There are more reasons for frequent urination, including neuropsychiatric factors, post-disease weakness, parasitic diseases and so on. Children with frequent urination need to be excluded from urinary tract infections, vulvar or penile local inflammation.
The treatment of this disease should be directed at the cause of the disease, the modern medical treatment is still not much.
Traditional Chinese medicine believes that frequent urination is mainly due to the weakness of the child's body, the kidney qi is not solid, the bladder constraints are incompetent, and its chemical is not declared. In addition, too much fatigue, the spleen and lungs two organs are weak, on the false can not control the next, the soil can not control water, the bladder gas flower power, and the occurrence of frequent urination. Therefore, frequent urination is mostly a deficiency, the clinical application of warm tonic lungs and kidneys, astringent and astringent can be effective.
[Clinical efficacy] The use of pure Chinese medicine in the treatment of this disease 79 cases, all cured. Generally 4~6 doses of symptoms significantly improved
Urinary avalanches: thirst, drinking, polyuria, frequent urination, generalized water loss, and in the long run can appear mental symptoms, headache, weakness, etc.
Urinary avalanches: thirst, drinking, polyuria, frequent urination, generalized water loss.
Diabetes insipindus (diabetes insipidus) refers to vasopressin (VP), also known as antidiuretic hormone (ADH), insufficient secretion (also known as central or pituitary diabetes insipidus), or defective renal response to vasopressin (also known as nephrogenic diabetes insipidus). A group of syndromes characterized by polyuria, irritable thirst, low specific gravity urine, and hypotonic urine.
Etiology
1. Primary (unexplained or idiopathic) uremic avalanches
Ranges from about 1/3 to 1/2. It usually begins in children and is rarely (<20%) associated with anterior pituitary hypopituitarism. This diagnosis can only be established after a careful search for secondary causes that are not present. When anterior pituitary hypopituitarism or hyperprolactinemia is present or when there is evidence of intra- or suprasellar pterygoid lesions on radiologic examination, the search for a cause should be pursued as far as possible, and the longer the failure to find a primary factor is followed closely, the more definitive the diagnosis of primary uremic avalanches becomes. Decreased neurons in the supraoptic nucleus and paraventricular nucleus and the presence of antibodies to the hypothalamic nucleus accumbens in the circulation have been reported in patients with primary uremia.
2. Secondary dysuria
Neoplastic or invasive damage to the hypothalamus or pituitary gland, including: pheochromocytomas, craniopharyngiomas, embryonal tumors, pineal tumors, gliomas, meningiomas, metastatic tumors, leukemias, histiocytoses, sarcoidosis, xanthomas, tuberculosis and infectious diseases of the brain (tuberculosis, syphilis, and vasculitic lesions).
3. Hereditary uraemic syndrome
Hereditary uraemic syndrome is very rare and can be a single genetic defect or part of the DIDMOAD syndrome. (It can present as uraemia, diabetes mellitus, optic nerve atrophy, deafness, also known as Wolfram syndrome).
4. Physical injury
Commonly found in the brain, especially the pituitary gland, hypothalamus region of the surgery, isotope therapy, after severe traumatic brain injury. Surgery-induced dysuria usually appears 1 to 6 days after surgery and disappears after a few days. After an interval of 1 to 5 days, the symptoms of urolithiasis disappear permanently or relapse into chronicity. Severe traumatic brain injury, often associated with skull fracture, can present with uremic avalanches, and in a few patients, anterior pituitary hypopituitarism. Trauma-induced dysuria can recover on its own, sometimes lasting up to 6 months before disappearing completely.
Symptoms of uremia can occur during pregnancy and disappear a few days after delivery. Schihan's syndrome may show symptoms of uremia after treatment with cortisone. AVP-resistant uraemic syndrome can occur during pregnancy and may be due to an increase in circulating placental vasopressinase during pregnancy. Such patients have increased plasma AVP levels, lack of response to high doses of AVP, and response to desmopressin therapy, with resolution of symptoms after delivery.
Pathogenesis
1. Physiology of vasopressin
(a) AVP synthesis and metabolism
Vasopressin is synthesized in neurons of the supraoptic nucleus of the inferior optic chiasm and the paraventricular nucleus, where its initial product is a prohormoneogen, which enters the Golgi to form hormone proximate, which is encapsulated in neurosecretory vesicles. The vesicles flow along the axons of the neuropituitary bundle to the neuropituitary gland, and during flow persuasion they produce active ninopeptides, namely, arginine vasopressin (AVP) and a molecular weight (neurophysin) and a glycopeptide composed of 39 amino acids by the action of enzymes. All three products are released into the peripheral blood.After being secreted by hypothalamic neurons, AVP travels down the thalamo-pituitary tract to the endings where it is stored in the neuropil. In recent years, it has been found that AVP fibers are also found in the lateral band of the median eminence, and AVP can also be secreted into the pituitary portal system, at the base of the third ventricle and in the vasomotor centers of the brainstem.
AVP binds to endothelial cells located in the distal tubules and collecting ducts of the kidneys and promotes the flow of water from the lumen to the interstitium, helping to maintain osmolality and fluid volume at a constant level.AVP is present in plasma at very low concentrations and does not have vasoactive effects, but high concentrations of AVP can cause vasoconstriction by acting on the V1 receptor. AVP present in brain axons may be involved in learning and memory processes, and AVP fibers in the median eminence may be associated with the promotion of ACTH release.
AVP concentrations in plasma and urine can be measured by immunoassay. With casual fluid intake, the neurohypophysis contains nearly 6 units or 18 mmol (20 μg) of AVP, and peripheral blood AVP concentrations range from 2.3 to 7.4 pmol/L (2.5 to 8 ng/L). Blood AVP concentrations varied with day and night, being highest late at night and early in the morning and lowest in the afternoon. During normal water administration, healthy individuals release 23 to 1400 pmol (400 to 1500 ng) of AVP from the pituitary gland and excrete 23 to 80 pmol (25 to 90 ng) of AVP from the urine in 24 hours. After 24 to 48 hours of water fasting, AVP release increases 3- to 5-fold, and blood and urine levels continue to increase.AVP is inactivated mainly in the liver and kidneys, and nearly 7% to 10% is excreted in the urine in its active form.
(II) Regulation of AVP release
1. Osmotic pressure receptors AVP release is affected by a variety of stimuli. Under normal conditions, AVP release is mainly regulated by osmolarity receptors in the inferior colliculus, and changes in osmolarity stimulate AVP production and release. The feedback regulatory mechanism of plasma osmolality changes and AVP release maintains plasma osmolality within a narrow range. In normal subjects given a 20 ml/kg water load, the mean plasma osmolality was 281.7 mOsm/kg-H2O in subjects given a water load and 287.3 mOsm/kg-H2O in subjects given hypertonic saline.
2. Volume regulation
Decreased blood volume stimulates the tonoreceptors of the left atrium and pulmonary veins by decreasing the inhibitory tone of the left atrium and pulmonary veins from the pressor receptor to the inferior colliculus, and by decreasing the tonic inhibitory tone from the pressor receptor to the inferior colliculus. inferior colliculus and stimulates AVP release by reducing the tonic inhibitory impulses from the pressure receptors to the inferior colliculus. In addition, vasodilatation caused by shouting, standing upright, and warm environments can stimulate this mechanism to restore blood volume. Volume reduction can result in circulating AVP concentrations up to 10 times those due to high osmolarity.
3. Pressure receptors
Hypotension stimulates carotid and aortic pressure receptors, which stimulate AVP release. Hypotension due to blood loss is the most effective stimulus, at which time plasma AVP concentration increases markedly, and at the same time can lead to vasoconstriction until the restoration of blood volume to maintain blood pressure.
4. Neuromodulation
Many neurotransmitters and neuropeptides in the inferior colliculus have the function of regulating AVP release. For example, acetylcholine, angiotensin II, histamine, bradykinin, gamma-neuropeptide can stimulate the release of AVP. With increasing age, AVP becomes more responsive to increased plasma osmolality, and plasma AVP concentration rises progressively. These physiologic changes may predispose the elderly to an increased risk of water retention and hyponatremia.
5. Drug effects Drugs that can stimulate AVP release include niacin, morphine, vincristine, cyclophosphamide, clofibrate, chlorosulfonylurea, and some tricyclic antidepressants. Ethanol may produce a diuretic effect by inhibiting neuropituitary function. Phenytoin sodium, chlorpromazine can inhibit the release of AVP and produce diuretic effect.
(C) AVP response to water fasting and water loading
Water fasting increases osmolality to stimulate antidiuretic hormone release. Maximal urinary osmolality after water fasting changes with medullary osmolality and other intrarenal factors. In normal subjects, plasma osmolality rarely exceeds 292 mOsm/kg-H2O after 18 to 24 hours of water fasting. plasma AVP concentration increases to 14 to 23 pmol/L (15 to 25 ng/L). AVP release was inhibited by water intake. In normal subjects, plasma osmolality decreased to an average of 281.7 mOsm/kg-H2O after drinking a load of 20 ml/kg of water.
(iv) Relationship between AVP release and thirst sensation Normally, the release of AVP and the sensation of thirst are coordinated, and both are induced by a mild increase in plasma osmolality. When the plasma osmolality rises above 292 mOsm/kg-H2O, thirst sensation becomes progressively more pronounced, and water consumption is not stimulated until urine concentration reaches its maximum limit. Thus, under normal conditions, mild hyperhidrosis caused by water loss enhances thirst perception and increases fluid intake to restore and maintain normal plasma osmolality. In contrast, when thirst is lost, fluid loss cannot be corrected in time by drinking, and hypernatremia occurs despite the fact that AVP release at this time maximally concentrates the urine.
(E) The role of glucocorticoids Adrenocorticotropic hormone and AVP have a gi-resistant effect on water excretion. Cortisone can raise the osmotic pressure threshold for AVP release caused by normal entry infusion of hypertonic saline, glucocorticoids can prevent water intoxication, and can be abnormal to the body's response to water loading in hypoadrenocorticism. Decreased urinary release in hypoadrenalism may be due in part to excess circulating AVP, but glucocorticoids can act directly on the renal tubules in the absence of AVP, decreasing water permeability and increasing free water excretion in the absence of AVP.
(F) The cytological mechanism of AVP action The mechanism of AVP action in small renal tubules: ① AVP binds to the V2 receptor on the membrane of the tubular cell on the opposite side of the lumen; ② hormone-receptor complexes activate adenylyl cyclase through guanylate-binding stimulating proteins; ③ the generation of cyclic adenosine monophosphate (cAMP) is increased; ④ c-AMP is transferred to the luminal surface of the cell membrane to activate the membrane protein kinase; ⑤ protein kinase leads to membrane kinase; ⑤ protein kinase leads to membrane kinase; ⑤ the membrane protein kinase activates the membrane kinase. ; ⑤ protein kinase leads to phosphorylation of membrane proteins; ⑥ increased permeability of the luminal surface membrane to water, resulting in increased water reabsorption. Many ions and drugs can affect the action of AVP. Calcium and lithium inhibit adenylate cyclase in response to AVP and also inhibit cAMP-dependent protein kinase. In contrast, chloropropamide enhances AVP-induced adenylate cyclase activation.
2. Dysfunction at any point in AVP production and release leads to pathogenesis. By comparing the changes in plasma and urine osmolality under normal water intake, water loading, and water fasting, it is possible to categorize central urosepsis into four types: type 1: when blood osmolality is markedly elevated during water fasting, but urine osmolality is rarely elevated, and there is no release of AVP when hypertonic saline is injected. This type does have AVP deficiency. Type (ii): when there is a sudden rise in urine osmolality during water fasting, but there is no osmolality threshold when saline is injected. These patients lack osmolarity sensory mechanisms and are able to stimulate AVP release only when severe dehydration results in hypovolemia. Type (iii): with increasing plasma osmolality, urine osmolality is slightly elevated and the threshold for AVP release is elevated. These patients have a slow AVP release mechanism or reduced osmoreceptor sensitivity. Type 4: The blood and urine osmolality curves are shifted to the right side of normal. In these patients, the release of AVP begins when the plasma osmolality is normal, but the amount of release is lower than normal. Patients with types ② to ④ have good antidiuretic effects on nausea, nicotine, acetylcholine, chlorosulfonylpropanilide, and antimycin, suggesting that AVP synthesis and storage are present and that it is released in response to an appropriate stimulus. In rare cases, patients with types ② to ④ may have asymptomatic hypernatremia with very mild urolithiasis, or even lack a basis for urolithiasis.
Clinical manifestations
Pituitary dysuria can occur at any age, usually in childhood or early adulthood, and is more common in males than in females, with a male-to-female ratio of about 2:1. The date of onset of the disease is usually clear. Most patients have polydipsia, thirst, and polyuria. Nocturia is significant, and urine output is relatively constant, usually more than 4L/d, up to 18L/d, but up to 40L/d has also been reported. Urine weight is less than 1.006, and up to 1.010 in partial uremia with severe dehydration. urine osmolality is mostly <200mOsm/kg-H2O. thirst is often severe, and water intake is roughly equal to water output in those with a normal thirst center. In general, uremic patients prefer cold drinks. If water intake is not restricted, it only affects sleep and causes weakness. Intelligence, physical development is close to normal. Thirstiness and polyuria can be aggravated by exertion, infection, menstrual cycle and pregnancy. Hereditary uremic disease starts at a young age, due to the underdevelopment of the thirst center can cause dehydration fever and hypernatremia, tumors and craniocerebral trauma surgery involving the thirst center in addition to localization of symptoms, but also hypernatremia (delirium, spasms, vomiting, etc.). Once uremia combined with anterior pituitary insufficiency uremia symptoms will instead be reduced, glucocorticoid replacement therapy after the reproduction or aggravation of symptoms.
Ancillary tests
1. Estimation of the relationship between plasma osmolality and urine osmolality
The normal relationship between blood and urine osmolality. If several simultaneous measurements of blood and urine osmolality in a polyuric patient fall on the right chin of the shadow, this patient has central or renal uremia. Renal dysuria is diagnosed if the response to vasopressin injection is less than normal (see Water Abstinence Test below) or if there is an increase in blood or urine AVP concentration. The relationship between blood and urine osmolality is useful, especially after neurosurgery or head trauma, and its use can quickly differentiate uremic avalanches from fluid overload given outside the gastrointestinal tract. Intravenous fluids can be temporarily slowed in these patients, and blood and urine osmolality can be measured repeatedly.
2. Water fasting test
Comparison of urine osmolality after water fasting with that after vasopressin administration is a simple and feasible method of determining urosepsis and distinguishing vasopressin deficiency from other causes of polyuria. This test is used to estimate osmolality due to urine osmolality, often in conjunction with the osmolality relationship 15-21.
Principle: Blood osmolality increases and circulating blood volume decreases in normal subjects after water fasting, both of which stimulate AVP release, resulting in decreased urine volume, increased urine specific gravity, and increased urine osmolality with little change in blood osmolality.
Methods Water fasting varied from 6 to 16 hours (usually 8 hours), depending on the severity of the disease. Body weight, blood pressure, plasma osmolality and urine specific gravity were measured before the test. Afterwards, urine volume, specific gravity and osmolality were measured every hour. When the change of urine volume was not significant and the change of urine osmolality was <30mOsm/kg-H2O for two consecutive times, it showed that the endogenous AVP secretion had reached the maximum value (mean value), and plasma osmolality was measured at this time, followed by subcutaneous injection of aqueous pressurization of 5u, and then urine was retained to measure the volume of urine and urine osmolality for one to two times.
Analysis of the results: normal people's body weight, blood pressure, blood osmolality after water fasting is not much change <295mOsm/kg-H2O, quiet osmolality can be greater than 800mOsm/kg-H2O. after injection of aqueous pressin, urine osmolality increased by no more than 9%, and psychotic polydrinkers are close to or similar to the normal people. Patients with central urosepsis have a >3% drop in rest after water fasting, and in severe cases, there may be a drop in blood pressure and irritability.According to the severity of the disease, it can be divided into partial urosepsis and complete urosepsis. The former plasma osmolality flat top value is not higher than 300mOsm/kg-H2O, urine osmolality can be slightly more than the plasma osmolality, urine osmolality can continue to rise after injection of aqueous pressor, complete uremic syndrome plasma osmolality flat top value is greater than 300mOsm/kg-H2O, urine osmolality is lower than the blood osmolality, urine osmolality rises by more than 9% after the injection of aqueous pressor and even doubly high. Renal wistar urolithiasis after water fasting urine can not be concentrated concentrate, injection of aqueous pressin is still unresponsive.
Characteristics of the test: this method is simple and reliable, and has been widely used. Side effects are that vasopressin increases blood pressure and induces angina, abdominal pain, uterine contractions, etc.
3. Hypertonic saline test
This test is rarely used in the diagnosis of uremia, which is used when the osmotic threshold for AVP release needs to be demonstrated, and is valuable in analyzing the characteristics of certain hyponatremia and hypernatremia.
4. Plasma AVP measurement
Partial diabetes insipidus and psychogenic polydipsia due to long-term polyuria, renal medulla due to washout (washout) caused by a decrease in the osmotic gradient, affecting the renal reactivity to endogenous AVP, so it is not easy to differentiate with partial renal diabetes insipidus, at this time, do a test at the same time as water retention determination of plasma AVP, plasma and urine osmolarity can help in the differential diagnosis.
5. The etiologic diagnosis of central dysuria
Once the diagnosis of central dysuria is established, the etiologic diagnosis must be further clarified. It is necessary to measure visual acuity, visual field, pteronasal radiographs, pteronasal CT, MRI, etc., to clarify the etiology.
Differential diagnosis
Uremia must be differentiated from other types of polyuria. Some can be differentiated by history (e.g., recent use of lithium or mannitol, surgery performed under methoxyflurane anesthesia, or recent kidney transplant). In other patients, the diagnosis will be suggested by physical examination or simple laboratory tests (e.g., diabetes mellitus, renal disease, sickle cell anemia, hypercalcemia, hypokalemia, primary waiver of aldosteronism).
Congenital nephrourette is a rare form of polyuria due to an unresponsiveness to AVP. It is less severe in females than in males, concentrates the urine during water fasting, and is effectively treated with large amounts of desmopressin. One family with this disease had an abnormal gene on the short arm of the X-linked chromosome. Most patients had V2 receptor abnormalities, and some patients abounded in post-receptor defects. All patients had normal V1 receptor function. When nephrogenic urosepsis cannot be differentiated from central urosepsis by osmolality measurements, elevated blood or urinary AVP concentrations associated with plasma osmolality can clarify the diagnosis of nephrogenic urosepsis.
Primary polydipsia or psychogenic polydipsia is sometimes difficult to differentiate from uremic avalanches, or both forms may be present. Chronic excess water intake leading to hypotonic polydipsia is confused with uremic avalanches. Intermittent heavy water intake can lead to water intoxication and dilutional hyponatremia, even if the ability to dilute urine is normal. This is rare, but these patients have an increased tendency to develop hyponatremia. The polydipsia and polyuria in these patients is often erratic and often without nocturnal polydipsia, in contrast to the chronic polydipsia from urination in uremia. The combination of low plasma osmolality and hypo-osmolality clarifies the diagnosis of primary polydipsia. The relationship is normal or often better than normal. When urine osmolality is stable in the water fasting test, it does not rise or rises very little after injection of vasopressin. Urinary osmolality may be lower than normal compared with blood osmolality due to the loss of the medullary osmolality gradient due to the inhibition of AVP release by prolonged massive water intake and prolonged polydipsia. Therefore, it is sometimes difficult to distinguish primary polydipsia from incomplete central urosepsis, and some patients may have both conditions.
Diagnosis
Diagnosis of dysuria can be made using plasma and urine osmolality measurements, which are reliable, safe, and allow the clinician to make a rapid diagnosis and begin treatment.
Therapeutic measures
Treatment principles:
1. Hormone replacement therapy.
2. Antidiuretic therapy.
3. Secondary urolithiasis with concomitant etiologic treatment.
4. Symptomatic supportive therapy.
(I) water vasopressin
Uremia can be treated with hormone replacement therapy. Vasopressin is ineffective when taken orally. Aqueous vasopressin 5 to 10 U subcutaneous injection, the effect can last 3 to 6 hours. This preparation is commonly used in the initial treatment of delirious patients with uremic avalanches secondary to traumatic brain injury or neurosurgical onset. Because of its short duration of action, it recognizes the recovery of neuropituitary function and prevents water intoxication in patients close to intravenous fluids.
(ii) Powdered uraemic syndrome
Lysopressin is a nasal spray that produces a 4- to 6-hour antidiuretic effect with a single application. In respiratory infections or allergic rhinitis, the nasal mucosa is edematous and absorption of this drug is reduced. In such cases and in patients with uremia with loss of consciousness, desmopressin should be injected subcutaneously.
(C) long-acting uradine
Long-acting uradine is ellagic acid pressin preparation, each milliliter contains 5U, starting from 0.1ml, according to the daily urine output can be gradually increased to 0.5 ~ 0.7ml / times, an injection can be maintained for 3 ~ 5 days, deep intramuscular injection. Mix well before injection, do not overdose to cause water intoxication.
(D) synthetic DDAVP (1-deamino-8-dextro-arginine vasopressin desmopresssin)
DDAVP increased antidiuretic effect and vasoconstrictor effect is only AVP 1/400, antidiuretic and antihypertensive effect of the ratio of 4,000:1, the effect of the time up to 12 to 24 hours, is the most ideal antidiuretic. 1 ~ 4 ml / injection can be increased to 5 ~ 0.7 ml / times, can maintain deep intramuscular injection. 1～4μ subcutaneous injection or intranasal administration of 10～20μg, the majority of patients with 12～24 hours of antidiuretic effect.
(E) Other oral drugs
Uremic patients with residual AVP release may respond to some oral non-hormonal agents. Chloropropamide stimulates AVP release from the pituitary gland and enhances the action of AVP on the renal tubules, possibly increasing tubular cAMP formation, but is ineffective in nephrogenic uraemia. 200 to 500 mg once daily acts as an antidiuretic. Actions begin several hours after absorption and may last up to 24 hours. Chloropropamide restores thirst and is useful in patients with thirst deficiency. This drug has some hypoglycemic effect, but regular meals may prevent hypoglycemia. Other side effects include hepatocellular damage and leukopenia. The mechanism of the antidiuretic effect of dihydroclonidine is unknown. The initial effect is salt diuresis, resulting in mild salt loss, a decrease in extracellular fluid, an increase in the reabsorption of water from the proximal tubule, a decrease in the amount of primary urine entering the distal tubule, an increase in the reabsorption of water from the proximal tubule, a decrease in the amount of primary urine entering the distal tubule, and the exact mechanism is not known. It is also effective in nephrogenic uremia, reducing urine output by about 50%. There is a synergistic effect with chlorosulfaniluric acid. The dose is 50-100mg/d in divided doses. It is advisable to take the drug with low-salt diet, avoid drinking coffee and cocoa feed. Antomin can stimulate the release of AVP, also used in the treatment of urolithiasis. 100～500mg, 3～4 times a day. Side effects include liver damage, myositis and gastrointestinal reactions. Acetamipridazine also produces an antidiuretic effect by stimulating the release of AVP, and is effective at 400 to 600 mg daily. However, this to have other toxic side effects and not widely used.
Secondary uremic syndrome should first consider the etiology of treatment, if the incurable can not also be treated according to the above drugs.