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Overview
The book benefits from an engaging and authoritative text, written by specialists in the field, and has several key features to help you really understand the subject:
- Chapter starter questions - to get you thinking about the topic before you start reading
- Break out boxes which contain essential key knowledge
- Clinical cases to help you understand the material in a clinical context
- Unique graphic narratives which are especially useful for visual learners
- End of chapter answers to the starter questions
- A final self-assessment chapter of Single Best Answers to really help test and reinforce your knowledge
This is followed by the Clinical Essentials chapter which provides an overview of the symptoms and signs of endocrine disease, relevant history and examination techniques, investigations and management options.
A series of disease-based chapters give concise descriptions of all major disorders, e.g. diabetes mellitus, hyperthyroidism and Addison’s disease, each chapter introduced by engaging clinical cases that feature unique graphic narratives.
The Emergencies chapter covers the principles of immediate care in situations such as diabetic and adrenal crises.
An Integrated care chapter discusses strategies for the management of chronic conditions across primary and other care settings.
Finally, the Self-Assessment chapter comprises 80 multiple choice questions in clinical Single Best Answer format, to thoroughly test your understanding of the subject.
The Eureka series of books are designed to be a 'one stop shop': they contain all the key information you need to know to succeed in your studies and pass your exams.
Product Details
| ISBN-13: | 9781787790377 |
|---|---|
| Publisher: | Scion Publishing Ltd. |
| Publication date: | 03/31/2015 |
| Series: | Eureka |
| Sold by: | Barnes & Noble |
| Format: | eBook |
| Pages: | 288 |
| File size: | 29 MB |
| Note: | This product may take a few minutes to download. |
About the Author
Thomas Fox
Antonia Brooke
Bijay Vaidya
Peninsula Medical School, UK
Read an Excerpt
CHAPTER 1
First principles
Overview of the endocrine system 1
The thyroid gland 8
The parathyroid glands 15
The hypothalamus 20
The pituitary gland 27
The adrenal glands 36
The pancreas 44
The gut 49
The male reproductive system 51
The female reproductive system 56
The pineal gland 61
Starter questions
Answers to the following questions are on page 63.
1. Do hormone levels change as we age?
2. Why does menstruation stop during extreme stress?
3. Do we all have the same hormone levels?
Overview of the endocrine system
The endocrine system consists of several anatomically and physiologically distinct glands. Each of these glands is a group of specialised cells that synthesise, store and secrete hormones.
Hormones are chemical messengers that travel in the bloodstream from an endocrine gland to another organ or group of organs to regulate a wide range of physiological processes. Hormones:
* stimulate or inhibit growth
* regulate metabolism by maintaining and mobilising energy stores
* promote sleep or wakefulness
* activate or suppress the immune system
* prepare the body for 'fight or flight' in response to acute stress
* produce the changes associated with puberty and reproduction
* affect mood and behaviour
Hormones also have a role in maintaining homeostasis, a state of physiological equilibrium achieved by adjusting the body's internal environment in response to changes in the external environment.
In contrast to the rapid effects of the nervous system, endocrine effects are usually slow to develop and produce a prolonged response lasting from minutes to weeks.
The human body produces many hormones for regulation of a myriad of physiological processes. New hormones continue to be discovered, and research is ongoing to explain their functions and how they interact to control the human body.
Endocrine glands
Endocrine glands release their products, hormones, into the blood. They have a rich blood supply to ensure efficient transport of hormones around the body.
The following are the major endocrine glands (Figure 1.1).
* Hypothalamus: as the main endocrine control centre, this tiny gland in the brain secretes many hormones that directly affect hormone production by other endocrine glands
* Pituitary gland: this is connected to the hypothalamus and produces a wide range of hormones controlling growth, metabolism and sexual development
* Pineal gland: this gland in the brain controls wakefulness
* Thyroid gland: this gland produces thyroid hormones, which set the body's metabolic rate, and calcitonin, which regulates calcium metabolism
* Parathyroid glands: these produce parathyroid hormone, which controls the absorption and excretion of calcium and phosphate
* Thymus gland: secretes thymosin, a hormone that stimulate the production of immune T cells
* Adrenal glands: these secrete many hormones that mediate the body's response to physiological and psychological stress, maintain fluid and electrolyte balance, and modulate blood pressure
* Pancreas: the endocrine cells of the pancreas release insulin and glucagon, which regulate blood glucose concentration
* Reproductive glands: these glands, the testes in males and the ovaries in females, produce sex hormones, which facilitate sexual maturation and enable reproduction
Although not major endocrine glands, the following organs produce and secrete hormones as part of their primary function.
* Intestine: several hormones are secreted from the gut to help control blood glucose concentration and growth
* Adipose tissue: hormones produced by body fat affect appetite and the feeling of fullness (satiety)
Other organs, such as the liver, kidney, heart and skin, have secondary endocrine functions unrelated to their primary function. For example, the main function of the liver is to metabolise carbohydrate, fat and protein. However, it also has secondary endocrine functions, such as producing the hormone insulin-like growth factor-1, which promotes the growth of body tissues.
An endocrine gland may produce more than one hormone, for example the thyroid gland produces thyroid hormones and calcitonin. This means that a single endocrine gland can help control multiple body functions.
Chemical classification of hormones
Hormones are grouped into three chemical classes (Table 1.1):
* peptides
* amines
* lipids (mainly steroids)
Peptide hormones
The hormones in this class are chains of amino acids (polypeptides). These chains range in length. They may be short and comprise only a few amino acids (e.g. antidiuretic hormone), or they may be very long molecules (e.g. follicle-stimulating hormone, FSH). Peptide hormones have a large molecular weight.
Amine hormones
Amine hormones are derived from aromatic amino acids such as tryptophan, phenylalanine and tyrosine. Aromatic amino acids have an aromatic side chain, i.e. one containing a stable, planar unsaturated ring of atoms.
Lipid hormones
Hormones in this class are derived from cholesterol and are either alcohols or ketones.
* Alcohol lipid hormones have names ending in '-ol' (e.g. oestradiol)
* Ketone lipid hormones have names ending in '-one' (e.g. aldosterone)
Hormonal signalling pathway
Hormonal signalling pathway involves hormone synthesis, storage (peptide and amine hormones only), release from endocrine cells, transport, receptor binding, release of the hormone or its breakdown products from the cells of the target organ, further transport and excretion (Figure 1.2).
1. Synthesis: the hormone is produced by cells in the endocrine gland
2. Storage: peptide and amine hormones are stored in preparation for rapid release when required (lipid hormones are not stored before release)
3. Release from endocrine cells: the hormone is released from the gland into the bloodstream
4. Transport: the hormone travels in the blood to the target organ either unbound, i.e. in a free state (peptide hormones and all amine hormones except thyroid hormone) or bound to transport proteins (lipid hormones and thyroid hormone)
5. Receptor binding: the hormone binds to membrane of the cells of the target organ or inside these cells
* A hormone binding to receptor molecules on the cell membrane changes the cell's metabolism through a cascade of reactions involving various 2nd messenger chemicals
* Intracellular binding of a hormone to nuclear or cytoplasmic receptors directly affects the expression of genes in the cell
6. Release from the cells of the target organ
* The cells secrete the hormone unchanged
* Alternatively, the cells metabolise the hormone to an inactive form
7. Further transport: the hormone or its breakdown products travel in the bloodstream to the liver or kidneys
8. Excretion: the hormone or its breakdown are excreted by the liver (in bile) or the kidneys (in urine)
Hormone synthesis and storage
Endocrine cells synthesise peptide and amine hormones from amino acids, and lipid hormones from cholesterol.
Peptide hormones
Hormones in this class are synthesised as precursor molecules. These prohormones undergo processing in the intracellular endoplasmic reticulum and Golgi apparatus. In the Golgi apparatus, the processed peptide hormones are packaged into secretory granules. They are stored in high concentration in these granules, ready for stimulated release from the endocrine cells into the bloodstream.
Amine hormones
These hormones are synthesised from aromatic amino acids. These amino acids are chemically altered by enzymes in the cells of endocrine glands to synthesise specific hormones. For example, in cells of the adrenal medulla, adrenaline (epinephrine) is synthesised from the amino acid tyrosine. Various enzymes catalyse the steps in adrenaline production; the final step is the conversion of noradrenaline (norepinephrine) to adrenaline by the enzyme phenylethanolamine-N-methyltransferase. Like peptide hormones, amine hormones are stored in secretory granules.
Lipid hormones
These are synthesised from cholesterol. The cholesterol is metabolised by enzymes in the cells of an endocrine gland to produce lipid hormones that are either alcohols or ketones.
The onset of action of lipid hormones is slower than that of amine hormones. Therefore, unlike amine and peptide hormones, lipid hormones are not stored in secretory granules for rapid release. Instead, they are synthesised as required, with the rate of synthesis directly determining blood concentration.
Hormone release
When an endocrine cell is activated, secretory granules (containing peptide or amine hormones) move to the cell surface. Here, the vesicular membranes of the granules fuse with the plasma membrane of the cell surface to release their contents to the exterior of the cell. This process is called exocytosis, which literally means 'out of cell'.
Membrane transport of lipid hormones (such as testosterone) occurs in a passive manner across the cell membrane due to the non-polarised nature of the lipid-rich cell membrane. This form of hormone secretion depends upon the difference in concentration of the hormone in the intracellular space (high) to equalise with the hormone concentration in the extracellular space (low) by random motion of molecules (Brownian motion).
Hormone transport
Peptide hormones are able to travel unbound (free) in the bloodstream, because they are hydrophilic ('water loving'). Amine hormones are also hydrophilic and also able to travel unbound in the blood. The hydrophobic thyroid hormones are the exception.
Peptide and amine hormones, other than thyroid hormones, are able to pass through capillary membranes to reach their target cells.
Lipid hormones are hydrophobic ('water hating'), so they must be bound to transport proteins in plasma to enable them to travel in the bloodstream. Lipid hormones undergo continuous and spontaneous binding and unbinding from their carrier molecules. Because lipid hormones are bound to transport proteins, they have a longer half-life (the time taken for half of the hormone molecules to be excreted or metabolised) than amine hormones, which are transported unbound.
Only a small fraction of lipid hormones present in the bloodstream are in an unbound state. For example, 99% of cortisol in the blood is bound to proteins; the unbound remainder, the free cortisol, is biologically active. This is true of all lipid hormones.
Hormone receptor binding
Hormones travel through the bloodstream and thus come into contact with many cell types. However, a cellular response is initiated only in cells with the specific receptors for a hormone. These receptors may be on the cell membrane or in the cytoplasm.
Multiple types of cell may have receptors for a particular hormone. This allows a hormone, for example thyroxine (T4), to bind to receptors in the cells of many different tissues and thus have widespread effects on metabolism throughout the body.
The effects of a hormone binding to a receptor in one type of cell will differ from those of the same hormone binding to a receptor on another type of cell due to differing downstream processes associated with each receptor. For example, when adrenaline (epinephrine) binds to β adrenergic receptors in cardiac myocytes, it causes the heart muscle to contract more forcefully; however, the same hormone causes muscle relaxation when it binds to β receptors in the bronchioles.
Peptide hormone receptors
Peptide hormones are lipophobic ('lipid hating'), so they are unable to diffuse freely through the cell membrane, which consists of two layers of lipid molecules. Therefore peptide hormone receptors composed of transmembrane proteins are necessary to communicate the hormonal message from outside the cell to the target molecules inside the cell.
The peptide hormone receptor is part of a signal transduction system (Figure 1.3). In this system, the hormone acts as the 1st messenger by binding to its receptor on the extracellular surface of the cell. This hormone-receptor binding activates 2nd messengers such as cyclic AMP (cAMP), which relay the signal within the cell.
1. The peptide hormone binds to its specific cell surface receptor
2. Hormone binding activates a coupled G-protein (G-proteins are a class of protein present in cell membranes and that transmit signals from hormones binding extracellularly)
3. The G-protein converts guanosine diphosphate to guanosine triphosphate
4. Guanosine triphosphate binds to and thus activates the enzyme adenylate cyclase
5. Adenylate cyclase catalyses the conversion of ATP to cAMP
6. The cAMP activates protein kinase A
7. Now activated, protein kinase A is able to phosphorylate (add a phosphate molecule to) various cell proteins, altering their structure and function and thus producing a cellular response to hormone binding at the cell surface
8. An enzyme called phosphodiesterase breaks down cAMP, thereby inactivating it
Amine hormone receptors
Most amine hormones, for example adrenaline (epinephrine) and dopamine, are lipophobic. Therefore, like peptide hormones, they are unable to diffuse through the cell membrane and instead must bind to cell surface receptors and activate 2nd messenger systems to induce a cellular response.
Thyroxine is an exception. This amine hormone is lipophilic, so it can diffuse through the cell membrane and directly modify gene transcription in the nucleus by binding to intracellular nuclear receptors in the same way as lipid hormones.
Lipid hormone receptors
Lipid hormones are lipid-soluble, so they can diffuse freely through the cell membrane. Once in the target cell, they bind with their receptors, which are in the cytoplasm (Figure 1.4). The combined hormone-receptor complex then diffuses across the nuclear membrane through a nuclear pore (a channel that permits passage of the hormonereceptor complex).
In the nucleus, the hormone-receptor complex binds to specific DNA sequences called hormone response elements. This binding either amplifies or suppresses the rate of transcription of particular genes; thus, protein synthesis is increased or decreased, respectively.
Hormone degradation and clearance
The blood concentration of a hormone is affected by the speed of its production and the speed of its clearance. Circulating hormone in the blood can be cleared in several ways.
1. The hormone binds to its receptor temporarily removing it from the circulation
2. The tissues metabolise the hormone to its inactive form
3. The hormone is excreted
* by the liver into the bile
* by the kidneys into the urine
Hormonal regulation
All endocrine glands have precise control mechanisms to ensure appropriate hormonal secretion. Production of each hormone is altered in response to the internal and external environment; external factors include temperature, and internal factors include blood glucose concentration.
Hormones maintain a state of optimum chemical balance in which the body can function as efficiently as possible; they also enable the body to respond appropriately to illness. For example, cortisol production is increased in times of illness, to induce physiological changes that help the body to respond to the effects of the stress from the illness. However, at the same time, the production of sex hormones is decreased to reduce fertility (as reproduction is not the survival priority at that point in time).
Feedback loops
All hormone production is controlled by feedback loops. These can be negative or positive.
Negative feedback loops
Most hormonal regulation occurs through negative feedback mechanisms, through which the effects of a hormone inhibit its secretion. Thus negative feedback helps maintain homeostasis by ensuring the controlled release of hormones. Under- or overproduction of a hormone, or abnormalities in its control mechanisms, can disturb the homeostatic balance.
An example of an endocrine negative feedback loop is the hypothalamic-pituitary-adrenal axis (Figure 1.5). The hypothalamus secretes corticotrophin-releasing hormone (CRH), which stimulates the anterior pituitary gland to secrete adrenocorticotrophic hormone (ACTH; also known as corticotrophin). In turn, ACTH stimulates the adrenal cortex to secrete glucocorticoids, including cortisol.
Glucocorticoids not only perform their respective functions throughout the body but also bind to receptors in the hypothalamus and the pituitary gland to inhibit the production of CRH and ACTH, respectively. These effects reduce the stimulus to the adrenal gland to produce cortisol and other glucocorticoids.
Positive feedback loops
In positive feedback, a hormone's effects stimulate its secretion. An example occurs in the female reproductive cycle. When luteinising hormone causes a surge in the production of oestrogen by the ovary, the released oestrogen stimulates the anterior pituitary gland to produce more luteinising hormone. This positive feedback mechanism results in the luteinising hormone surge that stimulates ovulation.
(Continues…)
Excerpted from "Endocrinology"
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