AF Flashcards
what is meant by AF?
Irregular heart beat from the atria of the heart resulting in ECG changes with an irregulary irregular heart rhythm with loss of p waves.
Have to think of which kind of AF the patient has.
what is meant by radial pulse?
A normal resting heart rate for adults is between 60-100 bpm and regular pattern of beats.
The radial pulse is felt on the wrist just under the thumb.
how would you diagnose AF?
-initially you would do a pulse check-radial pulse and see what the resting heart rate is.
A patient may have AF but there heart rate may still be within the normal resting heart rate what differs is the regularity of the heart beats.
how would you detect AF from an ECG?
- This is called a 12 lead ECG.
- Or you could do a single lead ECG but have to monitor a long enough time period to notice any changes in heartbeat.
- why is AF important to diagnose?
• Patient may be symptomatic (or not)
• There may be a reason or a treatable underlying cause
• Atrial fibrillation increases risk of stroke x 5
• Untreated patients with AF who have a stroke tend to have more fatal or debilitating strokes.
why is there an increase in risk of stroke for people who have AF?
why is there an increase in risk of stroke for people who have AF?
- Due to the fact that there is not enough blood flowing smoothly around in the atrium as the atrium is just fibrillating and has a tendency to clot formation in the left atrium (left atrium appendage)
- If the clot breaks off will travel around the circulation and can block arteries leading to an ischemic stroke.
what are the 3 stroke risk assessment for AF?
• Stroke Risk Assessment
– Estimation of the risk of stroke or systemic blood clot for a patient in AF in the next year
– And the standard treatment of anti- coagulants
• Bleeding Risk Assessment
– Estimation of the risk of bleeding for a patient in AF in the next year
– To monitor the risks of bleeding as anti-coagulation medication side effect is bleeding so important to monitor the patient who has AF to get the right balance
• Modifiable Risk Factor
–A risk factor that can be altered by a change in patient behaviour or by medical intervention
what are the 2 different options of treating AF?
- Rate control or Rhythm control
- Or controlling the rate of the arrythmia so that the patient is less symptomatic and so doesn’t do damage to the heart of the patient long term.
how do you reduce the risks associated with AF?
isk assessment and appropriate medication (anticoagulation)
• Management of co-morbidities- the patient has high blood pressure so we need to ensure that this is controlled as well.
what other considerations do you need to consider when treating someone who has AF?
- Patient preference: risk vs benefit
- Age
- Co-morbidities
- Renal / hepatic function
- Current drug therapy
- Allergies
- Family history/Social history
- Cost?
what is different on a ECG for someone who has AF?
- The ECG reading is not normal and is very irregular
- The AV node passes electrical signal down to the heart for it to contract.
- Irregular / absent P waves
- Usually originates from left atrium (pulmonary vein)
o Very common in elderly (20-55% of population > age 70)
why does pooling of blood occurs in people who have AF?
- Reduced atrial contraction so doesn’t contract as well as they should so there is a pooling of blood which sits in the atria, therefore risk of thrombus / embolic event where the clot may break of and travel through the blood stream where it can have a stroke or travel to the lungs and have an embolic effect or can get DVT
how is the QoL impaired for people who have AF?
QoL is impaired in all areas such as social, mental and physical functioning. AF is associated with significantly reduced exercise capacity as it causes them breathlessness. the impairment is worse for those who have HF or coronary heart disease
what is the stats for people who have AF?
- Every decade you are there is a risk factor by x2
- If you have a history of hypertension the estimated risk goes up by x1.5 or if your blood pressure is higher than 140mmHg.
- If you are obese increases the risk however the patient is malnourished so there is a potential risk
- Alcohol increases the risk
- Patient is considered a high risk person.
how does an underlying thyroid function causes a risk of AF?
the risk of AF is closely associated with underlying thyroid function. hyperthyroidism is associated with an increase risk of AF. the increased risk of AF increases with decreasing levels of thyroid stimulating hormone
how does the thyroid work
- Here is the hypothalamus and that secretes thyrotropin releasing hormone which encourages the increase of thyrotropin
- Then acts on the thyroid gland and cause the anterior pituitary gland to release the thyroid stimulating hormone which will go and work on the thyroid gland causing that to release T-3 for increased metabolism and growth
- The hormone will have a negative feedback effect both on the anterior pituitary gland and also back on the hypothalamus
- As the levels starts to rise, it will reduce how much TRH is released which will reduce how much TSH is released which will reduce how much T-3/T-4 is released.
- Will go back to the pituitary gland if there is not enough to release more and will feed back to the hypothalamus
how do you do a thyroid examination
- Get behind the patient find the thyroid cartilage , crico- thyroid membrane , then the first two rings of the trachea but fingers over the midline over the first two rings of the trachea this is where the thyroid lies
- Flatten fingers slide fingers slightly to the side and ask the patient to swallow and look if one hand went disproportion to another
- Push the thyroid gland with one hand and with the other hand rub with the other hand and do it vice versa.
- Do a lymph examination and see the hands for sweats and tremors.
- The thyroid doesn’t lie in the thyroid cartilage.
where is the thyroid gland located and what is it made up of?
- The thyroid gland is located at the back and is made up of cross section of a slice of a tissue within the structure of a thyroid gland.
- It is made up of follicles, consisting more of a mono layer of epithelial cells including a large core of viscous homogenous colloid.
- The yellow stuff is the colloid which is well supplied with blood which are the red structures
- These colloids acts as reservoirs of thyroid hormone which sits there waiting to be used.
- Thyroid hormone is released early in the morning for that day and the requirements is dependent on what was used in the previous day
what are the thyroid hormones made
- Thyroid gland produces thyroid hormones which regulates many metabolic processes in our body.
- The follicle cells produces the thyroid hormone (T-3 and T-4).
- T-3 and T-4 stimulates metabolic processes
- The hypothalamus consists of the inferior and anterior pituitary gland
- The hypothalamus secreted thyroid releasing hormone which causes the anterior pituitary gland to secrete thyroid stimulating hormone which causes the thyroid hormone to produce T-3 and T-4 which targets specific cells.
- There is a negative feedback loop where if there was too much production of T-3 and T-4 will inhibit the hypothalamus from secreting more thyroid releasing hormone.
How does the thyroid stimulating hormone thyroid hormone production?
- In the membrane of the thyroid there is G-protein coupled receptor which gets activated once bound to thyroid stimulating hormone.
- GDP is converted to GTP which increases cAMP which therefore increases the production of thyroid hormones.
how are thyroid hormones made?
- There is the follicular cells and the colloid inside if it. Surrounding it is blood vessels.
- There are many cations and anions in the bloodstream such as sodium, iodine and potassium
- Inside the follicles there is endoplasmic reticulum’s which synthesises thyroglobulin which gets sent and package up by the Golgi apparatus into the colloid
- The 3rd globulin is a carbon chain which consists of lots of tyrosine molecules attached to it. In the bloodstream , there are iodine ions and to synthesise thyroid hormones we need iodide.
- In the bloodstream there is a transporter called the sodium and iodide symporter which transports a sodium and also pumps up iodide at the same time .
- Iodide is now in the follicular cells. Sodium can go back out when potassium gets pumped back in and gets exchanged for sodium.
- The iodide in the follicular cells needs to be transported into the colloid because synthesis of thyroid hormones occurs in the colloid. It does this by a transporter called a pendrin which transports iodide (a negative charged) and at the same time it is exchanged for a chlorine.
- The iodide is in the colloid now and there is an enzyme in the colloid called peroxidase which oxidise the iodide to iodine.
- Iodine will then bind to the tyrosine rings in the thyroid globulin and one iodine can bind to a tyrosine (called MIT) or 2 iodine can bind to a tyrosine ring (called DIT).
- DIT-DIT and MIT-MIT and MIT-DIT can form ester bonds with each other so 2 tyrosine’s will bind together. These will form T-3 and T-4 hormones.
- MIT-DIT, T-3 and T-4 can still be part of the thyroid globulin structure which will all get packaged up by the pinocytosis into the follicular cells.
- In the follicular cells there are lysosomes which will bind to the endosomes containing the thyroid globulin and will release the tyrosine molecules from the whole structure.
- The lysosomes will break things apart because it is acidic which causes the T-3 and T-4 to separate and the MIT and DIT if present in the endosome, will be deionised to release the tyrosine and release the iodide molecules.
- T-3 and T-4 are lipid hormones it cannot travel through the bloodstream by themselves so they bind to these thyroid-binding proteins which allows them to be transported the bod to various cells and tissues to initiate the metabolic effects
- There is more T-4 secreted by the follicular cells than the T-3 HOWEVER T-3 is x10 more active so when they arrive at the target cells, T-4 is converted to T-3
- T-3 and T-4 can pass out of the membrane because they are lipid soluble and go into the skeletal muscle. The hormones will enter the nucleus which contains 2 receptors which initiates transcription for thyroid hormone responses ( thyroid hormone receptor and retinoid X receptor)
- When T-3 and T-4 binds to the receptors, it will initiate gene transcription for mRNAs that will promote the thyroid hormone response.
what is the synthesis and chemistry of thyroid hormones
The primary hormones secreted by the thyroid gland are tri-iodothyronine (T3), tetraiodothyronine (T4, Thyroxine) and calcitonin.
Calcitonin is concerned with calcium homeostasis, is secreted independently of the other thyroid hormones,
what occurs in the first stage of thyroid hormone synthesis
- uptake of plasma iodine follicle cells,
Iodine uptake must occur against a concentration gradient (normally about 25:1) so it is an energy -dependent process. Iodine is captured from the blood and moved to the lumen by two transporters: the sodium iodine symporter (NIS) located at the basolateral surface of the thyrocyte. The energy being provided by sodium potassium ATPase pump and Pendrin (PDS), an iodine/chloride Porter in the apical membranes. Uptake Is rapid (labelled iodine 125 I is found in the Lumen within 40 seconds of intravenous injection. Numerous mutations have been discovered in the NIS and PDS genes and this contributed towards thyroid disease).
what occurs in the second stage of thyroid hormone synthesis?
oxidation of iodine and iodination of tyrosine residues of thyroglobulin.
the oxidation of iodine and its incorporation into thyroglobulin is catalyzed by thyroperoxidase, an enzyme situated in the inner surface of the cell and the interface with the colloid. The reaction requires the presence of hydrogen peroxide (H202) is an oxidizing agent. Iodination occurs after the tyrosine has been incorporated into the thyroglobulin. Tyrosine residues are iodinated first position three on the ring, forming monoiodotyrosine (MIT) and then, in some molecules, at position five is well, following thy di-iodotyrosine (DIT).
While still incorporated into thyroglobulin, these molecules are then coupled in pairs, either MIT with DIT to form T3, or two DIT molecules to form T4. The mechanism for coupling is believed involved in peroxidase system similar to that involved in iodination. About 1/5 of the tyrosine residues in thyroglobulin are iodinated in this way. The iodinated thyroglobulin of the thyroid forms a large store of thyroid hormone within the follicle, with a relatively slow turnover. This is in contrast to some other endocrine secretions (e.g. adrenal cortex hormones), which are not stored but synthesized and released as required. The reaction requires hydrogen peroxide which is an anti-oxidizing agent
what occurs in the 3rd stage of thyroid hormone synthesis
The thyroglobulin molecule is taken up into the follicular cell by endocytosis. In the endocytic vesicles then fuse with lysosomes and proteolytic enzymes act of thyroglobulin, releasing T4 and T3 to be secreted into the plasma. The surplus MIT and DIT, which are released at the same time, are scavenged by the cells and the iodine is removed enzymatically and reused.
what catalyses the first stage of thyroid hormone synthesis
The initial steps in thyroid hormone synthesis (iodide incorporation into tyrosine residues of thyroglobulin and covalent binding of the residues) are catalyzed by haeme-containing peroxidases. Theoretically, severe iron deficiency could lower thyroperoxidase activity and interfere with thyroid hormone synthesis. Animal studies have documented that weanling rats fed iron-deficient diets have significantly lower T3 and T4 compared to rats fed adequate iron
what are the T3 and T4 hormones
- T3 – triiodothyronine, T4 - thyroxine
thyroxine (T4) and triiodothyronine (T3) are produced from thyroid follicular cells within the thyroid gland, a process regulated by the thyroid-stimulating hormone secreted by the anterior pituitary gland.
Linking two moieties of DIT produces T4.
Combining one particle of MIT and one particle of DIT produces T3.
how are MIT and DIT degenerated in the synthesis of thyroid hormone secretion
MIT and DIT are rapidly degraded by halogenases to free the iodide, which is then re-utilised by combination with thyroglobulin.
The T3 and T4 leave the follicular cells and enter the blood stream for distribution to the target tissues.
Approximately 95% of the thyroid hormone leaving the thyroid gland is in the form of T4 not active but biologically stable (thyroxine).
which thyroid hormones is more biologically active
- Within the target tissues deiodinase enzymes convert the T4 to either T3 (80%) or reverse-T3 (20%).
- T3 has a biological activity approximately 40 times greater than that of T4, whilst reverse-T3 is biologically inactive.
- Up to 90% of the biologically active thyroid hormone within the cell is in the form of T3.
- The plasma half-life of T4 is 6 - 8 days whilst that of T3 is one day.
describe the negative feedback loop of thyroid hormone secretion?
- Thyrotrophin releasing hormone (TRH), released from the hypothalamus in response to various stimuli, releases thyroid stimulating hormone (TSH also known as Thyrotrophin) from the anterior pituitary.
- The production of TSH is also regulated by a negative feedback effect of thyroid hormones on the anterior pituitary gland
- T3 is more active than T4 in this respect
- Somatostatin (also known as growth hormone-inhibiting hormone (GHIH)) also reduces basal TSH release.
- The other main factor influencing thyroid function is the plasma iodine concentration. About 100 nmol of T4 is on the site daily, necessitating uptake by the gland of approximately 500 nmol iodine each day (equivalent 70 µg of iodine). A reduced iodine intake, with reduced plasma iodine concentration, will result in a decrease of hormone production and an increase in TSH secretion. An increase plasma iodine has the opposite effect.
what is meant by the thyrotropin releasing hormone
Thyrotropin-releasing hormone (TRH), is produced by neurons in the hypothalamus, that stimulates the release of thyroid-stimulating hormone (TSH) and prolactin from the anterior pituitary.
Thyroid-Stimulating Hormone (TSH)
Thyroid stimulating hormone is produced by the pituitary gland. Its role is to regulate the production of hormones by the thyroid gland.
Thyroid-stimulating hormone (TSH) levels test
Thyroid function test, looks at levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) in the blood.
what is the mechanism of thyroid hormone action
Thyroid hormones are insoluble in water, therefore are transported in blood bound to plasma proteins usually albumin which is the rate controlling step.
The nutritional value will have an effect on the albumin levels ,patient is 50kg so she may not be getting enough protein so her plasma and albumin levels will be low
Over 99% of the circulating thyroid hormones are protein-bound:
• the majority ( approximately 75%) of T4 binding is to thyronine-binding globulin (TBG). If you are malnourished, the circulating thyroid levels goes down.
• 15-20% is bound to thyroxine-binding pre-albumin (TBPA)
• 5-10% is bound to albumin.
Only free (unbound) hormone is biologically active
describe the receptors of the thyroid hormone
The receptors for the thyroid hormones are intracellular, more specifically nuclear.
- That hormone needs to get inside the cell before it binds with an appropriate receptor
- Because Thyroid hormones influence gene transcription and thus protein synthesis;
what are the main biological effects of thyroid hormones
- increased in carb metabolism
- increased in the synthesis, metabolism and degradation of lipids
increased protein synthesis
how does the thyroid hormone have an effect in metabolism
the thyroid hormone produces a general increase in the metabolism of carbs, fats and proteins and regulates the processes and most issue by controlling the activity of some of the enzymes
however most effects are brought about in conjunction with other hormones such as insulin gucagon, corticosteroids.
there is an increase in oxygen consumption and heat production which manifests as an increase measured basal metabolic rate
the administration will result in augmented cardiac rate and output and increased tendency for AF
how does the thyroid hormone have effects on growth and development
the TH have a large effect on growth because of the actions of cells and indirectly influencing growth hormone production and potentiating its effects on its target tissue
the thyroid hormone is important for a normal response to parathyroid hormone and calcitonin as well as skeletal development
thyroid hormone is also important for normal growth and maturation of the CNS.
what is the mechanism of thyroid hormone action
- each cell at a cellular level, the mitochondria is working a bit harder .
- all carbohydrates metabolic increase so glycogenesis occurs in the muscle tissue and there will be effects in insulin
- this will affect patients w diabetes. If the patient was overweight, if you give her thyroid hormone and she was taking insulin, there will be a greater effect.
- Can also have an effect on catecholamines such as adrenaline, noradrenaline and the increase in glucose absorption in the GI tract
what is the pharmacological link between HYPERthyroidism and AF?
- In normal cardiac function, The Ca2+ is released by the sarcoplasmic reticulum which slows down the repolarisation and we get a plateau phase.
- Then the Ca2+ re-enters the sarcoplasmic reticulum causing the contraction of cardiac tissue so you get the big spike.
- This normal functioning goes wrong in hyperthyroidism.
- In hyperthyroidism, we have an increase in T3 which are biologically active.
- In cardiomyocytes, cellular Ca2+ storage capacity is increased by thyroid hormone . Effects of thyroid hormone on Ca21 handling in cultured chick ventricular cells. Modulation of SERCA2 expression by thyroid hormone and norepinephrine in cardiocytes: role of contractility.
- This results in increased outward currents and decreased inward currents => shorter Action Potential (AP) duration => atrial fibrillation
describe the APD cardiac action potentail in hyperthyroidism
- Pathogenies of AF in hyperthyroidism which is mediated by the effects of T-3.
- The T-3 effects has an increased sensitivity to the beta-1 adrenergic receptors and decreases sensitivity in the muscarine-2 receptors
- Also there is decreased heart rate variability which is mediated by the vagolytic effect of the T-3. T-3 can cause excitation of the vagal nerves
- Has decreased APD action potential duration – the length of time the whole PQRST takes to do. So it gets squashed which is AF because there is irregular rhythm so It goes faster.
- Medicated by T-3 affects the ionic channel activity (calcium). It does this by causing a decrease in the L-type calcium channel through mRNA expressions. This causes a genetic change to occur and this genetic change takes about 6-8 weeks to express itself
- Have an increased expression of the Kv or the potassium voltage channels where gene transcription is influenced. There is an increase in rate of potassium X flux which results in a shorter atrial refractory period
- There is an increase in automaticity in the pulmonary vein into the cardiomyocytes and therefore an increase in sopra (above) ventricular depolarisation which means in there is depolarisation across both the atriums and in the structures surrounding those spaces
what is the link between hyperthyroidism and AF
in those who have hyperthyroidism it is found that the beta 1 adrenergic and m2 muscarinic altered the receptors causing in increased sympathetic functions such as tachycardia and decreased atrial refractory period. also alters the ionic channels by:
- decreasing the L-type calcium channel mRNA expression
- increased expression of voltage gated potassium channel
these changes resulted in increased outward current and decreased inwards current resulting in shorter action potential duration
Activation of receptors to gene transcription and translation and the production of new α and β receptors.
- Thyroid hormone regulates a wide range of genes after its activation from the prohormone, thyroxine (T4), to the active form, triiodothyronine (T3).
- There are two genes that express the major thyroid hormone receptor isoforms. Mutations in both these genes have given rise to Resistance to Thyroid Hormone (RTH) syndromes (RTHβ, RTHα) that can have variable phenotypes for mutations.
- There are thyroid hormone receptors (TRs) with two TR isoforms: TRα and TRβ.
- TRα has one T3-binding splice product, TRα1, predominantly expressed in brain, heart, and skeletal muscle, and two non–T3-binding splice products, TRα2 and TRα3, with several additional truncated forms.
- TRβ has three major T3-binding splice products: TRβ1 is expressed widely; TRβ2 is expressed primarily in the brain, retina, and inner ear; and TRβ3 is expressed in kidney, liver, and lung.
how does different hormone levels influence the brain
Hormone levels will influence the brain , heart and skeletal muscle. The 2 non T-3 binding places produce a thyroid hormone receptor alpha 2 and thyroid hormone receptor alpha 3.
Thyroid hormone receptor beta has 3 major T-3 bonding splices beta 1 is expressed everywhere in the body. Beta 2 expressed primarily in the brain, retina, inner ear, kidney, liver, lung.
Stimulation of these receptors will have a clinical effect for patients on these sites
- Here is the pituitary gland, the brain and you have normal or high levels of thyroid stimulating hormone.
- It acts on the thyroid gland and causes a release of T-4 and T-4 which goes into the peripheral tissues and has a clinical action.
- In diagram A, the beta occurs in tissue expressing thyroid hormones receptor beta are caught and causes a rise in T-3 and T-4 due to impaired negative feedback
- In diagram B, the thyroid hormone receptor alpha because tissue is expressed predominantly thyroid hormone receptor alpha which appears in bone, gut and heart
- In contrast with TH-beta there is no effect on the negative feedback on the hypothalamic access by thyroid hormone
- However patients have an increase in serum of T-3 and T-4 ratio suggesting there is a downstream effect such that deiodinase will be affected.
what are the main effects of the thyroid hormones which increases the basal metabolic rate
- Increased in carbohydrate metabolism.
- Increased in the synthesis, mobilisation and degradation of lipids.
- Increased protein synthesis.
Thyroid hormones increase basal metabolic rate, and therefore oxygen consumption, in nearly every organ except what?
- Thyroid gland
- Anterior pituitary gland
- Brain
- Uterus
- Testes
- Spleen
describe the effects of HYPOthyroidism in the heart
- Hypothyroidism affects between 4% and 10% of the population, and the prevalence of subclinical hypothyroidism is reported to be as high as 10% in various studies.
- Hypothyroidism is diagnosed when low levels of the thyroid hormones result in elevated levels of thyroid-stimulating hormone (TSH).
- subclinical hypothyroidism is diagnosed when TSH levels are elevated above the upper limit of the assay reference range with normal thyroid hormone levels.
- Thyroid hormones play an important role in the normal function of heart and vascular physiology, and hypothyroidism produces profound cardiovascular effects.
- Arrhythmia and Hypothyroidism.
- It is well known that hyperthyroidism is associated with atrial fibrillation (AF). Similarly, hypothyroidism is associated with increased cardiovascular risk factors as well as subclinical and diagnosed
what are the different types of arrhythmia associated with hypo and hyper thyroids
- It is well known that hyperthyroidism is associated with atrial fibrillation (AF).
- Similarly, hypothyroidism is associated with increased cardiovascular risk factors as well as subclinical and diagnosed cardiovascular disease, both of which are thought to predispose one to AF.
what are the usual symptoms of hypothyroidism
Usual Lethargy Mild weight gain Cold intolerance Constipation Facial puffiness Dry skin Hair loss Hoarseness
what is the congenital causes of hypothyroidism
Athyreosis: an abnormal condition caused by absence or functional deficiency of the thyroid gland.
Ectopic thyroid is any thyroid tissue not located in its usual position
Thyroid dyshormonogenesis is a rare condition due to genetic defects in the synthesis of thyroid hormones.
Patients develop hypothyroidism with a goiter.
It is due to either deficiency of thyroid enzymes, inability to concentrate, or ineffective binding.
-iodine deficiency
what are the acquired causes of hypothyroidism
iodine deficiency autoimmunity antithyroid drugs iodine excess thyroid irradiation
what is meant by hashimotos disease
Autoimmune destruction of thyroid gland. May or may not be associated with hypothyroidism
- Hashimoto’s thyroiditis is caused by the immune system attacking the thyroid gland, making it swell and become damaged.
- As the thyroid is destroyed over time, it becomes unable to produce enough thyroid hormone. This leads to symptoms of an underactive thyroid gland (hypothyroidism), such as tiredness, weight gain and dry skin.
- The swollen thyroid may also cause a goitre (lump) to form in your throat.
- It may take months or even years for the condition to be detected because it progresses very slowly.
- It’s not understood what causes the immune system to attack the thyroid gland. Hashimoto’s thyroiditis is usually seen in women aged 30 to 50 and it sometimes runs in families.
- It cannot be cured, but symptoms can be treated with levothyroxine, thyroid hormone replacement medication usually taken for life.
- Surgery is needed only rarely – for instance, if your goitre is particularly uncomfortable or cancer is suspected.
what is the treatment for hypothyroidism
Replacement therapy with thyroxine. Monitor by measuring TSH: sufficient T4 will suppress TSH secretion.
Typically also need calcium and vitamin D therapy.
what drugs affects the thyroid function
Drugs which can induce goitre:
• Lithium - used in the treatment of bipolar depression,
• Iodides - contained in vitamin preparations and some cough remedies.
• Amiodarone – used for the treatment of atrial fibrillation: the structure contains iodine which will affect thyroid function
what is meant by hyperthyroidism?
Hyperthyroidism = more thyroid hormones than is needed by the body
(also referred to as thyrotoxicosis, or an overactive thyroid).
It can occur if you have:
• Graves’ disease - the most common cause.
– If the TSH level is low and the T4 level is high (below and above the reference range respectively) usually indicates an over-active thyroid.
– The ‘TSH receptor antibody’ test can establish Graves’ disease.
• A toxic multinodular goitre (a goitre is an enlarged thyroid gland).
• A solitary toxic thyroid adenoma (an adenoma is a clump of cells).
• Thyroiditis (inflammation of the thyroid gland) when it is temporary and self-limiting.
• It can also occur when too much replacement thyroxine (levothyroxine) is taken as a treatment for an underactive thyroid (hypothyroidism).
what are the symptoms associated with hyperthyroidism
weight loss lack of energy heat intolerance anxiety increased sweating increased appetite thirst palpitations loose bowel
what are the symptoms of grace disease
- The TSI level is abnormally high in persons with hyperthyroidism due to Graves’ disease.
- TSI is a form of immunoglobulin G (IgG) that can bind to thyrotropin (TSH) receptors on the thyroid gland. TSIs mimic the action of TSH, causing excess secretion of thyroxine and triiodothyronine
- Exophthalmos (bulging of the eye anteriorly out of the orbit.)
- Goitre (swelling in the neck resulting from an enlarged thyroid gland)
- Pre-tibial myxoedema infiltrative dermopathy, resulting as a rare complication of Graves’ disease. It is most commonly seen on the shins (pretibial areas) and is characterised by swelling and lumpiness of the lower legs.
what is the prevalence of graves disease
Causes of hyperthyroidism 0.2-0.4% population 8x more common in females
- Autoimmune thyroid diseases: Graves’ disease
- Toxic nodular goitre
- Toxic adenoma
what is the pharmacological treatment of hyperthyroidism
Management: Prescribing information
- Propylthiouracil - prevents the peripheral conversion of T4 to T3.
- Carbimazole - The anti-thyroid drugs carbimazole and methimazole act by inhibition of the synthesis of thyroid hormones by preventing the incorporation of the iodide into the thyroglobulin.
- Management: Prescribing information
why may beta blockers be used for the treatment of hyperthyroidism
Beta-blockers may be used for the rapid relief of adrenergic symptoms, and may be used in conjunction with specialist antithyroid drugs such as carbimazole and propylthiouracil.
The beta-blockers propranolol (used most commonly), metoprolol, and nadolol are licensed for the treatment of thyrotoxicosis as an adjunct to antithyroid drug treatment
what are the side effects of anti-thyroid drugs:
CARBIMAZOLE, PROPYLTHIOURACIL
Side effects of anti-thyroid drugs
- Nausea
- Vomiting
- Pruritus and urticarial rashes
- Leucopaenia (<0.1%)
- Fever
- Cholestatic jaundice
what is meant by dysrhythmia
- Any group of conditions in which electrical activity to the heart is irregular or is consistently faster or slower (bradycardia)than normal. A normal heart rhythm is a sinus rhythm which consists of p waves, QRS complex (most obvious part in an ECG) and a t wave and they occur regularly. Normal resting heart rate is around 60-100 bpm.
- The causes of dysrhythmia is altered impulse formation- the site or the rate of the formation of action potentials has changed
- or altered impulse conduction- the action potential originates from the sinus node which passes down the atria to the AV node to the bundle of his and then branches out into the left and right bundle branch then into the purkinje fibres
what are the different classes of dysrythmias
- in altered impulse formation this can relate to decreased automaticity of the SA node leading to a decrease in heart rate or it can cause increase in automaticity in the SA node leading to heart rate becoming too fast (tachycardia)
- automaticity means the ability of particular cells to generate an action potential which leads to ventricular contraction.
how can other pacemaker cells in the heart increase their automaticity
- These are cells which have pacemaker activity but are supressed by action potential being generated by the SA nodes.
- HOWEVER… under certain circumstances they can increase their automaticity above that in the SA nodes and start to drive the rhythm.
- Abnormal automaticity is when cells that don’t have any pacemaker activities. These happen in conditions of damage, cells that don’t produce action potentials and suddenly will have that property to generate action potentials and so drives the function of the heart.
- Triggered activity occurs when a single action potential is initiated in the SA node drives the formation of more than a single depolarisation or action potential in the atrial muscle wall. So a single action potential form a SA node may lead to multiple depolarisation of the atrial muscle or the ventricle muscle cell.
- Altered impulse conduction- for example a conduction block is where there is a block in the action potential through the AV node in the ventricles. This is called a AV block which can vary in severity for example you can see an increase in time in the conduction for an action potential to occur through the AV node or the action potential may fail to get through to the ventricles and this depends on the severity of the block.
describe what is meant by re entrant rhythms
- Atrial fibrillation and ventricular fibrillation is an example of dysrhythmia as it involves a lot of re- entrant loops.
- This where part of the atria become self- excitatory.
- So rather than the action potential passing through all the cells all at once and depolarise them once, the action potential is blocked and so goes round which produces lots of action potentials.
- They all spread out and depolarise the other muscle cells in the atrium and then work their way up to the AV node.
describe the normal pathway of electrical activity through the heart
- Generates action potential which passes through to the atrial muscle cells and then go to the AV node.
- The action potential is passed through the AV node with a delay which goes to the bundle of his and then branches out to the left and right bundle branches into the purkinje fibres where this cause a contraction of the ventricles.
- This forces blood wither to the lung (right ventricle) or through the circulation through the aorta to supply to the rest of the body with oxygen and nutrients.
describe the altered atomicity
Here is a normal SA node action potential which a resting potential around -60 millivolts.
The SA node has a pacemaker potential which drives this slow depolarisation until it hits the threshold.
After it reaches the threshold it rapidly depolarises and then repolarises back to his resting membrane potential.
Through the autonomic nervous system you can change the rate of generation of action potential in the SA nodes and the sympathetic activity through the release of adrenaline and noradrenaline will increase heart rate through its actions on beta-1 receptors on the heart.
These effects re occurring at the level of the pacemaker current.
- For example if we start to exercise then our sympathetic system will start to become activated and if we are resting after a meal then our parasympathetic system through the Vagus nerve will release AcH that will slow down the pacemaker current which will slow down the depolarisation and therefore slows down the rate of action potentials that are being generated.
what is meant by the sinus sick syndrome
Sick sinus syndrome is where in the SA node it automatically goes fater or slower than normal
Sick sinus syndrome thyrotoxicosis, infection, anaemia, alcohol and drug therapy.
- If you have an over active thyroid gland, will affect the heart rate
- Infection through an increase on body temperature can affect heart rate
- the ion channels are proteins which are designed to allow certain action potential to be the shape it is and all proteins are affected by temperature
- if you are anaemic your heart rate might go up because it is trying to pump blood and therefore oxygen around the body to demand the demand of your body.
- alcohol can affect the muscles in the heart
- drug therapy can affect heart rate
what is meant by ectopic beats
Ectopic beats are usually nothing to worry about. Where certain conditions have caused the pace maker cells that is normally being suppressed by SA nodes to increase it rate of action potential generation
what causes ectopic beats
Exercise, stress, pregnancy, menopause, and ageing.
• Fluctuations in potassium and magnesium levels in the blood.
• Intake of caffeine, alcohol, recreational drugs or some prescribed medications (decongestants, asthma medications beta-2 antagonists)
• Conditions affecting heart muscle including prior MI and heart failure
what is abnormal automaticity ( the ability to generate action potentials)
- Similar to previous section but these cells normally do not have pacemaker activity.
- Damage (e.g. following and MI as causes damage to the cells) causes cells to spontaneously depolarise.
- Although there may not be an ion channel there that allows the influx of positive ions, the damaged membrane allows positive ions to diffuse through it
what is meant by triggered activity
- Early or EADs (1st picture) – After depolarisation occurs early in the action potential. Normal atrial action potential. Starts to repolarise and then generates theses 3 depolarisations before the final repolarisation back to the resting membrane potential. This is generated from a single SA node action potential will generate 4 depolarisations in the ventricular muscle cell so therefore 4 contractions of the heart muscle cells which will lead to faster heartbeat.
- Late or LADS/DADs (2nd picture)- DADS happen after the repolarisation of the initial action potential.
- The delayed after depolarisation generates 2 action potentials for every stimulus that has arrived from the SA node
what are the causes of triggered activity
Early: dues to increases in action potential width.
Late: Due to large increases in intracellular Ca2+ or sometimes called calcium overload.
Altered conduction (Re-entrant rhythms)
describe re-entrant rhythms
Cause atrial/ventricular tachycardias and can degenerate to cause fibrillation.
They can be local (atria or ventricular) or global (involved in both) (see Wolff-Parkinson White syndrome)
They require changes in the conduction velocity (usually a slowing in the conduction velocity) and refractory period (an increase) of part of the cells that from part of the re-entrant circuit to set up the tachycardia.
Useful atrial fibrillation link
- An action potential that passes down and it meets an area of non-conducting tissue in the heart
- The action potential has to pass down the left hand side and the right hand side of this non- conducting tissue
- When it comes out the other end, it passes along the bottom and will die when it meets an action potential from the other side because all excitable cells have a refractory period, a period where it can’t be re-excited.
- A single action potential will generate a single action potential that comes out of the system
- HOWEVER… if there damage to some of the muscle cells in the circuit and these properties of conduction velocity and refractory period are changed appropriately.
- an action potential can pass down but can’t go down the blue region (bottom RHS) because it is refractory so it passes down another route from route 1 to 3 and up to 2 and because pathway 2 is recovered comes through this tissue slowly.
- by the time it comes out of the end pathway 1 is recovered so the action potential can just pass around the circuit generating lots of action potentials.
- will lead to tachycardia and if the number f action potentials are high enough can lead to fibrillation
what is meant by conduction block
In people with heart block, also called AV block, the electrical signal that controls the heartbeat is partially or completely blocked from reaching the ventricles.
Heart block is classified as Type 1, 2(number of action potentials don’t make it through the ventricles) or 3 with 3 being the most serious( practically no action potential doesn’t reach the ventricles)
Heart block can be caused by damage to the AV node or drug therapy.
what does re-entrant rhythms cause
Cause atrial/ventricular tachycardias (doesn’t contract properly so cardiac output is reduced ) and can degenerate to cause fibrillation.
They can be local (atria or ventricular) or global (involved in both) (see Wolff-Parkinson White syndrome)
They require changes in the conduction velocity (usually a slowing in the conduction velocity) and refractory period (an increase) of part of the cells that from part of the re-entrant circuit to set up the tachycardia.
how many types of re-entrant rhythms are there
Types of re-entrant rhythms- they all have one thing in common there is an imbalance between the conduction velocity and the refractory period in order to allow for the rhythm to be set up.
what are the different type of re-entrant rhythms
- Sinus node re-entrant tachycardia (SNRT), in which the re-entrant circuit involves the sinus node.
- AV nodal re-entrant tachycardia (AVNRT), in which the re-entrant circuit involves the AV node.
- Atrial re-entrant tachycardia, in which the re-entrant circuit is contained within the atria.
- Atrioventricular re-entrant tachycardia (AVRT), in which the re-entrant circuit contains an electrical connection (a “bypass tract”) between the atria and the ventricles. There are several varieties of bypass-tract re-entrant tachycardia, but the most well known is Wolff-Parkinson-White syndrome (WPW).
- Atrial flutter, which is a special type of atrial re-entrant tachycardia in which the re-entrant circuit is especially large.
- Atrial fibrillation is generally regarded as a special type of re-entrant atrial tachycardia in which multiple re-entrant circuits can develop within the atria.
what is the cause of re-entrant rhythms
• Caused by the following changes to one part of the circuit
– Increase in the refractory period and
– Slow retrograde conduction
• For many the re-entrant rhythm starts and stops instantaneously.
• Conditions can be caused following ischaemic event like tissue could change it properties, but also ageing.
explain how re-entrant rhythms work
- A re-entrant rhythm is set up when an action potential hits an area of non-conducting tissue (shown by the triangle in the middle)
- The action potential from the SA node could hit an area of non-conducting tissue and the action potential passes down the left hand arm and down the right hand arm around the non-conducting tissue.
- When it passes to can start to migrate backwards (bottom part of the 1st picture) where it will die out because all of the excitable cells have a refractory period.
- Refractory period is a period of time where no matter what you do you cannot re-excite the cell or stimulate it. The refractory period is relative to the width of the cardiac action potential.
- A single action potential and will pass around the non- conducting tissue and it will die when it meet the action potential coming from the other side.
- Every muscle cell and conducting cell in the system where the arrows are passing will only get excited once for a single action potential from the SA node.
Second picture explanation
- The grey area is where there is damage to the conducting tissue in one arm of the re-entrant. This arm will have slightly different conducting properties to the tissue that is present in the other arm of the loop
- Because the arm that has been damage there will be an increase in refractory period so it takes longer to recover and therefore has a longer time delay before that tissue can be re-excited.
- If a second action potential comes down the tissue on the left hand side with a normal refractory period has recovered and can conduct the action potential.
- HOWEVER… the tissue on the other side because it has an increased refractory period still hasn’t recovered and therefore the action potential hits that tissue and dies out (shown with red line)
- The action potential passes down and comes along the bottom and doesn’t die out because the tissue hasn’t been excited because of the block from the damaged arm and so it carried on and will start to work its way back up the arm of the damaged arm.
Third picture explanation (Left picture where conditions are normal and haven’t been damaged.
- If it hits the action potential hits the tissue on the broken arm the tissue has been recovered and therefore it is not refractory.
- The action potential can pass up through the tissue and as it comes out of the other sided, under normal conditions It will hit the tissue which is now in a refractory state because it has just been excited by this action potential
