Renal corpuscle is the major part of the uriniferous tubules; the functional unit of our kidneys. It can be affected by a variety of congenital, infectious, iatrogenic, and malignant diseases. Studying the normal structure of the human renal corpuscle is fundamental to nephrologist, radiologist, and pathologists. Moreover, understanding the normal structure of the renal corpuscle is a fundamental aspect in preclinical and clinical research. In this presentation, we have provided a detailed microscopic description of the renal corpuscle and its related structures in relation to their function. Lastly, we have linked many molecular structures to known renal conditions.
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Histological Structure of The Renal Corpuscle Suits its function- maha hammady.pptx
1. Histological Structure of The Renal
Corpuscle Suits its function
Maha Hammady
Assistant Lecturer of Medical Histology & Cell
Biology,
Faculty of Medicine Alexandria University
2. Bibliography
• Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular biology: Wolters Kluwer
Law & Business; 2019
• Mescher A. Junqueira’s basic histology text and atlas. 15th ed. new york: McGraw-Hill Education; 2018
• Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019
• Farquhar MG. The glomerular basement membrane: Not gone, just forgotten. J Clin Invest. 2006;116(8):2090-3.
• Andrews PM, Porter KR. A scanning electron microscopic study of the nephron. Am J Anat. 1974;140(1):81-115.
• Fujita T, Tokunaga J, Edanaga M. Scanning electron microscopy of the glomerular filtration membrane in the rat kidney. Cell Tissue
Res. 1976;166(3):299-314.
• Shirato I, Tomino Y, Koide H, Sakai T. Fine structure of the glomerular basement membrane of the rat kidney visualized by high-
resolution scanning electron microscopy. Cell Tissue Res. 1991;266(1):1-10.
• Andrews PM. Scanning electron microscopy of the nephrotic kidney. Virchows Arch B Cell Pathol. 1975;17(3):195-211.
• Bulger RE, Siegel FL, Pendergrass R. Scanning and transmission electron microscopy of the rat kidney. Am J Anat. 1974;139(4):483-
501.
• Kawasaki Y, Hosoyamada Y, Miyaki T, Yamaguchi J, Kakuta S, Sakai T, et al. Three-dimensional architecture of glomerular endothelial
cells revealed by fib-sem tomography. Front Cell Dev Biol. 2021;9:653472.
• Kawasaki Y, Hosoyamada Y, Miyaki T, Yamaguchi J, Kakuta S, Sakai T, et al. Three-dimensional architecture of glomerular endothelial
cells revealed by fib-sem tomography. Front Cell Dev Biol. 2021;9:653472.
• Spinelli F. Structure and development of the renal glomerulus as revealed by scanning electron microscopy. In: Bourne GH,
Danielli JF, Jeon KW, editors. International review of cytology: Academic Press; 1974. p. 345-81.
• Tokunaga J, Edanaga M, Fujita T, Adachi K. Freeze cracking of scanning electron microscope specimens. A study of the kidney and
spleen. Arch Histol Jpn. 1974;37(2):165-82.
• Webber WA, Lee J. The ciliary pattern of the parietal layer of bowman's capsule. Anat Rec. 1974;180(3):449-55.
33. 3-Slit diaphragm formed between the interdigitating secondary process of podocytes:
Congenital Nephrotic Syndrome
34. Bibliography
• Pawlina W, Ross MH. Histology: A text and atlas, international edition: With correlated cell and molecular biology: Wolters Kluwer
Law & Business; 2019
• Mescher A. Junqueira’s basic histology text and atlas. 15th ed. new york: McGraw-Hill Education; 2018
• Gartner L. Cell biology and histology. 8th ed. New York: Wolters Kluwer; 2019
• Farquhar MG. The glomerular basement membrane: Not gone, just forgotten. J Clin Invest. 2006;116(8):2090-3.
• Andrews PM, Porter KR. A scanning electron microscopic study of the nephron. Am J Anat. 1974;140(1):81-115.
• Fujita T, Tokunaga J, Edanaga M. Scanning electron microscopy of the glomerular filtration membrane in the rat kidney. Cell Tissue
Res. 1976;166(3):299-314.
• Shirato I, Tomino Y, Koide H, Sakai T. Fine structure of the glomerular basement membrane of the rat kidney visualized by high-
resolution scanning electron microscopy. Cell Tissue Res. 1991;266(1):1-10.
• Andrews PM. Scanning electron microscopy of the nephrotic kidney. Virchows Arch B Cell Pathol. 1975;17(3):195-211.
• Bulger RE, Siegel FL, Pendergrass R. Scanning and transmission electron microscopy of the rat kidney. Am J Anat. 1974;139(4):483-
501.
• Kawasaki Y, Hosoyamada Y, Miyaki T, Yamaguchi J, Kakuta S, Sakai T, et al. Three-dimensional architecture of glomerular endothelial
cells revealed by fib-sem tomography. Front Cell Dev Biol. 2021;9:653472.
• Kawasaki Y, Hosoyamada Y, Miyaki T, Yamaguchi J, Kakuta S, Sakai T, et al. Three-dimensional architecture of glomerular endothelial
cells revealed by fib-sem tomography. Front Cell Dev Biol. 2021;9:653472.
• Spinelli F. Structure and development of the renal glomerulus as revealed by scanning electron microscopy. In: Bourne GH,
Danielli JF, Jeon KW, editors. International review of cytology: Academic Press; 1974. p. 345-81.
• Tokunaga J, Edanaga M, Fujita T, Adachi K. Freeze cracking of scanning electron microscope specimens. A study of the kidney and
spleen. Arch Histol Jpn. 1974;37(2):165-82.
• Webber WA, Lee J. The ciliary pattern of the parietal layer of bowman's capsule. Anat Rec. 1974;180(3):449-55.
Editor's Notes
To get started, let's look at The functional unit of the kidney: “the uriniferous tubule”
uriniferous tubule is formed of the nephron which produces urine, and corresponds to the secretory part of other glands, and the collecting tubule which corresponds to the ducts of exocrine glands that modify the concentration of their product.
-Both human kidneys contain approximately 2 million nephrons.
-Beside urine production, nephrons are vital for regulation of blood volume, blood pressure and plasma osmolarity. -Each nephron is formed of an initial filtering part called (the renal corpuscle) and a tubular part specialized for re-absorption and secretion.
The renal corpuscle is the initial part of the nephron
It is a spherical structure formed of glomerulus, Bowman’s capsule and the mesangium.
-Bowman’s capsule a cup-shaped sac at the beginning of the nephron, where blood flowing through the glomerular capillaries undergoes filtration to produce the glomerular ultrafiltrate.
- It is a double-walled epithelial capsule that surrounds a tuft of glomerular capillaries.
-Each renal corpuscle has a “vascular pole”, where the afferent arteriole enters and the efferent one leaves, and a “urinary pole”, where the PCT begins.
-The outer parietal layer of a Bowman’s capsule is composed of a simple squamous epithelium supported externally by a basal lamina.
-while the inner visceral layer of a Bowman’s capsule consists of highly specialized stellate epithelial cells called “the podocytes”
Parietal cells play a structural role in supporting and maintaining Bowman’s capsule, they differentiate into podocytes to replace damaged or old ones.
This is a scanning election micrograph of the inner surface ot the parital layer of bowman’a capsule, showing one or two long cilia arise from each parietal cell.
- The space enclosed between the two layers of the capsule; termed the “urinary space”; collects the fluid filtered by the glomerular capillaries.
-Podocytes are specialized stellate epithelial cells. -multiple primary processes arise form their bodies, extending and curve around the length of glomerular capillaries.
-Each primary process branches into many parallel, interdigitating and regularly spaced secondary processes or “pedicels”, these pedicles wrap the glomerular capillaries like a tentacle of an octopus.
-Podocytes are key regulators of the glomerular filtration barrier as they support the integrity of the capillary loops and prevent the passage of plasma proteins into the glomerular ultrafiltrate.
-Podocytes have well organized cytoskeleton which is responsible for their unique shape.
-their Cell bodies and primary processes contain microtubules and intermediate filaments, such as vimentin and desmin
-while the core of pedicels contains actin filaments.
elongated spaces between the interdigitating foot processes, called “filtration slits” which are about 25 nm wide each.
Actin filaments permits slight movement of the the foot process to regulate the diameter of these slits.
-Glomerular capillary loops are uniquely located between two contractile arterioles: a wider afferent and a narrower efferent arterioles
(instead of an artery and a vein):
-these arterioles maintain high hydrostatic pressure within the glomerular capillaries resulting in the continuous filtration of plasma and prevent re-absorption of the filtrate.
This scanning electron miscrograph shows the freely floating Glomerular capillary within the Bowman's capsule.
-the third components of the renal corpuscle is the mesangium;( Gr: mesos: in the midst+ angion: vessels).
-the mesangium is formed of mesangial cells and their surrounding matrix
-Most of the mesangial cells resemble vascular pericytes in having contractile ability. they are difficult to be distinguished from podocytes in routine sections.
-Mesangial cells fill the spaces between capillaries at areas which lack podocytes. Moreover, they are not confined entirely to the renal corpuscle; some are located outside the corpuscle along the vascular pole, where they are also named as lacis cells and form part of the juxtaglomerular apparatus which share in blood pressure regulation.
The mesangial cells have various functions including:
Removal of trapped proteins from the GBM and filtration slit diaphragm,
they Participate in local renal immune and inflammatory responses by expression of antigen presenting cells surface markers and Synthesis and secretion of various molecules as IL-1 and platelet-derived growth factor (PDGF), in response to glomerular injury.
Mesangial cells also Share in regulating glomerular distension in response to increased blood pressure due to their contractile properties.
We need to pay a special attention to the filtration apparatus of the kidney: it is a barrier which has two discontinuous cellular layers: the endothelium of glomerular capillaries on one side and pedicels of the podocytes on the other side of a continuous layer of the glomerular basement membrane
let’s take a closer look to this tripartite structure
Starting form the capillary lumen, the first layer of this barrier is the glomerular endothelium
its fenestra are larger, more numerous, and more irregular in outline than their counterparts in other capillaries. Moreover, they lack the covering diaphragm.
-The glomerular endothelial cell membranes have numerous aquaporin-1 channels to facilitate fast passage of water through them.
The luminal surface of these capillaries has a well developed thick glycocalyx; 200 to 400 nm thick;
It consists of negatively charged proteoglycans (as versican, syndecan, and perlecan) and glycosaminoglycan sidechains (as heparan sulfate and chondroitin sulfate).
This glycocalyx represents significant permeability barrier despite presence of wide endothelial fenestra; its negative charge repulses the negatively charged plasma proteins, which prevents their filtration.
In addition, endothelium forms an initial physical barrier which prevent passage of blood cells and platelets into the urinary space.
-The second layer of the filtration barrier is Glomerular basement membrane (GBM), is a thick basal lamina which is formed by the fused membranes of both endothelium and podocytes.
-It is composed of a network consisting of type IV collagen, laminin, nidogen, and entactin,
together with heparin sulfate and proteoglycans,
as well as multi-adhesive glycoproteins.
These molecules form an organized fibrous network with heterogeneous pores of 10 nm thick, arranged into three parallel sandwiched-like layers.
These layers can be visialized by transmission electron microscopy as the following: Lamina rara externa, interna and densa.
This unique arrangement restricts passage of proteins larger than 70 kDa.
Smaller proteins (such polypeptide hormones) which are accidently filtered from plasma are degraded, and their amino acids resorbed back by the PCT.
+Mutation in the gene encoding for the α5 chain of type IV collagen gives rise to Alport’s syndrome. +Moreover, Collagen type IV is also the target in autoimmune diseases such as Goodpasture syndrome and post transplantation diseases.
The outermost layer of the filtration barrier is the filtration slits
-each filtration slit is about 30 nm wide. It is bridged with a zipper-like material termed slit diaphragm which is considered as “specialized occluding junctions”
-It is composed of Nephrin protein, various polyanionic glycoproteins and proteoglycans. These molecules interact to form a series of openings within the slit diaphragm with a negatively charged surface.
-Slit diaphragms are firmly anchored to numerous actin filaments within the foot processes of podocytes. Regulation and maintenance of the actin cytoskeleton of podocytes is a critical process for modulating its permeability by regulating size, patency, and selectivity of the filtration slits
+Mutations in the Nephrin gene are associated with congenital nephrotic syndrome.
And that brings us to the end. I’d like to thank you for your time and attention today.
