Ureteral Physiology and Pharmacology

Ureteral Anatomy

The ureters are retroperitoneal structures responsible for urine transport between the kidneys and the bladder. They are typically 22–30 cm in length and are composed of four layers. The inner layer is transitional epithelium, over which lies the lamina propria. The lamina propria is invested with a muscle layer that is composed of inner longitudinal and outer circular muscle fibers.Overlying the muscle is the adventitia, which contains the blood vessels and lymphatics coursing with the ureter.1

The urothelium is composed of seven layers of cells, which not only serve as protective barrier but are critical to function.2 Serving as the first line of contact with the urinary environment, the urothelium is able to sense chemical and mechanical changes within the lumen and then signal smooth muscle, neurons, and capillaries via the release of prostaglandins, catecholemines, and cytokines.2

The smooth muscle layer of the ureter accounts for ureteral peristalsis as well as structural support.3 It is divided into an inner helical layer and an outer mesh-like arrangement.3 The inner helical layer is responsible for peristalsis while the outer mesh-like layer offers structural support.3

Blood supply to the ureter above the pelvic brim arises medially from the renal artery, abdominal aorta, gonadal artery, and common iliac artery. Below the pelvic brim, arterial inflow

arises laterally from the internal iliac arteries and its branches.4

Umbrella cells form the urine plasma barrier and are found in the ureter as well as the bladder. They are unique in that they have the ability to increase and decrease size considerably in response to intraluminal pressure5 (Fig. 8.1).

Initiation and Modulation

of Peristalsis

Precise coordination between ureteral smooth muscle and neurotransmission is required for downstream propagation of urine between the kidneys and bladder. As with all smooth muscle, contraction of the ureter is the result of depolarization of the cell membrane.In the resting smooth muscle cell, the membrane potential is −50 to −80 mV.6 When stimulated by a chemical signal or direct signaling, sodium and potassium conductance increases the membrane potential to 50 mV,generating an action potential.The effect is an increase in permeability to calcium and subsequent calcium influx into cells.1 Intracellular calcium then activates calmodulin, which binds myosin light chain kinase and leads to myosin phosphorylation. Phosphorylated myosin then migrates up actin filaments, resulting in smooth muscle contraction.1

Mediators that increase intracellular calcium cause ureteral contraction. Interactions with