hepatorenal syndrome
Introduction
Introduction to liver and kidney syndrome Hepatorenal syndrome (HRS) is a manifestation of progressive oliguria or anuria, elevated blood urea nitrogen and creatinine in patients with severe liver disease, but no obvious organic lesions in renal pathology. Progressive, functional renal insufficiency. basic knowledge The proportion of illness: the incidence rate is 18% within 1 year after cirrhosis Susceptible population: patients with advanced liver cancer Mode of infection: non-infectious Complications: gastrointestinal bleeding
Cause
Causes of hepatorenal syndrome
(1) Causes of the disease
HRS is common in various types of decompensated cirrhosis (especially post-hepatitis cirrhosis, alcoholic cirrhosis, etc.), but also in other serious liver diseases, such as fulminant hepatic failure, severe viral hepatitis, primary and In the process of severe hepatocellular carcinoma such as secondary liver cancer and gestational fatty liver, patients have many incentives. The most common causes are upper gastrointestinal bleeding, massive ascites, excessive diuresis, postoperative infection, infection, diarrhea, and stress. Etc. However, some patients can have HRS without obvious incentives.
(two) pathophysiology
The exact pathogenesis of HRS is not fully understood. It is generally believed that hemodynamic changes in the kidney are mainly caused by severe liver dysfunction. It is characterized by renal vasoconstriction and intrarenal shunt, resulting in a decrease in renal blood flow (RBF) and a decrease in glomerular filtration rate (GFR), which causes renal failure. These changes are functional changes rather than organic damage. The exact mechanism for causing hemodynamic changes in HRS kidneys is unclear. Most scholars believe that non-single factors may be associated with factors such as reduced circulating blood volume, endotoxemia, vasoactive substances, and imbalances in certain hormones.
1. Systemic blood volume control disorder: Severe volume control disorder in HRS leads to a decrease in effective plasma volume, which reflexively causes intrarenal vasoconstriction and renal sodium retention through the neurohumoral system. For severe liver disease, due to upper gastrointestinal bleeding, massive ascites, massive diuresis and severe vomiting, diarrhea caused by a rapid decrease in circulating blood volume, resulting in a decrease in RBF and a significant decrease in GFR, thereby inducing FARF. In cirrhosis, the volume-controlled auto-stability is abnormal, and the volume-regulated liver-kidney reflex also occurs. Through the reflex mechanism of volume regulation, the sympathetic nerves that innervate the kidney are excited, resulting in increased secretion of renin-angiotensin. The internal blood vessels contract, the blood is shunted from the cortex to the medulla, and the renal cortex is ischemia, thereby reducing RBF and GFR. Increased production of aldosterone, increased renal tubular water, sodium reabsorption, and increased secretion of antidiuretic hormone, causing severe renal water and sodium retention, leading to HRS.
2. Endotoxemia: Endotoxemia (ETM) may be an important factor in the development of HRS in patients with severe liver disease. In the presence of HRS in patients with cirrhosis, the positive rate of endotoxin in blood and ascites is very high, and the detection of endotoxin is mostly negative in the absence of HRS. Endotoxin is a lipid and polysaccharide component of the cell wall of Gram-negative bacteria, which can cause fever, vasomotor disorder, blood pressure reduction, complement activation, schwartzman reaction, DIC, and affect immune function. In severe liver disease, due to intestinal dysfunction, Gram-negative bacteria in the intestine multiply, producing a large amount of endotoxin, and the intestinal absorption of endotoxin is significantly increased. In cirrhosis, due to the relatively low immune status of the patient, the function of the liver reticuloendothelial system is reduced, and the endotoxin reabsorbed from the gastrointestinal tract cannot be completely inactivated. This situation is even more serious when combined with infection. In severe liver disease, due to the detoxification function of liver cells, endotoxin absorbed by the intestine can enter the systemic circulation through the liver or collateral circulation. ETM can also aggravate liver damage, which affect each other and cause a vicious circle. Endotoxin has obvious renal toxicity, which can cause strong contraction of blood vessels in the kidney, redistribution of blood in the kidney, decrease of renal cortical blood flow, decrease of RBF and GFR, leading to oliguria and azotemia.
3. Vasoactive substances and hormone imbalance: The imbalance of vasoactive substances and certain hormones leads to intravascular renal vasoconstriction. These substances mainly include:
(1) Renin-angiotensin-aldosterone system (RAAS): RAAS has long been recognized as an important regulatory system for regulating renal blood flow and homeostasis under physiological and pathological conditions. Clinical studies have shown that plasma renin and aldosterone are elevated in patients with advanced cirrhosis. Its mechanism is associated with an increase in effective blood volume in patients with advanced cirrhosis and an increase in renin secretion, which is associated with an increase in angiotensin and aldosterone, and is associated with a decrease in renin-induced angiotensin, which in turn impairs the normal negative feedback mechanism. Renin is continuously secreted. In patients with cirrhosis, treatment with beta-blockers, although it can reduce renin activity, but affects renal blood regulation due to decreased stroke volume, can lead to a decrease in RBF; increased RAAS activity when treated with angiotensin-converting enzyme inhibitors The blood pressure of the person can be significantly reduced, while the blood pressure of the person with low activity is not obvious. Therefore, the above problems should be noted when using these drugs in cirrhosis.
(2) Prostaglandin (PG): When severe liver function is impaired, the disorder of prostaglandin metabolism in patients plays an important role in the pathogenesis of HRS. PG is a metabolite of arachidonic acid and is a group of substances with various physiological activities. Among them, PGE2, PGA2 and PGI2 have the function of dilating blood vessels, and PGF2a and thromboxane (TXA2) have the function of contracting blood vessels. Thromboxane B (TXB2) is a hydrolysate of TXA2, and the amount of TXB2 in urine increases during HRS. In patients with cirrhosis, regardless of the presence of ascites, the synthesis of PGE2 in the kidney was significantly reduced, the PGI2 in the urine decreased, and the TXB2 content increased. The imbalance between the arachidonic acid and vasoconstrictor metabolites plays an important role in the pathogenesis of HRS, which can lead to renal vasospasm and renal tissue ischemia.
(3) Kallikrein-Kallikre System (K-KS): Renal kallikrein is synthesized by distal renal tubular cells and then released into the small lumen and blood circulation. In cirrhosis, the concentration of kallikrein and bradykinin is decreased. In addition to the above changes in HRS, urinary kallikrein is also reduced. These factors also play an important role in the pathogenesis of HRS.
(4) pseudo-neurotransmitters: cirrhosis patients with elevated levels of aromatic amino acids in the blood, through the non-specific decarboxylation and hydroxylation to produce phenylethanolamine and guanamine, these pseudo-neurotransmitters and true neurotransmitters and Norepinephrine and other competitive binding receptors block the normal conduction of sympathetic nerves, causing small blood vessels to dilate, short-circuiting peripheral blood vessels, and reducing the effective blood volume of the kidneys, leading to renal failure.
(5) The role of atrial natriuretic peptide (atrial natriuretic peptide, ANP): ANP is released into the blood by atrial myocytes and is degraded in organs such as liver, kidney and lung. ANP has a lowering of blood pressure, an increase in GFR and sodium excretion, but does not cause an increase in persistent RBF. In addition, ANP also reduces plasma renin and aldosterone levels. When the liver is severely damaged, it will inevitably affect plasma ANP levels. A decrease in ANP secretion during cirrhosis is associated with a deficiency in renal sodium regulation, and a relative decrease may be associated with a decrease in atrial pressure and a decrease in internal venous pressure due to a reduction in effective blood volume. Although ANP levels were reported to be inconsistent in patients with refractory cirrhosis, ANP levels were significantly reduced in the presence of HRS.
(6) The role of glomerular vasopressin (GP): GP is a glucoside sugar with a molecular weight of less than 500D, secreted by the liver, which has the effect of reducing the tension of the renal arterioles and expanding it, which can promote GFR. Raise, but does not cause an increase in systemic blood pressure. In severe liver failure, GP activity is significantly reduced. This may be related to a decrease in liver synthesis GP. As the liver function worsens and the production of GP is significantly reduced, the GFR drops sharply, which can trigger the occurrence of HRS. In addition, vasoactive intestinal peptide (VIP) with dilated vasculature may be involved in the pathogenesis of HRS. Elevated vasopressin (ADH) is also associated with HRS oliguria.
4. Other factors have been reported that elevated blood bilirubin can cause renal vasoconstriction during cirrhosis. Portal hypertension and ascites formation can increase intra-abdominal pressure and renal vein pressure, which can cause renal blood flow and glomerular filtration rate to decrease.
Prevention
Hepatorenal syndrome prevention
1. Removal of incentives Although the pathogenesis of HRS has not been fully understood, most of them can find more obvious predisposing factors. Therefore, removing the incentives has important practical significance for preventing the occurrence of HRS.
2. Supplementing branched-chain amino acids, blood coagulation factors, immunoglobulins, etc. to improve liver function. If necessary, blood perfusion and hemodialysis can remove excessive endotoxin, thiol, blood ammonia and other harmful substances in the body, temporarily replacing liver function.
3. Use diuretics with caution, disable nephrotoxic drugs (aminoglycoside antibiotics), and use dopamine [2 ~ 3g / (kg / min)] in small doses to improve renal perfusion.
4. Avoid a large amount of fast ascites, properly supplement the albumin, and maintain a certain plasma colloid osmotic pressure. Expansion capacity: A patient with SBP is given a 20% albumin liquid to expand blood volume (1 to 1.5 g/kg, within 1 to 3 days) to prevent renal failure. Patients who underwent extensive ascites puncture and drainage were treated with low-salt albumin (8 g of low-alkaline albumin per 1 L of ascites) to prevent circulatory failure due to ascites.
Complication
Hepatorenal syndrome complications Complications, gastrointestinal bleeding
Complications are liver failure, gastrointestinal bleeding, infection and hyperkalemia.
Symptom
Hepatorenal syndrome symptoms Common symptoms Loss of appetite, fatigue, anorexia, azotemia, hepatorenal syndrome, flapping tremor, weight loss, ascites, renal tubular necrosis, oliguria
The clinical features of this syndrome are:
1. Severe liver disease manifestations HRS occurs in severe liver disease, such as acute severe hepatitis, advanced liver cancer, most of which occur in the end of liver cirrhosis, all patients have ascites, usually have different degrees of portal hypertension, jaundice, hypoproteinemia, Laboratory tests have shown varying degrees of abnormal liver function, may have hyponatremia, hypotension, severe hepatic encephalopathy.
2. A variety of incentives HRS a few occur without obvious incentives, but most have different incentives, such as strong diuretic, ascites and gastrointestinal bleeding, patients may have mild, moderate blood pressure, generally not serious Hypotension and shock.
3. Patients with impaired renal function generally have no history of chronic kidney disease. The original renal function can be completely normal. Nitrogenemia and oliguria generally progress slowly. Renal failure can occur within a few months and several weeks, but it can also be counted. Rapid emergence within the day, manifested as progressive and severe oliguria or anuria and azotemia, and hyponatremia and hypokalemia, severe anuria or oliguria can also be hyperkalemia, and even Sudden cardiac arrest can occur due to hyperkalemia; generally liver disease first aggravates, then renal failure, but also can occur at the same time, with renal failure, liver damage is increasing.
URS PH is acidic at HRS, urine protein is negative or trace, urine sediment is normal or there may be a small amount of red, white blood cells, transparent, granular cast or biliary tubular cell cast, glomerular filtration rate and renal plasma flow are significantly reduced Urine sodium is often <10mmol / L, urine osmotic pressure / plasma osmotic pressure > 1.5, renal concentration function is often maintained normal, urine specific gravity > 1.020, serum creatinine concentration is slightly increased, urine creatinine / serum creatinine > 20.
The course of hepatorenal syndrome is divided into three phases.
(1) Pre-nitrogenemia: In addition to the clinical manifestations of decompensated cirrhosis, renal function such as creatinine clearance rate, ammonia uric acid excretion rate and water load excretion ability have been impaired, blood urea nitrogen is generally Still normal, or short-term high, normal serum creatinine, low blood sodium, it is worth noting that oliguria progressively worsen, and is ineffective for general diuretics, this period is maintained for several days or extended for more than a month.
(2) Nitrogenemia period: Once entering the azotemia phase, all symptoms of hepatorenal syndrome become apparent.
Early: an average of 3 to 7 days, moderately elevated urea nitrogen, serum creatinine is still normal, clinical manifestations of loss of appetite, general malaise, weight loss, lethargy, often accompanied by refractory ascites, liver function can be progressive deterioration.
Late stage: azotemia is significantly aggravated within a few days, blood urea nitrogen and creatinine are progressively increased, and there are manifestations of hepatic encephalopathy such as thirst, nausea, anorexia, apathy, lethargy and flapping tremor, with obvious hyponatremia , can be less than 125mmol / L, urine sodium discharge is very low, often less than 10mmol / L, can have high blood potassium, oliguria, daily urine volume is less than 400ml, and decreased day by day, urine specific gravity or increased, part Acute tubular necrosis occurred in the late stage of the patient, and the urine specific gravity was lower than normal. The microscopic examination may show obvious abnormalities, and the urinary sodium excretion increased, which may be greater than 40 mmol/L, and the urinary lysozyme increased.
(3) End stage of azotemia: significant reduction in urine output or no urine, deep coma and hypotension, and finally death from liver failure, gastrointestinal bleeding, infection and hyperkalemia.
Examine
Examination of liver and kidney syndrome
Laboratory inspection
The laboratory tests of hepatorenal syndrome are as follows:
1. The performance of oliguria is often severe, occasionally mild, daily urine output <400 ~ 50ml (no urine).
2. Low urinary sodium In most patients, the urinary sodium level is less than 10 mEq/L, and the urine can be completely sodium-free.
3. Patients with hyponatremia hepatorenal syndrome can not effectively remove water load, especially in the absence of diuretic treatment, the hyponatremia will gradually increase.
4. The filtered Na discharge fraction is less than 1%, that is, the renal tubular function is normal, and Na can be reabsorbed.
5. Urine pH is often acidic unless in patients with alkali poisoning.
6. There may be trace proteins in the urine, and the appearance of proteinuria does not suggest an increase in renal damage.
7. Serum creatinine concentration increased progressively, but rarely reached high levels. In patients with obvious muscle consumption, serum creatinine is a means of detecting poor glomerular filtration rate. Over time, the serum creatinine concentration increased progressively, and patients often died before serum creatinine reached 10 mg/dl.
8. Acid-base imbalance cirrhosis with ascites The most common is respiratory alkalosis, sometimes the use of diuretics for the control of ascites, can lead to low-chlorine alkalosis, severe alkalosis continues to progress, can damage the kidney ammonia secretion mechanism, Returning ammonia to the liver, inducing hepatic encephalopathy, hepatorenal syndrome with azotemia, typical anion interstitial acidosis due to renal failure, may occur in combination with metabolic alkali and respiratory alkali (tribasic acid and alkali) Unbalanced).
Other auxiliary inspection
Patients with hepatorenal syndrome may have no significant renal impairment, but there are also literatures describing glomerular lesions associated with cirrhosis, which were once thought to be associated with hepatorenal syndrome.
1. Light microscopy The earliest reports of cirrhosis-related glomerular damage came from autopsy. Since 1965, there have been kidney biopsy reports of glomerular changes in patients with cirrhosis.
Light microscopy changes are mainly glomerular sclerosis, thickening of the basement membrane, thickening of the capillary wall, and occasional cell proliferation, thus suggesting the term cirrhotic glomerulosclerosis, the glomerular lens change is more Change, including glomerular mesangial hyperplasia, membranous glomerulonephritis, membrane proliferative glomerulonephritis, diffuse proliferative glomerulonephritis and crescentic glomerulonephritis, degree of disease from no to sclerosing change.
2. Immunofluorescence renal biopsy specimens immunofluorescence examination showed IgA with and without complement deposition, IgA mainly deposited in the glomerular mesangial area, especially in patients with alcoholic cirrhosis, except for IgA mesangial deposition, glomerular capillary Antibody deposition was also found in the vessel wall.
3. Ultrastructural examination of a few ultrastructural examinations showed that patients with cirrhosis had abnormal basement membrane changes under electron microscope, increased glomerular matrix, and electron densification in capillary basement membrane and glomerular mesangium. Deposition, mainly in the glomerular mesangial area, visible irregular black particles surrounded by clear bands.
Diagnosis
Diagnosis and differential diagnosis of hepatorenal syndrome
Diagnostic criteria
According to the cause, history and clinical and laboratory tests, the diagnosis of HRS is generally not difficult. The main criteria for diagnosis are:
1. Chronic or acute liver disease with progressive liver failure and portal hypertension.
2. Decreased glomerular filtration rate, serum creatinine level >132.6mol/L or 24h creatinine clearance <40ml/min.
3. No shock, progressive bacterial infection and evidence of current or recent use of nephrotoxic drugs, no gastrointestinal loss (recurrent vomiting or severe diarrhea) or loss of renal fluid (peripheral edema in patients with ascites weight loss > 500g / d, For several days, patients with peripheral edema lost weight >100 g/d.
4. There was no sustained improvement in renal function after discontinuation of diuretics and expansion with 1.5 L isotonic saline (serum creatinine decreased to below 132.6 mol/L, or creatinine clearance increased to above 40 ml/min).
5. Ultrasonographic evidence of urinary protein <500 mg/dl and no urinary tract obstruction or renal parenchymal lesions.
Additional criteria are: urine volume <500ml / d; urine sodium <10mEq / L; urine osmotic pressure > plasma osmotic pressure; urinary red blood cell count high power field <50; serum sodium concentration <130mEq / L.
Differential diagnosis
Nitrogenemia occurs in the late stage of liver disease. First, it should be determined whether it is pre-renal azotemia or renal failure. The two are essentially different, but the clinical manifestations are very similar and need to be distinguished. Secondly, to determine the liver failure of liver disease. Whether the type is acute tubular necrosis or hepatorenal syndrome, the treatment methods of the two are completely different. Furthermore, it is further clear whether the hepatorenal syndrome is true or false, and various diseases causing pseudohepatic and renal syndrome are unique. Medical history and clinical manifestations, it is not difficult to diagnose, but the cirrhosis and chronic renal parenchymal disease coexist is more difficult to distinguish from hepatorenal syndrome, should be carefully identified, solve the above three points, the diagnosis of hepatorenal syndrome can be established, Identification of liver and kidney syndrome and two other diseases.
According to clinical manifestations and laboratory tests, the diagnosis of hepatorenal syndrome is generally not difficult, but it needs to be differentiated from the following diseases:
1. Pre-renal azotemia often has incentives, such as heart failure and decreased plasma volume caused by various reasons. Due to insufficient renal blood volume perfusion, it may be characterized by oliguria, concentrated urine, and high specific gravity, but urea nitrogen. The increase is generally lighter, and the cardiotonic or expansion therapy has obvious curative effect. The liver and kidney syndrome has many clinical manifestations and characteristics of liver disease, and the effect on the expansion therapy is not significant.
2. Acute tubular necrosis The normal renal tubular function is: reabsorption of water and sodium, so low urine sodium content and urine concentration; urine lysozyme reabsorption, normal urinary lysozyme in the proximal tubules almost all Reabsorbed, so the urine lysozyme test is negative, acute tubular necrosis, urine specific gravity is low, fixed at 1.010 ~ 1.015, high sodium concentration, generally 40 ~ 60mmol / L, urine lysozyme test positive, urine routine examination Obvious protein and cast, etc., hepatorenal syndrome, oliguria with a high proportion of urine, and low urine sodium, which helps the identification of the two.
3. Liver disease with chronic nephritis chronic nephritis has edema, high blood pressure and other medical history, long course of azotemia, urine routine protein, castor and red blood cells, high specific gravity and fixed, urinary sodium increased significantly, these characteristics and liver and kidney There are significant differences in the syndrome.
4. Liver and kidney diseases at the same time Some diseases can cause damage to both organs of the liver and kidney. Some scholars call it pseudo-hepatic-renal syndrome, which is different from true liver and kidney syndrome. These diseases include:
(1) Systemic diseases:
1 connective tissue disease: systemic lupus erythematosus, nodular arteritis.
2 metabolic diseases: amyloidosis.
3 infectious diseases: acute or chronic viral hepatitis, sepsis sepsis, leptospirosis, yellow fever.
4 other: shock, pregnancy toxemia, obstructive jaundice, sarcoidosis.
(2) Toxic hepatitis caused by poisoning such as carbon tetrachloride, chlorpyrifos, methoxyflurane, tetracycline, streptomycin, sulfonamides, copper sulfate, chromium, etc.
(3) hereditary diseases such as polycystic disease, congenital liver fibrosis, sickle cell disease.
(4) tumor metastatic liver, kidney and adrenal tumors.
These diseases have their own characteristics, as long as a little analysis in the clinic, it is not difficult to distinguish from liver and kidney syndrome.
