EDITORIAL Alkalis and Skin John E. Greenwood, AM, BSc(Hons), MEChB, MD, DHlthSc, FRCS(Eng), FRCS(Plast), FRACS, * Jin Lin Tan, t Justin Choong Tzen Ming, t Andrew D. Abell, BSc(Hons), PhD, FNZIC, FRACI:!: The aim of this editorial is to provide an overview of the chemical interactions occur- ring in the skin of our patients on contact with alkaline agents. Strongly basic alkali is highly aggressive and will readily hydrolyze (or cleave) key biological molecules such as lipids and proteins. This phenomenon is known as saponification in the case of lipids and liquefactive denaturation for peptides and proteins. A short section on current first- aid concepts is included. A better understanding of the basic science behind alkali burns will make us better teachers and provide an insight into the urgency needed in treating these common and dangerous chemical injuries. (J Burn Care Res 2016;37:135-141) ALKALIS strontium, radium), and other compounds that pro- duce alkaline hydroxides in solution (such as gaseous Between July 1, 2009, and June 6, 2014, the Adult ammonia). They are often given the term caustic, Burn Service at the Royal Adelaide Hospital in defined as being able to burn or corrode organic tis- Adelaide, South Australia, dealt with 1913 admis- sue by chemical action. The general structure of an sions, of which 124 (6.5%) were injuries because of alkali is M+ -OH, where M+ is the alkali metal cation chemical qposure. Of these, 80 (4.2% of all admis- and -OH the caustic hydroxide anion. sions and 64.5% of chemical burns) were because of Alkalis (MOH) are strong bases and as a conse- alkalis. There were no deaths as a result of chemical quence are readily protonated by acids (HA) to pro- injury. Obviously, the proportion of chemical burns duce the conjugate acid of the alkali (H 0) and the admitted by an individual unit will reflect the haz- 2 salt of the acid (A-M+), in what is a classic acid/base ards within the catchment area. Published figures reaction. for chemical injury range between 3.2 and 18.7% of the total burn number,1-7 and the mortality rate for chemical injuries ranges from 0.7 to 30%.4,7,8 The word Alkali derives from Arabic (Al Qaly), They also readily hydrolyze organic compounds which literally translates as "calined ashes" since the such as esters and ami des as commonly found in key ash left after burning certain plant stems (eg, glass- biomolecules within the skin and more widely in wort), when dissolved in water, formed strong alka- cells. The basicity of alkalis means that in water they line solutions. Such ash was referred in Old English have a pH > 7 and as such will turn the acid-base as "Potash." In chemistry, an alkali is defined as a sol- indicator phenolphthalein from clear to pink or red uble base and we now know that these alkalis are the and litmus paper to blue. hydroxides of alkali metals (lithium, sodiulll, potas- Alkalis are common in industrial and household sium, rubidium, cesium, francium), alkaline earth settings. Many household cleaning agents, particu- metals (beryllium, calcium, magnesium, barium, larly oven or kitchen cleaners and car-cleaning prod- ucts (alloy wheel or paint or radiator) are strongly From the 'Adult Burn Service, Royal Adelaide Hospital, South caustic.9 As oven-cleaning agents, alkalis saponifY or Australia, Australia; and fMedical School and :f:Department of Chemistry, University of Adelaide, South Australia, Australia. hydrolyze "baked-on" food grease and fats, making Address correspondence to Dr. John E. Greenwood, AM; Adult their removal easier. Their ability to do the same to Burn Service, Royal Adelaide Hospital, North Terrace, Adelaide skin and ocular cornea or conjunctiva is what makes SOOO,South Australia, Australia. E-mail: john.greenwood@ health.sa.gov.au them dangerous. Chemical materials to unblock Copyright@ 201S by the American Burn Association "blocked" drains are similarly hazardous. In all of lSS9-047Xj201S these situations, the caustic agent is used to break- DOl: lO.1097/BCR.0000000000000222 down or hydrolyze grease, fats, and organic materials. 135 Journal of Burn Care & Research March/April 2016 136 Greenwood et at Kneeling in wet cement or concrete during "screed- 2. The hygroscopic nature of alkalis allows them ing" causes many burn injuries every year. In these to dehydrate cells leading to cell death. cases, calcium oxide ("lime," a constituent of cement 3. Alkalis attack proteins, forming water-soluble and concrete), dissolves in the water used when mix- alkali proteinates, which contain carboxylate ing, to form calcium hydroxide. This agent is less ions that cause subsequent and ongoing lique- aggressive than alkaline metal hydroxides and the factive necrosis. progressive burn is often painless, but deep. Burn surgeons concentrate mostly on the effect of alkalis LIPIDS on protein, where degradation by liquefaction (col- liquative or liquefactive necrosis), but considerable Fatty acids are the characteristic building blocks of lipid destruction occurs before structural protein is most lipids.1o These carboxylic acids contain a long exposed. hydrophobic (nonpolar) carbon chain of up to 24 carbon atoms that can be saturated (ie, no carbon- carbon double bonds) or unsaturated with one or PATHOPHYSIOLOGY more carbon-carbon double bond. Fatty acids form The severity of burn injury caused by alkali depends simple waxy esters, but more generally they combine on its basicity, concentration, volume, and state with other chemical structures to produce the dif- (solid vs liquid) which impacts on its ability to "pen- ferent classes of lipid. Triglycerides (fats) are formed etrate" and hence the duration of skin contact. on joining three fatty acids to glycerol, each via an There are three factors involved in the mechanism ester bond as shown in Figure lA. Phospholipids, the main component of cellular membranes, have one of of injury from strong alkali9: the fatty acid chains replaced by a polar head group 1. Saponification of fat results in the loss of the attached to one of the glycerol oxygens as shown in natUral water barrier provided by lipids, hence Figure 2A. There are a number of variants on this allowing increased water penetration of the theme, including sphingolipids that contain a modi- alkali. This exothermic reaction also contrib- fied glycerol subunit (such as choline) and also esters utes to thermal injury. of cholesterol. The nonpolar carbon chains of all these A B ""c II o H2C O,~ I I I o 0 ""c~ II o • OH Triglyceride C H2C~0~ n C1/',. : o.I~ ISaponification I. H2r~OH o • H2C~OH + Na+O'......,. ~ (1iO,c/'" C -. .""" ••• H2~~0 II I g : + 0 H2C~ OH A 'Soap' 'Alkoxide' Glycerol E Figure 1. Saponification. A. The ester linkage is the site vulnerable to attack by the alkali hydroxide. B. The hydroxide at- tacks the carbonyl carbon. C. Once attached, its presence weakens the ester bond to the glycerol spine which breaks leaving a carboxylic acid group on the fat and an "alkoxide" on the glycerol spine (D). The alkoxide is more basic than the OH of the carboxylic acid and it abstracts the proton to give the sodium carboxylate salt or "soap" and glycerol (after similar cleavage of all three triglyceride ester bonds). This process of soap formation is called saponification. Journalof Burn Care& Research Volume37, Number 2 Greenwood et at 137 A H'I-0 ....M~ H2CI-o,c~ CH3 Ii g .I . o~P~O=CH2 .. H3C= N ==""'" I A Phospholipid I 0- (phosphatidyl choline) CH3 Peptide Bond B H H I I HN-C - C-COOH 2 I I H H Glycine Glycine Figure 2. Phospholipid structure and peptide bond denaturation. A. Phospholipids have a similar structure to triglycerides, with one of the fatty acid chains replaced by a polar phosphate group. Additional groups are attached to the phosphate to give more complex lipids. B. The peptide bonds that link all the amino acids in protein are attacked in the same way that the hydroxide anion attacks the amide bond in ceramide. The destruction of the three-dimensional protein structure and libera- tion of the constituent water- and fat-soluble amino acids make the protein "liquefY." membrane lipids associate to form a bilayer, with the Fat Saponification polar head groups exposed to the aqueous environ- The term "saponification" is introduced into the ment. All these lipids contain one or more reactive dictionary of children embarking on a chemistry syl- ester linkages that can be hydrolyzed by a process labus early in their high school education. This pro- known as saponification as discussed below. cess can be illustrated by placing a drop of sodium or potassium hydroxide onto the pulp of the child's PROTEINS index finger, and encouraging them to rub index and thumb pulps together. The "slippery" sensation Proteins are linear polymers of amino acids experienced is hopefully short-lived as the hand is linked together by amide or peptide bonds1o then thrust under running water to dilute the alkali (Figure 2B). These linear sequences fold into a and stop the reaction. The teacher intones that the well-defined 3D-conformation (or shape) that alkali has converted the fats in the skin into soap, defines the function of the protein. This folding hence the slippery feeling. Although strong acids occurs at a number of levels; small segments of can also catalyze the process, hydrolysis of fats in the well-defined conformation referred to as second- commercial process of soap production is invariably ary structure (eg, an a-helix or l3-pleated sheet), performed by sodium or potassium hydroxide. the entire conformation of each chain (tertiary The process of saponification refers to the irrevers- ;tructure), and multi-subunit folding and inter- ible hydrolysis of the ester groups of natural fats and actions referred to as quaternary structure.