Unit 10: Graves disease (inputs and outputs)

Question 1

Diagram of thyroid hormones production in thyroid gland

Answer 1

Question 2

How does TSH increase thyroid hormone secretion

Answer 2

Increased proteolysis of thryoglobin stored in follicles to release T3/4
Increased activity of iodide pump to increase idodie trapping on colloid
Increased iodination of tyrosine
Increased size and activity of thyroid cells - transition from simple cuboidal to columanr and more infolding.
Increased number of thyroid cells

Question 3

What other factors can regulate thyroid hormone secretion?

Answer 3

Influences of negative feedback within the hypothalamus, pituitary, thyroid axis
Cold temperature - activates hypothalamus
Fasting - reduce leptin levels - inhibit TRH neurons leading to less secretion
Emotional - anxiety and excitement - activate SNS and inhibit thyroid hormones secretion

Question 4

How does thyroid hormone have an effect at its receptor?

Answer 4

Are amine hormones as based on a tyrosine residue. Are hydrophobic in nature, travel through the blood bound to protein called TBG. At the target cell diffuse through the cell membrane or enter by carrier mediated transport to act on nuclear receptors. T4 must be converted to T3 by deiodinase enzyme. Nuclear receptor is a heterodimer of retinoid X receptor and Thyroid hormone receptor, T3 and T4 bind directly to thyroid hormone receptor. Receptor is found on thyroid response element on DNA, then acts as a transcription factor for the production of multiple mRNAs for specific proteins.

Question 5

What are the causes of heart palpitations in hyperthyroidism?

Answer 5

1. Thyroid hormone acts on heart to increase beta adrenergic receptor expression - leads to increased sensitivity to catecholamines
   Which increase heart rate and contractility.
2. Worsened as build up a waste products and increased oxygen consumption lead to vasodilation in bv, triggers RAAS activation and effective arterial volume decreases - blood volume increases as consequence, cardiac output increases.

Question 6

How does hyperthyroidism cause an increase in body temperature?

Answer 6

1.Increase expression of UCP1 in brown adipose tissue – increase heat generation - by decoupling H+ transport and ATP synthase.

2. Increased futile cycle function - increased Na+ K+ pump, increased gluconeogneic enzymes, increased enzymes in fat and protein metabolism.

Question 7

What causes a loss of muscle mass in hyperthyroidism?

Answer 7

Originally a small spike in thyroid hormones may benefit thyroid function.
However, a prolonged spike in thyroid hormones leads to increased protein catabolism, leading to a loss of actin and mysoin, reduce cross bridge cycle formation - leads to reduced muscle tension - loss of muscle mass.

Increased protein catabolism as increased basal metabolic rate - increased reliance on alanine (protein) for ATP production.
Increased transcription/translation of enzymes needed for protein catabolism.

Question 8

What is the hereditary link behind Graves disease?

Answer 8

Having an immediate family member with an autoimmune disease increases the risk that you will also suffer from an autoimmune disease.

Question 9

How does iodide concentration effect thyroid gland function?

Answer 9

Small increase/decrease leads to a small increase/decrease in thyroid gland function
However an excessive decrease in iodide can stimulate thyroid gland - release of T3 and T4, for deiodination, or during proteolysis some iodide may be recycled to increase levels

An extreme increase in iodide inhibits the thyroid gland - by Woldd-Chalkoff effect - prevents iodindation of thyroglobulin. ***

Question 10

What is the pathophysiology of Graves disease?

Answer 10

TSHR peptide is engulfed by a APC and presented to a T cell, leads to B cell then plasma cell activation
TSHR autoantibodies are produced - known as TSI or TSAb
These mimic TSH by bind to TSHR causing increased secretion of T3 and T4
Leads to negative feedback decreases TSH from pituitary but no effect on TSI which continues to accumulate leading to increased T3 and T4 secretion from thyroid and decreased TSH - this is a primary hyperthyroidism

Question 11

What is the mechanism of action of proponolol?

Answer 11

Chemistry: structural analogue of adrenaline
Pharamcology: Binds to beta adrenergic receptors (GPCR) and acts as an antagonist - stops adrenaline from binding and having an effect. GPCR remains bound to GDP so remainsin inactive
This prevents the activation of the second messenger system mediated by adenylyl cyclase.

Inhibit Beta 1 receptors - found in heart - reduce heart rate and reduce heart rate contractility

Inhibit betta 2 receptors - found in smooth muscle such as bronchi - causes vasoconstriction.

Question 12

What are the common causes of
primary hyperthyroidism?

Answer 12

Graves disease - diffuse toxic adenoma
Toxic adenoma
Toxic mulitnodular goiter
Thyroid cancer
Drugs (iodine excess)

Question 13

What are the common causes of seocndary hyperthyroidism?

Answer 13

Pituitary adenoma
Gestational thyrotoxicosis

Question 14

What is the mechanism of action of carbimazole?

Answer 14

Metabolised to methimazole (active)
Inhibits peroxidase enzyme (TPO)
THis inhibits multiple stages of thyroid hormone production including:
- oxidising iodide to iodine
- adding idodine to thyroglobulin molecule
- coupling of DIT and MIT to form T3 and T4.

Question 15

What are the implications of long-term carbimazole use?

Answer 15

Bone marrow suppression - lead to agranulocytosis and neutropenia , compromised immunity leads to increased risk of sepsis and opportunistic infections.

Congenital abnormalities in developing foetus (must be prescribed contraceptives alongside)

Acute pancreatitis

Question 16

Why do people relapse after carbimazole stopped?

Answer 16

Immune system recovers - white blood cell production increases as bone marrow is no longer suppressed.
TSI is still produced - targets TSHR in thyroid to produce thyroid hormones.
Takes time for thyroid hormones to become too high
TPO is no longer inhibited for thyroid hormone production can continue.
Around 50% of patients relapse

Question 17

Mechanisms of radioiodine treatment

Answer 17

Radioactive iodine capusle is given. Is rapidly absorbed and distributed within the ECF of the body.
Sodium and iodide symporter concentrate iodine at the thyroid.
The majority travels to the thyroid gland and is taken up by follicular cells as iodine is needed to produce thyroid hormones.
Rest is excreted in urine
Gives of beta and gamma rays which reduce the activity of the thyroid gland - by destroying thyroid tissue.
Should be reseen in 6 weeks to check thyroid hormone levels.

Question 18

What is the mechanism of levothyroxine treatment?

Answer 18

is a synthetic T4 (isomer of T4), that mimics the activity of T4 and can be converted to T3 by deiodinase in the periphery.
Is given in the liquid or tablet form 40-80% is absorbed in the GIT - amount decreases with age.
Dosage is dependent on patient’s age and weight .
Give synthetic T4 rather than T3 as has a longer half life (7 days v 1day)

Question 19

What are some reasons why thyroidectomy may not be considered?

Answer 19

• Require life long levothyroxine treatment afterwards
• Risk of damage to parathyroid gland - affect calcium levels in the blood
• Risk of damage to recurrent laryngeal nerve - hoarse voice or vocal cord paralysis.

Question 20

What is a triage system and why is it used?

Answer 20

Allows patients to be sorted and organised into tiers based on clinical need with patients with greater health needs that are more emergency to be seen earlier to by the relevant member of staff.
Triage nurse allows early assessment of patients by qualified staff then referall to best qualified member of staff or waiting list.
Ensures patients receive help in the appropriate amount of time
Ensure patient sees the relevant member of staff
Ensures best use of healthcare staff time and resources.

Question 21

What blood tests are commonly used to diagnose thyroid problems?

Answer 21

Thyroid Function test - Free T3 and Free T4 (thyroxine), TSH levels
May also test for thyroid antibody (TSI or TPO auto-antibody) is suspect autoimmune disease

Question 22

Why is monitoring needed in thyroid disease treatment?

Answer 22

Ensure treatment is not under or over effective - ensures thyroid hormones remain of physiological range
Monitor for side effects of treatments - bone marrow suppresion in carbimzole treatment
Monitor to ensure symptoms are reduced - ensures treatment and diagnosis are correct.

Question 23

How can having a chronic illness impact on the doctor-patient relationship?

Answer 23

Patients have an increased knowledge of their condition and the implication on their life - more active on shared decision making often have more power in the consultation
Potentially more aggression as patient feels they have been constantly handed over in medical care and not yet received an effective cure
Trust - repeated interaction build up trust and rapport
NHS long term goals - encourages patient to self manage conditions and take responsibility for their health - patient may feel more in control or responsible for health than doctor (may or may not be a good thing).

Question 24

How do patients feel when treatment is ineffective?

Answer 24

Loss of self identity - unsure of own health and responsibility, loss of enjoyment in every day activity
Reduced quality of life - tiredn
Patients often fear they will be accused for being dramatic of symptoms, in long term illness loose support from family and friends (forget about illness) _ parsons sick role
Stress of relationships - emotional changes and demands
Embarassed by visible changes in thyroid gland or scar from surgery.

Question 25

What are the different types of doctor-patient relationships?

Answer 25

1. default
2. paternalistic
3. Consumerist
4. Mutualistic
5. Conflict

Question 26

What are the effects on the body during exercise?

Answer 26

Increased CO due to doubling stroke volume and increase in HR.

Increased diffusion, more uniform lung perfusion, recruitment of dormant capillaries and bronchodilation

Acid base mechanisms are usually maintained during aerobic exercise by increased ventilation, but metabolic acidosis may develop if buffering mechanisms are unable to cope with extra CO2 and lactic acid

Question 27

What are the effects of exercise of SV?

Answer 27

Increased venous return during exercise, leads to greater EDV in both the right and left ventriciles. This leads to greater stretch of the ventricular walls, which leads to greater contracility of the ventricular walls (frank starling mechanism). This leads to a greater stroke volume leading to increased cardiac output.

Question 28

What are the effects of exercise on nervous stimulation to the body?

Answer 28

Stimulate the release of catecholamines such as epinephrine which binds to beta adrenergic recptors in the heart. INcreased contractility and heart rate. Increased SV.

Mediatored through chemoreceptors

Question 29

What are the effects of exercise on afterload?

Answer 29

Decreased afterload: peripheral blood vessels in the skeletal muscle dilate, reducing systemic vascular resistance, makes it easier for blood to eject in systemic circulation. THis increases the ejection fraction and further increases stroke volume.

Question 30

What are the effects of exercise on myocardial performance?

Answer 30

Improved myocardiac performance: exercise training leads to structural and functional adapations of the myocardium, increased left ventricular wall thickness and imporved contractility, leads to greater cardiac output.

Question 31

What are the effects of cardio on health?

Answer 31

Decreases resting HR and strengths heart muscle. Promotes heart and lung health. Burns more calories.

Question 32

What are the effects of weight training on health?

Answer 32

Increases strength, boost metabolism (as more active skeletal muscle), increase muscle mass, prevent obesity and limit bone loss (tendons apply tension to bone which stimulates bones production).

Question 33

What are the effects of exercise on HR?

Answer 33

Periphery chemoreceptors (aortic body and carotid body) detect change in concentration of CO2 in the blood.

The chemoreceptor in the Aortic bodies (Via Vagus) and carotid body (Via glossopharyngeal) send the signal to the medulla oblongata (regulation of HR and BP).

Activation of the cardioacceleratory center sends sympathetic input to the heart via pre then postganglionic fibres from the superficial and deep cardiac plexus (which innervates the SAN and AVN) triggered by stress initiating fight and flight response.

The postganglionic fibres release noradrenaline (neurotransmitter), which act on B1 adrenoreceptors which increases Ca2+ conc which increases HR.

This increases the heart rate (a positive chronotropic effect), as well as the force of contraction (positive inotropic effect).

Question 34

What are the effects of regular exercise on the body?

Answer 34

Cardiac muscle becomes thicker and stronger, ventricles increase in size (cardiac hypertrophy) – stroke volume increases, greater transport of nutrients and oxygen.

Bradycardia – decreases resting heart rate. As stroke volume increased but CO demand at rest is the same

Question 35

What are the effects of maximal work output with exercise training?

Answer 35

Increased CO and stroke volume – lead to increased VO2 max as more efficient oxygen transport in the blood.
Larger diameter of capillaries and vasodilation of blood vessels to heart and lungs

Question 36

What limits maximum athletic performance?

Answer 36

Age – Maximal heart rate tends to be 220-age, due to decrease in pacemaker cells, decreases elasticity of arteries. VO2 max peaks at age 18-25 when lungs are fully developed then decliens by 1% a year. Loss of muscle mass and declining HR.

Gender – females lower VO2 max – women tend to have smaller hearts and smaller lungs,

Genetics – effetcs type of muscle fibres in the heart, size of body (heart and lungs),

Temperature – hot and humid conditions decrease VO2 max, body requires energy to decrease core body temperature, cause spike in heart rate and increased metabolic rate.

Question 37

What is the thermoregulatory response to exercise?

Answer 37

Temperature increases during exercise due to increased workload of skeletal muscle - hydrolysis of ATP.

Response:
Ach release from sympathetic efferent activates eccrine sweat glands - heat loss by evaporation.
Sympathetic tone decreases on vascular smooth muscle to cause vasodilation and increase blood flow to the skin - heat loss by radiation