tag:blogger.com,1999:blog-9567015407377487122024-03-16T11:22:09.282+02:00Medic GuideWelcome to a site dedicated to understanding, rather than memorising, the great subject of medicine.jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.comBlogger495125tag:blogger.com,1999:blog-956701540737748712.post-18681541340981417542010-08-06T11:32:00.000+02:002010-08-06T11:34:36.676+02:00These doctors must have a low workload...<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://3.bp.blogspot.com/_tN90RefJ5Hk/TFvXGxIqlxI/AAAAAAAAA1g/w2ligYIyIRs/s1600/Photo0128.jpg"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 400px; height: 300px;" src="http://3.bp.blogspot.com/_tN90RefJ5Hk/TFvXGxIqlxI/AAAAAAAAA1g/w2ligYIyIRs/s400/Photo0128.jpg" border="0" alt="" id="BLOGGER_PHOTO_ID_5502227881032062738" /></a><br /><br />Someone didn't think this sign through. It's from the same hospital I work at...jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com15tag:blogger.com,1999:blog-956701540737748712.post-18242578899124968412010-08-02T18:08:00.000+02:002010-08-02T18:37:33.679+02:00An approach to hypernatraemiaNow that <a href="http://medicguide.blogspot.com/2010/07/approach-to-hyponatraemia.html">we've dealt with the commonest derangement of sodium concentration</a>, it's time meet its rarer cousin: hypernatraemia. There are only two ways to become hypernatraemic: either you must lose water (at least in excess of sodium) or you must gain sodium (at least in excess of water).<br /><div><br /></div><div><b><span class="Apple-style-span" style="color:#990000;">What you'll need:</span></b> serum sodium, urine sodium, urine osmolality<sup>1</sup>, total urine daily volume.</div><div><br /></div><div>Once again, there are three main questions to answer in working up the patient with hypernatraemia:</div><div><br /></div><div><b><span class="Apple-style-span" style="color:#000099;">1. Is the hypernatraemia due to water loss or sodium gain?</span></b><span class="Apple-style-span" style="color:#000099;"> </span>You can solve this riddle just by looking at the patient. If their extracellular fluid volume is expanded (e.g. oedema), then they've gained sodium, either because:</div><div><ul><li><i>you gave it to them</i> (iatrogenic administration of hypertonic saline or hypertonic sodium bicarbonate) - look for a higher urine sodium concentration; or </li><li><i>they have an excess or mineralocorticoid</i> - look for hypertension, and a hypokalaemic metabolic alkalosis; urine sodium is variable.</li></ul><div>You can now stop looking. However, if the extracellular fluid volume is anything but overloaded, then the hypernatraemia is due to water loss, and you must answer the second question.</div></div><div><br /></div><div><b><span class="Apple-style-span" style="color:#000099;">2. Is this water loss renal or extrarenal?</span></b> You judge this by looking at the urine results. If the loss is extrarenal (e.g. gastrointestinal water loss, or insensible water loss), then the kidneys will respond appropriately by excreting a small volume (~500 mls), hypertonic (more than 800 mosmol/kg) urine. Hooray! Have you found your cause of hypernatraemia yet? If not, then the kidneys must be to blame, and you must answer the third question.</div><div><br /></div><div><b><span class="Apple-style-span" style="color:#000099;">3. Is the renal water loss due to a diuresis?</span></b> Either an <i>osmotic diuresis</i> (e.g. flushing out masses of glucose after a diabetic ketoacidotic episode has been treated) or a <i>diuretic</i> will cause water to be lost in the urine, usually in excess of sodium. In either case, the <span class="Apple-style-span" style="color:#009900;"><b>daily urine osmole excretion rate</b></span> will be high (more than 750 mosmol per day). Calculate this by multiplying the urine osmolality by the urine volume. For example, if the urine osmolality is 400 mosmol and the amount of urine passed in a day is 2.5 litres, then the daily urine osmole excretion rate will be:</div><div><b><br /></b></div><div style="text-align: center;"><i>400 ⨯ 2.5 = 1000 mosmol/day</i><b> </b></div><div><br /></div><div>If the excretion rate isn't high, then your patient sadly has <i>diabetes insipidus</i>. Further workup will include differentiating nephrogenic from central diabetes insipidus - for instance, by administering desmopressin.</div><div><u><br /></u></div><div><u><br /></u></div><div>Hopefully that wasn't too painful! In the next post, you'll have the opportunity to put your physiology to the test a bit...</div><div> </div><div><u><br /></u></div><div><u><br /></u></div><div><u><span class="Apple-style-span" style="font-size:small;">Notes:</span></u></div><div><span class="Apple-style-span" style="font-size:small;">1. In hypernatraemia, unlike hyponatraemia, you don't have to worry about </span><i><span class="Apple-style-span" style="font-size:small;">other</span></i><span class="Apple-style-span" style="font-size:small;"> osmolytes (like glucose) getting in the way of your reasoning. You can safely assume that hypernatraemia is a hyperosmotic state, and so you don't need to pull a serum osmolality.</span></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com6tag:blogger.com,1999:blog-956701540737748712.post-64320706627098829152010-07-30T21:33:00.000+02:002010-08-02T18:36:01.369+02:00An approach to hyponatraemiaHyponatraemia is arguably the commonest metabolic derangement in medicine, and yet it can be tricky to pin down. There are extensive and complicated algorithms that can be worked through, but I've condensed many of them into what follows below. <div><br /></div><div><b><span class="Apple-style-span" style="color:#990000;"><br /></span></b></div><div><b><span class="Apple-style-span" style="color:#990000;">What you'll need</span></b>: serum sodium, serum osmolality, urine sodium, urine osmolality.</div><div><br /><div><br /></div><div><b><span class="Apple-style-span" style="color:#000099;">1. Look at the serum osmolality</span>. </b>Since sodium is the major determinant of extracellular fluid's osmolality, a low sodium should be reflected by a low serum osmolality. If the osmolality is low, go to step 2. </div><div><br /></div><div><span class="Apple-style-span" style="color:#006600;">If the osmolality is high</span> instead, then you need to find the extracellular osmolyte that's sucking water from the intracellular compartment (thereby decreasing the sodium concentration). There are only two important causes here - glucose and mannitol.</div></div><div><br /></div><div><span class="Apple-style-span" style="color:#006600;">If the osmolality is normal</span>, then you may be dealing with a case of pseudohyponatraemia. This occurs when a <i> solid</i> is present in the blood in increased amounts. This solid takes up such an amount of space that there is less sodium per volume of blood. Examples of such offending substances are massively elevated triglycerides and the excessively elevated serum proteins that occur in Waldenström's macroglobulinaemia. </div><div><br /></div><div><b><span class="Apple-style-span" style="color:#000099;">2. Look at the extracellular fluid volume.</span></b> <span class="Apple-style-span" style="color:#006600;">If it's increased</span> (e.g. oedema), this implies that both sodium <i>and</i> water are excessively high in this patient (it's just that the water's increase outnumbers the sodium's increase here). The major diseases in this category are cirrhosis, cardiac failure, renal failure, and nephrotic syndrome.</div><div><br /></div><div></div><span class="Apple-style-span" style="color:#006600;">If the extracellular fluid volume is decreased</span> (e.g. the patient is dehydrated, or hypovolaemic) then sodium is being lost somewhere. If it's being lost in the urine, the urine sodium concentration will be inappropriately high (> 20 mmol/L). This occurs with diuretics and with hypoaldosteronism. If it's being lost elsewhere, the kidneys will try their best to hang on to any sodium, and so the urine sodium concentration will generally be less than 20 mmol/L. Such conditions include vomiting, diarrhoea, burns and even excessive sweating.<div><span class="Apple-style-span" style="color:#006600;"><br /></span></div><span class="Apple-style-span" style="color:#006600;">If the extracellular fluid volume is normal</span>, then there are three conditions to consider: SIADH, hypothyroidism and Addison's disease. These can usually be easily distinguished with a few further tests (e.g. TSH).<div><br /></div><b><span class="Apple-style-span" style="color:#000099;">3. Still no luck?</span></b> If none of the above categories fit, check that the patient's urine osmolality is appropriately low (it should be less than 100 mosmol/L). If this isn't the case, consider whether it's possible that the patient is drinking (or receiving via IV fluids) more than 20-30 L per day. Needless to say, this isn't a common cause of hyponatraemia! However, if it ever does manage to occur, the amount of water taken in will exceed the kidney's ability to excrete it, and the sodium concentration will drop accordingly.<br /><br />I think that the above schema is quite handy, but feel free to amend it to suit your own desires. Now, if you're feeling strong, click onwards and look at <a href="http://medicguide.blogspot.com/2010/08/approach-to-hypernatraemia.html">an approach to <i>hyper</i>natraemia</a>.jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com2tag:blogger.com,1999:blog-956701540737748712.post-66881751818123804902010-07-26T21:03:00.000+02:002010-07-30T22:16:04.151+02:00Sodium and Water (4) - The differenceOK, in the <a href="http://medicguide.blogspot.com/2010/07/sodium-and-water-3-sodium-balance.html">last post</a>, I alluded to the difference between maintaining the body's water balance and maintaining the body's sodium balance. It's quite an important distinction, and it's clinically relevant too.<div><br /></div><div>If you increase or decrease the total body water <i>independently</i> of its sodium content, then it follows that the sodium <b>concentration</b> will be altered. Think about it: if I have 100 mmol of sodium in one litre, but I then add 200 mls of water, I've changed the sodium <i>concentration</i> from 100 mmol/L to 83 mmol/L [100/1.2]. But changing the sodium concentration hasn't meant that I've changed the sodium <b>content</b> (amount) - which has remained the same, at 100 mmol, no matter how much water I've added.</div><div><br /></div><div><span class="Apple-style-span" style="color:#000099;"><i>Therefore, as a general rule, changes in sodium concentration reflect disturbed water homeostasis. </i><span class="Apple-style-span" style="color:#000000;">The problem will lie with one of the regulators of water balance, then: water intake or AVP.</span></span></div><div><br /></div><div>Now look what happens if I take a human body and force it to retain sodium. You might think that the sodium concentration would again be affected, but remember that sodium is highly osmotically active: it more or less drags an equal amount of water with it. Therefore, reabsorbing (or failing to excrete) sodium will <i>not</i> change the body's sodium concentration. Rather, it will cause there to be a rise in the total amount (content) of sodium and water in the body.</div><div><br /></div><div><i><span class="Apple-style-span" style="color:#000099;">Therefore, as a general rule, changes in sodium content cause hyper- or hypovolaemia.</span></i> Clinically, this manifests as oedema or dehydration/shock respectively. The problem lies with one of the regulators of sodium balance, usually the renin-angiotensin-aldosterone system.</div><div><br /></div><div>Before this gets too theoretical, let's look at a few clinical examples.</div><div><br /></div><div><ol><li><b>Cardiac failure</b> - in this state, the sodium concentration is often low, and the patient is oedematous. From this, we can infer that (1) water is being retained in excess of sodium, causing hyponatraemia, and (2) the body contains too much of both sodium and water, causing oedema. Sure enough, treatment involves water and salt restriction, and diuretics to promote water and salt loss.</li><li><b>Diarrhoea</b> - the sodium level here can be low, normal or high depending on whether sodium is lost in excess of water or vice versa. For the sake of argument, let's say that in this patient the sodium is low. Regardless of the sodium level, however, the patient is certainly dehydrated. Therefore, unlike in cardiac failure, the treatment of hyponatraemic diarrhoea will include giving (not restricting) sodium and water (e.g. via intravenous normal saline).</li></ol><div>In the next post, we'll discuss <a href="http://medicguide.blogspot.com/2010/07/approach-to-hyponatraemia.html">an approach to hyponatraemia</a>.</div></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com3tag:blogger.com,1999:blog-956701540737748712.post-6788000416700023932010-07-25T10:56:00.000+02:002010-07-26T21:29:44.144+02:00Sodium and Water (3) - Sodium Balance<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://1.bp.blogspot.com/_tN90RefJ5Hk/TEwEtuSQNXI/AAAAAAAAA1Y/QNCPygNtta8/s1600/sodium.jpg"><img style="float:right; margin:0 0 10px 10px;cursor:pointer; cursor:hand;width: 320px; height: 206px;" src="http://1.bp.blogspot.com/_tN90RefJ5Hk/TEwEtuSQNXI/AAAAAAAAA1Y/QNCPygNtta8/s320/sodium.jpg" border="0" alt="" id="BLOGGER_PHOTO_ID_5497774428677748082" /></a><div>In the <a href="http://medicguide.blogspot.com/2010/07/sodium-and-water-2-water-balance.html">previous post</a>, we discussed how the body regulates its free water content. Now we turn to sodium regulation.</div><div><br /></div><div>We can lose a minimum of about 100 mmol per day. Therefore, this is the amount that we need to ingest on a daily basis. You lose some sodium in your sweat, and some sodium in your faeces, but these are largely unregulated losses. The place where the body does its sodium bookkeeping is in the kidneys.</div><div><br /></div><div>Of the filtered load of sodium, about 98% is reabsorbed:</div><div><ol><li>Two thirds is reabsorbed in the proximal convoluted tubule.</li><li>One quarter is reabsorbed in the thick ascending loop of Henle (via the Na<sup>+</sup>/K<sup>+</sup>/2Cl<sup>-</sup> cotransporter)</li><li>About 5% is reabsorbed at the distal convoluted tubule (by the thiazide -sensitive Na<sup>+</sup>/Cl<sup>-</sup> cotransporter.</li><div><br />These channels aren't particularly regulated from a sodium perspective. Rather it is at the last stage that the body finally turns its attention to the fate of sodium.</div><br /><li>The remaining sodium reabsorption occurs at the distal proximal tubule, and in the cortical and medullary collecting tubules. This stage is sensitive to hormonal manipulation.</li></ol><div>And what are these sodium-controlling hormones? The most famous is <b><span class="Apple-style-span" style="color:#990000;">aldosterone</span></b>, which causes the principal cells in this area to reabsorb sodium (in exchange for potassium). Incidentally, it also performs as similar swap in the gut, although this is a less important phenomenon. </div></div><div><br /></div><div>A slightly less well-known hormone is <b><span class="Apple-style-span" style="color:#990000;">atrial natriuretic peptide</span></b>, which is secreted in response to atrial stretch. It promotes sodium loss directly (by inhibiting distal tubular sodium reabsorption) and indirectly (by decreasing <i>renin</i>, one of the controlling hormones for aldosterone release). </div><div><br /></div><div>In a similar class is <b><span class="Apple-style-span" style="color:#990000;">brain natriuretic peptide</span></b>, which is secreted in response to ventricular stretch and has similar properties to its atrial counterpart. (Note, it <i>doesn't</i> come from our brains, despite the name!)</div><div><br /></div><div>Between them, these three hormones regulate the <i>amount </i>of sodium in our bodies. They <i>don't</i> really regulate sodium concentration though - this is the job of the body's water balance system described in the <a href="http://medicguide.blogspot.com/2010/07/sodium-and-water-2-water-balance.html">previous post</a>. It's important not to get this mixed up. If your patient comes back with a low serum sodium <i>concentration</i>, he may still have a high total body sodium <i>content</i>. </div><div><br /></div><div>If this last point seems a bit oblique, don't worry: we'll spend a bit of time on it next.</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com2tag:blogger.com,1999:blog-956701540737748712.post-75044650784297064012010-07-24T14:57:00.000+02:002010-07-24T15:30:57.914+02:00Sodium and Water (2) - Water balance<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://4.bp.blogspot.com/_tN90RefJ5Hk/TErqmQVS24I/AAAAAAAAA1Q/iS9-wNGuOCg/s1600/MP900438618+(1).JPG"><img style="float:right; margin:0 0 10px 10px;cursor:pointer; cursor:hand;width: 214px; height: 320px;" src="http://4.bp.blogspot.com/_tN90RefJ5Hk/TErqmQVS24I/AAAAAAAAA1Q/iS9-wNGuOCg/s320/MP900438618+(1).JPG" border="0" alt="" id="BLOGGER_PHOTO_ID_5497464238099323778" /></a>To maintain a steady state, your intake of a substance must equal your loss of that substance, and water is no exception. So what are you <i>obligatory</i> water losses - those losses that you can't help but sustain?<div><br /></div><div>First up, the kidney can only concentrate substances up to a maximum of 1200 mosmol/L. Since we produce about 600 msomol of substances per day, that means that you have to urinate out about 500 ml per day, no matter how inconvenient this is.</div><div><br /></div><div>Next, we have evaporation from the skin, which totals a minimum of about 400 ml per day. If you're exercising, or out in the hot sun, this amount can increase to a staggering 5 L.</div><div><br /></div><div>Then there's evaporation from our respiratory tracts. The air we breathe in has a lot less water vapour in it than it ends up with as it descends into our lungs - water evaporates from our moist mucosa to join it. Under normal conditions, the amount of water lost in this way is about 350 ml, but this number will increase rapidly if you are breathing heavily or rapidly. </div><div><br /></div><div>Lastly, there is fluid loss in our stools, which as we all know aren't perfectly dry. The body is actually quite good at retaining fluid from our gastrointestinal tracts, and so we only lose an average of about 100 ml per day via defaecation.</div><div><br /></div><div>OK, so under optimal conditions, this means that we lose about 1400 ml per day, although usually it's a bit more than this. Therefore, this is the minimum amount if fluid we need to take in to keep in balance.</div><div><br /></div><div>Fortunately, we don't have to do the calculation consciously: <span class="Apple-style-span" style="color:#000099;">our intake of water is regulated by the sensation of thirst</span>. Osmoreceptors, located in the anterior hypothalamus, are stimulated by the rise in osmolarity that corresponds to water depletion. As a result, we drink more and the status quo is preserved.</div><div><br /></div><div>On the other hand, what if we've taken too much water on board, and need to excrete the excess? The kidneys come to the rescue here: they are capable of excreting urine with an osmolality of just 50 mosmol/L and so can get rid of large volumes of water (without necessarily increasing the renal losses of other substances). <span class="Apple-style-span" style="color:#000099;"> The principle determinant of renal water excretion is arginine vasopressin</span> (AVP, also known as antidiuretic hormone - ADH). This polypeptide hormone is secreted by the posterior hypothalamus and acts on the V2 receptors of the kidney (mainly in the collecting tubules and ducts). Binding of the hormone causes these cells to insert water channels (<span class="Apple-style-span" style="color:#990000;">aquaporins</span>) into their luminal membrane, thereby massively increasing the permeability of these cells to water. The water can then passively move from the 'urine' side back into the cells and hence back to the body.</div><div><br /></div><div>Between them, thirst and AVP are the two main mechanisms that preserve a constant body osmolality.</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com3tag:blogger.com,1999:blog-956701540737748712.post-9870869862295898202010-07-24T14:35:00.000+02:002010-07-25T12:43:02.375+02:00Ineffective vs effective osmolesHere's a challenge for you. In the <a href="http://medicguide.blogspot.com/2010/07/sodium-and-water-1-body-compartments.html">previous post</a>, I said that examples of ineffective osmolytes were urea and glucose. That's because these two substances, although osmotically active, could easily distribute themselves across the various body compartments and so wouldn't cause fluid shifts from one compartment to the other. Although this is true in health, what happens in the case of diabetes?<br /><br />The answer, of course, is that glucose becomes an effective osmolyte, capable for causing fluid shifts from the intracellular to the extracellular compartments. This is because diabetics have a (relative or absolute) lack of insulin, which is required for glucose entry into many cell types. Thus, for all intents and purposes, glucose becomes more confined to the extracellular compartment in diabetes.<br /><br />This has serious implications, since the resultant fluid shifts are a major part of the pathogenesis of both diabetic ketoacidosis and the hyperosmolar non-ketotic state, which you've probably heard about.jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com9tag:blogger.com,1999:blog-956701540737748712.post-60664440383159496292010-07-24T09:06:00.000+02:002010-07-25T12:43:10.105+02:00Sodium and Water (1) - Body compartments<div style="text-align: left;">The human body is approximately 50-60% water (on the higher end for men, on the lower end for women). This water is distributed in two major compartments - the intracellular fluid compartment and the extracellular fluid compartment, in a ratio of roughly 2:1.</div><div><br /></div><div>The extracellular fluid is further divided into interstitial fluid and plasma, in a ratio of about 3:1. Together, therefore, the breakdown looks something like this:</div><div><br /></div><div><img src="http://2.bp.blogspot.com/_tN90RefJ5Hk/TEqUfyz2jVI/AAAAAAAAA1I/Uh283nwP-Og/s400/Body+water.jpg" style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 400px; height: 162px;" border="0" alt="" id="BLOGGER_PHOTO_ID_5497369569095224658" /></div><div><br /></div><div>There are barriers between these compartments. Between the intracellular and extracellular compartments is the cell wall, and between the interstitial and plasma compartments lies the blood vessel wall (at its thinnest, just a single layer of endothelial cells).</div><div><br /></div><div>Water can move freely between these compartments without difficultly, but many other substances, some of them osmotically active, can't. Therefore, the <i>amount</i> of water in each compartment depends on the relative number of osmolytes in each compartment - water will always flow to the compartment with a higher osmolality. The major division is between the intracellular and extracellular portions:</div><div><ul><li>The major extracellular determinants of osmolality are sodium and its accompanying anions (chloride and bicarbonate, mostly).</li><li>The major intracellular determinants of osmolality are potassium and organic phosphates (ATP, creatinine phosphate and phospholipids).</li></ul>Hence, if the sodium concentration goes up in your extracellular fluid, water will tend to leave your cells and move to make up the difference there. Since water moves so quickly, <span class="Apple-style-span" style="color:#000099;">the osmolalities of the extracellular and intracellular compartment are always equal</span>. <span class="Apple-style-span" style="color:#000099;">This does not mean that the (shared) osmolality is <i>normal</i>, though.</span> In the sodium example above, the osmolality in <i>both</i> the intra- and extracellular comparments will be higher than normal (the normal range for osmolality is 275 - 290 milliosmoles / kg).</div><div><br /></div><div>Lastly, a word about the so-called<span class="Apple-style-span" style="color:#FF0000;"> </span><b><span class="Apple-style-span" style="color:#CC0000;">ineffective osmoles</span></b>. Osmolytes that (like water but unlike sodium) can move easily between compartments tend to increase the osmolality of both compartments <i>without</i> ever inducing water to shift compartments. Glucose and urea are two examples of such osmolytes. If I injected your extracellular fluid with extra urea, the osmolality of the compartment would increase temporarily, but since urea can move with ease to the intracellular compartment too, it would wouldn't have the opportunity to cause fluid shifts. It would merely increase the osmolality of <i>both</i> compartments simultaneously and there would be no net movement of water from any compartment. This is not the case with sodium, for example, which is effectively <i>stuck</i> in the extracellular compartment. Injecting your extracellular fluid with sodium would cause a rise in the osmolality of <i>only</i> this compartment, and fluid would flow out of the intracellular compartment until the osmolalities of both compartments were equal again (though both would be higher than before).</div><div><br /></div><div>You can estimate the osmolality of your body's fluids by the following equation (all concentrations in mmol/L):</div><div><br /></div><div style="text-align: center;"><i>osmolality = 2 ⨯ [Na<sup>+</sup>] + [urea] + [glucose]</i></div><div style="text-align: center;"><i><br /></i></div><div style="text-align: left;">If your glucose and BUN measurements are made in mg/dL (typical in the US), then the equation becomes:</div><div style="text-align: left;"><br /></div><div style="text-align: center;"><i>osmolality = 2 ⨯ [Na<sup>+</sup>] + [glucose]/18 + [BUN]/2.8</i></div><div><br /></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com3tag:blogger.com,1999:blog-956701540737748712.post-47804616499992986552009-11-24T20:40:00.000+02:002009-11-24T20:40:54.527+02:00Why do we measure hydrogen ions in pH?<p class="MsoNormal">Ever wondered why we measure the concentration of hydrogen ions as pH, rather than as mmols, by which so many other bodily substances are calibrated?</p> <p class="MsoNormal">First up, what does pH <i style="mso-bidi-font-style:normal">mean</i>? The ‘p’, by convention, stands for ‘-log’.<span style="mso-spacerun:yes"> </span>Thus the pH scale is a negatively logarithmic one.<span style="mso-spacerun:yes"> </span>The negative means that if the hydrogen ion concentration goes up, the pH is recorded as going down, and vice versa.<span style="mso-spacerun:yes"> </span>In other words, a pH of 3 is much more acidic than a pH of 7.<span style="mso-spacerun:yes"> </span>And as for why we use logarithms, this is simply a convenient calibration to use in certain circumstances, especially when the variability of the thing being measured (i.e. the variation in hydrogen ion concentration) covers several orders of magnitude.</p> <p class="MsoNormal"><o:p>But back to the question – why do we measure hydrogen ions by their negative logarithm, but not (say) sodium ions?<span style="mso-spacerun:yes"> </span>One of the problems is that the concentration of hydrogen ions is truly tiny when compared with other ions.<span style="mso-spacerun:yes"> </span>To use an example from my physiology textbook, the concentration of sodium in extracellular fluid (~140 mmol/L) is about 3.5 <i style="mso-bidi-font-style:normal">million</i> times as great as the normal concentration of hydrogen – which averages only 0.0004 mmol/L!<span style="mso-spacerun:yes"> </span>Therefore we’d need to move away from mmol/L anyway to prevent ourselves from eternally writing zeros when it comes to talking about hydrogen ion concentrations.</o:p></p> <p class="MsoNormal">However, if this were the only concern, we could just shift from talking about millimoles to micromoles, as we do (at least here outside <st1:country-region><st1:place>America</st1:place></st1:country-region>!) with creatinine.<span style="mso-spacerun:yes"> </span>(A normal value in a man might be 85 μmol/dL.)<span style="mso-spacerun:yes"> </span>The even smaller scale of nanomoles might have been even better.<span style="mso-spacerun:yes"> </span>There is another, truer reason, that we measure hydrogen ions in a logarithmic scale, and it turns out to be disappointingly capricious.</p> <p class="MsoNormal">As I alluded to above, logarithmic scales are useful when the data you are measuring cover several orders of magnitude.<span style="mso-spacerun:yes"> </span>Chemists did the first and most detailed work on hydrogen ion concentrations, and found that the concentrations in their experiments could rapidly vary by <i style="mso-bidi-font-style:normal">trillions </i>of times.<span style="mso-spacerun:yes"> </span>One minute the hydrogen ions might clock up a puny 0.000000005 mol/L, but then they added another chemical and found that this number jumped to 0.2 mol/L.<span style="mso-spacerun:yes"> </span>In circumstances like these, they found it easier to track the changes in logarithmic form.<span style="mso-spacerun:yes"> </span>The above jump, for instance would have been from 8.3 to 0.69 – much more manageably notated!</p> <p class="MsoNormal">And we in medicine simply inherited this way of dealing with hydrogen ions – even though the total variability of hydrogen ions in a (living) <i style="mso-bidi-font-style:normal">human being </i>is only about 15 fold.<span style="mso-spacerun:yes"> </span>We could have used picomoles and been quite happy, had it not been for the chemists.</p>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-75805010506691650842009-11-22T17:41:00.000+02:002009-11-22T18:03:19.701+02:00Why are the kidneys so redundant?<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://3.bp.blogspot.com/_tN90RefJ5Hk/SwlgjJmbRDI/AAAAAAAAA0k/hTkoqQmEl3Q/s1600/kidney.jpg"><img style="float:right; margin:0 0 10px 10px;cursor:pointer; cursor:hand;width: 400px; height: 317px;" src="http://3.bp.blogspot.com/_tN90RefJ5Hk/SwlgjJmbRDI/AAAAAAAAA0k/hTkoqQmEl3Q/s400/kidney.jpg" border="0" alt="" id="BLOGGER_PHOTO_ID_5406958984623768626" /></a>Forgive the provocative title; what I merely meant to point out is that the kidneys filter some 180 liters of fluid per day, and in the process consume more than 10% of the body's resting energy costs. So what, you might say, perhaps such resource consumption is necessary - anything less than this would no doubt have significantly deleterious effects.<div><br /></div><div>Except that it doesn't seem to. You only notice a rise in serum creatinine levels, or any other marker of uraemia, after fully 50% of the kidneys' function has been lost. In other words, as some donors know, you can make do with just <i>one</i> kidney! Such an extravagance would surely be penalised by evolution, for such resources can be better diverted into other things - like finding food, fighting rivals and mating (!).</div><div><br /></div><div>What is the solution to the paradox? I don't know, but two possible reasons for the maintenance of excess renal function in our ancestral past come to mind:</div><div><ol><li>Perhaps this increased capacity was required more frequently than we think. Prior to civilization, perhaps our diets contained a higher toxin load - a load that we now bypass thanks to both millennia of selective breeding for more human-friendly food and better food processing. Furthermore, perhaps states of hypovolaemia (which are liable to cause acute renal failure) were more common before. I'm thinking now of blood loss and dehydration...</li><li>More shrewdly, perhaps our normal bodily function <i>is</i> actually affected by a more modest decline in renal function than we currently think it is. For instance, perhaps (say) growth is relatively stunted by even a 10% decline in renal function (which would raise the retained collection of toxins by 10%). We only think the kidneys are so lavishly wasteful because the first abnormality that <i>we </i>can detect happens long after this point.</li></ol><div>I am indebted to <a href="http://www.ncbi.nlm.nih.gov/pubmed/17898101?dopt=Abstract">this</a> article for the second insight.</div></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com2tag:blogger.com,1999:blog-956701540737748712.post-14149866468722646312009-11-15T21:25:00.000+02:002009-11-15T21:35:21.720+02:00Biology in proportionWhat's the smallest biological object that you can see with your unaided eye? Probably the human egg cell at its biggest. It registers just before the 0.1mm limit at which our eyes can no longer make anything out.<div><br /></div><div>But how big is this cell relative to a bacterium? And what would an approaching virus look like that bacterium? Would it be a roughly equally sized monster, or (if it had eyes) would it have to strain to see the nearing enemy? Or are both scenarios incorrect, with the actuality lying somewhere in the middle?</div><div><br /></div><div>The point is that it can be hard to get a good feel for how sizes compare when it comes to biology (and medicine). I therefore suggest that you click <a href="http://learn.genetics.utah.edu/content/begin/cells/scale/">here</a> and attempt to remedy this. Simply slide the ruler along and you'll fly through a billion times magnification to get a sense of scale. Wonderful!</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com1tag:blogger.com,1999:blog-956701540737748712.post-22430011220719872592009-11-12T22:00:00.000+02:002009-11-12T22:06:01.495+02:00Paroxysmal hypertensionIf your patient has <i>episodic</i> (as opposed to persistent) spells of hypertension, which diagnostic avenues should you pursue? The list is actually quite small, and the one I was taught is as follows:<div><br /></div><div><ul><li>Anxiety disorders, including panic attacks (usually only a <i>mild</i> increase in BP)</li><li>Drug abuse (only some types, like cocaine)</li><li>Phaeochromocytoma</li></ul><div>Most of the other causes of hypertension lead to a <i>persistent</i> elevation of the blood pressure.</div></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-74601815701019656322009-11-10T19:16:00.000+02:002009-11-14T10:00:11.850+02:00What do the words "amyotrophic lateral sclerosis" mean?<a onblur="try {parent.deselectBloggerImageGracefully();} catch(e) {}" href="http://2.bp.blogspot.com/_tN90RefJ5Hk/Svmgptngz3I/AAAAAAAAAzs/1Dwasdky364/s1600-h/steven+hawking.jpg"><img style="float:right; margin:0 0 10px 10px;cursor:pointer; cursor:hand;width: 250px; height: 188px;" src="http://2.bp.blogspot.com/_tN90RefJ5Hk/Svmgptngz3I/AAAAAAAAAzs/1Dwasdky364/s400/steven+hawking.jpg" border="0" alt="" id="BLOGGER_PHOTO_ID_5402525866488024946" /></a>Amyotrophic lateral sclerosis (ALS) is the most common form of progressive motor neurone disease, and is characterised by the almost relentless loss of both upper and lower motor neurones.<span style="mso-spacerun:yes"> </span>It has achieved a certain infamy through some of its more famous sufferers, <s>like Steven Hawking.</s> [Edit: see below] There are lots of good articles on it out there, but I just wanted to answer a particular question: where does its bizarre name come from?<p></p> <p class="MsoNormal"><o:p> </o:p></p> <p class="MsoNormal">Amoytrophic should be broken down into its three Greek root words: a-myo-trophic.</p> <p class="MsoNormal" style="margin-left:35.0pt;text-indent:-17.0pt;mso-list:l0 level1 lfo1; tab-stops:list 36.0pt"><span style="font-family:Symbol; mso-fareast-font-family:Symbol;mso-bidi-font-family:Symbol;"><span style="mso-list:Ignore">·<span style="font:7.0pt "Times New Roman""> </span></span></span>‘<span class="Apple-style-span" style="color:#000099;">a</span>’ is similar to saying “not”<span style="mso-spacerun:yes"> </span>or “absent”, or “un-“</p> <p class="MsoNormal" style="margin-left:35.0pt;text-indent:-17.0pt;mso-list:l0 level1 lfo1; tab-stops:list 36.0pt"><span style="font-family:Symbol; mso-fareast-font-family:Symbol;mso-bidi-font-family:Symbol;"><span style="mso-list:Ignore">·<span style="font:7.0pt "Times New Roman""> </span></span></span>‘<span class="Apple-style-span" style="color:#000099;">m</span><span class="Apple-style-span" style="color:#000099;">yo</span>’ refers to muscle cells (e.g. myocardium – the “muscle of the heart”)</p> <p class="MsoNormal" style="margin-left:35.0pt;text-indent:-17.0pt;mso-list:l0 level1 lfo1; tab-stops:list 36.0pt"><span style="font-family:Symbol; mso-fareast-font-family:Symbol;mso-bidi-font-family:Symbol;"><span style="mso-list:Ignore">·<span style="font:7.0pt "Times New Roman""> </span></span></span>‘<span class="Apple-style-span" style="color:#000099;">t</span><span class="Apple-style-span" style="color:#000099;">rophic</span>’ means something close to “nourishing”, although in medical terminology it is often taken to mean something nearer to “growing”.</p> <p class="MsoNormal"><o:p> </o:p></p> <p class="MsoNormal">For instance, if you don’t use your muscles they may waste away.<span style="mso-spacerun:yes"> </span>The medical term for this would be “atrophy”, as in “a-trophy” – “not grow”.<span style="mso-spacerun:yes"> </span>Thus “amyotrophic” means (loosely) “wasting away of the muscles”.<span style="mso-spacerun:yes"> </span>This is a distinct clinical feature of ALS, and is due to the denervation of muscle fibres that occurs as the motor neurones die away.</p> <p class="MsoNormal"><o:p> </o:p></p> <p class="MsoNormal">Then there’s the “lateral sclerosis bit”.<span style="mso-spacerun:yes"> </span>ALS affects both upper and motor neurones; the former causes a thinning of the descending white matter tracts travelling from the brain down the spinal cord.<span style="mso-spacerun:yes"> </span>These tracts happen to be located largely in the lateral portion (and, to a slightly lesser degree, anterior portion) of the spinal cord.<span style="mso-spacerun:yes"> </span>As the tracts degenerate, they are replaced by the nervous system’s equivalent of fibrosis – gliosis.<span style="mso-spacerun:yes"> </span>And this of course gives the lateral (and anterior) portion of the spinal cord a particular firmness, with the attractive pathological term for hardening being “sclerosis”.</p> <p class="MsoNormal"><o:p> </o:p></p> <p class="MsoNormal">There you go!</p><p class="MsoNormal"><br /></p><p class="MsoNormal">Edit: Sorry, Stephen Hawking almost certainly does <i>not </i>have ALS. This disease typically kills in 3-5 years; he's been going for about 10 times as long. It is thought that he may have a variant form, or more probably one of the spinal muscular atrophies.<i></i></p>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com6tag:blogger.com,1999:blog-956701540737748712.post-78651210112536536492009-11-08T08:57:00.000+02:002009-11-08T09:22:11.417+02:00Can you calculate the haemoglobin concentration from only the haematocrit?Sort of. <div><br /></div><div>The <a href="http://medicguide.blogspot.com/2007/10/what-is-does-haematocrit-refer-to.html">haematocrit</a> (Hct) describes the proportion of one's blood that is made up of red blood cells. It's usual range is about 35-45% for women and 40-50% for men. The rest is almost all plasma, with a minor contribution coming from white cells and platelets.</div><div><br /></div><div>The other figure you need is the mean corpuscular haemoglobin concentration (MCHC). As the name hints, this is the concentration of haemoglobin in a particular volume of red cells. So, you can sort of see how knowing both (i) the concentration of haemoglobin within a bunch of red cells and (ii) the proportion of the whole blood that these red cells constitute could tell you the concentration of haemoglobin for the whole blood. Indeed, the formula is simple:</div><div><br /></div><div style="text-align: center;"><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="color:#CC0000;"><span class="Apple-style-span" style="font-size:medium;">Hct × MCHC = Hb</span></span></span></div><div style="text-align: center;"><br /></div><div style="text-align: left;">For instance, assuming a haematocrit of 40% and a MCHC of 35 g/dl, the Hb turns out to be:</div><div style="text-align: left;"><br /></div><div style="text-align: center;"><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="font-size:medium;"><span class="Apple-style-span" style="color:#666666;">0.40 </span></span></span><span class="Apple-style-span" style=" line-height: 19px; "><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="font-size:medium;"><span class="Apple-style-span" style="color:#666666;">×</span></span></span></span><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="font-size:medium;"><span class="Apple-style-span" style="color:#666666;"> 35 = 14 g/dl</span></span></span></div><div style="text-align: center;"><br /></div><div style="text-align: left;">You really should have the exact MCHC for the calculations (it's almost always given as part of a complete blood count), but if you're desperate you can estimate based on the normal range of 32 to 36 g/dl.</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com1tag:blogger.com,1999:blog-956701540737748712.post-79573682814687077382009-11-05T13:17:00.000+02:002009-11-05T14:57:09.669+02:00More on Anaemia of Chronic InflammationHere's a good chance to revise your understanding of iron metabolism with a discovery that's hot off the press.<div><br /></div><div>The body has no special method to get rid of iron. Any excess iron can only be lost by shedding cells that contain the element, such as red cells (in bleeding) and enterocytes (as part of faeces). Iron absorption therefore has to be closely scrutinized, and the chief regulator is a protein produced by the liver, called <b><span class="Apple-style-span" style="color:#CC0000;">hepcidin</span></b>. The 'export proteins' for iron are called <b><span class="Apple-style-span" style="color:#CC0000;">ferroproteins</span></b>, and were known to be present on cells participating in iron metabolism, including enterocytes (where iron is absorbed and some of it stored) and macrophages (which engulf aged red cells and recycle their iron).</div><div><br /></div><div>Hepcidin binds to and destroys ferroproteins, with the net result that iron is trapped within its storage sites. Under conditions of iron deficiency, therefore, hepcidin is down-regulated, permitting the ferroproteins to rapidly move iron out of the stores to the rest of the body. Conversely, cytokines (like IL-6) produced during inflammation up-regulate hepcidin, sequestering the iron away from microbes (real or imaginary) that the body assumes are causing the inflammatory response. This is one mechanism producing the familiar anaemia of chronic inflammation (ACI).</div><div><br /></div><div>OK, that's the background; now the new bit. It has long been known that, although characteristic of either condition, the microcytosis of iron deficiency is usually far worse than that of ACI. In fact, in about 70% of ACI cases, there isn't even a microcytosis! This is puzzling, though, since in either case the microcytosis is caused by a deficiency of iron to the developing red cells - there isn't enough iron in the body in the former, and the iron is inaccessible in the latter. Furthermore, the microcytosis might be supposed to be more severe in ACI, since in this condition iron's transport protein, <b><span class="Apple-style-span" style="color:#CC0000;">transferrin</span></b>, is also down-regulated. Yet the opposite pattern occurs. Why?</div><div><br /></div><div>A <a href="http://www.cell.com/cell-metabolism/abstract/S1550-4131(09)00067-9">recent study by Zhang et al.</a> located ferroproteins on erythroid precursors, a fact that came as a surprise to us all, since these cells would be the one cell type you would <i>least</i> expect to export iron - they're busy stuffing themselves full of iron-containing haemoglobin proteins! It therefore appears that the body sometimes needs to make use of this iron elsewhere in the body, in myoglobin, cytochromes, etc. But now think of the implication: during conditions of iron deficiency, hepcidin levels plummet, allowing the ferroproteins to release iron from the erythroid precursors to be used by the rest of the body. On the other hand, during inflammation, hepcidin production is ramped up, and the iron is trapped within the erythroid precursors, where it can presumably be used to continue red cell production.</div><div><br /></div><div>At a stroke this solves the puzzle of why the erythrocytes are so much worse off, iron-wise, in iron deficiency, compared to ACI.</div><div><br /></div><div><br /></div><div><span class="Apple-style-span" style="font-size:small;">Source</span>: <span class="Apple-style-span" style=" ;font-family:verdana, arial, helvetica, sans-serif;font-size:small;">Keel, Sioban B., Abkowitz, Janis L.</span></div><span class="Apple-style-span" style=" ;font-family:verdana, arial, helvetica, sans-serif;font-size:small;"><strong><a href="http://content.nejm.org/cgi/content/short/361/19/1904">The Microcytic Red Cell and the Anemia of Inflammation</a></strong><br />N Engl J Med 2009 361: 1904-1906</span>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-65847037212693538182009-09-30T15:49:00.000+02:002009-09-30T21:43:52.607+02:00Hardy-Weinberg Question #4<div>This is the latest of the Hardy-Weinberg questions that I've received - see the rest of them <a href="http://medicguide.blogspot.com/2007/11/feature-hardy-weinberg-equation-and.html">here</a>.</div><div><span class="Apple-style-span" style="color:#000099;"><b><br /></b></span></div><div><b><span class="Apple-style-span" style="color:#000099;">Question:</span></b></div><div><span class="Apple-style-span" style="font-style: italic; ">If the frequency of a homozygous dominant genotype is 0.49, what is the frequency of the homozygous recessive genotype?</span></div><i>The relevant equation is: p</i><sup><i>2</i></sup><i> + 2pq + q</i><sup><i>2</i></sup><i> = 1</i><div><br /></div><div><br /></div><div><b><span class="Apple-style-span" style="color:#000099;">Answer:</span></b></div><div>Remember that the equation provided in the question isn't just a random algebraic expression, it <i>means</i> something. 'p<sup>2</sup>' is traditionally taken to refer the frequency of the homozygous dominant genotype, '2pq' stands for the frequency of the heterozygous genotype, and 'q<sup>2</sup>' is the homozygous recessive genotype's frequency.</div><div><br /></div><div>Therefore, from the question:</div><div><br /></div><div style="text-align: center;">p<sup>2</sup> = 0.49<br />∴ p = 0.7</div><div style="text-align: center;"><br /></div><div style="text-align: left;">OK, now that we have the value for p, how do we get q's value? Well, for that we need the second of the two important Hardy-Weinberg equations. Recall that, since there are only two alleles assumed for this gene, all the 'p's and all the 'q's must collectively account for 100% of the total alleles. Hence:</div><div style="text-align: left;"><br /></div><div style="text-align: center;">p + q = 1<br />∴ 0.7 + q = 1 (substituting in the above value)</div><div style="text-align: center;">∴ q = 0.3</div><div style="text-align: center;"><br /></div><div style="text-align: left;">From here, it's really easy to get to the q<sup>2</sup> [the homozygous recessive frequency]: (0.3)<sup>2</sup> = 0.09.</div><div style="text-align: left;"><br /></div><div style="text-align: left;">Hope that helps!</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-50309243654281913082009-09-27T18:36:00.000+02:002009-09-27T19:03:35.645+02:00Why you can't see the colour of the car that hit youThe visual system is one of the best understood in all neuroscience (not that there aren't plenty of mysteries about it!), and its most salient features is its <i>economy</i>. The brain is an expensive organ, evolutionarily - pound for pound, it consumes 22 times more energy than muscle (which is itself rather expensive), and all this has to be repaid by eating more in reply. Therefore, any bit of it that doesn't absolutely <i>have</i> to be around won't make the cut as the aeons roll by.<div><br /></div><div>One way you could have designed the retina would be to cover it densely with both cones (for high acuity colour vision) and rods (for high sensitivity night vision). In this way, no matter where the photons landed, you would get the best image possible.</div><div><br /></div><div>But the eye chooses a more elegant system. It concentrates almost all its cones in and around the <i>fovea centralis</i>, a region near the centre of the eye. To some extent, it has put almost all its eggs in one basket, since any images that are attempting to form themselves elsewhere on the retina are left to the low quality rods to fumble with. The visual system makes up for this by constantly rotating the eyeball so that the centre of our visual field falls on it; in this way, whatever we are 'looking at' can be rendered in the highest possible quality.</div><div><br /></div><div>Furthermore, our brain hides this flaw from us by rapidly darting the eye around a particular scene, and patching the numerous, small high quality images together. It may surprise you to find out just how bad your peripheral vision actually is. The only way to do this is to keep your eyes absolutely still and then try to make out the details of something in the periphery of your vision. </div><div><br /></div><div>Reading is a good example. Place something with large letters in near to you. (Take care not to peek at what the text says, or the brain will cheat, as I've mentioned. One way of minimising this likelihood is to ask a friend to write something down instead.) If you are stringent about keeping your eyes staring straight ahead, it won't be possible to make out any letters even a few degrees from centre.</div><div><br /></div><div>Furthermore, since cones are used for both high-acuity vision <i>and </i>colour vision, you won't be able to make out the colour of an object seen only with your peripheral vision. If anything, this fact is even more surprising, but if you're as strict with your eyeball as before, you can easily confirm this.</div><div><br /></div><div>Note also how clever the brain is at filling in the details. After you have seen an object with your central (cone-dominated) visual apparatus, the brain will give the illusion of still seeing that object in colour long after it has moved to your peripheral vision, where this is no longer possible! Its amazing how good the virtual reality generator is...</div><div><br /></div><div>One thing the peripheral vision really is good at, though, is detecting movement. (It isn't hard to see how this might be beneficial.) The slightest movement, and the eyeballs rotate to lock the powerful central vision on to the object.</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com3tag:blogger.com,1999:blog-956701540737748712.post-14925313706366380962009-09-24T09:10:00.000+02:002009-09-24T09:20:20.517+02:00Swine flu vaccine nonsensePerhaps you, like me, think the anti-vaccination brigade are about as praiseworthy as Stalin. Yet you keep seeing and hearing trickles of nonsense from their corner, digested verbatim by concerned friends and family. If so, <a href="http://www.skeptic.com/eskeptic/09-09-23#feature">this article is for you</a>. It is by the redoubtable Dr Harriet Hall, and deals with as many of the misapprehensions (and lies!) about the swine 'flu vaccine as she can bear to read. At times, things get really funny:<br /><ul><li><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="color:#666666;"><span class="Apple-style-span" style="font-size:small;"><b>Claim</b>: Mercola says “Injecting organisms into your body to provoke immunity is contrary to nature.”</span></span></span></li><li><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="color:#666666;"><span class="Apple-style-span" style="font-size:small;"><b>Fac</b><b>t</b>: Nature kills people. Doing something contrary to nature is what medicine is all about. It’s a good thing.</span></span></span></li><li><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="color:#666666;"><span class="Apple-style-span" style="font-size:small;"><b>Claim</b>: “The potential for a weaponized vaccine to be the vector for a weaponized flu cannot be discounted.”</span></span></span></li><li><span class="Apple-style-span" style="font-family:arial;"><span class="Apple-style-span" style="color:#666666;"><span class="Apple-style-span" style="font-size:small;"><b>Fact</b>: Most far-fetched conspiracy theories are wrong. I have no trouble discounting this one. The potential may be there, but the likelihood is homeopathic.</span></span></span></li></ul><div>I do enjoy "homeopathic" as an adjective meaning "astronomically improbable".</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-25225071842059871902009-09-21T18:51:00.000+02:002009-09-21T19:50:26.963+02:00Do we think in English?... or whatever your language is, for that matter?<div><br /></div><div>We've all caught ourselves projecting phrases into our mind's ear, such as phone numbers you've just been read - "072255...", snatches of dusty arithmetic -"7 times 8 is 56", rhymes - "30 days hath September...", and the like. It is little auditory loops such as these, together with the absence of an alternate hypothesis, that convince most of us that we think "in English" (or whatever). But do we? If we believe that "earth is a planet", is there a bit of the brain dedicated to "earth", connected sequentially to another one for "is", followed by one for "a" and finally one for "earth", all the while keeping track of which part is subject vs object vs indefinite article, and so on? This sounds like a stretch, but then what else could be going on?</div><div><br /></div><div>Well, it may surprise you, but we <i>don't</i> think in any earthly language. All we need to show to refute the hypothesis is that some English sentences, while perfectly intelligible, don't contain enough information to cut it as a language of thought. Let me explain:</div><div><ul><li><b>Ambiguity</b> - Real newspaper headlines such as "Chinese Apeman Dated", or "Stolen painting found by tree" strike us as funny because they unintentionally have a second (bizarre) meaning. But we realise that the mistake was <i>inadvertent</i>; the writers knew which meaning of "dated" or "by" they meant. But if an English phrase can have more than one meaning, then English can't be the medium of thought.</li><br /><li><b>Co-reference</b> - In your history essay, you may begin by referring to "Adolf Hitler", but then later make reference to him with phrases like "Hitler", "the Führer", or "the leader of the Third Reich". As long as you write reasonably clearly, it is perfectly clear that you are referring to the same person - yet the language has changed! Once again, this means that there is something in the brain that is treating the phrases as the same thing. And that thing can't have been the language, which was as fickle as last season's fashions.</li><br /><li><b>Deixis</b> - Deixis is what linguists name those parts of language that are intelligible only in context. Take an old joke like "Every four seconds, a woman gives birth. She must be found and stopped." This only works because the first part of the sentence leads you down one interpretative alley ... and then the second corrects it. Again, this shows that the phrases themselves don't inexorably tie themselves to one - and only one - meaning, as would have to be the case if English really were the language of thought. Rather, there is some underlying (non-English!) interpretative function beneath the language that the joke is able to temporarily thwart.</li></ul><div>There are several other proofs too, but I think these will suffice. So if we don't think in English, in which language <i>do</i> we think? The answer from cognitive neuroscientists and others is that we think in an fairly abstract, subconscious "language" often called Mentalese. Calling it a language is a little confusing though, since we've just proved that it doesn't use "words" in the everyday sense of the term. Nonetheless, there must be some sort of information processing going on inside my cranium (using concepts and objects instead of words); one that obeys a specific logic ("grammar") that is robust enough to grant us "intelligence". For want of a better term then, we all think in Mentalese.</div><div><br /></div><div><span class="Apple-style-span" style="font-size: small;">The above ideas were largely taken from Steven Pinker's masterly "<a href="http://www.amazon.com/Language-Instinct-Steven-Pinker/dp/0060976519">The Language Instinct</a>". Read it.</span></div></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-38163432290750955712009-09-16T15:33:00.000+02:002009-09-30T21:46:35.366+02:00RNA interference - Part 2: regulation of gene expression(This post follows <a href="http://medicguide.blogspot.com/2009/09/microrna-part-1-ancient-antiviral.html">Part 1</a>.)<div><br /></div><div>Assuming that the microRNA-Dicer-RISC algorithm (usually collectively known as <b><span class="Apple-style-span" style="color:#000099;">RNA interference</span></b>) did initially evolve as a defence against viruses*, it might seem odd that this isn't its chief function today. Rather, RNA interference predominantly earns its keep by downregulating the expression of various genes.</div><div><br /></div><div>Assuming that the dicer-RISC sequence is already operational, how could you use it to modify gene expression of your own, normal genes? Hint: RNA interference only acts after the relevant gene has been transcribed into RNA (as its name suggests!), so we'll have to concentrate our efforts there. </div><div><br /></div><div>Any guesses? Well, what we could do is simply synthesise a short bit of RNA that is <i>complementary </i>to a part of the transcribed RNA sequence. That way, it would automatically bind to the target gene's RNA and form ... <i>double-stranded</i> DNA. And, as we've shown in the previous post, the presence of double-stranded DNA provokes an alarm response in the cell ("perhaps it's a virus!") that rapidly degrades it, and any copies of it (single stranded or double-stranded), by the Dicer-RISC mechanism of RNA interference.</div><div><br /></div><div>As so happens, that is exactly what occurs. Hundreds of our own genes encode small fragments of RNA complementary to other genes; these fragments are called<span class="Apple-style-span" style="color:#000099;"> </span><b><span class="Apple-style-span" style="color:#000099;">microRNA (miRNA)</span></b>. And if these fragments bind to their counterpart RNA, the RNA interference mechanism is activated. In all there are at least 500 miRNAs present in mammalian cells, collectively down-regulating 30% of our genes.</div><div><br /></div><div>Appropriately enough for such a new discovery, that isn't the end of the RNA interference story. For instance, it has also been implicated in keeping chromatin condensed, and in preventing transcription (in addition to translation). But that's enough for now...</div><div><br /></div><div><br /></div><div>Main source, including image: <a href="http://nobelprize.org/nobel_prizes/medicine/laureates/2006/adv.html">The Nobel Prize in Physiology or Medicine 2006 - Advanced Information</a>.</div><div><br /></div><div><span class="Apple-style-span" style="font-size:x-small;">* This is quite a big assumption, actually - the jury's still out.</span></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com5tag:blogger.com,1999:blog-956701540737748712.post-17723687565407765662009-09-15T20:56:00.000+02:002009-09-16T16:36:02.096+02:00RNA interference - Part 1: an ancient antiviralAs every textbook attests, three types of RNA have long been identified: messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA). However, the past decade and a half hasn't been kind to this convenient list. Several other kinds of RNA have now demanded inclusion, and foremost among them is probably microRNA (miRNA) and small interfering RNA (siRNA). The latter two are both intimately involved in the phenomenon known as <b><span class="Apple-style-span" style="color:#CC0000;">RNA interference</span></b>.<div><br /></div><div><span><span></span></span>The evolutionary origin of RNA interference is obscure, but I favour (if only for explanatory reasons) one theory in particular, namely that it is an ancient defence against viruses that has been adapted to meet other additional demands. Let me explain.</div><div><br /></div><div>Although all 'higher' lifeforms exclusively use DNA to store their genomes, viruses can use either DNA or RNA (or sometimes both!). In fact, most use RNA, in either a single- or a double-stranded form. The hardest part of fighting viruses is to find them - they are fundamentally just nucleic acid surrounded by a protein coat. The protein coat is usually their weakness, as it is something decidedly foreign that the immune system can recognise and attack. However, if a virus should inject its nucleic acid into a cell, the cell has almost no way to recognise the RNA or DNA as foreign - why would it? RNA is RNA!</div><div><br /></div><div>Usually what has to happen is that a selection of the virus' (foreign) proteins are displayed by the routine sampling process common to almost all cells - the protein fragments are attached to the MHC class I molecule, which strongly interacts with surveillance cells of the immune system. If a "non-self" molecule is detected, the immune cell will politely ask its infected counterpart to self-destruct (apoptosis) or, failing that, simply destroy the cell itself. (Viruses which disable the MHC I sampling process are dealt with by natural killer cells, as explained <a href="http://medicguide.blogspot.com/2009/06/what-are-natural-killer-cells.html">here</a>.)</div><div><br /></div><div><img src="http://1.bp.blogspot.com/_tN90RefJ5Hk/SrAc_RfRVZI/AAAAAAAAAzM/X-vaPn4cL3c/s400/RNA+interference.gif" style="float:right; margin:0 0 10px 10px;cursor:pointer; cursor:hand;width: 225px; height: 400px;" border="0" alt="" id="BLOGGER_PHOTO_ID_5381833428059641234" /></div><div>This method usually works well enough (or we'd all be dead), but it is frustratingly indirect - a cell has to be long on the road to helping the virus replicate before it can be stopped. Is there any hope at all of identifying viral RNA before it does its damage? Well, although RNA is RNA is RNA (etc.) there <i>is</i> one form of viral RNA that can be reliably distinguished from our own native RNA - double-stranded RNA, which is <i>never</i> normally produced by our cells.</div><div><br /></div><div>Just as you'd expect, our cells can not only recognise but also actively destroy any hint of double-stranded RNA (ds-RNA). A protein with the wonderful name of <b><span class="Apple-style-span" style="color:#000099;">Dicer </span></b>lives up to its name by slicing any identified ds-RNA into useless fragments, thereby preventing the RNA from being translated into a protein. Each of these RNA fragments is very small, by RNA standards, and they are collectively referred to as<b><span class="Apple-style-span" style="color:#000099;"> small interfering RNA</span></b><b><span class="Apple-style-span" style="color:#000099;">s</span></b> (siRNA).</div><div><br /></div><div>Furthermore, the process is vindictive. Once the ds-RNA has been cleaved, the bits bind a protein complex, called <b><span class="Apple-style-span" style="color:#000099;">RISC</span><span class="Apple-style-span" style="font-weight: normal;">, which stands for <i>RNA-induced silencing complex</i></span></b>. One of the two RNA strands is eliminated, but the other, still bound to RISC, acts as bait for other copies of the RNA molecule, attaching to them by the familiar base pairing rules common to all life (A to T, C to G). If this occurs, RISC cuts the newly-bound mRNA strand, but retains the other fragment in order to sleuth out more of these foreign RNA molecules. </div><div><br /></div><div>In this way, a cell may be purged of viral RNA. But this is only the tip of the proverbial iceberg when it comes to the power of microRNA, and it wasn't at all how miRNA was discovered. We'll cover that in the <a href="http://medicguide.blogspot.com/2009/09/rna-interference-part-2-regulation-of.html">next post</a>.</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-69074244250788661902009-09-10T21:58:00.000+02:002009-09-16T15:31:47.625+02:00An even better way to extract DNA...A while back <a href="http://medicguide.blogspot.com/2009/06/extracting-dna-in-your-kitchen.html">I quoted a passage</a> from "<a href="http://www.amazon.com/Your-Inner-Fish-Journey-3-5-Billion-Year/dp/0375424474">Your Inner Fish</a>" which detailed a method for harvesting and visualising some DNA. It has just been surpassed, however, by a derivation that's even easier to perform - and has the virtue of concluding by manifesting your <i>own </i>DNA. Here it is:<div><br /></div><div><span class="Apple-style-span" style="font-size:small;"><span class="Apple-style-span" style="color:#666666;">Put a teaspoon of washing-up liquid diluted with three teaspoons of water into the clean glass. Swish the salty water around your mouth vigorously for 30 seconds or so then spit it into the diluted washing-up liquid. Stir this firmly for a few minutes, then very gently pour a couple of teaspoons of ice-cold strong [> 50% by volume] alcohol down the side of the glass. ... [Y]ou must have a clearly demarcated water/alcohol boundary. </span></span></div><div><br /></div><div>The result? "Wait a few minutes and you'll see spindly white, thread-like clumps starting to form in the alcohol. This is your DNA." This delightful method comes from an even more delightful book called "<a href="http://www.amazon.co.uk/How-Fossilise-Your-Hamster-Experiments/dp/1846680441">How to Fossilise Your Hamster</a>." It's a must-read.</div><div><br /></div><div>Warning: non-medic friends might think you a little strange. But what do they know?</div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-56233083669207386292009-09-01T20:39:00.000+02:002009-09-02T22:44:17.954+02:00Macrocytosis: a nice breakdownWhen ever a complete blood count (CBC) is ordered, the haematology machines will dutifully spit out a <b>mean corpuscular volume</b> (MCV), measured in femtolitres (fL). (The 'femto' prefix is a bit like 'micro' as a prefix, but whereas the latter means 1 millionth-of-a-[whatever], femto- indicates one <i>trillionth</i>-of-a-[whatever]). The MCV is a measure of the red cells' average volume.<div><br /></div><div>An MCV of over about 100 fL is usually considered to define a <i>macrocytosis</i> (red cells with an abnormally high volume - which basically equates to red cells with an abnormally high size under the microscope). <span class="Apple-style-span" style="color:#000099;">The first thing to do when you find a macrocytosis is to differentiate between a megaloblastic and a non-megaloblastic picture</span>. This is largely done by getting a haematologist to look at a smear of the peripheral blood. With megalobastosis, you get:</div><div><ul><li><span class="Apple-style-span" style="text-decoration: underline;">Hypersegmented neutrophils</span>: neutrophils usually have 2-5 lobes. Megaloblastosis is defined by more than 5% of the neutrophils having 5 lobes, or any having 6 or more lobes.</li><li><span class="Apple-style-span" style="text-decoration: underline;">Oval macrocytes</span>: the red cells are obviously large, but in megaloblastosis they are <i>oval </i>in shape (as opposed to round).</li></ul><div><span class="Apple-style-span" style="color:#000099;">If you are dealing with a megaloblastic macrocytosis, the two commonest causes are folate deficiency </span>(check the red cell folate level)<span class="Apple-style-span" style="color:#000099;"> and B12 deficiency </span>(check the serum B12 level). Start there, and only look for other causes if both levels are normal despite the megaloblastic picture. Other causes include myelodysplasia, HIV infection and certain drugs.</div><div><br /></div><div><span class="Apple-style-span" style="color:#000099;">If you're</span><i><span class="Apple-style-span" style="color:#000099;"> </span></i><span class="Apple-style-span" style="color:#000099;">dealing with a non-megaloblastic macrocytosis, then you can use this handy mnemonic</span> that my haematology professor taught me - <span class="Apple-style-span" style="color:#CC0000;">ALARM</span>:</div><div><ul><li><b><span class="Apple-style-span" style="color:#CC0000;">A</span></b>lcoholism</li><li><b><span class="Apple-style-span" style="color:#CC0000;">L</span></b>iver disease</li><li><b><span class="Apple-style-span" style="color:#CC0000;">A</span></b>plastic anaemia</li><li><b><span class="Apple-style-span" style="color:#CC0000;">R</span></b>eticulocytosis</li><li><b><span class="Apple-style-span" style="color:#CC0000;">M</span></b>yelodysplasia, <b><span class="Apple-style-span" style="color:#CC0000;">m</span></b>arrow infiltration, or <b><span class="Apple-style-span" style="color:#CC0000;">m</span></b>yxoedema (i.e. hypothyroidism).</li></ul><div>That should help!</div></div></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com0tag:blogger.com,1999:blog-956701540737748712.post-19567844157691709552009-08-30T20:19:00.000+02:002009-09-01T14:58:17.487+02:00How does fluconazole work?<p class="MsoNormal">If you want to kill micro-organisms in the external world, you can take your pick of nasty chemicals to throw at them; most will work just fine.<span style="mso-spacerun:yes"> </span>However, if you want to kill a micro-organism that is <i style="mso-bidi-font-style:normal">inside </i>of you, you’ll understandably want to avoid yourself becoming collateral damage.<span style="mso-spacerun:yes"> </span>It therefore makes sense to try to target something specific to the micro-organism’s metabolism, so that you won’t get affected in the process.</p> <p class="MsoNormal"><o:p>This rationale applies to most of the antimicrobials we doctors prescribe, and fluconazole is no exception.<span style="mso-spacerun:yes"> </span>Fluconazole is one of the <i style="mso-bidi-font-style:normal">triazoles</i>, a group that also includes itraconazole and several related antifungals.<span style="mso-spacerun:yes"> </span>Their fungus-specific target is something called <i style="mso-bidi-font-style:normal">ergosterol</i>.<span style="mso-spacerun:yes"> </span>Fungi use it as a component of their cell membranes, where it serves a similar purpose to that of cholesterol in human cell membranes.<span style="mso-spacerun:yes"> </span></o:p></p> <p class="MsoNormal">What fluconazole does is to inhibit an enzyme responsible for the production of ergosterol.<span style="mso-spacerun:yes"> </span>This results in a toxic build up of precursors, and culminates in the inhibition of the fungus’ ability to grow and divide.</p> <p class="MsoNormal"><o:p>[If you <i style="mso-bidi-font-style:normal">really </i>want more details (and I for one don’t), the relevant step is the conversion of lanosterol to ergosterol, and the enzyme is the cytochrome-P450-dependent 14-α-demethylase.]</o:p></p><p class="MsoNormal">Reference: <a href="http://www.chestmed.theclinics.com/article/S0272-5231(09)00014-8/abstract">Overview of Antifungal Agents</a></p>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com2tag:blogger.com,1999:blog-956701540737748712.post-83982889996087731762009-08-27T18:16:00.001+02:002009-08-31T19:26:53.303+02:00Upper motor neuron vs lower motor neuron weakness<div style="text-align: auto;"><span class="Apple-style-span" style="border-collapse: collapse;"><p class="MsoNormal">Weakness of one or more of our limbs is most often neurological.<span style="mso-spacerun:yes"> </span>Classically, there are two distinct patterns of neurological weakness, and identifying the one you're dealing with is rather useful.<span style="mso-spacerun:yes"> I'm referring to</span> <i>upper motor neuron</i> vs <i>lower motor neuron</i> weakness, of course.<span style="mso-spacerun:yes"> </span></p><p class="MsoNormal">The ‘lower motor neuron’ is simply the last neuron to touch the relevant muscle.<span style="mso-spacerun:yes"> </span>It always starts in the spinal cord and ends in a muscle.<span style="mso-spacerun:yes"> </span>Damage to any of the neurons in the motor pathway <i style="mso-bidi-font-style:normal">before </i>this point (e.g. spinal cord, brainstem, or cerebrum) will give you an ‘upper motor neuron’ pattern of weakness.</p><p class="MsoNormal"><o:p></o:p></p> <p class="MsoNormal">Although both syndromes present with muscle weakness, they thereafter part company in the following ways:</p> <p class="MsoNormal"><br /></p> <table class="MsoTableGrid" border="1" cellspacing="0" cellpadding="0" style="border-collapse:collapse;border:none;mso-border-alt:solid windowtext .5pt; mso-yfti-tbllook:480;mso-padding-alt:0cm 5.4pt 0cm 5.4pt;mso-border-insideh: .5pt solid windowtext;mso-border-insidev:.5pt solid windowtext"> <tbody><tr style="mso-yfti-irow:0"> <td width="189" valign="top" style="width:142.0pt;border:solid windowtext 1.0pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><i style="mso-bidi-font-style:normal"><o:p> </o:p></i></p> </td> <td width="189" valign="top" style="width:142.05pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt: solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><b><span class="Apple-style-span" style="color:#CC0000;">Upper Motor Neuron</span><o:p></o:p></b></p> </td> <td width="189" valign="top" style="width:142.05pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:solid windowtext .5pt;mso-border-alt: solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><b><span class="Apple-style-span" style="color:#000099;">Lower Motor Neuron</span><o:p></o:p></b></p> </td> </tr> <tr style="mso-yfti-irow:1"> <td width="189" valign="top" style="width:142.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><i style="mso-bidi-font-style:normal">Tone<o:p></o:p></i></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Increased, with ‘clasp knife’ quality<o:p></o:p></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Decreased<o:p></o:p></p> </td> </tr> <tr style="mso-yfti-irow:2"> <td width="189" valign="top" style="width:142.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><i style="mso-bidi-font-style:normal">Clonus<o:p></o:p></i></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Present<o:p></o:p></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Absent<o:p></o:p></p> </td> </tr> <tr style="mso-yfti-irow:3"> <td width="189" valign="top" style="width:142.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><i style="mso-bidi-font-style:normal">Fasciculations<o:p></o:p></i></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Absent<o:p></o:p></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Present<o:p></o:p></p> </td> </tr> <tr style="mso-yfti-irow:4"> <td width="189" valign="top" style="width:142.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><i style="mso-bidi-font-style:normal">Muscle Wasting<o:p></o:p></i></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Absent, but disuse atrophy eventually results<o:p></o:p></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Present (within 2-3 weeks)<o:p></o:p></p> </td> </tr> <tr style="mso-yfti-irow:5"> <td width="189" valign="top" style="width:142.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><i style="mso-bidi-font-style:normal">Tendon Reflexes<o:p></o:p></i></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Increased.<span style="mso-spacerun:yes"> </span>Extensor plantar reflexes.<o:p></o:p></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Decreased or absent.<span style="mso-spacerun:yes"> </span>Flexor plantar reflexes.<o:p></o:p></p> </td> </tr> <tr style="mso-yfti-irow:6;mso-yfti-lastrow:yes"> <td width="189" valign="top" style="width:142.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:solid windowtext .5pt;mso-border-alt:solid windowtext .5pt; padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center"><i style="mso-bidi-font-style:normal">Distribution<o:p></o:p></i></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Whole limbs, with more weakness in the upper limb extensors and lower limb flexors<o:p></o:p></p> </td> <td width="189" valign="top" style="width:142.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:solid windowtext .5pt;mso-border-left-alt:solid windowtext .5pt; mso-border-alt:solid windowtext .5pt;padding:0cm 5.4pt 0cm 5.4pt"> <p class="MsoNormal" align="center" style="text-align:center">Specific muscle groups affected (e.g. in the distribution of a spinal segment, or just the proximal muscles, etc.)<o:p></o:p></p> </td> </tr> </tbody></table> <p class="MsoNormal"><span class="Apple-style-span" style="text-decoration: underline;"><br /></span></p><p class="MsoNormal">Of course, there are a few caveats and qualifications to be made to this handy list.<span style="mso-spacerun:yes"> </span></p><p class="MsoNormal"></p><ul><li>Although the deep tendon reflexes follow the above protocol, there are also superficial tendon reflexes (such as the abdominal or cremasteric) that obey the opposite pattern.<span style="mso-spacerun:yes"> </span>It is rare to test for these reflexes, though. </li><li><span style="font-family:Symbol; mso-fareast-font-family:Symbol;mso-bidi-font-family:Symbol;"><span style="mso-list:Ignore"><span style="font:7.0pt "Times New Roman""> </span></span></span>The pattern with cranial nerves is a little more complicated, since most of the muscles supplied by them receive <i style="mso-bidi-font-style:normal">bilateral</i> innervation.<span style="mso-spacerun:yes"> </span>For instance, the tongue is supplied by the XII cranial nerve from both the left <i style="mso-bidi-font-style:normal">and </i>the right side, and so damage to only one side won’t produce any discernible weakness.<span style="mso-spacerun:yes"> </span>The one large exception to this rule is the lower 2/3 of the facial nerve’s supply, which follows convention and is unilateral.<span style="mso-spacerun:yes"> </span>Therefore it is not uncommon to see a stroke patient with a drooping face – but with a forehead that is mysteriously spared.</li></ul><div>Lastly, the lopsided distribution of weakness found with upper motor neuron lesions produces a particular '<i>spastic posture</i>'. Since the weakness is greatest in the upper limb extensors, the limb tends to become flexed. The reverse is true for the lower limb, which is consequently extended. (Frustratingly, I can't seem to find a nice picture of this important clinical sign...)</div><p></p></span></div>jeremyhttp://www.blogger.com/profile/17353716090668341520noreply@blogger.com7