Glomerulus (kidney)

Scanning electron microscope view of the inner surface of an opened (broken) capillary with fenestrae visible.(100,000x magnification)

Capillaries of the glomerulus are lined by endothelial cells. These contain numerous pores - also called fenestrae - 50–100 nm in diameter.[4] Unlike those of other capillaries with fenestrations, these fenestrations are not spanned by diaphragms.[4] They allow for the filtration of fluid, blood plasma solutes and protein, at the same time preventing the filtration of red blood cells, white blood cells, and platelets.

The glomerulus has a glomerular basement membrane consisting mainly of laminins, type IV collagen, agrin and nidogen, which are synthesized and secreted by both endothelial cells and podocytes: thus the glomerular basement membrane is sandwiched between the glomerular capillaries and the podocytes. The glomerular basement membrane is 250–400 nm in thickness, which is thicker than basement membranes of other tissue. It is a barrier to blood proteins such as albumin and globulin.[5]

The part of the podocyte in contact with the glomerular basement membrane is called a podocyte foot process or pedicle (Fig. 3): there are gaps between the foot processes through which the filtrate flows into Bowman's space of the capsule.[4] The space between adjacent podocyte foot processes is spanned by slit diaphragms consisting of a mat of proteins, including podocin and nephrin. In addition, foot processes have a negatively charged coat (glycocalyx) that repels negatively charged molecules such as serum albumin.

The mesangium is a space which is continuous with the smooth muscles of the arterioles. It is outside the capillary lumen, but surrounded by capillaries. It is in the middle (meso) between the capillaries (angis). It is contained by the basement membrane, which surrounds both the capillaries and the mesangium.

The mesangium contains mainly:

• Intraglomerular mesangial cells. They are not part of the filtration barrier but are specialized pericytes that participate in the regulation of the filtration rate by contracting or expanding: they contain actin and myosin filaments to accomplish this. Some mesangial cells are in physical contact with capillaries, others are in physical contact with podocytes. There is two-way chemical cross talk among the mesangial cells, the capillaries, and the podocytes to fine-tune the glomerular filtration rate.
• Mesangial matrix, an amorphous basement membrane-like material secreted by the mesangial cells.

Diagram of the circulation related to a single glomerulus, associated tubule, and collecting system.

The glomerulus receives its blood supply from an afferent arteriole of the renal arterial circulation. Unlike most capillary beds, the glomerular capillaries exit into efferent arterioles rather than venules. The resistance of the efferent arterioles causes sufficient hydrostatic pressure within the glomerulus to provide the force for ultrafiltration.

Blood exits the glomerular capillaries by an efferent arteriole instead of a venule, as is seen in the majority of capillary systems (Fig. 4). [3] This provides tighter control over the blood flow through the glomerulus, since arterioles dilate and constrict more readily than venules, owing to their thick circular smooth muscle layer (tunica media). The blood exiting the efferent arteriole enters a renal venule, which in turn enters a renal interlobular vein and then into the renal vein.

Cortical nephrons near the corticomedullary junction (15% of all nephrons) are called juxtamedullary nephrons. The blood exiting the efferent arterioles of these nephrons enter the vasa recta, which are straight capillary branches that deliver blood to the renal medulla. These vasa recta run adjacent to the descending and ascending loop of Henle, and participate in the maintenance of the medullary countercurrent exchange system.

The filtrate that has passed through the three-layered filtration unit enters Bowman's space. From there, it flows into the renal tubule - the nephron - which follows a U-shaped path to the collecting ducts, finally exiting into a renal calyx as urine.

Scheme of filtration barrier (blood-urine) in the kidney. A. The endothelial cells of the glomerulus; 1. pore (fenestra).
B. Glomerular basement membrane: 1. lamina rara interna 2. lamina densa 3. lamina rara externa
C. Podocytes: 1. enzymatic and structural proteins 2. filtration slit 3. diaphragma

The main function of the glomerulus is to filter plasma to produce glomerular filtrate, which passes down the length of the nephron tubule to form urine. The rate at which the glomerulus produces filtrate from plasma (the glomerular filtration rate) is much higher than in systemic capillaries because of the particular anatomical characteristics of the glomerulus. Unlike systemic capillaries, which receive blood from high-resistance arterioles and drain to low-resistance venules, glomerular capillaries are connected in both ends to high-resistance arterioles: the afferent arteriole, and the efferent arteriole. This arrangement of two arterioles in series determines the high hydrostatic pressure on glomerular capillaries, which is one of the forces that favour filtration to the Bowman's capsule.[6]

If a substance has passed through the glomerular capillary endothelial cells, glomerular basement membrane, and podocytes, then it enters the lumen of the tubule and is known as glomerular filtrate. Otherwise, it exits the glomerulus through the efferent arteriole and continues circulation as discussed below and as shown on the picture.

The structures of the layers determine their permeability-selectivity (permselectivity). The factors that influence permselectivity are the negative charge of the basement membrane and the podocytic epithelium, and the effective pore size of the glomerular wall (8 nm). As a result, large and/or negatively charged molecules will pass through far less frequently than small and/or positively charged ones.[7] For instance, small ions such as sodium and potassium pass freely, while larger proteins, such as hemoglobin and albumin have practically no permeability at all.

The oncotic pressure on glomerular capillaries is one of the forces that resist filtration. Because large and negatively charged proteins have a low permeability, they cannot filtrate easily to the Bowman's capsule. Therefore, the concentration of these proteins tends to increase as the glomerular capillaries filtrate plasma, increasing the oncotic pressure along Ofa glomerular capillary.[6]

The rate of filtration from the glomerulus to the Bowman's capsule is determined (as in systemic capillaries) by the Starling equation:[6]

${\displaystyle \ GFR=K_{\mathrm {f} }[(P_{\mathrm {gc} }-P_{\mathrm {bc} })-(\pi _{\mathrm {gc} }-\pi _{\mathrm {bc} })]}$

• GFR is the glomerular filtration rate.
• K_f is the filtration coefficient – a proportionality constant
• P_gc is the glomerular capillary hydrostatic pressure
• P_bc is the Bowman's capsule hydrostatic pressure
• π_gc is the glomerular capillary oncotic pressure
• π_bc is the Bowman's capsule oncotic pressure

The walls of the afferent arteriole contain specialized smooth muscle cells that synthesize renin. These juxtaglomerular cells play a major role in the renin–angiotensin system, which helps regulate blood volume and pressure.