Ketonuria | |
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Ketonuria using Bayer Ketostix | |
Specialty | Endocrinology |
Ketonuria is a medical condition in which ketone bodies are present in the urine.
It is seen in conditions in which the body produces excess ketones as an indication that it is using an alternative source of energy. It is seen during starvation or more commonly in type 1 diabetes mellitus. Production of ketone bodies is a normal response to a shortage of glucose, meant to provide an alternate source of fuel from fatty acids.
Ketones are metabolic end-products of fatty acid metabolism. In healthy individuals, ketones are formed in the liver and are completely metabolized so that only negligible amounts appear in the urine. However, when carbohydrates are unavailable or unable to be used as an energy source, fat becomes the predominant body fuel instead of carbohydrates and excessive amounts of ketones are formed as a metabolic byproduct. Higher levels of ketones in the urine indicate that the body is using fat as the major source of energy.
Ketone bodies that commonly appear in the urine when fats are burned for energy are acetoacetate and beta-hydroxybutyric acid. Acetone is also produced and is expired by the lungs. [1] Normally, the urine should not contain a noticeable concentration of ketones to give a positive reading. As with tests for glucose, acetoacetate can be tested by a dipstick or by a lab. The results are reported as small, moderate, or large amounts of acetoacetate. A small amount of acetoacetate is a value under 20 mg/dL; a moderate amount is a value of 30–40 mg/dL, and a finding of 80 mg/dL or greater is reported as a large amount.
One 2010 study admits that though ketonuria's relation to general metabolic health is ill-understood, there is a positive relationship between the presence of ketonuria after fasting and positive metabolic health. [2]
In non-diabetic persons, ketonuria may occur during acute illness or severe stress. Approximately 15% of hospitalized patients may have ketonuria, even though they do not have diabetes. In a diabetic patient, ketone bodies in the urine suggest that the patient is not adequately controlled and that adjustments of medication, diet, or both should be made promptly. In the non diabetic patient, ketonuria reflects a reduced carbohydrate metabolism and an increased fat metabolism.
A wide variety of companies manufacture ketone screening strips. A strip consists of a thin piece of plastic film slightly larger than a matchstick, with a reagent pad on one end that is either dipped into a urine sample or passed through the stream while the user is voiding. The pad is allowed to react for an exact, specified amount of time (it is recommended to use a stopwatch to time this exactly and disregard any resultant colour change after the specified time); [3] [4] its resulting colour is then compared to a graded shade chart indicating a detection range from negative presence of ketones up to a significant quantity. In severe diabetic ketoacidosis, the dipstix reaction based on sodium nitroprusside may underestimate the level of ketone bodies in the blood. It is sensitive to acetoacetate only, and the ratio of beta-hydroxybutyric to acetoacetate is shifted from a normal value of around 1:1 up to around 10:1 under severely ketoacetotic conditions, due to a changing redox milieu in the liver. Measuring acetoacetate alone will thus underestimate the accompanying beta-hydroxybutyrate if the standard conversion factor is applied. [5]
Urine value | Designation | Approximate serum concentration | |
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mg/dL | mmol/L | ||
0 | Negative | Reference range: 0.5-3.0 [6] | 0.05-0.29 [6] |
1+ | 5 (interquartile range (IQR): 1–9) [7] | 0.5 (IQR: 0.1–0.9) [8] | |
2+ | Ketonuria [9] | 7 (IQR: 2–19) [7] | 0.7 (IQR: 0.2–1.8) [8] |
3+ | 30 (IQR: 14–54) [7] | 3 (IQR: 1.4–5.2) [8] | |
4+ | Severe ketonuria [10] | - | - |
Screening for ketonuria is done frequently for acutely ill patients, presurgical patients, and pregnant women. Any diabetic patient who has elevated levels of blood and urine glucose should be tested for urinary ketones. In addition, when diabetic treatment is being switched from insulin to oral hypoglycemic agents, the patient's urine should be monitored for ketonuria. The development of ketonuria within 24 hours after insulin withdrawal usually indicates a poor response to the oral hypoglycemic agents. Diabetic patients should have their urine tested regularly for glucose and ketones, particularly when acute infection or other illness develops.
In conditions associated with acidosis, urinary ketones are tested to assess the severity of acidosis and to monitor treatment response. Urine ketones appear before there is any significant increase in blood ketones; [11] therefore, urine ketone measurement is especially helpful in emergency situations.
The following is a glossary of diabetes which explains terms connected with diabetes.
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of consciousness. A person's breath may develop a specific "fruity" smell. The onset of symptoms is usually rapid. People without a previous diagnosis of diabetes may develop DKA as the first obvious symptom.
Ketone bodies are water-soluble molecules or compounds that contain the ketone groups produced from fatty acids by the liver (ketogenesis). Ketone bodies are readily transported into tissues outside the liver, where they are converted into acetyl-CoA —which then enters the citric acid cycle and is oxidized for energy. These liver-derived ketone groups include acetoacetic acid (acetoacetate), beta-hydroxybutyrate, and acetone, a spontaneous breakdown product of acetoacetate.
Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.
Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiological ketosis is a normal response to low glucose availability, such as low-carbohydrate diets or fasting, that provides an additional energy source for the brain in the form of ketones. In physiological ketosis, ketones in the blood are elevated above baseline levels, but the body's acid–base homeostasis is maintained. This contrasts with ketoacidosis, an uncontrolled production of ketones that occurs in pathologic states and causes a metabolic acidosis, which is a medical emergency. Ketoacidosis is most commonly the result of complete insulin deficiency in type 1 diabetes or late-stage type 2 diabetes. Ketone levels can be measured in blood, urine or breath and are generally between 0.5 and 3.0 millimolar (mM) in physiological ketosis, while ketoacidosis may cause blood concentrations greater than 10 mM.
Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies energy to certain organs, particularly the brain, heart and skeletal muscle, under specific scenarios including fasting, caloric restriction, sleep, or others.
Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in blood pH and requires medical attention. The most common cause of ketoacidosis is diabetic ketoacidosis but can also be caused by alcohol, medications, toxins, and rarely, starvation.
Alcoholic ketoacidosis (AKA) is a specific group of symptoms and metabolic state related to alcohol use. Symptoms often include abdominal pain, vomiting, agitation, a fast respiratory rate, and a specific "fruity" smell. Consciousness is generally normal. Complications may include sudden death.
Fatty acid metabolism consists of various metabolic processes involving or closely related to fatty acids, a family of molecules classified within the lipid macronutrient category. These processes can mainly be divided into (1) catabolic processes that generate energy and (2) anabolic processes where they serve as building blocks for other compounds.
Ketotic hypoglycemia is a medical term used in two ways: (1) broadly, to refer to any circumstance in which low blood glucose is accompanied by ketosis, and (2) also nutritional ketosis. It remains one of the more common causes of hypoglycemia in the age range.
β-Hydroxybutyric acid, also known as 3-hydroxybutyric acid or BHB, is an organic compound and a beta hydroxy acid with the chemical formula CH3CH(OH)CH2CO2H; its conjugate base is β-hydroxybutyrate, also known as 3-hydroxybutyrate. β-Hydroxybutyric acid is a chiral compound with two enantiomers: D-β-hydroxybutyric acid and L-β-hydroxybutyric acid. Its oxidized and polymeric derivatives occur widely in nature. In humans, D-β-hydroxybutyric acid is one of two primary endogenous agonists of hydroxycarboxylic acid receptor 2 (HCA2), a Gi/o-coupled G protein-coupled receptor (GPCR).
Starvation response in animals is a set of adaptive biochemical and physiological changes, triggered by lack of food or extreme weight loss, in which the body seeks to conserve energy by reducing the amount of food energy it consumes.
In enzymology, 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) is an enzyme that catalyzes the chemical reaction:
Free fatty acid receptor 2 (FFAR2), also termed G-protein coupled receptor 43 (GPR43), is a rhodopsin-like G-protein coupled receptor. It is coded by the FFAR2 gene. In humans, the FFAR2 gene is located on the long arm of chromosome 19 at position 13.12. Like other GPCRs, FFAR2s reside on the surface membrane of cells and when bond to one of their activating ligands regulate the function of their parent cells. FFAR2 is a member of a small family of structurally and functionally related GPRs termed free fatty acid receptors (FFARs). This family includes three other receptors which, like FFAR2, are activated by certain fatty acids: FFAR1, FFAR3 (GPR41), and FFAR4 (GPR120). FFAR2 and FFAR3 are activated by short-chain fatty acids whereas FFAR1 and FFAR4 are activated by long-chain fatty acids.
Frederick Madison Allen was a physician who is best remembered for his carbohydrate-restricted low-calorie diet for sufferers of diabetes mellitus. He was known for pioneering the "starvation diet".
High anion gap metabolic acidosis is a form of metabolic acidosis characterized by a high anion gap. Metabolic acidosis occurs when the body produces too much acid, or when the kidneys are not removing enough acid from the body. Several types of metabolic acidosis occur, grouped by their influence on the anion gap.
A urine test strip or dipstick is a basic diagnostic tool used to determine pathological changes in a patient's urine in standard urinalysis.
Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types: acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), lactic acidosis (LA), and hypoglycemia. Chronic complications develop over time and are generally classified in two categories: microvascular and macrovascular. Microvascular complications include neuropathy, nephropathy, and retinopathy; while cardiovascular disease, stroke, and peripheral vascular disease are included in the macrovascular complications.
Diabetes mellitus is a disease in which the beta cells of the endocrine pancreas either stop producing insulin or can no longer produce it in enough quantity for the body's needs. The disease can affect humans as well as animals such as dogs.
Exogenous ketones are a class of ketone bodies that are ingested using nutritional supplements or foods. This class of ketone bodies refers to the three water-soluble ketones. These ketone bodies are produced by interactions between macronutrient availability such as low glucose and high free fatty acids or hormone signaling such as low insulin and high glucagon/cortisol. Under physiological conditions, ketone concentrations can increase due to starvation, ketogenic diets, or prolonged exercise, leading to ketosis. However, with the introduction of exogenous ketone supplements, it is possible to provide a user with an instant supply of ketones even if the body is not within a state of ketosis before ingestion. However, drinking exogenous ketones will not trigger fat burning like a ketogenic diet.