What different kinds of Ketoacidosis are there?

With Focus on Alcohol

What is ketoacidosis?

Definitions

● Diabetes mellitus: syndrome or chronic hyperglycaemia due to relative insulin deficiency, resistance, or both

● Diabetic ketoacidosis: A life threatening complication of diabetes mellitus. Severe Insulin deficiency, hyperglycaemia (Blood Glucose >11mmol/L) is associated with metabolic acidosis due to raised ketone levels (>5 mmol/l).

Aetiology ● Previously undiagnosed diabetes

● Interruption of insulin therapy, or non-adherance to insulin therapy

● Inter-current illness

Symptoms● Vomiting● Thirst● Polyuria● Weight loss● Abdominal Pain

Signs● Ketonuria and Glycosuria● Vomiting● Kussmaul breathing: hyperventilation● Acetone smell on breath● Confusion and disorientation => Coma● Hypokalaemia: blood potassium concentration <3.5 mmol/L● Dehydration: decreased skin turgor, dry skin, sunken eyes.● Hypotension + Tachycardia● Pyrexia

Acidosis: a disorder where excess H ions are found in the extracellular fluid Acidosis can lead to Kussmal breathing in an attempt to ‘blow off’ CO2

Insufficient insulin production

Hyperglycaemia-Reduction in cellular uptake of glucose

Body metabolises fatty and amino acids.

High Concentration of ketone bodies

Excess acetyl CoA from lipid metabolism due to insufficient

oxaloacetateKetogenisis

Production of Ketone bodies (acetoacetate, B-

hydroxybutyrate, acetone) Acidosis

Pathogenesis

Pathophysiology

Pathophysiology

Alcoholic Ketoacidosis

Background● Alcohol Ketoacidosis (AKA) was first described by E.S. Dillon

in 1940 as a distinct syndrome. ● Dillon described a series of nine patients who did not suffer from

diabetes mellitus, but still suffered from severe ketoacidosis● A common factor for these patients was prolonged excessive

alcohol consumption

● AKA is well described in international emergency medicine literature, but it is rarely diagnosed by UK emergency physicians. ● One reason is because many of the clinical features of AKA is

common with other conditions that arise due to alcohol dependent patients.

Who is Affected by AKA?● AKA most commonly occurs in adults (aged 20-60) who

are chronic abusers of alcohol, but it has also been reported in less-experienced drinkers of all ages ● Patients who are diagnoses with AKA typically have a

recent history of binge drinking, little or no food intake (malnourished), and persistent vomiting

● There are no racial or sexual differences in incidence; the prevalence of AKA in a given community correlates with the incidence and distribution of alcohol abuse in that community

(Stanford University, 2009)

Metabolism of Alcohol● Alcohol is broken down by alcohol

dehydrogenase● CH3CH2OH + NAD CH3CHO + NADH + H+

● The increased levels of NADH prevent gluconeogenesis by preventing the conversion of cytoplasmic malate to oxaloacetate

● Glycolysis is also reduced because glyceraldehyde-3-phosphate is forced to run backwards because of high NADH concentration

(Stanford University, 2009)

Alcoholic Ketoacidosis● The blocking of

gluconeogenesis then means that lipolysis takes place to produce energy

● This lipolysis then means that the ketone levels in the body increase

● Therefore leading to ketoacidosis

Simple diagram of glycolysis and gluconeogenesis

Prognosis● Ketoacidosis is potentially a life threatening disease.

● However, with prompt medical attention the prognosis of alcoholic ketoacidosis is good.

Prognosis can depend on other factors:• Alcoholism• Liver Disease• Complications (gastrointestinal bleeding, pancreatitis,

pneumonia)

TreatmentTreated with:

• Fluids (saline and dextrose)• Carbohydrates• Phosphates• Thiamine (administered to alcoholics to prevent

neurological damage)To counteract the 3 major pathophysiologic effects:

extracellular fluid depletion, glycogen depletion, increased NAD+)

What to Drink with DiabetesWines● Red wine, dry wine and dry champagne are all relatively low in sugar.● Sweet wines and champagnes should be avoided.

Spirits• All highly distilled so should not contain sugars• Be careful not to mix spirits with sugary drinks Liqueurs• Kirsch, Irish Cream and Grand Marnier contain about 10g carbs per shot.• Creme de Menthe, Sambuca and Amaretto contain over 15g carbs per

shot. Beers• ‘Light’ beers have less than 10g carbs per pint.• Pilsners is meant to have little effect on blood sugar.• Regular lagers tend to range from 10-15g carbs per pint• Stouts, Porters and Guinness tend to have over 20g carbs per pint.

Bibliography● Ansstas MD, G. et al. Alcoholic Ketoacidosis; Treatment & Management. [online] Available at: http://emedicine.medscape.com/article/116820-treatment [Accessed 4 November 2012]●  ● Ansstas, G. MD, 2011. Alcoholic Ketoacidosis Treatment & Management. [online] Available at: http://emedicine.medscape.com/article/116820-treatment [Accessed 4 November

2012]●  ● Aston University, 2010. Helping new medical graduates to prescribe safely. [online] Available at: http://www1.aston.ac.uk/about/news/releases/2010/october/medical-graduates-to-

prescribe-safely/ [Accessed 30 October 2012]●  ● BBC, 2002. Alcohol May Prevent Diabetes. BBC News. [online] Available at: http://news.bbc.co.uk/1/hi/health/1988884.stm [Accessed 5 November 2012]● Chew, S.L. and Leslie, D., 2011. Clinical Endocrinology and Diabetes. UK: E● lsevier● Dominiczak, M.H., 2011. Flesh and Bones of Metabolism. UK: Elsevier ● Hughes, R., 2009. Diabetic Ketoacidosis. [online] Available at: http://totw.anaesthesiologists.org/2009/04/06/diabetic-ketoacidosis-128/ [Accessed 24 November 2012]●  ● Kerl, M.E. DVM., 2001. Diabetic Ketoacidosis Pathophysiology and Clinical and Laboratory presentation [pdf] 23(2) Available at: http://www.google.co.uk/url?

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●  ● Kumar, P. and Clarke, M.L., 2012 Clinical Medicine. Spain: Elsevier● McGuire, L.C., Cruickshank, A.M., and Munro, P.T., 2006. Alcoholic Ketoacidosis, Emerg Med Journal [online] 23(6) pp.417-420 Available at: http://www.ncbi.nlm.nih.gov/pmc/

articles/PMC2564331/ [Accessed 18 November 2012]●  ● Medline Plus, n.d. Alcoholic Ketoacidosis [online] Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000323.htm [Accessed 4 November 2012]●  ● MedlinePlus, 2010. Gentamicin Sulfate Injection. [online] Available at: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682275.html [Accessed 4 November 2012]●  ● Quinn, A., 2009. Metabolic Acidosis in Emergency Medicine. [online] Available at: http://emedicine.medscape.com/article/768268-overview [Accessed 25 November 2012]● Savage, M.W., Dhatariya, K.K., Kilvert, A., Rayman, G., Rees, J.A.E., Courtney, C.H., Hilton, L., Dyer, P.H., and Hamersley, M.S., 2011.Diabetes UK Position Statements and Care

Recommendations Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis [pdf] Available at: http://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CDAQFjAA&url=http%3A%2F%2Fwww.bsped.org.uk%2Fclinical%2Fdocs%2FJBDSDKAguidelines_May11.pdf&ei=8Q6yUMG7Ac-ThgeExoGoCw&usg=AFQjCNHNQZMfJo4-OzOJlsJM1Cb8R4BGWg&sig2=HWh9JtVA-WsRiqdT8DEqDA [Accessed 25 November 2012]