RED Endocrine 1 Learning objectives PDF

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Summary

1. Describe the various types of chemical 'inter-cellular messenger' in the body. Endocrine - The hormone is made and directly secreted into the blood and thenreaches its target cell to have an effect Neuroendocrine - The hormone is made in the nerve cell and is then secretedinto the blood and it ...

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1. Describe the various types of chemical 'inter-cellular messenger' in the body.   

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Endocrine- The hormone is made and directly secreted into the blood and then reaches its target cell to have an effect Neuroendocrine- The hormone is made in the nerve cell and is then secreted into the blood and it travels till it reaches its target cell Neurotransmitter- The neurotransmitter is made in the neurone and is stored in vesicles. Once an action potential arrives there is an influx of calcium ions at the presynaptic neurone and the calcium ions allow fusion of the vesicles with the presynaptic membrane. The NT is then released and travels across the synaptic cleft to bind to the NT receptors on the postsynaptic neurone Autocrine and Paracrine- Autocrine is where a cell secrets a hormone and then the same hormone then acts on the cell that secreted it. Paracrine is where a cell secrets a hormone and the hormone travels a short distance in the interstitial fluid to the neighbouring cell where it has an effect.

2. Describe and distinguish the basic structure, synthesis, release, transport and mechanism of hormone action of a) peptide, and b) steroid hormones Peptide Hormones are made from chains of amino acids examples are those hormones produced in the hypothalamus, ant and post pituitary and pancreas They are made in endocrine cells. Steps: 1. The gene for the peptide hormone is transcribed into mRNA in the nucleus 2. The mRNA is then transported into the cytosol of the cell 3. In the cytosol the mRNA binds to ribosomes present on the RER and is then translated into a protein 4. The first protein made is very large and called a pre-prohormone and located at the start of this molecule there is a pre-signal 5. The pre-signal tells the cell that the peptide is going to be exported out of the cell and therefore needs to be packaged 6. The amino acid sequence of the pre-prohormone allows protein folding and the formation of disulphide bonds and the attachment of carbohydrates (glycosylation) 7. After travelling through the RER, the preprohormone reaches the Golgi complex which is the processing plant of the cell 8. Additional processing and cleavage occurs of certain parts of the peptide which are not necessary turns the preprohormone into a prohormone and then a hormone 9. The hormone is then packaged into secretory granules and stored until it is ready to be released (upon the arrival of a stimulus) 10. Exocytosis of the secretory granule occurs; the granule moves towards the cell membrane and the membranes fuse together. Then get expulsion of the granule contents into the blood.

They are hydrophilic molecules therefore do not bind to plasma proteins and have a short half-life of minutes. Mechanism of action: 1. As peptide hormones are hydrophilic they cannot cross cell membranes therefore need to bind to a plasma membrane receptor on its target cell 2. There are two types of receptors – GPcR and Tyrosine kinase receptors 3. Activation of these receptors results in signal transduction and second messengers are generated that alter the activity of ion channels and in some cases gene expression 4. Effects of peptide hormones are immediate compared to steroid hormones

Steroid hormones are derived from cholesterol and include cortisol, aldosterone and sex hormones that act on the gonads Steroid hormone synthesis: 1. There are biosynthetic enzymes inside the endocrine cell in the Smooth Endoplasmic Reticulum and mitochondria which convert cholesterol into the relevant steroid hormone 2. The steroid hormones are lipophilic therefore cannot be stored which a membrane wrapped around them as they can escape via diffusion 3. Once the hormones are made they pass through the plasma membrane via simple diffusion 4. Once in the blood they are not very soluble due to the lipophilicity and therefore are highly protein bound and relies on this to be carried in the blood Biding to the plasma proteins is reversible and the bound form is inactive which then delays metabolism of the hormone as only the free unbound form is available for metabolism and this provides a circulating reservoir in the blood and a half life up to a few days Steroid hormone action: 1. The hormones reach their target cell from circulating in the blood and then diffuse into the cell as they are lipophilic. 2. There are intracellular receptors, cytosolic and nuclear receptors 3. Once bound to the receptor, the complex acts as a transcription factor and this regulates gene transcription by binding to promotor regions on the DNA sequence. They can increase or decrease gene expression and the effects are not immediate

3. Explain the physiological mechanisms involved in the regulation of hormone release, including feedback control, the endocrine axis, neuroendocrine reflexes, and diurnal rhythms. Feedback regulation- negative or positive Negative is where a consequence negatively controls processes to maintain a set point Positive is where a consequence enhances or amplifies the process further which can be detrimental

Endocrine axis- is the involvement of hypothalamic and pituitary tropic hormones The hypothalamus releases a hormone known as releasing hormone and this can act positively or negatively on the anterior pituitary which then releases tropic hormone. The tropic hormone acts positively on the peripheral endocrine gland to cause secretion of a peripheral hormone which then causes a target cell response. If there is overstimulation of the peripheral endocrine gland to produce peripheral hormone by the tropic hormone, negative feedback will occur where the high levels of peripheral hormone will have a negative impact on the hypothalamus and the anterior pituitary to release fewer hormones and this a long feedback loop where there is inhibition 1 and 2 levels up from the peripheral endocrine gland. There is also a short feedback loop where high levels of tropic hormone will negatively impact the hypothalamus to secrete less releasing hormone and the point of the feedback loops is to maintain a set point.

Diurnal rhythmsCortisol our stress hormone has a set diurnal pattern where the levels of cortisol rise during the night due to synthesis and this causes a peak in cortisol levels in the morning to help us deal with stress throughout the day. As the day progresses the levels of cortisol fall and then the body makes some more during the night.

4. Describe the basic mechanisms by which endocrine disorders may develop (including autoimmune). There are 3 ways that can endocrine disorder can develop: 1. Hormone excess- Due to a tumour or immunological factor 2. Lack of hormone- Genetic, immunological attack, destruction by disease 3. Decreased target level responsiveness at the level of the receptor or downstream enzyme 4. Autoimmune- in Type 1 diabetes- get autoimmune destruction of B islet cells this is due to genetic factors and/or environmental factors. Autoantigens are then produced which causes activation of the adaptive and innate immune responses to then cause cellular damage leading to disease

5. Outline the types and purposes of endocrine tests used in the investigation of endocrine disorders. 1. Signs and symptoms- Looking at the presenting complaint and using differential diagnosis to see which endocrine disorder it may come under 2. Endocrine investigations- using a baseline test to detect hormone levels or to use a dynamic test to check the integrity of feedback control a. Provocative or dynamic- tests the integrity of feedback control

i. Get simulation tests- if suspect hyposecretion Synacthen R test in primary adrenal insufficiency ( addisons diease)

ii. Get suppression test if suspect hypersecretion Low dose dexamethasone in cushings disease- get no decrease in cortisol BUT Get suppression with high dose dexamethasone. If levels of cortisol remain unchanged for high and low dexamethasone then other causes must be considered.

b. Single point tests- baseline reading of hormones

3. Imaging- detection of a tumour mass

6. Summarise the principles of treatment of endocrine disorders. 1. Hormone replacement if the patient is hormone deficiency 2. Drugs to block production of hormones if there is excess 3. Drugs to enhance cellular response if there is a lack of cell responsiveness 4. Radiotherapy or surgery if there is a tumour present...