ACUTE GLOMERULONEPHRITIS FATUROTI M.O CONTENT • INTRODUCTION • DEFINATION • EPIDERMIOLGY • AETIOLGY • PATHOPHYSIOLOGY • CLINICAL FEATURES • INVESTIGATIONS • TREATMENT INTRODUCTION • ACUTE GN is the term generally reserved for the variety of renal diseases in which inflammation of the glomerulus , manifested by proliferation of cellular elements, is secondary to an immunologic mechanism. • In earlier years, AGN often was known inappropriately as Bright disease, and almost any clinical presentation of gross hematuria was labeled.Most incidents of AGN appear to be associated with a post infectious state. Several bacterial and viral infections like staphylococcal and pneumonococcal infections, coxsackie virus B, echovirus type 9, influenza virus, and mumps • The most commonly recognized clinical picture (i.e, PSAGN) follows infection with group A beta hemolytic streptococci DEFINATION • ACUTE GLOMERULONEPHRITIS IS A NON SUPPRATIVE IMMUNE MEDIATED INFLAMATORY LESION OF THE GLOMERULUS . • IT IS USUALLY OF SUDDEN ONSET • IT IS XTERISED BY ACCUMULATION OF NITROGENOUS WASTE IN THE BLOOD FLIUD &ELECTROLTE DERANGEMENT EPIDERMIOLGY • IN THE TROPIC,CHILDERN OF THE PRESCHOOL AGE ARE COMMONLY AFFECTED,WHILE ELSEWHERE CHILDREN OF THE SCHOOL AGE ARE COMMONLY AFFECTED • No racial predilection appears to exist; the condition is reported in all ethnic and cultural groups. In urban populations, a predilection toward minority populations appears to exist; however, this may be related more to the socioeconomic factor of overcrowding than to any racial predilection • . The disease is more prevalent in males in all regions of the world; the male-to-female ratio range is 1.7-2:1. AETIOLGY • MOST INCIDENTS OF AGN APPEAR TO BE ASSOCIATED WITH A POSTINFECTIOUS STATE. SEVERAL BACTERIAL AND VIRAL INFECTIONS HAVE BEEN ASSOCIATED TO BE ITS CAUSESUCH AS STAPHYLOCOCCAL AND PNEUMONOCOCCAL INFECTIONS, COXSACKIEVIRUS B, ECHOVIRUS TYPE 9, INFLUENZA VIRUS, AND MUMPS • THE MOST COMMONLY OCCURING IS POSTSTRETOCOCCI AGN .THE ORGANISM IS THE B HEMOLYTIC LANCE FIELD GROUP A STEPTOCOCCUS • IN EUROPE /AMERICA MAY RESULT FROM A SORE THROAT INFECTION • THIS INFECTION MAY PRESENT AS IMPETIGO /2 SCABIETIC INFECTION. PATHOPHYSIOLOGY CHECK • Most forms of AGN are mediated by an immunologic process. For PSAGN, the evidence suggests that immune complexes, preformed by the combination of specific antibodies against streptococcal antigens, localize on the glomerular capillary wall and activate the complement system. The immunologic system also may be activated by streptococcal antigens that adhere to the glomerular structures and act as "planted antigens" or by alterations in endogenous antigens. The activation of the complement cascade then generates chemotactic plasma-activated complement 5 (C5a) and platelet-derived inflammatory mediators. Various cytokines and other cellular immunity factors initiate an inflammatory response manifested by cellular proliferation and edema of the glomerular tuft. At least 2 antigens isolated from nephritogenic streptococci, zymogen (a precursor of exotoxin B) and glyceraldehyde phosphate dehydrogenase (GAPDH), have been identified and are believed to be capable of initiating the immunologic response. • Although streptococcal infections are associated intimately with PSAGN, the mechanism of renal injury still is defined incompletely. Current evidence suggests that the inflammatory lesion in the glomerulus is associated with the fixation of soluble streptococcal antigen-antibody complexes. • Several investigators have detected streptococcal antigen in renal biopsy material obtained early in the course of infection; however, the major evidence supporting an immune complex type of nephritis has been the finding of nodular deposits of immunoglobulin G (IgG) and the third component of complement (C3) on the capillary basement membrane. The finding of C3 in the renal glomerulus usually is associated with decreased serum concentrations of C3 and total hemolytic complement. • Decreased concentration of properdin and C3 proactivator and inconsistent decreases in the early components of complement indicate that complement activation occurs primarily by the alternate pathway. Reduced serum concentrations of C3 have been demonstrated in 80-92% of children with PSAGN. Values return to normal in most children within 6-8 weeks. The fourth component of complement (C4) value also may be depressed; however, this is an inconsistent finding. • PSAGN can occur in epidemics, or, more commonly, it can be sporadic. The sporadic form is seasonal; the winter- spring peak is associated with respiratory infection, and the summer-fall peak most often is associated with pyoderma. The most common serotype of group A beta hemolytic streptococci associated with nephritis from nasopharyngeal infections is type 12, whereas type 49 most often is recovered during outbreaks of pyoderma- related PSAGN. In individuals with pharyngitis-related AGN, the latent period is approximately 10 days, and more than 80% of patients exhibit a significant rise in serum titer of antistreptolysin-O (ASO). • Conversely, a latent period is difficult to define in persons with impetigo-related AGN, and a rise in the titer of ASO is observed in only 50% of patients. Serum concentrations of other streptococcal indicators (eg, antihyaluronidase [AH] titer, antideoxyribonuclease B titer [anti-DNase B]) usually are elevated in individuals with PSAGN secondary to either pharyngeal or skin infections. When a variety of antibody titers is used, almost 95% of patients with PSAGN demonstrate evidence of a prior streptococcal infection. • Although renal biopsies now are indicated rarely in children with typical PSAGN, they have contributed substantially to the understanding of this disease. Irrespective of the degree of severity of the initial inflammatory response, the histologic picture is consistent and specific. As observed by light microscopy, glomerular changes are generalized and diffuse. The glomerular tufts usually appear enlarged and swollen, and a moderate-to-marked increase in proliferation of mesangial and epithelial cells is present. • Polymorphonuclear leukocytes also are observed often as part of the inflammatory process. In persons with the most severe disease, the glomeruli appear bloodless due to the associated edema of the capillary walls, which impedes glomerular perfusion. A direct correlation exists between the severity of the histologic process and the clinical manifestations of the disease during the acute phase, and possibly the prognosis. • Granular deposits of IgG and C3 typically are found when the specimen is studied by immunofluorescent microscopy; other immunoglobulins (Igs) and fibrinogen often are observed. Electron microscopy of renal tissue from patients with PSAGN usually reveals subepithelial electron-dense deposits (humps). • In most patients with moderate-to-severe AGN CLINICAL FEATURES • THEY INCLUDE ; • FACIAL PUFFINESS; The edema first collects in those sites where tissue resistance is low, such as the periorbital area. Later, it becomes more generalized, and, in those few patients in whom loss of albumin is exaggerated with resultant hypoalbuminemia, the edema even may simulate that of the nephrotic syndrome • REDUCTION IN URINE VOLUME; Glomerular inflammation (ie, cellular proliferation, edema) reduces glomerular filtration without a coexistent decrease in total renal blood flow.The reduced volume of GF and the normal tubular function lead to an increase in the reabsorption of salt and water, with resulting oliguria and edema • APATHYHypertensive encephalopathy has been reported in approximately 5% of hospitalized children and is the most serious early complication of this disease. • In these patients, hypertension usually is severe and is accompanied by signs of central nervous system dysfunction such as headache, vomiting, depressed sensorium, confusion, visual disturbances, aphasia, memory loss, coma, and convulsions. SEIZURES 2 TO UREAMIA • Hypertensive encephalopathy has been reported in the occasional individual with minimal or no edema and with minimal urinary abnormalities. • DIFFICULTY IN BREATHING;. Circulatory congestion is apparent in most children admitted to the hospital but is responsible only rarely for significant early symptoms. – Dyspnea, orthopnea, and cough may be present. – Pulmonary rales often are audible. – At times, the only evidence of congestion is detected on chest radiograph. – In the patient with an otherwise normal cardiovascular system, cardiac failure is unusual • • HYPERTENSION; Hypertension is the third cardinal feature of PSAGN and is reported in 50-90% of children who are hospitalized with AGN. – The pathogenesis of the hypertension is unknown; however, pathogenesis probably is multifactorial and related only in part to ECF volume expansion. – The magnitude of the increase in BP is highly variable; however, systolic pressures greater than 200 mm Hg and diastolic pressures greater than 120 mm Hg are not unusual – ALTERED URINE COLOURATION; Gross hematuria occurs at onset in 30-50% of children with PSAGN who require hospitalization. – The urine usually is described as being smoky, cola colored, tea colored, or rusTY • SMOKY DARK BROWN FRANKLY BLOODY • CONSISTUTIONAL SYMPTOMS LIKE malaise, lethargy, anorexia, fever, abdominal pain, and headache. Observant parents also may note oliguria. • HISTORY OF the siblings and/or household contacts of children affected with PSAGN IS IMPORTANT – An insidious onset of edema is more indicative of other forms of renal disease. – An occasional child may have a scarlatiniform rash or evidence of a viral exanthema, but petechial or purpuric rashes suggest other conditions. – Almost characteristic by their absence are arthralgia, arthritis, carditis, hepatic involvement, and GI bleeding • INVESTIGATIONS • URINALYSIS;RED CELL CAST OBSERVERED IN FRESH URINE SAMPLES/HEAM GRANULAR CAST • PROTEINURIA EVIDENCEND BY DIP STICK OF +1/+2 corresponding to less than 2 g/m2/d when assessed quantitatively • S.G;ELEVATED • FBC/PLATELET; RBC/PLATELET IS DECREASED [ANEMIA] • UREA/CR –ELEVATED • SERUM PROTEIN LOW • FRACTIONATING NA IS <1%IN AGN NEPHROTIC SYNDROME DEHYDRATION/ UNLIKE AKI WC IS >1% • RENAL USS Renal ultrasonography generally demonstrates normal to slightly enlarged kidneys bilaterally with some evidence of increased echogenicity. • ASOTITRE SHLD BE DOCUMENTEDLook for evidence of streptococcal infection in all patients. • Cultures from either the pharynx or skin may be positive; however, high streptococcal antibody titers are more compelling. • A number of laboratory tests can be used to measure antibodies to a variety of streptococcal antigens (eg, ASO, AH, anti-DNase B) or to combinations of antigens (eg, streptozyme test). • Whatever test is used, a rise in the titer of the antibody, measured at an interval of 2-3 weeks, is more meaningful than a single measurement. • C3/C4 SHLD BE INVESTEGATED;These tests help to differentiate poststreptococcal from other postinfectious forms of AGN • Chest radiographs commonly demonstrate central venous congestion in a hilar pattern, the degree of which parallels the increase in ECF volume. TREATMENT • THERE COMPLICATIONS • PULMONARY EDEMA • CCF • AKI • HYPERTENSIVE ENCEPHALOPATY • UTI DD • Postinfectious glomerulonephritis Poststreptococcal After other bacterial infections Postviral infectionsthe most common are varicella-zoster virus, cytomegalovirus, and the Epstein-Barr virus. Postparasitic infections IgA-associated glomerulonephritisEvidence of a prior streptococcal illness usually is lacking in individuals with HSP nephritis, and complement values (C3 and/or C4) usually are normal. Henoch-Schönlein purpura (HSP) nephritis Other IgA nephritis (Berger disease) presents as an episode of gross hematuria occurring during the early stages of a respiratory illness Others (less common) Chronic GN (recurrence and/or relapse) Shunt nephritis Familial nephritis Rapidly progressive (crescentic) GN SLE nephritis occasionally may be confused with PSAGN when an acute exacerbation of the previously present nephropathy is present. SELF SLIDE • Most patients with acute GN exhibit milder symptoms and/or signs somewhere between the extremes described below. – At one extreme is the asymptomatic child whose disease is discovered only by examination of the urine. Based on surveillance studies of the siblings and/or household contacts of children affected with PSAGN, at least 50% of persons with laboratory evidence of nephritis (ie, abnormal urinalysis) appear to have no symptoms or signs of clinical illness. – At the other extreme is the child who presents with severe disease manifested by oliguria, edema, hypertension, and azotemia and with proteinuria, hematuria, and urinary casts (cylindruria). • In those patients whose acute GN is the result of a postinfectious cause (ie, PSAGN being the most common), a latent period of 7-21 days between onset of the streptococcal infection and development of clinical GN is characteristic. – This latent period, more clearly defined after pharyngeal infections than after pyoderma, averages approximately 10 days. – The development of clinical nephritis (ie, hematuria and/or edema) either during or within 2-5 days after the onset of a respiratory infection is atypical and suggests the possibility of some other form of GN. • Gross hematuria and/or edema represent the most common clinical presentation. – One or both findings usually appear abruptly and may be associated with various degrees of malaise, lethargy, anorexia, fever, abdominal pain, and headache. Observant parents also may note oliguria. – An insidious onset of edema is more indicative of other forms of renal disease. – An occasional child may have a scarlatiniform rash or evidence of a viral exanthema, but petechial or purpuric rashes suggest other conditions. – Almost characteristic by their absence are arthralgia, arthritis, carditis, hepatic involvement, and GI bleeding. – Edema is the most frequent presenting symptom. • According to some investigators, edema is found in approximately 85% of patients. • Edema usually appears abruptly and first involves the periorbital area, but it may be generalized. • The degree of edema varies markedly and depends on a number of factors, including the severity of glomerular involvement, the fluid intake, and the degree of hypoalbuminemia. – Gross hematuria occurs at onset in 30-50% of children with PSAGN who require hospitalization. • The urine usually is described as being smoky, cola colored, tea colored, or rusty. • Observant parents may note oliguria. • Clots are exceedingly rare in persons with AGN. • Hypertension is the third cardinal feature of PSAGN and is reported in 50-90% of children who are hospitalized with AGN. – The pathogenesis of the hypertension is unknown; however, pathogenesis probably is multifactorial and related only in part to ECF volume expansion. – The magnitude of the increase in BP is highly variable; however, systolic pressures greater than 200 mm Hg and diastolic pressures greater than 120 mm Hg are not unusual. – Hypertensive encephalopathy has been reported in approximately 5% of hospitalized children and is the most serious early complication of this disease.
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