There are many reasons for frequent urination, including neuropsychiatric factors, physical weakness after illness, parasitic diseases and so on. Children with frequent urination, urinary tract infection and local inflammation of vulva or penis should be excluded.
The treatment of this disease should be aimed at the cause, and there are not many treatment methods in modern medicine.
Chinese medicine believes that frequent micturition is mainly caused by children's weak constitution, unstable kidney qi and insufficient bladder restraint. In addition, fatigue, spleen and lung deficiency, upper deficiency can not be controlled, soil deficiency can not make water, bladder weakness, frequent urination. Therefore, frequent micturition is mostly asthenia, and clinical application of warming lung and kidney and astringent essence can achieve curative effect.
[Clinical Efficacy] 79 cases of this disease were treated with pure Chinese medicine, and all of them were cured. Generally, the symptoms are obviously improved after 4~6 doses.
Diabetes insipidus: polydipsia, polydipsia, polyuria, frequent urination, systemic dehydration, as well as mental symptoms, headache, fatigue and so on. It may happen a long time later.
Diabetes insipidus refers to a group of diseases caused by insufficient secretion of vasopressin (VP), also known as antidiuretic hormone (ADH), or insufficient response of kidney to vasopressin (also known as renal diabetes insipidus), characterized by polyuria, polydipsia, low specific gravity urine and diabetes.
etiology
1. Primary diabetes insipidus (unexplained or idiopathic diabetes insipidus)
About 1/3 ~ 1/2. Usually onset in children, rarely (< 20%) accompanied by anterior pituitary dysfunction. The diagnosis can only be determined if the secondary cause does not exist after careful search. When anterior pituitary hypofunction or hyperprolactinemia occurs, or there is evidence of intrasellar or suprasellar lesions in radiological examination, we should try our best to find the cause. The longer the close follow-up can not find the primary factor, the more definite the diagnosis of primary diabetes insipidus will be. It has been reported that there are fewer neurons in supraoptic nucleus and paraventricular nucleus in patients with primary diabetes insipidus, and there are antibodies in hypothalamic nucleus in circulation.
2. Secondary diabetes insipidus
Neogenic or invasive damage to hypothalamus or pituitary gland, including chromophobe cell tumor, craniopharyngioma, embryonic tumor, pineal tumor, glioma, meningioma, metastatic tumor, leukemia, histiocytosis, sarcoidosis, xanthoma, sarcoidosis and brain infectious diseases (tuberculosis, syphilis, vascular diseases).
3. Hereditary diabetes insipidus
Hereditary diabetes insipidus is very rare, which can be a single genetic defect or a part of DIDMOAD syndrome. (It can be manifested as diabetes insipidus, diabetes, optic atrophy and deafness, also known as Wolfram syndrome).
4. Physical damage
It is common in the brain, especially after pituitary and hypothalamic surgery and isotope therapy, and after severe brain injury. Diabetes insipidus caused by operation usually appears 1 ~ 6 days after operation, and disappears after a few days. After an interval of 1 ~ 5 days, the symptoms of diabetes insipidus disappeared or recurred permanently and became chronic. Severe brain trauma, often accompanied by skull fracture, may lead to diabetes insipidus. In severe cases, a few patients were accompanied by hypopituitarism of anterior pituitary. Diabetes insipidus caused by trauma can recover on its own, and sometimes it can last for 6 months before it completely disappears.
The symptoms of diabetes insipidus may appear during pregnancy and disappear a few days after delivery. The symptoms of diabetes insipidus can appear in patients with Sheehan syndrome after cortisone treatment. AVP-resistant diabetes insipidus may occur during pregnancy, which may be caused by the increase of vasopressin enzyme in placenta during pregnancy cycle. The plasma AVP level of these patients increased, and they did not respond to high-dose AVP, but responded to desmopressin treatment, and the symptoms were relieved after delivery.
pathogenesis
1. vasopressin physiology
(A) AVP synthesis and metabolism
Vasopressin is synthesized in neurons of hypothalamic supraoptic nucleus and paraventricular nucleus, and its initial product is prohormone, which enters Golgi body to form prohormone and is wrapped in neurosecretory vesicles. Vesicles flow to the neurohypophysis along the axon of the neurohypophysis bundle. In the process of persuasion, nine active peptides, namely arginine vasopressin (AVP), a molecular weight (neurohypophysin) and a glycopeptide composed of 39 amino acids, are produced by the action of enzymes. All three products are released into the peripheral blood. After AVP is secreted by hypothalamic neurons, it travels down the thalamus-neurohypophysis bundle to the end and is stored in the neurohypophysis. In recent years, it has been found that there are also AVP fibers in the lateral area of the median eminence, and AVP can also be secreted into the pituitary portal system, at the bottom of the third ventricle and the motor center of brain stem blood vessels.
AVP combines with endothelial cells located in the distal convoluted tubule and collecting duct of the kidney, which promotes the flow of water from the lumen to the interstitium and helps to maintain a constant osmotic pressure and body fluid volume. The concentration of AVP in plasma is very low and has no vasoactive effect. However, high concentration of AVP can cause vasoconstriction when it acts on V 1 receptor. AVP existing in the axons of the brain may participate in the process of learning and memory, and AVP fibers in the median eminence may be related to the promotion of ACTH release.
The concentration of AVP in plasma and urine can be determined by immunoassay. Under the condition of random intake of liquid, the neurohypophysis contains nearly 6 units of AVP or 65438±08 mmol(20μg μ g), and the concentration of AVP in peripheral blood is 2.3 ~ 7.4 pmol/L (2.5 ~ 8 ng/L). The concentration of AVP in blood varies with day and night, with the highest in late night and early morning and the lowest in afternoon. Under normal water supply, healthy people release AVP 23 ~1400 pmol (400 ~1500 ng) from pituitary gland, and excrete AVP 23 ~ 80 pmol (25 ~ 90 ng) from urine within 24 hours. After 24 ~ 48 hours without water, the release of AVP increased by 3 ~ 5 times, and the levels in blood and urine continued to rise. AVP is mainly inactivated in liver and kidney, and nearly 7% ~ 10% of AVP is excreted from urine in active form.
(2)AVP release regulations
1. The release of osmotic pressure receptor AVP is influenced by various stimuli. Under normal circumstances, the release of AVP is mainly due to the regulation of osmotic pressure receptors in hypothalamus, and the change of osmotic pressure stimulates the production and release of AVP. The feedback regulation mechanism of plasma osmotic pressure change and AVP release keeps plasma osmotic pressure in a narrow range. The average plasma osmotic pressure was 28 1.7 mosm/kg H2O after 20ml/kg water load for normal people, and 287.3/kg H2O after hypertonic saline injection for people with water load.
2. Capacity adjustment
Decreased blood volume stimulates tension in the left atrium and pulmonary veins, and stimulates AVP release by reducing the tension inhibition impulse from baroreceptor to inferior colliculus. In addition, the vasodilation caused by shouting, standing upright and warm environment can stimulate this mechanism to restore blood volume. The decrease of volume can make the circulating AVP concentration reach 10 times of that caused by high osmotic pressure.
3. baroreceptor
Hypotension stimulates carotid and aortic baroreceptors and stimulates AVP release. Hypotension caused by blood loss is the most effective stimulus. At this time, the plasma AVP concentration is obviously increased, which can also lead to vasoconstriction until the blood volume is restored to maintain blood pressure.
4. Neuroregulation
Many neurotransmitters and neuropeptides in inferior colliculus have the function of regulating AVP release. Such as acetylcholine, angiotensin ⅱ, histamine, bradykinin and γ -neuropeptide can stimulate the release of AVP. With the increase of age, the reactivity of plasma osmotic pressure increases with the increase of AVP, and the plasma AVP concentration also increases gradually. . These physiological changes may increase the risk of water storage and hyponatremia in the elderly.
5. Drugs that can stimulate AVP release include nicotine, morphine, vincristine, cyclophosphamide, clofibrate, chlorpromazine and some tricyclic antidepressants. Ethanol can induce diuresis by inhibiting the function of neurohypophysis. Phenytoin sodium and chlorpromazine can inhibit the release of AVP and produce diuretic effect.
(C) AVP response to water prohibition and water load
Lack of water will increase osmotic pressure and stimulate the release of antidiuretic hormone. After water shortage, the maximum urine osmotic pressure changes with the osmotic pressure of renal medulla and other intrarenal factors. After 65438 08 ~ 24 hours without water in normal people, the plasma osmotic pressure rarely exceeds 292 mosm/kg H2O. The plasma AVP concentration increased to14 ~ 23 pmol/l (15 ~ 25 ng/l). After entering the water, the release of AVP will be inhibited. After drinking 20ml/kg water load, the average osmotic pressure of plasma decreased to 2865438±0.7 mosm/kg H2O.
(IV) Relationship between AVP release and thirst Under normal circumstances, AVP release and thirst are harmonious, both of which are caused by a slight increase in pulp osmotic pressure. When the plasma osmotic pressure rises above 292 mosm/kg H2O, the thirst will gradually become obvious, and drinking water will not be stimulated until the urine concentration reaches the maximum. Therefore, under normal circumstances, mild hypernatremia caused by dehydration can enhance thirst and increase fluid intake, thus restoring and maintaining normal plasma osmotic pressure. On the contrary, when thirst is lost, the loss of body fluids cannot be corrected in time by drinking water. Although AVP release can concentrate urine to the maximum extent at this time, hypernatremia will still occur.
(V) The role of glucocorticoid Adrenocorticoids and AVP have antagonistic effects on water excretion. Cortisone can increase the osmotic pressure threshold of AVP release caused by normal infusion of hypertonic saline, and glucocorticoid can prevent water poisoning and react abnormally to water load when adrenal cortex function decreases. When adrenal function is decreased, the decrease of urine release ability may be partly caused by excessive AVP in circulation, but glucocorticoid can directly act on renal tubules when AVP is deficient, reducing water permeability and increasing free water excretion when AVP is deficient.
(VI) Cytological Mechanism of AVP Action Mechanism of AVP on small renal tubules: ①AVP binds to V2 receptor on renal tubule cell membrane opposite the lumen; ② Hormone receptor complex activates adenylate cyclase through guanylate binding stimulating protein; ③ The production of cyclic adenosine monophosphate increased; ④c-AMP is transferred to the lumen cell membrane, which activates the protein kinase on the membrane; ⑤ Protein kinase leads to phosphorylation of membrane proteins; ⑥ The permeability of the cavity membrane to water is increased, which increases the reabsorption of water. Many ions and drugs can affect the action of AVP. Calcium and lithium inhibit the response of adenylate cyclase to cAMP, and also inhibit camp-dependent protein kinase. On the contrary, chlorpromazine enhanced the activation of adenylate cyclase induced by AVP.
2. Dysfunction in any link of 2.AVP production and release will lead to the onset. By comparing the changes of plasma and urine osmotic pressure under normal drinking water, water load and water cut-off, central diabetes insipidus can be divided into four types: ① type: when water cut-off, the blood osmotic pressure increases obviously, while the urine osmotic pressure rarely increases, and no AVP is released when hypertonic saline is injected. This type does have AVP defects. Type Ⅱ: urine osmotic pressure suddenly rises when water is forbidden, but there is no osmotic pressure threshold when normal saline is injected. These patients lack osmotic pressure sensing mechanism and can only stimulate AVP release when severe dehydration leads to poor learning ability. ③ Type: With the increase of plasma osmotic pressure, urine osmotic pressure increased slightly and AVP release threshold increased. These patients have a slow release mechanism of AVP, or the sensitivity of osmotic pressure receptors is reduced. ④ Type: Both blood and urine osmotic pressure curves move to the right of normal values. When the plasma osmotic pressure was normal, the patient began to release AVP, but the release amount was lower than normal. ② ~ ④ Patients have good antidiuretic effects on nausea, nicotine, acetylcholine, chlorosulfonylurea and atropine, suggesting that the synthesis and storage of AVP exist and can only be released under proper stimulation. In rare cases, asymptomatic hypernatremia may occur in patients with type ② ~ ④, and diabetes insipidus is very mild, even lacking evidence of diabetes insipidus.
clinical picture
Pituitary diabetes insipidus can be seen at any age and usually occurs in childhood or early adulthood. There are more men than women, and the ratio of men to women is about 2: 1. Generally speaking, the date of onset is clear. Most patients have symptoms such as polydipsia, polydipsia and polyuria. At night, micturition is remarkable, and the urine volume is relatively fixed, generally above 4L/d, but not more than 18L/d at most, but it is also reported to reach 40L/d. The menstrual flow of urine volume is less than 65,438+0.006, and diabetes insipidus with severe dehydration can reach 65,438+0.065,438+00. The urine osmotic pressure of most of them is less than 200 mosm/kg H2O. Thirst is often severe, and the water intake and water output of people with normal thirst center are roughly the same. Diabetes insipidus generally likes cold drinks. If drinking water is not restricted, it will only affect sleep and cause weakness. Intellectual and physical development is close to normal. Excessive drinking and diuresis can be aggravated by fatigue, infection, menstrual cycle and pregnancy. Hereditary diabetes insipidus begins in childhood, which can cause dehydration, fever and hypernatremia due to hypoplasia of thirst center. The operation of tumor and craniocerebral trauma involves thirst center, hypernatremia (delirium, spasm, vomiting, etc. In addition to local symptoms, it may also occur. Once diabetes insipidus is complicated with anterior pituitary dysfunction, the symptoms of diabetes insipidus will be alleviated, and the symptoms will reappear or worsen after glucocorticoid replacement therapy.
accessory examination
1. Evaluation of the relationship between plasma osmotic pressure and urine osmotic pressure.
Normal relationship between blood scholarship and urine osmotic pressure. If the blood and urine osmotic pressure measured by a patient with polyuria fall on the right side of the shadow many times at the same time, the patient has central diabetes insipidus or renal diabetes insipidus. If the response to vasopressin injection is lower than the normal level (see water shortage test below) or the AVP concentration in blood or urine increases, it is diagnosed as renal diabetes insipidus. The relationship between blood and urine osmotic pressure is very useful, especially after neurosurgery or head trauma, which can quickly distinguish diabetes insipidus from excessive fluid given outside gastrointestinal tract. For such patients, intravenous infusion can be temporarily slowed down and the osmotic pressure of hematuria can be measured repeatedly.
2. Water prohibition test
Comparing urine osmotic pressure and vasopressin after water deprivation is a simple and feasible method to determine diabetes insipidus and distinguish vasopressin deficiency from polyuria caused by other reasons. This test is used to evaluate urine osmotic pressure, and is often used in combination with osmotic pressure relationship 15-2 1.
Principle: Normal people's blood osmotic pressure increases and circulating blood volume decreases after water shortage, both of which stimulate the release of AVP, resulting in the decrease of urine volume, the increase of urine specific gravity and the increase of urine osmotic pressure, while the blood osmotic pressure has little change.
Methods according to the severity of the disease, the water ban time was 6 ~ 65438 06 hours (usually 8 hours). Body weight, blood pressure, plasma osmotic pressure and urine specific gravity were measured before the test. After that, urine volume, urine specific gravity and urine osmotic pressure were measured every hour. When the urine volume changes little for two consecutive times and the urine osmotic pressure change is less than 30 mosm/kg H2O, the endogenous AVP secretion has reached the maximum (average). At this time, the plasma osmotic pressure was measured, then 5u of vasopressin was injected subcutaneously immediately, and then the urine volume and urine osmotic pressure 1 ~ 2 times were measured.
Results Analysis: The body weight, blood pressure and osmotic pressure of normal people did not change much < 295 mosm/kg H2O, but the osmotic pressure was more than 800 mosm/kg H2O. After injection of vasopressin, urine osmotic pressure increased by less than 9%, and mental polydipsia was close to or similar to normal people. The rest patients with central diabetes insipidus decreased by more than 3% after water cut. In severe cases, symptoms such as decreased blood pressure and irritability may occur, which can be divided into partial diabetes insipidus and complete diabetes insipidus according to the severity of the disease. The plateau value of plasma osmotic pressure in the former is not higher than 300 mosm/kg H2O, and the urine osmotic pressure can slightly exceed the plasma osmotic pressure. After injection of vasopressin, the osmotic pressure of urine can continue to increase. The plateau value of plasma osmotic pressure in complete diabetes insipidus is higher than 300 mosm/kg H2O, while the plateau value of urine osmotic pressure is lower than that of blood osmotic pressure. After injection of vasopressin, the osmotic pressure of urine increased by more than 9%, even several times. Renal gestational diabetes insipidus can't concentrate after water cut, and there is still no response after vasopressin injection.
Experimental characteristics: This method is simple and reliable, and has been widely used. The side effect is that vasopressin raises blood pressure and induces angina pectoris, abdominal pain and uterine contraction.
3. Hypertonic saline test
This test is rarely used for the diagnosis of diabetes insipidus. It can be used when it is necessary to prove the change of osmotic pressure threshold published by AVP, and it is of certain value in analyzing some characteristics of hyponatremia and hypernatremia.
4. Determination of plasma AVP
Partial diabetes insipidus and mental polydipsia are difficult to distinguish from partial renal diabetes insipidus because of long-term polyuria, and the osmotic gradient of renal medulla decreases due to washing out, which affects the responsiveness of kidney to endogenous AVP. At this time, it is helpful to do a water-forbidden test and simultaneously determine plasma AVP, plasma and urine osmotic pressure.
5. Etiological diagnosis of central diabetes insipidus
Once the diagnosis of central diabetes insipidus is established, the etiological diagnosis must be further clarified. Vision, visual field, sella turcica, CT and MRI are needed to determine the cause.
differential diagnosis
Diabetes insipidus must be differentiated from other types of polyuria. Some can be confirmed by medical history (such as recent surgery under anesthesia with lithium or mannitol, methotrexate or recent kidney transplantation). In other patients, physical examination or simple laboratory examination will prompt diagnosis (such as diabetes, nephropathy, sickle cell anemia, hypercalcemia, hypokalemia, primary aldosteronism).
Congenital renal diabetes insipidus is a rare polyuria caused by unresponsiveness to AVP. Women's illness is lighter than that of men, and urine can be concentrated when water is forbidden. It is effective to use desmopressin in large quantities. A family with this disease has an abnormal gene on the short arm of the X-ray chromosome. Most patients have V2 receptor abnormalities, and some patients are rich in post-receptor defects. V 1 receptor function was normal in all patients. When osmotic pressure measurement can not distinguish renal diabetes insipidus from central diabetes insipidus, the increase of blood or urine AVP concentration related to plasma osmotic pressure can clearly diagnose renal diabetes insipidus.
Primary polydipsia or psychogenic polydipsia is sometimes difficult to distinguish from diabetes insipidus, or both forms may coexist. Long-term excessive drinking water leads to confusion between hypotonic polyuria and diabetes insipidus. Intermittent drinking a lot of water, even if the ability to dilute urine is normal, can also lead to water poisoning and diluted hyponatremia. This phenomenon is rare, but these patients have an increasing tendency to develop low sodium. These patients who drink too much urine are often unstable and often do not have polyuria at night, which is different from diabetes insipidus who drinks too much urine for a long time. Combined with low plasma osmotic pressure and low osmotic pressure, primary polydipsia can be diagnosed A normal or often normal relationship. In the water-forbidden test, when urine osmotic pressure is stable, the urine osmotic pressure does not rise or rises very little after vasopressin injection. Urine osmotic pressure can be lower than the normal value compared with blood osmotic pressure due to the long-term inhibition of AVP release by drinking plenty of water and the loss of renal medullary osmotic pressure gradient caused by long-term polyuria. Therefore, it is sometimes difficult to distinguish between primary polydipsia and incomplete central diabetes insipidus, and some patients may have both.
diagnose
Diabetes insipidus can be diagnosed by measuring the osmotic pressure of plasma and urine. This method is reliable and safe, and clinicians can quickly diagnose and start treatment.
Treatment measures
Principles of treatment:
1. Hormone replacement therapy.
2. Antidiuretic therapy.
3. Secondary diabetes insipidus should be treated simultaneously.
4. Symptomatic support treatment.
(1) vasopressin
Diabetes insipidus can be treated with hormone replacement. Oral vasopressin is ineffective. Intravenous injection of vasopressin 5 ~ 10U can last for 3 ~ 6 hours. This preparation is usually used for the initial treatment of patients with diabetes insipidus after brain trauma or neurosurgery. Due to the short-term drug effect, it can identify the recovery of neurohypophysis function and prevent water poisoning in patients close to intravenous infusion.
(II) Powdered diabetes insipidus
Lysine vasopressin is a nasal spray, which can produce antidiuretic effect for 4 ~ 6 hours after once use. In the case of respiratory tract infection or allergic rhinitis and nasal mucosa edema, the absorption of such drugs is reduced. In this case, patients with diabetes insipidus who have lost consciousness should be injected with desmopressin subcutaneously.
(3) Long-acting diabetes insipidus stops.
Long-acting urapidil is a preparation of tannic acid vasopressin, containing 5U per ml, starting from 0. 1 ml, and gradually increasing to 0.5 ~ 0.7 ml/time according to daily urine output. One injection can last for 3 ~ 5 days, and it is injected into the deep muscle. Stir well before injection to avoid water poisoning caused by excessive hair.
(d) Synthetic DDAVP( 1- deaminase -8-D- arginine vasopressin desmopressin)
The antidiuretic effect of DDAVP is only 1/400 of AVP, the ratio of antidiuretic effect to pressor effect is 4000: 1, and the action time is 12 ~ 24 hours. DDAVP is the most ideal antidiuretic drug at present. 1 ~ 4 μ g subcutaneous injection or nasal administration 10 ~ 20 μ g, most patients have 12 ~ 24 hours antidiuretic effect.
(5) Other oral drugs.
Diabetes insipidus patients with residual AVP release function may respond to some oral non-hormonal preparations. Chlorosulfonylurea can stimulate the pituitary gland to release AVP, strengthen the effect of AVP on renal tubules, and may increase the formation of cAMP in renal tubules, but it has no effect on renal diabetes insipidus. 200 ~ 500 mg, once a day, can play an antidiuretic role. It takes effect a few hours after absorption and lasts for 24 hours. Chlorosulfonylurea can restore thirst and has certain curative effect on patients with thirst deficiency. This medicine has a certain hypoglycemic effect, but eating on time can avoid hypoglycemia. Other side effects include liver cell damage and leukopenia. The antidiuretic mechanism of dihydrogram urine plug is not clear. At first, it plays the role of salt diuresis, causing slight salt loss, reducing extracellular fluid, increasing the reabsorption of water by proximal convoluted tubule, reducing the initial urine volume entering distal convoluted tubule, increasing the reabsorption of water by proximal convoluted tubule and reducing the initial urine volume entering distal convoluted tubule. The exact mechanism is not clear. It is also effective for renal diabetes insipidus, which can reduce urine volume by about 50%. It has synergistic effect with chlorosulfonyl propionate urine. The dose is 50 ~ 100 mg/d, and it is taken in multiple times. When taking medicine, eat a low-salt diet and avoid drinking coffee and cocoa feed. Antonyms can stimulate the release of AVP and can also be used to treat diabetes insipidus. 100 ~ 500mg, 3 ~ 4 times a day. Side effects include liver injury, myositis and gastrointestinal reaction. Amidamidine can also produce antidiuretic effect by stimulating the release of AVP, 400 ~ 600 mg per day is effective. However, it has other side effects and is not widely used.
Secondary diabetes insipidus should first consider the cause of treatment. If it cannot be cured, it can also be treated with the above drugs.