Renal interstitial damage



Renal interstitial loss due to various physiological diseases.

One of the symptoms and signs of hypokalemia nephropathy when renal interstitial is impaired. Hypokalmicnephropathy is a chronic interstitial nephritis or kidney disease caused by persistent hypokalemia, also known as kalium-losing nephropathy. The manifestation of hypokalemia nephropathy is mainly caused by tubule dysfunction, mainly due to decreased dysfunction, manifested as polydipsia, polydipsia, nocturia, nocturnal urinary incontinence, renal hypotonia, and poor response to vasopressin. There is a small amount of proteinuria and cast in the urine. Early potassium loss can cause metabolic alkalosis. After renal interstitial damage, metabolic acidosis occurs due to renal tubular acidification dysfunction. The disease is easy to be complicated by pyelonephritis, the clinical manifestations of urinary tract infection, and chronic renal insufficiency gradually appears as the disease progresses. In addition to the symptoms of nephropathy, the patient's systemic manifestations mainly include hypokalemia symptoms, such as muscle weakness in the limbs, soft paralysis of the intestines, weakened tendon reflexes, and arrhythmia.

Renal interstitial damage, diabetes insipidus and impaired renal concentrating function in the late stage of chronic nephritis can cause polyuria, that is, the amount of urine exceeds 2,500 ml.



The disease is caused by chronic hypokalemia, the cause of hypokalemia is mainly due to insufficient potassium intake, excessive loss (digestive tract loss and loss of urine), various diuretics and steroids. Hormone application, chronic kidney diseases such as renal tubular acidosis, Bartter syndrome, Liddle syndrome, renin secretory tumor, Cushing's syndrome and hydroxylase deficiency diseases. Common clinical hypokalemia is:

1. Non-nephrotic hypokalemia The potassium excretion of the kidneys has not increased, and the increase in potassium intake by cells due to various reasons is also one of the common causes of hypokalemia. The hypokalemia caused by increased potassium intake in the cells is mostly temporary, and in most cases no special treatment is needed. Hypokalermic periodic paralysis is a rare autosomal dominant hereditary disease in which patients can suddenly develop hypokalemic muscle weakness, and blood potassium is often less than 3mmol/L. The cause of the disease is not fully understood, and acetazolamide can effectively improve muscle weakness. Some patients with hyperthyroidism may also have clinical manifestations of periodic paralysis, and blood potassium may also be temporarily reduced. However, the cause may not be exactly the same, acetazolamide is not effective, and -blockers can significantly improve the symptoms of muscle weakness. In addition, potassium deficiency, or potassium loss in the intestine due to acute and chronic diarrhea is also the main cause of non-nephrogenic hypokalemia.

2. Increased urinary potassium excretion caused by various causes of renal hypokalemia is the most important cause of hypokalemia, collectively referred to as renal hypokalemia. In addition to the performance of hypokalemia, patients are often accompanied by metabolic acidosis or metabolic alkalosis. Blood pressure is mostly normal in hypokalemia with metabolic acidosis, and hypokalemia patients with metabolic alkalosis are mostly hypertensive.

(1) hypokalemia accompanied by acidosis: since hypokalemia can compensate for the concentration of plasma sodium bicarbonate, most patients have a tendency to cause alkali poisoning. Conversely, if hypokalemia patients are accompanied by metabolic acid Poisoning is a great help for diagnosis. Because hypokalemia with acidosis is only seen in renal tubular acidosis, including proximal convoluted tubules and distal convolutic acidosis, and diabetic ketoacidosis. Diabetic ketoacidosis The osmotic diuretic effect caused by hyperglycemia and the discharge of a large number of negatively charged ketone bodies from the urine promote the discharge of urinary potassium, accompanied by a significant decrease in the total potassium content of the body. However, in the early stage of acidosis, due to the redistribution of intracellular and extracellular potassium, hypokalemia may not be obvious. If potassium is not treated with insulin and alkaline drugs, it can cause severe or even fatal hypokalemia.

(2) hypokalemia and normal blood pH or metabolic alkalosis:

1 Primary aldosteronism, serum aldosterone levels increased, so that the sodium ions entering the distal convoluted tubules increased significantly, due to sodium-potassium exchange urinary potassium excretion increased. In addition to elevated levels of blood aldosterone and hypokalemia, patients also have clinical manifestations of hypertension and metabolic alkalosis, while plasma renin activity is mostly reduced. Since hypokalemia can feedback inhibition of the secretion of aldosterone from the adrenal cortex, serum aldosterone levels in patients with severe hypokalemia do not increase accordingly. In patients with hypertension caused by normal or other causes, serum aldosterone after intravenous saline or hydrocortisone should be lower than 110.96nmol/L (4ng/dl), while serum aldosterone level is not inhibited, which is helpful for the disease. diagnosis. Adrenal tumors have higher levels of blood aldosterone and lower potassium levels, which must be treated surgically. Adrenal hyperplasia can be tested with spironolactone (Antisophthora) for anti-aldosterone treatment. Most patients with hypokalemia and hypertension can be corrected. The concentration of 18-hydroxy and 18-oxycortisone in the urine of some patients with hyperaldosteronism is increased, and the dexamethasone suppression test is positive, which is a rare autosomal dominant hereditary disease. These patients taking thiazide diuretics can cause extremely severe hypokalemia, while taking low-dose dexamethasone (0.75 mg) can effectively correct hypokalemia and lower blood aldosterone.

2 secondary aldosteronism: the disease is often associated with renal vascular disease, such as renal artery stenosis, renal vasculitis, etc., clinically can also be manifested as hypokale alkalosis and high blood pressure. However, it should be noted that not all secondary aldosteronism has hypokalemia. Renal vascular epithelioma (Robertson-Kihara syndrome) is a rare glomerular para-balloon device that causes aldosterone to increase due to its secreted renin. It is also clinically characterized by hypokalemia and hypertension. Lateral renal venous renin activity was significantly increased. Some extra-renal malignant tumors may also have an increase in aldosterone, but serum levels are mainly increased by inactive renin levels.

3 congenital mineralocorticoid syndrome: due to the low activity of congenital 11-hydroxysterol dehydrogenase (11-OHSD), which causes the conversion of cortisol in the kidney to inactive hydroxycortisol, resulting in a large amount of cortisol The mineralocorticoid receptor binds and activates it, exerts a mineralocorticoid-like effect, and clinically shows an increase in aldosterone. Drugs such as licorice, cottonseed phenol and sodium carbenoxate also inhibit the 11-OHSD, resulting in the clinical manifestations of increased mineralocorticoid. There have been reports of mineralocorticinosteroids in the literature due to the intake of food or drugs containing licorice.

4 Liddle syndrome: a familial disease. Clinically, there are mainly hypokalemia, hypertension and alkalosis. The intrinsic pathophysiological feature is a significant increase in the reabsorption of the distal renal tubule sodium, resulting in a capacity expansion that further inhibits the production of renin and aldosterone. Therefore, the blood aldosterone level of the disease is reduced. Sodium retention is the cause of high blood pressure, and increased sodium reabsorption results in increased potassium excretion resulting in hypokalemia and alkalosis. The patient's erythrocyte membrane sodium ion outflow disorder is also one of the characteristics of this disease. Potassium-sparing diuretics such as triamterene and amiloride can be used for the treatment of this disease. On the contrary, spironolactone (anti-Shutong) is not effective for this disease and should not be used.

5 Cushing's syndrome: About 30% of Cushing's syndrome patients may have hypokalemia, especially in patients with Cushing's syndrome secondary to ectopic corticosteroid secretion, the incidence of hypokalemia is higher. Because glucocorticoids bind to the mineralocorticoid receptor, they also produce mineralocorticoid-like effects that increase potassium excretion in the kidneys. Recently, it has been found in animal experiments that glucocorticoids can increase the glomerular filtration rate and increase the amount of fluid flowing through the renal tubules, which is the main cause of increased urinary potassium excretion.

6 hypochlorine syndrome: hypochloremia is also one of the causes of hypokalemia and metabolic alkalosis, patients without high blood pressure. Hypochloremia often occurs in frequent vomiting or a large loss of chloride ions due to gastrointestinal decompression. In addition, long-term use of large doses of thiazide or loop diuretics is also an important cause of hypochloremia.

7Bartter syndrome: Intrinsic is a rare hereditary disease, 80% of patients are under 15 years of age, and most patients are accompanied by growth retardation. People over the age of 50 are extremely rare. The pathological feature of this disease is the proliferation of the para-balloon device. Patients may have high renin and hyperaldosteronism, so hypokalemia is also a clinically prominent symptom. Because the production of prostaglandins and kinins is also significantly increased, the patient is resistant to the effects of angiotensin II and norepinephrine, so the patient has no hypertension. Studies have found that the hypokalemia of this disease is not completely caused by increased aldosterone. Because of the restriction of sodium intake, taking spironolactone (aspartate), ammonia lutastatin or excision of the adrenal gland can often effectively reduce patients with aldosteronism. Excretion of urinary potassium, but these methods can not correct the hypokalemia of Bartter syndrome. Conversely, prostaglandin inhibitors such as indomethacin (indomethacin) can correct all metabolic disorders and abnormalities in this disease, suggesting that prostaglandin production may be the most important cause of this disease. In addition to the prostaglandin inhibitors, the treatment of this disease should also be timely potassium supplementation. For those who have more urinary potassium excretion, they need to give potassium-sparing diuretics, among which Amiloride is most effective.

8 Magnesium deficiency: Magnesium deficiency can also cause hypokalemia caused by increased urinary potassium excretion. The reason is not clear. In some patients, urinary potassium excretion can be reduced after supplementing a sufficient amount of magnesium. The clinical manifestations of hypomagnesemia are similar to those of hypocalcemia. The main manifestations are symptoms of neuromuscular stress such as muscle tremor, irritability, photophobia, and psychosis. In severe cases, convulsions and convulsions may occur.

9 diuretics: thiazides, acetazolamide, mercury diuretics, and diuretics such as furosemide and etanic acid can increase the output of urinary potassium and lead to hypokalemia. The main reason is that these drugs inhibit the reabsorption of renal tubule sodium and water, the sodium and water reaching the distal convoluted tubules are significantly increased, and the Na+-K+ exchange is increased to increase the urinary potassium excretion. In addition, these diuretics (except acetazolamide) can also cause metabolic alkalosis, further increasing the excretion of urinary potassium. In addition to diuretics, there are many other drugs that cause hypokalemia, and the mechanisms that cause hypokalemia are not exactly the same.


an examination

Related inspection

Urine routine renal angiography serum 1 microglobulin (1-MG)

If the clinical cause of significant potassium loss, and the typical clinical and laboratory performance of renal tubular involvement, the diagnosis of this disease can be considered.

Laboratory inspection:

1. Urine examination: visible urine protein and cast, see more white blood cells when infected. The urine concentration dilution test showed that the concentration function decreased, the urine specific gravity decreased (the phenol red and the aminopurine acid excretion rate decreased), and the urinary prostaglandin E increased.

2. Blood examination: BUN and Scr in the early stage of the disease can be normal, and serum creatinine and urea nitrogen levels increase when renal failure occurs as the disease progresses. The characteristic change is a decrease in serum potassium and an increase in renin and aldosterone.

Other auxiliary inspections:

The pathological change of this disease is tubulointerstitial nephritis with progressive renal failure. The presence of vacuoles in the proximal convoluted tubule is a pathological feature of hereditary or acquired hypokalemia nephropathy, ie, there are many vacuoles in the renal tubular epithelial cells, especially in the proximal tubule lesions, and the vacuoles do not contain fat or glycogen. The glomeruli and renal blood vessels are generally harmless. Long-term hypokalemia causes tubulointerstitial fibrosis, which forms scars and kidney atrophy. Pathophysiological changes are a variety of renal dysfunction, accompanied by potassium loss, which is characterized by vasopressin-resistant urinary concentrating dysfunction, increased ammonia production, and decreased glomerular filtration rate. In the human body, the characteristic structure associated with potassium loss changes to vacuolization of the tubular epithelium due to pool expansion of the endoplasmic reticulum of the cell. This damage is mainly limited to the proximal tubules, which have only focal changes. Regular renal biopsy and imaging examinations show the above characteristic changes.


Differential diagnosis

Pay attention to the differentiation of chronic interstitial nephritis caused by other causes. Such as chronic pyelonephritis, hypercalcemia and nephritis.

Chronic pyelonephritis is a chronic inflammatory lesion caused by bacterial infection of the kidney, mainly invading the renal interstitial and renal pelvis, renal pelvis tissue. As the inflammation continues or recurs, the renal interstitial renal pelvis and renal pelvis are damaged, and scars are formed and the kidneys are atrophied and dysfunctional. Usually, the patient may only have backache and/or low fever, but there is no obvious urinary pain, urinary frequency and urgency symptoms. The main manifestations are increased nocturia and a small amount of white blood cells and protein in the urine. Patients with a history of long-term or recurrent urinary tract infections may develop uremia at an advanced stage.