3rd year, 3rd rotation

1. NEPHROTIC SYNDROME THE SWOLLEN CHILD

4. CLASSIFICATION

6. M:F = 2:1

7. < 7 years old

8. steroid-sensitive nephrotic syndrome

9. do not progress to renal failure

10. often precipitated by respiratory infections

11. Features:age between 1 and 10 years no macroscopic haematuria normal blood pressure normal complement levels normal renal function.

13. PATHOPHYSIOLOGY Primary disorder:

14. Edema: - under fill theory: hypoalbuminemia - over fill theory:↑ tubular NaClreabsorption secondary to RAAS -> intravascular expansion -> fluid shift following pressure gradient Hypercholesterolemia - hypopratenemia -> hepatic lipoprotein synthesis -> ↑serum lipid (cholesterol, lipoprotein) -> lipid metabolism

17. A low urinary sodium (<20mmol/L) and a high packed cell volume

18. Thromboembolism

19. hypercoagulable state due to urinary losses of antithrombin, thrombocytosis

20. exacerbated by steroid therapy

21. increased synthesis of clotting factors

22. increased blood viscosity from the raised haematocrit,

23. This is usually arterial and may affect the brain, limbs and splanchnic circulation

24. Hypercholesteroleamia

28. Colour changes

29. Initiating factor? (bee sting)

31. PHYSICAL EXAMINATION Assessment of hydration status identifies fluid imbalances (dehydration, overhydration) Blood pressure: hypertension Henoch-Schönleinpurpura (purpura) Systemic lupus erythematosus (malar rash) Rales heard on lung auscultation suggest extravascular fluid from overload or hypoalbuminemia Palpation and percussion of the abdomen may reveal ascites or masses Liver enlargement is present in several multisystem diseases (systemic lupus erythematosus, infections, polycystic disease) and in glomerulosclerosis

33. Postural orthostatic proteinuria

35. Haematuria (other thn MCD)

37. Antistreptolysin O titre and throat swab

40. 40 mg/m2/48 hr (max 60mg/dose) for further 4 weeks

41. Prednisolone regime for relapses:

42. 60 mg/m2/day (max 80mg/day) until remission

45. diuretic

46. blood pressure control : ACEi (captopril, enalapril), angiotensin II receptor antagonist

47. hyperlipidaemia

48. Immunosuppressive therapy:

49. Steroids

50. cyclophosphamide

51. Cyclosporin, tacrolimus, mycophenolatemofetil

52. Indications for renal biopsy

53. A renal biopsy is also NOT required prior to cytotoxictherapy

54. Steroid resistant nephroticsyndrome

55. Secondary NS

58. Cataracts

59. Striae

60. Severe cushingoid features

61. behavioural changes, a rounded face, central obesity and the tendency to bruise more easily, hirsutism

62. Osteoporosis

63. Proximal myopathy

66. Dietary advice: no added salt, normal protein with adequate calories

67. Prophylactic antibiotics: oral penicillin particularly in during relapse with gross oedema

68. Hypovolaemia: infuse salt poor albumin or 5% albumin, plasma protein derivatives or human plasma

70. If exposed to chickenpox and measles varicella-zoster immunoglobulin (VZIG) should be given within 72 hours after exposure to chickenpox / single dose of intravenous immunoglobulin.

72. EDUCATION Education: Parents and school teachers should be provided with information regarding the disease which includes: Advice and precaution of infection Danger of sudden steroid withdrawal (adrenal crisis) Immunisation: While the child is on corticosteroid treatment and within 6 weeks after its cessation, only killed vaccines may be safely be administered to the child. Live vaccines can be administered 6 weeks after cessation of corticosteroid therapy

73. PROGNOSIS

74. Acute nephritic syndrome NUR AMIRA BINTI MOHD ASRI

75. CASE SCENARIO A 7 year old Malay boy was admitted 3 days ago with the chief complaints of facial puffiness and passing smokey and frothy urine for 1 week. The facial puffiness initially started off as periorbitaloedema which then progressed to involve the entire face within a week. Urinary output was also decreased. He also complaint of fever for one week which was of low grade, intermittent with no chills and rigor. There is also presence of an erythematous itchy skin lesion on his right elbow which was first noticed 2 weeks back. There is no history of sore throat, flu, blood transfusion, nausea, and vomiting, rashes, dyspnoea and chest pain. General examinations revealed pallor, high blood pressure of 139/96 mmHg, and an erythmatous scaly circular skin lesion on his right elbow. Urine biochemistry revealed protein 3+, RBC 4+. Blood urea was raised to 500 umol/L.

76. NEPHRITIC SYNDROME It is a clinical complex, usually acute onset, characterized by: oedemaeg facial puffiness Microscopic/macroscopic haematuria (tea-coloured urine) hypertension Oligouria (decreased urine output) Azotemia/uremia (excess urea in urine)

77. The lesions that cause nephritic syndrome have in common proliferation of cells within in glomeruli, accompanied by a leukocytic infiltration. This inflammatory reaction injures the capillary walls, permitting escape of RBC into the urine(hematuria) , and induced hemodynamics changes that lead to a reduction in GFR which are manifested clinically by oligouria, reciprocal fluid retention and azotemia Hypertension is the result of the fluid retention by kidney secretion of renin.

78. NEPHROTIC SYNDROME GLOMERULONEPHRITIS Acute poststreptococcal GN lgA nephropathy NEPHRITIC SYNDROME Henoch-schönleinpurpura SLE

79. POSTSTREPTOCOCCAL AGN The commonest cause of nephritic syndrome Usually followed a nephritogenic streptococcal pharyngitis or impetigo with a strain of group A beta-hemolytic streptococci Immune-mediated inflammation Occurs most frequently in children 2 to 12 years old Boys are frequently affected This is diagnosed by evidence of a recent streptococcal infection (culture of the organism, raised ASOT) and low complement C3 levels, that return to normal after 6-8 weeks Long term prognosis is good

80. Epidemiology of post acute strep GN 121 of the 124 nephritis patients had poststreptococcal infection. (Department of paediatrics, HUSM, July 1987-June 1988) Globally-incidence has decreased in the past 3 decades Most commonly-sporadic Despite that,epidemic cases in some poor and rural communities

81. pathogenesis

82. Streptococcal infection Immune complex formation +deposited in GBM Complement system activated Low serum complement Immune injuries Cellular proliferation GBM fracture Capillary lumen narrowed hematuria proteinuria Glomerular blood flow decreased oligouria GFR low Distal sodium reabsorption Retention of water and sodium Edema and hypertension Blood volume increased

84. Twice as common in boys

85. peaks during winter months

86. Is often preceded by an upper respiratory infection

87. Unknown cause however it is postulated that genetic predisposition and antigen exposure increase circulating lgA levels.

88. By immunofluorescence and electron microscopy the findings may be similar to those of IgAN

89. The combination of

90. Skin rashes(symmetrical distributed over the buttocks,extensor surface of arms and legs and the ankles.

91. Athralgia (knees and ankles)

92. Periarticularoedema

93. Colicky abdominal pain, GI petechiae,hematemesis, melaena, intussusception

95. Criteria for diagnosis of SLE signs Malar rash (butterfly rash) Photosensitivity Oral and nasopharyngeal ulcers Pleuritis and pericarditis Non erosive arthritis ( more than 2 joints with effusion and tenderness. Investigation data Protenuria(>500mg/24 hrs) or RBC cellular cast in urine Positive anti-dsDNA Evidence of presence of antiphospholipid antibodies

97. lgA NEPHROPATHY Affects children and young adults Begins as an episode of gross hematuria that occurs within 1 or 2 days of a nonspecific upper respiratory tract infection. Is one the most common causes of recurrent microscopic or gross hematuria and is the most common glomerular disease revealed by renal biopsy The pathology hallmark is the deposition of lgA in the mesangium Prognosis is good in children immunofluorescence with anti-IgA antibodies deposited in the mesangium

98. Familial nephritis The commonest familial nephritis is Alport’s syndrome X-linked recessive disorder Is associated with nerve deafness and ocular defect The mother may have hematuria Can progress to end-stage renal failure by early adult life in males.

99. Basic workup of a child with hematuria History-age,gender,sosioeconomicstatus,familyhistory,drug history Physical examination-height,weight,bloodpressure,funduscopy,presence or absence of abdominal mass,skinappearance,genitalia,edema,complete physical examination. Laboratory-urinalysis (includingmicroscopic examination and RBC morphology), urine culture, complete blood count (including platelets), serum electrolytes, creatinine,calcium, serum complement, random urine for total protein, creatinine, renal imaging studies. Nelson p758

100. Dalliana Adia Bte Abd Latif 2008402292

104. Ask about symptoms of swelling-facial, perioral,pedal edema, or ascites

105. Symptom of pulmonary edema/ CHF (egdyspnoea with exertion, orthopnoea, SOB)

106. Gross hematuria (eg dark, rust, coke, tea coloured)

107. Family hx, other family member with nephritis or renal failure- Alport syndromeThe general terms GN and nephritis are not specific enough to be very useful for treatment or prognosis!!!

108. Epistaxis, headache, encephalopathy- severe hypertension Oligouria Nonspecific symptoms eg malaise, fever, anorexia, weakness For tubulointestinal nephritis- try to obtain a history of a known etiology (eg bacterial, viral, drug related, metabolic, other) TIN, usually hx of polyuria than oliguria

109. Investigation Laboratory FBC- anemia, leucocytosis Urinalysis and culture- hematuria, proteinuria, RBCs cast,other cellular masts, pyuria? Bacteriological an serology- Anti streptolysin-O titer (>200IU/mL), Anti-DNAse B, throat swab/skin swab, lupus serology, serum IgA Measure complement level- C3 RFT- blood urea, serum creatinine, electrolytes, BUN

110. Acute poststreptococcal GGN- low C3, positive ASOT and anti DNAase B TIN- hematuria, eosinophilia, sterile pyuria, low grade proteinuria, eosinophiluria, urinary WBc casts

111. Imaging Renal ultrasonography- usually to exclude other causes of hypertension and hematuria but usually not conducted in real cut nephritic sydrome

112. Histology light microscopy: lymphocytes, PMN leukocytes Immunofluoroscene- IgG, IgA, IgM, or complement Electron- deposit in mesangial, subendothelial, or subepithelial

113. Post-streptococcal nephritis Urinalysis ASOT Low complement C3 levels- return to normal after 3-4 weeks

114. Management Treat the primary pathology- immunosuppressive med eg steroids or cyclophosphamide in lupus Supportive care- Fluid and electrolyte balance, diuretics, Ca channel blocker, ACEi, monitor rapid deterioration in renal function Diet- fluid restriction, sodium, potassium restriction, Ca supplement Dialysis

115. Complication Complication of severe hypertension (e.g. cerebral haemorrhage, seizure, enchepalopathy,stroke, end organ damage) Complication of renal failure (e.g. hyperkalemia, fluid overload, electrolyte abnormality, uremic symtoms, anemia, abnormal bone mineralization, sexual dysfunction, poor growth, anorexia) Complication of primary disease (eg SLE)

116. Nephrotic and nephritic

118. Have a good fortune ahead!!! 