Atn csbrp

Editor's Notes

• #8: Some of the more common nephrotoxins associated with acute tubular necrosis are listed on this slide.
• #12: Relative hypoxia in the outer medulla predisposes to ischemic injury in the S3 segment of the proximal tubule. The thick ascending limb is also located in this hypoxic region of the kidney and, depending on tubular reabsorptive demand, may also undergo ischemic injury. The thick ascending limb may, however, be more protected against ischemic injury, because this nephron segment possesses more glycolytic machinery for ATP synthesis than the S3 segment.
• #14: Vascular factors contributing to the pathogenesis of ischemic ARF. ET, endothelin; PG, prostaglandin. Figure modified with permission from the Journal of Nephrology (15).
• #15: Usual production of endothelin is low, but increases in injury while NO is lowered in injury
• #20: Acute tubular necrosis showing focal loss of tubular epithelial cells (arrows) and partial occlusion of tubular lumens by cellular debris (D) (H&E stain). The histologic findings in ischemic acute tubular necrosis may be disproportionately small in comparison to the magnitude of renal dysfunction. Focal necrosis of single proximal tubular cells and clusters of cells is seen in the majority of cases of ATN. Portions of tubules not involved by necrosis commonly show effacement of the proximal tubule brush border. Other pathologic findings include flattening of the tubular epithelium and dilatation of the tubular lumina. Many of the flattened tubular cells exhibit signs of regeneration – i.e., mitoses and large hyperchromatic nuclei. Regenerative changes and foci of necrosis are often seen in the same biopsy specimen. Distal nephron segments are characteristically occluded by urinary casts of hyaline, granular, and pigmented varieties.
• #21: Tubular epithelial degeneration and hyaline amphophilic casts (positive with immunologic stains for myoglobin) in a patient with rhabdomyolysis and myoglobinuric acute tubular necrosis.
• #31: Leather texture of the surface. Normal kidney: 10x5cms (lengthxwidth)
• #39: PSC = Primary sclerosing cholangiitis.
• #42: Features: Fragmented RBCs, nRBCs, Polychromatic cells and Thrombocytopenia.
• #43: TTP mainly genetically mediated or immunological mediated – effect is low clipping of ADAMTS13 there by reducing the enzyme activity.
• #44: Pathogenesis of idiopathic TTP caused by ADAMTS13 deficiency. Multimeric VWF adheres to endothelial cells or to connective tissue exposed in the vessel wall. Platelets adhere to VWF through platelet membrane GPIb. In flowing blood, VWF in the platelet-rich thrombus is stretched and cleaved by ADAMTS13, limiting thrombus growth. If ADAMTS13 is absent, VWF-dependent platelet accumulation continues, eventually causing microvascular thrombosis and TTP.
• #48: TTP was once fatal in 90% of individuals who developed the disease.  Now that plasma exchange is available, survival can be as high as 80%.  In many cases the blood vessel damage in the kidneys and brain will reverse with time. HUS has a good prognosis.  During the active phase of the disease kidney failure can often be severe enough to require manual blood cleaning with dialysis.  Fortunately this is usually temporary.  In fact kidney function almost always returns to the normal range within a few months
• #49: TTP and HUS have different treatments.  To prevent death and serious organ damage TTP requires immediate treatment with plasma exchange (PLEX) – see Figure. This process allows the abnormal glue (vWF) that causes TTP to be exchanged for normal vWF.  Treatments usually last a few hours each and continue every 1-2 days for about 2 weeks.  For those with repeated episodes of TTP, a medication called rituximab is being tested to see if its use can prevent recurrences of the disease. In contrast, HUS usually improves on its own.  Patients will require hospitalization for fluids and monitoring while the disease is worsening.  If kidney function declines too much, manual blood cleaning with dialysis may be necessary.   As the causative bacterial infection resolves, toxin leaves the body and symptoms of HUS begin to improve. In many of the more atypical TTP/HUS disease patterns the optimal treatment has not yet been standardized.  These are often treated (like TTP) with plasma exchange, but there is currently some debate about this.