Nephritic syndrome Notes


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This Osmosis High-Yield Note provides an overview of Nephritic syndrome essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Nephritic syndrome:

Poststreptococcal glomerulonephritis

Goodpasture syndrome

Hemolytic-uremic syndrome

IgA nephropathy (NORD)

Rapidly progressive glomerulonephritis

NOTES NOTES NEPHRITIC SYNDROME GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Diseases caused by inflammation, damage to glomeruli of kidney; become more permeable, allow red blood cells (RBCs) into urine → hematuria CAUSES ▪ Children/adolescents: IgA nephropathy, post-streptococcal glomerulonephritis, hemolytic uremic syndrome ▪ Adults: systemic lupus erythematosus, Goodpasture’s syndrome, rapidly progressive glomerulonephritis COMPLICATIONS ▪ Acute kidney failure SIGNS & SYMPTOMS ▪ Damaged, permeable glomeruli → hematuria, proteinuria ▪ Decreased glomerular filtration rate → edema, hypertension ▪ Less waste product excreted → uremia DIAGNOSIS LAB RESULTS ▪ Protein/blood, RBC casts in urine ▪ Decreased glomerular filtration Kidney biopsy ▪ Changes under light/electron microscope, immunofluorescence TREATMENT MEDICATIONS ▪ Edema ▫ Diuretics (furosemide), medical nutrition therapy ▪ Blood pressure control ▫ Angiotensin converting enzyme inhibitors (ACE) inhibitors OTHER INTERVENTIONS ▪ Reduce salt, potassium intake OSMOSIS.ORG 825
ACUTE PROLIFERATIVE GLOMERULONEPHRITIS PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Inflammation of glomeruli, complication of bacterial infection ▪ AKA poststreptococcal glomerulonephritis ▫ Commonly arises several weeks after group A beta-hemolytic streptococcus infection ▪ Type III hypersensitivity reaction ▫ IgG/IgM antibodies bind to bacterial antigens, form immune complexes → complexes travel through bloodstream to glomerulus, deposit in glomerular basement membrane ▪ Immune complex/complement deposits trigger immune reactions ▫ Activate complement system → enzyme cascade → formation of membrane attack complex → damage to podocytes, mesangial cells ▫ Recruit inflammatory cells → proteases, oxidants release → basement membrane damage → hematuria, proteinuria → nephritic syndrome ▪ Nephritic syndrome: hematuria, oliguria, edema, hypertension ▪ Fever, headache, malaise, anorexia, nausea CAUSES ▪ Group A beta-hemolytic streptococcus infection RISK FACTORS ▪ Most commonly in children (who are biologically male) ▫ Six weeks after impetigo, 1–2 weeks after throat infection COMPLICATIONS ▪ Rapidly progressive glomerulonephritis, renal failure 826 OSMOSIS.ORG DIAGNOSIS LAB RESULTS ▪ Protein/blood in urine ▪ Antibodies against group A streptococcus (e.g. anti-DNase B antibodies, antiStreptolysin O antibody) ▪ Decreased complement levels Renal biopsy ▪ Light microscopy ▫ Mesangial proliferation → hypercellular glomerulus ▪ Electron microscopy ▫ Subepithelial deposits of immune complexes, “humps” ▪ Immunofluorescence ▫ “Starry sky,” granular deposition of IgG, complement in basement membrane, mesangium TREATMENT ▪ Usually supportive
Chapter 117 Nephritic Syndrome Figure 117.1 The effect of crescentic glomerulonephritis on the nephron. Figure 117.2 The constituent parts of the crescent seen in crescentic glomerulonephritis. Figure 117.3 Histological appearance of the glomerulus in post-infective glomerulonephritis. The glomerulus is expanded and compressed due to infiltration of neutrophils and other inflammatory cells. OSMOSIS.ORG 827
GOODPASTURE'S SYNDROME PATHOLOGY & CAUSES ▪ AKA anti-GBM antibody disease; damage of basement membrane in lungs, kidneys; mostly composed of Type IV collagen ▪ Damaged by Type II hypersensitivity reaction ▫ IgG antibodies (rarely IgM/IgA) bind to alpha 3 folded chain → activate complement system → damage collagen fibers of basement membrane RISK FACTORS ▪ Bimodal distribution with peak incidence age 20–30 (biologically male), 60–70 (biologically female) ▪ Genetic: predisposition for genes that code for HLA-DR15 (immune molecule; identifies, binds to foreign molecules) ▪ Environmental: infection, smoking, oxidative stress, hydrocarbon-based solvents DIAGNOSIS LAB RESULTS Renal biopsy ▪ Light microscopy ▫ Crescentic glomerulonephritis ▪ Electron microscopy ▫ Diffuse thickening of glomerular basement membrane ▪ Immunofluorescence ▫ Linear deposition along basement membrane TREATMENT MEDICATIONS ▪ Corticosteroids, cyclophosphamide, plasmapheresis to filter plasma/fluid of blood (reduces risk of chronic renal failure) COMPLICATIONS ▪ Chronic renal failure; require dialysis/kidney transplant; hemoptysis SIGNS & SYMPTOMS ▪ Pulmonary manifestations usually occur before renal ones; minority (20–40%) with only renal manifestations ▫ Damaged lung alveoli → cough, hemoptysis, dyspnea ▫ Kidney filtration problems (e.g. hematuria, proteinuria) → nephritic syndrome 828 OSMOSIS.ORG Figure 117.4 Histological appearance of the kidney in a case of crescentic glomerulonephritis caused by Goodpasture’s syndrome.glomerulonephritis on the nephron.
Chapter 117 Nephritic Syndrome Figure 117.5 Immunofluorescence with positive signal for antibodies to IgG. In addition the IgG deposition is linear. These features are consistent with Goodpasture’s syndrome. HEMOLYTIC-UREMIC SYNDROME PATHOLOGY & CAUSES ▪ Small blood clots in tiny blood vessels, mostly in kidneys → RBCs break down, kidney function decreases → urea levels in blood increase ▪ Triggered by bloody diarrhea ▫ Diarrhea-positive/D+ hemolytic uremic syndrome (HUS/typical HUS) Atypical hemolytic uremic syndrome ▪ D-hemolytic uremic syndrome ▫ No preceding diarrhea ▪ Damage to endothelial cell lining of glomerular capillaries from infections not related to diarrhea, medication, autoimmune causes ▪ Infants, children ▫ Streptococcus pneumoniae presents as pneumonia/meningitis ▪ Familial forms ▫ Genetically increased tendency for endothelial cell damage CAUSES ▪ Escherichia coli (E. coli) from contaminated food/drink ▫ Enterohemorrhagic E. coli (EHEC, serotype O157:H7); may be caused by other strains ▫ E. coli attaches to intestinal wall → secretes Shiga-like toxin → absorbed by intestinal blood vessels → attaches to immune cells → toxins from white blood cells (WBCs) bind to endothelial cells of glomerular capillaries → inhibition of protein synthesis → apoptosis → many tiny blood clots form in kidneys RISK FACTORS ▪ Children < five years old, people 75+ years old, genetic predisposition to endothelial cell damage OSMOSIS.ORG 829
SIGNS & SYMPTOMS ▪ Bloody diarrhea ▪ Weakness, fatigue, lethargy, jaundice due to red blood cell destruction ▪ Fever, blood clots: affect brain blood supply → visual disturbances, altered mental status, seizures, stroke → death DIAGNOSIS TREATMENT MEDICATIONS Typical, D+ hemolytic uremic syndrome ▪ Shiga-like toxin clears in days to weeks, antibiotics not recommended as dead bacteria potentially release more toxins Atypical hemolytic uremic syndrome ▪ Identify underlying cause LAB RESULTS ▪ Requires thrombocytopenia, microangiopathic hemolytic anemia (MAHA), acute renal failure ▪ Proteinuria, hematuria ▪ Schistocytes/helmet cells ▪ D+ hemolytic uremic syndrome ▫ Shiga toxin (ELISA), gene encoding Shiga toxin (PCR) ▪ Differential diagnosis ▫ Thrombotic thrombocytopenic purpura (TTP) hemolytic uremic syndrome: measure ADAMTS13 activity in plasma ▫ Disseminated intravascular coagulation (DIC): DIC panel (e.g. pTT, INR, d-dimer, fibrinogen) Figure 117.6 90% of hemolytic-uremic syndrome cases are a result of a prior infection with Shiga toxin producing E. coli. 830 OSMOSIS.ORG Figure 117.7 Histological appearance of acute thrombotic microangiopathy which is the pathological mechanism of renal failure in hemolytic uremic syndrome. Endothelial damage caused thrombus formation in small capillaries.
Chapter 117 Nephritic Syndrome IgA NEPHROPATHY PATHOLOGY & CAUSES ▪ AKA Berger’s disease; abnormal IgA forms, deposits in kidneys → kidney damage ▪ Abnormal post-translational modification of IgA → development of IgA immune complexes preferentially deposited in mesangium → alternative complement pathway activated → cytokines released → macrophages migrate to kidney → glomerular injury → RBCs leak into urine ▪ Associated with gastrointestinal (GI)/ respiratory tract infections RISK FACTORS ▪ Most common nephropathy worldwide; usually presents in childhood ▪ Highest prevalence in people of East Asian/ European ancestry ▪ Family history of chronic nephritis, alcohol consumption, recurrent infections DIAGNOSIS LAB RESULTS ▪ RBCs, RBC casts Renal biopsy ▪ Light microscopy ▫ Mesangial proliferation, immune complexes deposited in mesangium ▪ Electron microscopy ▫ Immune complexes deposited in mesangium ▪ Immunofluorescence ▫ Mesangial IgA deposits, +/- IgA, +/- IgM TREATMENT MEDICATIONS ▪ Corticosteroids ▫ Prevent immune system making defective IgA1, anti-glycan IgG COMPLICATIONS ▪ Nephrotic syndrome, chronic kidney disease SIGNS & SYMPTOMS ▪ Episodic hematuria ▫ Sometimes accompanying upper respiratory tract infections ▪ Asymptomatic microscopic hematuria ▫ With subnephrotic proteinuria ▪ Classic nephrotic syndrome/kidney injury (minority) Figure 117.8 Immunofluorescence with positive signal for antibodies to IgA immunoglobulin. The pattern of deposition in the glomerulus is granular. OSMOSIS.ORG 831
RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS PATHOLOGY & CAUSES ▪ Inflammation of kidney’s glomeruli → crescent-shaped proliferation of cells in Bowman’s capsule → renal failure within weeks/months ▪ Inflammation damages glomerular basement membrane → inflammatory mediators, complement proteins, fibrin, monocytes macrophages pass into Bowman’s space → expansion of parietal layer of cells into thick, crescent-moon shape → may undergo sclerosis/scarring TYPES Primary ▪ Idiopathic Secondary ▪ Type I: anti-GBM antibodies ▫ Goodpasture syndrome ▪ Type II: immune complexes ▫ Poststreptococcal glomerulonephritis, systemic lupus erythematosus, IgA nephropathy, Henoch-Schonlein purpura ▪ Type III: anti-neutrophilic cytoplasmic antibodies (ANCA) ▫ Cytoplasmic ANCA (C-ANCA): Wegener’s granulomatosis ▫ Perinuclear ANCA (P-ANCA): microscopic polyangiitis, Churg-Strauss syndrome COMPLICATIONS ▪ If untreated: rapid progression to acute renal failure 832 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ Nephritic syndrome ▫ Hematuria, oliguria, edema, hypertension DIAGNOSIS LAB RESULTS Kidney biopsy ▪ Light microscopy: crescent-shaped glomeruli Immunofluorescence ▪ Type I: linear, antibodies bind to collagen of glomerular basement membrane ▪ Type II: granular, immune complex deposition in subendothelium ▪ Type III: negative (pauci-immune) ▫ Type III associated with ANCAs in blood TREATMENT MEDICATIONS ▪ Pulse methylprednisolone, then prednisone/cyclophosphamide/rituximab/ plasmapheresis OTHER INTERVENTIONS ▪ If renal failure irreversible ▫ Dialysis/kidney transplant
Chapter 117 Nephritic Syndrome OSMOSIS.ORG 833

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