The Endocrine System at a Glance (I)

3152(Smbc – click to view full size).

Compare with the book:

Adrenal steroid synthesis

(There are other diagrams in the book which look quite a bit more like the SMBC one than does the table above, but none of them deal with 17α-hydroxylase, progesterone, androstenedione and their friends and acquaintances…).

No, I didn’t get all of the stuff covered in this book, but this would probably also be a bit much to expect. There were however more than a few principles presented here which I’d sort of come across elsewhere which I now have a much better understanding of than I used to do. Many of the things covered (but far from all of them) were things I’d read about before, e.g. in McPhee et al. and Sperling et al. But there was also some new stuff in there.

The book has ~118 pages, plus some pages with reading comprehension questions in the back, but the page count is a very deceptive metric if you want to estimate the amount of work required to get through the book; I may be wrong, but I think most people will find it very hard to read even close to 10 pages per hour, certainly ‘in the long run’ (after the first couple of hours) and certainly if they want to understand the stuff and do not have a medical background. You probably need to be willing to look stuff up every now and then to follow what’s going on. I basically read the book two to four pages at a time, with lots of short breaks. Actually I’m not sure this is a good book to read at all if you do not have some medical knowledge – as they state in the introduction: “The book is aimed at undergraduate medical students […] it should also be a useful source of information for clinical medical students and junior doctors”.

The book belongs in the same series as the nutrition text by Barasi I read a while back (another book covering topics which were also looked at in the book, e.g. stuff like energy homeostasis), and it suffers from the same main problem I had with that publication; there’s not a single source provided in the publication. Actually that’s not entirely true as I think one of the graphs were described in the text and so you were told where the numbers came from in that case; but almost all numbers provided are provided without any indication of where they come from, and you have no way to figure out what kind of research they are based on. “Diabetics are three times more likely to have a stroke and 15 times more likely to undergo lower limb amputation than non-diabetic subjects”, they write in the text, yet the latter number is likely to be an underestimate as: “The relative risk of an individual with diabetes undergoing a lower extremity amputation was 20.3 in 2004 and 21.2 in 2008, compared with that of individuals without diabetes.” (link). Given that some of the other numbers included in the book clearly have not been updated since the previous editions – there’s a particularly hilarious forecast of obesity in the UK which provides a linear forecast (using OLS) of what’s likely to happen (?) to the obesity rate from the year 1998 and forward, based on the numbers observed during the previous two decades… (the third edition of the book which I read was published in 2011) – I find it highly unlikely that the mismatch between the relative risk numbers is the result of outcome improvements observed since 2008. The authors are incidentally British, which is why I refer to the specific ~20 RR estimate – I’m assuming they’re relying on UK/British numbers when providing their estimates, even though even that is actually unclear, so relying on such numbers seemed the most fair way to evaluate the accuracy of the estimate. The discrepancy in question is not one of a kind – for example elsewhere they write that: “Macrovascular complications are the major cause of death in people with Type 2 diabetes, accounting for 50% of deaths in this group” – which again seems to be a significant underestimate: “Subjects with both type 1 and type 2 diabetes are at increased risk of developing cardiovascular disease, with approximately three-quarters of patients with diabetes ultimately dying from vascular causes” and: Mortality from CVD accounts for more than 60% of deaths in patients with type 2 diabetes mellitus”. (Quotes from Betteridge and Nicholls’ Managing Cardiovascular Complications in Diabetesblog link here. 50% is way too low).

I assume most of the numbers included in the book are reasonably in line with the evidence, and there aren’t many numbers to begin with as the book deals almost exclusively with key principles etc., but I do find it annoying and slightly troubling that the numbers seem to be a little bit off in areas where I actually know something about those things they talk about, and regardless of whether they’re wrong or not you should provide a damn source anyway. I don’t think it would be that hard to add a few sources without making drastic changes to the format of the book, as one could just add a number in the text and a source in the back. I should make clear that to the extent the estimates provided in the publication are ‘wrong’ I believe them to be wrong on account of being based on old data; I don’t think any inaccuracies in the book are due to the authors ‘not knowing what they’re talking about’.

As might be inferred from the screenshot above the book is very technical, and so it’s a bit difficult to blog. There are many  chapters where most of the coverage consists of complicated diagrams as well as verbal coverage of the same stuff dealt with in those diagrams, and little else. I have tried in my coverage below to mostly cover stuff from the book which I thought might at least be reasonably easy to understand for people reading along here.

“Endocrinology is the study of endocrine hormones and of the organs involved in endocrine hormone release. Classically, hormones have been described as chemical messengers, released and having their actions at distant sites. It is now clear, however, that there is a close relationship between hormones and other factors such as neurotransmitters and growth factors acting in a paracrine or autocrine fashion. Hormones are essential for the maintenance of normal physiological function and hormonal disorders occur at all stages of human life. Clinical endocrinologists thus look after patients of all ages and with a very wide range of disorders”

“Hormones are chemical messengers. They may be classified several ways […]: 1 Autocrine: acting on the cells that synthesized them […] 2 Paracrine: acting on neighbouring cells. An example is insulin, secreted by pancreatic β cells and affecting secretion of glucagon by pancreatic α cells. 3 Endocrine: acting on cells or organs to which they are carried in the bloodstream or through another aqueous ducting system, such as lymph. Examples include insulin, estradiol and cortisol. 4 Neuroendocrine: this is really paracrine or endocrine, except that the hormones are synthesized in a nerve cell (neurone) which releases the hormone adjacent to the target cell (paracrine), or releases it into the bloodstream, which carries it to the target cell […] 5 Neural: this is neurotransmission, when a chemical is released by one neurone and acts on an adjacent neurone […]. These chemicals are termed neurotransmitters. […] 6 Pheromonal transmission is the release of volatile hormones, called pheromones, into the atmosphere, where they are transmitted to another individual and are recognized as an olfactory signal.”

“The movement of chemicals between cells and organs is usually tightly controlled. Diffusion is the movement of molecules in a fluid phase, in random thermal (Brownian) motion […] Facilitated transport is the transport of chemicals across membranes by carrier proteins. The process does not require energy and cannot, therefore, transport chemicals against a concentration gradient. […] Active transport uses energy in the form of adenosine triphosphate (ATP) or other metabolic fuels. Therefore chemicals can be transported across the membrane against a concentration gradient […] Ion channels mediate active transport, and consist of proteins containing charged amino acids that may form activation and inactivation ‘gates’. Ion channels may be activated by receptors, or by voltage changes through the cell membrane. Channels of the ion Ca2+ can be activated by these two methods. Osmosis is the passive movement of water through a semipermeable membrane, from a compartment of low solute concentration to one which has a greater concentration of the solute.”

“Hormones interact with target cells through a primary interaction with receptors which recognize the hormones selectively. There are several different receptor systems, which vary in mechanism and timing […] Receptor antagonism is an important aspect of endocrinology and drug use generally […] antagonists play a large part in the treatment of endocrine disease. The molecule which binds to the receptor and elicits the normal cellular response is termed the agonist. The ligand which binds, but elicits no response, is the antagonist. Antagonists act at the membrane in different ways. For example the β-receptor blocker propranolol competes with epinephrine at its binding site. The anticonvulsant phenytoin blocks ion channels.”

“Living systems possess their own internal environment, which has to survive within an external environment. […] Internal control is achieved through integration of the different systems: neural, biochemical and physical. In all cases, the fundamental components of these systems are: (i) signals; (ii) transducers; (iii) sensors; and (iv) responders. […] Integration of endocrine systems is achieved through a complex interplay of regulatory feedback mechanisms operated through both hormonal and neural communication networks. The most important mechanisms are those commonly called feedback, whereby systems limit each other’s activity around a preset oscillator. […] In endocrinology, the brain–pituitary–target gland axes provide examples of feedback mechanisms in action […]. For virtually every anterior pituitary hormone, a corresponding hypothalamic releasing hormone has been discovered, and in some cases a corresponding inhibitory hypothalamic hormone has been found […]. Feedback systems may involve more than two hormones […] Understanding basic feedback mechanisms is vital in clinical endocrinology where it forms the basis of diagnostic testing. […] Characteristically, endocrine disorders disrupt normal feedback mechanisms and this feature is exploited in the interpretation of a number of endocrine function tests. Furthermore, certain hormones rise in response to stressful stimuli and this too can be utilized for diagnostic purposes. […] Most hormones: • Are subject to diurnal or ultradian rhythms • Are secreted in a pulsatile fashion • Are controlled by feedback from target organs (usually negative) • Develop autonomous secretion in pathological states […] As a general rule: • If the clinical suspicion is of hormone excess then suppression tests are used • If the clinical suspicion is of hormone deficiency then stimulation tests are used”

“Many endocrine conditions have an autoimmune aetiology and patients frequently exhibit antibodies to multiple endocrine organs and have evidence of associated autoimmune disease […] Autoimmunity may be defined as an attack by the host’s immune system on the host’s own tissues. These attacks may be transient immune reactions to infection, for example, which resolve spontaneously. They may, however, become chronic, with pathological consequences. Endocrine autoimmunity often involves an immune attack on specific endocrine glands, for example Addison’s disease, Graves’ disease, Hashimoto’s thyroiditis and insulin-dependent diabetes mellitus, where the gland is damaged or destroyed altogether [‘type 1 diabetes mellitus’ is much better than ‘insulin-dependent diabetes mellitus’ [IDDM] in this context – I dislike the unfortunate naming convention applied, given that many type 2 diabetics, as mentioned before here on this blog, will require insulin-injections over time. I’ve previously seen an estimate which I reported here on the blog which indicated that half of type 2 diabetics will need insulin within 6 years of diagnosis, but the original source for that quote has been taken down and I didn’t write down who the authors were so I can’t find the original estimate. I don’t really trust wikipedia on these things, but the article on insulin includes the (likewise unsourced) observation that: “Over 40% of those with Type 2 diabetes require insulin as part of their diabetes management plan”. As something like ~85% of all diabetics are type 2 diabetics, type 2’s make up a substantial majority of all IDDM cases if that estimate can be trusted. Regardless of precisely how many type 2 diabetics are treated with insulin it’s a very substantial number of patients, and the relevant distinction here, when thinking about autoimmunity-mediated organ damage, is between type 1 and type 2, though that distinction is admittedly also not perfect. This post has more about specific subtypes of diabetes, as does this commentas the remarks included in the latter link in particular illustrates, this stuff is complicated and none of the applied diagnostic conventions really distinguish 100 percent between auto-immune and not-autoimmune, though the type 1/2 distinction comes much closer than does the IDDM/NIDDM distinction, which is one of the reasons why the latter distinction is these years rarely used in lieu of the type 1/2 categorization convention]. These are examples of mainly organ-specific autoimmune diseases […]. In systemic autoimmune disease, on the other hand, the immune system attacks several tissues that may be anatomically distant from each other. Examples of systemic autoimmune disease include rheumatoid arthritis, scleroderma and systemic lupus erythematosus (SLE). There may be both organ-specific and systemic components in most, if not all, autoimmune diseases.”


September 10, 2014 - Posted by | Books, Diabetes, Immunology, Medicine

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