Laminitis
Laminitis is a disease of the feet of ungulates, found mostly in horses and cattle involving inflammation of the laminae. Clinical signs include foot tenderness progressing to inability to walk, increased digital pulses, and increased temperature in the hooves. Severe cases with outwardly visible clinical signs are known by the colloquial term [|founder], and progression of the disease will lead to perforation of the coffin bone through the sole of the hoof or being unable to stand up, often requiring euthanasia.
Laminae
The bones of the hoof are suspended within the axial hooves of ungulates by layers of modified skin cells, known as laminae or lamellae, which suspend the bony column from the hoof wall, contributing to shock absorption during locomotion. In horses, there are about 550–600 pairs of primary epidermal laminae, each with 150–200 secondary laminae projecting from their surface. These interdigitate with equivalent structures attached to the surface of the coffin bone, known as dermal laminae. The secondary laminae contain basal cells which attach via hemidesmosomes to the basement membrane. The basement membrane is then attached to the coffin bone via the connective tissue of the dermis.Pathophysiology
Laminitis literally means inflammation of the laminae, and while it remains controversial whether this is the primary mechanism of disease, evidence of inflammation occurs very early in some instances of the disease. A severe inflammatory event is thought to damage the basal epithelial cells, resulting in dysfunction of the hemidesmosomes and subsequent reduction in adherence between the epithelial cells and the basement membrane. Normal forces placed on the hoof are then strong enough to tear the remaining laminae, resulting in a failure of the interdigitation of the epidermal and dermal laminae between the hoof wall and the coffin bone. When severe enough, this results in displacement of the coffin bone within the hoof capsule. Most cases of laminitis occur in both front feet, but laminitis may be seen in all four feet, both hind feet, or in cases of support limb laminitis, in a single foot.Mechanism
The mechanism remains unclear and is the subject of much research. Three conditions are thought to cause secondary laminitis:- Sepsis/endotoxemia or generalized inflammation
- Endocrinopathy
- Trauma: concussion or excessive weight-bearing
Inflammatory events that are associated with laminitis include sepsis, endotoxemia, retained placenta, carbohydrate overload, enterocolitis, pleuropneumonia, and contact with black walnut shavings. In these cases, there is an increase in blood flow to the hoof, bringing in damaging substances and inflammatory cells into the hoof.
;Endocrinopathy
Endocrinopathy is usually the result of improper insulin regulation, and is most commonly seen with pituitary pars intermedia dysfunction and equine metabolic syndrome, as well as obesity and glucocorticoid administration. In cases of EMS, most episodes occur in the spring when the grass is lush.
;Trauma
Mechanical laminitis starts when the hoof wall is pulled away from the bone or lost, as a result of external influences. Mechanical laminitis can occur when a horse habitually paws, is ridden or driven on hard surfaces, or in cases of excessive weight-bearing due to compensation for the opposing limb, a process called support limb laminitis. Support limb laminitis is most common in horses suffering from severe injury to one limb, such as fracture, resulting in a non-weight bearing state that forces them to take excessive load on the opposing limb. This causes decreased blood flow to the cells, decreasing oxygen and nutrient delivery, and thus altering their metabolism which results in laminitis.
Theories of pathophysiology
;Matrix metalloproteinasesOne of the newest theories for the molecular basis of laminitis involves matrix metalloproteinases. Metalloproteinases are enzymes that can degrade collagen, growth factors, and cytokines to remodel the extracellular matrix of tissues. To prevent tissue damage, they are regulated by tissue inhibitors of metalloproteinases. In cases of laminitis, an underlying cause is thought to cause an imbalance of MMPs and TIMPs, favoring MMPs, so that they may cleave substances within the extracellular matrix and therefore break down the basement membrane. Since the basement membrane is the main link between the hoof wall and the connective tissue of P3, it is thought that its destruction results in their separation. MMP-2 and MMP-9 are the primary enzymes thought to be linked to laminitis.
;Theories for development
There are multiple theories as to how laminitis develops. These include:
- Enzymatic and inflammatory theories: The enzymatic theory postulates that increased blood flow to the foot brings in inflammatory cytokines or other substances to the hoof, where they increase production of MMPs, which subsequently break down the basement membrane. The inflammatory theory states that inflammatory mediators produce inflammation, but recognizes that MMP production occurs later. Therefore, this is possibly a 2-step process, beginning with inflammation and leading to MMP production and subsequent laminitis.
- Vascular theory: Postulates that increases in capillary pressure, constriction of veins, and shunting of blood through anastomoses to bypass the capillaries, causes decreased blood and therefore decreased oxygen and nutrient delivery to lamellae. The end-result would be ischemia, leading to cellular death and breakdown between the lamellae. Subsequently, increased vascular permeability leads to edema within the hoof, compression of small vessels, and ischemia. Vasoactive amines may be partially to blame for changes in hoof blood flow.
- Metabolic theory: Insulin affects multiple processes within the body, including inflammation, blood flow, and tissue remodeling. Change in insulin regulation may lead to laminitis. Hyperinsulinemia has been shown to cause increased length of the secondary lamellae and epidermal cell proliferation.
- Traumatic theory: Concussion is thought to directly damage lamellae, and increased weight-bearing is thought to decrease blood supply to the foot.
Rotation, sinking, and founder
Rotation is the most common form of displacement, and, in this case, the tip of the coffin bone rotates downward. The degree of rotation may be influenced by the severity of the initial attack and the time of initiation and aggressiveness of treatment. A combination of forces result in the deep digital flexor tendon literally pulling the dorsal face of the coffin bone away from the inside of the hoof wall, which allows the coffin bone to rotate. Also, ligaments attaching the collateral cartilages to the digit, primarily in the palmar portion of the foot, possibly contribute to a difference in support from front to back. The body weight of the animal probably contributes to rotation of the coffin bone. Rotation results in an obvious misalignment between PII and PIII. If rotation of the third phalanx continues, its tip can eventually penetrate the sole of the foot.
Sinking is less common and much more severe. It results when a significant failure of the interdigitation between the sensitive and insensitive laminae around a significant portion of the hoof occurs. The destruction of the sensitive laminae results in the hoof wall becoming separated from the rest of the hoof, so that it drops within the hoof capsule. Sinking may be symmetrical, i.e., the entire bone moves distally, or asymmetric, where the lateral or medial aspect of the bone displaces distally. Pus may leak out at the white line or at the coronary band. In extreme cases, this event allows the tip to eventually penetrate the sole of the foot. A severe "sinker" usually warrants the gravest prognosis and may, depending upon many factors, including the quality of aftercare, age of the horse, diet and nutrition, skill, and knowledge and ability of the attending veterinarian and farrier, lead to euthanasia of the patient.
Phases of laminitis
Treatment and prognosis depend on the phase of the disease, with horses treated in earlier stages often having a better prognosis.;Developmental phase
The developmental phase is defined as the time between the initial exposure to the causative agent or incident, until the onset of clinical signs. It generally lasts 24–60 hours, and is the best time to treat a laminitis episode. Clinical laminitis may be prevented if cryotherapy is initiated during the developmental phase.
;Acute phase
The acute phase is the first 72 hours following the initiation of clinical signs. Treatment response during this time determines if the horse will go into the subacute phase or chronic phase. Clinical signs at this time include bounding digital pulses, lameness, heat, and possibly response to hoof testing.
;Subacute phase
The subacute phase occurs if there is minimal damage to the lamellae. Clinical signs seen in the acute phase resolve, and the horse becomes sound. The horse never shows radiographic changes, and there is no injury to the coffin bone.
;Chronic phase
The chronic phase occurs if damage to the lamellae is not controlled early in the process, so that the coffin bone displaces. Changes that may occur include separation of the dermal and epidermal lamellae, lengthening of the dermal lamellae, and compression of the coronary and solar dermis. If laminitis is allowed to continue, long-term changes such as remodeling of the apex and distal border of the coffin bone and osteolysis of the coffin bone can occur.
The chronic phase may be compensated or uncompensated. Compensated cases will have altered hoof structure, including founder rings, wide white lines, and decreased concavity to the sole. Horses will be relatively sound. On radiographs, remodeling of the coffin bone and in cases of rotational displacement, the distal hoof wall will be thicker than that proximally. Venograms will have relatively normal contrast distribution, including to the apex and distal border of the coffin bone, and the coronary band, but "feathering" may be present at the lamellar "scar."
Uncompensated cases will develop a lamellar wedge, leading to a poor bridge between P3 and the hoof capsule. This will lead to irregular horn growth and chronic lameness, and horses will suffer from laminitis "flares." Inappropriate hoof growth will occur: the dorsal horn will have a tendency to grow outward rather than down, the heels will grow faster than the toe, and the white line will widen, leading to a potential space for packing of debris. The solar dermis is often compressed enough to inhibit growth, leading to a soft, thin sole that may develop seromas. In severe cases where collapse of the suspensory apparatus of P3 has occurred, the solar dermis or the tip of P3 may penetrate the sole. The horse will also be prone to recurrent abscessation within the hoof capsule. Venogram will show "feathering" into the vascular bed beneath the lamellae, and there will be decreased or absent contrast material in the area distal to the apex of the coffin bone.