12 renal failure_pti
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patholophysiology of Renal Failure Pathophysiology（病理生理学） Pathology uploaded by prabesh 杰诗
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12 renal failure_pti
- 1. Dept. of PathologyDept. of Pathology Medical CollegeMedical College Hunan Normal UniversityHunan Normal University (( 湖南 范大学医学院病理学教研室师湖南 范大学医学院病理学教研室师 )) 1 Chapter 12Chapter 12 Renal FailureRenal Failure （ 衰竭）肾脏（ 衰竭）肾脏
- 2. Outline 11 22 33 44 2 Introduction Acute Renal Failure Chronic Renal Failure Uremia
- 3. Section 1 Introduction 11 22 3 Normal Functions of Kidney Renal Failure
- 4. Structure of the Kidney Section 1 Introduction 5
- 5. Normal Functions of the Kidney Section 1 Introduction ♠Excretion Metabolic wastes, drugs, toxins ♠Regulation of Homeostassis Water and electrolytes, acid-base balance ♠Encocrine Renin, EPO, 1,25-(OH)2-Vit D3 (active form) 6
- 6. Section 1 Introduction ♠ The working unit of the kidney, 1 million of them per kidney. ♠ Made up of a Glomerulus and a tubule. ♠ Filters and cleans the blood. 9 The Nephron
- 7. 10 Urine Formation in the Kidney Section 1 Introduction
- 8. Section 1 Introduction Characteristics of the Renal function ♠ Strong compensatory ability ♠ Functional compensation and compensatory hypertrophy ♠ Self-regulation of renal blood flow 11
- 9. Section 1 Introduction Renal Failure ♠ Renal failure is a medical condition in which the kidneys fail to adequately filter waste products from the blood. ♠ Manifested as disturbance of water, electrolyte and acid-base as well as endocrine dysfunction. 12
- 10. Section 1 Introduction Classification of the Renal Failure Acute Renal Failure (The kidneys abruptly stop working) Chronic Renal Failure (The kidneys lose their functions gradually) Uremia 13
- 11. Outline 11 22 33 44 14 Introduction Acute Renal Failure Chronic Renal Failure Uremia
- 12. 1515 Acute Renal FailureAcute Renal Failure a.a. DefinitionDefinition b.b. Etiology and ClassificationEtiology and Classification c.c. PathogenesisPathogenesis d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
- 13. Section 2 Acute Renal Failure ♠ Acute Renal Failure (ARF) is a heterogeneous group of disorders, which is characterized by bilateral renal function, leading to the retention of waste products and metabolic and organ dysfunction. ♠ The central link is sharp decrease of glomerular filtration rate (GFR). Definition 16
- 14. 1717 Acute Renal FailureAcute Renal Failure a.a. DefinitionDefinition b.b. Etiology and ClassificationEtiology and Classification c.c. PathogenesisPathogenesis d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
- 15. Etiology and Classification Section 2 Acute Renal Failure a. Pre-renal ARF (55-60%) b. Intra-renal ARF (35-40%) c. Post-renal ARF (5%) 18 a. b. c.
- 16. Section 2 Acute Renal Failure Pre-renal ARF (Functional) ♠ RBF ↓→ renal perfusion ↓ → Kidney ischemia ♠ Prolonged ischemia → Intra-renal ARF ♠ Causes Hemorrhage or hypovolemic shock Impaired cardiac output Diuretic therapy 19
- 17. ♠ Resulting from urinary tract obstruction ♠ Caused by Enlarged prostate Inflammation Bladder tumor Bilateral urethral stones etc… Section 2 Acute Renal Failure Post-renal ARF 20
- 18. 21 Urinary obstruction Net Filtration P↓ RBF ↓ Capsule P ↑ Interstitial P ↑ GFR↓ Oliguria Post-renal ARF Vessel constriction Section 2 Acute Renal Failure
- 19. ♠ Resulting from the injury to the kidneys directly. ♠ Acute tubular necrosis (ATN) is the most common cause, accounting for about 75-80% of ARF. ♠ Associated with 50% of ARF deaths. Section 2 Acute Renal Failure Intra-renal ARF (Parencymal) 22
- 20. ♠ Ischemia-reperfusion injury of the Kidney ♠ Nephrotoxic substances ♠ Exogenous poisons Antibiotics (Gentamycin), chemotherapy drugs, bacterial toxin, immunosuppressants, etc. ♠ Endogenous poisons Myohemoglobin (Rhabdomyolysis), hemoglobin, uric acid, etc. Section 2 Acute Renal Failure Etiology of acute tubular necrosis (ATN) 23
- 21. Section 2 Acute Renal Failure Index Pre-renal ARF Intra-renal ARF Specific gravity >1.020 <1.015 Osmotic pressure (mOsm/L) >500 <350 Sodium (mmol/L) <20 >40 Urine Cr/Serum Cr ratio >40:1 <20:1 Protein (-) (++) Urinary sediment Normal Urinary casts Cell debris Mannitol Diuresis Effective Ineffective Table 1 Comparison of the urine characteristics between pre- renal and intra-renal ARF 25
- 22. 26 Urinary Casts
- 23. 2828 Acute Renal FailureAcute Renal Failure a.a. DefinitionDefinition b.b. Etiology and ClassificationEtiology and Classification c.c. PathogenesisPathogenesis d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
- 24. ♠ The decrease of Glomerular Filtration Rate (GFR) is the central link. Section 2 Acute Renal Failure Pathogenesis of ARF 29 Causes → GFR ↓↓↓→ Dysfunction of the urinary function (Oliguria or Anuria)
- 25. Section 2 Acute Renal Failure Pathogenesis of ARF ♠ Abnormal renal hemodynamics ♠ Injury of the renal tubules ♠ Injury of the filtration membrane 30
- 26. ♠ Abrupt decrease of renal blood flow ♠ Decrease of the renal perfusion pressure ♠ Constriction of the renal vessel ♠ Obstruction of the renal vessel ♠ Redistribution of renal blood flow ♠ Ischemia of renal cortex ♠ Hyperemia of renal medulla Section 2 Acute Renal Failure Abnormal Renal Hemodynamics 31
- 27. Section 2 Acute Renal Failure Decrease of the renal perfusion pressure 20 80 180 Blood pressure （ mmHg) 32
- 28. Section 2 Acute Renal Failure ♠ Activation of sympathetic-adrenal medulla system 33 ♠ Activation of renin-angiotensin system(RAS) ♠ Imbalanced production of endothelin and nitric oxide (NO) Constriction of the renal vessel
- 29. Section 2 Acute Renal Failure 35 Blood viscosity ↑Blood viscosity ↑ Microthrombosis DIC Microthrombosis DIC Renal ischemia or poisons Renal ischemia or poisons Impairment of renal vascular endothelium Impairment of renal vascular endothelium Synthesis of ATP ↓Synthesis of ATP ↓ Endothelium SwellingEndothelium SwellingRenal vessel obstruction Renal vessel obstruction Sodium pump dysfunctionSodium pump dysfunction ♠ Usually occurring in sepsis, shock, severe burn. Obstruction of the renal vessel
- 30. ♠ Abrupt decrease of renal blood flow ♠ Decrease of the renal perfusion pressure ♠ Constriction of the renal vessel ♠ Obstruction of the renal vessel ♠ Redistribution of renal blood flow ♠ Ischemia of renal cortex ♠ Hyperemia of renal medulla Section 2 Acute Renal Failure Abnormal Renal Hemodynamics 36
- 31. ♠ Normally ♠ Cortical nephrons: 85% ♠ Medullary nephrons: 15% ♠ More blood goes to medulla → Ischemia of renal cortex Section 2 Acute Renal Failure 37 Redistribution of renal blood flow
- 32. Section 2 Acute Renal Failure Pathogenesis of ARF ♠ Abnormal renal hemodynamics ♠ Injury of the renal tubules ♠ Injury of the filtration membrane 38
- 33. ♠ Synthesis of ATP ↓ → Activity of sodium pump ↓ ♠ Oxygen free radicals ↑ ♠ Phospholipase activity ↑ - Structure of cell membrane destroyed ♠ Apoptosis (or necrosis) of renal tubular epithelial cells Section 2 Acute Renal Failure 39 Acute tubular injury
- 34. Section 2 Acute Renal Failure Pathogenesis of ARF ♠ Abnormal renal hemodynamics ♠ Injury of the renal tubules ♠ Injury of the filtration membrane 42
- 35. Section 2 Acute Renal Failure 43 Injury of the glomerular filtration membrane
- 36. Section 2 Acute Renal Failure 44 Renal Ischemia or Poisons Abnormal Renal hemodynamics Renal tubule injury Decrease of renal blood flow Ischemia of renal cortex Injury of the glomerular filtration membrane GFR↓ Oliguria or Anuria Redistribution of renal blood flow Renal tubule obstruction
- 37. 4545 Acute Renal FailureAcute Renal Failure a.a. DefinitionDefinition b.b. Etiology and ClassificationEtiology and Classification c.c. PathogenesisPathogenesis d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
- 38. • Alterations of function and metabolism Section 2 Acute Renal Failure 46 ♠Oliguric ARF ♠Non-oliguric ARF Types of ARF
- 39. Section 2 Acute Renal Failure 47 a. Oliguric stage b. Diuretic stage c. Recovery stage Three Stages of Oliguric ARFThree Stages of Oliguric ARF
- 40. Section 2 Acute Renal Failure 48 (1) Edema and/or water intoxication GFR ↓GFR ↓ ADH ↑ADH ↑ Water retentionWater retention Dilutional hyponatremia, edema, and heart dysfunction, etc. Dilutional hyponatremia, edema, and heart dysfunction, etc. Oliguric stage Water excretion ↓Water excretion ↓
- 41. ♠ Most dangerous syptom, main cause of death Section 2 Acute Renal Failure 49 (2) Hyperkalemia HyperkalemiaHyperkalemia Oliguria anuria Oliguria anuria Potassium excretion ↓ Potassium excretion ↓ Tissue injury Catabolism↑ Tissue injury Catabolism↑ Release of Potassium from cells ↑ Release of Potassium from cells ↑ Metabolic acidosis Metabolic acidosis Arrhythmia, sudden death. Oliguric stage
- 42. Section 2 Acute Renal Failure 50 (3) Metabolic acidosis Metabolic acidosis Metabolic acidosis Inhibition of cardiovascular system and CNS, drowsiness, coma, etc. Reabsorption of NaHCO3 ↓ Reabsorption of NaHCO3 ↓ Oliguric stage
- 43. ↑ urea, creatinine, and uric acid nitrogen Section 2 Acute Renal Failure 51 (4) Azotemia AzotemiaAzotemia Azotemia: Too much nitrogen in plasma Oliguric stage
- 44. ♠ Oliguria (urine volume <400 ml/d) ♠ Anuria (urine volume <100 ml/d) ♠ Lasts for 7-14 days ♠ Cellular casts and/or granular casts Section 2 Acute Renal Failure 52 Oliguric stage Urinary abnormalities
- 45. ♠ Urine volume >400 ml/d → 3000-5000 ml/d after 5-7 days. ♠ Caused by: ♠ Recovery of renal blood flow and glomerular filtration function ♠ Removal of renal tubule obstruction ♠ Osmotic diuresis (accumulation of urea during Oliguric stage) ♠ Water-electrolyte disturbance: excess loss of water and sodium, hypokalemia, etc. ♠ Lasts for about 2 weeks. Section 2 Acute Renal Failure 53 Diuretic stage
- 46. ♠ The volume and component of urine return to normal, water-electrolyte balance is restored. ♠ Lasts for 6 months – 1 year. ♠ Characterized by healing of tubular epithelial cells. ♠ A few cases will develop into Chronic Renal Failure (CRF). Section 2 Acute Renal Failure 54 Recovery stage
- 47. • Alterations of function and metabolism Section 2 Acute Renal Failure 55 ♠Oliguric ARF ♠Non-oliguric ARF Types of ARF
- 48. ♠ Caused by renal tubule reabsorption dysfunction (GFR is normal or mildly decreased) ♠ Characteristics ─ Normal or mildly increased urine volume ─ Progressive azotemia ─ Shorter course of disease, less complications, better prognosis ─ May develop into oliguric ARF (more severe and worse prognosis) Section 2 Acute Renal Failure 56 Non-oliguric ARFNon-oliguric ARF
- 49. Non-oliguretic type of ARF Possible mechanisms: • Unable to form high osmosis in medulla • Weak tubuloglomerular feedback • Dysfunction of tubules has precedence over decreased GFR 57 Section 2 Acute Renal Failure
- 50. 5858 Acute Renal FailureAcute Renal Failure a.a. DefinitionDefinition b.b. Etiology and ClassificationEtiology and Classification c.c. PathogenesisPathogenesis d.d. Alterations of Metabolism andAlterations of Metabolism and FunctionFunction e.e. Pathophysiological Basis ofPathophysiological Basis of Prevention and TreatmentPrevention and Treatment
- 51. Section 2 Acute Renal Failure 59 Principles of prevention and treatment ♠ Prevention – Primary disease and risk factors control – Diuresis ♠ Treatment – Hyperkalemia – Water intoxication – Metabolic acidosis – Azotemia – Inflammation – Nutritional support – Blood purification therapy Death Triad of ARF
- 52. 60 Blood Purification Therapy - Dialysis
Editor's Notes
- www.3lian.com
- Only 0.5 million is required for normal function. Filters and cleans the blood, discards excess water and wastes. Keeps the body in balance (Homeostasis).
- Caused by inadequate blood flow to the kidney, renal and systemic diseases and disorders related to the urinary tract obstruction. Failed to excrete the metabolites and other toxic wastes adequately.
- www.3lian.com
- These disorders are named as pathologic processes.
- RBF = Renal blood flow
- Obstruction from renal calyx to urethral meatus. May be recovered after the obstruction is relieved, but also may result in renal atrophy under continuous obstruction.
- Rather than indirectly as a secondary consequence of inadequate perfusion or urinary tract obstruction.
- Pre-renal: Functional; Intra-renal: Parenchymal. Cr (creatinine): 肌酐 Mannitol: 甘露醇 Cast: 管型
- Normal GRF: 125 ml/min (or 180 L/day).
- OFR increases as the result of increased production (impaired endothelium) and decreased clearance (decreased GSH).
- OFR increases as the result of increased production (impaired endothelium) and decreased clearance (decreased GSH).
- Water intoxication will cause Dilutional hyponatremia, edema (systemic, pulmonary, brain), and heart dysfunction, etc.
- Potassium excretion ↓ is because of ↓ in distal tubular K+-Na+ exchange. Another reason may be that transfusion of stored blood.
- &lt;400 ml/d or &lt;17 ml/h Normal plasma osmotic pressure 280-310. Granular casts[edit] The second-most common type of cast, granular casts can result either from the breakdown of cellular casts or the inclusion of aggregates of plasma proteins (e.g., albumin) or immunoglobulin light chains. Depending on the size of inclusions, they can be classified as fine or coarse, though the distinction has no diagnostic significance.
- The reabsorption and acidification of urine by renal tubule are still unrecovered in the early stage.
- Infusion: 量入为出。