1、Acute Renal Failure：,Gu Yong Division of Nephrology Huashan Hospital Affiliated to Fudan University,ARF,1. Definition and concept 2.Pathogenesis 3.Pathology and pathophysiology 4. Acute tubular necrosis 5.Special type of ARF 6.Handling of ARF,Definition of ARF,Syndrome Quick decline of GFR A series
2、of clinical manifestation Accumulation of nitrogen-containing tastes,Incidence of ARF,Common hospitalization：5% ICU： 30%,Hou SH et al. Am J Med.1983；74：243,Features of ARF,Kidney：complete restoration of function High incidence of complication High morbidity & mortality Other organs damage,Classifica
3、tion of ARF,Prerenal：Hypoperfusion, functionality：55%-60% Renal： 35%-40% Postrenal：urinary tract： 5%,Causes of prerenal ARF,Low volume: bleeding, lost from G-I, kidney, skin, third space Low cardiac output: myocardium, valve, Systemic vasodilatation: medicine, infection, allergy,liver failure Renal
4、arterial systole：shock, medicine,liver failure,Renal ARF,Renal great vessels Glomerule Acute tubular necrosis：ischemia/poisoning Tubules and interstitium,Postrenal ARF,Position: Ureter bladder neck Anterior urethra,Cause： Stone, coagulated blood, Crystal,edema, deligation Tumor, fibrosis, stenosis,
5、prostate gland etc.,ATN,Pathology Pathophysiology Course of disease Diagnosis and differential diagnosis Complication,Decline of GFR in ARF,Abnormal renal hemodynamics Tubular impairment: obstruction, back flow,Factors involved in renal hemodynamics,Endothelin： increasing receptor blocking EDNO： dec
6、reasing Others：Platelet Activating Factor (PAF)Adenosine Medulla edema Tubuloglomerular feedback: TGF,Tubular impairment,Obstruction： Caducous epithelial cells and components Cast Back flow: Impaired integrity of epithelial cells According to histology: tubular cells fall off and necrosis, cast,Meta
7、bolic change after tubular cell damage,Decreased ATP Cellular swelling Increased intracellular calcium Intracellular acidosis Activation of phosphatidase Activation of protease Oxidative stress,Consequence of damaged tubular cells,Intact Sublethal Death: Apoptosis/necrosis Depend on: different site,
8、 toxin concentration, time,Necrosis Apoptosis in ARF,Necrosis： cellular swelling, chondriosome change Destroy membranous Integrity Release protein lysase peripheral cell damage/inflammation,Apoptosis： Active energy consumption process cell nucleus shrinkagesmall DNA fragment cell membrane：blebbing b
9、ut integrity apoptotic body phagocytosis No peripheral cell damage and inflammation,Depend on severity of impairment,Repair, Regeneration and Recovery,Recovery of Sublethal cells Scavenge necrotic cells and intracavitary casts Regeneration of epithelial cells: replace necrotic and caducous cells Tub
10、ular epithelial cells integrity and function restoration,Course of ATN,Initiation: no parenchyma impairment Maintenance: parenchyma impairment: 1-2 weeks, may be 11 months Recovery,Diagnosis and differential diagnosis of ATN,Diagnosis: medical history, physical examination, Urine Analysis, blood tes
11、tOther examinationspast medical history, drug history Differential diagnosis: Acute or ChronicClassificationCauses,Special type of ARF,Tumor Renal transplantation Pregnancy Lung diseases Operation on vessels of heart Liver diseases Nephrotic Syndrome Drugs,Why kidney easy to be damaged by drugs?,Lar
12、ge volume of blood flow: 25-30% heart stroke volume Active metabolism Largest endothelial cell surface Rich enzymatic system Transcellular transport Concentration function Much oxygen consumption, little oxygen supply (medulla),Complication of ARF (1),Metabolic Hyperkalemia Metabolic acidosis Hypona
13、tremia Hyponatremia Hyperphosphatemia Hypermagnesemia Hyperuricemia,Cardiovascular Pulmonary edema Arrhythmias Pericarditis Pericardial effusion Hypertension Myocardial infarction Pulmonary embolism Pneumonitis,Gastrointestinal Nausea Vomiting Malnutrition Gastritis Gastrointestinal ulcers Gastroint
14、estinal bleeding Stomatitis or gingivitis Parotitis or pancreatitis,Complication of ARF (2),Neurologic Neuromuscular irritability Asterxis Seizures Mental status changes Somenolence Coma,Hematologic Anemia Bleeding,Infectious Pneumonia Wound infections IV infectionsSepticemia Urinary tract infection
15、,Other Hiccups Decreased insulin catabolism Mild insulin resistance Elevated PTH Reduced 1,25-dihydroxy-and 25-hydroxycitamin D Low total T3/T4 Normal free thyroxine,Handling of ARF（1）,Prerenal Renal effective perfusion Fluid supplement: Whole blood, plasma, crystal fluid Heart: volume load, arrhyth
16、mia Cirrhosis Others,Handling of ARF (2),Renal： Prevention： Prerenal factors: volume, cardio-respiratory function Use of drugs Especially Vasoactive agent Diuretic Others,Dopamine,1-3ug/kg/min Increase RPF and GFR Perspective study：not proved Arhythmia/myocardial ischemia,ANP,Increase GFR: expansion
17、 of afferent arteriole of glomerulus / increased kf Inhibit sodium transport, decrease oxygen consumption Experiments showed effective Not clinically confirmed,Diuretic,Large dose Decrease volume load Mortality and dialysis rate unchanged Mannitol： No clinical evidence Increase the volume Low sodium
18、（shift）,Others,Growth factor: Insulin-Like G-F Endothelin receptor antagonist RGD polypeptide: inhibit tubular obstruction ATP supplement Scavenge ROS Leukocyte adhension inhibiting： Anti-CD18 Anti-ICAM-1 Anti-P-selectin ON RESEARCH NOW,Special treatment of ARF (not ATN),Corticosteroid Immunosuppres
19、sive agent Plasmapheresis Antiplatelet Blood pressure control,Complication treatment,Metabolism：water-electrolyte, acid-base balance Nutrition Anaemia,Dialysis,Questions： Prognosis？ Style？ Dosage？ Indication？,Dialysis,Peritoneal dialysis Acute intermittent hemodialysis Chronic continuous hemofiltrat
20、ion/hemodialysis,Dialysis Absolute Indications,Oliguria, urinary volume 12h BUN 30mmol, Scr 1000mol/L Hyperkalemia 6.5mmol/L Pneumonedema, no response to diuretic Metabolic acidosis, arterial blood gas analysis pH 7.2 Uremic encephalopathy Uremic pericarditis,Indication of CRRT therapy,Cardiovascula
21、r function unstable MOF Severe ARF,Comparison of replacement therapy (CRRT & IHD),Volume control/toxin cleaning Electrolyte acid-base disturbance correcting Nutrition lost Other organs protection Mediators of inflammation, endotoxin and pyrogen scavenging Survival rate,Survival rate,CRRT better than
22、 IHD: toxin cleaning, volume control, cardiovascular system, electrolyte and acid-base disturbance correcting Survival rate in CRRT group is not better than IHD group,Postrenal ARF,Principle： To relieve obstruction as soon as possible Nephrologist, Urol and Radiol：Work hand in hand,Prognosis of ARF,No obvious changes in mortality age, multi-organ involved Primary diseases：gynecology：15% poisoning：30% trauma/major operation：60-90% Extent of increase in urine volume and Scr 50% remain dysfunction,
