Renal Insufficiency

1. Renal Insufficiency

2. “To be a great champion you must believe you are the best. If you’re not, pretend you are….!”– Muhammad Ali

3. TOPICS • Introduction • Acute renal failure • Chronic renal failure • Uremia

4. Functions of kidney The kidneys are a pair of small organs that lie on either side of your spine at about waist level. They act as filters that keep your blood free of by-products and toxins. • The kidneys excrete these compounds with water to make urine. • They also eliminate excess body water while selectively reabsorbing useful chemicals and allowing waste to pass freely into the bladder as urine. • They allow you to continue to consume a variety of foods, drugs, vitamins and supplements, additives, and excess fluids without worry that toxic by-products will build up to harmful levels.

5. The kidneys play an essential role in maintaining electrolyte and acid-base balance. • They produce some hormones including renin, prostaglandins, erythropoietin, and active vitamin D. • So, they are crucial in the regulation of blood pressure, formation of matured red blood cells, and metabolism of calcium and phosphorus.

6. Functions of the Kidney • Waste excretion • Electrolyte balance • Fluid balance • pH • Osmolality • Hormone production

7. Anatomy of Kidney

9. Manifestation of renal dysfunction • Glomerulus · decreasedGFR · glomerular filtration membrane permeability alteration • Renal tubule · concentrative function decline (hyposthennuria/isosthennuria) · water, electrolyte, acid-base disorder · others • Endocrine disorder · hypertension · anemia · renal osteodystrophy · others

10. 体内VitD3的代谢过程 紫外线 25-羟化酶 1α-羟化酶 7-脱氢胆固醇 VitD3 25-(OH)VitD3 1,25-(OH) 2VitD3 （皮肤） （肝微粒体） （肾线粒体）

11. Acute Renal Failure, ARF

12. Definition • Etiology & classification Prerenal failure Intrinsic renal failure Post(obstructive) renal failure • Pathogenesis • Clinical manifestation • Therapy

13. 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 accompany-ing accumulation of nitrogenous wastes in the body.

14. 急性肾功能衰竭的定义 急性肾功能衰竭（acute renal failure，ARF）是指各种病因引起双侧肾脏在短期内泌尿功能急剧降低，导致机体内环境出现严重紊乱的病理过程和临床综合症。 肾泌尿功能障碍表现为GFR迅速下降，出现少尿无尿；内环境紊乱主要表现为氮质血症、高钾血症和代谢性酸中毒。 急性肾功能衰竭根据尿量减少与否，分为少尿型（成人每日尿量少于400ml）和非少尿型（成人每日尿量大于400ml）两种类型。急性肾衰病情凶险，临床较常见，但若及时诊治，预后较好。

15. Etiology • Pre-renal (~70% of cases) resulting from impaired blood flow to or oxygenation of the kidneys. • Intrinsic-renal (~25% of cases) resulting from injury to or malformation of kidney tissues. • Post-renal (<5% of cases) resulting from obstruction of urinary flow between the kidney and urinary meatus.

16. Causes • Prerenal failure - Diseases that compromise renal perfusion • Decreased effective arterial blood volume - Hypovolemia, CHF, liver failure, sepsis • Renal arterial disease - Renal arterial stenosis (atherosclerotic, fibromuscular dysplasia), embolic disease (septic, cholesterol)

17. 肾前性急性肾功能衰竭的发生机制 肾前性因素 休克的原因（失血、失液、感染、急性心衰、 严重过敏反应）和其它（肝肾综合征） ADH有效循环血量Ald 血压降低 肾灌流压 肾血管收缩 肾血流量 肾小球有效滤过压 GFR 尿量

18. Intrinsic renal failure - Diseases of the renal parenchyma, specifically involving the renal tubules, glomeruli, interstitium • ATN, ischemia, toxins (eg, aminoglycosides, radiocontrast, heme pigments, cisplatin, myeloma light chains, ethylene glycol) • Interstitial diseases - Acute interstitial nephritis, drug reactions, autoimmune diseases (eg, systemic lupus erythematosus [SLE]), infiltrative disease (sarcoidosis, lymphoma), infectious agents (Legionnaire disease, hantavirus) • Acute glomerulonephritis • Vascular diseases - Hypertensive crisis, polyarteritis nodosa, vasculitis

19. Postrenal failure - Diseases causing urinary obstruction from the level of the renal tubules to the urethra • Tubular obstruction from crystals (eg, uric acid, calcium oxalate, acyclovir, sulfonamide, methotrexate, myeloma light chains) • Ureteral obstruction - Retroperitoneal tumor, retroperitoneal fibrosis (methysergide, propranolol, hydralazine), urolithiasis, papillary necrosis • Urethral obstruction - Benign prostatic hypertrophy; prostate, cervical, bladder, colorectal carcinoma; bladder hematoma; bladder stone; obstructed Foley catheter; neurogenic bladder.

20. Causes of ARF in tertiary care hospital setting

21. 急性肾功能衰竭病因与分类 • 肾前性ARF （早期为功能性ARF） 有效循环血量减少引起肾血流量急剧减少是肾前性ARF发生的关键因素 。 • 肾性ARF（亦称器质性ARF） 由肾脏实质病变引起。急性肾小管坏死（acute tubular necrosis，ATN）是临床上最常见、最重要的ARF类型，约占ARF的75%～80% 。 • 肾后性ARF 因双侧性尿路梗阻引起，如尿路结石、肿瘤、前列腺疾患等。

22. Pathogenesis of ARF • Decreased renal blood flow Renal hypoperfusion Vasoconstriction Vascular obstruction • Redistribution of renal blood flow I. Renal hemodynamics factors

23. II. Nephronal factors • Tubule injury Tubule obstruction Passive backflow

24. Acute Renal Failure, IntrinsicAcute Tubular Necrosis • Renal hypoperfusion/ischemia • Nephrotoxic agents (both endogenous and exogenous) • Mortality 50% • Bronchopulmonary infections, sepsis, cardiovascular disease, bleeding disorders • Complete Recovery 25%, Incomplete 20%, No Recovery 5%

25. Acute Tubular NecrosisNephrotoxic Agents • Exogenous • Antibiotics • Contrast • Diuretics • Chemotherapeutics • Analgesics • Solvents, metals, chemicals • HIV meds • Antiulcer meds • Anesthetics • Endogenous • Pigment nephropathy • Crystal deposition • Tumor-specific syndromes

26. Acute Tubular Necrosis Cell Hypoxia Depletion of ATP Hypoxanthine Impaired function Of plasma membranes And ATPases Ca++ imbalance Na-K imbalance Cell Swelling Disrupt cytoskeleton Activate phospholipases Formation of xanthine oxidase Uncoupling of oxidative phosphorylation Disrupt lipid bilayer Reperfusion injury Free radicals

27. Acute Tubular Necrosis • Leads to… • Loss of cell polarity • Brush border loss • Impaired cell-cell adhesion • Impaired tight junction • End results… • Impaired solute and water transport • Sloughing of tubule cells  obstruction • Back leakage of filtrate

28. 急性肾功能衰竭的发病机制 急性肾衰发病机制的中心环节是GFR的降低。 一 肾血流动力学异常 • 肾血流急剧减少 肾灌注压下降肾血管收缩肾血管阻塞 • 肾内血流重分布 二 肾小管损伤 • 肾小管阻塞 • 原尿返流 三 肾小球超滤系数降低

29. Characteristics & clinical courses • Oliguric phase • Diuretic phase • Recovery phase

30. Oliguric phase Usually lasting for 1 to 6 weeks,the average duration is between 7 & 10 days. • Features of urine: I. Oliguria or Anuria II. Hematuria and casts III. Low specific gravity and osmolality IV. Urinary [Na+] above 20mM • Azotemia • Metabolic acidosis • Hyperkalemia • Hypervolemia / Hypertension • Others: edema, water intoxication，tachypnea

31. Urinary Indices in ARF

32. 功能性肾衰和器质性肾衰（ATN）的鉴别 功能性肾衰器质性肾衰 尿液性质 尿比重 尿渗透压 尿钠 尿肌酐/血肌酐 尿常规 治疗与反应 >1.020 <1.015 >500mOsm/L <400mOsm/L <20mmol/L >40mmol/L >40 <20 正常 蛋白尿、管型、红细胞、白细胞 应迅速补充血容量 需严格控制补液量 使肾血流恢复，GFR 量出而入 补液后 尿量迅速增多 尿量持续减少 病情明显好转 甚至使病情恶化

33. Muddy Brown Cast

34. Red Cell Cast

35. White Cell Casts

36. Diuretic phase As healing begins, improvement is reflected in the production of more than 400 ml of urine per day. • Fluid and electrolyte abnormalities. • Cr may still rise for 1-2 more days. Recovery phase

37. ARF的主要机能代谢变化和临床表现 一 少尿期 1.少尿、无尿 2.氮质血症：指肾功能衰竭时，由于GFR下降，含氮的代谢产物如尿素、肌酐、尿酸等在体内蓄积，引起血中非蛋白氮的含量增加（＞28.6mmol/L，或＞40mg/dl）。 3.水中毒：当肾排水功能障碍的情况下，一旦水摄入稍多，就易造成稀释性低钠血症，大量水份进入细胞内，引起脑水肿、肺水肿、心力衰竭。因此对少尿期ARF患者，要严格控制摄入水量。 4.高血钾：主要由GFR降低和肾小管泌钾障碍引起，机体代谢分解增强使钾释放增多及酸中毒引起细胞内钾向细胞外转移，都能促使血钾进一步增高。严重高血钾可导致室颤和心跳骤停。高钾血症是ARF患者第一周死亡的最常见原因。 5.代谢性酸中毒：主要由GFR降低、肾小管排酸保碱作用减退、体内分解代谢加强使固定酸产生过多等原因引起。

38. 二 多尿期 经过少尿期后，当每天尿量大于400ml，说明病人已进入多尿期。进行性尿量增多是肾功能开始恢复的一个标志。多尿期的早期，GFR仍较正常为低，主要因肾小管修复再通而修复的肾小管浓缩功能仍很差，一方面排出代谢产物的能力不足，一方面出现多尿。这时患者仍可存在氮质血症，也可能存在高钾血症。尿量过多常使患者发生水、电解质紊乱，主要倾向是脱水、低血钾和低血钠，所以对这些病人要注意预防。 三 恢复期 患者自我感觉好转，逐步能自理生活和进行劳动。尿量逐渐恢复正常，血尿素氮和肌酐也接近正常。

39. Nonoliguric acute renal failure 非少尿型ARF近年来有逐渐增多的趋势；这可能与病人医疗意识加强、医疗诊治手段提高及肾毒性抗生素广泛应用有关。其机制为：① 不同肾单位受损程度不一，小部分肾单位的肾血流量和肾小球滤过功能存在；② 肾小管重吸收功能障碍远较肾小球滤过功能降低为重；③ 肾髓质形成高渗状态的能力降低，使尿液浓缩功能下降，故发病后尿量无明显降低，在400～1000 ml/d左右。非少尿型ARF较少尿型ARF病情轻、预后好，但因症状轻而不太明显，容易延误病人的就诊或引起医生的漏诊。非少尿型ARF不及时治疗，则会转化为少尿型ARF。

40. Management • Renal Diet • Acidosis • Hyperuricemia • Hypertension • Volume overload • Protein Load • Newer Agents：ANF • Dialysis • Kidney Transplantation Hospital inpatients with ARF ~50% mortality rate

41. Dialysis indications I. Serum abnormalities unresponsive to medical therapy • Severe Acidosis • Severe Hyperkalemia II. Uremia • Mental status changes (usually delirium) • Nausea and vomiting • Pericarditis (pericardial friction rub) III. Volume Overload

42. Peritoneal Dialysis

43. Hemodialysis • Blood is circulated through artificial cellophane membrane that permits a similar passage of water and solutes

44. Chronic Renal Failure, CRF

45. Definition • Etiology • Pathogenesis • Clinical manifestation • Therapy

46. Definition • Chronic renal failure (CRF) is defined as a permanent reduction in glomerular filtration rate (GFR) sufficient to produce detectable alterations in well-being and organ function. This usually occurs at GFR below 25 ml/min.

47. CRF is characterized by progressive and irreversible loss of large numbers of functioning nephrons. Serious clinical symptoms often do not occur until the number of functional nephrons falls to at least 70 per cent below normal. In fact relatively normal blood concentrations of most electrolytes and normal body fluid volumes can still be maintained until the number of functioning nephrons decreases below 20-30percent of normal.

49. 慢性肾功能衰竭的定义 慢性肾功能衰竭是由于各种肾脏疾病引起肾单位进行性破坏，以致残存的有功能的肾单位不能充分排出代谢废物和维持内环境恒定的缓慢发展的一种肾功能损害的病理过程。机体逐渐出现代谢废物和毒物的潴留，水、电解质与酸碱平衡紊乱，以及肾内分泌功能障碍，并可伴有全身各系统功能受损的临床症状。 因为肾组织的破坏是逐渐发生的，而且肾脏又有较强的代偿能力，故慢性肾衰常常是缓慢发展，病程迁延数月、数年以至更长的时间，最后常导致尿毒症而死亡。尿毒症是指急、慢性肾功能衰竭最危重的阶段。

50. Causes of CRF Any disorder that permanently destroys nephrons can result in chronic renal failure. Most common causes of CRF are: • Diabetic nephropathy • Hypertensive nephrosclerosis • Glomerulonephritis • Interstitial nephritis • Polycystic kidney disease