Chapter Paper 1 Answers
James Day, Amy Thomson, Tamsin McAllister, Nawal Bahal in Get Through, 2014
The human kidneys are paired organs situated in the retroperitoneum, which are responsible for urine formation, regulation of body water, sodium and other electrolyte balance as well as having an endocrine function. Each kidney contains over 1 million nephrons, which are the functional units of the kidney. The kidneys receive 20–25% of cardiac output at rest, receiving 500 ml per 100 g renal tissue per minute. This blood is filtered at the glomerulus producing 125 ml·min−1 of glomerular filtrate, totalling 180 L·day−1. The glomerular filter consists of the glomerular basement membrane, the podocyte foot processes and capillary endothelial cells. Together they prevent the passage of large and negatively charged molecules. Twenty percent of the plasma entering the glomerulus is filtered into Bowman’s capsule.
Mechanisms of Chronic Glomerular Injury
Robin S. Goldstein in Mechanisms of Injury in Renal Disease and Toxicity, 2020
The glomerulus is composed of a capillary network lined by endothelial cells: a central region of contractile mesangial cells with their surrounding extracellular matrix material; the visceral layer of epithelium along the outer aspect of the glomerular basement membrane; and the parietal epithelial layer of Bowman’s capsule. These structures comprise the histologic loci which can be affected in a variety of immunologic, toxic, age-related, renoprival, and genetic experimental disease models. The resident glomerular cell types (i.e., visceral epithelial cell, contractile mesangial cell, bone marrow-derived macrophage); the mesangial matrix; and the permselectivity characteristics of the glomerular basement membrane bear particular importance. Also, the mesangium forms the centrilobular area of the glomerulus and extends into the capillary wall, thus lying in an intracapillary position. Between capillary loops, the glomerular basement membrane reflects over the mesangium, which results in the mesangium being directly adjacent to the fenestrated endothelium lining these capillaries. This unique anatomical arrangement allows for diffusion of micro- and macromolecules as well as the infiltration of blood-borne cells (i.e., monocytes and platelets) into the mesangial space, thus generating the potential for myriad humoral and intercellular interactions during pro-inflammatory states, which can serve to propagate chronic glomerular injury.
Renal and urinary tract diseases
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
Once other hereditary nephropathies have been excluded, true Alport syndrome is almost always X-linked, with variable expression in females and deafness a variable feature even in affected males. Microscopic haematuria is probably the most accurate clinical detector of heterozygous females. Renal electron microscopic detection of extensive thickening and splitting of the glomerular basement membrane helps to distinguish true Alport syndrome from various other hereditary nephropathies, most of which are dominantly inherited when onset is in adult life. Pathogenic variants in the gene for one of the chains of type IV collagen is now known to be responsible. Specific variants can usually be identified in affected families, so that accurate carrier detection and prenatal diagnosis are possible. Molecular analysis is also helpful in the rare autosomal Alport families, also due to type IV collagen defects but involving different chains; it has largely replaced renal biopsy in the distinction from other nephropathies.
Focal and segmental glomerulosclerosis in murine models: a histological and ultrastructural characterization with immunohistochemistry correlation of glomerular CD44 and WT1 expression
Published in Ultrastructural Pathology, 2018
Sufia Husain, Ibrahim Ginawi, Abdelhafiz Ibrahim Bashir, Hala Kfoury, Tariq Eid Al Johani, Hanan Hagar, Lama Raddaoui, Mohammed Al Ghonaim, Abdulkareem Alsuwaida
Glomerulus is the functional unit of the kidney comprising of parietal epithelial cells (PECs), podocytes (visceral epithelial cells), endothelial cells and mesangial cells (Figure 1a and 1b). The podocytes are specialized cells that completely line and cover the urinary side of the glomerular capillary basement membrane with its primary and secondary processes. The endothelial cells line the luminal side of the glomerular capillary basement membrane. Together the podocytes, glomerular basement membrane (GBM) and the endothelial cells form the glomerular filtration barrier. Not only are these structures interdependent, they are each very crucial in the normal function of the kidney. Podocyte injury accounts for the majority of proteinuric renal diseases.1 In these podocytopathic diseases, podocytes lose the arrangement of primary and secondary foot processes due to alteration of the actin cytoskeleton leading to effacement or fusion of the podocyte foot processes resulting in loss of glomerular barrier function, proteinuria and nephrotic syndrome.2 Podocytes however do not typically regenerate following injury, they are terminally differentiated with limited mitotic potential thereby making the management of podocytopathic diseases challenging.1
Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress
Published in Drug and Chemical Toxicology, 2022
Eyup Altinoz, Zulal Oner, Hulya Elbe, Nuray Uremis, Muhammed Uremis
The glomerular filtration barrier consists of the glomerular basement membrane, the glomerular endothelial cells, and podocytes. Elevated ROS levels lead to the disturbance of the glomerular filtration rate (Pedraza-Chaverrí et al.2000). Increased plasma BUN and Cr levels show the disturbance of glomerular function (Mohan et al.2010). Although BUN elevates remarkably in kidney parenchymal injury, Cr might be more important than BUN in the onset of kidney damage (Erdem et al.2000). Our data are in agreement with the previous studies (El‐Sayed et al.2017, Khames et al.2017). Bilgic and Armagan reported that DOX-induced nephrotoxicity in rats led to an increase in BUN and Cr levels (Bilgic and Armagan 2020). Previous studies have demonstrated that many antioxidant chemicals exhibit therapeutic or protective effects on DOX-induced nephrotoxicity in rats. Therefore, in the present study, the use of linalool as therapeutic and protective showed significant improvement in BUN and Cr levels in DOX-induced kidney damage by inhibiting oxidative stress.
The effect of amiloride in decreasing albuminuria in patients with diabetic kidney diseases: a prospective, crossover, open-label study
Published in Renal Failure, 2021
Ruizhao Li, Zhiyong Xie, Li Zhang, Ying Huang, Jianchao Ma, Wei Dong, Zhilian Li, Yuanhan Chen, Huaban Liang, Yanhua Wu, Xingchen Zhao, Wenjian Wang, Zhiming Ye, Shuangxin Liu, Wei Shi, Xinling Liang
The impairment of the glomerular filtration barrier is an important pathophysiological basis for albuminuria in DKD. The glomerular filtration barrier consists of endothelial cells, the glomerular basement membrane (GBM), and podocytes. Podocytes have a prominent role in maintaining the integrity of the glomerular filter. Podocytes injury would lead to the effacement of foot processes and the detachment or apoptosis of podocytes [21]. The loss of integrity of the podocyte seal results in the diffusion and convection of proteins from the circulation into the urinary space and finally leads to the occurrence of albuminuria [22]. Moreover, several pathogenic mechanisms involved in podocyte injury would beget ultrastructural changes in podocytes and albuminuria. Previous researches had found that mutation of the gene encoding the podocyte-expressed protein nephrin would result in congenital albuminuria [23]. Disorder of cross-talk between podocytes and the other cells involved in the glomerular filtration barrier might also lead to albuminuria. Several studies [19,24–26] had found that the podocyte lesion is the primary causes for glomerular diseases characterized by massive proteinuria, such as minimal change nephropathy (MCD), focal glomerulosclerosis (FSGS), membranous nephropathy (MN), lupus nephritis (LN), DKD and is related to disease progression.
Related Knowledge Centers
- Kidney
- Basal Lamina
- Glomerulus
- Endothelium
- Podocyte
- Ultrafiltration
- Bowman'S Capsule
- Mesangial Cell
- Nephrin
- Goodpasture Syndrome