Uremic pneumonia

　　1. Etiology

　　1. Increased permeability of alveolar-capillary

　　(1) Small molecule substances: including urea, guanidine substances, and amines. Urea is the most abundant metabolic substance in body fluids. In the middle and late stages of chronic renal failure, the serum concentration of urea gradually increases. The clinical symptoms of uremia, such as headache, fatigue, nausea, vomiting, drowsiness, and tendency to bleed, are all related to urea. It can also cause diffuse damage to the alveolar-capillary membrane, increasing its permeability. The longer urea stays in the body, the greater its toxicity. Guanidine substances are the metabolic products of certain amino acids and creatinine. Normally, about 10g are excreted in the urine daily. In patients with uremia, as the level of serum creatinine rises, the level of guanidine substances in the serum also increases in parallel. The effects of guanidine substances are similar to those of urea. Amines include aliphatic amines, aromatic amines, and polycyclic amines. Aliphatic amines and aromatic amines can inhibit the activity of certain enzymes, affecting metabolism. Polycyclic amines can promote red blood cell lysis, inhibit the production of erythropoietin, inhibit the activity of Na+-K+-ATPase and Mg-ATPase, increase the permeability of the microcirculation, and promote the formation of uremic pulmonary edema.

　　(2) Middle molecular substances: Including hormones with normal structure but increased concentration, high concentrations of normal metabolic products, and the lysates of cells or bacteria. High concentrations of middle molecular substances can cause peripheral neuropathy, erythropoiesis inhibition, inhibition of various antibody production, and a decrease in cellular immune function. Parathyroid hormone (PTH) is particularly notable for its diffuse damage to the alveolar-capillary membrane, and it can also affect myocardial function and myocardial cell metabolism.

　　(3) Immune factors: Since the glomerular basement membrane and the pulmonary capillary basement membrane have the same antigenic determinants, the etiology of uremia, such as chronic glomerulonephritis and nephrotic syndrome, can damage the pulmonary capillary basement membrane, causing changes in its permeability.

　　2. Increased volume load

　　Animal models of acute renal failure induced by ureteral ligation show pulmonary lesions, proving that the pathogenesis depends on excessive water intake. Uremic patients with reduced urine output and anuria lead to increased volume load, which is the most important pathophysiological change and one of the main reasons for the formation of pulmonary edema.

　　3. Decreased plasma colloid osmotic pressure

　　Large amounts of proteinuria, malnutrition, and anemia, among other factors, lead to a decrease in plasma colloid osmotic pressure, causing fluid to渗出到 interstitium, resulting in interstitial edema. The regulation of trans-pulmonary capillary fluid flow is conducted according to the Starling formula, that is, the net fluid flow is determined by the trans-membrane net pressure difference (△P), the trans-membrane colloid osmotic pressure difference (△π), and the membrane filtration coefficient (Kf) interacting with each other. Normally, a certain balance is maintained between △P and △π, which is mainly regulated by the lymphatic system. Primary pulmonary edema occurs due to changes in membrane Kf, with an increase in fluid leakage exceeding lymphatic drainage, leading to fluid accumulation in the interstitial tissue of the lung. Secondary pulmonary edema is caused by changes in △π or △P, leading to the entry of fluid from pulmonary capillaries into the pulmonary interstitium. Patients may not necessarily show an excessive overall fluid volume, but they may have increased intracardiac pressure and pulmonary wedge pressure.

　　4. Left ventricular insufficiency

　　During uremia, myocardial function is impaired, leading to left ventricular insufficiency and increased pulmonary capillary pressure, causing pulmonary edema and decreased pulmonary compliance. In the late stage of uremia, cardiovascular abnormalities seen on chest X-rays are not necessarily related to blood urea nitrogen (BUN) or creatinine (Scr), indicating that the formation of pulmonary edema is a result of multiple factors.

　　5. The effects of oxygen free radicals, adhesion molecules, and cytokines

　　During uremia, due to the reduction in the number of residual renal units, increased production of oxygen free radicals due to creatinine metabolism and increased susceptibility to infection, the patient's overall antioxidant capacity is significantly reduced, and these superoxide anions cannot be quickly and effectively cleared, leading to the intensification of tissue damage while clearing foreign bodies. Hypochlorous acid accelerates creatinine metabolism, and the metabolites formed are easily penetrating into the cell to cause cytotoxicity and damage the tissue. The lung is highly sensitive to hypochlorous acid, playing a major role in lung tissue damage caused by neutrophils. During hemodialysis, due to the use of biologically incompatible membranes, complement activation leads to leukocyte aggregation in the pulmonary microcirculation, releasing various lysosomal enzymes, causing lung damage. There is also evidence that leukocyte aggregation in the pulmonary microcirculation is related to increased expression of surface adhesion molecules and increased leukocyte activity.

　　6. Respiratory muscle impairment

　　Due to malnutrition during uremia, lack of active vitamin D3, hyperparathyroidism, malnutrition, and other factors, muscle weakness and disuse occur, leading to changes in chest wall compliance, affecting lung function, which is manifested by a decrease in maximum inspiratory pressure, maximum expiratory pressure, and transdiaphragmatic pressure.

　　7. Other factors

　　Inadequate management of fluid intake in clinical practice, metabolic acidosis, and electrolyte disorders also easily cause pulmonary edema.

　　Second, pathogenesis

　　grossly observed, the two lungs show diffuse rubber-like hardness changes, and there is an increase in weight. Microscopically, the lesions in the lungs are prominent, and abundant proteinaceous纤维素性 hyaline fluid is found in the alveoli, sometimes with dense hyaline blocks. There may be mononuclear cell infiltration, amyloid deposition in the basal membrane of the alveoli and small blood vessels, and there may also be pulmonary hemorrhage and hemosiderin pigmentation, which can lead to fibrosis. 20% of cases have fibrinous pleurisy. With the recurrence and prolongation of the course, repeated attacks of pulmonary edema and pulmonary calcification, pulmonary fibrosis is often seen in autopsies, with the lungs showing diffuse patchy changes, or fibrous tissue replacing the entire subsegment.

　　Commonly associated with infection in other parts:

　　1. Pleurisy:Pleurisy caused by the stimulation of the pleura by pathogenic factors. The most common symptom is chest pain. Chest pain often appears suddenly, with varying degrees of severity, which may only occur during deep breathing or coughing in patients, or may persist and worsen with deep breathing or coughing.

　　2. Endocarditis:An inflammatory disease caused by Neisseria catarrhalis invasion of the endocardium, with pathogenic microorganisms contained in the thrombi (thrombi) formed on the surface of the heart valves. The manifestations include: fever, heart murmurs, etc.

　　1. Difficulty breathing

　　Mostly mild to moderate, characterized by the ability to lie flat, with an incidence rate of 30% to 80%, varying in reports. When the condition is severe, shortness of breath is obvious, presenting with deep and large breathing. Cough is the next common symptom, with an incidence rate of 50% to 65%, usually dry cough or coughing up small amounts of white mucous sputum. When complicated with infection, large amounts of yellow purulent sputum may appear. Fever occurs in 12.9% of cases, with body temperature around 38℃, mostly due to concurrent infection of the lungs or other parts. Hemoptysis accounts for 8% to 32%, with rare massive hemoptysis. Some patients may also feel chest distension and pain. Severe kidney disease is necessary, with renal function tests meeting the criteria for uremia. It is more common in cases of oliguria, anuria, excessive intake of water and sodium, or insufficient ultrafiltration during dialysis.

　　The most common clinical symptom of uremic pneumonia is dyspnea, but the patient can lie flat. The typical X-ray chest film shows extensive small or large patchy exudative shadows in both lower lungs, which can change rapidly in a short period of time. Blood tests show no increase in total white blood cell count and neutrophil ratio, sputum culture shows no pathogenic bacteria, and X-ray chest film findings do not correspond to infection. Arterial blood gas analysis shows hypoxemia and metabolic acidosis. Pulmonary function tests show the earliest decrease in diffusion function, which always exists, and restrictive ventilation changes account for more than 51%. The effect of anti-infection is not significant, and the efficacy of hemodialysis is significant.

　　2. Cyanosis

　　The incidence is about 6.3%, nearly half of the patients may have no pulmonary signs, more than 50% of the patients can hear crackling sounds on both lungs by auscultation, 30% to 40% of the patients have low respiratory sounds in both lower lungs, and some patients can hear dry wheezes.

　　In the early stage of renal function damage, even if there are no pulmonary symptoms, the patient should be monitored for pulmonary function step by step. The decrease in pulmonary diffusion function and the degree of restrictive ventilation damage during the whole course are related to the degree of renal function decline. For those with abnormal pulmonary function, attention should be paid to the occurrence of pulmonary edema. When the creatinine clearance rate of the patient is less than 10ml/min, it is necessary to establish dialysis access and carry out long-term dialysis treatment to prevent the occurrence of pulmonary edema.

　　Blood gas analysis shows metabolic acidosis, hypoxemia, early and middle stage PaCO2 decrease or normal, when PaCO2 increases significantly, it indicates severe condition.

　　First, the imaging characteristics of the lungs

　　1. Diverse morphology:It can be butterfly-shaped, granular, solitary or disseminated small patchy, solitary or multiple large patchy, mass-like or multiple nodular, and various kinds of shadows. The typical butterfly-shaped is rare, accounting for about 4% to 10%, and the increase and roughness of pulmonary markings are the most common, accounting for 71%.

　　2. Uneven density:The density can be light or heavy, and can be uniform or mixed with various imaging.

　　3. Uncertain location:It can be located on both sides or one side of the lungs, can be located in both sides of the entire lung or the middle and lower fields of both lungs, and can also be seen in one side of the entire lung or a segment of a lung lobe. The overall impression: the right lung is more than the left lung, the middle and inner zones are more than the outer zones, and the middle and lower lung lobes are more than the upper lung lobes. The lower lobe of the right lung is easily affected.

　　4. Fast-changing:After treatment with hemodialysis, cardiotonic, diuretics, and other treatments, with the improvement of renal and cardiac function, pulmonary shadows can be significantly absorbed or completely dispersed in a short time.

　　Second, pulmonary imaging classification

　　1. Pulmonary congestion type:The most common clinical type, accounting for about 60%, characterized by enlargement, blurring, and thickening of pulmonary markings at both hilum.

　　2.Interstitial pulmonary edema type:The hilum shadow is enlarged, with unclear edges, increased and thickened pulmonary markings in both lungs, about 13% show K line, B line accounts for 7%, and A line 2% to 3%.

　　3. Alveolar pulmonary edema type:Both lungs show extensive small or large patchy shadows with low density, continuous and blurred, typical butterfly wing shape, accounting for about 19% of clinical cases.

　　4, Pulmonary interstitial fibrosis type:Most of the lung fields have linear and reticulated shadows, accounting for about 21% of clinical cases.

　　5, Cardiac enlargement:Pulmonary alveolar and interstitial edema is more common with cardiac enlargement and heart failure, with a heart and chest ratio of more than 0.5 accounting for 61%.

　　6, Pleurisy:Small or moderate effusion, generally only the costodiaphragmatic angle becomes blunt, accounting for 31% in clinical practice.

　　Third, CT and high-resolution CT and magnetic resonance imaging (MRI)

　　It has been widely used in clinical practice and can detect the subclinical pulmonary edema in these patients, which is more specific and sensitive.

　　Fourth, pulmonary function

　　Uremic patients have abnormal lung function in the early stage, among whom 47% of patients have abnormal lung function when chest X-rays are still normal, indicating that pulmonary function tests are of certain significance for the early detection of lung invasion in uremic patients.

　　The vital capacity, forced expiratory vital capacity, and 1-second forced expiratory volume are all below the normal predicted values. The pulmonary ventilation function, diffusion function, and large and small airway ventilation function of uremic patients have decreased, manifested as a decrease in the forced expiratory one-second rate (FEV1%), 50% and 25% of the vital capacity maximum expiratory flow rate (V25, V50), a decrease in the diffusion capacity of carbon monoxide, and a negative correlation between the decrease in the above pulmonary function indicators and the increase in plasma urea nitrogen concentration. The most important change is the diffusion function of carbon monoxide (DLCO), which decreases in the early stage of uremia. Pulmonary alveolar edema, secondary pulmonary interstitial fibrosis, which reduces the area of pulmonary alveolar capillaries, and a decrease in hemoglobin in pulmonary capillaries during anemia are all pathological bases for the decrease in diffusion function. With the progression of the disease, mixed ventilatory dysfunction becomes more obvious.

　　Firstly, what foods are good for uremic pneumonia?

　　1, During the period of azotemia and uremia, patients should mainly follow a low-protein diet, and the protein should mainly be animal protein containing essential amino acids, such as milk, eggs, fish, lean meat, etc. The daily protein intake is 20 grams.

　　2, Uremic patients often have low blood calcium levels, and they can eat more foods high in calcium, such as fish, shrimp, bone broth, etc.

　　3, Winter melon, cucumber, tomatoes, lotus root, cabbage, radish, cabbage, amaranth, enoki mushrooms, silver ear, oyster mushrooms, pumpkin, vegetable cucumber, luffa.

　　4, A small amount of fruit: Apples, pears, peaches, watermelons, jujubes.

　　Secondly, what foods should not be eaten for uremic pneumonia?

　　1, When the urine output decreases, it is not advisable to eat foods high in potassium, such as kelp, mushrooms, lima beans, bananas, oranges, spinach, etc.

　　2, Tofu products: Tofu, tofu intestines, roasted bran.

　　3, Beans and bean products are prohibited foods for uremic patients: soybeans, mung beans, adzuki beans, kidney beans, lentils, tofu, bean curd, soy milk.

　　4, Dried fruits and candied fruits: Watermelon seeds, peanuts, walnuts, cashews, millet, dried grapes, dried peaches, dried apricots, dried persimmons.

　　5, Dairy products: Ice cream and more than two cups of milk.

　　6, Vegetables: Kelp, nori, pickled vegetables, salted vegetables. These vegetables are prohibited foods for uremic patients.

　　7. Meat: Salted or cured meat, such as: salted fish, cured meat, ham, salted duck, sausage, salted egg, preserved egg, sardine can, offal, kidneys, brain.

　　8. Seafood: Shrimp, clam, oyster, crab.

　　9. Starch: Salted bread, salted biscuits.

　　10. Fats: Beef fat, salted oil, margarine.

　　11. Sugar: Black sugar, brown sugar.

　　12. Condiments: Salt, soy sauce, bean paste, sweet and spicy sauce, curry powder, Shacha sauce, monosodium glutamate, etc. beyond the allowable amount.

　　13. Others: (1) Various foods and canned goods added with sodium, salt, or soy sauce; (2) Various products with alkaline powder, yeast powder, baking soda powder, miso, chicken essence, beef essence, ginseng essence, beef juice.

　　First, treatment

　　1. Hemodialysis:Complete dialysis can remove excess water and uremic toxins, relieve symptoms, and is currently the most basic and important treatment method in clinical practice. The recovery of ventilation function after dialysis is earlier than that of diffusion function, especially the recovery of small airway ventilation function is fast, which may be related to the easy resolution of small airway edema and the slower resolution of alveolar edema. China reported that various indicators of pulmonary function improved significantly after 2 months of hemodialysis.

　　2. Peritoneal dialysis:Uremic patients generally should use this dialysis method less, because when the peritoneal dialysis fluid is implanted >3L, it raises the diaphragm, causing atelectasis of the lower lobe, atelectasis, pneumonia, pleural effusion, and other pulmonary complications, which directly affect pulmonary function, especially the most obvious decrease in diffusion function. If the dialysis fluid volume and intraperitoneal pressure are strictly controlled, after 3 months of dialysis, pulmonary function can also be significantly improved.

　　3. Renal transplantation:The history of renal transplantation is nearly 40 years, and it has now become an important means of treatment for uremia.

　　(1) Favorable factors for the recovery of cardio-pulmonary function after renal transplantation

　　① Recovery of urination function is beneficial to the stability of the internal environment of the body and the improvement of cardio-pulmonary function.

　　② Anemia improved, red blood cell count increased, oxygen-carrying capacity restored.

　　③ Hypertension returned to normal.

　　④ Corrected calcium and phosphorus metabolism disorder.

　　(2) Unfavorable factors for the recovery of cardio-pulmonary function after renal transplantation

　　① The application of high-dose corticosteroids and immunosuppressants is prone to induce pulmonary infection.

　　② The carbon monoxide diffusion function in lung function is difficult to recover after transplantation. The most likely explanation is that before transplantation, due to repeated episodes of pulmonary edema, it has progressed to pulmonary fibrosis, which can further reduce the residual volume of the transplant recipient.

　　4. Other treatments

　　(1) Prevention of pulmonary infection: ① Antiviral treatment can be chosen with antiviral powder, 1-2 bags, 3 times/day, taken orally; Isatis root powder, 1-2 bags, 3 times/day, taken orally; Ribavirin tablets 0.2g, 3 times/day, taken orally; other antiviral drugs should be used with caution for nephrotoxicity. ② According to drug sensitivity tests, anti-infection drugs can be chosen with ceftriaxone (ceftriaxone), 1-2g, intravenous injection, once/day, it can be routinely used as long as the liver function is normal. Erythromycin, rifampicin, cefoperazone, ampicillin (ampicillin), piperacillin, and others can be used at conventional doses when there is mild renal impairment. For moderate or severe renal impairment, the dosage should be reduced.

　　(2) Strengthen nutrition and prevent anemia: Low-protein, low-phosphorus diet; supplement sufficient essential amino acids and vitamins. The essential amino acid therapy is 0.1-0.2g per kilogram of body weight per day, taken orally in 3-4 doses. Vitamin B complex, vitamin C are provided in conventional doses, and vitamin B6 needs to be supplied in larger doses. Blood transfusion may be given when necessary.

　　(3) Reduce cardiac load and improve pulmonary edema symptoms: ①Limit the intake of water and sodium. ②Diuretic application: Furosemide (Lasix) can be used, starting with a dose of 20-80mg. If the efficacy is not satisfactory, increase the dose. Thiazide and potassium-sparing diuretics are ineffective. ③Cardiotonic application: There is always controversy about the use of digitalis, and most scholars believe that its clinical application is still necessary and cannot be replaced by other drugs. Short-acting digitalis glycosides and digoxin should be selected, and the toxicity of digitalis should be paid close attention to. ④Vasodilator application: Vasodilators can improve the clinical manifestations of pulmonary edema, and phenylephrine (benzylidine), sodium nitroprusside, nitrates are commonly used in clinical practice. ⑤Other drugs: Aminophylline, Chuanxiong, Salvia miltiorrhiza, and other drugs have reports of improving uremic pulmonary edema.

　　(4) Symptomatic treatment: ①The first choice for cough suppression is central non-narcotic cough suppressants, such as dextromethorphan tablets, dextromethorphan syrup, cough suppressant tablets, white mold cough suppressant tablets, etc. ②Expectorants are suitable for those with thick phlegm that is difficult to cough up, and can be selected from ambroxol (Mucosolvan), N-acetylcysteine, etc. ③Oxygen therapy is provided according to the condition of respiratory difficulty.

　　Second, prognosis

　　Chronic renal failure is an irreversible and progressive disease. The survival rate of patients with uremic pulmonary edema who undergo hemodialysis increases year by year, reaching over 90% per year, 70% after 3 years, and it is not uncommon after 10 years. As long as dialysis is fully performed, nutrition is good, anemia is corrected in a timely manner, and pulmonary infection is prevented, the edema itself is no longer the main factor affecting the prognosis.