Pathophysiology Of Edema Formation In Nephrotic Syndrome Biology Essay

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Brian, age 52, is an old teacher, feeling unwell for several months. Presented, He had not been sleeping at all well, often getting up in the night to urinate, and was feeling extremely fatigued and also noticed that his ankles seemed swollen. Blood and urine test revealed that Brian was suffering from nephrotic syndrome. Further renal biopsy is done and cellular pathology report is need to be diagnosed the main cause of Brian symptoms. In this report we are going to discuss, how kidney disease can be progressive, leading to end-stage renal disease and the Current methods to diagnose kidney disease and, in particular, progressive kidney disease, include monitoring urine for elevated protein levels and conducting renal biopsies and available treatments for kidney disease, specifically progressive kidney disease.(1,14)

Fig 2

Fig 1

The presence of nephrotic-range proteinuria, edema, hyperlipidemia, and hypoalbuminemia is defined as nephrotic syndrome.(7) Excessive protein excretion (3.5g or more) characterizes nephrotic range proteinuria. (7,9,14) A collection of clinical findings which is a result of massive renal losses of protein is called nephrotic syndrome, which is not a disease, but manifestation of different glomerular diseases. (7,17,22) If kidney damage is advanced, waste products such as creatinine and urea nitrogen may build up in the blood.(4,9) Proteinuria and Hypoalbuminemia, with plasma albumin level less than 3gm/dl and edema of the ankles suggest the clinical feature that reveals Brian is suffering with nephrotic syndrome. (1,7,22) Additionally biopsy and the cellular pathology findings as showed in Fig 1 and Fig 2 revealed membranous glomerulonephritis.



In adult’s membranous glomerulonephritis accounts for nearly 30% of the cases of nephrotic syndrome,(1,7,11) which is diagnosed by renal biopsy and seen by light microscopy with H&E staining showing the thickening of the glomerular basement membrane walls with some glomeruli completely sclerosed, is the basic change in membranous glomerulonephritis which are both scattered and uniform and accompanied little in the way of cellular proliferation.(1,7), The presence of spikes along the basement membrane in the presence of argyrophilic material projecting out from the glomerular basement membrane towards the epithelial space is indicated by silver staining. Intense thickening of the glomerular capillary walls occur if the disease further progresses uncertainly, using reduplication of the glomerular basement membrane. (7,11,14) The presences of electron-dense immune complex’s deposits are revealed by electron microscopy. Which further on immunofluorescence are found to contain IgG which is usually accompanied by C3 in a distinctive granular pattern demarcate the glomerular basement membrane. In similar advanced conditions, the intensity of IgG staining may be moderated.(8,18) The analysis of Immunoglobulin G subclass is important in identifying membrane glomerulonephritis underlying the anti-glomerular basement membrane disease.(19) 60% of individuals with membranous glomerulonephritis show proteinuria preserves of which only 40% suffer from this disease which terminates to renal failure after 2 to 20 years. (7,22) Fractional or comprehensive reduction of proteinuria with supplementary benign course is seen in 10% to 30 % of individuals. Individuals between the ages of 30 to 50 years are more at the risk of developing the disease, as it gradually progresses with no known cause. (7)

Membrane glomerulonephritis is a form of chronic immune complex nephritis. It is an autoimmune disease. Chronic renal failure is accounted in a large percent of patients by glomerulonephritis, which is most frequently known as nephrotic syndrome and sometimes as asymptomatic proteinuria with or without the presence of hypertension.(11,14) It is a leading cause of nephrotic syndrome in adults.

Figure 3. Possible Mechanisms of the Formation of Subepithelial Deposits in Experimental Models and Patients with, Membranous Nephropathy. (24)

Antibodies and glomerular deposits of immunoglobulin prompt membranous glomerulonephritis. (19) Injury resulting from deposition of soluble circulating antigen-antibody complexes in the glomerulus and injury by antibodies reacting in situ within the glomerulus, either with insoluble fixed glomerular antigen or with molecule planted within the glomerulus can establish injury associated with antibody.(8) In addition glomerular injury can be caused by antibodies directed against glomerular cell components. In the membranous glomerulonephritis, the target of injury is the glomerular visceral epithelial cell or podocyte which is a highly specialized and significantly differentiated cell that rests on the outside of the glomerular basement membrane. (7, 8 ,18) Further, proteinuria follows the formation of sub epithelial deposits, which is linked by podocyte flattening and effacement. With the passage of time, increase in the accumulation of extracellular matrix protein synthesis by podocytes causes thickening of glomerular basement membrane. (7,14) Scientists have focused on the models of rats for passive Heymann nephritis to develop specific therapy for membranous glomerulonephritis. (20) (Resembles human disease) Membranous glomerulonephritis is an immune-mediated disease as the first area of search was to identify the antigen responsible for the membranous lesion was suggested to researches by presence of sub epithelial deposits. (1, 14) A second major area of research has been recognized that antibody binding to the membranous antigen activates complement, leading to the insertion of C5b-9 (membrane attack complex) into the podocyte plasma membrane.( 8,19) Over the past 10 years studies it has been clearly documented the critical role for C5b-9-induced podocyte injury leading to the development of proteinuria.(9) The mechanisms underlying the podocyte response to C5b-9 injury, which include hypertrophy, matrix production, and the maintenance of a well-differentiated and inactive phenotype, to determine how these events translate into proteinuria and progressive glomerulosclerosis is the third area of research.(9,18,14) This study provides further insights into the complexities of C5b-9-induced injury to podocytes, and also into the pathogenesis of membranous glomerulonephritis. The components of the nephrotic syndrome bear a logical relationship to one another. Increased permeability to plasma proteins is the consequence of disarrangement in the capillary walls of the glomeruli, proteins escape from the plasma into the glomerular filtrate by increased permeability resulting from their structural or physiochemical alterations. (7, 22)

Figure 4. Overview of pathophysiology of edema formation in nephrotic syndrome (25)

Due to the fact that Brian had long hours standing job he developed decreased serum albumin, which resulted in hypoalbuminemia. Hypoalbuminemia and primary retention of salt and water by the kidney result from drop in plasma colloid osmotic pressure, is the generalized edema of the nephrotic syndrome. (1, 7) As fluid escapes the vascular tree into the tissues there is an associated drop in the plasma volume, with diminished glomerular filtration. (7) The cause of membranous glomerulonephritis is idiopathic. Often, distinguishing between idiopathic and secondary causes is not possible based on clinical evidence alone, 85% of cases of membranous glomerulonephritis is idiopathic. (14) Lupus and hepatitis, concomitant mesangial or subendothelial deposits may be present in secondary membranous glomerulonephritis including infections like hepatitis B, syphilis, schistosomiasis, malaria, malignant tumors particularly carcinoma of the lung and colon melanoma as well as exposure to inorganic salts (gold, mercury) and drugs like penicilamine, caporal , no steroidal anti-inflammatory agents.(7,21) Available treatments for kidney disease, specifically progressive kidney disease, include the use of steroids, alkylating agents and cyclosporine. (15)This treatment is controversial because of the variable course of the disease, the overall effectiveness of corticosteroids and other immunosuppressive therapy in controlling the progress of the disease has been difficult to evaluate. (15 , 21) The above mentioned diagnostic methods often are inadequate since significant damage to the kidney can occur prior to diagnosis. (1) The above mentioned treatments frequently are unsuccessful in halting the progression of kidney disease and, therefore, unsatisfactory, since they often are accompanied by adverse side effects, such as cellular and systemic toxicity. The methods described here in helps for diagnosing, treating, halting the progression and reducing the severity of kidney disease in a human.(7,15) The methods provide an effective manner to treat kidney disease and, ultimately, prevent end-stage renal disease. Successful treatment of the underlying cause may be curative as a low-salt diet is a key to reducing anasarca. (21)

Protein restrictions may or may not be useful in reducing the rate of progression of chronic renal failure. Diuretics help in controlling edema especially Loop diuretics are most often used. NSAIDs help to decrease the proteinuria and have been largely supplanted by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). ACE inhibitors decrease proteinuria and control hypertension; ARBs are used for patients intolerant of ACE inhibitors. (15) Hepatic 3-methylglutaryl coenzyme a reductase inhibitors help in treating hypercholesterolemia.(21) Routine anticoagulation is controversial as anticoagulation is generally continued indefinitely and Antivirals may be useful in hepatitis-associated membranous nephropathy. (15,21,)

A younger patient presented with similar symptoms but no abnormalities were shown with the light microscope, the glomeruli seem normal. No staining were found using immunohistochemistry. Proximal convoluted tubules are loaded heavily with droplets of proteins and lipids, but this is secondary to the tubular reabsorption passing through the glomeruli of the lipoproteins. When it is placed under electron microscope its shows the uniform and diffuse effacement of the foot processes of the podocytes.(7,23)The cytoplasm appears flattened of the podocytes over the external aspects of the glomerular basement membrane, demolishing the link of the arcades between the glomerular basement membrane and the podocytes. Thus, electron microscope revealed minimal-changed disease. Minimal change disease is one of the common causes of nephrotic syndrome, the name is given to the infection that follows on from heavy leakage of protein into the urine. It may develop at any age but it is most common between ages 1 and 7 years.(7) Minimal change disease usually responds well to treatment with high doses of prednisolone.(15,21) This often discontinues the protein leak within days or weeks, although it may take longer in adults. The dose of steroids is then gradually reduced.


This report has presented evidence to support the notion that when renal function is impeded due to conditions such as membranous glomerulonephritis, early treatment measures must be implemented to prevent renal failure. Corticosteroids and other immunosuppressive therapies were employed to overcome the renal dysfunction and stabilize the patient.(15,21) If these measures were not taken, renal dysfunction may continue to deteriorate and result in adverse renal disease. This syndrome has been identified as a condition that may ultimately lead autoimmune conditions (Systemic lupus erythematosus SLE). (15)