NEPHROTIC SYNDROME PATHOPHYSIOLOGY شرح بالعربي

NEPHROTIC SYNDROME PATHOPHYSIOLOGY شرح بالعربي Lecture outline A-First part Definition Complications . Pathophysiology Aetiology Clinical presentation Diagnosis 2-Second part Treatment Definition Nephrotic syndrome is the combination of nephrotic-range proteinuria with a low serum albumin level and edema. Nephrotic-range proteinuria is the loss of 3 grams or more per day of protein into the urine or, on a single spot urine collection, the presence of 2 g of protein per gram of urine creatinine. Normal and abnormal proteinuria Normal levels of protein in the urine are less than 150 mg/day. This is primarily composed of Tamm-Horsfall protein(secreted by the tubules.),with less than 30 mg/day being albumin. Clinical practice guidelines identify levels of albuminuria greater than 30 mg/day that persist formore than 3 months as defining chronic kidney disease (CKD). Normal glomerulous & filtration barrier Glomerular filtration barrier 1-Endothelium – lined on the luminal side by the negatively charged protein podocalyxin, has pores which are 50–100nm in diameter. 2-Glomerular basement membrane (GBM) – which is rich in type IV collagen, laminin 11, and the negatively charged heparan sulphate. 3-Podocytes: with 30–40nm filtration slits (gaps between podocytes) bridged by the negatively charged nephrin‐rich slit diaphragms with 8nm pores. Complications of nephrotic syndrome 1-Thromboembolism. 2- Increased susceptibility to infections 3-Accelerated atherosclerosis. 4-Malnutrition. Pathogenesis of the Components of & complications of Nephrotic Syndrome Proteinuria Albumin molecule with a diameter of 7.2nm would have been totally filtered by the above barrier (with the smallest pores, i.e. slit diaphragms being 8nm sized) were it not for the fact that the negative charges on all the three layers in this barrier repel the negatively charged albumin. Glomerular proteinuria can be caused by the lack of negative charges on the filtration barrier ,as well as disease processes causing abnormal physical widening of the filtration pore. Oedema Oedema in nephrotic syndrome is due to the movement of fluid from vascular space to the interstitium due to low plasma oncotic pressure,this leads to decrease in intravascular volume. Which causes stimulation of the renin-angiotensin system (RAS) leads to aldosterone‐induced sodium retention in the distal tubule. Water is passively reabsorbed along with sodium in the tubules. Hypoalbuminaemia and Hyperlipidaemia Whilst the liver increases the synthesis of albumin to compensate for hypoalbuminaemia. Hypoalbuminaemia causes the liver to increase lipoprotein synthesis in an attempt to correct the low plasma oncotic pressure, leading to the development of hyperlipidaemia. Hypercoagulability The incidence of both venous and arterial thrombosis is almost eight times higher in patients with nephrotic syndrome compared to the general population ,which is highest in Membraneous Nephritis. Hypercoagulability is due to , decreased levels of antithrombin and plasminogen (due to urinary losses) and increased hepatic synthesis of procoagulant proteins . Increased Infections Increased urinary loss of opsonizing factors is postulated to lead to increased risk of infections in this patient group . Opsonization is an immune process which uses opsonins to cover foreign pathogens for elimination by phagocytes. Without an opsonin, such as an antibody, the negatively-charged cell walls of the pathogen and phagocyte repel each other. In addition, ascites and pleural effusions provide a good culture medium for the bacteria to grow easily. Aetiology of nephrotic syndrome Primarily glomerular pathology: ● Mininal change disease (MCD) ● Focal segmental glomerulosclerosis (FSGS) ● Membranous nephropathy (MN) ● Membranoproliferative glomerulonephritis (MPGN) mesangiocapillary glomerulonephritis (MCGN) Age of onset of Nephrotic Syn. Clinical presentation New-onset edema, particularly in the lower extremities, is the most common presenting symptom of NS. Depending on disease severity, patients may have edema extending to the proximal lower extremities, lower abdomen, or genitalia. Ascites, periorbital edema, hypertension, and pleural effusion are also possible presenting features. Patients may report foamy urine, exertional dyspnea or fatigue, and significant fluid-associated weight gain. Diagnosis of Nephrotic Syndrome Diagnostic steps 1-Confirmation and grading of proteinuria . A-24-hour urine proteinuria. B-The protein-to-creatinine ratio. 2-Assessment for complications. 3-Identification of the underlying disease.