Unit II. Genitourinary systemmmmmmm.pptx

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1. Unit II. Genitourinary system Disorders Yomilan G. (BSc, MSc in pediatrics) 9/18/2022 Yomilan G., MSc in pediatrics 1

2. Can you mention some of Genitourinary system Disorders? 9/18/2022 Yomilan G., MSc in pediatrics 2

3. I. Nephrotic Syndrome (NS) 9/18/2022 Yomilan G., MSc in pediatrics 3

4. Nephrotic Syndrome:- 9/18/2022 Yomilan G., MSc in pediatrics 4

5. Introduction Nephrotic syndrome is not by itself a disease. Is a collection of syndromes caused by many diseases that effect the kidney. Resulting in severe, prolonged loss of protein in the urine (proteinuria). Decreased blood levels of protein (albumin). (hypoalbuminemia). Retention of excess salt and water (edema). Increased level of fat in the blood (hyperlipidemia). 9/18/2022 Yomilan G., MSc in pediatrics 5

6. Nephrotic syndrome Is resulted from increased permeability of Glomerular basement membrane ( GBM ) to plasma protein. NS is an autoimmune process that occurs 1 week after an immune assault. Children have sign of Hyper albuminuria , hypoalbuminemia , Hypovolemia , Hyperlipidemia. It is clinical and laboratory syndrome characterized by massive proteinuria, which lead to hypoproteinemia ( hypo-albuminemia), hyperlipidemia and pitting edema. 9/18/2022 Yomilan G., MSc in pediatrics 6

7. Age of onset: 18 months to 6 years. 75 to 90% will relapse at least once. Majority stop relapsing before adulthood with no permanent kidney damage if treated properly. Not inherited . Small family incidence. 9/18/2022 Yomilan G., MSc in pediatrics 7

8. Nephrotic Criteria:- 9/18/2022 Yomilan G., MSc in pediatrics 8 Massive proteinuria: Qualitative: 3+ or 4+, Quantitative: >40 mg/m2/ hr in children (selective). Hypo-proteinemia : Total plasma proteins < 5.5g/dl and serum albumin < 2.5g/dl . Hyperlipidemia: Serum cholesterol > 5.7mmol/L Edema: pitting edema in different degree.

9. Nephritic Criteria… Hematuria: RBC in urine (gross hematuria) Hypertension: ≥ 130/90 mmHg in school-age children ≥ 120/80 mmHg in preschool-age children ≥ 110/70 mmHg in infant and toddler’s children Azotemia （ renal insufficiency): Is an increased level of serum BUN 、 Cr Hypo- complementemia : Decreased level of serum c3 9/18/2022 Yomilan G., MSc in pediatrics 9

10. Classification: A-Primary Idiopathic NS (INS): Major type. The cause is still unclear up to now. Recent 10 years ,increasing evidence has suggested that INS may result from a primary disorder of T– cell function. Accounting for 90% of NS in child. Mainly discussed. B-Secondary NS: NS resulted from systemic diseases, such as anaphylactoid purpura , systemic lupus erythematosus, HBV infection. C-Congenital NS: rare type. 1st 3month of life ,only treatment renal transplantation . 9/18/2022 Yomilan G., MSc in pediatrics 10

11. Secondary NS Drug, Toxic, Allergy : Mercury, snake venom, vaccine, pellicillamine , Heroin, gold, NSAID, captopril, probenecid, volatile hydrocarbons. Infection : HBV, HIV, shunt nephropathy, reflux nephropathy, leprosy, syphilis, Schistosomiasis, hydatid disease. Autoimmune or collagen-vascular diseases : SLE, Hashimoto’s thyroiditis, Henoch- Schonlein purpura (HSP), Vasculitis. 9/18/2022 Yomilan G., MSc in pediatrics 11

12. Metabolic disease : Diabetes mellitus Neoplasma : Hodgkin’s disease, carcinoma ( renal cell, lung, neuroblastoma, breast, and etc ) Genetic Disease : Alport syndrome, Sickle cell disease, Amyloidosis, Congenital nephropathy Others : Chronic transplant rejection, congenital nephrosclerosis 9/18/2022 Yomilan G., MSc in pediatrics 12

13. NB:- Nephrotic syndrome is 15 times more common in children than in adults. Most cases of primary nephrotic syndrome are in children and are due to minimal-change disease. The age at onset varies with the type of nephrotic syndrome. 9/18/2022 Yomilan G., MSc in pediatrics 13

14. Pathophysiology : The Main Trigger Of primary Nephrotic Syndrome and Fundamental and highly important change of pathophysiology is Proteinuria. 9/18/2022 Yomilan G., MSc in pediatrics 14

15. Pathogenesis of Proteinuria:- Increase glomerular permeability for proteins due to loss of negative charged glycoprotein. Degree of proteinuria:- Mild less than 0.5 g/m2/day. Moderate 0.5 – 2 g/m2/day. Sever more than 2 g/m2/day. 9/18/2022 Yomilan G., MSc in pediatrics 15

16. Pathogenesis of hypoalbuminemia Due to hyperproteinuria ----- Loss of plasma protein in urine mainly the albumin. Increased catabolism of protein during acute phase. 9/18/2022 Yomilan G., MSc in pediatrics 16

17. Pathogenesis of hyperlipidemia:- Response to Hypoalbuminemia → reflex to liver --→ synthesis of generalize protein ( including lipoprotein ) and lipid in the liver ,the lipoprotein high molecular weight no loss in urine → hyperlipidemia. Diminished catabolism of lipoprotein. 9/18/2022 Yomilan G., MSc in pediatrics 17

18. pathogenesis of edema:- Reduction of plasma colloid osmotic pressure↓ secondary to hypoalbuminemia Edema and hypovolemia Intravascular volume↓ antidiuretic hormone (ADH ) and aldosterone(ALD)  water and sodium retention Edema. Intravascular volume↓ glomerular filtration rate(GFR)↓ water and sodium retention  Edema 9/18/2022 Yomilan G., MSc in pediatrics 18

19. How many pathological types causes nephrotic syndrome? 9/18/2022 Yomilan G., MSc in pediatrics 19

20. Clinical Manifestation In NS , the male preponderance of 2:1 1.Main manifestations: Edema (varying degrees) is the common symptom Local edema: edema in face , around eyes( Periorbital swelling), in lower extremities. Generalized edema (anasarca), edema in penis and scrotum 9/18/2022 Yomilan G., MSc in pediatrics 20

21. 2-Non-specific symptoms: Fatigue and lethargy, loss of appetite, nausea and vomiting, abdominal pain, diarrhea, body weight increase, urine output decrease, pleural effusion (respiratory distress ). 9/18/2022 Yomilan G., MSc in pediatrics 21

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23. 9/18/2022 Yomilan G., MSc in pediatrics 23

24. Clinical features Puffiness of the face especially around the eyes – is apparent on arising in the morning but subsides during the day. Swelling of the abdomen and lower extremities. Generalized edema Ascites and /or Pleural effusions Striae Profound weight gain Decreased urine output during edematous phase Pallor, irritability, lethargy, and fatigue GI disturbances . 9/18/2022 Yomilan G., MSc in pediatrics 24

25. Clinical features… Respiratory difficulty –to pleural effusion Labial or scrotal swelling due (edema) Edema of the Intestinal mucosa may cause diarrhea, anorexia and poor intestinal absorption. Decreased urine out put Dark, foamy and Frothy urine. Poor intestinal absorption. 9/18/2022 Yomilan G., MSc in pediatrics 25

26. Clinical features… Skin pallor Malnutrition from pour appetite and Loss of protein Blood pressure is normal or slightly decreased. Susceptible to infection like cellulites ,pneumonia, peritonitis or septicemia. 9/18/2022 Yomilan G., MSc in pediatrics 26

27. Investigations:- 1-Urine analysis:- Proteinuria: 3-4 + SELECTIVE. 24 urine collection for protein >40mg/m2/ hr for children. Volume: Oliguria (during stage of edema formation) Microscopically :- Microscopic hematuria 20%, large number of hyaline cast. 9/18/2022 Yomilan G., MSc in pediatrics 27

28. Investigations… 2. Bood test: A-serum protein: decrease > 5.5gm/dL , Albumin levels are low ( ＜ 2.5gm/dL). B-Serum cholesterol and triglycerides: Cholesterol ＞ 5.7mmol/L (220mg/dl). C-- ESR↑ ＞ 100mm/ hr during activity phase Hemoglobin level increased . 3. Renal function: Kidney Biopsy 9/18/2022 Yomilan G., MSc in pediatrics 28

29. Differential Diagnosis of NS: 1-Protein –losing enteropathy 2-Hepatic Failure. 3-HF 4-Protein energy malnutrition 5-Acute and chronic GN 6-urticaria? Angio edema 9/18/2022 Yomilan G., MSc in pediatrics 29

30. Complications of NS:- 1-Infections : Infections is a major complication in children with NS. It frequently trigger relapses. Nephrotic pt are liable to infection because: Loss of immunoglobins in urine. The edema fluid act as a culture medium Use immunosuppressive agents. Malnutrition The common infection : URI, peritonitis, cellulitis and UTI may be seen. Organisms: encapsulated (Pneumococci, H.influenzae ), Gram negative ( e.g E.coli 9/18/2022 Yomilan G., MSc in pediatrics 30

31. Complication … Vaccines in NS;- Polyvalent pneumococcal vaccine (if not previously immunized) when the child is in remission and off daily prednisone therapy. Children with a negative varicella titer should be given varicella vaccine. 9/18/2022 Yomilan G., MSc in pediatrics 31

32. Complication….. 2-Hypercoagulability (Thrombosis). Hypercoagulability of the blood leading to venous or arterial thrombosis: Hypercoagulability in Nephrotic syndrome caused by: Higher concentration of I,II, V,VII,VIII,X and fibrinogen Lower level of anticoagulant substance: antithrombin III Decrease fibrinolysis. Higher blood viscosity Increased platelet aggregation Overaggressive diuresis 9/18/2022 Yomilan G., MSc in pediatrics 32

33. 3- ARF : pre-renal and renal 4- Cardiovascular disease :- Hyperlipidemia, may be a risk factor for cardiovascular disease. 5- Hypovolemic shock 6-Others: Growth retardation, malnutrition, adrenal cortical insufficiency. 9/18/2022 Yomilan G., MSc in pediatrics 33

34. Management of NS: General (non-specific ) Corticosteroid therapy 9/18/2022 Yomilan G., MSc in pediatrics 34

35. General therapy:- Hospitalization :- for initial work-up and evaluation of treatment. Activity: Usually no restriction , except massive edema, heavy hypertension and infection. Diet : Hypertension and edema: Low salt diet (<2gNa/ day) only during period of edema or salt-free diet Severe edema: Restricting fluid intake. 9/18/2022 Yomilan G., MSc in pediatrics 35

36. General therapy… Avoiding infection: very important. Diuresis : Hydrochlorothiazide (HCT) ： 2mg/ kg.d Antisterone : 2 ～ 4mg/ kg.d Dextran ： 10 ～ 15ml/kg , after 30 ～ 60m Followed by Furosemide (Lasix) at 2mg/kg . 9/18/2022 Yomilan G., MSc in pediatrics 36

37. Induction use of albumin: Albumin + Lasix (20 % salt poor). Severe edema Ascites Pleural effusion Genital edema Low serum albumin 9/18/2022 Yomilan G., MSc in pediatrics 37

38. Corticosteroid—prednisone therapy:- Prednisone tablets at a dose of 60 mg/m 2 /day (maximum daily dose, 80 mg divided into 2-3 doses) for at least 4 consecutive weeks. After complete absence of proteinuria, prednisone dose should be tapered to 40 mg/m 2 /day given every other day as a single morning dose. The alternate-day dose is then slowly tapered and discontinued over the next 2-3 mo . 9/18/2022 Yomilan G., MSc in pediatrics 38

39. Treatment of relapse in NS: Many children with nephrotic syndrome will experience at least 1 relapse (3-4+proteinuria plus edema). Daily divided-dose prednisone at the doses noted earlier (where he has the relapse) until the child enters remission (urine trace or negative for protein for 3 consecutive days). The pred- nisone dose is then changed to alternate-day dosing and tapered over 1-2 mo. 9/18/2022 Yomilan G., MSc in pediatrics 39

40. According to response to prednisone therapy: 9/18/2022 Yomilan G., MSc in pediatrics 40 Remission : no edema, urine is protein free for 5 consecutive days. Relapse : edema, or first morning urine sample contains > 2 + protein for 7 consecutive days. Frequent relapsing : > 2 relapses within 6 months (> 4/year). Steroid resistant : failure to achieve remission with prednisolone given daily for 28 days.

41. Side Effects With Long Term Use of Steroids Steroid toxicity 9/18/2022 Yomilan G., MSc in pediatrics 41 Hyperglycemi Myopathy Peptic ulcer poor healing of wound. Hirsutism Thromboembolism Stunted growth Cataracts Pseudotumor cerebri Psychosis Osteoporosis Cushingoid features Adrenal gland suppression

42. Alternative agent:- When can be used: Steroid-dependent patients, frequent relapsers , and steroid-resistant patients. Cyclophosphamide Pulse steroids Cyclosporin A Tacrolimus Microphenolate 9/18/2022 Yomilan G., MSc in pediatrics 42

43. Nursing Care Provide skin care to edematous skin; don’t use adhesive strip bandage, tape or I.M injection. Provide warm soaks to decrease periorbital edema Elevate the head of the bed to facilitate to breath well Turn the child frequently to prevent pressure on the skin 9/18/2022 Yomilan G., MSc in pediatrics 43

44. Nursing Care…. Provide scrotal support and place padding between body parts to prevent irritation Test the first void of the day for protein Feed small, frequent meals with restricted salt Measure intake and output and daily weight 9/18/2022 Yomilan G., MSc in pediatrics 44

45. Nursing care… Measure the abdominal girth daily if child has ascites Prevent contact with persons who have an infection because to avoid infection to the child. Anticipate diuresis in 1 to 3 weeks Maintain bed rest during rapid diuresis Monitor hydration status and vital signs 9/18/2022 Yomilan G., MSc in pediatrics 45

46. Nursing care… Corticosteroid ( prednisone ) single dose ( complication growth retardation hypertension, Gastro intestinal bleeding , syndrome bone demineralization, infection & DM . Provide information to the parents related to the disease condition of their child. Educate the parents about home care-restricted Fluid intake, salt free diet, skin care, regular medication, Inform about follow up care. 9/18/2022 Yomilan G., MSc in pediatrics 46

47. II. Acute renal failure in children 9/18/2022 Yomilan G., MSc in pediatrics 47

48. outline Objective Etiologies and pathogenesis of ARF Classification Diagnosis and management 9/18/2022 Yomilan G., MSc in pediatrics 48

49. Objectives Understand the etiology and pathogenesis of ARF. Request appropriate investigations. Manage a child with acute renal failure. 9/18/2022 Yomilan G., MSc in pediatrics 49

50. 9/18/2022 Yomilan G., MSc in pediatrics 50 KIDNEY FUNCTIONS Filter Blood Plasma, Eliminate Wastes Regulate Blood Volume, Pressure. Regulate Fluid Osmolarity Secrete Renin Secrete Erythropoietin ( Epo ) Regulate P co 2 , Acid-base Balance Synthesize Calcitrol ( Vitamin D ) DETOXIFY Drugs

51. 9/18/2022 Yomilan G., MSc in pediatrics 51 Nephron Nephron is a functional unit of the kidney where urine is formed. Stages in urine formation: Filtration Reabsorption Secretion

52. filtration Reabsorption Secretion Reabsorption of water Nephron 9/18/2022 Yomilan G., MSc in pediatrics 52

53. - Blood pressure forces Small molecules From the Glomerulus to the capsule 9/18/2022 Yomilan G., MSc in pediatrics 53 1. Filtration Filtrates: glucose, amino acids uric acid, urea

54. 9/18/2022 Yomilan G., MSc in pediatrics 54 2. Tubular Reabsorption Return of filtrates from blood at the proximal tubule through diffusion and active transport

55. 9/18/2022 Yomilan G., MSc in pediatrics 55 3. Tubular Secretion -movement of molecules from blood into the distal convoluted tubule Molecules: drugs and toxins

56. Acute renal failure or AKI Definition : Loss of renal function measured by a decline in GFR that develops over a period of hours to days. Manifested by : Oliguria : A decreased urine amount. In children < 0.5ml/kg/h, in infants < 1ml/kg/h Anuria : no urine production for over 24 hours. 9/18/2022 Yomilan G., MSc in pediatrics 56

57. Estimation of GFR It can be estimated by measuring serum creatinine. It is calculated as: GFR(ml/1.73 SA/ min) = (height in centimeter* K)/creatinine(mg/dl) K is 0.33 for preterm infants <1yr of age, K is 0.45 for term infants who are AGA, K is 0.55 for children and for adolescent girls and K is 0.7 for adolescent boys. 9/18/2022 Yomilan G., MSc in pediatrics 57

58. 9/18/2022 Yomilan G., MSc in pediatrics 58

59. Pathophysiology Three phases in the development of ARF. Initiation phase: ischemia or a toxin sets in motion a sequence of events which produce an injury to tubular epithelial cells. 9/18/2022 Yomilan G., MSc in pediatrics 59

60. Pathophysiology… Maintenance phase: GFR remains relatively low for several days. Recovery phase: characterized by gradual and progressive restoration of GFR and tubular function. 9/18/2022 Yomilan G., MSc in pediatrics 60

61. Pathophysiology… Three major factors that may account for the development of ARF: Renal hemodynamics, Nephronal factors, Metabolic/cellular factors 9/18/2022 Yomilan G., MSc in pediatrics 61

62. Renal hemodynamics Tubular injury Decreased cortical BF altered reabsorption of solute & water Release of vasoactive compounds Increased cortical VR Diminished GF dynamics Decreased GFR ARF 9/18/2022 Yomilan G., MSc in pediatrics 62

63. Nephronal factors in ARF proximal tubule injury epithelial cell necrosis Loss of tubule integrity impacted cellular debris Back leak of solute/fluid tubule obstruction diminished GFR diminished tubule flow ARF 9/18/2022 Yomilan G., MSc in pediatrics 63

64. Cellular and metabolic mechanisms Oxygen free radical production contributing to an ischemic insult. Calcium accumulation in tissues who have undergone necrosis contributing to renal cell injury: Uncouples oxidative phosphorylation. Activation of membrane bound phospholipase Activation of intracellular proteases 9/18/2022 Yomilan G., MSc in pediatrics 64

65. Cellular … Inhibition of Na/K-ATPase. Direct effect on intracellular pH. Depletion of tissue adenine nucleotide levels which is a source of energy and concomitant increase in nucleosides, adenosine, and inosine. These are responsible for renal vasoconstriction following an ischemic insult. 9/18/2022 Yomilan G., MSc in pediatrics 65

66. Etiology of ARF Pre renal Etiology: oliguria due to inadequate perfusion of the kidneys. Renal Etiology: Renal parenchymal cell injury or disease Post renal Etiology: results from mechanical obstruction to urine flow 9/18/2022 Yomilan G., MSc in pediatrics 66

67. Etiology of ARF 9/18/2022 Yomilan G., MSc in pediatrics 67

68. Pre renal ARF Hypo perfusion of kidneys. Renal function (GFR) falls when BP falls below auto regulatory range. Readily reversible with prompt correction of hypo perfusion. Decreased cardiac out 9/18/2022 Yomilan G., MSc in pediatrics 68

69. 9/18/2022 Yomilan G., MSc in pediatrics 69

70. Diagnosis P/E: signs of volume depletion, CHF Rise in Bilirubin to Creatinine ratio greater than 20 ( BUN:Cr >20 ) Urine-sodium <10 mEq /lit (neonates<20 mEq /lit) Urine-osmolarity >500 mOsm /L (neonates >400 mOsm /L) Fractional excretion of sodium <1%(neonates <2.5%) Urine sediment normal or granular casts Response to trial bolus of isotonic fluid (10-20ml/kg). 9/18/2022 Yomilan G., MSc in pediatrics 70

71. 9/18/2022 Yomilan G., MSc in pediatrics 71 Diagnosis… Laboratory Evaluation: Serum creatinine BUN(can be elevated due to hypovolemia) Bilirubin to Creatinine ratio is helpful in classifying cause of ARF: Ratio> 20:1 suggests prerenal cause Ratio 10-15:1 suggests intrinsic renal cause

72. Therapy Prompt correction of hypo-perfusion to prevent renal cell injury Isotonic fluid (RL, NS) Blood transfusion IV albumin, 1g/kg in severe Hypo-albuminemia Correct cardiac failure with inotrops 9/18/2022 Yomilan G., MSc in pediatrics 72

73. Intrinsic renal injury Etiology Ischemia Renal vascular insult: thrombosis, Hemolytic uremic syndrome (HUS). Toxins: drugs, venoms Endogenous substances: tumor lysis syndrome, Hg, Rhabdomyolysis Rhabdomyolysis is a potentially life-threatening syndrome resulting from the breakdown of skeletal muscle fibers with leakage of muscle contents into the circulation. Immune mediated, Acute glomerulonephritis (AGN). 9/18/2022 Yomilan G., MSc in pediatrics 73

74. Diagnosis Sediment : hematuria, proteinuria, RBC casts, renal tubular epithelial cells Urine-sodium > 40 mEq /l Urine-osmolarity < 350 mOsm /L Fractional excretion of sodium > 2% 9/18/2022 Yomilan G., MSc in pediatrics 74

75. Therapy Use of manitol and diuretics controversial, may help at the initiation phase. Manitol 0.5g/kg, Frusemide 1-5mg/kg Fluid balance If patient euvolemic replace losses: Insensible Water Loss (IWL)+urine out put + other losses Fluid could be replaced as 5% DW or ¼ NS. 9/18/2022 Yomilan G., MSc in pediatrics 75

76. Therapy… Hyperkalemia : Calcium gluconate 10% 0.5 ml/kg IV over 2-4 min with ECG monitoring 7.5% sodium bicarbonate, 2-3 mEq /kg over 30-60 min Glucose 0.5g/kg, with 0.3u of insulin per gram of glucose Cation exchange resin (Kayexalate), 1g/kg PO or rectally with 1-2 ml/kg sorbitol or 5% glucose Dialysis 9/18/2022 Yomilan G., MSc in pediatrics 76

77. Therapy … Hyperphosphatemia and hypercalcemia seldom need therapy Calories : 400cal/m 2 after first 2-3 days to decrease catabolism Hypertension : fluid and salt restriction, antihypertensives, Dialysis: In severe fluid overload, severe hyperkalemia, intractable acidosis, dialysable toxins, massive tumor lysis 9/18/2022 Yomilan G., MSc in pediatrics 77

78. Postrenal ARF Only bilateral obstruction leads to ARF Etiology : Internal ureteral or bladder obstruction External compression: abdominal mass Bladder paralysis: spinal cord injury Neurogenic bladder dysfunction Vesico-uretheral reflux 9/18/2022 Yomilan G., MSc in pediatrics 78

79. 9/18/2022 Yomilan G., MSc in pediatrics 79 Obstruction of urinary tract Important to rule out early : potential for recovery inversely related to duration

80. Diagnosis Palpation of the bladder Bladder catheterization U/S: large distended bladder, hydronephrosis 9/18/2022 Yomilan G., MSc in pediatrics 80

81. Therapy Remove the obstruction Bladder decompression by indwelling catheter surgery 9/18/2022 Yomilan G., MSc in pediatrics 81

82. 9/18/2022 Yomilan G., MSc in pediatrics 82

83. iii. ACUTE GLOMERULONEPHRITIS 9/18/2022 Yomilan G., MSc in pediatrics 83

84. Acute poststreptococ c al glomerulonephritis (APSGN) This is the most common form of GN in children, 80 to 90% of Post-Infectious Glomerulonephritis (PIGN). It is characterized by- Sudden onset of gross hematuria Edema Hypertension Renal insufficiency(oliguria) 9/18/2022 Yomilan G., MSc in pediatrics 84

85. Etiology and epidemiology It follows infection of throat or skin Latency period Pharyngitis; 1 to 2 wks Pyoderma ; 3 to 6wks It is a disease of school ages (5 to 15yrs) Rare before 3yrs of, one case report shows at age of 8mo. 9/18/2022 Yomilan G., MSc in pediatrics 85

86. Cot’d … May occur as sporadic or epidemics Pharengitis common during winter Pyoderma during winter Occurs only in 10-15% children who are infected with nephritogenic strains 50 to 85% pts with PSGN are asymptomatic 9/18/2022 Yomilan G., MSc in pediatrics 86

87. Pathology Involved kidney is usually enlarged Light microscopy- glomeruli enlarged and relatively bloodless with diffuse mesangial proliferation Immunoflouresence -” lumpy –bumpy ” deposits on glomerular basement membrane and in the mesangium Electron microscope- ” hump ” on the endothelial side the glomerular basement membrane due accumulation of immune complexes. 9/18/2022 Yomilan G., MSc in pediatrics 87

88. Pathogenesis It is thought to be immune mediated disease Presumably Ag- Ab complexes are formed in the circulation and deposited in the glomeruli. This deposited immune complexes may incite glomerular damage through activation of the complement system (alternate pathway). 9/18/2022 Yomilan G., MSc in pediatrics 88

89. Clinical manifestation Onset is usually abrupt Hematuria and edema are the most common complaints Microscopic hematuria in virtually all children with the disease Urine has a characteristic color, which is tea or cola color Gross edema is uncommon but periorbital edema esp. in the morning is common Hypertension is mild to moderate but occasionally may be sever enough to cause hypertensive encephalopathy which is the major acute complication of AGN. ARF and CHF may occur in some patients 9/18/2022 Yomilan G., MSc in pediatrics 89

90. Natural course of PSGN Spontaneous resolution typically begins in the 1 st wk Edema with in 7 to 10days Hypertension with in 2 to 3 wks Complete resolution in 95% Microscopic hematuria may persist up to 1 to 2yr End stage renal disease is rear (5%) Death is rare and if occur due to ARF. 9/18/2022 Yomilan G., MSc in pediatrics 90

91. Diagnosis U/A-demonstrates RBCs, RBC and WBC casts and proteinuria polymorphonuclear leukocytes (PMNLs) are common Serum complement usually decreased Confirmation of diagnosis needs clear evidence of invasive strept . Infection -ASO titer(not usually + ve in pyoderma) -anti DNase B titer -anti hyaluronidase -anti streptokinase 9/18/2022 Yomilan G., MSc in pediatrics 91

92. Indications for renal biopsy include Development of nephrotic syndrome (10-20%) ARF Normal complement level Absence of evidence of strept . Infection Persistence of hematuria, proteinuria diminished RFT and/or low complement level for more than 2 months. 9/18/2022 Yomilan G., MSc in pediatrics 92

93. Complications Hypertension is seen in 60% of patients and may be associated with hypertensive encephalopathy in 10% of cases. Acute renal failure and uremia Heart failure Hyperkalemia and hyperphosphatemia Hypocalcemia, acidosis and seizure 9/18/2022 Yomilan G., MSc in pediatrics 93

94. Treatment No specific therapy Early Abc Rx doesn’t eliminate the risk of PSGN. Mx is that of ARF Restriction of salt and fluid is recommended to Rx ARF, hypertension and edema. Furosemide 1-2mg/kg will provide a brisk diuresis and can be repeated at 6-8hrs interval. Hypertensive encephalopathy and seizure are medical emergencies - IV diazoxide or hydralazine . 9/18/2022 Yomilan G., MSc in pediatrics 94

95. Cot’d … It is infrequent for hypertension to last more than few days except in more sever cases of PSGN. Oral antihypertensive therapy is recommended in such patients Anti biotic therapy has no effect on the course of the disease however penicillin Rx is recommended to limit the spread of the infection. 9/18/2022 Yomilan G., MSc in pediatrics 95

96. IV. Fluid and Electrolyte General Principle 9/18/2022 Yomilan G., MSc in pediatrics 96

97. CONTENTS Anatomy of body fluids Classifications of body fluid changes -Volume changes -Concentration changes -Composition changes Electrolytes, electrolyte disturbances and their management- 9/18/2022 Yomilan G., MSc in pediatrics 97

98. ANATOMY OF BODY FLUIDS Wide range of normal values size , wt ,sex Water content 50-70% of total body weight (60% in males Vs 50% in females +/-15%). Fat less water and muscle more water Newborns highest % of body water 75-80% and at 4 yrs 65% TBW. BODY WATER has three functional compartments namely Intracellular 30-40% TBW Interstitial fluid 15% and Extracellular fluid - 20% Intravascular fluid or plasma 5% 9/18/2022 Yomilan G., MSc in pediatrics 98

99. Intracellular fluid – largest proportion in skeletal muscles Females less ICF b/s of large fat & less muscle. Potassium and magnesium are principal cations phosphates and proteins are major anion. Extracellular fluid –the major cation is sodium and the major anions are chloride and bicarbonates Interstitial fluid has in turn two compartments Rapidly equilibrating functional component Slowly equilibrating nonfunctional component -represents 10% of interstitium = 2%tbw -it is connective tissue water -called transcellular water CSF, JOINT FLUIDS 9/18/2022 Yomilan G., MSc in pediatrics 99

100. Diffusion b/n ECF and ICF is slight. Plasma - more proteins {organic anions}. total concentration of cations is higher . total concentration of inorganic anions is lower. Holds true with Gibbesdonnan equilibrium which states that the product of [ same pair of ions ] on one side of semipermeable membrane is equal to the product of [ same pairs ] on the other side. Water flows freely between ECF and ICF but net flow of water is achieved when there is concentration changes between the two otherwise no net flow. 9/18/2022 Yomilan G., MSc in pediatrics 100

101. Obligatory water loss through urine is about 500-800 ml per 24hr even without taking any and there is also mandatory insensible loss of about 600 ml per 24 hr. Water of oxidation is the water product of the oxidative process in the catabolism of food Water of solution is the water that hold CHOs and proteins in solution in the body and released when the body is starved for 4-5 days and starts to use stored CHOs and proteins. 9/18/2022 Yomilan G., MSc in pediatrics 101

102. ELECTROLYTE COMPOSITION OF BODY FLUIDS 9/18/2022 Yomilan G., MSc in pediatrics 102

103. Salt gain and losses Dietary intake is about 3-5gm {50-90 meq } /day Balance primarily by kidney and in reduced intake the renal excretion can be as low as 1meq per 24 hr. Sweet is hypotonic with Na+ of 15meq/ lt so practically sweet can be considered as loss of pure water GI losses are isotonic or slightly hypotonic . Distributional or sequestration of fluids in third space is loss of isotonic fluid of ECF. 9/18/2022 Yomilan G., MSc in pediatrics 103

104. Classification of body fluid changes Three major categories a- disturbance of volume b- disturbance of concentration c- disturbance of composition Volume changes occurs with loss of isotonic fluid or addition of isotonic fluid If there is depletion ,the depletion is from the ECF and there will not be transfer of fluid from the ICF to the ECF since there is no concentration change. Diagnosis is usually by clinical signs of water deficit or excess but one can use some laboratory investigations to see the indirect changes of fluid deficit of excess because fluid content of body can’t be measured directly. 9/18/2022 Yomilan G., MSc in pediatrics 104

105. BUN –rises with ECF deficit because of decreased GFR Serum Creatinine may not change so the two can be used to differentiate the prerenal and renal azotemia Hct and other formed elements of the blood show change with volume changes if the loss is not blood. Concentration of sodium is unrelated to fluid volume although the tonicity of extracellular fluid is determined mainly by sodium. 9/18/2022 Yomilan G., MSc in pediatrics 105

106. VOLUME DEFICIT- the most common fluid disorder in surgical patient The most common causes are losses from GI (-vomiting, nasogastric suction, fistula drainage) other commom causes include :sequestration in soft tissue injury and infection, intraabdominal and retroperitoneal inflammatory processes, peritonitis, burn) 9/18/2022 Yomilan G., MSc in pediatrics 106

107. Signs and symptoms include CNS and CVS sns and sxs arise early in the case of Acute rapid losses and tissue signs may take >24hrs Skin turgor may not be applicable in elderly and in pts who have lost significant weight recently. In severe fluid deficit body Temperature will be changing with environmental temperature Severe fluid depletion depresses all body systems and change of clinical Presentation ---no fever, no leucocytosis , no pain etc … 9/18/2022 Yomilan G., MSc in pediatrics 107

108. Principles of fluid resuscitation Maintenance fluid - the normal daily need of the body Normally about 2 liters of water is enough if kidneys are normal Affected by different factors Increased in fever, sweating, burns, tachypnea, surgical drains, polyuria, ongoing GI losses Decreased in oliguric renal failure, edematous state, hypothyroidism, humidified air 9/18/2022 Yomilan G., MSc in pediatrics 108

109. Principles of fluid resuscitation… Replacement fluid – is the replacement of the fluid which is already lost from the body or is constantly being lost by essentially the same kind of fluid a. R eplacement of deficit b. Replacement of ongoing loss In both the amount of fluid replaced is dependent on the amount lost or being lost. 9/18/2022 Yomilan G., MSc in pediatrics 109

110. Perioperative fluid management Maintenance requirement- Replacement of fluid losses - NPO losses = No of hrs NPO x maintenance fluid - NG tube suctioning - bowel preparation – can lead to about 1lt/ dy of GI loss Third space losses depends on the location and duration of surgical procedure, tissue trauma, ambient temperature and room ventilation . Quadrant calculation = ¼ maintenance for each quadrant of abdomen involved in infection in peritonitis and the quadrants involved In surgery Replacement of lost fluid or blood- crystalloid for blood replacement 3 units of crystalloid for each unit of blood lost. Postoperatively the third space fluid remains for about 3-4 days and go back to the ECF because of decreased ADH & aldosterone. 9/18/2022 Yomilan G., MSc in pediatrics 110

111. Fluid excess -generally can be considered as iatrogenic but can be coused by renal insufficiency ,cirrhosis and congestive heart failure. 9/18/2022 Yomilan G., MSc in pediatrics 111

112. Concentration changes Na+ is primarily responsible for the osmolality of ECF contributing about 90% of osmolality Osmolality of other ions can change without significant change with the osmolality of ECF so basically it will bring about compositional change like K+ concentration SODIUM – normal value 135-145 meq / lt -essential in water balance and neuromuscular membrane excitability -hypo- and hyper-natremia can be diagnosed clinically but manifests late and when severe -regulation at cellular level Na+-K+ pump and regulation at body level is by aldosterone through renin angiotensin system -daily requirement is about 1mmol/kg NaCl 9/18/2022 Yomilan G., MSc in pediatrics 112

113. Hyponatremia Is the decreased sodium level in the body Is most common electrolyte disturbance -Acute symptomatic < 130meq/ lt –Increased ICP -Excessive intracellular water -Systemic hypertension because of increased ICP -Rapid development of oliguric renal failure Chronic hyponatremia asymptomatic until Na=120meq/L but dangerous in the presence of increased ICP as in closed head injury leading to cellular oedema . 9/18/2022 Yomilan G., MSc in pediatrics 113

114. Hyponatremia… Common causes: loss of Na from fluid loss, Diuretics, vomiting , sweating , syndrome of inappropriate secretion of antidiuretic hormone (SIADH) , renal failure Failure of Na –k pump, DKA ,hypoxia, liver failure Dilution of Na+ from fluid overload Over administration of hypotonic solution 9/18/2022 Yomilan G., MSc in pediatrics 114

115. Signs and symptoms Water intoxication Muscle twitching ,hypoactive tendon reflexes, increased ICP Change in BP and pulse due to increase in ICP Salivation, lacrimation, watery diarrhea, fingerprinting of skin Oliguria progressing to anuria severe hyponatremia - convulsions, loss of reflexes, 9/18/2022 Yomilan G., MSc in pediatrics 115

116. Treatment – I/O, Wt , V/S, Level of consciousness, serum Na+ & osmolality Restrict hypotonic fluids Encourage foods and fluids with more sodium Carefull use of hypertonic solutions 9/18/2022 Yomilan G., MSc in pediatrics 116

117. Hypernatremia Is the increased sodium level in the body Dry sticky mucosal membrane Usually have elevated body temp. even to fatal levels called heatstroke causes include renal failure, decreased fluid intake hypertonic Iv fluids, tube feedings, excessive salt ingestion Diabetes insipidus {dec. ADH}, Aldosteronism {Na+H2O retention 9/18/2022 Yomilan G., MSc in pediatrics 117

118. Hypernatremia…. signs and symptoms restlessness, weakness, Tachycardia and hypotension, oliguria Decreased saliva and tears, dry and sticky mucosal membrane Red and swollen tongue with flashed skin Severe signs delirium and maniac sign Delirium is a serious disturbance in mental abilities that results in confused thinking and reduced awareness of the environment. 9/18/2022 Yomilan G., MSc in pediatrics 118

119. Treatment- I/O, Wt , V/S, LOC, serum Na and osmolality Careful use of hypotonic or isotonic solutions Restrict high sodium food or fluid Seizure precautions 9/18/2022 Yomilan G., MSc in pediatrics 119

120. Potassium normal value is 3.5-5.5 meq / lt daily dietary intake is about 50-100 meq 98% of potassium in the body is intracellular 150 meq / lt major cation of ICF with daily obligate renal loss of 20 meq important in cardiac and neuromuscular activity extremely rapid turnover in the ECF 9/18/2022 Yomilan G., MSc in pediatrics 120

121. Potassium… Regulation at cellular level by Na-K pump and regulation at body level by kidney controlled by aldosterone in exchange for Na+. our body is sensitive to slight changes to K+ concentration important in acid base balance – competes with H+ for renal tubular excretion in exchange for Na+ large quantities of K+ are released from ICF in to ECF during severe injury, surgical stress, acidosis & catabolic state 9/18/2022 Yomilan G., MSc in pediatrics 121

122. Hypokalemia Is the decreased potassium level in the body May induce metabolic alkalosis : Renal excretion of H+ for K+ retention and cellular exchange of K+ for H+ Its renal excretion is increased if large quantities of Na+ are available for excretion causes -Excessive renal excretion as in diuretics and hyperaldosteronism -Movement of K+ into the cells as in metabolic alkalosis and insulin -Prolonged use of K+ free Iv fluids causing hemodilution -Loss of GI excessive vomiting ,suctioning, diarrhea, laxatives -Renal tubular acidosis ,hepatic failure ,Cushing syndrome -Acute alcoholism, trauma /operation. 9/18/2022 Yomilan G., MSc in pediatrics 122

123. Hypokalemia… Signs and symptoms -Weakness ,nausea, vomiting, constipation, motility disorders -Hypotension, elevated pulses {decreased cardiac output} -EKG changes low voltage, flattened T-waves, depressed ST segement , prolonged QT interval Treatment –cardiac monitoring and watch for digitalis toxicity if on Rx -one has to attain urine output of at least 30 ml/ hr before initiation of any k+ Rx -never give K+ iv push it should be diluted and given in drips -best dealt with prevention 9/18/2022 Yomilan G., MSc in pediatrics 123

124. Hypokalemia… Precautions on K+ supplement No more than 40 meq in an hour and in a liter of fluid Not given to oliguric patients Not to pts with in 24hr of severe surgical stress/trauma 9/18/2022 Yomilan G., MSc in pediatrics 124

125. Hyperkalemia Is the increased potassium level in the body Causes K+ supplement, receiving old blood Na+-K+ pump failure as in movement of k+ out of the cell, hypoxia and acidosis Cell destruction as in crash injuries, burns, and hemolysis Inadequate k+ excretion as in decreased aldosterone adrenalectomy or Addison's disease Addison's disease is called adrenal insufficiency: too little cortisol production 9/18/2022 Yomilan G., MSc in pediatrics 125

126. Hyperkalemia… Signs and symptoms The signs of a significant hyperkalemia are limited to the cardiovascular and gastrointestinal systems. GI :nausea, vomiting, intermittent intestinal colic, diarrhea CVS: heart block, diastolic cardiac arrest EKG-high peaked T-waves, disappearance of T-waves Widened QRS complex, depressed ST segment 9/18/2022 Yomilan G., MSc in pediatrics 126

127. Hyperkalemia…. Treatment Place pt on cardiac monitoring Withholding of exogenous K+ and control cause Temporary suppression of myocardial effect of K+ can be achieved by injection of 1gm of 10% calcium gluconate under EKG monitoring Transiently reduced by administration of 40meq of sodium bicarbonate with 1000cc of 10% D/W and 20 IV of regular insulin Definitive management –cation exchange resins like kayexalate or by dialysis. 9/18/2022 Yomilan G., MSc in pediatrics 127

128. Reading assignment Magnesium Calcium 9/18/2022 Yomilan G., MSc in pediatrics 128

129. V. Urinary tract infections in children 9/18/2022 Yomilan G., MSc in pediatrics 129

130. PREVALENCE AND ETIOLOGY Urinary tract infections (UTIs) occur in 3–5% of girls 1% of boys. In girls, the first UTI usually occurs by the age of 5 yr, with peaks during infancy and toilet training. In boys, most UTIs occur during the 1st yr of life; UTIs are much more common in uncircumcised boys. Male : female ratio In the 1st yr of life, is 2.8–5.4 : 1 Beyond 1–2 yr, 1 : 10 9/18/2022 Yomilan G., MSc in pediatrics 130

131. Etiologies UTIs are caused mainly by colonic bacteria. In females, 75–90% of all infections are caused by Escherichia coli, followed by Klebsiella spp. and Proteus spp. Some series report that in males older than 1 yr of age, Proteus is as common a cause as E. coli; others report a preponderance of gram-positive organisms in males. Staphylococcus saprophyticus and enterococcus are pathogens in both sexes. Viral infections, particularly adenovirus, also may occur, especially as a cause of cystitis. 9/18/2022 Yomilan G., MSc in pediatrics 131

132. Risk factors Female gender Uncircumcised male    Vesicoureteral reflux   Toilet training    Voiding dysfunction    Obstructive uropathy    Urethral instrumentation    Wiping from back to front in females    9/18/2022 Yomilan G., MSc in pediatrics 132

133. Risk factors Bubble bath   Tight clothing (underwear)    Pinworm infestation    Constipation    Bacteria with P fimbriae    Anatomic abnormality (labial adhesion)    Neuropathic bladder    Sexual activity    Pregnancy 9/18/2022 Yomilan G., MSc in pediatrics 133

134. CLINICAL MANIFESTATIONS AND CLASSIFICATION The 3 basic forms of UTI are pyelonephritis, cystitis, and asymptomatic bacteriuria. 9/18/2022 Yomilan G., MSc in pediatrics 134

135. pyelonephritis Inflammation of the renal parenchyma is termed as acute pyelonephritis, whereas if there is no parenchymal involvement, it is called pyelitis . Acute pyelonephritis may result in renal injury, termed pyelonephritic scarring Pyelonephritis is the most common serious bacterial infection in infants <24 mo of age who have fever without a focus . 9/18/2022 Yomilan G., MSc in pediatrics 135

136. pyelonephritis is characterized by any or all of the following: abdominal or flank pain, fever, malaise, nausea, vomiting, and, occasionally, diarrhea. Newborns may show nonspecific symptoms such as poor feeding, irritability, and weight loss. 9/18/2022 Yomilan G., MSc in pediatrics 136

137. Acute lobar nephronia (acute lobar nephritis) is a localized renal bacterial infection involving >1 lobe that represents either a complication of pyelonephritis or an early stage in the development of a renal abscess. Renal abscess may occur following a pyelonephritis or may be secondary to a primary bacteremia (S. aureus). Perinephric abscesses may be secondary to contiguous infection in the perirenal area (e.g., vertebral osteomyelitis, psoas abscess) or pyelonephritis that dissects to the renal capsule. 9/18/2022 Yomilan G., MSc in pediatrics 137

138. Cystitis & asymptomatic bacteriuria Cystitis Inflammation of the bladder; symptoms include dysuria, urgency, frequency, suprapubic pain, incontinence, and malodorous urine. Cystitis does not cause fever and does not result in renal injury . 9/18/2022 Yomilan G., MSc in pediatrics 138

139. Asymptomatic bacteriuria A positive urine culture without any manifestations of infection. It is most common in girls. The incidence is 1–2% in preschool and school-age girls and 0.03% in boys. The incidence declines with increasing age. Is benign and does not cause renal injury, except in pregnant women, in whom asymptomatic bacteriuria, if left untreated, can result in a symptomatic UTI. 9/18/2022 Yomilan G., MSc in pediatrics 139

140. Diagnosis The correct diagnosis of UTI depends on having the proper sample of urine. In toilet-trained children use midstream urine sample If the culture shows >100,000 colonies of a single pathogen, or if there are 10,000 colonies and the child is symptomatic, the child is considered to have a UTI. In uncircumcised males, the prepuce must be retracted; if the prepuce is not retractable, this method of urine collection may be unreliable. 9/18/2022 Yomilan G., MSc in pediatrics 140

141. Diagnosis In infants, the application of an adhesive, sealed, sterile collection bag after disinfection of the skin of the genitals can be useful, particularly if the culture is negative. A positive culture may reflect a contaminant, particularly in girls and uncircumcised boys. In such cases, if the urinalysis result is positive, the patient is symptomatic, and there is a single organism cultured with a colony count greater than 100,000, there is a presumed UTI. If any of the above criteria are not met, confirmation of infection with a catheterized or supra pubic puncture sample is recommended. 9/18/2022 Yomilan G., MSc in pediatrics 141

142. Diagnosis Renal scintigraphy with dimercaptosuccinic acid (DMSA) may be warranted in select cases in which the diagnosis of acute pyelonephritis is necessary but uncertain because of equivocal urinalysis or culture results ( eg , in a septic-appearing infants who received antimicrobial therapy before the urine culture was obtained). 9/18/2022 Yomilan G., MSc in pediatrics 142

143. Diagnosis Pyuria (leukocytes in the urine) suggests infection, but infection can occur in the absence of pyuria ; consequently, this finding is more confirmatory than diagnostic. Conversely, pyuria can be present without UTI. Nitrites and leukocyte esterase usually are positive in infected urine. Microscopic hematuria is common in acute cystitis. White blood cell casts in the urinary sediment suggest renal involvement, but in practice these are rarely seen. if a child is symptomatic, UTI is possible, even if the urinalysis result is negative. 9/18/2022 Yomilan G., MSc in pediatrics 143

144. Dipstick test Dipstick technique(qualitative study) The presence of leukocyte esterase on dipstick analysis is suggestive of UTI. However, a positive leukocyte esterase test does not always signal a true UTI The nitrite test is highly specific, with a low false-positive rate. However, false-negative tests are common because urine needs to remain in the bladder for at least four hours to accumulate a detectable amount of nitrite. Thus, a negative nitrite test does not exclude a UTI 9/18/2022 Yomilan G., MSc in pediatrics 144

145. Microscopic examination In standard microscopy, a centrifuged sample of unstained urine is examined for white blood cells (WBC) and bacteria. When performed in this way, pyuria is defined as ≥ 5 WBC/high power field ( hpf ) and bacteriuria as the presence of any bacteria per hpf . The sensitivity of a centrifuged urine specimen is at best 81 percent, so urine culture should be obtained in children with suspected UTI who have a negative standard microscopic examination. 9/18/2022 Yomilan G., MSc in pediatrics 145

146. Investigations CBC with differential ESR CRP(c reactive protein) Abdominal ultrasound Voiding cystouretrography KUB Renal scintigraphy RFT 9/18/2022 Yomilan G., MSc in pediatrics 146

147. Treatment ,Cystitis If treatment is initiated before the results of a culture and sensitivities are available, a 3- to 5-day course of therapy with trimethoprim-sulfamethoxazole is effective against most strains of E. coli. Nitrofurantoin (5–7 mg/kg/24 hr in 3 to 4 divided doses) also is effective and has the advantage of being active against Klebsiella-Enterobacter organisms. Amoxicillin (50 mg/kg/24 hr) also is effective as initial treatment but has no clear advantages over sulfonamides or nitrofurantoin . 9/18/2022 Yomilan G., MSc in pediatrics 147

148. Treatment,pylonephrites Patients who are dehydrated b/c of persistent vomiting should be admitted to hospital. Ceftriaxone 75 mg/kg BID for 10-14 days Ampicilin 100mg/kg/24 hrs QID plus Gentamicin 3-5mg/kg/24h For UTI caused by pseudomonas in those >17 yrs Ciprofloxacin is effective . Surgical drainage if renal or perinephric abscess 9/18/2022 Yomilan G., MSc in pediatrics 148

149. Complications ,chronic Renal insufficiency ESRD(end stage renal disease) Secondary arterial hypertension 9/18/2022 Yomilan G., MSc in pediatrics 149

150. References schwartz principles of surgery uptodate 14.1 and 16.3 ACS textbook of surgery Sabstan text book of surgery Nelson text Book of Pediatrics,20 th edition 9/18/2022 Yomilan G., MSc in pediatrics 150