Skeletal muscle system disease

Prepared by: Siti Norhaiza Binti Hadzir

Normal skeletal muscle

It is composed of fascicles of muscle fibers (myofibrils) that represent the cellular unit.

A myofibril is a long, cylindric, multinucleate cell that is the contractile unit of the muscle.

Line A show the width of one cell (fiber). Note the striations characteristics of this muscle type. These cells are multicellular, B marks one nucleus.

Muscle Disease-Introduction

Myopathy- neuromuscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness.

"Myopathy" simply means muscle disease (myo- Greek "muscle" + patho-Greek "suffering").

Muscle disease- Diagnosis

General clinical considerations- family history, age of onsets, history of drugs, distribution of muscle weakness and rate of progression.

Special investigation of neuromuscular electrical activity (electromyograph)

Laboratory test- muscle biopsy

- serum enzymes (CK)

- chromosomal analysis

Muscle weakness

Inability to exert force to the degree that would be expected given the individual's general physical fitness.

Occur due to lack of energy producing molecules or a failure in the balance of electrolytes within and surrounding the muscle cell necessary for neuromuscular function.

Causes of myopathy

Rhabdomyolysis

Normal muscle which is overused will end up weak or spasm until rested.

In severe cases of overuse, especially where movements are strong and erratic as might occur during convulsions, damage to muscle cells may result.

Severe damages muscle cells release myoglobin, a condition known as rhabdomyolisis.

Biochemical Changes in Rhabdomyolysis

Damage muscle cells will leak myoglobin into the plasma.

Release myoglobin in plasma will be filtered at the glomerulus and cause an orange and brown color.

Myoglobinuria must be distinguished from hematuria (the urine contains no RBC in myoglobinuria) and hemoglobinuria (by immunoassay or spectroscopy).

The damage muscle cells release large amounts of K+ into the extracellular fluid causing hyperkalemia.

Damage cell tend to take up calcium ions, reducing serum calcium concentration (hypocalcemia).

Severe muscle damage is frequently accompanied by a reduction in blood volume.

This is due to hemorrhage in severe trauma, or indirectly because of fluid sequestration in the damaged tissue.

Investigation of Rhabdomyolisis

Total creatine kinase in serum

Urine myoglobin

Serum potassium

Serum calcium

Serum creatinine

Skeletal muscle disorders

Primary muscle disease e.g muscular dystrophies

Inflammation of muscle (myositis)

Disorders of neuromuscular Transmission (Myasthenia Gravis)

Duchenne Muscular Dystrophy (DMD)

The disease is due to the absence of a gene located on the short arm of the X chromosome at the Xp21 site.This results in the absence of the gene product dystropin in skeletal muscle, a consistent finding in Dunchenne’s disease.Dystropin is a membrane-associated structural protein that serves as a strut to maintain muscle fiber integrity during contraction

The progression of the disease

Affected person (male) are normal at birth and manifest the disease in early childhood.1st affects the muscle of the pelvic girdle (difficult getting up from seated position)Walking is difficult (have to use wheelchair)Death commonly results from involvement of respiratory muscles.

Investigation of DMD

A positive Gower's sign reflects the more severe impairment of the lower extremities muscles. The child helps himself to get up with upper extremities: first by rising to stand on his arms and knees, and then "walking" his hands up his legs to stand upright.

Creatine kinase (CK-MM) levels in the bloodstream are extremely high.

An electromyography (EMG) shows that weakness is caused by destruction of muscle tissue rather than by damage to nerves.

Genetic testing can reveal genetic errors in the Xp21 gene.

A muscle biopsy (immunohistochemistry or immunoblotting) or genetic test (blood test) confirms the absence of dystrophin.

Inflammation of muscle (Myositis)

Infectious disease (bacteria, viral, parasitic, exotoxic

Immune disease (SLE)

Other causes (radiation, ischemia)

Disorders of Neuromuscular Transmission

Myasthenia Gravis is a clinical syndrome resulting from failure of neuromuscular transmission due to blockage and destruction of acetylcholine receptors by autoantibody.

Myasthenia gravis is therefore an organ-specific autoimmune disease.

MG is characterized by muscle weakness that is typically aggravated by repeated contraction.

Myasthenia Gravis

Muscle with the smallest motor units are affected first, the most typical clinical presentation being weakness of ocular muscles causing drooping of the eyelid

The disease sometimes progress to include facial muscles, limb girdle muscles, and respiratory muscles

Diagnosis of MG

Edrophonium (Tensilon)-short acting drug produce immediate improvement in muscle weakness when administered IV

EMG-↓ in amplitude of muscle action potentials when muscle is subjected to repeated voluntary contraction

Serum assay for anti-Ach receptor antibody

Myositis Dystrophies MG Myopathies

CK +++ ++ - +

Aldolase ++ +++ - +

Amino-transferase

++ ++ - +

LDH ++ ++ - +

Other useful test

Biopsy EMG,

biopsy

EMG, Ach-receptor Ab

EMG,

biopsy

Thank you