proportion). Finally, the number of inpatients is unnecessarily increased due to misleading ion intensity measurements.
Direct measurement of weight osmolality
Since the osmolality estimated from specific gravity, refractive index, and ionic strength is generally inaccurate, direct measurement should be used when it is necessary to know the exact total solute concentration. Because the boiling point method and the osmotic pressure method are time consuming and technically relatively difficult, it is common to directly measure the weight osmolality using the freezing point reduction method or the steaming point reduction method, both of which are in clinical laboratories. It can be seen that the two methods provide reliable measurement parameters of the osmolality of serum and urine. However, if a volatile substance (such as alcohol or other volatile substances) is present in the sample, the vapor pressure gauge cannot show a change in the weight osmolality. As can be seen from the table below, the osmotic pressure gap is extremely useful for screening patients who are suspected of having an excessive alcohol intake, but if a vapor meter is used to measure the osmolality, there is no indication of osmotic pressure. If the laboratory needs to do an alcohol screening test, the Freezing Point Reducer provides the only direct measurement of the weight osmolality.
Table 2. Comparison of solute concentration measurement methods
Exchange between body fluids
The osmotic pressure is formed by the difference in the amount of protein and electrolyte on both sides of the cell membrane and is the most important factor regulating the movement of water molecules between cells and blood vessels.
The hydrostatic pressure pushes the fluid outward from the capillary arterial end, resulting in loss of fluid in the blood vessel, an increase in protein concentration, and an increase in hydrostatic pressure between tissues. Therefore, at the venous end of the capillary, the hydrostatic pressure of the interstitial space is slightly higher than the venous pressure. An osmotic effect produced by the protein is called colloid oncotic pressure to draw water molecules from the intercellular space back into the blood vessel. As shown in Table 2, the combination of low hydrostatic pressure and high capillary colloid osmotic pressure is important to control the balance of intravascular and interstitial fluids.
Physiological response of human body to changes in plasma osmolality
Although the body can get water balance from the intake of water, the body loses about 2-3 liters of water every day, most of which is lost from the urine. The average human body loses 1 liter of water per day from sweat, feces, and breathing (not sensitive to water loss), so the body must compensate for these losses through water intake, which would otherwise lead to dehydration. The human body has a very complex conditioning system, and in most cases, the weight osmolality or plasma volume balances water loss and intake.
Osmotic regulator
The hypothalamus (a regulatory center at the base of the brain) responds to an increase in the osmolality of less than 1% (the response is usually elevated serum sodium) and activates the following two protective responses.
Dry thirst sensor: responds to an increase in osmotic pressure, thereby increasing the body's water intake, reducing the weight permeation molar concentration, and returning the body to a normal state. On a relatively minor aspect, the thirst sensor can also respond to a reduction in the vascular volume. The thirst reaction leads to water intake being one of the most important factors in maintaining the body's normal water-electrolyte balance. For patients with neurological disorders, the elderly, newborns, and those who do not have the ability to drink water (including infants), this signal usually does not respond, so they are prone to dehydration.
Anti-urea (ADH) hypothalamus also produces a hormone called anti-urea that responds to elevated osmolality, causing increased permeability of the kidney collecting tube and increasing the osmolality of urine. Trying to return plasma permeability to normal.
Although ADH can reduce the loss of water from urine, it can only reduce the total water in the body by about 1-1.5 liters per day.
Table 4: Weight osmolality and volume adjustment
Although the body's water is regulated by the permeability every day, if the body needs to retain normal plasma volume, the body can avoid the signal from the osmotic sensor. The volume regulator responds to changes in 1% plasma permeability, but it is less sensitive than the permeability regulator, yet they are very potent.
Antidiuretic (ADH): Although changes in weight osmolality usually control the production of ADH, when the blood volume drops by about 5-10%, the hypothalamus can still increase the secretion of ADH, when the blood volume drops by more than 10-15%. When the plasma osmolality decreases, the hypothalamus can produce a large amount of ADH. Clearly, maintaining a moderate volume of blood vessels is more important than maintaining a normal plasma weight osmolality.
Renin/Angiotensin/Aldosterone: Renin is secreted when renal blood flow is reduced or the amount of renal distal tubule sodium is reduced. Renin catalyzes the production of angiotensin I, which indirectly causes the production of angiotensin II (AGII). The latter is an effective blood vessel tone substance that increases blood flow to the kidneys. In addition, AGII is the most effective aldosterone stimulator, and aldosterone can enhance the retention of sodium by the exchange of sodium ions with potassium ions and hydrogen ions in the distal convoluted tubules of the kidney. Through this binding mechanism, renin increases blood flow by increasing total sodium in the body and arterial resistance.
Anterior atrial urea (AND): An increase in anterior chamber myocardial contraction stimulates the production of AND. AND can cause renal blood to be diverted to the nephron of the renal cortex, minimizing sodium reabsorption. In addition, AND inhibits the adrenal gland to secrete adrenaline. These two effects reduce plasma volume and total body sodium.
Kidney regulation of water and solute concentrations
Since many of the hormones regulate the target organs primarily in the kidneys, normal kidney function is the basic guarantee for maintaining normal water and electrolyte balance. Since the first step in kidney secretion is glomerular filtration, and it is a non-selective filtration, substances that are harmful to the body are excreted into the urine. A normal person excretes approximately 180 liters of water and 25,000 mmol of sodium into the urine per day. The function of the renal tubules is to regulate the excretion of water and electrolytes to maintain normal blood volume. For a normal kidney, most of the reabsorption of sodium, chlorine and water is done by the osmotic gradient, which requires a disease-free kidney to change the height found in the central part of the kidney. The osmolality of the weight, the regulation of the urine electrolyte and water is ultimately achieved by the synergistic action of aldosterone and anti-urea. When aldosterone is deficient, approximately 3-5% of the sodium filtered into the urine will be lost, while ADH deficiency can cause 10% of the water to be lost. Figure 3 shows this phenomenon.
"normal" value of urine solute concentration
Whenever the laboratory is required to provide "normal" values ​​for urine solute concentration and osmolality, renal function is best understood by the word "appropriate". For example, for a dehydrated patient, if the urine is found to be extremely dilute and the urine has a osmolality of 50, it should be considered as an inappropriate, although this can be done in a normal person. See you in the middle. Similarly, if the patient's urine sodium concentration is 100 mmol/L, it should also be considered inappropriate. In our own laboratory, we do not provide a normal reference value for the osmolality and electrolyte concentration of urine.
Concentration and dilution
The kidneys can excrete urine of different concentrations through the function of the renal tubules. In the case of dehydration, ADH stimulates the maximum storage of water so that the urine has a osmolality of 1200 mosm/kg. When the water intake is excessive, the maximum dilution can produce a osmolality as small as 50 mosm/kg. These values ​​can vary in children and with age; those older than 65 years of age cannot achieve a maximum concentration of 700 mosm/kg, while the maximum dilution is usually not less than 100-150 mosm/kg.
Urine electrolyte
In normal people, the excretion of urine electrolytes is related to salt intake. Total urinary sodium excretion in a normal individual is a good indicator of sodium intake, which has been used as a tool to monitor sodium intake in hypertensive patients. However, when the plasma volume changes, the hormone stimulates the kidneys to alter the excretion of sodium to achieve a rebalancing state. In a patient with a decreased blood volume, it is typically shown that when the urinary sodium concentration is less than 10 mmol/L, aldosterone acts on the renal tubules, reducing the loss of urinary sodium that has been filtered by the glomerulus to less than 0.5%. When the blood volume is too large, the excretion of urinary sodium will increase significantly, up to 5% or more of the filtered sodium urinary sodium, and the stool sodium concentration is greater than 2 times or more of the blood sodium concentration.
III. Testing of solute status
Penetration gap
Osmotic Gap is a theoretical concept (similar to anion gap) that was originally used as an indicator of the accuracy of an instrument for checking the osmolality. The osmotic gap is the difference between the actual osmolality and the measured osmolality, which is calculated from the molar concentration of all major solutes present in the serum. The two commonly used formulas for calculating the osmolality of the norm are as follows:
1.86 x Na+ + 18 + 2.8 + 3.8
18 2.8 3.8
The osmotic gap suggests the presence of a small molar amount of small molecule compound. For practical purposes, it is believed that the substances causing the osmotic gap are only alcohol (methanol, isopropanol, ethylene and propylene glycol), acetone, acetylsalicylic acid and paraldehyde. Ethanol can also be produced if it cannot be measured in the laboratory and is not considered in the above two formulas. Only nonionic substances can affect the osmotic gap, for example, acid decomposes and binds to one base, directly replacing HCO3; since we have multiplied the anion by NA+ and multiplied by 2, resulting in an increase in "undetermined" anions Therefore, no infiltration gap is created. The presence or absence of osmotic gaps affects the methods used to measure the osmolality of the past. Since most of the substances that cause the osmotic gap are volatile (except aspirin), the osmometer used to measure the evaporation point reduction does not detect the presence of these substances. Fortunately, the labs in most hospitals in our country use the freezing point reduction method, which accurately measures the presence of these substances.
Free water removal rate
Free water clearance is a theoretical concept that refers to increasing the ability of the kidney to excrete to drain more or less water, rather than the amount of permeation that the kidney itself needs to treat by glomerular filtration. . It reflects the ability of the renal tubule to modulate and dilute due to changes in the patient's blood volume. The free water removal rate is the difference between the total water removal rate (urine volume) and the required water removal rate (permeation clearance rate), which is defined by the following formula:
C water = C urine - C penetration = V - U penetration x V = V x (1 - U penetration)
--------- --------
P infiltration P penetration
If the kidney does not have a net weight absorption of water, but excretes urine with the same molar concentration of blood permeation, then the free water removal rate is zero. In the case of a decrease in blood volume, the normal response is to increase the secretion of anti-urea, resulting in the excretion of a concentrated urine having a lower moisture content than blood, and thus the free water clearance rate is negative. Similarly, excessive intake of water inhibits the secretion of ADH, leading to excretion of diluted urine, where free water clearance is positive. If all conditioning systems and kidneys work properly, the urine solute concentration will be appropriate for the condition of the body fluid.
Clinical application of serum weight osmolality
Screening for ingestion toxicity (osmotic gap = molar concentration of solute)
·Alcohol (methanol, isopropanol)
·Glycerin (ethylene, propylene glycol)
Monitoring of the concentration of osmotically active substances · Evaluation of mannitol · hyponatremia · Elimination of hypoallergenic blood sodium · Presence of other osmotic substances (glycine, glucose)
Screening for ingestion poisoning
Perhaps the most useful point of weight osmolality is for the assessment of patients suspected of taking toxic substances. If the toxin is present in millimolar concentrations, the weight osmolality (detection of all uncharged toxins by freezing point or detection of non-volatile toxins with a vapor pressure gauge) will increase. The calculated permeation gap (see Equations 1 and 2) as the difference between the measured and calculated weight osmolality provides an estimate of the molar concentration of any additional material. Among these toxins, alcohols such as methanol, ethanol, propanol, ethylene, propylene glycol glycerin, salicylic acid (aspirin and related substances) and triacetyl acetyl can be obtained from the osmolality by weight. If these substances can be quantified by a quantitative method, the mg/dL concentration can be calculated by multiplying the permeation gap by a factor (molecular weight/10).
Monitoring of osmotic active substance concentration
In the treatment of patients with cerebral edema, osmotically active substances such as mannitol are usually used to aspirate the water in the cells to reduce edema. Since there is no easy way to understand the concentration of mannitol, it has been suggested to use osmotic gaps to estimate the concentration of mannitol, the purpose of which is to maintain the osmotic gap at 10 mosm/kg. Here it is shown that it is necessary to choose a method with good precision to measure the weight osmolality and electrolyte. If the penetration gap reaches 50 mosm/kg, it is possible to damage the kidneys.
Assessment of hyponatremia
Because sodium (along with its anion) is the primary substance involved in the formation of serum osmolality, most patients with hyponatremia also have a reduced osmolality. Sometimes hyponatremia is not associated with hyponatremia, which is commonly seen in patients with elevated serum glucose because glucose allows water to leave the cell fluid to dilute serum electrolytes. The osmolality of diabetics often increases, but sometimes it is within the normal range. A rough estimate is that for every 100 mg/dL of glucose, the sodium concentration is reduced by 1.6-2.0 mmol/L. This increases the osmolality by 5.6 mosm/kg for glucose and 3.2-4.0 mosm/kg for sodium, so the allowable range of variation is 100 mmol per liter. The sodium concentration of L will increase by 1.5-2.5 mosm/kg. An increase above this range suggests that excessive water loss is due to the presence of high sodium or other osmotically active substances, and below this range suggests excessive sodium loss.
Although the serum osmolality is normal, other osmotically active substances such as mannitol (mentioned above) and glycine may cause the same phenomenon. Glycine is a component of a perfusate used by urologists for clear vision when undergoing prostatectomy (TURP) through the urethra. Because it is perfused under pressure, if the doctor cuts into the sinus (sinus sinus) In the prostate is extremely rich, glycine may be inhaled into the blood circulation. In about 5-10% of cases, a large amount of perfusate is inhaled to dilute serum sodium. Although this liquid is harmless to the patient, the increase in liquid and glycine can cause other problems. This amount of liquid inhalation and the rate of metabolism of glycine can be estimated by the osmotic gap.
Finally, since most methods measure sodium in plasma rather than sodium in water (usually regulated by osmotic sensors), serum sodium levels tend to be falsely reduced in patients with reduced plasma water levels. If serum sodium is measured using a wet spectrophotometer or ion selective electrode method (most instruments do not require dilution of the sample), this phenomenon occurs in patients with a significant increase in total protein or lipids. Since the weight osmolality is related to the solute concentration in the water, the osmolality for such a patient may also be normal.
Urine weight osmolality
Since the osmolality is the most accurate method for measuring total solute concentration, it provides the best estimate of the function of the kidney's concentrating function, which is necessary to evaluate changes in kidney function. Urine weight osmolality is the measurement of total urine solutes, which are mainly metabolic wastes such as creatinine urea (about 80% of total solutes in normal urine). In patients with kidney disease, the proportion of total solute in the urine is increased by electrolytes. For some people with too much blood in the blood (such as glucose, ethanol), the amount of these substances in the urine can exceed 30% of the total solute. For this reason, urine osmolality should generally be considered in conjunction with urinary electrolytes and urinary creatinine.
Urine weight osmolality application
Assessment of increased urine output
· Primary thirst (low blood, low urine weight permeation molar concentration)
·Diabetes insipidus (high blood, low urine weight permeation molar concentration)
· Diabetes (high blood, high urine weight osmolality)
Assessment of decreased urine output
· Dehydration (high urine weight osmolality, free water clearance is negative)
· Acute tubular injury (free water clearance is zero)
Renal acidification defect assessment
·Urine infiltration gap = NH4 + excretion
Increased urine output
In most patients, an increase in urine output is caused by one of three causes of polyuria. The most common is due to excessive intake of water, which becomes polydipsia, which is a sense of water (heart-related thirst) caused by psychological disorders, or due to dry mouth or inhibition. Hiccup caused a lot of water (primary thirst). In both types of thirst, urine osmolality is at a maximum dilution capacity, typically less than 100 mosmo/kg.
Excessive intake of water can also be caused by a lack of ADH (central diabetes insipidus) or a weak response of the kidney to ADH (renal diabetes insipidus, usually caused by drugs such as lithium). In both forms, the osmolality of urine can be extremely reduced, but the serum osmolality of patients with diabetes insipidus is slightly elevated, while the osmolality of serum weight in patients with thirst is decreased. of. Traditional teaching will describe the use of a test called “water ban†to evaluate such patients. In theory, normal people will respond to urine by a osmolality of more than 300 mosmo/kg, but urine collapse Patients with symptoms do not respond to this. Distinguishing between central and renal diabetes insipidus is an increase in urinary weight osmolality observed after ADH ingestion. In fact, prolonged urine output can impair the maximum responsiveness of the kidney to ADH. As a result, in both types of polyuria, the observations are often very similar. Repeat this test after correcting polyuria (use ADH if necessary) and the results are easier to interpret.
In diabetic patients, an increase in glucose in the urine causes loss of water, and this patient exhibits an increase in the osmolality of typical urine and serum.
Reduced urine output
The reduction in urine output can be due to problems with the kidney itself or the body is trying to retain water and electrolytes. In most cases, acute urine loss due to kidney disease is caused by acute tubular damage (acute tubular necrosis, ie ATN, tubular necrosis due to reduced drug, toxin or blood flow; or tissue Interglomerulonephritis; inflammation caused by drugs).
When the renal tubules are damaged, the urine osmolality is close to the plasma concentration (about 290 mosmo/kg) and the free water clearance is close to zero. However, many medical and clinical pathology textbooks have examined the detection of urine electrolytes and urinary sodium excretion. In ATN patients, the free water clearance rate is abnormal one day earlier than the sodium test. In fact, sodium excretion usually remains low for 2-3 days after the onset of ATN.
If the reduction in urine output is due to a decrease in renal blood flow, the body will attempt to retain water and sodium to reduce further reductions in blood flow. In this case, the osmolality of the urine will be extremely high (although sodium excretion is usually maintained at a low level within 2-3 days after the onset of ATN). Urine weight osmolality and electrolyte elevation are helpful in the assessment of patients suspected of having abnormal secretion of ADH, which has a tendency to have a high urinary weight osmolality, and the osmolality during the water ban is not normal. The rise will not fall after the water is taken. This dynamic test observation is necessary for clinical diagnosis.
Evaluation of urine acidification
Under normal circumstances, the main acid excreted by the kidneys is NH4+. In some kidney diseases, the kidneys do not maximize acid or reabsorb hydrogen carbonate; such renal insufficiency is collectively referred to as renal tubular acidosis. This patient's excretion of ammonia ions is reduced. Since it is not easy to directly measure ammonia, some indirect measurements have been proposed. One of the most accurate methods is the calculation of the urine permeation gap. The urine permeation gap is expressed by the following formula:
Example of weight osmolality - [2 x (Na+ + K+) + urea + glucose]
——— ———
2.8 18
Fecal weight permeation molar concentration:
The detection of osmolality of fecal weight is sometimes very useful for the evaluation of patients with diarrhea. In normal feces, most of the small molecules are reabsorbed (except for electrolytes), so most of the osmotically active substances in the feces are derived from the electrolyte. The osmotic clearance of feces is the difference between the measured osmolality and the calculated osmolality (defined as the sum of Na and K ions in feces multiplied by 2) or, more accurately, the serum weight permeation concentration.
Separation of secretions from osmotic diarrhea
Osmotic diarrhea
·There are unabsorbed solutes, abuse of laxatives, malabsorption
Secretory diarrhea
· Damage to the intestinal mucosa by toxins (inflammation, infection, drugs)
Most diarrhea is caused by infection or bacterial toxins and can return to normal in a short time. The osmolality of fecal weight has little effect on such patients. If diarrhea lasts longer than 1 week and fecal culture is negative, the cause of diarrhea is more difficult to determine. Gastroenterologists describe diarrhea as two types: osmotic diarrhea and secretory diarrhea. In osmotic diarrhea, some unabsorbed material is present in the feces, preventing normal absorption of water (such as the working principle of laxatives). In such patients, a typical performance is a molar osmolality greater than 50 mosm/kg. Osmotic diarrhea can be seen in patients who use excessive amounts of laxatives, as well as in patients with nutritional malabsorption.
If endogenous intestinal mucosal damage causes water and electrolyte malabsorption, then secretory diarrhea occurs, which is common in those mechanical diseases of the intestine, such as inflammation, tumors, and decreased blood flow.
An important consideration in measuring the osmolality of fecal weight is that bacteria produce osmotically active substances during metabolism, so the measurement of osmolality of fecal weight must be completed within 30 minutes after sample collection, or the sample should be stored before analysis. In the refrigerator.
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