泌尿系统教学课件：Renal Insufficiency 病生.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,Renal Insufficiency,INDEX,Acute renal failure(ARF),Chronic renal failure(CRF),Functions of the Kidney,1.Excretion,Remove waste product from the body,；,Regulate electrolyte and acid-base balance.,2.,Endocrine,Produce renin,、,EPO,、,and prostaglandins,Active VitD,3,Inactivate gastrin,、,PTH.,Renal insufficiency,Diseases,Dysfunction,of,excretion,and,endocrine,Symptoms,and signs,Edema,hypertension,oliguria,polyuria,proteinuria,anemia,osteodystrophy.,Causes,1.Primary renal diseases,Primary,glomerular diseases,Primary,tubular,diseases,Interstitial nephritis,et al.,2.Secondary renal,lesion,Circulatory system diseases,immunity diseases,metabolic,diseases,hematopathy(,血液病）,et al.,Part I,Acute Renal Failure(ARF),Definition,Etiology&classification,Pathogenesis,Alteration of Metabolism and Function,Prevention&Treatment,I Definition,Acute renal failure(ARF)is defined as a,precipitous,and,significant,(50%),decrease in,glomerular filtration rate(,GFR,)over,a period of hours to days,with an accompanying,accumulation of nitrogenous wastes,in the body.,water intoxication,azotemia,hyperkalemia,metabolic acidosis,Morbidity and mortality,急性肾衰竭,迄今为止仍是威胁人类生命的危重病症，第二次世界大战时其死亡率高达,91%,，越南战争时期由于透析技术的应用，其死亡率降为,68%,。近年来单纯急性肾衰竭的死亡率为,7%23%,，而复杂性急性肾衰竭的死亡率仍高达,50%80%,。,急性肾衰竭,的死亡率取决于原发病的严重程度，以往的研究表明，急性肾衰竭的病因不同，其死亡率有明显差别，如缺血性原因者死亡率为,30%,，而中毒性原因者死亡率仅为,10%.,1,.,causes,Prerenal,Intrarenal,Postrenal,2,.,urine volume,Oliguric,(400ml/day),3,.,renal lesion,functional,organic,obstructive,II Etiology and Classifications,Causes and classification,Pre-renal(70%of cases),functional renal failure;prerenal azotemia,Intra-renal(25%of cases),parenchymal renal failure,Post-renal(1.020 500 40:1 20:1,Urinary sediment,(,)(+),Urine protein,(-),Mannitol test,urine volume urine volume(-),III)Postrenal failure,-,Diseases causing urinary obstruction from the level of the renal tubules to the urethra,Tubular obstruction from crystals,Ureteral,（输尿管）,obstruction,Cause and classification,renal pelvis,ureter,urinary bladder,Characters of,Post-renal ARF,1,),intact,renal tubular and glomerular functions,2,),reversible,if underlying cause is corrected,in,time,(T,o rule out the obstruction quickly is very important.,),III Pathogenesis of ARF,Most of the manifestations of ARF are caused by the decreased urine volume.,Waste substance,The basic pathogenesis of ARF is to explain the reasons of decreased urine volume.,GFR and tubular reabsorption are the main factors to determine the urine volume.,Glomerular-tubular balance,1%excrete,Decreased GFR and increased reabsorption in tubule will lead to decreased urine volume.,efferent,arteriol,GFR,Pathogenesis of ARF,(induced by ATN),(I)Changes of renal hemodynamics (effects on glomerular function),(II)Effects of tubular injury,(III)Glomerular Kf,(I)Changes of renal hemodynamics,1 Decreased renal blood flow,Inferior vena cava,Adrenal,gland,Kidney,Aorta,Ureter,Bladder,Urethra,Renal blood flow:20%,30%of cardiac output(1200 ml/min).,Net Filtration Pressure,Blood hydrostatic pressure,(,BHP,),60 mmHg,out,Colloid osmotic pressure,(,COP,),-32 mmHg,in,Capsular pressure,(,CP,),-18 mmHg,in,Net filtration pressure,(,NFP,),10 mmHg,out,NFP,BHP,60 out,COP,32 in,CP,10 out,18 in,Systemic BP80mmHg,Renal artery BP is decreased,Glomerular hydrostatic pressure is decreased,Obstruction of urinary tract,Increased,Bowmans capsule pressure,Glomerular effective filtration pressure is decreased,Decreased urine volume,(,A)Decreased systemic pressure (B)Increased tubular pressure,Glomerular colloid,osmotic pressure,Glomerular hydrostatic pressure,Bowmans capsule pressure,Afferent arteriole,efferent arteriole,1)Decreased renal blood presure,BP 80mmHg,CO RBF,BP(50-70mmHg)GFR (1/2 2/3),BP(40mmHg)GFR=0,2)Renal vasoconstriction,Shock and trauma(low CO),Increased activity in sympathetic system,Constriction of afferent arteriole,RBF decrease,Decreased urine volume,Baroreceptor in aortic arch and carotid sinus,Contraction of renal artery,(A)Increased activity of sympathetic system,Low renal artery,pressure,Increased Na,+,in the distal tubule stimulate the,Macula densa,Stimulate the release of renin from the,juxtaglomerular apparatus,Constriction of afferent artery(AII),Decreased GFR,(B)Increased activity of renin-angiotension system,Ischemia and poisoning,Injury of proximal tubule and reduced Na,+,reabsorption,Constriction of afferent arteriole,Injury of endothelium of renal vessels by hypoxia,acidosis,Increased synthesis and release of endothelin,Decreased effective filtration,pressure and GFR,Decreased urine volume,(C)unbalance of endothelin and NO,decreased synthesis and release of NO,Kidney is the main organ to produce PGE2.,The role of PGE2 is dilating blood vessels.,The production of PGE2 is reduced before the development of ARI caused by gentamycin(,庆大霉素,)poisoning.,(D)Decreased production of vasodilatory prostaglandins(PGE2),3,）,Renal vessel,obstructionA,swelling of endothelial cell,ischemia,Na,+,-K,+,-ATPase,Renal toxic substances,cell membrane,permeability,calcium pump dysfunction,free radical,endothelial,cellular injury,B,microthrombus formation in renal vessel,Calcium overload,Cell edema,(I)Changes of renal hemodynamics,2.Renal blood flow re-distribution,renal cortex ischemia GFR,renal medulla hyperemia Renal tubular injury,(II)Renal tubular injury,1 Morphologic changes,morphologic change,Muddy Brown Cast,White blood Cell Casts,Red blood Cell Cast,character of renaltubule cell damage,A.Necrotic lesion,tubulorrhexis lesion,(renal poisoning and renal ischemia persistently,),：,involve all renal tubule,，,especially loop of Henle.,focal necrosis of nephron,epithelial cell necrosis,basement membrane is destroyednephrotoxic lesion(,Renal poisoning),:,involve,proximal tubule,，,all Nephron damage,，,epithelial cells necrosis,basement membrane is integrity,B.Apoptotic lesion,：,distal tubule,Na,+,、,K,+,-ATP,酶,Ca,2+,-ATP,酶,细胞内钠水潴留 胞浆内游离钙,细胞内,Ca,2+,超载,ATP,缺血、中毒,细胞水肿,OFR,生成,清除,脂质过氧化,GSH,磷脂酶活性,PGs,、,LTs,细胞损伤,(,坏死；凋亡,),线粒体,Ca,2+,ADP,、毒物,细胞损伤机制（了解）,1,）,Tubule obstruction,2),Loss of tubule integrity:initial urine back-leakage,2 Effect of tubular injury,1,）,Tubule obstruction,Reduced urine volume,Injury of proximal tubule cells(necrosis),Long time of,renal ischemia,Renal poisoning,Detach from basement membrane,and slough into the tubule lumen,and become impacted(tube cast),Increase,Bowmans capsule pressure,Tubule obstruction,Urine flow,Denuded,tubular,membrane,Injured,tubular,cells,Obstruction,from debris and,necrotic cells,Loss of tubule integrity,（,passive back-leakage,）,Severe ischemia and poisoning of tubule,Epithelial cell necrosis and loss of tubule integrity,(become leaky),Back leaking of urine to peritubular interstitial space,Press the tubule,Decreased urine volume,Press blood vessels,intratubular pressure,RBF,high interstitial pressure,43,Glomerular lesion,filtration surface area,Glomerular,permselectivity,GFR,(III)Glomerular Kf,IV Clinical Course and manifestation,Two types of ARF:,oliguric,(400ml/d),ARF.,Clinical Course and manifestation,1 Oliguric phase,（,days,weeks,）,Manifestations:,a)changes of urine,b)azotemia,c)metabolic acidosis,d)hyperkalemia,e)Water intoxication,（,I,）,oliguric ARF,A changes of urine,(a)reduced urine volume:,less than 400 ml/24h(oliguria),less than 100 ml/24h(anuria),Mechanism:RBF decrease,renal tubule obstruction and urine back-leakage,(b)urine sediment investigation:,In prerenal ARF:(-or+,?,),In ATN:(+),contain:RBC,WBC,epithelial cells,and casts,(c)specific gravity and osmolality:,ATN:Low specific gravity=1.0101.015,(N:1.015-1.025),Osmolality of urine =or plasma,Cause,:,The ability of concentration and dilution is lost,in ATN.,Pre-renal AFR:,(d)urinary Na,+,concentration:,In pre-renal ARF with normal reabsorption of tubule,urine Na,+,40 mmol/L,Actually,during oliguria,the amount of sodium entering Bowmans capsule is decreased,the Na,+,in urine is elevated because of deficient tubular reabsorption of sodium.,B Water intoxication (Hypotonic hypervolemia,dilutional hyponatremia,),Causes:,(a)oliguria with more water intake,(b)increased production of metabolic water,(catabolism),(c),Transfuse fluid,Fluid retention,Hypervolemic hyponatremia,Cell edema,C Azotemia,(NPN40 mg/dl),(a)Concept of azotemia:,increased concentration of nonprotein nitrogens(NPN)in the blood.,(normal:2035 mg/dl),The nonproteins include urea,uric acid,creatinine etc.,(b)Reasons:,a)oliguria,b)increased catabolism,of proteins.,血浆尿素氮,(,blood urea nitrogen,，,BUN,),常用指标,内生肌酐清除率,(,creatinine clearance rate,C,Cr,),血浆肌酐,(serum creatinine,S,Cr,),D Hyperkalemia,most,serious,Urinary excretion of K,+,Tissue destruction,Metabolic acidosis,Transfuse non-fresh blood,high K,+,diet,Hyperkalemia,Movement of K,+,from cells into ECF,E Metabolic acidosis,progressive,difficult to correct,GFR excretion of acid production,Secretion of H,、,NH,3,reabsorption of HCO,3,Catabolism,，,acid production,Metabolic acidosis,Hyperkalemia,2 Diuresis phase,（,4W,）,Diuresis phase begins if the urine volume is,over 400 ml/L,which reflects the improvement of ARF.,(A)Causes of diuresis:,a)Normal RBF and no tubule obstruction.,b)Concentration function of tubule is not recovered,completely.Water and sodium can not be absorbed,normally.The osmolality of urine remains low.,c)Osmotic diuresis.,(B)manifestations of diuresis phase:,polyuria,，,400 ml/d,；,Early stage,：,Hyperkalemia,Azotemia,Metabolic acidosis,Late stage,：,dehydration,hypokalemia,hyponatremia,infection.,25%,of the deaths in ARF occurs in diuresis phase.,3 Phase of functional recovery,The process of full recovery can take up to a year or more.,50%cases are restored to health.,50%cases become to CRF or die.,Influence factors:,(a)presence or absence of preexisting renal disease,(b)age of patients,(c)length of the oliguria phase,(II)Nonoliguric ARF,Some patients may develop an acute loss of renal function without oliguria (urine volume400 ml/day).,Characters:,higher GFR than oliguria ARF,character of urine:volume 1280ml/24h,lower osmolality,low specific gravity,higher urinary Na+concentration than normal(lower than oliguric ARF),fewer complications,low mortality rate,no or mild hyperkalemia,still high BUN,Nonoliguric oliguric,V Treatment principles,(I),Prevention,1)Identify at risk patients,treat the underlying,disease,；,Avoid nephrotoxic agents,2,)Monitor serum electrolytes,Treatment principles,(II)Treatment,Make the patient safe,Volume overload,Hyperkalemia,Control Azotemia,Acidosis,infection,Specific treatments,dialysis,Fluid therapy,Fluid therapy needs to be closely monitored to maintain normovolemia.,Fluid intake=insensible fluid loss,+urine volume,+any ongoing losses,metabolic water,For hyperkalemia,Oliguric renal failure is often complicated by hyperkalemia,increasing the risk in cardiac arrhythmias,Treatment of hyperkalemia:,sodium bicarbonate,insulin+hypertonic,glucose,dialysis,nutrition,provide adequate caloric,intake,limit protein intake to control increases in BUN,minimize potassium and phosphorus intake,limit fluid intake,For metabolic acidosis,NaHCO,3,may be administered,3,Chronic Renal Failure,CRF,Definition,Etiology,Pathogenesis,Alteration of Metabolism and Function,Prevention&Treatment,I Definition,Dysfunction of excretion and endocrine,etiological factors destruct nephron,waste product ,acid-base and electrolyte disorders,，,dysfunction of endocrine,65,II Causes of CRF,Renal diseases,chronic glomerulonephritis(NO.1)et al,Vascular disorders,：,diabetes mellitus,、,hypertensive disease,、,Periarteritis nodosa(,结节性动脉周围炎）,et al,renal interstitium:chronic pyelonephritis(,慢性肾盂肾炎）,Chronic nephritis,et al,Urinary tract obstruction,：,urinary calculus(,尿结石）,tumor,prostatic hyperplasia,（前列腺增生）,et al,66,compensatory stage,Renal insufficiency,stage,Renal failure,stage,Uremia,stage,III Clinical Course of CRF,67,stage,Ccr,（,ml/min,）,BUN,(mmol/L),Cr,(umol/L),Clinical symptoms,compensatory,50,9,178,Primary disease,no specifical symptoms,Renal insufficiency,20,50,9,20,186,442,fatigue,，,mild,anemia,，,digestive tract,discomfort,Renal failure,10,20,20,28,451,707,anemia,，,metabolic acidois,，,hypocalcemia,、,hyperphosphorus,、,polyuria and nocturia,Uremia,28.6,707,Uremic symptoms,68,Intact nephron hypothesis,Glomerular hyperfiltration hypothesis,Renal tubular-renal interstitium hypothesis,Trade-off hypothesis,IV Pathogenesis,of CRF,69,Intact nephron hypothesis,causes,Progressive reduction in the number of nephrons,Destroy nephron persistently,Renal compensation insufficiency,Renal failure,Compensatory glomerular,hyperfiltration,Glomerulosclerosis,70,Renal tubular-,renal interstitium,hypothesis,Causes(Urine protein,cytokine,inflammatory factor,complement),renal tubular epithelial cellapoptosis,necrosis,Renal tubular atrophy,Renal tubular epithelial cell activated and proliferation,Renal function aggravate progressively,Trade-off hypothesis,Decreased GFR,Increased concentration of some solutes,Stimulate release of related regulatory factors(hormones),Increase the solutes excretion,(good),Further metabolic disorders,Aggravate the CRF,(bad),Decreased GFR,Increased serum concentration of phosphate,Stimulate release of parathormone(PTH)by parathyroid glands,Increase the phosphate excretion from kidneys,(good),Stimulate calcium release from bone,P ,Ca,2+,osteomalacia,(bad),Decreased phosphate excretion,Decreased serum ionized calcium,73,V Changes of Function and Metabolism,(I),characteristics of urine,：,1.volume,：,nocturia,polyuria,（,2000ml/d,）,oliguria oliguria(28.6mmol/L),CCR=,Ucr Vu,Pcr,III,acid-base and electrolyte disorders,1,Dehydration,(A)due to polyuria,nocturia.,The ability to dilute the urine is preserved with a reduced ability to concentrate the urine.,(B)Diarrhea,vomiting may quickly cause dehydration.,Dehydration will lead to hypovolemia,decreased GFR and further deterioration of renal function.,The water intake should be of sufficient quantity and frequency(day and night)to compensate for the polyuria.,2,Hypervolemia,General edema,Congestive heart failure.,Cause:,excess water intake,fixed urine volume(oliguria),3.Sodium imbalance,In normal persons sodium excretion may vary from nearly zero to more than 20g/day in response to a variable intake.,Patients with CRF lose the ability to regulate the sodium balance.,(A)Sodium deficiency and hyponatremia,Increased loss from kidneys:Osmotic diuresis,renal tubule fluid flow quicky(intact nephron),methylguanidine inhibit sodium reabsorption,Vomitting,diarrhoea,(B)Sodium excess,(which leads to edema,hypertension),Oliguria in terminal stage,Taking more,4.Potassium imbalance,(1)Normal serum K,+,:maintained until the stage of renal failure.(GFR=10%25%),Causes of normal serum K,+,(A)increased excretion from renal tubular and collecting duct(aldosterone secretion increase),(B)increased excretion from intestine.,(2),Hypokalemia,Causes,:A)polyuria in early stage,B)vomiting,C)diarrhea,D)restrict intake,(3)Hyperkalemia,Causes:A)oliguria in end-stage,B)acidosis,C)acute infection,82,5.,Ca P,：,P(1.6mmol/L)