Equine laminitis – aetiology, pathogenesis and prevention

Equine laminitis is a prevalent disease that affects thousands of equids of all shapes and sizes throughout the year. Despite laminitis commonly being thought of as only affecting ponies, in fact, horses are commonly affected too.

Once an equid has suffered with laminitis, it is subsequently more susceptible and, therefore, management with an understanding of pathogenesis is important for prevention.

The aetiology of laminitis is complex, with the pathology stemming from a number of causes that are anatomically distant from the hoof. Laminitis results in deterioration of the lamellae and this facilitates movement of the pedal bone due to the degeneration of connections. The aetiology and pathogenesis are closely linked, with vascular, enzymatic and systemic inflammation being pathways for the development of laminitis. Yet, the disease is not fully understood.

Matrix metalloproteinases (MMPs) enzymes are essential for the maintenance and repair of the epidermal lamellae. However, MMPs production is stimulated and increased by endotoxins circulating in the vascular system and are thought to cause degeneration of the lamellae.

Vascular alterations including ischaemia (possibly caused by vasoactive amines) are seen in a number of aetiologies. Equids suffering from systemic inflammatory response syndrome (SIRS) are consequently at risk of laminitis. SIRS can result from intestinal disease, caused by exposure to bacterially derived endogenous toxins that pass through the mucosa barrier from the hindgut and trigger activity from inflammatory cytokines. This is understood to contribute to, or cause, the development of laminitis in some models.

Damage to the cellular components of the basement membrane causes disintegration of attachments between the basement membrane and the pedal bone. The basement membrane forms the structural base of the hoof and is an extracellular matrix comprised of a number of different tissue types, including laminin-332 and collagen type IV¹. The sheer weight of the equid tears the connections already weakened, thus causing further damage and suffering.

During the initial stages of laminitis, vasodilation occurs in the hoof and this causes a rise in the hoof temperature, which is known to be detrimental². The aetiology of laminitis determines the extent of vasodilation and, subsequently, the hoof temperature; however, vasodilation itself is only one causation.

There are different stages of laminitis – developmental, acute and chronic. The developmental stage is the initial pathogenesis, whereby pathogens begin to affect the body – for example, in the carbohydrate overload (CHO), black walnut extract administration (BWE) and metritis causations. At this point the hooves are not affected (Figure 1a). This developmental stage lasts for a period of approximately one to three days.

The acute phase occurs when degeneration of the lamellae is initiated (Figure 1) approximately 30 hours after induction⁴. The period of time taken to develop acute laminitis is dependent on the aetiological mechanisms. MMPs are responsible for the deterioration and disintegration of the basement membrane, causing separation between the filaments of the basement membrane and the lamellae⁵.

Chronic laminitis is the final stage of the disease, whereby the extent of the damage to the lamellae has weakened attachments and, therefore, movement (sinking, rotation or both) of the pedal bone. Rotation is caused when connections disintegrate at the dorsal area, consequently forcing rotation of the pedal bone from the flexor tendon⁶. At this point the degree of displacement of the distal phalanx determines the outcome.

Causes and pathogenesis

CHO-induced laminitis commonly occurs from consumption of grass high in non-structural carbohydrate (NSC). A high NSC content is deemed to be 134g/kg ⁷. Fructan is the most harmful NSC and is a type of sugar formed from fructose polymers. Fructan is digested in the hindgut and microflora aid in fermentation. If too much fructan is consumed, fermentation increases, resulting in an alteration of the pH of the hindgut and a build-up of lactic acid^5,8. This enables Gram-positive bacteria to increase, hence resulting in deterioration of the mucosa, which causes permeability.

Consequently, bacterial-associated by-products from the hindgut are passed into the circulatory system. Translocation of bacterial by-products causes CHO-induced laminitis as stimulation of enzymes such as MMPs from pathogenic bacteria is believed to cause degeneration in the hoof.

Sepsis is known to result in the development of laminitis when the causation stems from CHO⁹. Equids are highly susceptible to laminitis when the body is under attack from pathogenic bacteria. Metabolic diseases cause the majority of cases of laminitis, therefore understanding the aetiology is key to treatment and management.

Pituitary pars intermedia dysfunction (PPID) is a neurodegenerative disease of the pituitary gland where the hypothalamic–pituitary adrenocortical develops abnormalities, usually in the form of an adenoma¹⁰. PPID is an endocrine associated complication that causes surplus amounts of adrenocorticotropin (ACTH) to be excreted¹¹.

PPID is understood to be caused by oxidative exposure to the pituitary gland¹⁰, which is thought to trigger the development of laminitis, as a significant rise that is greater than what is expected by season in the ACTH levels predisposes laminitis¹¹. This is due to ACTH affecting insulin and its ability to control glucose levels, hence causing hyperinsulinaemia (heightened levels of glucose) and insulin resistance, which is toxic to the laminae and causes cells to alter becoming misshapen and collapse, causing laminitis.

Equine metabolic syndrome (EMS) also causes dysregulation of insulin and is often seen in obese ponies that have the classic EMS phenotype, “cresty neck” and a body condition score greater than three with generalised or regional obesity. With modern management, native breeds in particular are very susceptible to obesity. This genetic predisposition can cause both insulin resistance and hyperinsulinaemia.

Weight loss does increase insulin sensitivity¹², which reduces the susceptibility to laminitis. Furthermore, there is a heritable element to EMS, especially if grazing was scarce during gestation, and this is why it is vital to keep ponies in particular slim.

The causation of hyperinsulinaemic laminitis is understood to be triggered by the structural collapse of the laminae tissue from the epidermal cells becoming damaged. This is understood to be caused by overproduction of the insulin-like growth factor. Subsequently, the receptor of insulin and the receptor of the growth factor-1 form bonds are disproportionate to demand¹³.

There is a correlation between the severity of the laminitis and the amounts of insulin in the blood (a reduction in insulin also decreased the severity of lameness)¹⁴. Although there are similarities between PPID and EMS, the main difference is PPID individuals show heightened amounts of ACTH in the blood plasma.

One cause of laminitis most likely under recognised and reported is laminitis caused from the consumption of toxic plants, which can result in endotoxaemia. For example, the black locust tree, red oak tree, hoary alyssum plant, white clover^15,16 and walnut tree all cause laminitis.

There is extensive research on laminitis induced by exposure to the black walnut tree extract Juglans nigra for research. BWE causes an immunological reaction and, therefore, systemic inflammation¹⁷. Leukocytes are involved in the pathogenesis of laminitis, by causing inflammation in the laminae tissue.

Leukocytes are thought to be translocated from the circulatory system to the hooves. BWE increases the blood plasma levels of the neutrophil elastase and this causes degeneration of the basal membrane¹⁸. Exposure to black walnut shavings, when mistakenly used for bedding, can also result in the development of laminitis¹⁹.

Supporting limb laminitis occurs when the hoof takes a substantial proportion of the horse’s weight, often through injury to the contralateral limb. This results in ischaemia to the hoof, as movement is required to facilitate the capillaries to refill, which leads to laminitis in the single weight-bearing limb. It is thought deprivation of arterial blood causes laminitis²⁰.

Prevention

Achieving and maintaining a slim body condition score of 2.5 to 3 is crucial, as being overweight predisposes laminitis and EMS. The bodyweight should be assessed on a regular basis using a weight tape to monitor the weight throughout the year (Figure 2).

It is essential to regulate and control the calorie intake of all equids – especially those prone to laminitis. Obesity significantly increases the risk of laminitis, due to increasing the danger of insulin resistance and EMS. Furthermore, dietary-induced laminitis usually occurs from eating foodstuffs too high in NSC – for example, grass and cereal grains.

First and foremost, the grazing area must be restricted and time spent away from pasture is important. In a 24-hour time frame an equid can consume a comparable amount of NSC that is used to induce laminitis in a study⁷. Hence, reducing availability is a must.

Using electric fencing is one of the most effective ways to control grazing areas and, therefore, grass intake. Using a tracking system is useful if you want to encourage movement, but still limit grass availability. The NSC level of the grass increases during daylight hours – particularly by mid-afternoon – so it is advisable, especially through the growing season, to only allow grazing early in the morning or through the night⁷.

Respiration of the plant occurs during the night and, therefore, the sugars are used, lowering the NSC levels. However, as the NSC content of the grass can increase when temperatures are below 5˚C²¹, do not allow grazing when the temperature is too low to enable grass to use the sugars.

Soaking hay is a must for any laminitic, as it reduces the NSC levels of hay, therefore allowing the forage requirements to be met without feeding too many calories. The NSC level of hay varies depending on type, but also the time of the day and the weather conditions when cut. For example, to keep the NSC levels to a minimum, hay should be cut during the morning and left to dry in cloudy weather²¹ to achieve this.

To reduce the NSC levels, hay should be soaked in water for more than 30 minutes, but 3 to 12 hours is needed for a significant reduction of the NSC content²².

As soaking hay also removes necessary nutrients, it is important to feed a supplement to ensure the dietary requirements are met. Hay must be fed immediately after soaking to limit bacteria and spore growth.

If the equid is sound then exercise is a useful method for prevention of EMS and insulin resistance. Exercise increases the body’s sensitivity to insulin as it causes upregulation of the glucose transporter GLUT4 and this enables the body to increase its scope for glucose transport¹².

Final thoughts

Regardless of aetiology, laminitis ultimately results in deterioration of lamellae tissue. However, aetiology affects pathogenesis and therefore determines the degree of lameness and damage caused. It is understood pathogenesis is closely related to aetiology, but the precise causations of some types of laminitis such as PPID and EMS are not fully understood. This is because laminitis can be induced by both vascular and enzymatic complications²³.

Interestingly, the pathogenesis of CHO-induced laminitis does not develop if dilation of capillaries in the hoof does not occur. This suggests laminitis in the CHO model is caused by enzymatic activity alone with vascular complications occurring post-development of laminitis²⁴. Weight management and maintaining a slim body condition score, regardless of the season or breed, cannot be overlooked.

Ponies in particular should be managed as if they are laminitic, even if they have not ever suffered with laminitis. As aforementioned, there is a heritable element to EMS and therefore obesity prevention is a must. Moreover, reaching a healthy body condition score/weight is probably the most useful tool in laminitis management as this is directly linked to insulin levels and the metabolism. The reason why laminitis developed must be addressed, as this is something often overlooked in the long term.