Laminitis - Causes and Consequences PDF

Laminitis – Causes and Consequences Luke Edwards MRCVS “Were a Veterinary Surgeon asked the question from what disease a horse experienced the most suffering, he would methinks, require little reflection before he determined in favour, or rather disfavour, of the one I am about to describe. There...

Laminitis – Causes and Consequences Luke Edwards MRCVS “Were a Veterinary Surgeon asked the question from what disease a horse experienced the most suffering, he would methinks, require little reflection before he determined in favour, or rather disfavour, of the one I am about to describe. There may be, and no doubt are , other morbid conditions from which the animal suffers more acutely for the time: but there is no one in which his pain, while poignant to the extreme, is apt to be so protracted.” - William Percivall, British cavalryman, 1871. • • • • Very common problem in First-opinion practice. Causes huge amount of equine suffering and welfare issues. A considerable drain owner emotions/finance/time A common cause of euthanasia • Often (badly) dealt with by owners without (enough) veterinary involvement . LAMINITIS – INFLAMMATION OF THE LAMELLAE “An acute onset lameness of variable severity involving one or more feet” - Dyson 2003 “the failure of the attachment between the distal phalanx (coffin bone) and the inner hoof wall” - Pollitt 1999 - i.e. a lameness arising from damage to the laminae of the hoof. Anatomy of the Hoof. • • • • • Lamellae – “Thin sheet” About 600 Primary lamellae per hoof About 150 Secondary lamellae per primary lamellae Tubular horn grows down from the coronary band Intertubular horn grows down from the coronary band between the tubules Anatomy of the Sole • No lamellae on sole of foot. • Weight bearing mostly done through lamellae, frog and walls of hoof. • Excessive pressure on solar corium (dermis) tissue = painful. • Horse “suspended” from the lamellae Blood supply and metabolism • Foot – very well vascularised. • Aterio-venous shunts present in laminae. • Constant supply of glucose needed to keep basement membrane structures intact. • A single horses’ hoof uses more glucose per day than its brain. • Glucose uptake in the foot not insulin mediated. • • • • • Theories of Laminitis Anything that damages the lamellae, technically is “laminitis” Maybe multiple different, causes all leading to failure of the foot. Maybe interaction between causes. Some causes far more common than others. Much research has been done on the underlying causes, many theories put forward but none could explain the “whole” picture. • In last 20 years major breakthroughs in laminitis research started to “fill the gaps”. Multiple causes Common pathway Lamellar Failure Theories of Laminitis - Historical Ancient Greeks (380 BC): • Xenophon describes “barley disease” - a lameness associated with overfeeding. • “Among horses those at pasture are free from all ailments except foot-ill, but they suffer from this and sometimes cast the hooves…. Evidence of the aliment- the right testicle twitches…..” Aristotle (330BC). Theories of Laminitis - Historical The Romans • Columella – 55 AD – describes laminitis as “blood descending to the feet” • Chiron - ( 4thC) - describes the horse being unable to walk with blood and heat in the feet • Apsyrtus (4th C) suggests dietary restriction. Medieval • 1250 – Jordanus Ruffus – recommends removing the entire sole of the foot. • 1523 – Fitzherbert describes “morfounde” – (founder) Theories of Laminitis - Historical • Chest founder/metastatic founder - caused by journeys on ships “twice kicked himself out (of the slings) and was near lost. He stood on the deck of the vessel for some time while they were putting a fresh pair of slings on him and nearly killed the second mate of the vessel by kicking him overboard…” William Tomkinson - on the departure of his charger “Bob” for the Napoleonic wars. Theories of Laminitis - Modern Modern Theories 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Vascular Theory Endotoxemic\sepsis\inflammatory theory Carbohydrate overload theory Supporting limb laminitis Mechanical laminitis Glucose deprivation theory Metal matrix proteinase theory Free radical theory Corticosteroid induced laminitis Endocrinopathic laminitis REAL and COMMON Endocrinopathic laminitis REAL and UNCOMMON Endotoxic/septic/inflammatory laminitis Mechanical laminitis Supporting limb laminitis Glucocorticosteroid induced laminitis Carbohydrate overload Irrelevant or just b*ll*cks Free radical theory Glucose deprivation theory Metal matrix proteinases Black Walnut laminitis Vascular Theory (Hood et–al, 1980’s) Vascular theory Theories of Laminitis ModernVasoconstriction to foot Vascular Theory • Laminitis caused by alterations in blood flow to digit – leading to tissue hypoxia, ischemia, tissue necrosis, inflammation and ultimately laminar failure Evidence for:• Vascular changes well proven- both vasoconstriction and vasodilation Evidence against:• No consistent pattern of change found (may depend where and when you measure blood flow) • Histopathological signs of inflammation not always present in pasture associated laminitis. • What initiates the vascular changes? Practical relevance :• Rationale for use of anti-inflammatories and blood modifying agents Hypoxic foot Reflex vasodilation Reperfusion injury Compartment syndrome Ischaemia Tissue inflammation and necrosis LAMINAR FAILURE AND PAIN Theories of Laminitis – Modern- Endotoxins Endotoxic/sepsis/inflammatory theory. • Laminitis caused by the effects of endotoxins and other inflammatory substances on the foot. Evidence for: Laminitis well recognised as a potential complication of SIRS/Endotoxemia in horses. e.g. retained foetal membranes, colitis, post colic surgery, pleuropneumonia. Evidence against:• Not every endotoxic horse gets laminitis. • Most laminitics not endotoxic. • Injection of endotoxins to horses does not reliably induce laminitis. Practical relevance :• Definite concern in hospitalised horses • Not common in ambulatory practice • Not related to the “pasture associated laminitis” seen in ambulatory practice Supporting Limb Laminitis Theories of Laminitis – Modern- Supporting Limb laminitis Supporting limb laminitis Horses which are non-weight bearing on one leg often develop laminitis in the contralateral limb. Due to failure of circulatory “foot pump” and tissue ischaemia? Evidence for: • Definitely does occur – in very severe lameness (fractures etc.) Evidence against:• Limited to severe lameness – not every lame horse gets laminitis • Not representative of pasture associated laminitis Practical relevance :• Really hospitalised horses only. Theories of Laminitis – Modern- Mechanical Laminitis Mechanical Laminitis Any force which physically tears hoof from the laminae is technically laminitis. Either occurs as a (very) traumatic one-off incident or as a result of chronic forces on an already weakened digit. Evidence for: • Logically can occur. Probably quite common in severe chronic laminitis Evidence against:• Little researched evidence, mostly anecdotal, difficult to prove condition exists. Practical relevance :• Assess forces on hoof when examining laminitics. Theories of Laminitis – Modern- Other Theories Free Radical Theory: Laminitis due to free radical damage to foot. Probably true but very minor component of condition. Can make lots of money selling anti-oxidant hoof supplements. Led to vets treating laminitis with DMSO. Glucose deprivation theory A hypoglcemic digit will fail. True –but minor component of condition. Led to some vets giving i.v. glucose to laminitics Metalloproteinase (MMPs) theory MMPs are enzymes responsible for cleaving the proteins connecting keratinocytes to Basement membranes. Go out of control in laminitis. True- but minor component. Led to vets (unsuccessfully) treating laminitics with oxytetracycline (which has anti-MMP action) Black Walnut theory :Exposing horses to extract of Black walnut in feed ,or just in bedding causes severe laminitis. True – but not relevant (experimental model only) Acid Blood theory :Horses with acidic blood get laminitis. Give sodium bicarbonate as a preventative. Complete bo***cks. Theories of Laminitis – Modern-Glucocorticoids Glucocorticoid induced laminitis • Glucocorticoid administration to horses can cause laminitis. • Long held belief that glucocorticoids practically contra-indicated in horses Evidence for: • Well documented evidence that this can occur - even after one-off intra-articular doses. • • • • Evidence against: Modern epidemiological studies shown risk is genuine, but actually quite low. Deliberately trying to induce laminitis by giving steroids (for research purposes) rarely works. Using high doses of steroids or using them in animals already predisposed to laminitis likely to increase the risk. Oral prednisolone shown to be quite safe. Practical relevance :• Corticosteroids can be given to equines, clients should be informed that there is a risk, but it is low. Theories of Laminitis – Modern- Carbohydrate Overload Carbohydrate Overload Laminitis (90’s-00’s) Excessive carbohydrate intake overwhelms small intestine and overspills into large bowel. Bacterial proliferation causes hindgut acidosis, causing the release of a wide variety of laminitis-inducing substances. Endotoxin released “Equine laminitis: Loss of hemidesmosomes in hoof secondary epidermal lamellae correlates to dose in an oligofructose induction model: An ultrastructural study. Equine Veterinary Journal 36(3):230-5 · May 2004” Theories of Laminitis – Modern- Carbohydrate Overload Fructans and carbohydrate overload theory. • Fructans are sugars used by plants as temporary energy stores (c.f. glycogen). • Mammalian digestive tracts lack the enzymes to digest fructans therefore they spill into the large bowel intact. • Bacteria can digest fructans. • Fructan overload therefore implicated as the source of pasture-associated laminitis. • Fructan level in plants depends on may factors, including, type of plant, part of plant, growing season, ambient temperature, sunlight levels, “stress” levels • Highly variable, can change from hour-to-hour – can’t predict pasture levels. Theories of Laminitis – Modern- Carbohydrate Overload Evidence for: • Large quantities of oral fructans will reliably induce laminitis in experimental studies. • Could easily explain pasture-associated laminitis. • Evidence against: • Can horses physically consume enough fructans in a day to cause laminitis ? • Controversial – most experts consider it unlikely, although some disagree. • Histopathological signs similar to endotoxic/septic/inflammatory laminitis (Ponies may eat 40% of their required intake (in DM) within 3 hours- and there are 24 hours in a day!) Practical relevance :• Current thinking is that Carbohydrate overload is just a form of endotoxic/septic/inflammatory laminitis (since a form of colitis is induced) and does not reflect pasture-associated laminitis. • Concept still widespread with horse owners. • Lead to use of in-feed antibiotics to prevent hindgut fermentation. Theories of Laminitis – Modern- Endocrine Endocrinopathic laminitis: Research over last 20 years has discovered that up to 90% of laminitis cases have a underlying endocrinopathy i.e. 1. Equine Metabolic Syndrome (EMS) 2. Pituitary Pars Intermedia Dysfunction (PPID) 3. EMS and PPID together The chance of an individual suffering from laminitis if it does not have EMS or PPID is low. This discovery has been labelled “The Laminitis Revolution” and has been a huge advance in equine welfare, with major practical implications. 4. 5. 3. 4. Allows treatment of the underlying cause. Gives a name and number. Practical diagnostic tests available. Treatments or treatment plans available. Theories of Laminitis – Modern- Endocrine Equine Metabolic Syndrome • Syndrome obesity, insulin dysregulation and laminitis. • “Thrifty” genotype leading to “survivor” phenotype enabling horses to survive in harsh conditions by putting on weight in good times to prepare for hard times. • UK horses never experience “hard times” and so just get fatter and fatter… • Lack of recognition of obesity in horse owners. • Recent social trend to treat horses as “toys” causes welfare problems. Yes NO! NO! NO! Katie Price is the true cause of laminitis Do Wild Horses get laminitis? • Yes! Brumbys – severe laminitis in lush wet season Mustangs – soon become fat , tame and laminitic after capture New Zealand “Kaimanawa” horses 25% hooves had laminitic changes on PM studies. Theories of Laminitis – Modern- Endocrine Insulin Dysregulation and laminitis • Experimental studies have clearly demonstrated that hyperinsulinaemia is the trigger cause of EMS related laminitis. • • Sustained hyperinsulinaemia will reliably induce laminitis in normal (non-EMS) horses. • Hyperinsulinaemia damages cytoskeleton of laminar cells and also has vasoactive properties (remember foot glucose metabolism insulin independent). • EMS laminitis – would explain most cases of pasture-associated laminitis. • Anecdotally, periods of grass growth (Spring, Autumn) or episodes of frosted grass are associated with more cases of laminitis. Most (but not all) epidemiological studies back this up. • Perhaps it not so much the “sugars in the grass” that we need to worry about, more their effect on insulin dysregulation. Theories of Laminitis – Modern- Endocrine Pitutary Pars Intermedia Dysfunction and Laminitis. • • • • Equine Cushing’s Syndrome. Equines 15 years or older. Extremely common in UK aged horse populations. Testing for PPID and monitoring treatment large part of modern leisure horse practice -good for preventing laminitis • Exact mechanism by which PPID initiates laminitis unknown. • Maybe complex interactions between PPID and EMS- subject of much research. • Concurrent PPID and EMS thought to worsen the prognosis of laminitis Advanced case of PPID – most cases seen in practice do not display as obvious signs. Dr Harvey Cushing Consequences of Laminar Failure • The pedal bone is free to move within the foot. • Where it goes and how far depend on the forces acting on the bone and the extent and severity of laminar failure. Laminar attachment – resisting other forces Pull of deep flexor – rotational force on pedal bone Ground Reaction force- levering hoof capsule from pedal bone Weight of horse- driving bone down Consequences of Laminar Failure NORMAL FOOT Depth from coronary band to tip of extensor process- variable but approx. 10 mm in normal horses- place metallic marker Distance form dorsal surface PIII to hoof should be constant. Note position of tip of fog- place metallic marker Assess depth of sole – esp at tip of PIII Dorsal surface of PIII and PII in line – dependent on HPA Movement of the pedal bone No movement: Mild cases might not have any pedal bone movement (or it is so slight not to be visible on radiographs). Important to explain to owner that this does not imply the animal has not got laminitis. Capsular rotation – the hoof capsule diverges form the dorsal surface of PIII, but PIII itself remains aligned with PII. Common. Bony rotation – the hoof capsule diverges form the dorsal surface of PIII, and PIII itself is rotated palamarly around the DIP. Implies significant pull of DDF and usually a sign of severe damage. Less common. NB: The terms “Capsular rotation” and “Bony rotation” are suggested, but are not universally used, often any movement is called “rotation”. This can lead to a lot of confusion and misunderstanding between vets, owners and farriers. Movement of the pedal bone Sinker: Vertical displacement of PIII downwards (with or without rotation) Sole depth thin. Distance from tip of extensor process to coronary band increased (>14mm often considered hopeless prognosis – but does depend on other factors) Usually implies very serious pathology, horses usually very painful. Consequences of pedal bone movement In the acute stage – the resultant gap becomes a haematoma/seroma /necrotic mess. If this gets infected a foot abscess will result. Foot abscesses are a common complication of laminitis – usually 2-3 weeks post the acute stage – warn the client. The forces on the foot stretch the white line junction – providing an easy ingress route for abscess –causing bacteria. Eventually the haematoma is replaced by poor quality, dysplastic horn – a lamellar “wedge” Radiographic changes to the pedal bone may occur – esp. “Turkish slipper” changes at the tip Downward the pedal bone drags the coronary band with it leading to a compromised (crushed) blood supply to the coronary band. Abnormal horn growth results – the toe goes slower than the heels leading to diverging hoof rings (parallel growth rings just indicate a change in growth rate) The hoof attempts to remodel itself around the new position of the pedal bone leading to abnormal hoof shapes (which may lead to chronic lameness). Learning Objectives: • To understand the causes of laminitis and appreciate which causes are most prevalent. • To understand the functional consequences of lamellar damage