End-Stage Renal Failure and Biochemistry - Case Study Example

Assignment Discuss Clinical Biochemistry findings in a patient with End Stage Renal Failure. Name Institutional Affiliation Date Abstract End stage renal disease is defined by a marked loss kidney function. The kidney function is determined by nephrons which are actively involved in the blood filtration, reabsorption and excretion of wastes through the glomerular, tubular and collecting duct systems. Prolonged injury to the kidneys through pathologies, drugs, toxins or any other pathways that trigger renal dysfunction may lead to loss of renal function through nephron dysfunction. Renal compensatory hypertrophy is initiated and this damages the remaining nephrons. Inflammatory response mechanisms to the injured nephrons change the morphology and ultimately the functions of the renal parenchyma. Renal disease progresses though a fibrosis pathway triggering glomerulosclerosis, tubulointerstitium inflammation, depleting peritubular capillaries, and reduced glomerular filtration rate. Hormonal influence changes as some are insufficiently produced causing an array of renal disease related symptoms. Declining renal function leads to elevated serum creatinine. Treatment at end stage renal failure is renal replacement therapy and regular follow ups with a nephrologist. The method for developing this report involved conducting searches in e-publication journals selected on the basis of their relevance to the topic. The documents are also fairly recent to ensure that only updated information is used to accumulate the evidence in the paper. Introduction End stage renal failure (ESRF) is a kidney pathology characterised by the loss of the renal function (Puelles et al. 2011). Renal function is said to be lost or reduced when the glomerular filtration rate has consistently remained low and confirming the establishment of renal disease (Gorriz & Martinez-Castelao 2012). Blood samples are usually tested to check for creatinine. Elevated creatinine levels in the blood indicate that the excretion function of the kidney is being lost, a common diagnostic feature in ESRF (Muntner et al. 2009). This paper discusses ESRF by explaining the anatomy of the nephron and the glomerular and tubular functions in health and disease. The abnormalities from laboratory investigations in ESRF are explained; treatment methods discussed, and follow up suggestion given. Anatomy of the nephron with diagrams if appropriate The nephron forms the basic structural and functional unit of the kidney (Murawski et al. 2010). The kidneys purify toxic metabolic waste products from the blood and reabsorbs useful components back into the bloodstream (Kurts et al. 2013). The main components making up a single nephron are a glomerulus, and a tubular segment which connect to a collecting duct (Kurts et al. 2013). The glomerulus is a highly vascular loop surrounded by the by the Bowman’s capsule in the kidney cortex (Lopez-Novoa et al. 2011). It forms the site where blood that has entered the kidney through the afferent arteriole is filtered. Parietal epithelial cells are found lining the surface of glomerulus (Murewski et al. 2010). The glomerulus also contains the mesangium which has many capillaries involved in the blood filtration. The glomerulus filtration barrier comprises of endothelial cells, a glomerular basement membrane and podocytes, also known as the visceral epithelial cells which serve as filters (Kurts et al. 2013). The tubular segment is made up of the proximal tubule, the loop of Henle, and the distal tubule (Kurts et al. 2013). The tubular has epithelial cells to reabsorb useful substances from the filtrates. The tubular connects to the collecting duct where the remaining non-reabsorbed part of the filtrate is emptied into the collecting duct and transported to the ureter for excretion (Kurts et al. 2013). Figure 1: Anatomy of the nephron (Kurts et al. 2013) Glomerular and tubular function in health and disease The glomerular function entails blood filtration. When the blood enters the glomerulus, molecules smaller than the protein albumin are drained from the filter into the tubule (Kurts et al. 2013). The dense capillary network and concurrent blood flow forms a high osmotic gradient in the renal medulla resulting in the concentration of the filtrate. The epithelial cells lining the tubular involve in the selective reabsorption of water, amino acids, small molecule proteins, electrolytes, and carbohydrates from the filtrate. As reabsorbtion occurs, important body processes are regulated including acid-base and electrolyte balance, plasma osmolality, extracellular volume and blood pressure. The tubular function is a high energy-demanding process (Lopez-Novoa et al. 2011). Compounds which are not reabsorbed in the tubular are passed into the collecting duct, forming urine. The interstitium, referring to the space between the tubules functions as the intra-renal immune system. Dendritic cells, macrophages and fibroblasts are found at the interstitium. In health, the kidneys appear dense with nephrons and vasculature and the tubulointerstitium mass comprise about 80% of the kidney volume (Puelles et al. 2011). However, persistent injuries to the glomerulus or tubule due to disease, toxins, or nutrient depletion among other renal failure trigger invoke mechanisms that lead to an irreversible decline of renal function when the injury threshold is reached (Lopez-Novoa et al. 2011). Initial kidney injury leads to a decrease in the number of functioning nephrons. The remaining nephrons respond by overworking to compensate for the loss of function, explained as the overload hypothesis. However, the compensatory process only further damages and leads to the loss of more nephrons, which explains the loss of kidney function as the disease progresses to end stage. The fibrosis hypothesis also explains the glomerular and tubular pathogenesis (Hodgkins & Schnaper 2012). Glomerulosclerosis, which is the accumulation of extracellular matrix components in the glomeruli mediated by TGF-β (transforming growth factor beta) cause a decline in the glomerulus filtration rate (GFR) (Lopez-Henandez & Lopez-Novoa 2012). Persistent injury to the tubular due to depleted energy and nutrient supply caused by the low GFR rate activates the tubular cells which interact with the interstitial tissue fibroblasts, dendritic cells and macrophages initiating an inflammatory process (Hodgkins & Schnaper 2012). Further pathologic changes occur in the renal parenchyma and progressive loss of kidney function (Hodgkins & Schnaper 2012). In summary, accumulation of extracellular matrix components in the glomeruli, decreasing GFR, increasing interstitial volume and fibrosis in the tubular, depleting peritubular capillaries, morphological changes in tubular epithelial cells and intense interstitial inflammation are all correlated with declining renal function in end stage kidney disease (Gorriz & Martinez-Castelao 2012). Hormonal influences Significant interactions exist between the endocrine system and kidney function (Basu & Mohapatra 2012). The kidney secretes the hormone erythropoietin, responsible for elevating haemoglobin production in response to low oxygen in the tissues (Kalantar-Zadeh et al., 2010). The kidneys also secrete calcitrol responsible for maintaining serum calcium at normal levels (Sprague & Moe 2013). These hormones are deficient in ESRF leading to anaemia due to lack of erythropoietin, and hypocalcemia, due to lack of calcitrol. Untreated hypocalcemia leads to renal osteodystrophy and secondary hyperparathyroidism (Sprague & Moe 2013). Renal development and physiology is influenced by the thyroid hormones (Basu & Mohapatra 2012). Thyroid hormones have pre-renal and intrinsic renal effects that increase the renal blood flow and balance the GFR (Basu & Mohapatra 2012). Hypothyroidism is correlated with reduced GFR, a pathophysiology in glomerulonephritis (Sprague & Moe 2013). Hyperthyroidism is correlated with increased GFR, and increased activation of the renin-angiotensin-aldosterone pathway that increases the risk of developing hypertension or congestive heart failure (Basu & Mohapatra 2012). In ESRF, reduced secretion of aldosterone from the zona glomerulosa region of the adrenal cortex interferes with the reabsorption of sodium ions from the tubule, distorting water-electrolyte balance, leading to edema or fluid volume overload in the body (Reddy et al. 2014)). The kidney is also under the influence of sex hormones. Hormonal dysfunction in ESRF is clinically accompanied by sexual dysfunction especially in dialysed patients (Suzuki & Kondo 2012). However, estrogen is shown to have nephroprotective effects thereby reducing glomerulosclerosis and tubulointerstitial fibrosis thereby delaying the progression of end stage renal failure in younger women (Suzuki & Kondo 2012). Estrogen works with regulatory factors such as parathormone, and vitamin D fibroblast growth factor 23 which regulate phosphorus-calcium metabolism disturbances experienced in chronic renal disease (Suzuki & Kondo 2012). Reduced insulin function in ESRF exacerbates hyperkalemea, which is of the accumulation of potassium in the blood due to reduced glomerular function (Reddy et al. 2014). Laboratory findings with explanation of abnormalities Laboratory investigations involve a blood test which will reveal elevated creatinine levels in a patient with ESRF, usually above 1.2 mg/dL (Muntner et al. 2009). Creatinine is a product from muscle metabolism. Elevated serum creatinine result indicates that the GFR is reduced, hence the loss of kidney function to excrete the metabolic waste (Muntner et al. 2009). Serum creatinine levels are normal in early stages of the disease (Muntner et al. 2009). Elevated levels indicate the progression of the disease to end stage. GFR level in healthy people is 90 mL/min/1.73 m2 and usually less than 15 mL/min/1.73 m2 (Muntner et al. 2009). The patient should be referred to a nephrologist at moderate stage renal dysfunction when the GFR is between 30 and 59 mL/min/1.73 m2 (Muntner et al. 2009). The patient should be prepared for renal replacement therapy as the severe stage when GFR is between 15 and 29 mL/min/1.73 m2 (Muntner et al. 2009). Treatment Treatments given in the earlier stages of the disease are meant to control risk factors and delay the progression of the disease to ESRF. Treatment may involve hormonal replacement (Youssef 2012). Parenteral iron is given to replace erythropoietin work haemoglobin levels up to at least 9 to 12g/dl (Kalantar-Zadeh et al., 2010). Phosphate binders are also given to control the serum phosphate levels as they are elevated when the disease advances (Sprague & Moe 2013). Medications that control hyperlipidemia, blood pressure and other cardiovascular risks including angiotensin concerting enzyme inhibitors (ACEIs) are given (Reddy et al. 2014). Patients may still progress to ESRF while on the medication and the most effective, life-prolonging treatment is renal replacement therapy, usually in the form of dialysis or a kidney transplant. There are two common types of dialysis. Home hemodialysis is provided in the home of the patient with ESRF with the use of dialysis equipment designed for home use (Apel et al. 2013). The dialysis may be prescribed at three times a week depending with the patient’s needs. On the other hand, peritoneal dialysis is ongoing (Apel et al. 2013). It involves introducing fluids via a catheter that is permanently inserted in the patient’s peritoneum in the abdomen. The system is designed to flush out the fluids every night as the patient sleeps. Complications may arise from catheter-related infections (Apel et al. 2013). Compared to other treatment options, renal transplantation has the highest success rate in increasing the survival rate of patients with ESRF (Kalantar-Zadeh et al., 2010). However, complications of surgery increase the risk of mortality in renal transplant patients (Apel et al. 2013). Follow up confirmatory or monitoring testing if any Patients who are on home hemodialysis are followed up by their nephrologist, who gives them the dialysis prescription (Kalantar-Zadeh et al., 2010). The patients are also connected to a dialysis unit just in case they need back up treatments or case management (Sprague & Moe 2013). Patients on peritoneal dialysis should be continuously monitored to ensure that the dialysis is adequate, and that complications are managed in a timely fashion (Kalantar-Zadeh et al., 2010). Conclusion The renal function purifies blood by processes that excrete toxic metabolic wastes and reabsorb important components to the body. The overall function of the kidney is enabled by the nephron, its basic building unit. Healthy kidneys have numerous nephrons conducting the glomerular function involved in the filtration of blood and the tubular function involved in the reabsorption of components thereby regulating the body processes to achieve the required balance. These include blood pressure, hormonal and electrolyte balance regulations. Prolonged injury to the kidneys by factors such as disease, drugs and toxins may cause the nepron to lose its function in a progressive manner. Nephrons become fewer in number as the renal disease progresses. The glomerular filtration rate reduces significantly and both the glomerulus and tubular segments show a marked nephropathy in ESRF. The production and role of hormones that interact with the kidneys change, resulting in an array of symptoms witnessed in renal disease including anaemia, oedema, hyperlipidimia, and osteopathy. ESRF is clinically diagnosed when creatinine levels are markedly elevated in the blood sample. Treatment is by dialysis or kidney transplantation. The treatment methods may prolong life but there is marked morbidity, indicating need for further improvement in future endeavours. References: Apel, M, Maia, V, Zeidan, M, Schinkoethe, C, Wolf, G, Reinhart, K, & Sakkr, Y 2013, ‘End-stage renal disease and outcome in a surgical intensive care unit’, Critical Care, vol. 17, R298, doi:10.1186/cc13167. Basu, G, & Mohapatra, A 2012, ‘Interactions between thyroid disorders and kidney disease’, Indian Journal of Endocrinology and Metabolism, vol. 16, no. 2, pp. 204-213. Gorriz, J & Martinez-Castelao, A 2012, ‘Protenuria: Detection and role in native renal disease progression’, Transplantation Reviews, vol. 26, no. 1, pp. 3-13. Hodgkins, K & Schnaper, W 2012, ‘Tubulointerstitial injury and the progression of chronic kidney disease’, Pediatric Nephrology, vol. 27, no. 6, pp. 901-909. 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