1、Chronic Renal Failure Internal Medicine,Xu Xiaoqi Shanghai Second Medical Uni. 2005.10.6,Content,DefinitionEtiologyPathogenesis of CRFPathogenesis of uremic syndromeClinical presentationsDiagnosisTreatment,Definition（定义）,CRF is a permanent, usually progressive, diminution in renal function to a degr
2、ee that has damaging consequences for the patient. It is characterized by an increasing inability of the kidney（肾脏） to maintain normal low levels of the products of protein metabolism(such as urea), normal blood pressure and hematocrit, and sodium, water, potassium, and acid-base（酸碱） balance.,This o
3、ccurs when glomerular（肾小球） filtration rate (GFR) is reduced by at least 50mL/min. It can be mild, moderate, or servere.End-stage renal disease (ESRD，终末期肾病) is the degree of renal failure that would cause the death of the patient unless some form of RRT is initiated.,The progression of CRF leads, in
4、the majority of instances, to end stage renal disease (ESRD) at which point renal replacement therapy is required.,The rate of progression of CRF varies according to the underlying nephropathy and between individual patients. Age, gender, race, proteinuria（蛋白尿）, lipids, hypertension, smoking.,It has
5、 been suggested that it is faster in CGN （慢性肾小球肾炎）compared with chronic interstitial nephropathies (CIN，慢性间质性肾炎) or hypertensive nephrosclerosis(HNS，高血压肾硬化).,Proteinuria is the only continuous variable identified as an independent risk factor.,CAUSES OF CHRONIC RENAL FAILURE (1),Glomerulaopathy（肾小球病
6、变）primary glomerular disease:focal and segmental glomerulonephritis（肾小球肾炎）membranopriliferative GNIgA nephropathymembranous nephropathysecondary glomerular disease:diabetic glomerulosclerosis（糖尿病肾硬化）amyloidosis,light chain diseaseHIV-associated nephropathySLE（红斑狼疮）,Wegners granulomatosis,tubulointer
7、stitial disease（小管间质病变）reflux nephropathyanalgestic nephropathyobstructive nephropathyheavy metalsdrug hypersensitivity Hereditary diseases（遗传性疾病）autosomal dominat polycystic kidney diseasemedullary cystic diseaseAlports syndrome,CAUSES OF CHRONIC RENAL FAILURE (2),Obstructive nephropathies（梗阻性肾病）pr
8、ostatic diseasenephrolithiasis（肾结石）retroperitoneal fibrosis/tumorcongenital vascular disease hypertensive nephrosclerosissclerodermavasculitisrenal artery stenosis (ischemic nephropathy),CAUSES OF CHRONIC RENAL FAILURE (3),注：2000年全国血透病人原发病资料缺少中南、山东、北京、东北资料,2002年年底上海市尚存3416例 慢性肾功能衰竭血透患者主要原发病因,2002年全年
9、腹透患者中 575例慢性肾功能衰竭患者主要原发病因,Pathogenesis of chronic renal failure,Figure Hypotheses for the pathogenesis of glomerusclerosis (Adapted with permission from EI Nahas),Figure Hypotheses for the pathogenesis of tubulo-interstitial fibrosis. (Adapted with permission from EI Nahas.),hyperperfusion GCP,loss
10、of nephron,adaption of remaining nephrons,glom hypertrophy,mes.proliferation, focal GS, proteinuria ,tubu-inters. atrophy,ESRD,glom dis,vasc dis,tubu-inters dis,nephroarteriolosclerosis,HBP+ hyperlipidemia,atherosclerosis,Renovascular renal failure,Ca P PTH,Aquired renal cystic disease,小结-慢性肾衰竭发病机制,
11、肾小球高灌注、高压、高滤过 肾小管高代谢-小管间质损伤 高血压 脂质代谢代谢异常,Pathogenesis of the uremic syndrome,Uremic Toxins,Products of protein metabolismurea: 50 mmol/Lsympt: malaise不适, vomiting, bleeding, headache guanidine compounds(methylguanidine)sympt: anorexia食欲减退,vomiting,pruritus瘙痒, twitch颤动, unconsciousness Products of ba
12、cteria metabolism: phenol,amine,indole (uremic encephalopathy, nausea, vomiting, deterioration of renal function ),Middle molecular weight solutes: MW 500-5000uremic peripheral neuropathy, disorder of lipid metabolism, renal osteodystrophy, CVD Others: aluminum, zinc,Disorder of nutrition & metaboli
13、sm,Catabolic metabolism分解代谢: Anabolic metabolism合成代谢: Intake: ,Trade-off hypothesis,GFR ,Ca P , PTH, Tubule excretion of P,Serum Ca,parathyroid,2o hyperparathriodism,Endocrine metabolic disorder,Erythropoietin 1,25(OH)2D3 PTH Insulin resistance,小结尿毒症症状的发生机制,尿毒症毒素 营养与代谢失调 矫亡失衡学说 内分泌异常,Clinical Presen
14、tations,Late(GFR 60 mg/dL) cardiac failure anemai serositis confusion, coma anorexia vomiting peripheral neuropathy hyperkalemia metabolic acidosis,FEATURES OF CHRONIC RENAL FAILURE,Early hypertension proteinuria,elevated BUN or sCr nephrotic syndrome recurrent nephritic syndrome gross hematuria,Gas
15、troenterologic （胃肠道）manifestations prominent and frequently encounteredanorexia nausea, vomiting,diarrheauremic gastroenteritis peptic ulcer, bleedingunpleasant , metallic taste (uremic fetor),Cardiovascular and pulmonary diseasehypertension （高血压）congestive heart failure（充血性心衰）pericarditisatheroscle
16、rosisrespiratory system symptoms,Hemotologic anemia （贫血）(GFR 30-40 ml/min)EPO,inhibitor factor,shorten of RBClife span, short of materials, loss bleeding diathesis （出血倾向）gastrointestinal, vaginal, pericardial, intracranial leukocyte （白细胞）abnormalities,Neurologic manifestations central nervous sympto
17、muremic encephalopathy （尿毒症脑病）(fatigue疲劳,sleep disturbance, headache, muscular irritability,lethargy嗜睡, seizure, coma) peripheral nervousrestless leg syndrome（不安腿综合症）,paresthesias感觉异常, motor weakness, paralysis瘫痪 autonomic neuropathy,Dermatologic manifestations（皮肤表现）pallor苍白, hyperpigmentation, prur
18、itus Renal osteodystrophy（肾性骨营养不良）high-bone turnover dis: osteitis fibrosa cystica, osteoporosis, osteosclerosislow-bone turnover dis: osteomalacia骨软化, osteopenia骨量减少mixed Endocrine abnormalities Infectioncellular immune function is depressed,Metabolic disturbancecarbohydrate （碳水化合物）metabolismglucos
19、e tolerance （葡萄糖耐量） is reduced insulin（胰岛素）resistancehyperlipidemia: triglyceride（甘油三酯）,Fluid, electrolyte（电解质） and acid-base disturbancesodium （钠）and waterpotassium（钾）metabolic acidosis（代谢性酸中毒）abnormalities of calcium, phosphate （钙、磷） and vitamin D metabolism,Diagnosis & Differential diagnosis,Hist
20、oryPhysical examinationLab (urinalalysis,renal function, biochemical analysis of blood)X-ray,ultrasound, radiorenogram,Classification of the severity of renal failure,Treatment,Primary disease and reversible factors treatment Conservative treatment Treatment of complications of uremia Blood purifica
21、tion Renal transplantation,General Recommendations (1),The following general recommendations can be made for the management of patients with progressive CRF. Frequent clinic follow-up is required with particular attention to the detction, monitoring, and treatment of hypertension. Emphasis should al
22、so be on a simultaneous reduction of proteinuria (evidence-based statement). It is reasonable to advise patients with progressive CRF to avoid a high-protein diet, but caution should be exerted when recommending dietary protein restriction with its inherent risk of undernutrition. It may be better t
23、o start dialysis a few months earlier and be well nourished than risk malnutrition with its associated increased morbidity and mortality on dialysis.,General Recommendations (2),Attention should be paid to the management of the complications of CRF including metabolic acidosis, hypocalcemia, and hyp
24、erphosphatemia with the associated renal osteodystrophy (evidence-based statement). Potential nephrotoxins should be avoided including nonsteroidal anti-inflammatory agents; ACE inhibitors should also be used with careful monitoring.,General Recommendations (3),Nephrologists should refrain from impo
25、sing unnecessary and unproven interventions on their patients with CRF. Such interventions should first undergo the rigors of clinical trials. Clinical trials in progressive CRF remain, however, very difficult to conduct in view of the heterogeneity of the population studied, which necessitates very
26、 large number of patients and lengthy follow-up to reach definitive conclusions.,Potentially reversible factors in CRF,Volume depletion; Intravenous radiographic contrast; Selected antimicrobial agents (for example,aminoglycosides and amphotericin B);Nonsteroidal anti-inflammatory agents; including
27、cyclo-oxygenase type 2 inhibitors;Angiotensin-converting enzyme inhibition and angiotensin-2 receptor blockers;Cyclosporine and tacrolimus;Obstruction of the urinary tract.,Prevention additional injury,在碘造影剂使用前应给予足够水分（Patients should be adequately hydrated before receiving iodinated radiocontrast ma
28、terial） 在手术前应适当补充血容量(Adequate hydration is necessary before certain surgical procedures) 化疗前化疗中应补充血容量(Adequate hydration is essential before and during chemotherapy) 肾病患者中避免NSAID( NSAID should be avoided in patients with renal diseases) 肾损药物应避免或加强监测(Nephrotoxic drugs should be avoided or carefully m
29、onitored),Diet therapy,Enough calorie intake:126-147KJ Low protein diet: 0.6-0.8g/kg/d,60% high quality protein Essential amino acid supplement -ketoacid supplement Vitamin supplement: folic acid, Vit C, Vit B6, Vit D,Treatment of complications,Cardiovascular Hypertension: Target: Upro 1g/d 125/75 m
30、mhg Rx: restriction of sodiumdiuretic ACEICCB,Heart failure Restriction of water and sodium Large dose of furosemide Vascular dilation Digoxins Blood purification Correction of electrolytes and acid-base disturbance Improvement of anemia,Pericarditis Increase dialysis frequency or time corticosteroi
31、ds surgery,Anemia Recombinant human erythropoietin50 u/kg tiw, iHtarget: Hb 100-120g/L, Hct 30-35% Iron Folic acid,Renal osteodystrophy Recover the imbalance of Ca, Prestriction of intakephosphate binding Vitamin D supplement Partial parathyroidectomy,fluid,electrolytes and acid-base disturbance,Flu
32、id and electrolytes water intake = urinary output + 500 ml Na intake: 3 g/d Hyperkalemia Metabolic acidosisbiocarbonate 13.5 mmol/L iV,Control infection Remove uremic toxins from gastrointestinal Traditional Chinese medicine,Blood purification,Hemodialysis Peritoneal dialysis,Healthy Kidney,Renal Re
33、placement,Physical Basis,Location and Structure Location of the Kidneys inside of the Body,Left Kidney,Right Kidney,Right Ureter,Large Intestine,Liver,Lung,Superior Vena Cava,Heart,Aorta,Spleen,Small Intestine,Left Ureter,Bladder,Diseased Kidney,Physical Basis of Dialysis Semipermeable Membrane,Bact
34、eria,Medium sized Molecules, e.g. b2-Microglobulin,Water Flow is Easily Possible,Erythrocyte, Red Blood Cell,Albumin, as Example of a Big Protein Molecule,Electrolytes,The semipermeable membrane functions similar to a fine sieve, only molecules that are small enough can pass.,Healthy Kidney,Renal Re
35、placement,Physical Basis,Diseased Kidney,Hemodialysis Flow Scheme Hemodialysis,Blood Pump,Anti-Coagulation,Blood to the Patient,Blood from the Patient,Dialyzer,Fresh Dialysate,Used Dialysate,Healthy Kidney,Renal Replacement,Physical Basis,Diseased Kidney,Hemodialysis Dialyzer,Blood Inflow,Dialysate
36、Outflow,Bundle of Capillaries in the Housing,Dialysate Inflow,Blood Outflow,The dialysate flows outside of the capillaries, blood within the capillaries countercurrently.,Solute Transfer across the Capillary Walls,Healthy Kidney,Renal Replacement,Physical Basis,Diseased Kidney,Peritoneal Dialysis Ho
37、w is Peritoneal Dialysis Done?,Peritoneum,Peritoneal Dialysis Solution,Bag with Fresh Solution,Implanted Catheter,Bag for Used Solution,Peritoneal dialysis is done by filling specially composed peritoneal dialysis solution into the abdominal cavity. The solute transfer between blood and the solution
38、 happens by diffusion.The water removal from the patient is an osmotic process.,Healthy Kidney,Renal Replacement,Physical Basis,Diseased Kidney,Kidney Transplantation Location of a Kidney Transplant,Aorta,Connection of Renal Artery and Vein to the Pelvic Vessels,Liver,Kidney Transplant in the Fossa Iliaca, Not at the Position of Healthy Kidneys,Connection of the Ureter to the Bladder of the Recipient,Healthy Kidney,Renal Replacement,Physical Basis,Diseased Kidney,Quiz,慢性肾衰竭是一种疾病吗？它包括了哪些疾病？ 尿毒症各种症状的发病机制是什么？ 慢性肾衰竭的临床分期是如何区分的？ 慢性肾衰竭早期和晚期的主要临床表现有哪些？ 慢性肾衰竭非透析治疗原则是什么？ 透析的指征与方法有哪些？ Reference,
