Biochemical investigations and management of sickle cell nephropathy.pptx

Editor's Notes

• #4: Sickle cell disorder is an autosomal recessive disorder caused by a point mutation causing substitution of thymine for adenine in the sixth codon of the beta globin-chain gene, this causes coding of amino acid valine instead of glutamate in position 6 of the beta-globin chain
• #5: In Sickle cell disease (SCD), there is inheritance of HbS in the homozygous state or with another abnormal Hb (compound heterozygotes) and clinical manifestations
• #7: Claire C. Sharpe, Swee L. Thein, Sickle cell nephropathy – a practical approach British Journal of Haematology September 2011
• #8: Claire C. Sharpe, Swee L. Thein, Sickle cell nephropathy – a practical approach British Journal of Haematology September 2011
• #10: Onset of CKD gradual, requires ongoing monitoring Microalbuminuria: early manifestation, prevalent in older patients Endstage Renal Disease (ESRD): serious complication in a minority
• #13: The pathobiology of sickle cell disease. The formation of deoxyHbS leads to RBC sickling and vascular stasis. Stasis induces vascular occlusion, which either leads to infarction or resolves and causes ischaemia–reperfusion and its accompanying processes. Recurrent cycles of ischaemia–reperfusion in microcirculatory beds amplify organ injury (the ‘big bang’ effect) because they induce inflammation and endothelial dysfunction, both regionally and systemically. Endothelial dysfunction promotes adhesion of RBCs and WBCs to the endothelium. This adhesion is critical because it impedes the transit of RBCs through the microcirculation, thereby promoting RBC sickling and vascular stasis. This vascular stasis explains why RBC sickling occurs in the microcirculation, despite the fact that the time required for sickling usually exceeds RBC transit through the microcirculation. Additional pathobiological pathways include haemolysis and increased free plasma haemoglobin. Plasma haemoglobin scavenges NO from the endothelium. Autoxidation and degradation of HbS lead to the release of free haem, which is toxic to the endothelium via its pro-oxidant and proinflammatory properties. Abbreviations: deoxyHbS, deoxygenated HbS; HbS, sickle haemoglobin; NO, nitric oxide; pO2, partial pressure of oxygen; RBC, red blood cell; WBC, white blood cell. Nath, K., Hebbel, R. Sickle cell disease: renal manifestations and mechanisms. Nat Rev Nephrol 11, 161–171 (2015). https://doi.org/10.1038/nrneph.2015.8
• #14: Salient pathogenetic processes in the development of sickle cell nephropathy. Sickle cell nephropathy largely reflects an underlying functional vasculopathy. This vasculopathy leads to a perfusion paradox, wherein medullary hypoperfusion occurs in conjunction with kidney and/or cortical hyperperfusion. The renal vasculopathy also leads to aberrant renal vascular responses to stress that occur systemically or in distant organs and tissues. This response is characterized by enhanced renal vasoconstriction and resultant vasoocclusion. Recurrent cycles of ischaemia and ischaemia–reperfusion injury thus occur, thereby leading to subclinical and clinical acute kidney injury. These processes summate in the initiation and progression of sickle cell nephropathy
• #18:  https://doi.org/10.1111/j.1365-2141.2011.08853.x
• #22: Symptoms develop slowly and aren't specific to the disease Can have no symptoms, but people may experience: Whole body: fatigue, high blood pressure, loss of appetite, malaise, or water-electrolyte imbalance Nausea and vomiting, muscle cramps, loss of appetite, swelling via feet and ankles, dry, itchy skin, shortness of breath, trouble sleeping, urinating either too much or too little
• #24: Urine is an unstable fluid; it changes composition as soon as it is eliminated through micturition.[7] Accurate collection, storage, and handling are crucial to maintaining the sample’s integrity.  A complete urinalysis consists of three components or examinations: physical, chemical, and microscopical.  Preservatives: Although used occasionally, they can alter the accuracy of the results. Some examples include:Thymol: May generate false-positive reactions for albumin. Formaldehyde: May cause false-positive results for leukocyte esterase, peroxidase reaction, urobilinogen, and glucose if strips are used. Hydrochloric Acid: Although used to preserve cell structures and determine steroid concentrations, it affects the sample's pH.  Mercury Salts: May produce false-negative results for leukocyte esterase reaction.  Boric Acid: While commonly used to preserve bacteria present in urine, this substance may reduce the sensitivity of the leukocyte reagent on dipsticks and alter initial pH values. Moreover, excessive concentrations may prevent bacterial growth in samples reserved for culture. roteinuria can my categorized as a glomerular pattern, a tubular pattern, and an overflow pattern  According to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines, albuminuria can be classified into three stages: A1 (less than 30 mg/g creatinine; normal to mildly increased), A2 (30 mg/g to 300 mg/g creatinine; moderately increased, formerly termed as "microalbuminuria"), and A3 (greater than 300 mg/g creatinine; severely increased) Haematuria Dipstick test for blood detects primarily the peroxidase activity of erythrocytes, but myoglobin and hemoglobin can also catalyze this reaction. Thus, a positive test result indicates hematuria, myoglobinuria, or hemoglobinuria.