Tag Archives: medicine

Phlegm and Horseradish

This week I’m carrying on with the theme of colours in medicine. Today we saw Janet. She is a 55 year old enthusiastic smoker who had been sent up to the emergency department because she was short of breath and had bad pain in the right side of her chest when she coughed or breathed in deeply.

“I’m coughing up some really nasty green phlegm” she told us.

I love the word phlegm.  So much better than the usual word usually used by doctors – sputum, because it is understood by patients and means much the same.  So many of the words we use in medicine are Latin or Greek, presumably designed to suggest we know more than we really do.  I tried an experiment of banning Latin and Greek words on the ward round when there is an English equivalent. It didn’t last long. Abdomen was replaced by “belly”, sternum became “breastbone”, tumour was “lump”, but many terms like myocardial infarction became too cumbersome and imprecise – “death of heart muscle due to lack of blood supply”. Also, phlegm means something else – there is a wonderful quote by one of my heroes in medicine, William Osler, at  the end of this blog about why doctors need it.

Anyway, back to Janet. We looked in the sputum pot Janet had been using and indeed there was a big, greenish-gray glob of phlegm. Slightly to the consternation of the young doctor with me, I turned the pot upside down – the glob remained stuck to the bottom .

At this point I normally ask one of two really interesting questions:

“Why is infected sputum green?”

“Why does it stick to the bottom of the pot?”

We will only have time for the first one today. The most common answer I get is that the bacteria are green. That is not the case. It is white cells (polymorphonuclear leukocyes, polymorphs or neutrophis) in the phlegm which turn green when they get angry (much like the Incredible Hulk).

neutrophi 2

Neutrophils cruising around the circulation looking for action

If you look at infected sputum under the microscope, it is stuffed full of neutrophil leukocytes. They are truly professional at killing bacteria and get very angry when they find them. How do they know they are there? When the lung cells are attacked by germs they send out chemical signals called cytokines (such as interleukin 8). Neutrophils respond to this “help! I’m being attacked!” signal by following the cytokine scent. They normally cruise around in the circulation but when they “smell” the cytokine they follow where it has come from. This gets them quite excited. What gets them more excited is when they “smell” bacteria. They hunt them down and engulf them. There is a wonderful youtube video of neutrophils chasing and eating bacteria to a Benny Hill theme tune:

http://www.youtube.com/watch?v=KxTYyNEbVU4

When they have caught and trapped enough bacteria they get really angry. In fact suicidally angry. They undergo what is known as “respiratory burst”. This involves the activation of three enzymes; NADPH oxidase, superoxide dismutase (SOD) and myeloperoxidase (MPO). Ordinary, harmless oxygen is made into the slightly nastier superoxide by NADPH oxidase, and this is then turned into the more nasty hydrogen peroxide by superoxide dismutase. Whereas hydrogen peroxide is not pleasant for bacteria, their tiny evil forms will quake when around them everything turns green. The Incredible Hulk in the form of the lurid green MPO is after them.

Neutrophil 3

MPO is an enzyme which is green because it contains haem, a complex but common iron-containing chemical arrangement that is used in a whole range of useful and colourful biological molecules, such as haemoglobin and liver enzymes which inactivate drugs (p450s). The purpose of MPO is to convert hydrogen peroxide into hypochlorite by combining with a chloride anion. Hypochlorite is a really nasty chemical which is intended to deal the final blow.

Most homes have a bottle of hypochlorite under the kitchen sink or in the bathroom cupboard – Domestos in the UK or Chlorox in the US. And as the adverts say – it kills 99% of all household germs….Dead!

domestos

Now give a thought for the poor neutrophil. In all that excitement it produced enough hypochlorite to kill not only 99% of germs but also to kill itself. But just when you thought that it had completely disintegrated with its own toxic, green chemical soup, the neutrophil comes up with a new trick, Terminator fashion. It forms a net around the debris to stop the remaining 1% of germs from getting away. The net is made from dead neutrophil DNA and other stringy compounds, and is thought to be important in both stopping the evil germs that have survived escaping and protecting surrounding host tissue from the damage. Understanding this has given me a renewed respect for neutrophils – determined, courageous and willing to give up their lives to save the world, even using their dead bodies to inflict more damage on the enemy and protect their gene-identical brother and sister cells.

You can learn more about neutrophil nets from the paper which first described them:

http://www.sciencemag.org/content/303/5663/1532.abstract

You will have to register but it is worth it.

In the title I promised horseradish. All horseradishes contain several haem–containing peroxidases, and it seems that when the plant is attacked by insects (or people) this enzyme is activated and will generate bleach-like molecules which contribute to its famous hot and burning taste. So next time you eat wasabe (a particularly potent type of Japanese horseradish), give a thought to how those bacteria feel when being attacked by neutrophils.

wasabe

These are wasabe peas. I would suggest you don’t eat more than two or three at once. Is wasabe  green because it contains loads of haem containing peroxidase? I’d like to think so but maybe you could let me know.

The quote from William Osler:

“Imperturbability means coolness and presence of mind under all circumstances, calmness amid storm, clearness of judgment in moments of grave peril, immobility, impassiveness, or, to use an old and expressive word, phlegm. It is the quality which is most appreciated by the laity though often misunderstood by them; and the physician who has the misfortune to be without it, who betrays indecision and worry, and who shows that he is flustered and flurried in ordinary emergencies, loses rapidly the confidence of his patients” From Aequanimitus, William Osler 1889. See full text at:

http://www.medicalarchives.jhmi.edu/osler/aequessay.htm

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Toast and diabetes

Sometimes I notice when coming onto the assessment unit there is a smell which is a combination of stale urine/bowel gas and air freshener. But when I started at 8 this morning everything is overpowered by the wonderful scent of fresh toast. The domestics are pushing trolleys on which is piled not only toast, but also cornflakes and porridge (that’s oatmeal for US readers), jam and cups of tea.

Slide1

 

I like seeing patients first thing in the morning, because if they have eaten and kept down their breakfast they are not likely to be too unwell – and there’s a good chance they will be able to go home.

This morning my first patient was Brian, a 57 year old man who has type 1 diabetes and was admitted from clinic with an infected foot ulcer. He had eaten his breakfast.  His diabetes specialist was concerned about osteomyelitis (infection in the underlying bone) and wanted him to have an MRI scan and intravenous antibiotics.

Brian has had diabetes since the age of 10, and has poor eyesight due to diabetic retinopathy, and poor kidney function due to diabetic nephropathy. Both are caused by damage to small blood vessels from diabetes.

The first question I asked the young doctor who was with me was the obvious one:

“Why does toast go brown when it is cooked?”

She looked at me in a slightly worried but kindly way, not sure how to respond – she had only been working on the unit for a week or so and was keen to give a good impression.

The answer is that the glucose molecules, which make up starch combine chemically, when heated, to wheat protein – something called a Maillard reaction, to produce a brown carbohydrate/protein complex. The chemistry is complicated, but this reaction is vital to producing all sorts of wonderful foodstuffs (apart from toast), including the really tasty brown, crispy coating on cooked meat, the main taste of gravy, soy sauce, Worcester sauce, the tasty bits on the surface of fries and, indeed, the brown surface of cornflakes which gives them a taste of more than plain wheat flakes.

You may be interested to know that there is an International Maillard Reaction Society – http://www.imars.org/online/

I can imagine that when delegates go to meetings they might dress up as Louis Camille Maillard –

Louis Camille Maillard.jpg

Also there is probably some caramelization of the starch glucose molecules. When heated sugars alone will form polymers which are brown-coloured tasty caramels and are used for all sorts of purposes such as food colouring (eg. the brown in cola).

So how does this relate to Brian’s diabetes?

Well, the reason that his blood vessels are damaged by diabetes is because, just like in the toast, high levels of blood glucose (which is the main problem in diabetes) combine with protein in blood vessels. In particular glucose undergoes the same Maillard reaction with the amino acid lysine which has an amine group sticking out.

The formation of the glucose/protein complex is not easily reversible and causes permanent damage to blood vessel function, resulting in eye, kidney, skin, heart, brain and a whole lot of other problems for diabetics.

The result of the Maillard reaction between sugar and lysine creates what are known as advanced glycation end-products (AGEs). There is now a huge literature about AGEs and AGE receptors called RAGEs.  Many think AGEs are also important in aging and dementia, and there is evidence that RAGEs may be either a protective or more damaging. A good review about AGEs and diabetic vascular injury is:

http://circ.ahajournals.org/content/114/6/597.short

This is my first ever post and I would love to have feedback.

Disclaimer: Patients described in this blog are not real, but typical of those we see in our hospital