Thyroid 101

The thyroid gland is one branch of the endocrine system that is located in the neck that has two lobes connected by an isthmus. The hypothalamus secretes Thyrotropin-releasing hormone (TRH) which stimulates the anterior pituitary to secrete Thyroid-stimulating hormone (TSH). TSH acts on the thyroid gland to secrete the hormones triiodothyronine (T3) and thyroxine (T4). Within the circulation T4 is converted to its active metabolite T3. There are two different types of thyroid cells. Follicular cells produce the thyroid hormones T3 and T4. The parafollicular cells produce calcitonin. Calcitonin causes calcium reabsorption and maintains calcium homeostasis.

Synthesis of Thyroid Hormones is from iodine and tyrosine. Triiodothyronine (T3) has three atoms of iodine per molecule and thyroxine (T4) has four atoms of iodine per molecule. The hormones are created from thyroglobulin which is a protein within the follicular space that is originally created within the rough endoplasmic reticulum (RER). Thyroglobulin contains 123 units of tyrosine with reacts with iodine within the follicular space. A sodium-iodide symporter pumps iodide actively into the cell where it enters the follicular lumen from the cytoplasm by the transporter pendrin. In the colloid, iodide is oxidized to iodine by the enzyme called thyroid peroxidase. Iodine is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain. This forms the precursors of the thyroid hormones monoiodotyrosine (MIT), and diiodotyrosine (DIT). The adjacent tyrosyl residues are then paired together and subsequently the entire complex re-enters the follicular cell by endocytosis. Proteolysis liberates triiodothyronine and thyroxine and they enter the blood stream. Of the hormones secreted from the gland, 80-90% is T4, and only about 10-20% is T3. The production of T3, and T4 is primarily regulated by thyroid-stimulating hormone (TSH) which is released by the anterior pituitary gland. The thyroid hormones provide negative feedback to the thyrotropes TSH and TRH; when the thyroid hormones are high, TSH production is suppressed, and when levels are low, TSH secretion is increased.

After secretion, there is a very small percentage of the thyroid hormones that travel freely in the blood and that are metabolically active. Most are bound to thyroxine-binding globulin (TBG), transthyretin, and albumin. They act upon their respective tissues by crossing the cell membrane and binding to intracellular nuclear thyroid hormone receptors, which bind with hormone response elements and transcription factors to modulate DNA transcription. This modulation is what drives protein synthesis within the target tissue to actively project its physiological function within on the tissue and body.

Calcitonin is secreted by the parafollicular cells which helps maintain calcium homeostasis. Calcitonin is produced in response to high blood calcium. This causes inhibition of the release of calcium from the bone by decreasing the activity of osteoclasts. Osteoclasts are cells which break down bone. Bone is constantly reabsorbed by osteoclasts and created by osteoblasts, so calcitonin is effectively stimulates movement of calcium into bone. The effects of calcitonin are opposite of those of the parathyroid hormone (PTH) produced by the parathyroid gland.

Function

The primary function of the thyroid gland is the production of the thyroid hormones that have downstream metabolic, cardiovascular, and developmental effects. The basal metabolic rate is increased which effects all tissues. Gut adsorption and motility is increased. The generation, uptake by cells and breakdown of glucose is increased. The thyroid hormones also increase the breakdown of fats which increases free fatty acids, but contrary to believe, thyroid hormones decrease cholesterol levels.

There is an increase in cardiac output, as well as rate of breathing, intake and consumption of oxygen and increase in oxidative respiration within the mitochondria. These factors combine increase vascular pressure and elevate the bodies temperature.

The thyroid hormones are important for normal development. The cells of the developing brain are a major target for the thyroid hormones. They play a crucial role in brain maturation during fetal development. The thyroid hormones also play a role in maintaining normal sexual function, circadian sleep rhythm, and thought patterns.

The overarching effect is an augmented flight-or-fight response. It increases the release of the catecholamines which drives sympathetic innervation.

Clinical Significance

Hyperthyroidism is an excessive production of the thyroid hormones, most commonly a result of Graves Disease. Graves disease, also known as toxic diffuse goiter is an autoimmune disease that results in an enlarged thyroid. The exact cause is unknown, however it appears to be a combination of both genetic and environmental factors. An antibody, called the thyroid-stimulating immunoglobulin (TSI) which mimics the effect of TSH. This causes an increased T3 and T4, and an increased radio iodine uptake. Laboratory tests will show a decreased level of TSH, because there is negative feedback on the pituitary, but because of the antibody, production of the thyroid hormones continuous. One of the classic findings of Graves disease is exophthalmos, which is bulging of the eyes. This is often accompanied by irritability, muscle weakness, sleeping problems, increased heart rate and blood pressure and unintentional weight loss. Patients may complain of being “hot” all the time, illustrating a poor tolerance of heat.

Hypothyroidism is an underactive thyroid gland which results in decreased secretion of thyroid hormones. One of the most common causes is an autoimmune disorder called Hashimotos thyroiditis or chronic lymphocytic thyroiditis. The disease is characterized by gradual destruction of the thyroid gland. There are various antibodies that have been identified targeting against thyroid peroxidase, thyroglobulin, and TSH receptors. There is activation of cytotoxic T-cells in response to a cell mediated immune response affected by helper T-cells that drives thymocyte destruction. Cytokine release recruits macrophages within the gland to further drive destruction. Early on in the disease there may be no clinical evidence or symptoms of Hashimotos, but as the disease progresses, so does the clinical presentation. The most common symptoms are fatigue, weight gain, feeling cold, joint and muscle pain, depression, and bradycardia. This disease is about seven times more common in women than in men. Diagnosis is from TSH and T4 levels, imaging, along with other clinical symptoms. The thyroid gland may become firm, large and lobulated. There is lymphocytic infiltration and fibrosis that is seen.

These are not all the causes of hyper/hypothyroidism, but these are the most common, and in most cases, the most severe.

 

 

 

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Bloods Journey Through the Heart

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The heart drives the circulatory system as it pushes blood through an intricate system of blood vessels including arteries, capillaries, and veins. Blood is essential as it carries oxygenated blood from the lungs to the tissues and transports waste products like carbon dioxide away where it is expelled from the body.

The heart is hollow and its strong musculature allows it to contract to pump blood to the arteries to be delivered to the rest of the body. One of the most fundamental aspects of the circulatory system is that veins deliver deoxygenated blood to the heart and arteries deliver oxygenated blood away from the heart. Within the heart there are four chambers; right atrium and ventricle, left atrium and left ventricle. These chambers are separated by valves. There are four valves that separate the different chambers; the mitral valve, tricuspid valve, aortic valve, and the pulmonary valve. The tricuspid valve separates the right atrium and right ventricle. The mitral valve separates the left atrium and left ventricle. The aortic valve is what separates the left ventricle and the aorta. The pulmonary valve separates the right ventricle and the pulmonary artery. Valves work to allow blood flow through into the following chamber while not allowing blood to flow back through. A reverse in the blood flow is called regurgitation and is a serious medical condition that should be addressed. Each valve has two cusps with the exception of the tricuspid valve as it has three.

The heart works like machine constantly pumping blood that is fed to it. There are two venous systems that dump into the right atrium; the inferior vena cava and the superior vena cava. The inferior vena cava carries deoxygenated blood from the lower body back to the heart and conversely the superior vena cava carries deoxygenated blood back to the heart from the upper body and head. The right atrium contracts and pumps blood through the tricuspid valve into the right ventricle. When the right ventricle is filled the tricuspid valve closes off preventing regurgitation.

The right ventricle then contracts that pushes blood through the pulmonary valve and into the pulmonary artery to be carried to the lungs. once inside the lungs blood flows the tiny capillary vessels in the lungs where there is exchange of carbon dioxide and oxygen. Oxygen from the alveolar air sacs diffuses through the capillaries into the blood while at the same time carbon dioxide passes from the blood into the air sacs. The carbon dioxide is then exhaled as one respirates normally. The blood is now oxygenated and travels back through the pulmonary veins where it dumps into the left atrium.

As the left atrium contracts blood is pushed through the mitral valve into the left ventricle. When the ventricle has reached capacity the mitral valve closes, again blocking regurgitation. The left ventricle then contracts and the blood is pushed through the aortic valve into the aorta and the coronary arteries. The aorta supplies the rest of the body with oxygenated blood. The coronary arteries is actually what supplies the heart with oxygen to keep the tissue alive.

There is a right coronary artery and a left coronary artery. The right coronary artery supplies the right atrium and right ventricle. It branches into the posterior descending artery. The left main coronary artery branches into the circumflex artery and the left anterior descending artery. It supplies oxygenated blood to the left atrium and the left ventricle.