Explain why the patient with myasthenia gravis cannot generate consistent action potentials in the muscle fiber.

Number 1 post: RW

According to the National Institute of Health, Osteoarthritis is a degenerative joint disease, in which the tissues in the joint break down over time. It is the most common type of arthritis and is more common in older people. People with osteoarthritis usually have joint pain and, after rest or inactivity, stiffness for a short period of time. The most commonly affected joints include the hands, knees, hips, neck and lower back. Osteoarthritis affects each person differently. For some reason, osteoarthritis is relatively mile and does not affect day-to-day activities. For others, it causes significant pain and disability. Joint damage usually develops gradually over years, although it could worsen quickly in some people. (2019).

Osteoarthritis is a disease of articular cartilage and subchondral bone in diarthrodial joints. It was believed that OA was exclusively a degenerative disease of the cartilage, however, latest evidence has proven that OA is a multifactorial entity, involving multiple derangements. It is also known that the cartilaginous tissue is not the only one involved. Given its lack of vasculature and innervation, the cartilage, by itself is not capable of producing inflammation or pain at least on early stage of the disease. hence, the source of pain is mainly derived from changes to the non-cartilaginous components of the joint, like the joint capsule, synovium, subchondral bone, ligaments, and peri-articular muscles. As the disease advances, these structures are affected and changes including bone remodeling, osteophyte formation, weaking of periarticular muscles, laxity of ligaments, and synovial effusion can become evident. (Mora et al., 2018).

Osteophytes are thought to stabilize an osteoarthritic joint, thereby preventing structural progression. Meagre longitudinal data suggest, however, that they are associated with an increased risk of structural progression. Large osteophytes do not affect the risk of structural progression. They are strongly associated with malalignment to the side of the osteophyte, and any relation they have with progression is partly explained by the association of malalignment with progression. Osteophytes are so common as a radiographic feature of osteoarthritis that they have been used to define the presence of disease. they most often appear as they margin of the joint, originally as outgrowths of cartilage and subsequently undergo endochondral ossification. Growth factors such as transforming growth factor beta potentiate their growth. (Felson et al., 2013).

NSAIDS are widely used to alleviate the symptoms of OA. It remains controversial as to what effects these agents have on the progression of OA. In vitro studies showed several types of NSAIDS inhibited the synthesis and protected the chondrocytes against apoptosis, while others had no effects. Preliminary clinical trials revealed some NSAIDs such as indomethacin had a negative influence on joint structure, other NSAIDs such as diclofenac and naproxen had no acceleration of radiographic damage to OA within 2-years of treatment. So far, there are no convincing data to show the widely used NSAIDs and recommended selective COX-2 inhibitor have favorable effects of cartilage. Therefore, it is necessary and valuable to clarify the effects of these NSAIDs on cartilage in patients with OA using validated non-invasive methods such as MRI. (Ding, 2002).

Obesity is widely acknowledged as a risk factor for both incidence and progression of osteoarthritis and has a negative influence on outcomes. Loss of at least 10 pounds of body weight, coupled with exercise, is recognized as a cornerstone in the management of obese patients with osteoarthritis, and can lead to significant improvement in symptoms, pain relief, physical function, and health-related quality of life. (Bliddal etal., 2014).

According to the CDC, there is no cure for OA, so doctors usually treat OA symptoms with a combination of therapies, which may include increasing physical activity, physical therapy with muscle strengthening exercises, weight loss, medications, supportive devices such as crutches, or canes and surgery. In addition to these treatments, people can gain confidence in managing their OA with self-management strategies. These strategies help reduce pain and disability so people with osteoarthritis can pursue the activities that are important to them. (2020).

Number 2 post: RB

A 30-year-old female presents with muscle weakness and fatigue. Abnormal electromyography testing and a positive increase in ACTH receptor test is reported. Her final diagnosis is Myasthenia Gravis.

Described the normal synaptic transmission at the neuromuscular junction (NJM).

To be able to understand how the neuromuscular junction works (NMJ) understanding what is normal to abnormal and the role of neurotransmitter in the generation of muscle contraction needs to be understood. The brain has several neurotransmitters including, acetylcholine, norepinephrine, dopamine, and serotonin the brain is an organ with millions of neurons and an extensive circuitry that allows receiving and transmitting signals from the environment in response to stimuli (Dlugasch & Story , 2021). Neurotransmitter modulators such as Acetylcholine receives signals from the cerebral cortex which then binds to nicotinic acetylcholine receptor on muscle cell membrane that resulted in muscle contraction (action potentials). The neuromuscular junction has three main parts; presynaptic membrane which is the membrane of an axon terminal, post synaptic membrane the membrane of the skeletal muscle also known as motor end plate, and synaptic cleft gap between pre and post synaptic membrane. Our brain sense a signal in the form of action potential from the cerebral cortex (upper motor neuron) this then activates the lower motor neuron through the axon terminals to the muscle fibers where innervation happen, the NMJ is the area where motor neuron meets the skeletal muscle fiber when the lower motor neuron is activated there is an influx of calcium ions into the presynaptic membrane followed by the release of acetylcholine into the synaptic cleft Acetylcholine binds to nicotinic receptors this leads to the generation of an action potential which eventually resulted in muscle contraction (Omar, Marwaha, & Bollu, 2021). Myasthenia Gravis is an immunologically mediated disorders affecting the end plate region of the postsynaptic neuromuscular junction, this is analogous to having a gatekeeper where an individual will be check (action potential) whether the command from the king/ authority (cerebral cortex) will be allowed to enter the kingdom (muscle contraction), any disturbances or discrepancy of information will disallow/inhibit the contraction.

Why is ACTH increased?

Anticholinergic antibodies can also activate the classical pathway of the classical pathway complement pathway this is a family of small proteins that work in an enzymatic cascade to fight off bacterial infections the activation of CCP causes inflammation and destruction of the muscle cells. ACTH is a peptide hormone that binds to corticotrope cells that is being release when the hypothalamus detects stressful stimuli such as infection and acts on inflammatory state and due to thymoma.

Explain why the patient with myasthenia gravis cannot generate consistent action potentials in the muscle fiber.

Myasthenia gravis results in the weakness of the voluntary skeletal muscle because of inadequate nerve stimulation (Dlugasch & Story , 2021). It is a rare, autoimmune neuromuscular junction disorder. When the motor neuron releases acetylcholine the normal pathophysiology is the binding with nicotinic acetylcholine receptor on the muscle cell membrane to create muscle contraction in MG there is a hypersensitivity which causes cytotoxic injury at the end plate of the neuromuscular junction which inhibits the binding of acetylcholine resulting in lysis or death of the host cells the antibodies from the B-cells inappropriately makes antibodies that bind to nicotinic receptors on the muscle cells arresting the binding or resulted in the inability of the nicotinic receptors to bind with acetylcholine preventing the muscle from contracting.

Treatment for the patient involves pyridostigmine-what does this drug do and how would it benefit our patient?

Pyridoxine or neostigmine is an acetylcholinesterase inhibitors which acts to degrades acetylcholine thereby preventing the acetylcholinesterase from breaking down resulting in the increased of acetylcholine around the muscle cells and this helps to counteract the effect of acetylcholine antibodies receptors, this helps counteracts the effect of acetylcholine antibodies, thereby minimizing the effect or sign and symptoms of myasthenia gravis, additionally immunosuppressive drugs such as prednisone can be utilized and for those individual who fails to react with medications a surgical intervention can be done or what we call thymectomy. There is no treatment with myasthenia gravis supportive and prevention of myasthenia crisis which is life-threatening is the goal of treatment.