Chronic Kidney Disease PDF - University of Guyana

Chronic Kidney Disease Group 11 Course: Integrated Case Seminars Lecturer: Dr. Sharlene Goberdhan Date: 28th May, 2024 GROUP MEMBERS JOSHUA MELVILLE 1041743 JOSHUA SINGH 1048313 NAOMI HOPE 1025479 RUCHIRA GUYADEEN 1034902 TRINELLA ROACHE 1048314 Table of contents...

Chronic Kidney Disease Group 11 Course: Integrated Case Seminars Lecturer: Dr. Sharlene Goberdhan Date: 28th May, 2024 GROUP MEMBERS JOSHUA MELVILLE 1041743 JOSHUA SINGH 1048313 NAOMI HOPE 1025479 RUCHIRA GUYADEEN 1034902 TRINELLA ROACHE 1048314 Table of contents 1 Case Study 4 Histology 2 Introduction 5 Physiology 3 Anatomy 6 References 1 Case Study Case Study A 47-year-old woman is brought to the emergency department because of a 1-day history of severe pain in her lower back. The pain is 8 out of 10 in intensity and radiates down her legs. She has hypertension, type 2 diabetes mellitus, and major depressive disorder. Her current medications include sertraline, insulin and enalapril. She appears uncomfortable. Her temperature is 37.3°C (99.1°F), pulse is 102/min, respirations are 15/min, and blood pressure is 132/94mmHg. Examination shows multiple excoriation marks on the upper extremities and 2+ pitting oedema of the lower extremities. There is severe tenderness to palpation over the L2 vertebra; range of motion is limited. Neurologic examination shows no focal findings. An x-ray of the spine shows decreased bone density and a wedge compression fracture of the L2 vertebra. Laboratory studies show the following: Case Study Haemoglobin 9.6g/dL Leukocyte Count 8700/mm3 Platelet Count 170,000/mm3 Serum: Sodium 138 mEq/L Potassium 4.5 mEq/L Calcium 7.9mg/dL Phosphorous 5.3mg/dL Urea Nitrogen 33mg/dL Creatinine 3.8mg/dL Glucose 150mg/dL 1 Introduction Chronic Kidney Disease CKD refers to the long standing, progressive destruction of renal function for longer than 3 months. If left untreated, CKD may lead to kidney failure. Diabetes and high blood pressure are the leading causes of CKD. There are 5 stages of CKD: (Stages of chronic kidney disease (CKD), 2024) 1 Anatomy  1. Describe the cortex, medulla and renal fascia of the kidney. Renal Cortex The cortex forms the outer portion of the kidney between the renal capsule and the medulla.It forms a continuous smooth outer zone which extends between the renal pyramids as renal columns It is a highly vascularized part which is consist of the renal corpuscles and proximal and distal convoluted tubules except for parts of the loop of Henle which descend into the medulla. The renal corpuscle has two (2) structures: the glomerulus and bowman’s capsule(glomerular capsule) (Kidneys, 2023). Renal medulla The medulla is the inner part of the kidney. It consists of cone- shaped renal pyramids that contains a dense network of nephrons. The medulla is consists of 8 to 12 renal pyramids , which contain straight tubules (Henle's loops) and collecting tubules It is also consist of minor calyces which unites to form major calyx Other structures include : Vasa recta Collecting ducts Nephron Loops Interstitium (Kidneys, 2023). Renal Fascia The kidney renal capsule is surrounded by the renal fascia.The renal fascia is a dense, elastic connective tissue envelope, enclosing the kidney and adrenal gland. The renal fascia consist of two distinct structures: the anterior renal fascia (Gerota's fascia), and posterior renal fascia; they fuse laterally to form the lateroconal fascia. However, the renal fascia divide the fat into two regions. The perirenal (perinephric) fat The pararenal (paranephric) fat · (Charmley, 2023). Renal Fascia 2. What is the blood supply, venous drainage, lymphatic drainage and nerve supply to the kidney? Blood Supply: The kidneys are supplied with blood via the renal arteries (Jones, 2024). Renal arteries enter the kidney via renal hilum. Segmental branches of the renal undergo further divisions to supply the renal parenchyma (Jones, 2024). Venous Drainage: The kidneys are drained of venous blood by the left and right renal veins (Crumble, 2023). These leave the renal hilum and empty directly into the inferior vena cava (Jones, 2024). Lymphatic Drainage: Renal lymphatics drain directly into the lumbar lymph trunks. Which then drain into the thoracic duct, cisterna chyli and to the para-aortic nodes (Crumble, 2023). Nerve Supply: Both sympathetic and parasympathetic divisions of the ANS innervates the kidneys (Crumble, 2023). Left lesser splanchnic nerve Vagus nerve 1 Histology What are some histopathologic changes that occur in Chronic Renal Disease? Normal structure of the Glomerulus Histopathologic changes in CKD can be found in 4 areas: Glomeruli: There is often glomerulosclerosis, which is scarring of the glomeruli. This can include segmental or global glomerulosclerosis. Tubules: Tubular atrophy and interstitial fibrosis are common findings. Interstitium: Increased interstitial fibrosis and inflammation can be seen. Blood Vessels: Arteriosclerosis, characterized by thickening and hardening of the walls of the renal arteries and arterioles, is often present. Glomeruli Mesangial Expansion Conditions such as diabetes and hypertension can trigger mesangial cells to produce ECM proteins in response. Hyperglycemia-induced matrix accumulation is mediated by TGF- β. Ang II also mediates matrix accumulation indirectly through TGF- β upregulation. The activation of the renin-angiotensin system in the kidney stimulates an increase in Ang II In situations such as hypertension, mechanical forces have been found to stimulate matrix component accumulation. Increase in glomerular pressures in perfused glomeruli have been shown to lead to significant increases in mesangial cell stretching. (Qian et al., 2008) MESANGIAL EXPANSION MESANGIAL EXPANSION Glomerulus shows a Glomerulus showing Mesangial Kimmelstiel-Wilson nodule Expansion Glomerular Basement Membrane Thickening In response to the threat of filtration barrier malfunction, the podocyte may adapt by activating a series of cell signaling pathways that ultimately will increase synthesis of GBM components and lead to GBM thickening. GBM structural changes may reduce cell binding and promote podocyte detachment Increase in the filtration pressure intensify the mechanical stress experienced by podocytes. Podocytes then respond by depositing additional GBM matrix in an attempt to resist the applied force and prevent further detachment. (Marshall, 2016) GBM Thickenin g Renal glomerular basement membrane diffuse thickening under light microscope (PASM staining, ×400). Tubules & Interstitium Tubular Atrophy & Interstitial Fibrosis The presence of plasma proteins in the tubular filtrate may directly injure the tubulointerstitium. Cytokines (such as TGFβ), when present in the tubules, will recruit monocytes, macrophage, and T-cells. The inflammatory infiltrate leads to mesangial matrix deposition, promoting the collapse of glomeruli. The cellular infiltrate and cytokines also damage tubular epithelial cells. (Khamis, 2019) The earliest change involving the tubules is thickening of the tubular basement membranes. As the disease progresses, there is increase in the degree of interstitial fibrosis and tubular atrophy. Proximal tubules with thickened tubular basement membranes Trichrome stain highlighting interstitial fibrosis. ARTERIOLES Arteriolar Hyalinosis Hypertension also causes thinning of the media and, at the sites where smooth muscle cells are atrophic or missing, induces accumulation of hyaline material This process, known as hyalinosis, is characterized by loss of smooth muscle cells. As a consequence of hyalinosis and cell loss, the wall of small vessels becomes more expansive, allowing the endothelial permeability and migration of plasma proteins to the media. (Sun et al., 2020) Arteriolar hyalinosis typically involves both the afferent and efferent arterioles and some consider this finding to be the most specific for diabetic nephropathy. Arteries show varying degrees of intimal fibrosis, but is often mild. Glomerulus shows hyalinosis of both afferent and efferent arterioles Artery showing intimal fibrosis (arrow) SUMMARY Electron Microscopy showing the Diffuse Glomerulosclerosis, PAS stain glomerular changes during CKD (Gaied et al., 2019) In what portion of the nephron is Creatinine primarily secreted? Creatinine is filtered by the glomerulus and secreted by the proximal tubule such that creatinine clearance overestimates GFR by 10% to 20%. (Garimella, et al. 2021) 1 Physiology  Discuss the significance of the patient's laboratory findings HEMATOLOGY Hemoglobin Leukocyte Count Platelet Count Level: 9.6 g/dL Level: 8700/mm³ Level: 170,000/mm³ Normal Range: 13.8-17.2 g/dL (M) Normal Range: Normal Range: 12.1-15.1 g/dL (F) 4,000-11,000/mm³ 150,000-450,000/mm³ Interpretation: Low. This suggests Interpretation: Normal. This Interpretation: Normal. anemia, which could be due to indicates no evident infection or Platelets are essential for blood various causes such as iron inflammation. clotting, and this level indicates deficiency, chronic disease, or renal adequate clotting function. insufficiency. the kidney consumes oxygen, mainly to generate potential energy for tubular reabsorption  SERUM ELECTROLYTES AND METABOLITES Sodium (Na+) Potassium (K+): Level: 138 mEq/L Level: 4.5 mEq/L Normal Range: 135-145 mEq/L. Normal Range: 3.5-5.0 mEq/L. Interpretation: Normal. Sodium is Interpretation: Normal. crucial for fluid balance and nerve Potassium is vital for heart and function. muscle function. Calcium Phosphorus Level: 7.9 mg/dL Level: 5.3 mg/dL Normal Range: 8.6-10.2 mg/dL. Normal Range: 2.5-4.5 mg/dL. Interpretation: Low. This could indicate Interpretation: High. This can be hypocalcemia, which might be due to associated with kidney dysfunction, vitamin D deficiency, renal disease, or hyperparathyroidism, or excessive dietary other metabolic conditions. intake.  SERUM ELECTROLYTES AND METABOLITES Blood Urea Nitrogen (BUN) Creatinine Level: 33 mg/dL Level: : 3.8 mg/dL Normal Range: 7-20 mg/dL. Normal Range: 0.6-1.2 mg/dL. Interpretation: High. Elevated Interpretation:High. This BUN can indicate kidney strongly suggests renal dysfunction, dehydration, or high impairment or chronic kidney protein intake disease. Glucose Level: 150 mg/dL Normal Range: 70-99 mg/dL. (fasting) Interpretation: High. This may indicate hyperglycemia, suggesting a possible diagnosis of diabetes or prediabetes. Discuss the role of erythropoietin in the management of chronic renal failure. Erythropoietin is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. In patients with chronic renal failure (CRF), the kidneys' ability to produce EPO is compromised, leading to anemia. The administration of exogenous EPO is a key therapeutic approach to manage this anemia. (Erythropoietin, n.d) Erythropoietin Administration RhEPO is used to complement the poor endogenous synthesis of EPO in CRF patients. It is provided via subcutaneous or intravenous injections, usually beginning with a lower dose and adjusting dependent on patient response. Mechanism of Action Administration and Distribution of RhEPO RhEPO is injected subcutaneously or intravenously, and it travels to the target tissues, mostly the bone marrow. Binding to EPO Receptors: On the surface of the bone marrow, rhEPO binds to erythropoietin receptors, or EPOR. Transmission of Signals STAT5 is activated by binding, which also activates the JAK2 pathway. STAT5 facilitates the transcription of genes essential for cell survival, proliferation, and differentiation. Erythroid Cell Proliferation and Differentiation: Gene expression promotes the growth and maturation of erythroid progenitor cells into mature erythrocytes. Enhanced Red Blood Cell Count: The blood's ability to carry oxygen is improved when freshly created red blood cells are discharged into the circulation. (Erythropoietin, n.d) Clinical Benefits Benefits of EPO Administration Lowers the need for blood transfusions by raising hemoglobin levels. Improves quality of life by reducing symptoms associated with anemia. May help CRF patients' cardiovascular outcomes. (Erythropoietin, n.d)  References Charmley, S. (2023, March 3). What to know about the renal medulla. https://www.medicalnewstoday.com/articles/kidney-medulla Crumble, L (2023, October 30). Neurovascular supply of the kidney. KenHub. https://www.kenhub.com/en/library/anatomy/neurovascular-supply-of-the-kidney Jones, O (2024, April 16). The Kidneys. TeachMeAnatomy. https://teachmeanatomy.info/abdomen/viscera/kidney/ Kidneys. (2023, November 3). Kenhub. https://www.kenhub.com/en/library/anatomy/kidney Thomas, H.Y., Ford Versypt, A.N. Pathophysiology of mesangial expansion in diabetic nephropathy: mesangial structure, glomerular biomechanics, and biochemical signaling and regulation. J Biol Eng 16, 19 (2022). https://doi.org/10.1186/s13036-022-00299-4 Garimella, P. S., Tighiouart, H., Sarnak, M. J., Levey, A. S., & Ix, J. H. (2021). Tubular Secretion of Creatinine and Risk of Kidney Failure: The Modification of Diet in Renal Disease (MDRD) Study. American journal of References Qian, Y., Feldman, E., Pennathur, S., Kretzler, M., & Brosius, F. C., 3rd (2008). From fibrosis to sclerosis: mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes, 57(6), 1439–1445. https://doi.org/10.2337/db08-0061 Sun, D., Wang, J., Shao, W., Wang, J., Yao, L., Li, Z., & Ohno, S. (2020). Pathogenesis and Damage Targets of Hypertensive Kidney Injury. Journal of translational internal medicine, 8(4), 205–209. https://doi.org/10.2478/jtim-2020-0033 Marshall C. B. (2016). Rethinking glomerular basement membrane thickening in diabetic nephropathy: adaptive or pathogenic?. American journal of physiology. Renal physiology, 311(5), F831–F843. https://doi.org/10.1152/ajprenal.00313.2016 Stages of chronic kidney disease (CKD). National Kidney Foundation. (2024, May 21). https://www.kidney.org/atoz/content/stages-chronic-kidney-disease-ckd Khamis, S. (2019, April 30). Kidney biopsy of the month- the tubulointerstitium part 1: The cortex. Renal Fellow Network. https://www.renalfellow.org/2019/02/11/kidney-biopsy-of-the-month-the-tubulointerstitium-part-1-the-cor tex/ References Gaied, J., Smit, UiTM, R., An, B., Liu, S., Ltd, R. T. P., Keshab, Weaam, & MD, D. J. (2019, May 24). Kidney biopsy of the month: Diabetic nephropathy. Renal Fellow Network. https://www.renalfellow.org/2019/05/24/kidney-biopsy-of-the-month-diabetic-nephropathy/ Erythropoietin: Uses, interactions, mechanism of action | DrugBank Online. (n.d.). DrugBank. https://go.drugbank.com/drugs/DB00016