myopathies Flashcards

Question

diff heterozyg/homozyg HYPP

Answer 1

N/H horses from asymptomatic to daily episodic muscle fasciculations and weakness Respiratory distress can occur in N/H and H/H Foals **homozygous** for HYPP usually show clinical signs of disease in the **first few days** of life that include **dysphagia, respiratory stridor,** periodic obstruction of the upper respiratory tract Adults that are H/H usually have **more frequent and severe episodes** of HYPP compared with N/H horses and **more severe signs of upper airway obstruction** during an episode.Homozygous affected horses also have a **high-pitched whinny** even between episodes.

Answer 2

Feeds high in potassium, starving, anesthesia, heavy sedation, trailer rides (caleche), and stress Exercise does not seem to induce clinical signs

Answer 3

Sodium channels are normally briefly activated to allow transient sodium entry into muscle cells during the initial phase of the muscle action potential. mutation results in a **failure of a subpopulation of sodium channels to inactivate when serum potassium concentrations are increased**. Failure of inactivation results in membrane depolarization, which manifests as muscle fasciculations and can eventually lead to depolarization block manifesting as muscular paresis or paralysis.

Answer 4

feeding **grain or corn syrup** to stimulate insulin-mediated movement of potassium into cells and by initiating **light exercise**. administration of **epinephrine, calcium gluconate** (increase in extracellular calcium concentration increases the muscle-membrane threshold potential, which attenuates membrane hyperexcitability) **IV dextrose** alone or combined with **sodium bicarbonate** With severe dyspnea caused by laryngeal or pharyngeal obstruction, a **tracheostomy** can be necessary managment: Restricting dietary potassium = between 0.6% and 1.1% total potassium concentration and meals containing less than 33 g of potassium. **Maj source pot is forage**. **Pasture grazing need not be restricted** because the gradual consumption of grasses, which have a high water content, prevents a spike in blood potassium concentrations. **Regular exercise** and frequent turnout are beneficial. In cases where dietary management is insufficient to control episodes of HYPP, **Acetazolamide or hydrochlorothiazide**

Answer 5

GBE1, autosomal recessive quarter horse (10% carrier) and paint horse (5% carrier) highest prevalence is seen in Western pleasure horses at 26% followed by cutting (14%) and working cow horses (10%)

Answer 6

Most foals homozygous for GBED seem to be **aborted or stillborn** based on the high prevalence of heterozygosity for GBED (4% were Gb/Gb, with most being aborted within the second trimester) If foals survive to term, they usually appear **weak and hypothermic at birth** but, with support to nurse, can appear normal for the first weeks of life Early in life, affected foals usually have a **slightly dull mentation and flexural limb deformities** that are corrected by bandaging or tetracycline administration Within weeks, GBED progresses to involve **difficulty rising or respiratory failure or sudden death** following hypoglycemic seizures or cardiac arrest. Regardless of the degree of intensive care provided, all affected foals studied to date have **died or been euthanized by 18 weeks of age**. leukopenia and **moderate increases in CK**, aspartate transaminase, and gamma glutamyl transferase activities.

Answer 7

The GBE provides an energy-dense structure through **adding branching alpha-1,6 glycosidic linkages to the glycogen polymer** The production of straight chains of glycogen without branch points drastically **decreases the number of nonreducing ends** within the glycogen molecule, thereby **limiting the rates of both synthesis and degradation**. Glucose-dependent tissues such as **skeletal myocytes, cardiac myocytes, and cardiac Purkinje fibers** are subject to catastrophic energy deficits

Answer 8

in skeletal muscle, Purkinje fibers, or cardiac myocytes **basophilic globules and eosinophilic crystalline inclusions** in hematoxylin and eosin stains and deeply magenta inclusions in periodic acid–Schiff (PAS) stains **lack of normal PAS staining for the presence of glycogen** and the accumulation of **abnormal PAS-positive amylase resistant inclusions** In contrast with polysaccharide storage myopathy (PSSM), cardiac and skeletal muscle tissues from GBED foals have little background staining for glycogen

Answer 9

invariably fatal by 18 weeks of age. H

Answer 10

**1-14 years** Acute clinical signs include tucking up of the abdomen, stretching out, **fasciculations in the flank, muscle stiffness, sweating**, reluctance to move forward, pawing, rolling, and overt firm muscle contractures. The **hindquarters** are frequently most affected Signs of pain usually begin **after 15 minutes of exercise** and can last for more than 2h. y 10% temporary recumbency. +/- Severe **coliclike pain and myoglobinuric renal failure** Acute episodes are usually associated with **markedly increased serum CK** activity of greater than 35,000 U/L and myoglobinuria. Although abnormal **polysaccharide can be present in cardiac myocytes in P/P horses, there seems to be no clinical evidence of cardiac disease.**

Answer 11

DRAFT HORSES many **asymptomatic** Clinical signs occur most often in horses fed **high-grain diets, exercised irregularly**, with little turnout, or horses that undergo general **anesthesia**. homozygotes: **progressive weakness and muscle loss** resulting in difficulty rising in horses with **normal CK**. LIGHT BREED a lack of energy when under saddle, reluctance to move forward, stopping and stretching out. **fasciculations or pain** on palpation of lumbar muscles. **CK are often increased** in unmanaged horses, **even when horses are rested**, or increase from normal values by 2-fold or more after 15 minutes of light exercise.

Answer 12

The dominant gain-of-function mutation in the GYS1 gene encoding **glycogen synthase** results in greater than 1.8-fold **higher glycogen concentrations** in skeletal muscle and **accumulation of amylase-resistant polysaccharide** in a small percentage of fast-twitch muscle fibers. **same relative activation of branching enzyme**. less highly branched polysaccharide that becomes resistant to amylase digestion. **high serum CK activity following 15 minutes of light aerobic exercise** is associated with a deficit in energy metabolism (measured as high myofiber inosine monophosphate concentrations). **myophosphorylase is inactive when glycogen synthase is active**, resulting in minimal glycogen metabolism. Alternatively or in concert, dysregulation of glycogen concentrations could prevent nutrient switches (AMP kinase) to fully activate enzymes such as pyruvate dehydrogenase during exercise, limiting adequate acetyl coenzyme A (CoA) for oxidative metabolism. **unable to generate enough acetyl CoA** from either carbohydrate or fat metabolism to fuel muscle contraction.

Answer 13

false-negative if biopsy samples are small or if horses are less than 2 years of age numerous subsarcolemmal vacuoles and dense, crystalline PAS–positive, amylase-resistant inclusions in fast-twitch fibers

Answer 14

**acepromazine, xylazine**, or, in more painful horses, **detomidine combined with butorphanol** **in hydrated horses, nonsteroidal antiinflammatory** drugs such as ketoprofen,phenylbutazone, or flunixin meglumine methocarbamol: variable results **CRI detomidine, lidocaine, butor** for severe cases **Dantrolene** repeated in intervals of 4 to 6 hours in severe rhabdomyolysis because it **decreases the release of calcium from the sarcoplasmic reticulum**, which provokes muscle contractures and necrosis. Caution is advised when administering dantrolene to horses with concomitant PSSM1 and HYPP because it **can increase serum potassium concentrations and precipitate an episode of HYPP**. **small padock**

Answer 15

**Prolonged rest should be avoided** because serum CK activity and clinical signs of PSSM1 are more severe in horses without access to turnout. 2 weeks allowed for dietary adaptations before commencing exercise, program gradually introduced and consistently performed, regulating both the duration and the intensity of exercise, and minimizing days without some form of exercise. common to have subclinical increases in CK activity when exercise is reintroduced, and a return to normal levels often requires 4 to 6 weeks of gradual exercise. fed hay with **less than 12% nonstructural carbohydrate** (NSC) forage 2% body weight **at least 13% of daily digestible energy as fat**. **limit grain** **Long-chain fats** (in corn oil and rice bran) decrease postexercise serum CK activity in horses with PSSM1, whereas **odd-chain fat (C7) is detrimental**. **Vitamin E should be fed to horses receiving high-oil diets** because of the potential additional oxidant stress of fats. **grazing muzzle** may be needed to reduce sugar intake **fasting for 6 hours before exercise** to increase plasma free fatty acids.

Answer 16

wide variety of presentations from asymptomatic to debilitating. With **adherence to both diet and exercise recommendations, at least 70% of horses show notable improvement** in clinical signs and many return to acceptable levels of performance. **Homozygous P/P horses have more severe clinical signs, as do horses with both the GYS1 and RYR1 mutations.**

Answer 17

**RYR1**: skeletal muscle calcium release channel (ryanodine receptor) **autosomal dominant** Homozygosity seems to be lethal **quarter and paint**, prevalence <1% Halter and pleasure horse lines have the highest prevalence.

Answer 18

Rhabdomyolysis may be induced by exercise and anesthesia increased body temperature during episodes

Answer 19

RYR1, GYS1 mutation–positive horses have **more severe episodes** of exertional rhabdomyolysis, **higher serum CK** activity after exercise, and a **poorer response to the diet and exercise regimes** recommended for PSSM1 During a**nesthesia, clinical signs of hyperthermia, hypercapnea, and acidosis**. hemoconcentration, hyperkalemia, hypercalcemia, hyperphosphatemia, hyperglycemia, and increased creatinine level.

Answer 20

**decreases the activation and increases the deactivation threshold of the ryanodine receptor (calcium release channel)**. remains open, causing a drastic **efflux of calcium** **from the sarcoplasmic reticulum** and inducing a **persistent muscle contracture**. The process of reuptake of myoplasmic calcium into the sarcoplasmic reticulum **consumes large amounts of oxygen and ATP and generates carbon dioxide and excessive heat**. Myofibers are damaged by the depletion of ATP and possibly the high temperatures.

Answer 21

samples **often lack any histopathologic changes**. can contain mild myopathic changes, including **increased variation in fiber sizes, centrally located nuclei, fiber necrosis, glycogen depletion**, and **ringbinden fibers**.

Answer 22

**Dantrolene** binds to RYR1 and inhibits calcium release. (before anesth) external application of alcohol, fans, **chilled IV fluids with sodium bicarbonate, and mechanical ventilation**. However, once a fulminant episode is underway under anesthesia, it is difficult to prevent cardiac arrest.

Answer 23

**MYH1** myosin heavy chain 1 gene **autosomal codominant with variable penetrance**. present in the fastest contracting muscle fibers, type **2X** **quarter horses (7%) , paint horses, Appaloosas** highest MYH1 mutation prevalence was found in reining (24%), working cow (17%), and halter (16%) horse stallions

Answer 24

*Nonexertional Rhabdomyolysis*: **muscle pain, stiffness**, and potentially recumbency, frequently affecting young horses. some cases, horses have a concurrent **Streptococcus equi** equi infection. **Myoglobinuria** is common with high serum **CK**. **35% subsequently develop acute muscle atrophy typical of immune-mediated myositis**. *Immune-Mediated Myositis*: in horses **<8 y or > 17 y**, **rapid symmetric atrophy of lumbar and gluteal muscles**. semimembranosus and semitendinosus muscles are relatively unaffected. Muscle mass usually recovers gradually over months. Horses **homozygous for MYHM (My/My) have more severe and recurrent atrophy** (80 vs 20%) that **does not always fully recovery**. **neutrophilia and increased fibrinogen level** During acute phase **CK and AST increased** ****Fever 44%**** **Recurrence of clinical signs is common (50%** of cases) and more often seen in homozygous. *Systemic Calcinosis*: in association with clinical signs of immune mediated myositis. early indicator : **ventral edema**. malaise, mild fever, stiffness, muscle atrophy, and diverse organ failure (**respiratory distress, colic, laminitis**). mild leukocytosis, hyperfibrinogenemia, and hyperphosphatemia, with a product of total **Ca level multiplied by P level > 65 mg/dL**

Answer 25

reported in 39% of cases being recently exposed to infectious diseases such as **S equi equi or Streptococcus zooepidemicus**; influenza virus, equine herpes virus 1 and 4, Corynebacterium pseudotuberculosis (Fig. 3), and Anaplasma phagocytophilum a **respiratory** virus; or **vaccination with influenza, equine herpes virus, or S equi equi.** within few weeks

Answer 26

*Nonexertional Rhabdomyolysis*: affect the activity of the **myosin ATPase** enzyme of type **2X** muscle fibers. role for **abnormal actin/myosin interaction** is postulated *Immune-Mediated Myositis*: activated by release of the mutant form of **myosin heavy chain** from myofibers **following muscle damage (trauma, vaccination**). MYH1 mutation is also postulated to lead to conformational changes in myosin that **activate Toll-like receptors** and autoimmunity. shared epitopes between bacteria such as the **M protein of Streptococcus** sp and myosin. *Systemic Calcinosis*: cytokines , such as **TNF-alpha and IL6**, -> activation of the receptor activator of nuclear factor kappa B ligand (**RANKL**) -> enhanced **bone resorption**. hyperphosphatemia induce dystrophic calcification through passive calcium phosphate deposition, an active process promoting the **conversion of smooth muscle cells to osteogenic cell types, directly increasing PTH secretion** and transcription, and **interference with renal production of 1,25-dihydroxyvitamin D** levels.

Answer 27

Muscle biopsy samples with *nonexertional rhabdomyolysis* are often normal, **30% show marked glycogen depletion**, and less than **18% of muscle samples contain lymphocytic infiltrates** *immune-mediated myositis*: **gluteal and epaxial** muscles of horses have **lymphocytic infiltrates** in myofibers and surrounding small blood vessels **without glycogen depletion** combination of sarcolemmal MHC I and II expression and lymphocytic infiltration. more **CD4+** than CD8+ T lymphocytes. *systemic calcinosis*: **multinucleated giant cells and dystrophic calcification** of muscle fibers

Answer 28

*Nonexertional Rhabdomyolysis*: Acute management **same than PSSM**. **Dantrolene** until serum CK activity has declined significantly *Immune-Mediated Myositis*: **Antiinflammatory doses of corticosteroids for approximately 1 month** combined with antibiotics if infection is present Horses with **nonexertional rhabdomyolysis and immune-mediated myositis can make a full recovery.** Muscle mass regenerates over weeks to months. However, the **MYH1 mutation results in recurrent episodes in almost 50% of horses.** Horses homozygous **My/My are more likely to have frequent episodes and more severe episodes with less return of normal muscle mass** Horses with systemic signs of **calcinosis have a grave prognosis.**

Answer 29

Minimizing **exposure to infectious agents**, using **intranasal vaccines or intramuscular vaccines that cause the least muscle irritation**, spreading out **vaccines at 1-month intervals**, and **avoiding immunostimulants** are advised. **Strangles vaccination is contraindicated** in My/N and My/My horses.

Answer 30

halter horse performance group of quarter horses

Answer 31

PSSM2, myotonic dystrophy, lipid storage myopathy, centronuclear myopathy, myofibrillar myopathy, and recurrent exertional rhabdomyolysis.

Answer 32

inflam lymphocytes myodegen macrophagesFMT

Answer 33

Double loci with MYH1 include those causing **MH, GBED, and HYPP** triple loci include those causing **MH and GBED**.

Answer 34

A phagocytophilum, which infects and replicates in **leukocytes** **Ixodes ricinus** vasculitis fever, lethargy, anorexia, icterus, and limb edema **neurologic and muscle disease was seen in 41% and 18%** of the cases. **anemia**, **leukopenia** with neutropenia and lymphopenia, **thrombocytopenia**, and **hyperbilirubinemia**. **Elevated CK Hyperfibrinogenemia** is more commonly seen in horses with neurologic and muscle disease Muscle manifestations in horses with anaplasmosis should prompt the clinician to test for the **MYH1** mutation in QH and related breeds. highly responsive to **tetracyclines** with signs improving or resolving within hours to days

Answer 35

1. enzootic calcinosis due to the ingestion of toxic plants with calcinogenic effects: **Solanaceae** (eg, Solanum glaucophyllum and Cestrum diurnum) and Gramineae (eg, Trisetum flavescens), contain **vitamin D-like or active metabolites of vitamin D3** 2. tumoral calcinosis 3. systemic calcinosis with a suspected underlying immune-mediated process + Chronic renal failure, secondary hyperparathyroidism, vitamin D intoxication

Answer 36

oral **aluminum hydroxide and IV sodium thiosulfate**, glucocorticoids

Answer 37

Boxelder maple (**Acer negundo**, ash-leaved maple, box elder) and sycamore maple (**A pseudoplatanus**) Ingestion of the **seeds or seedlings** in **fall or spring** toxine: **hypoglycine A**

Answer 38

hypoglycine A is metabolized in the mitochondrial matrix in a enzymatic process of transamination and oxidative carboxylation, similar to other BCAAs. The resulting toxic metabolite methylenecyclopropylacetyl-CoA (**MCPA-CoA**) **inhibits** multiple flavin adenine dinucleotide (FAD)–dependent mitochondrial **acyl-coenzyme A dehydrogenases** that catalyze the first step of **fatty acid ß-oxidation** and are involved in amino acid catabolism. Methylenecyclopropylglycine (**MCPG**), a homolog of MCPA present in lower concentrations than HGA in both maple species, may contribute to the pathogenesis through in vivo formation of the toxic metabolite methylenecyclopropylformyl-CoA. The latter is a potent inhibitor of **enoyl-CoA hydratases**, the catalysts of the second step of fatty acid ß-oxidation Inhibited mitochondrial ß-oxidation leads to cellular energy depletion and accumulation of fatty acids with resulting acute myonecrosis and **lipid storage myopathy.**

Answer 39

affects highly oxidative (type 1) myofibers, abundant in postural and respiratory muscles, and cardiac myocytes depend highly on fatty acids as an energy source

Answer 40

acute **muscular weakness, stiffness, muscle tremors**, prolonged recumbency, **myoglobinuria**, depression, **congested mucous membranes, sweating and tachycardia**. **colic**, cardiac **arrhythmias**, dyspnea, dysphagia, esophageal obstruction, bladder distention, and **dysuria** **Mortality rates from 70% to 90% in the first 2 to 3 days**

Answer 41

markedly elevated **CK** increased **cardiac troponin 1** **hyperglycemia and hypocalcemia** elevated **serum acyclcarnitine and urine organic acids** **hypoglycin A or MCPA in serum, urine or muscle**

Answer 42

White snakeroot toxine : tremetone

Answer 43

1. more frqt (80 vs 17%) atrophy than heteroz, more rapid 2. 50% homoz 3. stifness 40% homoz vs 18% heterozyg, normal 17% 4. fewer homoz vs heteroz 5. 50% heteroz 20% homoz 6. vacc: Strangles, influeza, herpesvirus, patho: S. equi, C. pseudotuberculosis, Anaplasma phago, herpes virus, influenza 7. heteroz=homoz 8. dantrolene 9. leucocytosis

Answer 44

fever, other illness decreased survival

Answer 45

Warmblood behavioural change, pigment retinoathy, lower vit E Quarter inonstant menace resp, abnormal mentation, more increased serum pNfH

Answer 46

low sensitivity Quarter and horses <5y more likely to have increase highly specif serum > 1 ng/mL CSF > 3ng/mL can indic CVCM/NAD can only be interpreted if infect/trauma ae excluded

Answer 47

Quarter: increased metab rate of alpha tocopherol, increased exp cytochrome P450 CYP4F2 (vitE metab in liver) increased lipid peroxidation in SC downregul glutamate recept, cholest biosynthetisis pathway (liver X recept upregul) -> exessive oxysterol

Answer 48

neutralize hydroxul radicals and lipid peroxidation products protecting cells from damage caused by oxidative stress

myopathies Flashcards

(72 cards)