Monday, March 3, 2008

The Uriniferous Tubules - The Functional Unit of the Kidney

The functional unit of the kidney is the uriniferous tubule, a highly convoluted structure that modifies the fluid passing through it to form to form urine as its final output. This tubule consists of two parts, the nephron (Gr. nephros kidney) and the collecting tubule. There are approximately 1-4 million nephrons per kidney [3] which are drained by a single collecting tubule. Multiple collecting tubules join in the medulla to form larger and larger ducts [2].

The Nephron

The nephron consists of a dilated portion, the renal corpuscle (located in the cortex); the proximal convoluted tubule; the thin and thick limbs of Henle's loop; the distal convoluted tubule; and the collecting tubules and ducts.

There are two types of nephrons, depending on the location of their renal corpuscles and the length of their Henle loop. (See Figure 2)

1. Cortical Nephrons
Shorter cortical nephrons have their renal corpuscles in the cortex and have short loops of Henle that do not go beyond the outer region of the pyramid. The thin segment in these nephrons is confined to a small part of the descending limb, and the distal thick segment begins at the hairpin turn [4].

2. Juxtamedullary Nephrons
These longer juxtamedullary nephrons have their renal corpuscles close to the base of a pyramid and have long loops of Henle with long thin segments. The thick descending limb does not extend beyond the outer stripe of the medulla. The thin limb begins here and extends deep into the inner region of the medullary pyramid. The thick ascending limb begins at a deeper level than that at which the thick descending limb ends. (In other words, the thin ascending limb is shorter than the thin descending limb.) [4]

The Renal Corpuscle

The renal corpuscle, an oval to round structure about 200 to 250 µm in diameter, is composed of a tuft of capillaries, the glomerulus, which is surrounded by a hollow capsule of tubular epithelium called Bowman's capsule.



The glomerulus is composed of tufts of fenestreated capillaries supplied by the afferent glomerular arteriole and drained by the efferent glomerular arteriole (Figure 4 above). The normal connective tissue cells are replaced by a specialized cell type know as mesangial cells. These provide the scaffold to support capillary loops. They also have contactile and phagocytic properties [5].

The capillaries constituting the glomerulus are similar to fenestrated type of capillaries. Their endothelial cells are highly attenuated, except for the region containing the nucleus, but the pores are usually not covered by a diaphragm [2].

Investing in the glomerulus is a basal lamina consisting of three layers. The lamina densa - the middle layer - is about 100 nm thick and consists of type IV collagen. The laminae rarae contain laminin, fibronectin and proteoglycans and are located on either side of the lamina densa. Lamina rara interna - between the endothelial cells of the capillary and the lamina densa and lamina rara externa - between the lamina densa and the visceral layer of Bowman's capsule.


The visceral layer of Bowman's capsule is composed of endothelial cells that are highly modified to perform a filtering function. These large cells, called podocytes, bear numerous long, tentacle-like cytoplasmic extensions, primary processes, which follow but usually do not come in close contact with the longitudinal axes of the glomerular capillaries. Each primary process gives rise to numerous secondary processes, called pedicels, that embrace the capillaries of the glomerulus by interdigitating with pedicels from neighoring processes of different podocytes forming the filtration slits [2,3]. These filtration slits, however, are not completely open; instead, they are covered by a thin slit diaphragm which acts as part of the filtration barrier [2].











The Proximal Convoluted Tubule


Bowman's space drains into the proximal convoluted tubule at the urinary pole. In this region the simple squamous epithelium of Bowman's capsule is continuous with the cuboidal, or low columnar epithelium of the proximal convoluted tubule (PCT). The PCT is the longest and widest part of the nephron, and constitutes the majority of tubular sections seen in the cortical labyrinth. It follows a tortuous course, then terminates by straightening out and passing into the nearest medullary ray to become the thick descending limb of the loop of Henle. The PCT is about 15 mm long, and the entire proximal thick segment can be up to 25 mm long [4]. The cuboidal cells of this epithelium contain numerous elongated mitochondria and thus have an acidophilic cytoplasm. The cell apex has abundant microvilli about 1 µm in length, which form a brush border. PCTs are surrounded by peritubular capillaries and associated with the apical cytoplasm of the cells are numerous canaliculi which increase the capacity of the PCT cells to absorb macromolecules. Pinocytotic vesicles are formed by the evagination of the apical membranes and contain macromolecule that have passed through the glomerular filter [3].