Page 1 of 18 Nephritic vs. Nephrotic Syndrome Terminology: Glomerulus: A network of blood capillaries contained within the cuplike end (Bowman s capsule) of a nephron. Glomerular filtration rate: The rate at which substances are filtered from the blood of the glomeruli in the Bowman s capsules of the nephrons. It is calculated by the measuring of the clearance of creatinine and is an index of renal function. Glomerulitis: Lesions of the glomeruli associated with acute or chronic kidney diseases. Such lesions are recognized by electron microscopic examination and immunofluorescent staining techniques. Glomerulonephritis: Group of kidney diseases involving the glomeruli that mostly is the result of antibody-antigen reactions that localize in the kidneys because of their filtration function. Inflammatory response: Response of the tissues of the body to irritation or (inflammation) injury, characterized by pain, swelling, redness, and heat. The process involve increased blood flow to the area bringing with it immune proteins and leukocytes. Syndrome: A combination of signs and/or symptoms that forms a distinct clinical picture indicative of a particular disorder. Basement membrane: The thin delicate membrane that lies at the base of an epithelium. Podocyte: A podo-comb. forms indicate an association with foot. In this instance it means footcell or cell that forms a foot. Hyalinization: The hyaline is an amorphous material, pink, homogeneous, resulting from combination of plasma proteins, increased mesangial matrix and collagen.
Page 2 of 18 ANCA: Antineutrophil cytoplasmic antibodies (ANCA) have been proven to be useful diagnostic tools in patients with systemic vasculitis and glomerulonephritis. These antibodies exist in two types, a cytoplasmic pattern (canca) and a perinuclear pattern (panca). The effect of the main ANCA subtypes on renal outcome and its relationship to demographic findings and clinical features of patients with ANCA-associated glomerulonephritis has not been adequately studied. Acronyms: GBM - Glomerular basement membrane Anatomy and physiology: Position of the Glomerulus in the kidney. wongturn.files.wordpress.com/.../glomerulus.jpg opened 14/2/11
Page 3 of 18 The normal Glomerulus: Components and function academic.kellogg.cc.mi.us/herbrandsonc/bio201... opened 14/2/11 The function of a Glomerulus is the filtration of waste products into the kidney tubule. It consists of an afferent arteriole bringing the dirty blood into the Glomerulus. The arteries than split into a tuft of smaller capillaries called the Glomerulus. Because of the pressure inside the glomeruli substances are then selectively forced out of the capillaries (glomeruli) into the capsular space and enter the Proximal convoluted tubule. By selective we mean molecules of a certain size can pass through and bigger molecules are kept in blood and then exit the Glomerulus via the Efferent arteriole and rejoin the circulation. Bigger molecules include macromolecules like albumin and globulin.
Page 4 of 18 Normal renal handling of albumin. (a) Normal glomerulus and proximal tubule. Albumin (represented by green spheres) normally remains within the capillaries of the glomerular tuft, and does not escape into the urinary (Bowman's) space. The normal excretion of protein is < 0, 15 g/24 hour. (b) Glomerular filtration barrier. This barrier comprises the innermost Glomerular endothelial cells, GBM, and outermost podocytes; and serves to serially limit albumin escaping from the capillary loops. Podocytes attach to the outermost aspect of the GBM by foot processes. The slit diaphragm size allows small molecules through but inhibited the larger molecules like proteins and lipids to filter in to the proximal tube. www.nature.com/.../v74/n1/images/ki2008128f2.jpg opened 14/2/11 Disorders of the glomerulus: Disorders that affect the glomerulus can be divided into two groups one type is associated with the immune system via immune complexes - nephritic syndrome (inflammatory response) and the non-inflammatory glomerular diseases -nephrotic syndrome.
Page 5 of 18 Nephritic syndrome: Nephritic syndrome is defined as an inflammatory response causing rupture of the glomerular capillaries and leading to hematuria (blood in urine). Causes: Nephritic syndrome Cause Description Postinfectious glomeulonephritis Post-Streptococcal glomerulonephritis Immune complexes are deposited in the GBM. The glomeruli appear big, hypercellular with lots of inflammatory cells IgA nephropathy Children swollen face Berger disease Clinical Features of Nephritic Syndrome Children and young adults after respiratory infections Increased IgA trapped in the glomerulus activating complement. Nephritic syndrome is defined by: hematuria (RBC s in urine) RBC casts on microscopic examination of urinary sediment. Often one or more elements: mild to moderate proteinuria (subnephrotic proteinuria of < 3.0 g per 24 h), (normal <0,15g/24 hour) edema, due to loss of proteins, more fluid move into the tissue, causing swelling of the face (especially eye area) and limbs hypertension, due to retention of salt and water elevated serum creatinine oliguria ( 400 ml/day of urine) Normal : 750 to 2000 ml/24hr elevated serum urea (Azotemia )
Page 6 of 18 Laboratory tests: Urine analysis: Appearance: tea-color to coke color Dipstick: increased protein (quantitative measurement: < 3.0 g per 24 h), (normal <0,15g/24 hour) positive haemoglobin and red blood cell strip medsci.indiana.edu/.../urinrev/media/cse4c.jpg opened 17/2/11 Serum: Increased creatinine (normal male: 64 104 µmol/l female: 49-90 µmol/l) Decreased creatinine clearance (normal > 90 ml/min) Increased urea (normal male: 0.21 0.43 mmol/l female: 0.16 0.36 mmol/l) Decreased serum albumin (35 52 g/l) Other: Renal biopsy Serum complement profile Serologic tests Fluorescent staining for deposits immune complexes
Page 7 of 18 Nephrotic syndrome: Nephrotic syndrome is defined as an increase permeability of the basement membrane leading to massive proteinuria (proteins in the urine). This is mainly to the loss of foot processes or podocytes (refer to picture on Normal renal handling of Albumin pg 4). Causes: Nephrotic syndrome Cause: Description: Systemic non-renal diseases Diabetes Renal diseases: Minimal change disease Mainly in children Pathogenesis unknown Called minimal change disease because under the light microscope the glomerulus appears normal Focal segmental glomerulosclerosis Prognosis good Primary or secondary to diseases like HIV and heroin use. Microscopically a section will show some glomeruli show partial or segmented hyalinization Membranous glomerulonephritis Prognosis not good Autoimmune reaction, immune complexes are deposited on the GBM which appears thickened. Primary causes are intrinsic to the kidney; secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis) or cancers.
Page 8 of 18 Clinical Features of Nephrotic Syndrome The nephrotic syndrome: proteinuria of >3.5 g per 1.73 m2 per 24 h (in practice, >3.0 to 3.5 g per 24 h), (normal <0,15g/24 hour) hypoalbuminemia, (normal 35 52 g/l) edema, due to loss of proteins and retention of fluids in tissue hyperlipidemia, reason not well understood lipiduria Muehrke s nails, horizontal white bands on all fingernails associated with low serum albumin hypercoagulability, a thrombotic complication, such as deep vein thrombosis of the calf veins or even a pulmonary embolus, may be the first clue indicating nephrotic syndrome ( This is due to decrease function of protein S and decreased levels of the protein Antithrombin III) Laboratory tests: Urine analysis: Appearance: foamy but no blood Dipstick: increased protein (quantitative measurement: >3.5 g per 24 h), (normal <0,15g/24 hour) Serum: Increased serum lipids/hyperlipidemia (3-5.2 mmol/l) Decreased serum albumin ( 35 52 g/l) Hyponatremia decreased Sodium levels (due to edema but the severity can be due to pseudohyponatremia and measurement error often occurring in lipeamic serum.
Page 9 of 18 Serum protein electrophoresis pattern: Normal Nephrotic syndrome indicating low albumin and increase in some of the globulins. emedical.50g.com/images/image44.gif Other: Renal biopsy Case studies: Case 1: A 48year female with a 20-year history of type I diabetes. Her main complaint was ankle swelling extending up to her mid shin and, for the first few hours of the day, some swelling around her eyes. Examination had confirmed pitting ankle oedema. Blood tests reveal: Serum albumin of 18g/L (normal 35-55g/L) Serum cholesterol of 8.2mmol/L Urine: Urine dipstick shows 3+ of protein.
Page 10 of 18 d.imagehost.org/0473/proteinuria.jpg opened 17/2/11 Her urine had a foamy appearance with high protein and no RBC s or haemaglobin A biopsy of her kidney revealed thickening or the GBM and a reduced number of podocytes. Nephritic syndrome medsci.indiana.edu/.../urinrev/media/cse4c.jpg opened 17/2/11 Case 2: An 8-year-old white girl is referred for evaluation of hematuria, proteinuria, and hypertension. She has had recurrent episodes of gross hematuria.
Page 11 of 18 Picture on left of the patient during diagnosis and picture on right before the syndrome. jpg.كتورفين/ 4.bp.blogspot.com/.../s400 opened 17/2/11 The first was at 3 years of age and was attributed to a urinary tract infection, but a urine culture was negative. She was treated with 10 days of antibiotics, and the symptoms resolved. The second episode, at age 5 years, was attributed to acute poststreptococcal glomerulonephritis, although an antistreptolysin O (ASO) titer was normal, and complement studies were not ordered. Blood pressure at that time was 120/80 mm Hg (normal for age and height is 94/54 mm Hg). The girl had not done follow-up test at that time and now presents with increased Blood pressure Gross hematuria Generalized edema Urinalysis of tea-colored urine shows RBC: too-numerous-to-count dysmorphic red blood cells (RBCs), White blood cells, Proteinuria RBC casts.
Page 12 of 18 l medsci.indiana.edu/.../urinrev/media/cse4c.jpg opened 17/2/11 h6.ggpht.com/.../image%5b6%5d.png?imgmax=800 opened 17/2/11 Fluorescence staining of clumped IgA complexes in the glomerulus 1.bp.blogspot.com/.../s400/ANCAGN.jpg opened 17/2/11 Biopsy of a patient with nephritic syndrome: The ruptured capillaries of the glomerulus are visible on the right causing hematuria.
Page 13 of 18 medsci.indiana.edu/.../urinrev/media/cse4c.jpg opened 17/2/11 Conclusion: Case 1 has nephrotic syndrome due to diabetes causing massive proteinuria (>3.5g/l), hiperlipedemia and hypoalbunemia. Case 2 has nephritic syndrome because of the hematuria, hypertention and proteinuria (< 3.0 g/l). She had previous urinary tract infection and post streptococcal glomerulus nephritis.
Page 14 of 18 Proteinuria Urine dipstick 3+ protein quantitative >3.5g/l Urine dipstick increase protein, quantitative < 3,0g/l Clinical picture: History of diabetes, HIV,drug(heroin) abuse or SLE Edema Signs of hypercoagubility DVT ext Urine foamy Clinical picture: History of streptococcal or respiratory infection Edema Hypertension Oliguria Urine tea or coke color Blood tests: Urine tests: Increased serum lipids Decreased serum albumin Hyponatremia Increased lipids Increased proteins Appear foamy Blood tests: Increased creatinine Decreased creatinine clearance Increased urea Decreased serum albumin urine tests: hematuria (RBC s in urine) RBC casts on microscopic examination of urinary sediment. Appearance is tea colored or coke colored Other tests: Decreased anti-thrombin III Decreased protein-s function Protein electrophoresis decreased albumin band Kidney biopsy showing changes in GBM Other tests: Renal biopsy Serum complement profile Serologic tests Fluorescent staining for deposits immune complexes Nephrotic syndrome Nephritic syndrome
Page 15 of 18 References: www.pathologystudent.come talked www.medicalcriteria.com/.../neph_nephrotic_nephritic.htm www.clinicalreview.com/ business.highbeam.com... Magazines Art magazines Pulse emedicine.medscape.com... Nephrology Glomerular Diseases pedsinreview.aappublications.org/cgi/content/full/29/10/342 www.answers.com... Literature & Language Dictionary en.wikipedia.org/wiki/podocyte library.med.utah.edu/webpath/.../urine/urine.html www.merckmanuals.com/professional/sec17/ch235/ch235d.html www.ncbi.nlm.nih.gov/pubmed/10907029 braintalk.blogs.com/neurotransmitter/files/pedistroketeam.ppt pediatrics.aappublications.org/cgi/content/full/119/6/e1404