Glomerular Structure
Functions & Clinical Correlates
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Glomerular Structure
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What is Glomerulus?
Glomerulus is the filtration unit for a nephron.
1) Glomerular Capillary Tuft
Afferent arterioles break down in many capillary loops that anastomose and form efferent arterioles called as Glomerular Capillary Tuft. Efferent arterioles further divide into peritubular Capillaries present near the Proximal Convoluted Tubule (PCT) and end up forming the vein. Tuft is covered by the double layer of epithelial cells having foot processes called podocytes.
There are two types of epithelial cells, visceral and parietal epithelial cells. These are connected with each other as well as with proximal convoluted tubule.
Glomerulus consist of glomerular capillary tuft covered by the epithelial cells, these cells combine to form the Bowman’s capsule.
2) Mesangium
Adjacent to the glomerular capillary tuft, there are mesangial cells that produce connective tissue through which capillaries pass. This whole structure made by capillary tuft and connective tissue is called mesangium.
3) Endothelial cells
The glomerular capillary cell lining contains thousands of perforated structures, due to that special feature of capillaries these called as fenestrated capillaries.
The size of the holes in capillaries is about 70 to 100nm, filtered material passes through theses fenestration, they are also called as perforated endothelial cells.
4) Glomerular Basement Membrane. (GBM)
It is present between the capillary endothelial lining and epithelial cells.
Lamina Densa
Central area of the basement membrane under electron microscope is thick and dense called Lamina Densa. Less dense area of GBM are electro lucent and called Lamina Rara.
There are two sides of Lamina Rara, internal and external. The area adjacent to the capillaries called Lamina Rara Interna. The area adjacent the Bowman’s capsule is called Lamina Rara Externa. Basement membrane is made up of type IV collagen. This collagen consists of triple helix of alpha peptide chain.
Negatively charged poly anionic proteoglycans make the GBM electronegative.
Negatively charged molecules are also present on the endothelial and epithelial surface so whole filtration membrane becomes electronegative.
NOTE:
Alpha peptide chain has a domain called as globular non-collagenous domain of type IV collagen.
Clinical Correlates of Glomerular Structure
a) Anti glomerular basement membrane glomerulonephritis
In some patients, autoantibodies are formed against the glomerular basement membrane, lead to hematuria and proteinuria called as Anti glomerular basement membrane glomerulonephritis.
Antibodies which are formed called anti GBM auto antibodies.
b) Goodpasture’s Syndrome
In some patients, antibodies are not only formed against the GBM but also against the alveolar basement membrane, causing hematuria and hemoptysis called as Goodpasture’s Syndrome.
c) Hereditary Nephritis.
Alpha chains become mutant and defective triple helix results in abnormal weak GBM. In early life, these patients develop hematuria and glomerular injury called as hereditary nephritis.
5. Epithelial Cells
Visceral epithelial cells have foot processes that contain finger like projections which facilitate binding to GBM and are interconnected
Visceral epithelial cells have foot processes that contain finger like projections which facilitate binding to GBM and are interconnected
==NOTE:
Parietal Epithelial cells do not have foot processes.
6. Glomerular Filtration Barrier
Fluid filtrates through three layers.
1. Endothelial layer ……………………….. Fenestrated capillaries.
2. GBM……………………………………….Type IV collagen.
3. Epithelial layer……………………………Filtration Slits.
NOTE:
Filtration slits have filtration diaphragm made up of a protein called as Nephrin.
In some pathologies, Nephrin is either mutant or body develops auto antibodies against it, So, when Nephrin is impaired, filtration diaphragm is destroyed and glomerular system starts filtering out pathological amount of proteins causing proteinuria.
1) Glomerular filtration Barrier is a size barrier, so the filtration depends upon the size of molecule.
Examples: Glucose and amino acids filter easily but plasma protein cannot be filtered due to its large size.
Red blood cell (7—8 micron), White blood cells (12—14 micron), Platelet (1—2 micron), usually these are very large molecules and none of them filters freely.
2) It is also a charge barrier. Positive charged ions filter more easily and negative charged ions are repelled.
Plasma protein (Albumin, Globulins, Fibrinogen) do not filter easily, size of the albumin is small enough to be filtered but due to charge resistance it repelled.
Clinical Correlates
Minimal Change disease
In this disease cytokines are formed which neutralize the electronegativity on the glomerular filtration membrane, hence membrane cannot repel the albumin and filters easily. Patient develops hypoalbuminemia. Due to loss of podocytes, lot of proteins starts releasing into urine.
7. Mesangial cells
Mesangial cells have some special properties;
a) Contractile cells: Present around the capillaries.
b) Phagocytic cells: Can engulf antigen antibody complex
c) Proliferative cells: In some diseases, these cells can proliferate and produce extra amount of connective tissues, compress the cap
d) Receptors for Angiotensin II.
Neuromuscular Junction
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