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(BQ) Part 2 book Oh''s intensive care manual has contents: Endocrine disorders, endocrine disorders, infections and immune disorders, severe and multiple trauma, environmental injuries, pharmacologic considerations, metabolic homeostasis,.... and other contents.
Part Eight Endocrine Disorders 58 Diabetic Emergenciesâ•… 629 59 Diabetes Insipidus and Other Polyuric Syndromesâ•… 637 60 Thyroid Emergenciesâ•… 652 61 Adrenocortical Insufficiency in Critical Illnessâ•… 660 62 Acute Calcium Disordersâ•… 666 This page intentionally left blank 58 Diabetic emergencies Richard Keays Diabetes mellitus is due to an absolute or relative deficiency of insulin The sustained effect of poor glycaemic control results in a wide array of end-organ damage as a consequence of small- and large-vessel pathology Mortality and morbidity are related to the progress of this damage but often there are acute metabolic deteriorations that can be life-threatening Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS) are two of the most common acute complications of diabetes, both accompanied by hyperglycaemia The pathophysiological changes that occur in both disease states represent an extreme example of the super-fasted state Coma may also result from severe hypoglycaemia due to overtreatment – usually with insulin DIABETES MELLITUS Type I insulin-dependent diabetes mellitus (IDDM) has a peak incidence in the young rising from months to 14 years and declining thereafter In 25% of patients the presentation is with ketoacidosis, especially in those under years of age Usually the fasting plasma glucose is >7.8╯mmol/L and glucose and ketones may be present in the urine In the asymptomatic patient with an equivocal fasting plasma glucose, an impaired glucose tolerance test may be demonstrated Type II non-insulin-dependent diabetes mellitus (NIDDM) is prevalent in the elderly but can occur at any age Truncal obesity is a risk factor and there is ethnic variation in susceptibility Diagnosis is often delayed and may be incidental from blood or urine sugar screening.1 Increasingly it is recognised that individuals can be in a prediabetic state of impaired glucose regulation for many years, which makes them to 15 times more likely to progress to diabetes It may present with classical symptoms, as a diabetic emergency, with complications of organ damage or vascular disease EPIDEMIOLOGY The worldwide prevalence of diabetes is estimated to be 366 million people in 2011 Diabetes mellitus affects about 6% of the world’s population and is set to rise to 552 million sufferers by 2030.2 Most of these (97%) will have type II diabetes but the resources required to treat the complications of type I diabetes are such that health care costs are equivalent between the two groups The annual incidence of DKA is around 14 episodes per thousand patients with diabetes and it has been estimated in the USA that about $1 billion are spent each year in treating DKA Hospital admissions for DKA have gone up by 30% in the last decade and this is most likely due to the increase in ketosis-prone type II diabetics HHS represents approximately 1% of primary admissions to hospital with diabetes as compared with DKA The mortality rate in HHS remains high at 5–20%, whereas the mortality in DKA has been falling dramatically in recent years and is less than 1% but still remains high in the elderly.3 An interplay of both genetic and environmental factors contribute to disease development In type I diabetes there is some evidence for genetic susceptibility but environmental factors play a greater part It varies across race and regions, being highest in northern Europe and the USA and lowest in Asia and Australasia Genetic factors in type diabetes are evidently crucial, with a concordance between monozygotic twins approaching 100% PATHOGENESIS Normal carbohydrate metabolism depends upon the presence of insulin (Fig 58.1) However, different tissues handle glucose in different ways; for example, red blood cells lack mitochondria and therefore pyruvate dehydrogenase and the enzymes involved in β-oxidation, whereas liver parenchymal cells are able to perform the full range of glucose disposal (Fig 58.2) Both DKA and HHS result from a reduction in the effect of insulin with a concomitant rise in the counterregulatory hormones such as glucagon, catecholamines, cortisol and growth hormone Hyperglycaemia occurs as a consequence of three processes: increased gluconeogenesis, increased glycogenolysis and reduced peripheral glucose utilisation The increase in glucose production occurs in both the liver and the kidneys as there is a high availability of gluconeogenic precursors such as amino acids (protein turnover shifts from balanced synthesis and degradation to reduced synthesis and increased degradation) Lactate and glycerol also become available owing to an increase in skeletal muscle glycogenolysis and an increase in adipose tissue 630 Diabetic emergencies Glycogen Triglycerides Glocogenesis Lipolysis Proteolysis Fatty acids Glucose Amino acids Oxidation Glycolysis Pyruvate Figure 58.1 Sources and fate of acetyl CoA *Pyruvate conversion by pyruvate dehydrogenase (PDH) is essentially irreversible, therefore no net conversion of fatty acids to carbohydrates can occur TCAâ•›=â•›tricarboxylic acid Protein Deamination + oxidation PDH* Sterols Fatty acids Acetyl CoA Oxidation TCA Ketone bodies Acetoacetate Hydroxybutyrate Lactate Electron transport Pentose phosphates Glucose Glucose 6-P Glucoronides 13 Glycogen 11 12 Pyruvate Lactate H+ Figure 58.2 Glucose metabolism within hepatocyte: (1) glucose transport GLUT-1; (2) hexokinase phosphorylation; (3) pentose phosphate pathway (hexose monophosphate shunt); (4) glycolysis; (5) lactate transport out of cell; (6) pyruvate decarboxylation; (7) tricarboxylic acid cycle; (8) glycogenesis; (9) glycogenolysis; (10) lipogenesis; (11) gluconeogenesis; (12) glucose-6-phosphate (G 6-P) hydrolysis and release of glucose; (13) glucuronidation Acetyl CoA 10 CO2 Fat lipolysis respectively Lastly, there is an increase in gluconeogenic enzyme activity enhanced further by stress hormones Although hepatic gluconeogenesis is the main mechanism for producing hyperglycaemia a significant proportion can be produced by the kidneys.4 What is unclear is the temporal relationship of these changes, although an increase in both catecholamines and the glucagon/insulin ratio are early features.5 Decreased insulin and increased epinephrine levels activate adipose tissue lipase causing a breakdown of triglycerides into glycerol and free fatty acids (FFAs) Once again glucagon is implicated as hepatic oxidation of FFAs to ketone bodies is stimulated predominantly by its inhibitory effect on acetyl-CoA carboxylase The resultant reduced synthesis of malonyl-CoA causes a disinhibition of acyl-carnitine synthesis and subsequent promotion of fatty acid transport into mitochondria where ketone body formation occurs Both cortisol and growth hormone are capable of increasing FFA and ketone levels and once again the exact contribution of insulin deficiency or stress hormone increase to ketogenesis is undetermined As ketone bodies are comparatively strong acids, a large hydrogen ion load is produced owing to their dissociation at physiological pH The need to buffer hydrogen ions depletes the body’s alkali reserves and ketone anions accumulate, accounting for the elevated plasma anion gap By contrast, HHS does not share the ketogenic features of DKA Reduced levels of FFAs, glucagon, cortisol and growth hormone have been demonstrated in HHS relative to DKA although this is by no means a consistent observation However, the presence of higher levels of C-peptide in HHS (with lower levels of growth hormone) relative to DKA suggests there is just enough insulin present in HHS to prevent lipolysis but not enough to promote peripheral glucose utilisation.6 Hyperosmolarity, which is a prominent feature of HHS, is caused by the prolonged effect of an osmotic Clinical presentation diuresis with impaired ability to take adequate fluids It has been shown that, even when well, patients who have suffered from HHS have impaired thirst reflexes However, the hyperosmolarity seen in about one-third of patients with DKA results from a shorter osmotic diuresis and to variable fluid intake due to nausea and vomiting – which is often ascribed to the brainstem effects of ketones Interestingly, hyperglycaemia with or without ketoacidosis leads to a significant increase in proinflammatory cytokine production, which resolves when insulin therapy is commenced.7 This has led others to postulate a wider beneficial anti-inflammatory effect attributable to insulin therapy This proinflammatory, pro-thrombotic state may explain the relatively high incidence of thrombotic events associated with diabetic emergencies CLINICAL PRESENTATION DKA and HHS represent the two extremes of presentation due to the absolute or relative deficiency of insulin However, up to one-third of cases can present with mixed features.8 DKA develops over a shorter time period whereas HHS appears more insidiously – see Table 58.1 Polyuria, polydipsia and weight loss are experienced for a variable period prior to admission and, in patients with DKA, nausea and vomiting are also common symptoms Abdominal pain is commonly Table 58.1 Comparison of DKA and HHS PRESENTATION DKA HHS Prodromal illness Days Weeks Coma ++ +++ Blood glucose ++ +++ Ketones +++ or + Acidaemia +++ or + Anion gap ++ or + Osmolality ++ +++ 631 seen in children and occasionally in adults and may mimic an acute abdomen Dehydration presents with loss of skin turgor, dry mucous membranes, tachycardia and hypotension Mental obtundation occurs more frequently in HHS than DKA as more patients, by definition, are hyperosmolar and the presence of stupor or coma in patients who are not hyperosmolar requires consideration of other potential causes for altered mental status.9 However, loss of consciousness is not a common presentation with DKA or HHS (