Acute and Long-term Biological Effects of Shock Wave Lithotripsy (Part I)

Shockwave lithotripsy (SWL) has proven to be a very effective treatment for kidney stones and can be used to treat many types of stones. And precisely because shockwave lithotripsy is a non-invasive treatment, SWL has been clinically popular since the eighties of the last century.

Despite this, SWL can also cause vascular and tissue damage to the kidneys and surrounding organs. Acute injury to SW, sometimes with very serious consequences, leads to renal scarring, which can be accompanied by permanent loss of renal function and may be associated with potentially serious long-term adverse effects. A retrospective study suggested that lithotripsy may cause osteoporosis. In addition, more research has focused on the relationship between SWL and the development of diabetes and hypertension.

Therefore, it is necessary to understand the biological effects of shock waves on the body, the physical mechanism of shock wave damage to the body, and how to reduce or prevent the damage of shock waves to tissues.

01 Advantages and limitations of SWL

Shockwave lithotripsy is a method in which a generator is used outside the body to generate high-energy sound pulses (shock waves) to break up kidney and ureteral stones in the body. Therefore, SWL is the only non-invasive treatment for urinary stones.

Within the first few years of SWL application, SWL was considered to be able to handle stones of any anatomical location, treating stones of almost any composition. However, with the further use of shockwave lithotripsy for urinary stones, urologists soon discovered that SWL had limited capabilities in treating urinary stones. Sometimes SWL lithotripsy works too well, and obstruction of the debris in the ureter may occur due to the limited ability of the ureter to remove stones.

Nowadays, SWL is used for uncomplicated solitary stones or upper urinary tract stones with a load of less than 2 cm. Not all mineral types of stones respond well to SW. Calcium oxalate monohydrate, dicalcium phosphate and cystine stones have high resistance to SW. It is important to note the remnants of stone fragments after SW, which in many cases may become the source of new stone production.

Compared with invasive treatments such as ureteroscopy and percutaneous nephrostomy, SWL has a lower rate of stone removal and a higher rate of stone recurrence. Despite this, SWL is still a very effective treatment for stones, is non-invasive, and can usually be treated on an outpatient basis, with more than 70% of uncomplicated upper segment stones being treated with SWL as the first choice.

02 Shockwaves and stone crushers

Although different crushers have different principles for generating shock waves (e.g. electromagnetic EML, hydroelectric EH spark plug, piezoelectric, etc.), the acoustic pulses they produce are very similar. Its waveform is characterized by a positive phase wave with a pressure of 20-110 MPa, followed by a negative phase wave with a pressure of -5-10 MPa (1 megapascal = 10 atmospheres). The phase of a normal-phase wave is very short (about 1 μs) and reaches peak pressure almost instantaneously. The pulses of some of the positive phase waves constitute the "shock force" of the SW.

The shockwave focusing mechanism means that the lithotripsy machine will focus the generated shockwave on a specific elongated area of space in the patient's body (such as a cigar-shaped area), and break up the stones located in this space area by focusing. Different crushers have different focal areas (focal volume), acoustic pressure, and energy density. SW's physical studies have shown that the width of the SW focal area (focal spot) is an important parameter of SW lithotripsy, and when the width of the focal area exceeds the diameter of the stone, the stone will break better. Most lithotripters have a focal spot of about 6-10 mm, but some lithotripters have a very narrow focal spot (≤4 mm) while others have a wider focal spot (about 16-18 mm).

03 How shock waves break stones and damage tissues

Although the shock wave generated by an extracorporeal lithotripsy machine is very energy-intensive, it may still take hundreds or even thousands of shockwaves to break a stone into particles that are fine enough (about 2 mm) to facilitate its expulsion from the body. Stone fragmentation is a gradual process, and stones can also be ineffective due to repeated stress fatigue. Under the action of the shock wave, the stone produces microcracks, which gradually elongate and expand until the stone breaks up.

In short, the mechanism of stone crushing mainly focuses on two aspects, cavitation effect and normal stress effect, cavitation effect refers to the bubble produced by SW negative phase wave in the urine around the stone, after which the bubble rapidly increases and bursts, and produces a more powerful secondary SW from the burst point, and at the same time produces a strong liquid micro-jet, and the pressure is focused on the surface of the stone. Clusters of bubbles produce a cavitation effect, and the bursting of the bubbles erodes the surface of the stone. The cavitation effect may be active throughout the stone fragmentation process, but it seems that the cavitation effect is more important in the process of crushing, because when the stone fragments are too small, other effects cannot be effective. Therefore, cavitation is crucial for stone crushing, but cavitation is also a major contributor to tissue damage.

The fragmentation of large stones is due to compression-induced internal stress, which is in the positive pressure phase of the shock wave. Compression waves (or sound waves) pass through the stone and the fluid surrounding the stone and cause internal stress inside the stone in several ways. Recent studies using numerical simulations have shown that stress waves are emitted from the surface of the stone into the interior of the stone, where the stress wave is amplified by different angles of incidence and irregularities of the incidence. Compression/sound waves also play a role in squeezing the stone from the outside. A narrow and strong hoop stress wave conducts along the stone. The intrinsic circumferential stress is the key to stone fragmentation, and in vitro studies have shown that if the compression wave is blocked on the surface of the stone, the fragmentation effect of the stone will be significantly reduced. The significance of these findings is that stones break better when the crusher has a larger focal width than the stone diameter.

The mechanisms involved in stone fragmentation contribute to the understanding of the mechanisms of tissue damage in SWL. Because stone fragmentation is a gradual process, the body is subjected to repeated SW effects (hundreds to thousands of SWs). The cavitation effects and shear forces that lead to stone fragmentation are also involved in the damage to the body. Kidney damage caused by SWL is mainly vascular hemorrhagic lesions. There is substantial evidence that cavitation is a major factor in vascular damage. For example, when SW produces cavitation effect, the injection of microbubbles into the vascular system can increase the damage to the vascular system, while also inhibiting the tensile phase of SW, which is necessary to drive the bubble to enlarge and reduce tissue damage.

Nowadays, it is difficult to understand the exact mechanism by which cavitation effects destroy the walls of blood vessels, especially in the case of damage to tiny blood vessels. In vitro studies have shown that the mechanism by which cavitation effects destroy the blood vessel wall may involve the dilation of air bubbles, the rupture of air bubbles. Regardless of how air bubbles cause blood vessels to rupture, it is important that blood vessels exposed to cavitation effects are not susceptible to damage under normal physiological conditions. However, the blood vessels that collect blood in the hematoma are susceptible to cavitation effects, and damage from cavitation effects is rare in normal blood circulation. A study in pigs showed that hundreds of SWs, in pig kidneys, were needed to trigger cavitation. This seems to indicate that a necessary condition for cavitation to occur is constant repetition pressure. The cavitation effect depends on the growth of cavitation nuclei and bubbles that are produced in a continuous cycle. But what is a natural cavitation nucleus?

If the circulating blood flow is not a good medium for cavitation, then the observable cause of bleeding due to cavitation may be due to other damaging events. Perhaps there is a defect in the blood vessels, and the blood must be collected in order to have a cavitation effect and further perpetuate the damaging event. A recent study modeled the properties of various tissue materials within the kidney, showing that shear forces may accumulate within the soft tissues, but only if SW delivery is faster than tissue relaxation time. The degree of shear force induced displacement/deformation predicted by the model will depend on the structural characteristics of the tissue, i.e., different kidney regions, which have different characteristics, and the shear force is greatest near the apex of the renal papilla. Studies in pigs have shown that renal papillae are particularly sensitive to SWL damage. Therefore, the cumulative shear model may be in good agreement with the experimental results and may help explain why kidney damage is reduced when the SW rate is slow.

——To be continued——