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109-562: Glycogen is a molecular polymer of glucose (a polysaccharide ) used to store energy, and is important for maintaining glucose homeostasis in the blood, as well as for providing energy for skeletal muscle and cardiac muscle contraction. Molecules of glucose are linked into linear chains by α-1,4- glycosidic bonds . Additionally, branches of glucose are formed off of the chain by α-1,6-glycosidic bonds. 2 molecules of glucose are joined into an α-1,4-glycosidic bonds by an enzyme known as glycogen synthase . This bond may be broken by amylase when

218-465: A generator, that have hit a piece of x-ray film. This film is then exposed to produce an image. The photons that hit the film are actually those that have been reflected, rather than absorbed, by the animal's body. Different tissue types absorb photons to varying degrees, leading to differing levels of darkness ( radiodensity ) on the x-ray film. An anatomical structure is delineated by comparing its radiodensity those tissues surrounding it. Interpretation of

327-455: A given activity, and competing at a very high athletic level. Metabolic causes of lameness include hyperkalemic periodic paralysis (HYPP) and polysaccharide storage myopathy , which directly affect muscular function. Circulatory causes of lameness occur when blood flow to an area is compromised. This may be due to abnormal blood clotting, as in the case of aortic-iliac thrombosis , or decreased blood flow (ischemia) to an area, such as

436-433: A horse move is repeated after each additional flexion test or nerve block to determine its effect on the animal. Lameness is graded on a scale. This allows the practitioner to help quantify a lameness in order to determine relative severity, assess the degree of change after flexion tests or nerve blocks, and to determine the improvement of lameness over time once treatment has been implemented. The most commonly used scale in

545-431: A horse to stand with the stifles rotated out. Hip and pelvic pain can produce a toe-out, stifle out, hock-in stance and that remains present at the walk. Asymmetry of the muscular structure, due to muscle atrophy, usually occurs on the side of the lame limb. Hind limb lameness or pelvic fracture can cause unilateral atrophy of the middle gluteal or gracilis muscles. Damage to the suprascapular nerve can lead to atrophy of

654-412: A horse, but only to give their impression of the horse on that day. Therefore, pre-purchase examinations make no guarantees of the future health or soundness of the horse. The pre-purchase exam may range in scope depending on the desire of the buyer, from a simple examination with hoof and flexion tests, to multiple radiographs, ultrasound, and advanced imaging techniques including MRI. A detailed history

763-403: A key component of the pre-purchase examination . These examinations evaluate the horse to give the potential buyer information regarding present soundness of the horse. Veterinarians may comment on aspects that could inhibit the use of the horse for the buyer's intended activity, such as subclinical osteoarthritis or conformational defects. However, the veterinarian is not there to "pass" or "fail"

872-401: A lameness when the lame leg is on the inside or outside of the circle. At times, it may be helpful to evaluate the horse under saddle, since the weight of the rider can accentuate lameness. In cases of decreased performance, it can be useful to watch a horse performing certain discipline-specific movements, which may be the only time the rider notices a change in the horse's abilities. Gait

981-410: A localized swelling with pain can indicate an abscess. Examiners will also "hoof test" each foot by applying a metal instrument that squeezes the foot to test for deep pain. Diffuse sensitivity occurs with fracture or infection of the coffin bone, and laminitis. More localized sensitivity can be found with sole bruises, puncture wounds, hoof abscesses, and hot nails. Sensitivity over the middle third of

1090-465: A longer period of time (aerobic activity), due to an energy deficit in the muscle. Glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals , fungi , and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms of energy reserves, creatine phosphate being for very short-term, glycogen being for short-term and

1199-425: A low-starch, high-fat diet. Low-starch diets produce low blood glucose and insulin levels after eating, which may reduce the amount of glucose taken up by the muscle cells. High fat diets increase free fatty acid concentrations in the blood, which may promote the use of fat for energy (via free fatty acid oxidation) over glucose metabolism. Horses with the most severe clinical signs often show the greatest improvement on

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1308-399: A muscle biopsy is recommended for horses displaying clinical signs of PSSM but who have negative results for GSY1 mutation. A muscle biopsy may be taken from the semimembranosis or semitendinosis (hamstring) muscles. The biopsy is stained for glycogen, and the intensity of stain uptake in the muscle, as well as the presence of any inclusions, helps to determine the diagnosis of PSSM. This test

1417-475: A persistently elevated CK at rest, which differentiates the disease from recurrent exertional rhabdomyolysis, in which horses have normal CK concentrations between episodes. Some affected animals may remain subclinical, others may have mild signs that do not impede athletic performance, while some horses will have clinical signs that prevent any forced exercise. Rarely, horses will die from acute episodes of rhabdomyolysis. The reason for such variability of phenotype

1526-619: A radiograph therefore requires the surrounding structures to have enough of a difference in radiodensity to allow it to stand out. While this is obvious in tissue such as bone, soft tissues of the leg do not stand out well on radiographs. Therefore, radiographs are best used to evaluate boney changes rather than soft tissue damage. One exception of this rule is the use of contrast, injected into synovial structures, which allows these structures to stand out on radiographs. Common uses for radiographs are to evaluate for suspected fractures, bone chips, laminitis, and navicular changes. Ultrasound measures

1635-464: A reaction catalysed by UTP—glucose-1-phosphate uridylyltransferase . Glycogen is synthesized from monomers of UDP-glucose initially by the protein glycogenin , which has two tyrosine anchors for the reducing end of glycogen, since glycogenin is a homodimer. After about eight glucose molecules have been added to a tyrosine residue, the enzyme glycogen synthase progressively lengthens the glycogen chain using UDP-glucose, adding α(1→4)-bonded glucose to

1744-435: A solution to storing glucose in the cell without disrupting osmotic pressure. As a meal containing carbohydrates or protein is eaten and digested , blood glucose levels rise, and the pancreas secretes insulin . Blood glucose from the portal vein enters liver cells ( hepatocytes ). Insulin acts on the hepatocytes to stimulate the action of several enzymes , including glycogen synthase . Glucose molecules are added to

1853-516: A sudden need for glucose, but one that is less compact than the energy reserves of triglycerides ( lipids ). As such it is also found as storage reserve in many parasitic protozoa. Glycogen is a branched biopolymer consisting of linear chains of glucose residues with an average chain length of approximately 8–12 glucose units and 2,000-60,000 residues per one molecule of glycogen. Like amylopectin, glucose units are linked together linearly by α(1→4) glycosidic bonds from one glucose to

1962-399: A veterinarian. Therefore, non-weight bearing lameness should be assessed by an equine professional in a timely manner, especially if it is associated with trauma, laceration, or recent joint injection. Flexion tests are a diagnostic tool involving the application of sustained pressure on a particular set of joints. The limb is forcibly flexed for between 30 seconds and 3 minutes, depending on

2071-800: Is RYR1, which is responsible for calcium regulation in muscle cells. RYR1 mutation causes malignant hyperthermia , a rare but potentially fatal disorder usually associated with anesthesia. While RYR1 mutation is rare in horses, including the general Quarter Horse population, it is much more common in Quarter Horses with GSY1 mutation. Horses with both mutations are more likely to have a severe PSSM phenotype, including higher levels of blood creatine kinase (CK), more severe exercise intolerance, more severe episodes of rhabdomyolysis (more frequent muscle fasciculations, more frequent episodes that are not associated with exercise, acute death), and poor response to PSSM treatment. Additionally, defects in both GSY1 and

2180-570: Is a clinical sign, and not a diagnosis. Pain is the most common cause of lameness in the horse. It is usually the result of trauma or orthopedic disease, but other causes such as metabolic dysfunction, circulatory disease, and infection can also cause pain and subsequent lameness. Orthopedic causes of lameness are very common and may be the result of damage to the hoof, bone, joints, or soft tissue. Horses are predisposed to orthopedic lameness by conformational flaws, poor hoof balance, working on poor footing, repetitive movements, poor conditioning for

2289-410: Is a common veterinary problem in racehorses , sport horses , and pleasure horses . It is one of the most costly health problems for the equine industry , both monetarily for the cost of diagnosis and treatment, and for the cost of time off resulting in loss-of-use. Lameness is most commonly caused by pain, but may also be the result of neuromuscular disease or mechanical restriction. Lameness itself

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2398-481: Is an analogue of starch , a glucose polymer that functions as energy storage in plants . It has a structure similar to amylopectin (a component of starch), but is more extensively branched and compact than starch. Both are white powders in their dry state. Glycogen is found in the form of granules in the cytosol /cytoplasm in many cell types, and plays an important role in the glucose cycle . Glycogen forms an energy reserve that can be quickly mobilized to meet

2507-457: Is an exaggerated upward movement that is watched for during weight bearing. Additionally, horses with a hind limb lameness will tend to reduce the degree of leg use. To do so, some horses will reduce the contraction time of the gluteals on the side of the lame leg, leading to a "hip roll" or "hip dip" and appearance that the hip drops a greater degree on the side of the lame leg. These apparently contradictory statements ("hip hike" vs "hip drop" on

2616-425: Is bearing weight. When viewed from behind, this is seen as a "hip hike." If the horse is more painful as it is pushing off a limb, it will not push off with as much force, and the pelvis will rise less on the lame side relative to the same point of the stride when the sound leg is on the ground. This is seen as the "hip roll" when viewed from behind. Other signs that indicate hind limb lameness include "plaiting" with

2725-553: Is caused by an autosomal dominant genetic mutation known as GSY1. This mutation causes an up-regulation of glycogen synthase, and high levels of glycogen synthase relative to glycogen branching enzyme (GBE). This altered ratio of glycogen synthase to GBE results in glycogen molecules with long chains and few branches, making these molecules somewhat amylase resistant. The GSY1 mutation is associated with altered glucose metabolism (but normal glycogen metabolism), as well as accumulation of high levels of glycogen and abnormal polysaccharide in

2834-420: Is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase to produce monomers of glucose-1-phosphate: In vivo, phosphorolysis proceeds in the direction of glycogen breakdown because the ratio of phosphate and glucose-1-phosphate is usually greater than 100. Glucose-1-phosphate is then converted to glucose 6 phosphate (G6P) by phosphoglucomutase . A special debranching enzyme

2943-512: Is especially short acting, and is therefore usually not used for lameness evaluations. The longer-acting anesthetic mepivacaine is most-commonly used for nerve blocks, because ideally the block should last throughout the lameness exam to avoid false positives with subsequent blocks as they are performed up the leg. Bupivicaine is very long-lasting (up to 4–6 hours), and is most commonly used for analgesia following surgery rather than for nerve blocks. Although nerve blocks are very important to

3052-443: Is evaluated for symmetry. This includes the overall fluidity of the horse's motion, length of stride, loading of a leg, how the hoof lands on the ground (flat, toe, or heel-first), range of motion of the joints, deviations in body position, and position of the head and neck. The first evaluation of the horse is used to determine the severity of lameness and to help pinpoint which part of the body may be affected. The process of watching

3161-560: Is formed by the self-glucosylation of the glycogenin, forming a short primer chain. From the C-chain grows out B-chains, and from B-chains branch out B- and A-chains. The B-chains have on average 2 branch points, while the A-chains are terminal, thus unbranched. On average, each chain has length 12, tightly constrained to be between 11 and 15. All A-chains reach the spherical surface of the glycogen. Glycogen in muscle, liver, and fat cells

3270-399: Is in front of the horse, i.e. angled forward, while the caudal phase is when the leg is underneath the horse, i.e. angled backward. For a hind leg, the cranial phase occurs when the lower leg is under the body of the horse, and the caudal phase is when the limb is out behind the body of the horse. A normal horse with have a cranial phase and a caudal phase of equal length: the horse will bring

3379-402: Is injected, it is given a few minutes to take effect. The block is then tested by pushing a blunt object, such as a ballpoint pen, into the area that is supposed to be desensitized. If the horse does not react to this pressure, the area is desensitized, and the horse is trotted to see if the lameness has improved. Improvement indicates that the cause of lameness was from a structure desensitized by

Equine polysaccharide storage myopathy - Misplaced Pages Continue

3488-686: Is known as the sliding filament theory . Skeletal muscle relies predominantly on glycogenolysis for the first few minutes as it transitions from rest to activity, as well as throughout high-intensity aerobic activity and all anaerobic activity. During anaerobic activity, such as weightlifting and isometric exercise , the phosphagen system (ATP-PCr) and muscle glycogen are the only substrates used as they do not require oxygen nor blood flow. Different bioenergetic systems produce ATP at different speeds, with ATP produced from muscle glycogen being much faster than fatty acid oxidation. The level of exercise intensity determines how much of which substrate (fuel)

3597-607: Is mild using subjective visual cues. Additional methods of detection and quantification of lameness can therefore be helpful. Several systems are in use and under development for this purpose, both in research and clinical practice. Among these are the Lameness Locator system based on uniaxial accelerometers, the Equigate system based on six degrees of freedom inertial measurement units, the Equinalysis system, and

3706-540: Is needed to remove the α(1→6) branches in branched glycogen and reshape the chain into a linear polymer. The G6P monomers produced have three possible fates: The most common disease in which glycogen metabolism becomes abnormal is diabetes , in which, because of abnormal amounts of insulin, liver glycogen can be abnormally accumulated or depleted. Restoration of normal glucose metabolism usually normalizes glycogen metabolism, as well. In hypoglycemia caused by excessive insulin, liver glycogen levels are high, but

3815-415: Is normal for the horse. In general, it is harder to detect hind limb lameness when compared to lameness in a front limb when using visual cues. The classic sign of lameness in a front leg is a prominent "head bob." Viewed from the side, the horse raises its head and neck when the lame leg hits the ground, which helps to unload the lame leg. This is sometimes remembered by the adage "down on sound." A head bob

3924-400: Is not actually causing the horse discomfort. False results can also be secondary to practitioner error if the anesthetic is accidentally administered into a location that was unintended, such as a synovial structure rather than around a nerve. Additionally, individual horses have variation in their neural anatomy, and if atypical patterns are present, a given block may block an area unintended by

4033-430: Is not fractal in nature. This has been subsequently verified by others who have performed Monte Carlo simulations of glycogen particle growth, and shown that the molecular density reaches a maximum near the centre of the nanoparticle structure, not at the periphery (contradicting a fractal structure that would have greater density at the periphery). Glycogen was discovered by Claude Bernard . His experiments showed that

4142-465: Is not fully understood. Temperament, sex, and body type have no effect on degree of clinical signs. However, environmental factors such as diet and exercise, whether the horse is heterozygous or homozygous for the mutated GSY1 allele, and the presence of modifying genes all play a role. Additionally, some affected horses may have PSSM Type 2, which will produce different cellular changes and subsequently different phenotypic effects. One such modifying genes

4251-412: Is often associated with reduced cranial phase and lengthened caudal phase of the stride. At times, lameness may be heard. Usually the horse has a stronger, louder sound on the beat where the sound hooves hits the ground, but a softer, less resonate sound occurring on the beat where the lame leg is hitting the ground. Again, this is because the horse is landing with less force as it tries to avoid weighting

4360-445: Is one of the most frequent signs associated with affected horses (reported in ~37% of affected animals), other common signs include gait abnormalities, shifting lameness , muscle weakness that may result in an inability to rise, colic-like pain , and muscle fasciculation, atrophy, and/or stiffness (most commonly seen in the semimembranosus, semitendinosus, and longissimus muscles). These clinical signs usually first become apparent when

4469-412: Is required to pass glucose into the blood, the glycogen they store is available solely for internal use and is not shared with other cells. This is in contrast to liver cells, which, on demand, readily do break down their stored glycogen into glucose and send it through the blood stream as fuel for other organs. Skeletal muscle needs ATP (provides energy) for muscle contraction and relaxation, in what

Equine polysaccharide storage myopathy - Misplaced Pages Continue

4578-528: Is secreted in increasing amounts and stimulates both glycogenolysis (the breakdown of glycogen) and gluconeogenesis (the production of glucose from other sources). Muscle glycogen appears to function as a reserve of quickly available phosphorylated glucose, in the form of glucose-1-phosphate , for muscle cells. Glycogen contained within skeletal muscle cells are primarily in the form of β particles. Other cells that contain small amounts use it locally as well. As muscle cells lack glucose-6-phosphatase , which

4687-627: Is seen in unaffected horses, and are reduced down to levels considered normal for a resting non-PSSM horse. This demonstrates that glycogen metabolism is actually normal in these animals. However, PSSM horses synthesize muscle glycogen at double the rate of a normal horse once exercise has ceased, which leads to elevated muscle glycogen. The exact mechanism of abnormal glucose metabolism has not yet been established, but it may have similarities to phosphofructokinase deficiency in humans. Quarter Horse-related breeds with PSSM show insulin sensitivity, which improves glucose uptake by cells, and these horses clear

4796-512: Is slowly increased over time (i.e. they are slowly conditioned). Additionally, they are much more likely to develop muscle stiffness and rhabdomyolysis if they are exercised after prolonged stall rest. Horses generally have fewer clinical signs when asked to perform short bouts of work at maximal activity level (anaerobic exercise), although they have difficulty achieving maximal speed and tire faster than unaffected horses. They have more muscle damage when asked to perform lower intensity activity over

4905-432: Is sometimes seen in laminitis . Infectious causes of lameness are the result of inflammation and damage to tissue. These include problems such as cellulitis , hoof abscesses, and septic arthritis . Mechanical lameness is caused by a physical abnormality, such as scar tissue, that prevents normal motion of a limb. Mechanical lameness does not cause pain. Classic examples of mechanical lameness include upward fixation of

5014-431: Is stored in a hydrated form, composed of three or four parts of water per part of glycogen associated with 0.45  millimoles (18 mg) of potassium per gram of glycogen. Glucose is an osmotic molecule, and can have profound effects on osmotic pressure in high concentrations possibly leading to cell damage or death if stored in the cell without being modified. Glycogen is a non-osmotic molecule, so it can be used as

5123-428: Is suspected, such as a fracture, bucked shins in racehorses (cannon bones), or splints (splint bones). Specialized manipulative tests can be used to help identify specific areas of pain: The majority of lameness originates in the hoof. For this reason, the hoof is closely scrutinized in shape, balance, shoeing, wear pattern, and for the presence of cracks, and contracted or sheared heels. Chronic lameness will change

5232-442: Is the first step of a lameness exam. One of the first steps of the lameness examination is to evaluate the horse at rest. A good evaluation of conformation , including overall body type, can help the practitioner determine the potential cause of lameness. Certain conformational defects can predispose a horse to injury, and knowledge of correct conformation can help narrow down possible causes of injury, especially when combined with

5341-480: Is the only method for diagnosing Type 2 PSSM. Horses with Type 1 PSSM will usually have between 1.5-2 times the normal levels of glycogen in their skeletal muscle. While abnormalities indicating muscle damage can be seen on histologic sections of muscle as young as 1 month of age, abnormal polysaccharide accumulation may take up to 3 years to develop. Horses with PSSM have elevated levels of muscle glycogen at rest. During exercise, glycogen levels are depleted faster than

5450-421: Is the primary enzyme of glycogen breakdown. For the next 8–12 hours, glucose derived from liver glycogen is the primary source of blood glucose used by the rest of the body for fuel. Glucagon , another hormone produced by the pancreas, in many respects serves as a countersignal to insulin. In response to insulin levels being below normal (when blood levels of glucose begin to fall below the normal range), glucagon

5559-414: Is used for ATP synthesis also. Muscle glycogen can supply a much higher rate of substrate for ATP synthesis than blood glucose. During maximum intensity exercise, muscle glycogen can supply 40 mmol glucose/kg wet weight/minute, whereas blood glucose can supply 4 - 5 mmol. Due to its high supply rate and quick ATP synthesis, during high-intensity aerobic activity (such as brisk walking, jogging, or running),

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5668-433: Is usually easy to see when one leg is lame, but can be subtle in very mild unilateral lameness, or in the case of bilateral front limb lameness. A horse may also try to reduce impact on a lame front leg by tensing of the muscles of the shoulder. In this case, it will stiffen the limb just before it hits the ground, a sign that may be noticed by an astute observer. Evaluation of hind limb lameness can be difficult. Generally,

5777-650: The Arabian , Lipizzaner , Morgan , Mustang , Peruvian Paso , Rocky Mountain Horse , Standardbred , Tennessee Walking Horse , Thoroughbred , and National Show Horse . It has been suggested that the GSY1 mutation provided some benefit to hard working animals with poor-quality diets, and is now damaging members of those "thrifty" breeds that are managed with moderate to low levels of work and diets high in non-structural carbohydrates. PSSM Type 1 (homozygous or heterozygous for

5886-412: The blood of humans at all times; in fasting individuals, blood glucose is maintained constant at this level at the expense of glycogen stores, primarily from the liver (glycogen in skeletal muscle is mainly used as an immediate source of energy for that muscle rather than being used to maintain physiological blood glucose levels). Glycogen stores in skeletal muscle serve as a form of energy storage for

5995-536: The brain . The uterus also stores glycogen during pregnancy to nourish the embryo. The amount of glycogen stored in the body mostly depends on oxidative type 1 fibres , physical training, basal metabolic rate , and eating habits. Different levels of resting muscle glycogen are reached by changing the number of glycogen particles, rather than increasing the size of existing particles though most glycogen particles at rest are smaller than their theoretical maximum. Approximately 4 grams of glucose are present in

6104-424: The triglyceride stores in adipose tissue (i.e., body fat) being for long-term storage. Protein, broken down into amino acids, is seldom used as a main energy source except during starvation and glycolytic crisis (see bioenergetic systems ) . In humans , glycogen is made and stored primarily in the cells of the liver and skeletal muscle . In the liver, glycogen can make up 5–6% of the organ's fresh weight:

6213-543: The GSY1 mutation) is more common in Quarter Horses and their related breeds, and draft breeds, while PSSM Type 2 (negative for the GSY1 mutation) is more commonly seen in other breeds, including warmbloods. There is no sex predilection to the disease. Horses with Type 1 PSSM usually appear normal at rest, but show signs of exertional rhabdomyolysis ("tying up") such as shortened stride, stiffness, firm musculature, sweating, pain or reluctance to exercise, when asked to perform light work. While episodes of exertional rhabdomyolysis

6322-583: The SCNA4 gene, responsible for hyperkalemic periodic paralysis (HYPP) in Quarter Horses and related breeds, has been found in 14% of Halter horses. A combination of both of these genes can cause severe rhabdomyolysis should the horse become recumbent due to an HYPP attack. A genetic test is available for Type 1 PSSM. This test requires a blood or hair sample, and is less-invasive than muscle biopsy. However, it may be less useful for breeds that are more commonly affected by Type 2 PSSM, such as light horse breeds. Often

6431-816: The United States is a 1–-5 scale of the American Association of Equine Practitioners (AAEP). Other scales are more commonly used outside of the United States, including a 1–10 scale in the United Kingdom. AAEP Lameness Grading Scale Non-weight bearing lameness (grade 5) is most commonly the result of a hoof abscess. While very painful, most hoof abscesses are quite treatable and do not cause long-term lameness. However, fractures and septic synovial structures (such as an infected joint pouch or tendon sheath) can also cause non-weight bearing lameness, and require emergency evaluation and treatment by

6540-423: The angle of the hoof wall relative to the pastern, has been associated with health of the soft tissues of the lower leg. Long toes force the horse to pivot (break over) further forward over the toe. The toe acts as a lever arm, and its increased length makes it harder for the heels to rotate off the ground. This increases strain on the deep digital flexor tendon and the ligaments of the navicular bone. The bottom of

6649-431: The athlete's glycogen stores are depleted after long periods of exertion without sufficient carbohydrate consumption. This phenomenon is referred to as " hitting the wall " in running and "bonking" in cycling. Glycogen depletion can be forestalled in three possible ways: When athletes ingest both carbohydrate and caffeine following exhaustive exercise, their glycogen stores tend to be replenished more rapidly; however,

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6758-546: The blood of glucose more quickly after eating than unaffected horses. This provides easy access to glucose by the muscles, which can then use the substrate to produce glycogen. The GSY1 defect, which up-regulates the glycogen synthase enzyme, allows the muscles to use this glucose to rapidly produce glycogen for storage in the muscle. Surprisingly, increased insulin sensitivity is not seen in draft horse breeds. Dietary and exercise manipulation may be used to counteract these metabolic changes. Approximately 50% of horses that adhere to

6867-484: The body wishes to break down glycogen into glucose for energy. Glycogen branching enzyme is responsible for the required α-1,6-glycosidic bonds needed to start a branch off of these linear chains. Any disruption to this system results in a glycogen storage disease . There are currently 2 subcategories of glycogen storage diseases in horses: Type 1 polysaccharide storage myopathy, glycogen branching enzyme deficiency, and Type 2 polysaccharide storage myopathy. Type 1 PSSM

6976-419: The chains of glycogen as long as both insulin and glucose remain plentiful. In this postprandial or "fed" state, the liver takes in more glucose from the blood than it releases. After a meal has been digested and glucose levels begin to fall, insulin secretion is reduced, and glycogen synthesis stops. When it is needed for energy , glycogen is broken down and converted again to glucose. Glycogen phosphorylase

7085-537: The diet. Dietary recommendations usually include a combination of calorie restriction, reduction of daily NSC content, and an increase in dietary fat. Diet recommendations need to be balanced with the animal's body condition score and exercise level, as it may be beneficial to wait on increasing dietary fat after an obese animal has lost weight. The diet should have <10% of digestible energy coming from NSC, and 15-20% of daily digestible energy coming from fat. Horses with PSSM show fewer clinical signs if their exercise

7194-469: The dietary recommendations, and 90% of horses that adhere to both dietary and exercise recommendations, have few to no episodes of exertional rhabdomyolysis. For most horses, diet has a significant impact on the degree of clinical signs. PSSM horses fed diets high in nonstructural carbohydrates (NSC), which stimulate insulin secretion, have been shown to have increased severity of rhabdomyolysis with exercise. Current recommendations for horses with PSSM include

7303-423: The examiner, leading to false positives. Joints present additional problems. A large volume of anesthetic placed into a joint can diffuse out over time, blocking the surrounding structures. Additionally, there are some cases where joint pain can respond better to perineural blocking rather than blocking of the joint. There is relatively low agreement between practitioners trying to identify a lame leg when lameness

7412-427: The foot are inhibited when they travel through the fetlock area. A positive result from this block will not be able to differentiate foot pain from pain in the pastern or fetlock region. More information may be gained from blocking the foot first, then the fetlock, since it allows for greater specificity in determining the cause of lameness. The duration of the anesthetic varies depending on the substance used. Lidocaine

7521-410: The frog is consistent with navicular syndrome, but can also occur with sheared heels. To distinguish these two, the hoof testers may be applied over the heels, which will be sensitive in the case of any heel-related pain, such as sheared, contracted, or bruised heels. The hoof wall may also be percussed (struck with a hammer), which will produce a positive response in cases of hoof cracks that are causing

7630-533: The glycogen branching enzyme. Subsequently, glycogen molecules are produced with few branches, which greatly decreases the number of nonreducing ends, drastically slowing the rate at which the molecule can be synthesized or broken down. This causes low levels of muscle glycogen that is very resistant to amylase. This disease is usually seen in Quarter Horse foals and is fatal. Type 2 PSSM is a category for disorders that lead to abnormal deposition of glycogen in

7739-403: The ground) is compared at various points in the stride. The pelvis normally rises and falls with each step. Horses with pain during the early stance phase of the trot will not allow the pelvis to drop as much when the lame leg is weighted, trying to avoid extra weight on the painful leg. Subsequently, the pelvis will not fall as much downward when the lame leg is bearing weight as when the sound leg

7848-543: The high insulin levels prevent the glycogenolysis necessary to maintain normal blood sugar levels. Glucagon is a common treatment for this type of hypoglycemia. Various inborn errors of carbohydrate metabolism are caused by deficiencies of enzymes or transport proteins necessary for glycogen synthesis or breakdown. These are collectively referred to as glycogen storage diseases . Long-distance athletes, such as marathon runners, cross-country skiers , and cyclists , often experience glycogen depletion, where almost all of

7957-464: The higher the exercise intensity, the more the muscle cell produces ATP from muscle glycogen. This reliance on muscle glycogen is not only to provide the muscle with enough ATP during high-intensity exercise, but also to maintain blood glucose homeostasis (that is, to not become hypoglycaemic by the muscles needing to extract far more glucose from the blood than the liver can provide). A deficit of muscle glycogen leads to muscle fatigue known as "hitting

8066-410: The hind feet, which can be seen in cases of sacro-iliac pain, carrying the hindquarters to one side or drifting in one direction, decreased impulsion, and the saddle slip to one side. Several other signs are applicable to both front and hind limb lameness. One method is to look at the relative time a leg spends in the cranial (forward) phase of the stride. For a front leg, this is when the lower leg

8175-404: The hoof should also be examined. The shape of the sole, size of the frog, and shape of the bars can indicate overall health of the hoof. Holes in heel bulb usually indicate a hoof abscess that has ruptured. The horse's shoeing can also provide clues to the examiner. The application of corrective shoes or pads may indicate past problems requiring special shoeing. This can be especially helpful during

8284-632: The hoof wall, indicate a past episode of laminitis. Concavity of the dorsal (front) surface of the hoof can indicate chronic laminitis. The sole may become convex if the coffin bone begins to push through the bottom of the hoof. Correct hoof balance allows for even distribution of forces through the leg and hoof. Poor hoof balance, due to conformational flaws or poor trimming, can cause lameness from musculoskeletal injury, and poor hoof balance has been associated with increased risk of catastrophic injury in racehorses. Side-to-side (mediolateral) imbalance can cause sheared heals and hoof cracks. The hoof angle, or

8393-568: The horse and the back half move in unison. The canter may also be used for lameness evaluation. Resistance to picking up the canter or to engage the hind end can suggest pain in the sacro-iliac joint, pelvis, or hind leg. Lameness may be accentuated under certain conditions. Therefore, the moving examination is often performed both in a straight line and on a circle, and may be repeated on different footings. Hard footing tends to make joint and bone injury more apparent, while soft, deep footings tend to accentuate soft tissue injury. Circles may accentuate

8502-507: The horse is placed into training as a young animal; however, affected horses will show histological changes consistent with muscle damage at one month of age, and may also show elevations in creatine kinase (CK), an enzyme that elevates with muscle damage. Concurrent illness, such as respiratory or gastrointestinal infection, can lead to elevations in CK and potentially life-threatening rhabdomyolysis, even without exercise. Horses with PSSM often have

8611-412: The horse pain, laminitis, or a gravel (hoof abscess travelling up the hoof wall towards the coronary band). The horse is evaluated in motion, usually at the walk and trot, but occasionally also in the canter. The walk is often the best gait to evaluate foot placement. The trot is generally the best gait to localize the lameness to a particular leg, because it is a symmetrical gait where the front half of

8720-451: The horse's history. The horse's stance is also evaluated. Frequently resting a particular leg, "pointing" a foot (holding a leg out in front of the body), or standing in an abnormal position can indicate compensation for an injury. Shifting of weight is normal in the hind legs, but frequent shifting of weight in the front legs, or placing both front feet in front of the body, can indicate bilateral forelimb lameness. Stifle pain sometimes causes

8829-617: The horse, feeling for heat, swelling, and sensitivity to pressure indicating pain. Palpation is usually most thoroughly performed in the lower limb, but a comprehensive exam will include palpation of the back, pelvis, and neck. Joints should be palpated for pain, effusion of joint pouches, thickening of the joint capsule, and checked for range of motion. Major ligaments and tendons, such as the superficial and deep digital flexor tendons, inferior check ligament, suspensory ligament, and distal sesamoidean ligaments, should also be palpated along their entire length. Individual bones may be palpated if injury

8938-427: The joint and practitioner preference, and the horse is immediately trotted off. An increase in lameness following a flexion test suggests that those joints or surrounding soft tissue structures may be a source of pain for the horse. Flexion tests help narrow down the source of lameness to a certain part of the leg, but they are non-specific because they almost always affect more than one joint and because they also affect

9047-422: The lame leg) can be explained by when the horse perceives pain during the stride. If the pain is perceived during the early stance phase of the stride, the horse will try to unweight the leg and produce a "hip hike." If the pain is perceived during the pushoff phase of the stride, the horse does not push with as much force, subsequently reducing the height the pelvis is raised, and leading to a "dipping" motion during

9156-404: The lameness examination, they are not foolproof. Multiple studies have shown that the anesthetic can migrate, especially if the horse is evaluated long after blocking or if a large amount of anesthetic is used. If the anesthetic migrates to the structure that is causing the horse pain, the horse will have a positive block, and the examiner will conclude that the lameness originates in an area that

9265-413: The leg as far forward as it does backward. In a lame horse, the cranial phase will be shorter when compared to the caudal phase, so it appears to spend more time with the leg backward than it does forward. A shortened cranial phase is most commonly seen in cases of bilateral lameness, lameness of the upper limb (such as shoulder or hip pain), and osteoarthritis of the hocks. Decreased fetlock drop during

9374-427: The liver contained a substance that could give rise to reducing sugar by the action of a "ferment" in the liver. By 1857, he described the isolation of a substance he called " la matière glycogène ", or "sugar-forming substance". Soon after the discovery of glycogen in the liver, M.A. Sanson found that muscular tissue also contains glycogen. The empirical formula for glycogen of ( C 6 H 10 O 5 ) n

9483-441: The liver of an adult, weighing 1.5 kg, can store roughly 100–120 grams of glycogen. In skeletal muscle, glycogen is found in a low concentration (1–2% of the muscle mass): the skeletal muscle of an adult weighing 70 kg stores roughly 400 grams of glycogen. Small amounts of glycogen are also found in other tissues and cells, including the kidneys , red blood cells , white blood cells , and glial cells in

9592-479: The minimum dose of caffeine at which there is a clinically significant effect on glycogen repletion has not been established. Glycogen nanoparticles have been investigated as potential drug delivery systems . Equine lameness Lameness is an abnormal gait or stance of an animal that is the result of dysfunction of the locomotor system . In the horse , it is most commonly caused by pain, but can be due to neurologic or mechanical dysfunction. Lameness

9701-466: The motion capture based Qhorse system The most common forms of diagnostic imaging for use during a lameness exam are radiographs ("x-rays"), to evaluate bone and joint lesions, and ultrasound , to evaluate soft tissue lesions. These modalities are best applied if the general location of lameness is known from flexion tests and nerve blocks. These methods are both non-invasive and relatively cheap. Radiographs ("x-rays") are made by photons, produced by

9810-422: The muscle itself; however, the breakdown of muscle glycogen impedes muscle glucose uptake from the blood, thereby increasing the amount of blood glucose available for use in other tissues. Liver glycogen stores serve as a store of glucose for use throughout the body, particularly the central nervous system . The human brain consumes approximately 60% of blood glucose in fasted, sedentary individuals. Glycogen

9919-488: The muscles of the horse. Additionally, some horses have been shown to have insulin sensitivity, which improves glucose uptake by muscle cells and contributes to excessive glycogen storage that is already elevated secondary to the GSY1 mutation. Low levels of glycogen branching enzyme leads to a condition known as glycogen-branching enzyme deficiency. This condition is caused by a mutation of the GBE1 gene responsible for producing

10028-409: The muscles of the shoulder (supraspinatus and infraspinatus). Neck muscle atrophy can be seen with cervical vertebral malformation (Wobbler's disease), articular facet osteoarthritis, and neurologic causes of lameness. Asymmetry in a limb can also occur due to swelling of a joint or soft tissue. For this reason, each leg should be compared to its partner. After a visual exam, the practitioner palpates

10137-469: The navicular bursa, although muscle damage and arterial blood flow have also been evaluated with ultrasound in cases of lameness. Ultrasound is especially useful for determining the size and shape of lesions within structures, allowing quantification of an injury. Ultrasound may be used after diagnosis, to monitor the progression of healing of a lesion. It is also used to guide injections of treatments (steroids, stems cells, platelet rich plasma) directly into

10246-404: The nerve block. Nerve blocks are performed in a step-wise fashion, beginning at the most distal (lower) part of the limb and moving upward. This is due to the fact that blocking a nerve higher up will desensitize everything it innervates distal to the blocking location. For example, blocking the leg at the level of the fetlock will also block the entire foot, since the nerve fibers that innervate

10355-414: The next. Branches are linked to the chains from which they are branching off by α(1→6) glycosidic bonds between the first glucose of the new branch and a glucose on the stem chain. Each glycogen is essentially a ball of glucose trees, with around 12 layers, centered on a glycogenin protein, with three kinds of glucose chains: A, B, and C. There is only one C-chain, attached to the glycogenin. This C-chain

10464-513: The nonreducing end of the glycogen chain. The glycogen branching enzyme catalyzes the transfer of a terminal fragment of six or seven glucose residues from a nonreducing end to the C-6 ;hydroxyl group of a glucose residue deeper into the interior of the glycogen molecule. The branching enzyme can act upon only a branch having at least 11 residues, and the enzyme may transfer to the same glucose chain or adjacent glucose chains. Glycogen

10573-449: The painful leg. Lastly, behavioral changes and decreased performance may indicate pain, even if obvious clinical lameness is not evident. A lameness exam is used to try to pinpoint the cause of lameness in the horse, which subsequently guides treatment. It is the first step to evaluate decreased performance in an equine athlete, even if the horse does not appear overtly lame, to rule out any pain-associated cause. Lameness exams are also

10682-598: The patella and fibrotic myopathy, but any type of adhesion (often secondary to scarring during healing post-injury) or fibrosis can cause mechanical lameness. Neurologic lameness may be the result of infection, trauma, toxicities, or congenital disease. Neurological evaluation of a lame horse may be warranted if the cause of the lameness is not obvious. Signs more commonly associated with a neurologic cause include unilateral muscle atrophy, paresis , paralysis , or dysmetria . Neurologic causes of lameness include: Manifestations of lameness include any alteration in gait from what

10791-402: The pelvis on the lame side as it is bearing weight, trying to shift weight off of the painful leg in a manner similar to raising of the head in front limb lameness. This is a sudden, short upward motion of the hemi-pelvis or gluteal muscles. The hip of the lame leg does not always rise above the level of the hip of the sound leg, which can be confusing to those looking for a "hip hike." Instead, it

10900-505: The pre-purchase exam, when the lameness history of the horse may not be readily available. Digital pulse evaluation is important when addressing the hoof. An increased digital pulse often indicates that the lesion is in the foot, and are usually most significantly increased in horses with laminitis . The coronary band may also be palpated. Cool swelling can indicate coffin joint effusion, swelling with an increase in temperature can indicate laminitis, firm swelling can occur with ringbone , and

11009-455: The reflection of high frequency sound waves off of tissues. Different tissues absorb or reflect ultrasonic waves to different degrees, which may be picked up by the machine and turned into an image. Because ultrasound does not easily cross bone or air, it is best used for the evaluation of soft-tissue structures. It is therefore a complementary imaging modality to radiographs, and is most commonly used to look for injury to ligaments and tendons, and

11118-414: The shape of the hoof capsule, since the lame limb is not weighted as much as its partner, making the capsule more upright, narrow, with a higher heel on the lame limb and more flattened on the sound one. Hoof or horseshoe wear can indicate breakover and if the horse is dragging its toes. Change in shape of the hoof wall is also common in horses with laminitis. "Founder rings," or thickened concentric rings in

11227-500: The skeletal muscles of the horse that is not due to mutations in GSY1 or GBE1. PSSM is most prevalent in American Quarter Horses and their related breeds ( Paint horse , Appaloosa , Appendix Quarter Horse ), Draft horse breeds (especially Belgian Draft and Percherons ), and Warmblood breeds. The Belgian Draft been shown to have a 36% prevalence of PSSM. Other breeds that have been diagnosed with PSSM include

11336-407: The soft tissue structures around the joint, not just the joint itself. Additionally, they must be interpreted carefully due to the risk of false negatives and false positives. Nerve blocks involve injecting a small amount of local anesthetic around a nerve or into a synovial structure (such as a joint or tendon sheath) in order to block the perception of pain in a specific area. After the substance

11445-430: The stance phase of the stride may be seen in cases of lameness, with the lamer leg producing less drop than the sound leg as the horse tries to relieve weight on the painful limb. Decreased height to the stride (flight arc), or dragging of the toes, also indicates lameness, as the horse avoids bending its joints. In the front limb, decreased flight arc is usually seen in cases of shoulder, knee, or fetlock joint pain, and

11554-431: The swing phase of the stride as the horse brings the limb forward. In some cases, both a hip hike and a hip drop can be seen in the same horse. Some practitioners simply look for the side with the greater overall deviation, which occurs in the lame leg Another method to detecting hind limb lameness requires watching the pelvis from the side. The entire pelvis is evaluated, and its relative position vertically (relative to

11663-408: The viewer watches the hip, sacrum, gluteal muscles, or hemi-pelvis (pelvis of one side of the body) when examining lameness in the hind end. Examination should be performed both watching the horse from behind while trotting away from the examiner, and from the side as the horse passes. When watching from behind, the viewer often looks for a "hip hike" or "pelvic hike." This occurs when the horse raises

11772-451: The wall" or "the bonk" (see below under glycogen depletion) . In 1999, Meléndez et al claimed that the structure of glycogen is optimal under a particular metabolic constraint model, where the structure was suggested to be "fractal" in nature. However, research by Besford et al used small angle X-ray scattering experiments accompanied by branching theory models to show that glycogen is a randomly hyperbranched polymer nanoparticle. Glycogen

11881-436: Was established by August Kekulé in 1858. Sanson, M. A. "Note sur la formation physiologique du sucre dans l’economie animale." Comptes rendus des seances de l’Academie des Sciences 44 (1857): 1323-5. Glycogen synthesis is, unlike its breakdown, endergonic —it requires the input of energy. Energy for glycogen synthesis comes from uridine triphosphate (UTP), which reacts with glucose-1-phosphate , forming UDP-glucose , in

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