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Hyperglycemic Crises

Diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus. Diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis is characterized by hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus and ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis due to an absolute insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin deficiency. Hyperosmolar hyperglycemic state occurs due to a relative deficiency of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin or insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing, leading to severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus and elevated serum osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation. Triggering factors include inadequate insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy, underlying infection, concurrent medical illness, or drug side effects. Diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship tend to be younger, with type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, who present with acute symptoms, including abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. On the other hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy, HHS patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are generally older, with type 2 Type 2 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, and will have gradual onset of symptoms, including altered mental status Altered Mental Status Sepsis in Children and neurologic changes. Both sets of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will have polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation, polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus, and evidence of severe dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration. Diagnosis is based on laboratory values demonstrating hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus with ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis or hyperosmolality. Management involves aggressive fluid rehydration Rehydration Dengue Virus, insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy, and correction of electrolyte abnormalities.

Last updated: Apr 25, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus

  • Both DKA and HHS are characterized by: 
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with DKA will have ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HHS have more severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus and hyperosmolality.
  • Both of these diagnoses can run on a spectrum, and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may present with features of both DKA and HHS.

Epidemiology

  • DKA:
    • More frequently seen in younger patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 
    • Mostly seen in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Accounts for approximately 14% of all hospital admissions for diabetics
    • Mortality rate Mortality rate Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status: 0.2%–2% (increased mortality Mortality All deaths reported in a given population. Measures of Health Status in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma, hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia, and oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation)
  • HHS:
    • Usually associated with older individuals (≥ 65 years)
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will usually have type 2 Type 2 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus.
    • Accounts for fewer hospitalizations than DKA (< 1%)
    • Mortality rate Mortality rate Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status: 10%–20%
      • 10 times higher than DKA
      • Usually due to the precipitating cause
      • Increased mortality Mortality All deaths reported in a given population. Measures of Health Status in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma and hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension

Etiology

  • Both HHS and DKA:
    • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (most common)
    • Inadequate or noncompliance Noncompliance Clinician–Patient Relationship with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin treatment
    • Acute illnesses (e.g., stroke, myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, pancreatitis Pancreatitis Inflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis. Acute Pancreatitis, surgery, trauma)
    • Medications:
      • Corticosteroids Corticosteroids Chorioretinitis
      • Olanzapine Olanzapine A benzodiazepine derivative that binds serotonin receptors; muscarinic receptors; histamine h1 receptors; adrenergic alpha-1 receptors; and dopamine receptors. It is an antipsychotic agent used in the treatment of schizophrenia; bipolar disorder; and major depressive disorder; it may also reduce nausea and vomiting in patients undergoing chemotherapy. Second-Generation Antipsychotics
      • Lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly
      • Clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics
    • Drugs:
      • Alcohol
      • Cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
  • HHS:
    • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration
    • Medications:
      • Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
      • Beta blockers
      • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers
      • Total parenteral nutrition Total parenteral nutrition The delivery of nutrients for assimilation and utilization by a patient whose sole source of nutrients is via solutions administered intravenously, subcutaneously, or by some other non-alimentary route. The basic components of tpn solutions are protein hydrolysates or free amino acid mixtures, monosaccharides, and electrolytes. Components are selected for their ability to reverse catabolism, promote anabolism, and build structural proteins. IPEX Syndrome
    • Endocrine disorders:
      • Cushing’s syndrome
      • Acromegaly Acromegaly A condition caused by prolonged exposure to excessive human growth hormone in adults. It is characterized by bony enlargement of the face; lower jaw (prognathism); hands; feet; head; and thorax. The most common etiology is a growth hormone-secreting pituitary adenoma. Acromegaly and Gigantism
      • Thyrotoxicosis Thyrotoxicosis A hypermetabolic syndrome caused by excess thyroid hormones which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid hyperplasia; thyroid neoplasms; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by nervousness; tachycardia; fatigue; weight loss; heat intolerance; and excessive sweating. Thyrotoxicosis and Hyperthyroidism
  • DKA:
    • New-onset diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
    • Medications:

Pathophysiology

Normal physiology

The normal response to increased serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance involves the release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin by pancreatic beta cells. This leads to:

  •  ↓ glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions secretion Secretion Coagulation Studies in pancreatic alpha-cells → ↓ gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis and glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy → ↓ glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance production
  • glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance uptake by muscle and adipose cells Adipose Cells Fat Necrosis of the Breast

Pathophysiology of DKA

  • Hormone abnormalities:
    • Absolute insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin deficiency
    • glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions
    • Additional hormone changes, which oppose insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin:
  • Hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus results from:
    • glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance utilization by peripheral tissues
    • glycogenolysis Glycogenolysis The release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase. Glycogen Metabolism
    • gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis:
      • amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids delivery from muscle
      • ↑ glycerol delivery from adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Adipose Tissue: Histology
  • Severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus leads to: 
    • osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation → draws water out of cells → dilutes sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia concentrations
    • Glucosuria Glucosuria Diabetes Mellitus osmotic diuresis Osmotic diuresis Volume Depletion and Dehydration, resulting in:
      • Water and electrolyte loss ( sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia
      • Dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration  
      • osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation
      • Impaired renal function
  • Ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis results from:
    • lipolysis Lipolysis The metabolic process of breaking down lipids to release free fatty acids, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the digestive tract, circulating lipids in the blood, and stored lipids in the adipose tissue or the liver. A number of enzymes are involved in such lipid hydrolysis, such as lipase and lipoprotein lipase from various tissues. Nonalcoholic Fatty Liver Disease → ↑ free fatty acids Fatty acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated. Fatty Acids and Lipids → ↑ ketone production ( ketogenesis Ketogenesis Ketone Body Metabolism)
    • bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes → consumed as a buffer → ↑ anion gap Anion gap Metabolic Acidosis
  • Acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis and hyperosmolality results in:
    • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia shifts out of cells → ↑ extracellular potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia, ↓ intracellular potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia
    • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia is then excreted in the urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat → ↓ total body potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia
Insufficient or absent insulin

Pathophysiology of diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis

Image by Lecturio.

Pathophysiology of HHS

  • Hormone abnormalities:
    • insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin or insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
    • Other similar hormone changes of DKA
  • Hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus occurs through the same process as DKA.
  • Since some insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin is present, ketogenesis Ketogenesis Ketone Body Metabolism is prevented → no acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis
  • Severe hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus leads to the same osmotic diuresis Osmotic diuresis Volume Depletion and Dehydration and sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia changes.
  • Hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus will be more severe than DKA → more severe hyperosmolar state
  • Despite the lack of acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis, the hyperosmolar state will still lead to similar shifts in potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia.

Clinical Presentation

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor of DKA

  • Rapid onset of symptoms (over 24 hours):
    • Polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation
    • Polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Diffuse abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
    • Weakness
    • History of weight loss Weight loss Decrease in existing body weight. Bariatric Surgery → common with a new diagnosis of type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Physical exam findings:
    • Vitals:
      • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
      • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
      • Hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia
      • Rapid, deep respirations (Kussmaul respirations) → compensatory hyperventilation Hyperventilation A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide. Respiratory Alkalosis
    • Fruity breath → exhaled acetone Acetone A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. Ketone Body Metabolism
    • Evidence of severe dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration:
      • Dry mucous membranes
      • Sunken eyes Sunken eyes Rotavirus
      • Decreased skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions turgor
      • Anhidrosis
      • Decreased urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat output

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor of HHS

  • Gradual development of symptoms (over days to weeks):
    • Polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation 
    • Polydipsia Polydipsia Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as diabetes mellitus; diabetes insipidus; and nephrogenic diabetes insipidus. The condition may be psychogenic in origin. Diabetes Insipidus
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Neurologic changes:
      • Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia
      • Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium
      • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma (in severe disease)
      • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
      • Sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology deficits
      • Vision Vision Ophthalmic Exam changes
  • Physical exam findings:
    • Vitals:
      • Similar to DKA
      • Kussmaul respirations are not usually seen
    • Altered mental status Altered Mental Status Sepsis in Children, lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, or coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
    • Similar findings of severe dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration to DKA
    • Transient focal neurologic changes may be seen in some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:

Diagnosis

Initial findings

Table: Main differences between DKA and HHS on workup
Laboratory test Diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis Hyperosmolar hyperglycemic state
Serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance > 250 mg/dL > 600 mg/dL
Serum bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes ↓↓ > 18 mEq/L
Anion gap Anion gap Metabolic Acidosis Generally normal
Serum osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables > 320 mOsm/L
Serum ketones Ketones Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups. Basics of Carbohydrates ( beta-hydroxybutyrate Beta-hydroxybutyrate Butyric acid substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver. Ketone Body Metabolism, acetone Acetone A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. Ketone Body Metabolism) Positive Small or negative
Urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat ketones Ketones Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups. Basics of Carbohydrates Positive Small or negative
Arterial blood gas Arterial blood gas Respiratory Alkalosis
  • pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance: ↓
  • pCO2: ↓
pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance: > 7.3

Other findings

  • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia (Na):
    • Generally ↓ due to sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia loss, extracellular dilution, and pseudohyponatremia (corrected sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia = measured serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia +  2 mEq/L for each 100 mg/dL of glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance above 100 mg/dL)
  • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia (K):
    • Normal or ↑ (despite an actual potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia deficit)
    • Will start to ↓ with correction of acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis and insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin administration
  • Creatinine: ↑ due to hypovolemia Hypovolemia Sepsis in Children and acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
  • Complete blood count:
    • Leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus → not necessarily related to infection
    • Bandemia → should be concerning for infection
  • Lipid panel:
    • cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism
    • triglycerides Triglycerides Fatty Acids and Lipids
    • Will ↓ with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin therapy
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification imaging (computed tomography (CT) or magnetic resonance imaging (MRI)):
    • For patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with altered mental status Altered Mental Status Sepsis in Children
    • Evaluates for cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, especially in children

General workup for precipitating factors

  • Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction:
    • Electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) ( ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG))
    • Troponin
  • Infection:
    • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children → rule out urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infection
    • Blood cultures Cultures Klebsiella
    • Chest radiograph → rule out pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
  • Toxicology:
    • Drug screen
    • Alcohol level

Management and Complications

Management of DKA

  • Admit patient to the intensive care unit ( ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus).
  • Aggressive intravenous (IV) fluid administration:
    • Begin with normal saline Normal saline A crystalloid solution that contains 9. 0g of sodium chloride per liter of water. It has a variety of uses, including: as a contact lens solution, in ophthalmic solutions and nasal lavage, in wound irrigation, and for fluid therapy. Intravenous Fluids:
      • If corrected Na is < 135 mEq/L, continue normal saline Normal saline A crystalloid solution that contains 9. 0g of sodium chloride per liter of water. It has a variety of uses, including: as a contact lens solution, in ophthalmic solutions and nasal lavage, in wound irrigation, and for fluid therapy. Intravenous Fluids.
      • If corrected Na remains normal or elevated, consider changing to 0.45% saline.
  • IV insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin infusion (K must be > 3.3 mEq/L):
    • Hourly serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance monitoring
    • Close monitoring of serum electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes and anion gap Anion gap Metabolic Acidosis (every 2–4 hours)
    • Provide potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia supplementation to maintain a K of 4–5 mEq/L.
    • Mild DKA may be managed with frequent subcutaneous (SC) insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin administration
  • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes (NaHCO3) can be given if the patient’s pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance is < 6.9.
  • Identify and treat the underlying cause.
  • DKA has resolved once the serum anion gap Anion gap Metabolic Acidosis has normalized (< 12 mEq/L) and glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance is 150–200 mg/dL:
    • Can initiate SC insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin if the patient is tolerating oral intake
    • Overlap with the IV insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin infusion for 2–4 hours to prevent recurrence of hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus and acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis.
Treatment algorithm diagram for diabetic ketoacidosis

Treatment algorithm for diabetic ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis

Image by Lecturio.

Management of HHS

  • Admit patient to the ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus.
  • Aggressive intravenous (IV) fluid administration:
    • HHS patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship typically have a fluid deficit of approximately 7–12 L.
    • Begin with normal saline Normal saline A crystalloid solution that contains 9. 0g of sodium chloride per liter of water. It has a variety of uses, including: as a contact lens solution, in ophthalmic solutions and nasal lavage, in wound irrigation, and for fluid therapy. Intravenous Fluids:
      • If the corrected Na is < 135 mEq/L, continue normal saline Normal saline A crystalloid solution that contains 9. 0g of sodium chloride per liter of water. It has a variety of uses, including: as a contact lens solution, in ophthalmic solutions and nasal lavage, in wound irrigation, and for fluid therapy. Intravenous Fluids.
      • If the corrected Na remains normal or elevated, consider changing to 0.45% saline.
    • Add dextrose Dextrose Intravenous Fluids to fluids once the glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance reaches 300 mg/dL.
    • Monitor urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat output and hemodynamics Hemodynamics The movement and the forces involved in the movement of the blood through the cardiovascular system. Vascular Resistance, Flow, and Mean Arterial Pressure.
  • IV insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin infusion (K must be > 3.3 mEq/L):
    • Hourly serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance monitoring
    • Close monitoring of serum electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes (every 2–4 hours)
    • Provide potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia supplementation to maintain K at 4–5 mEq/L.
  • Identify and treat the underlying cause.
  • HHS is resolved when the patient’s mental status has improved, serum osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation is < 315 mOsmol/kg, and glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance is 250–300 mg/dL:
    • Can initiate subcutaneous (SC) insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin if the patient is tolerating oral intake
    • Continue the IV insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin infusion for 2–4 more hours to minimize the recurrence of hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus
Treatment algorithm hyperosmolar hyperglycemic state

Treatment algorithm hyperosmolar hyperglycemic state

Image by Lecturio.

Complications

  • Cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema:
  • Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) arrhythmia: from electrolyte abnormalities
  • Noncardiogenic pulmonary edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema:
  • Thromboembolic disease:
  • Mucormycosis Mucormycosis Mucormycosis is an angioinvasive fungal infection caused by multiple fungi within the order, Mucorales. The fungi are ubiquitous in the environment, but mucormycosis is very rare and almost always occurs in patients who are immunocompromised. Inhalation of fungal spores can cause rhinocerebral or pulmonary mucormycosis, direct inoculation can cause cutaneous mucormycosis, and ingestion can cause gastrointestinal mucormycosis. Mucorales/Mucormycosis:
    • An opportunistic rhino-cerebral infection that may occur due to immunosuppression in DKA
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will have symptoms of acute sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess.

Differential Diagnosis

  • Alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis: a complication of alcohol use and starvation for > 24 hours, resulting in ketosis and high anion gap Anion gap Metabolic Acidosis acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis without hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will present with nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Diagnosis is made through the history and laboratory findings suggesting ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis with a normal glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, which helps differentiate this condition from DKA. Treatment includes IV fluid hydration with saline, dextrose Dextrose Intravenous Fluids, thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies, and vitamins.
  • Fasting and starvation ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis: low-carbohydrate intake leading to hepatic ketone production. Ketone levels are mildly elevated and serum bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes remains > 17 mEq/L. Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels are typically normal, but hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia can occur with starvation, which differs from DKA. In starvation ketoacidosis Ketoacidosis A life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma. Metabolic Acidosis, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, altered mental status Altered Mental Status Sepsis in Children, evidence of dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration, and tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination. Intravenous fluids Intravenous Fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids and electrolyte correction may be required.
  • Toxic-metabolic encephalopathy Encephalopathy Hyper-IgM Syndrome: a disruption of normal physiologic functions in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification caused by other conditions, such as infection, renal dysfunction, electrolyte abnormalities, and medications.  Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with somnolence, disorientation Disorientation St. Louis Encephalitis Virus, motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology abnormalities, or seizure. Laboratory tests can help distinguish the cause and differentiate this condition from HHS. Treatment focuses on the underlying cause.
  • Salicyclate poisoning: toxicity Toxicity Dosage Calculation due to a large ingestion of salicylates. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will have confusion, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures. Laboratory evaluation will show an anion gap Anion gap Metabolic Acidosis acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis, respiratory alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, elevated salicylate level, negative ketones Ketones Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups. Basics of Carbohydrates, and normal glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance. This evaluation will differentiate the condition from DKA. Treatment includes activated charcoal Charcoal An amorphous form of carbon prepared from the incomplete combustion of animal or vegetable matter, e.g., wood. The activated form of charcoal is used in the treatment of poisoning. Antidotes of Common Poisonings, sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes, and potential hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome to enhance salicylate elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy.
  • Methanol Methanol A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. Metabolic Acidosis poisoning: toxicity Toxicity Dosage Calculation due to ingestion of methanol Methanol A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. Metabolic Acidosis. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have blurry vision Vision Ophthalmic Exam or blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, appear inebriated or comatose Comatose A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem reticular formation. Hyponatremia, and have Kussmaul respirations. Workup will show an anion gap Anion gap Metabolic Acidosis acidosis Acidosis A pathologic condition of acid accumulation or depletion of base in the body. The two main types are respiratory acidosis and metabolic acidosis, due to metabolic acid build up. Respiratory Acidosis, osmolar gap, respiratory alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, and negative ketones Ketones Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups. Basics of Carbohydrates, which differs from DKA. A high degree of suspicion is required, and a volatile alcohol test can establish the diagnosis. Treatment includes fomepizole Fomepizole A pyrazole and competitive inhibitor of alcohol dehydrogenase that is used for the treatment of poisoning by ethylene glycol or methanol. Antidotes of Common Poisonings, ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism, or hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome.

References

  1. Brutsaert, E.F. (2020). Hyperosmolar hyperglycemic state (HHS) [online]. MSD Manual Professional Version. https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/hyperosmolar-hyperglycemic-state-hhs
  2. Brutsaert, E.F. (2020). Diabetic ketoacidosis (DKA) [online]. MSD Manual Professional Version. https://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/diabetic-ketoacidosis-dka
  3. Avichal, D., and Blocher, N.C. (2019). Hyperosmolar hyperglycemic state. In Griffing, G.T. (Ed.), Medscape. Retrieved November 16, 2020, from https://emedicine.medscape.com/article/1914705-overview
  4. Hamdy, O. (2019). Diabetic ketoacidosis (DKA). In Khardori, R. (Ed.), Medscape. Retrieved November 17, 2020, from https://emedicine.medscape.com/article/118361-overview
  5. Hirsch, I.B., and Emmett, M. (2020). Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Epidemiology and pathogenesis. In Mulder, J.E. (Ed.), UpToDate. Retrieved November 16, 2020, from https://www.uptodate.com/contents/diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults-epidemiology-and-pathogenesis
  6. Hirsch, I.B., and Emmett, M. (2020). Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis. In Mulder, J.E. (Ed.), UpToDate. Retrieved November 16, 2020, from https://www.uptodate.com/contents/diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults-clinical-features-evaluation-and-diagnosis
  7. Hirsch, I.B., and Emmett, M. (2020). Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment. In Mulder, J.E. (Ed.), UpToDate. Retrieved November 16, 2020, from https://www.uptodate.com/contents/diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults-treatment

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