Anal fissure is an independent disease, distinct from ulcers in other parts of the body. It has special clinical manifestations, namely: (1) severe pain; (2) prone to occur at the posterior midline of the anus; (3) low healing rate; (4) lack of granulation tissue; (5) non-growing skin around the fissure; (6) high anal canal pressure; and (7) commonly accompanied by hypertrophy of the anal papilla and sentinel piles. For 100 years, although many scholars have proposed numerous theories attempting to elucidate the causes of these characteristics, a satisfactory answer has yet to be provided.
### Traditional Theories on the Etiology of Anal Fissures
1. **Injury**
- **Skin Tear Theory:** In 1908, Ball was the first to propose the injury theory, hypothesizing that anal fissures result from the downward extension of a tear in the anal valve caused by hard fecal masses, forming a linear wound. He compared it to tearing the skin of the nail groove, with the torn flap becoming "sentinel piles" due to edema and repeated abrasions. However, this author ignored the fact that anal fissures typically occur below the dentate line, far from the anal valve, which remains intact without signs of tearing. Therefore, this theory is not valid and is rarely cited today.
- **Blaisdell's Gate Theory:** In 1973, Blaisdell, based on the anatomical arrangement of the external sphincter, pointed out that the superficial muscle fibers of the external sphincter form a "Y"-shaped fork at the posterior part of the anus, creating a minor triangle with the subcutaneous muscle fibers. This area lacks muscular support, making it a weak zone. He believed that the subcutaneous part resembles a fence, positioned horizontally at the posterior edge of the anus, and when hard fecal masses pass over it, the skin can easily tear. He advocated cutting the subcutaneous part of the external sphincter to treat anal fissures. However, it has been shown that the base of the anal fissure is not the subcutaneous part of the external sphincter but the internal sphincter, meaning the external sphincter is not the cause of anal fissures.
- It is worth noting that while many theories claim that fecal trauma is the main factor in the onset of anal fissures, they cannot explain why some fissures heal spontaneously while others become chronic. According to statistics, only one-quarter of patients with anal fissures have a history of constipation. Some cases of diarrhea are even inducements for anal fissures. A survey conducted by Hamanel in 1977 of 772 patients with anal fissures found that only 10% experienced defecation difficulties (≥3 days), while 75% had 1-3 bowel movements. It can be determined that most anal fissures are not caused by hard fecal masses, so they are not definitive evidence of anal fissures.
2. **Infection**
- **Crypt Gland Infection Theory:** In 1932, Rankin, Bargen, and Buie proposed that infection of the anal crypts could lead to anal fissures. Since the anal glands are mostly located in the posterior part of the anal canal, this seems to explain why anal fissures often occur at the posterior midline of the anus. However, ulcers caused by infections look entirely different from anal fissures. Rankin et al. also pointed out that anal fissures are varicose ulcers because the subcutaneous veins of the anal canal are dilated, and cryptitis can lead to phlebitis, which in turn leads to skin lesions. Lesioned skin loses its resistance to trauma, resulting in anal fissures. According to this theory, it seems possible to explain the difficulty in healing anal fissures, but it cannot answer why anal fissures tend to occur posteriorly. Although they assumed it was due to the susceptibility of the anorectal angle to traumatic injury, there is insufficient evidence.
- **Residual Epithelium Infection Theory:** In 1982, Shafik attempted to explain why anal fissures tend to become chronic using embryology. He pointed out that during the formation of the anal canal in the embryonic stage, the original anus overlaps with the hindgut to form the anorectal sinus, which disappears after birth. If the subcutaneous epithelium of the anorectal sinus remains in the anal canal of patients with anal fissures, it can be exposed and infected due to skin damage. Since this type of tissue is poorly differentiated and buried under the skin, it acts like "dead bone," preventing the wound from healing. However, Dohrenbusch et al. (1986) repeated Shafik's observations and found that what Shafik called residual epithelium was actually anal gland tissue, so this hypothesis does not hold.
3. **Comb Membrane Band Theory:** This theory on the etiology of anal fissures was proposed by Miles in 1919. Currently, it is still widely cited in literature related to anal fissures in China. However, it was already determined in the 1950s that the comb membrane band is actually the internal sphincter. The so-called "comb membrane band" described by Miles as formed by hyperplasia of subcutaneous fibrous tissue does not exist. The comb membrane band incision he advocated is, in fact, an internal sphincterotomy.
### Modern Concepts of Anal Fissures
In the 1950s, Eisenhammer's work gave modern concepts to the etiology of anal fissures. He first discovered that the muscle bundles at the bottom of the anal fissure were the internal sphincter rather than the subcutaneous part of the external sphincter, proposing that the cause of anal fissures is spasm or fibrosis of the internal sphincter, rather than the so-called comb membrane band. Treatment for anal fissures should adopt internal sphincterotomy rather than comb membrane band incision. He not only corrected the misunderstanding about the comb membrane band but also protected the subcutaneous part of the external sphincter from destruction. His arguments are now widely accepted. Several issues need clarification:
1. **Is Internal Sphincter Spasm the Cause or Result of Anal Fissures?** Almost all chronic anal fissures are accompanied by high tension of the internal sphincter and high anal pressure. Schouten (1996) recently measured the average maximum resting anal pressure (MARP), finding that patients with anal fissures had significantly higher pressures than the normal control group (121.07±16.97 mmHg vs. 68.78±24.48 mmHg). Northmaun et al. (1974) found that during rectal distension, the internal sphincter of patients with anal fissures did not relax but instead contracted excessively. Such abnormal activity of the internal sphincter is generally considered the result of chronic inflammatory stimulation of anal fissures or a reflexive reaction caused by pain. However, this hypothesis lacks experimental basis and may be misleading. When local anesthetics are used, the pain of anal fissures disappears, but MARP does not decrease, suggesting that spasm is not secondary to pain. Many pieces of evidence indicate that internal sphincter spasm often precedes the onset of chronic anal fissures, being the cause rather than the consequence. For example:
- **Psychological Factors:** A considerable proportion of patients with anal fissures have had psychological disorders before the onset of the disease. Kumar et al. (1980) confirmed that mental stress can increase anal pressure, i.e., enhance the reflexive activity of the internal sphincter. Long-term exposure to mental stress can lead to changes in β1-adrenergic receptors. Chronic patients with anal fissures show increased sensitivity of their internal sphincters to β2-agonists, so psychological factors may be one of the triggers for anal fissures.
- **Nitric Oxide (NO) Metabolism Disorder:** Normally, the inhibitory reflex of the internal sphincter is closely related to NO. Rattan et al. confirmed that NO can cause concentration-dependent relaxation responses in the internal sphincter. NO is an inhibitory neurotransmitter released from the non-adrenergic non-cholinergic (NANC) nerve endings of the gastrointestinal tract. In patients with anal fissures, the internal sphincter exhibits paradoxical contraction during the rectoanal inhibitory reflex, indicating that the release of NO is impaired. Therefore, NO may be involved in the pathogenesis of primary anal fissures.
- **Degeneration of the Nerve Plexus of the Internal Sphincter:** Shafik (1991) found during anal sphincter biopsy that patients with high-tension constipation had degenerative changes in the nerve plexus within the internal sphincter. He believed that these changes affect the rectoanal inhibitory reflex, leading to the inability of the internal sphincter to relax. It may mainly affect the parasympathetic nervous system, causing excessive sympathetic nervous system activity. Therefore, the spasm of the internal sphincter in anal fissures may be related to the degeneration of its nerve plexus.
- **Changes in Neuropeptides:** Anderson and Bloom stimulated the sacral nerves and found that vasoactive intestinal peptide (VIP) in brain-gut peptides has an inhibitory effect on the internal sphincter, while substance P (SP) has an excitatory effect. Patients with internal sphincter spasm have reduced VIP and increased SP in their blood, thus increasing muscle tone.
- **Clinical Evidence:** High sphincter tension can induce ischemia of the anal canal skin, leading to the formation of anal fissures. If the sphincter tension is reduced and the blood supply to the anal canal skin is restored, the anal fissure will heal. Therefore, internal sphincter spasm is the cause rather than the consequence of anal fissures.
2. **Negative Correlation Between Anal Pressure (MARP) and Anal Canal Skin Blood Flow Perfusion Pressure (ADBF):** In 1986, Gibbons and Read proposed that internal sphincter spasm, i.e., elevated anal pressure, can lead to ischemia of the anal canal skin. Schouten (1994) simultaneously detected 178 patients with various anal diseases, including anal fissures, using a Doppler laser skin blood flow meter and an anorectal pressure meter. The results supported Gibbons' argument, namely:
- Healthy individuals have skin blood flows of 1.5±0.7V, 0.7±0.3V, 1.7±0.8V, and 1.6±0.5V in the anterior, posterior, left, and right quadrants of the anal canal, respectively. The blood perfusion pressure in the posterior commissure region is significantly lower than in other areas of the anal canal.
- Chronic anal fissure patients have significantly higher MARP than the control group and other anal disease patients, while ADBF is much lower.
- After anal anesthesia, MARP decreased from 63±21 mmHg to 32±15 mmHg, and ADBF at the posterior midline increased from 0.79±0.22V to 1.31±0.35V.
The above results indicate that the pathophysiological essence of anal fissures is high anal pressure and low blood flow.
3. **Anal Fissures Are Ischemic Ulcers:**
- **Anatomical Evidence:** Klosterhalfen et al. (1989) observed the local anatomy of the anal arteries through cadaver angiography and found that only 15% of normal people have good anastomosis of the branches of the bilateral anal arteries at the posterior commissure, while 85% do not have anastomosis. The density of small vessels in this area is lower than in the anterior commissure and sides, forming a hypovascular zone. The small branches of the anal arteries penetrate the intervals of the internal sphincter and enter the muscle vertically, possibly being compressed by the spastic contraction of the muscles, aggravating the ischemia of the posterior commissure. Recently, Lund (1999) observed the distribution of small arteries in the skin regions and internal sphincter regions of each quadrant of the anal canal using histological methods and found that within a 1 cm interval above and below the dentate line, the number of small arteries in the posterior region is significantly lower than in other regions (Table 2).
The data show that the posterior midline has poorer blood supply than other areas. Gibbons et al. pointed out when analyzing the impact of sphincter spasm on the blood supply of the anal canal that usually the systolic pressure of large arteries is 120 mmHg, the pressure of small arteries within the sphincter is about 85 mmHg, and the normal resting pressure of the anal canal is within this range. If sphincter spasm causes anal pressure to rise above the pressure of the small arteries, the vascular perfusion pressure of the anal canal skin area can drop to 35 mmHg. If this occurs in the lower extremities, it can cause ischemic ulcers and lower extremity rest pain, so there is no reason to believe that the same situation would not occur in the anal canal.
**Clinical Experimental Evidence:** Schouten (1996) measured the MARP and ADBF before and after lateral internal sphincterotomy in 27 patients with chronic anal fissures and made comparative observations. The results showed (Table 3) that the preoperative MARP of the patients was significantly higher than that of the control group, and the blood flow at the site of the anal fissure was significantly less than that of the posterior midline in the control group. After the operation, MARP significantly decreased (35%), and the blood flow at the site of the anal fissure significantly increased (65%). Within 6 weeks, 24 of the 27 patients healed, and both MARP and ADBE returned to normal values (Table 3).