Etiology and pathogenesis of renal failure2017-05-06 17:55
There are many causes of acute tubular necrosis, which can be classified into two categories:
A, renal toxic substances poisonous to the kidney, such as drugs, sulfonamides in carbon tetrachloride, mercury, bismuth, agent two chloro sulfonamide (dichlorphenamide); polymyxin antibiotics in lycopene, vancomycin, kanamycin, gentamicin and cephalothin, cefaloridine, kanamycin, abelcet vitamin B, and iodine contrast agent, methoxyflurane anesthesia; biological toxins such as snake venom, bee venom, fish mushroom, cantharidin (Cantharidin), can cause acute renal tubular necrosis in certain conditions.
Two, renal ischemia severe renal ischemia such as severe trauma, extensive burns, surgery, massive hemorrhage, postpartum hemorrhage, severe infection, septicemia, dehydration and electrolyte imbalance, especially with shock, are easily lead to acute tubular necrosis.
In addition, intravascular hemolysis (such as blackwater fever and primaquine hemolysis caused by favismand ABO blood transfusion, arsenic poisoning) released from hemoglobin, and muscle mass trauma (such as muscle crush injury, inflammation) of myoglobin, excreted by kidney, renal tubular damage can be caused by acute renal tubule necrosis.
The pathogenesis of acute tubular necrosis is not yet fully understood. It happened with the following: 1. The glomerular filtration rate is extremely reduced (usually below 5ml/min, the majority of only 1 2ml/min) the mechanism may be due to the various causes of renal tubular ischemia or poisoning, occurrence of renal tubular epithelial cell injury, the proximal tubular sodium reabsorption is reduced, so that the original urine the sodium content increased. When it flows through the distal tubule of the macula densa, stimulate the juxtaglomerular apparatus (juxta glomerular apparatus) increased in the kidneys release renin, angiotensin II activity, glomerular arterioles contraction, spasm, especially lead to glomerular blood flow decreased outer cortical glomerular filtration rate, extreme reduction. In addition, may also be due to renal ischemia, renal blood perfusion of the afferent arteriole reduced, directly stimulate the juxtaglomerular cell to release renin angiotensin II increased, resulting in contraction of afferent arterioles, decreased glomerular filtration rate and aldosterone secretion, promote sodium and water retention. Some scholars believe that glomerular filtration rate is due to capillary endothelial damage, swelling, caused by decreased permeability of the filtration membrane. The tubular lumen obstruction, injury after necrosis of renal tubular epithelial cells and inflammatory exudate, blood red protein (muscle), into a mass and tube type, the occlusion of the lumen, urine nasty blocked, and oliguria; on the other hand, intraluminal urine swelling, and will increase the pressure in the kidney so, a further decline in glomerular filtration rate. Rupture of the renal tubular wall, overflow of the original urine. After the injury of the renal tubules, the wall of the tube ruptured, and the original urine in the tube overflowed to the outside of the tube, resulting in less urine. Some people think that the various reasons (shock, trauma, crush injury etc.) in acute renal failure induced by renal ischemia, the main reason is that the occurrence of reperfusion after ischemia, renal ischemia and filtration early to reduce or stop (oliguria or urine) is a kind of self protective mechanism of renal reabsorption, alleviating the burden of the renal tubular cells, reduce the oxygen consumption, increase the tolerance to hypoxia, once the renal ischemia were improved (reperfusion), can produce a large number of superoxide anion, the renal tissue injury, severe acute renal failure in a variety of physiological abnormalities is composed of characteristic syndrome, pathogenesis in the course of each different periods have different significance.
Oliguria after polyuria, renal tubular epithelial begin a new life, at this time due to the pathogenic factors has been lifted, ischemic and toxic substances have been eliminated, blood circulation has been restored; the new tubular epithelial cells still lack the ability to concentrate urine, urine specific gravity is less than 1.015; the metabolites of azotemia and retention the osmotic diuresis, the urine volume increased, called the polyuria stage.
With the naked eye, the volume of the kidney was increased, the quality of the kidney was soft, the renal cortex was pale, ischemia, and the medulla was dark red. Microscopically, the renal tubular epithelium was flattened, and some of them showed cloudy swelling, degeneration and shedding. Poisoning caused by kidney, degeneration and necrosis of epithelial cells in proximal tubules, the basement membrane to protect its integrity; induced by renal ischemia, epithelial cell necrosis, scattered in the tubular section, the basement membrane rupture, often ulceration and renal interstitial small round cell infiltration and visible edema, a part of the patients died of acute renal tubular necrosis in kidney, no morphological changes of renal tubules under the microscope, so named tubular necrosis, is not very appropriate, but in these cases, the electron microscope, sometimes can still be seen in renal tubular epithelial cells mitochondria deformed, endoplasmic reticulum disappeared, micro cilia, some parts have a micro fissure in basement membrane. There was no change in glomerular and renal arterioles, and only when disseminated intravascular coagulation occurred, there was a fibrinous thrombus in the glomerular capillaries. At fifth to 6 days of the disease, necrotic tubular epithelial cells begin to develop. If the basement membrane is intact, the newly formed epithelial cells will soon be covered in the basement membrane, so that the morphology of the renal tubules returned to normal. However, the basement membrane is broken, the epithelial cells can not be regenerated, and the defect is replaced by connective tissue.