USMLE Internal Medicine Review 11 07 Pathogenesis of Graves

USMLE Internal Medicine Review 11 07 Pathogenesis of Graves

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Let’s start our USMLE Review with Hypothyroidism and Hyperthyroidism from the Gold Standard USMLE Foundations of Medicine Audio Review program.

 

Play USMLE Audio MP3 11 07 Pathogenesis of Graves Below

 

Begin 11 07 Pathogenesis of Graves Transcription

In the pathogenesis of Graves’ disease T cell lymphocyte become sensitive to antigens within the thyroid gland and stimulate which other lymphocytes to synthesize antibodies to these antigens?

  • B cell lymphocytes are stimulated to synthesize antigen-antibodies.

Lymphocytes account for about what percentage of the total white blood cell count?

  • Lymphocytes normally make up about 2% of total white blood cells but increase in response to infection.

T cells are lymphocytes which have circulated through the thymus gland to become what?

  • To become thymocytes.

Why are T cells also sometimes referred to as killer cells? Pause the tape for this.

  • T cells secrete special chemical compounds which assist B cells in destroying foreign protein. T cells also play a significant role in the body’s resistance to the growth and spread of cancer cells.

And what is the primary role of B cell lymphocytes?

  • Function of B cells is to seek out, identify and bind with specific intruders, allergens or antigens.

Once activated to where do B cells travel?

  • Once activated B cell lymphocytes travel to the spleen and lymph nodes where they rapidly produce cells that create and secrete large amounts of antibody.

Student doctor please pause the tape and summarize the role of T and B cell lymphocytes in the pathogenesis of Graves’ disease.

  • In the pathogenesis of Graves’ disease T cell lymphocytes become sensitive to antigens within the thyroid gland and stimulate B cell lymphocytes to synthesize antibodies to these antigens. T cells sometimes called killer cells due to their propensity to destroy foreign proteins are lymphocytes which have circulated though the thymus to become thymocytes. They’re also important in the body’s resistance to the growth and spread on cancer. B cell lymphocytes seek out, identify, and bind with specific allergenic or antigenic intruders. Once activated, B cell lymphocytes travel to the spleen and lymph nodes where they rapidly produce cells which create and secrete large amounts of antibody.

One of the antibodies synthesized by B cells is directed against the TSH receptor site in the thyroid cell membrane and can stimulate thyroid cells to greater growth and function.

What is this antibody?

  • TSH-R antibody.

Its presence is correlated with active Graves’ disease and with relapse. While it is unclear what exactly triggers an acute episode, we’ll list 5 factors which may insight the immune response of Graves’ disease.

First is pregnancy, especially in which phase?

  • The post-partum phase.

Second, excess of which trace element?

  • Excess Iodide, 80% of which is located in the thyroid gland.

Third, therapy with which anti-manic agent?

  • Lithium therapy.

Fourth, which two type of infections?

  • Bacterial and viral infections.

And fifth, withdrawal from which type of hormonal agent related to the pituitary gland?

  • This hormone aids carbohydrate processing among other functions. Glucocorticoid withdrawal. It’s also been postulated that stress can trigger an episode of Graves’ disease, but the evidence for this is not particularly solid.

Student doctor please pause the tape and repeat five factors which may insight the immune response of Graves’ disease.

  • Factors which may insight the immune response of Graves’ disease include pregnancy, especially in the postpartum phase, excess iodide, lithium therapy, bacterial or viral infections, and glucocorticoid withdrawal. Stress also appears to be a factor but the evidence is unsubstantiated.

Ophthalmopathy is a condition often associated with hyperthyroidism and thyrotoxicosis. Its pathogenesis appears to involve cytotoxic lymphocytes, killer cells, and cytotoxic antibodies sensitized to which common antigen?

  • The common antigen is either a 64kDa antigen related to thyroglobulin or to TSH-R.

This common antigen is located in which three structures? Please pause the tape and list them.

  • The antigen common to the cytotoxic lymphocytes and antibodies in the pathogenesis of ophthalmopathy is found in orbital fibroblast, orbital muscle, and thyroid tissue.

Cytokines from the sensitized lymphocytes cause inflammation of the orbital fibroblasts and which other orbital inflammatory condition?

  • Orbital myositis.

The inflammation results mainly in swollen orbital muscles and two other conditions. First, a bulging of the globes?

  • Proptosis.

Second, the term for double vision?

  • Diplopia. Redness, congestion, and conjunctival and periorbital edema may also be present in ophthalmopathy.

Student doctor please pause the tape and summarize the pathogenesis of ophthalmopathy.

  • Ophthalmopathy is a condition often associated with hyperthyroidism and toxicosis. Its pathogenesis appears to involve cytotoxic lymphocytes or killer cells and cytotoxic antibodies sensitized to a common antigen, either a 64kDa antigen related to thyroglobulin or possibly to TSH-R. A common antigen is found in orbital fibroblasts, orbital muscle and thyroid tissue. Cytokines from the sensitized lymphocytes cause inflammation of orbital fibroblasts and orbital myositis, resulting in swollen orbital muscles, proptosis of the globes, and diplopia. Redness, congestion, and conjunctival and periorbital edema may also be present with ophthalmopathy.

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