肾功能衰竭课件_8

Renal Failure 1 Section I . Introduction 2 But also regulate a variety of material in plasma to maintain the homeostasis of internal environment (osmolality and acid-base balance) Kidneys are the principal excretive organs Not only excrete waste metabolic products to remove various harmful substances, Besides, kidneys also produce some bioactive substances renin, prostaglandins (regulation of blood pressure) erythropoietin (formation of matured RBCs) active vitamin D (metabolism of calcium and phosphorus) 3 But also regulate a variety of material in plasma to maintain the homeostasis of internal environment (osmolality and acid-base balance) Kidneys are the principal excretive organs Not only excrete waste metabolic products to remove various harmful substances, Besides, kidneys also produce some bioactive substances renin, prostaglandins (regulation of blood pressure) erythropoietin (formation of matured RBCs) active vitamin D (metabolism of calcium and phosphorus) 4 The following pathologic process is termed renal failure: Glomerular filteration rate Retention of metabolic wastes, Disturbanc of internal environment Uremia Renal Failure Acute renal failure (ARF) (CRF) Cronic renal failure a serial of clinical manifestations Various causes Severely impair renal function 5 1. Causes of renal dysfunction (1) Primary renal disease (2) Renal injury secondary to systemic diseases. 6 1. Causes of renal dysfunction (1) Primary renal disease (2) Renal injury secondary to systemic diseases. 1) Glomerular disease 2) Renal tubular disease 3) Interstitial nephritis 4) Others: glomerulonephritis; nephrotic syndrome renal glucosuria; aminoaciduria, renal tubular acidosis acute or chronic interstitial inflammation renal injury, tumor, calculus; obstructive nephropathy; vascular nephropathy 7 1. Causes of renal dysfunction (1) Primary renal disease (2) Renal injury secondary to systemic diseases . 1) Circulatory system diseases: 2) Auto-immune and connective tissue diseases: 3) Metabolic diseases: 4) Hematological diseases: 5) Others: Shock, AS, thrombosis, etc. Lupus nephritis, renal injury by rheumatoid arthritis, etc Nephropathy caused by amyloidosis, diabeti c or hyperuricemia Renal injury by plasmacyte disease, multiple myeloma or leukemia Heart failure, hepatic disease, endocrine disease and malignant tumors 8 The anatomic and functional unit of kidney is nephron, which consists of glomerulus and renal tubule. Each human kidney has approximately 1 million nephrons. The glomerular function is to form original urine by filtration, while the tubule perform reabsorption and secretion. The basic presentation of RF include: 2. The basic manifestation of RF (l) Dysfunction of glomerule (2) Dysfunction of renal tubules (3) Dysfunction of renal endocrine 9 Renal blood flow Effective filtration pressure of the glomerule Kf (LPA, permeability and total filtration area) 125ml/min 180L/day 1.5L/day 99% 20% of CI Abnormality of urinary quality Alteration of urinary quantity (l) Dysfunction of glomerule Permeability (of glomerular filtration membrane) GFR (hematuria PTH: parathyroid hormone) 180L/d 99% 1.5L/d 11 Dysfunction of reabsorption Proximal convoluted tubule: glucosuria, phosphuria, aminoaciduria, Na+ and H2O retention, renal tubular acidosis Acid-base Disturbances Proximal tubule (secrete H+, NH4+, NH3 ; reabsorb HCO3); Medullary loop (reabsorb b HCO3 and NH3) Distal tubule (secrete H+) Dysfunction of concentration and dilution Henles (medullary) loop and collecting tubule: polyuria, Isosthenuria (isotonic), Hyposthenuria (hypotonic) 2) Types of renal tubular dysfunction 12 Renal Hypertension (3) Dysfunction of renal endocrine Increased secretion of rennin Renin Increased secretion of endothelin ET Declined Kallikrein-kinin system (KKS) Kinin Inadequate synthesis of prostaglandins from arachidonic acid PGE2 , I2 13 EPO HCI 1,25-(OH)2- D3 PTH Renal aneamia Ulceration Renal osteodystrophy Decreased eryhropoietin Decreased 1-a-hydroxylase Weakened inactivation to PTH Weakened inactivation to gastrin (90% formed in kidney) 14 Section 2. Acute Renal Failure 15 Oliguria or anuria Retention of nitrogenous wastes (azotemia) water/electrolyte acid-base disturbance Rapidly and severely decline of GFR Kidneys fail to excretion and regulation in hours to days Various causes Oliguria is usually emphasized in the past, but in some cases, patients have high level BUN (azotemia) while urine volume does not change. It is called non-oliguria ARF 16 l. Causes and classification Acute renal failure (ARF) may result from a wide variety of diseases (shock, heart failure, severe infection, hepatic diseases), trauma, surgical procedures, drugs, renal toxins and urinary tract obstruction. According to causes, ARF may be divided into three main categories: Prerenal Intrarenal acute renal failure Postrenal 17 caused by any disorder external to the kidneys that rapidly and severely decreases the blood supply to the nephron. caused by disease of the renal tissue itself, affecting the blood vessels, glomeruli or tubules. caused by obstructive disorders (uretal or urethral) that can block or partially block urine flow, while the kidneys blood supply and other functions are initially normal. ( l ) Prerenal failure (functional RF or prerenal azotemia) (2) Intrarenal failure (parenchymal RF) (3) Postrenal failure (Obstructive RF, Postrenal azotemia) 18 Sudden decrease of renal perfusion Hypovolemia, Acute heart failure Expanded vascular bed volume (Hepatorenal syndrome Anaphylactic shock, etc. ) Renal vascular blockage or auto-regulation disturbances ( l ) Prerenal failure Azotemia(urinary Cr/plasma Cr 40 ) Oliguna ( 1.020 No RBC, WBC or cast in urine GFR Na+, H2O reabsorption 19 (2) Intrarenal failure Causes: intrinsic (parenchymal) renal diseases 1. Renal tubular diseases 2. Glomerular diseases 3. Renal interstitial diseases 4. Renal blood vessel diseases Acute Tubular Necrosis (most common) Acute renal ischemia Acute renal poisoning Renal tubule blocked by Hb or Mb Glomerulonephritis, pye1onephritis, etc Severe infection, drug allergy, etc Thrombosis, DIC, etc 20 Clinical features: 1. Oliguria or Non-oliguria 2. Isothenuria the specific gravity of urine become fixed at 1.010 or 0.285 mOsm / L (equal to the osmotic concentration of plasma), implying an inability of the kidney to concentration or dilute the urine. 3. Urinary Na+ 40mmo l/L (ability to reabsorb Na + ) 4. Hematuria. 5. Azotemia(urinary Cr/plasma Cr l .020 500 mmol / L 40 mmol / L Urine Cr / Plasma Cr 40 2 FENa 2 Urinary sediment Normal Proteins, cells, casts 36 2) Diuresis phase If the patient pass through the oliguria phase safely, the tubular EC may regenerate and the renal function would recover gradually. An increasing urine volume is a signal of renal EC healing, and suggests the start-up of diuresis phase if it is more than 400 ml per day. After then, the urine volume increasing doubly up to 3-5L/day and may last about one month. 37 The mechanisms for diuresis including: a) The RBF metabolic acidosis; water intoxication (2) How to differentiate the functional and parenchymal ARF INDEXES F - ARF P - ARF Urine specific gravity Urine Na+ Urine Cr / Plasma Cr Urinary sediment Todays question Normal Proteins, cells, casts 40 40 mmol / L l .020 50 28.6 707 BCr = blood level of creatinine 52 Decompensatory stage Compensatory stage Renal failure stage Uremic stage Clinical manifestation Asymptomatic % of normal clearance rate of Cr Clinical Asymptomatic CCr GFR BUN BCr (%) (ml/min) (mmol/L) (umol/L) 30 50 28.6 707 Uremic Stage (4) 56 2. Pathogenesis Despite primary causes, the pathogenesis of CRF is a process in which the nephrons to be damaged continually the renal function to be declined progressively until failed. The degree of renal dysfunction depends on the number of intact nephron The remnant nephrons (so called intact nephrons) are compensatory hypertrophy, but their number decreasing day by day and finally become decompensatory. 57 Injuries basement membrane permeability Mesangial cells overload and damaged Proteinuria Mesangial cells proliferation and increased Cast formation production of extracellular matrix Tubule blocked Glomerulosclerosis There are two principal types of nephron injury: (1) Glomerulosclerosis (2) Tubulointerstitial injury 1) Alteration of glomerular basement membrane permeability 2) Hemodynamic alterations of intact nephrone 2) Hemodynamic alterations of intact nephrone 58 There are two principal types of nephron injury: (1) Glomerulosclerosis (2) Tubulointerstitial injury The number of nephron decreasing day by day glomerular hyperfiltration further glomerular injury pressure and flow in glomerular capillary of remnant nephron 1) Alteration of glomerular basement membrane permeability 2) Hemodynamic alterations of intact nephrone 59 There are two principal types of nephron injury: (1) Glomerulosclerosis (2) Tubulointerstitial injury Compensatory hypertrophy in remnant nephron metabolism oxygen consumption free radical production Tubulointerstitial injury 60 There are two principal types of nephron injury: (1) Glomerulosclerosis (2) Tubulointerstitial injury Compensatory hypertrophy in remnant nephron metabolism oxygen consumption free radical production Tubulointerstitial injury Inflammatory response fibrin deposition in tubules and surrounding interstitium 61 There are two principal types of nephron injury: (1) Glomerulosclerosis (2) Tubulointerstitial injury Loss of some nephrons leads to compensatory hyperfunction of others, increasing their vulnerability to damage and going to a vicious cyclethe nephrons to be continuously lost and the GFR progressively decreased until the renal function failed. 62 3. Alteration of function and metabolism (1) Disturbance of water, electrolyte and acid-base balance (2) Azotemia (3) Renal hypertension (4) Hematologic disorders 1) Renal anemia; 2) Tendency of bleeding (5) Renal Osteodystrophy 63 (1)Disturbance of water, electrolyte and acid-base balance l) Water disturbance Alteration of urine volume Changes in urine osmotic pressure 2) Electrolyte disturbance Natrium; Potassium; Calcium Hyperosmolarity diuretic effect; Decreased ability of urine concentration caused by destruction of osmolar gradient in medulla. c) Oliguria (30ml/min): P remain normal Inhibiting reabsorption of phosphorus by tubule phosphorus release from bone 20 5 15 L 100 10 40 70 3030 NE 68 b) Hypocalcemia Ingestion and absorption of Ca2+ inadequacy PCato maintain CaP constant phosphorus excreting through intestine interfering absorption of Ca2+ 1-hydroxylase 1,25-(OH)2-D3 intestinal absorption of Ca2+ Inactivation PTH 69 3) Metabolic acidosis when GFR 28.6 mmol/L (40 mg/dl). Urea, creatinine, uric acid 1) Blood urea nitrogen (BUN): BUN is not a ideal index for renal function: It is just increasing if the decrease of GFR more than 50%. It may influenced by exogenous urea (protein intake) or endogenous urea (infection, alimentary tract bleeding) 71 2) Creatinine (Cr): Cr is end-product of creatine and phosphocreatine metabolism. Although Cr is rarely influenced by protein intake, it is also not sensitive during early stage of CRF. However, the clearance rate of Cr (CCr ) is closely related to GFR, as it can be filtrated through glomerulus freely but can not be reabsorbed by tubule, and only small amount may be secreted by proximal tubule. CCr = UV/ P (U = urinary level of Cr, V = urine volume per min, P= plasma level of Cr) 72 (3) Renal hypertension 1) Sodium and H2O retention (sodium-dependent hypertension) 2) Increased activity of renin-angiotensin system (renin-dependent hypertension) 3) Decreased anti-hypertension agents secreted by kidney (Kallikrein-kinin system and PG system) 73 1) Sodium and H2O retention (sodium-dependent hypertension) 2) Increased activity of renin-angiotensin system (renin-dependent hypertension) 3) Decreased anti-hypertension agents secreted by kidney (Kallikrein-kinin system and PG system) Ability of excreting Na+, H2O Na+, H2O retention blood volume cardiac output hypertension more sensitive of blood wall vasoconstriction (3) Renal hypertension 74 (3) Renal hypertension 1) Sodium and H2O retention (sodium-dependent hypertension) 2) Increased activity of renin-angiotensin system (renin-dependent hypertension) 3) Decreased anti-hypertension agents secreted by kidney (Kallikrein-kinin system and PG system) Disorder of renal circulation hypoxia activating RAA AII vasoconstriction peripheral resistance Aldosterone Na+, H2O retention hypertension 75 (3) Renal hypertension 1) Sodium and H2O retention (sodium-dependent hypertension) 2) Increased activity of renin-angiotensin system (renin-dependent hypertension) 3) Decreased anti-hypertension agents secreted by kidney (Kallikrein-kinin system and PG system) Renal dysfunction Renal hypertension (vicious circle) 76 (4) Hematologic disorders 1) Renal anemia (97%) Decreased production of RBC Synthesis of erythropoietin; Deficiency of hematopoietic material (iron, folic acid) RBC-inhibiting factors inhibit RBC production; Aluminium toxication (inhibiting synthesis of hematin, interfering iron transfer and stem cells proliferation) Increased destroy or loss of RBC Hemolysis, Hypersplenism Bleeding (Toxic substances: Guanidines, Amines, Phenols, PTH, Al, etc.) 77 2) Tendency of bleeding (17-20%) The main cause is the abnormality of platelet quality rather than its quantity. Uremia CRF Uremic toxins TXA2 ,PGI2 (guanidines, phenol) Vasopressin receptor Platele dysfunction Decreased adherence, aggregative function and release of PF3 78 (5) Renal Osteodystrophy (renal osteopathy) 1) Disorder of Vitamin D metabolism 2) Disorder of Calcium and phosphorus metabolism and secondly hyperparathyroidism 3) Aluminium accumulation 4) Acidosis 79 Renal osteodystrophy Chronic RF (dysfunction of excretion and endocrine of kidney) Excretion of P Aluminium accumulation absorption of Ca2+ Secondly hyperparathyroid PTH hypocalcemia Hyperphosphatemia Ca2+ in bone bone lysis Acidosis 1,25-(OH)2-D3 Calcification of bone 80 Section 4. Uremia 81 Uremia Retention of metabolic end-product and endogenous toxin Disturbance of water/electrolyte and acid-base balance Disorder of endocrine function End-Stage of ARF or CRF a series of auto-toxic symptoms 82 1. Pathogenesis (1) Uremic toxin: (more than 100) (2) PTH (3) Aluminium 83 (1) Uremic toxin: (more than 100) Urea; Guanidines; Amine and phenol； Middle molecular weight toxins 1) Urea -principal end product of protein metabolism May lead to headache, Anorexia, nausea, vomiting, glucose tolerance bleeding 84 2) Guanidines second abundant nitrogenous matter The only confirmed pathway for guanidines synthesis is: Both with strong toxicity May induce almost symptoms of uremia. Methyl guanidine Guanidino succinic acid (Normal pathway)(RF) Guanidino acetic acid Excretion Arginine Creatinine 85 3) Amine and phenol Produced by enteric germs, mainly toxic to nerve system 4) Middle molecular weight toxins (500-5000 Dalton) Can removed by peritoneal dialysis but not hemodialysis May lead to peripheral or central nerve disorder, RBC and platelet injury, cellular immune and endocrine dysfunction, etc. 86 1) Mechanism: hypocalcemia stimulating thyroid proliferation secondly hyperparathyroidism PTH decreased elimination and degradation of PTH by kidney (2) PTH 87 2) Toxicity of PTH: Inducing renal osteodystrophy Neural toxicity (decreasing neural transmission) Anemia and bleeding (inhibiting RBC production and Platelet aggregation) Infection (inhibiting WBC migrating, phagocytosis and Ab production) Myocardium injury, vasodilation and B.P. Soft tissue necrosis Increasing protein catabolism nitrogenous substances Increasing serum cholesterol and triglyceride 88 2) Toxicity Inhibiting enzymes, toxicity to cell nuclear May induce dialytic encephalopathy, osteomalacia and small-cell anemia. (3) Aluminium 1) Mechanism: 95% of Al combined with transferrin in plasma, thus difficult to remove by dialysis 89 2. Functional and metabolic alterations System Altered function Manifestation Nerve system Increase in metabolic Uremic encephalopathy products (urea, guanidine) Peripheral neuropathy Cardiavascular Activation RAS Hypertension; system Excess ECF Congestive heart failure Elevated BUN Uremic pericarditis Respiratory Acidosis Kussmauls respiration system Heart failure, Na+/H2O retention Pulmonary edema Hypoalbuminemia Urea stimulation Uremic pleuritis 90 System Altered function Manifestation Digestive Urea ammonia Anorexia, nausea, system Vomiting, diarrhea gastrin HCl Ulceration Endocrine Ability of hormone Disorder of endocrine system secretion or elimination Sexual function impaired Skin Ca2+, urea deposition Itch, urea cream Immune Impaired cellular immunity Infection Metabolism Glucose tolerance Hypoproteinemia Hypertriglyceridemia 91 (1) Preventi