Canis ISSN: 2398-2942

Ketoacidosis pathophysiology

Contributor(s): Vetstream Ltd

Introduction

  • Diabetic ketoacidosis Diabetic ketoacidosis is a serious, life threatening condition - successful treatment requires attention to metabolic consequences.

Ketone production

  • In the normal animal free fatty acids (FFA) are released from adipose tissue in the process of lipolysis and are used as fuel or assimilated by the liver in the presence of reduced insulin concentrations and increased glucagon concentrations.
  • They are used to build triglycerides, metabolized in the tricarboxylic acid cycle or converted to ketone bodies.
  • In the face of a relative or absolute insulin deficiency the cells are unable to uptake and utilize glucose.
  • Ketone bodies can be used by peripheral tissues and the liver as an alternative source of energy and are therefore life-saving in the short-term.
  • Production is normally carefully controlled by a homeostatic mechanism. If this balance is disturbed a number of processes are activated which together produce a decompensated state which inevitably progresses towards death unless averting action is taken.
  • As the rate of ketone body production begins to exceed the rate at which they can be used, ketonemia develops with associated acidosis.
  • Once the concentration in the blood exceeds the renal threshold ketonuria Urinalysis: ketone develops and this provides an alternative mechanism for ketone removal from the body.

Insulin antagonism

  • Ketoacidosis Diabetic ketoacidosis is often associated with conditions which increase concentrations of diabetogenic hormones:
    • Infection: increases concentrations of cortisol and glucagon.
    • Congestive heart failure: increases concentrations of catecholamines and glucagon.
    • Pyrexia: increases concentrations of cortisol, catecholamines, growth hormone and glucagons.

Fasting

  • During fasting the body mobilizes lipid deposits for fuel and this increases ketone production.
  • Inappetance is therefore associated with ketonemia and this results in further anorexia creating a vicious cycle of ketone production.
  • Ketonemia also stimulates nausea which further suppresses appetite.

    It is therefore very important not to withhold insulin if a diabetic patient fails to eat, as, in the absence of insulin, ketonemia may develop rapidly.The recommendation is to administer 50% of the insulin dose to an inappetant diabetic patient.

Dehydration

  • Dehydration is common in diabetic patients due to fluid loss in urine and insufficient compensation.
  • Anything which further reduces fluid intake may push a diabetic animal into a ketotic state.
  • A reduction in intravascular fluid volume reduces glomerular filtration rate and thus the ability of the patient to excrete glucose and subsequently ketones and hydrogen ions in the urine.
  • Once ketonemia develops the anionic charge of the ketones in the blood necessitates a loss of sodium, potassium, calcium and magnesium ions from the kidney (to maintain a neutral body charge).
  • This increased electrolyte excretion reduces the concentration gradient in the Loop of Henle and hence the kidney's ability to concentrate urine → further dehydration is inevitable.

Other complications associated with ketosis

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