Ketoacidosis
Encyclopedia
Ketoacidosis is a metabolic state associated with high concentrations of ketone bodies
, formed by the breakdown of fatty acids and the deamination
of amino acid
s. The two common ketones produced in humans are acetoacetic acid
and β-hydroxybutyrate
.
Ketoacidosis is a pathological metabolic state marked by extreme and uncontrolled ketosis
. In ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acid
s that the pH
of the blood
is substantially decreased. In extreme cases ketoacidosis can be fatal.
Ketoacidosis is most common in untreated type 1 diabetes mellitus
, when the liver breaks down fat
and proteins in response to a perceived need for respiratory substrate. Prolonged alcoholism may lead to alcoholic ketoacidosis. Fasting leads to ketosis but not ketoacidosis.
Ketoacidosis can be smelled on a person's breath. This is due to acetone
, a direct byproduct of the spontaneous decomposition of acetoacetic acid
. It is often described as smelling like fruit or nail polish remover. Ketosis may also smell, but the odor is usually more subtle due to lower concentrations of acetone.
via the metabolism
of fatty acids (ketosis
) and the body is producing insufficient insulin
to slow this production. The excess ketone bodies can significantly acidify the blood. The presence of a high concentration of glucose in the blood (hyperglycemia
) caused by the lack of insulin
can lead to further acidity. In healthy individuals this normally does not occur because the pancreas
produces insulin in response to rising ketone/blood glucose concentration.
Acidity results from the dissociation of the H+ ion at physiological pH of metabolic ketone bodies such as acetoacetate, and β-hydroxybutyrate
.
Acetone has no easily liberated proton, and is thus non-acidic in human biochemical environments
and alcoholic ketoacidosis.
In diabetic
patients, ketoacidosis is usually accompanied by insulin
deficiency, hyperglycemia
, and dehydration
. Particularly in type 1 diabetics the lack of insulin in the bloodstream prevents glucose
absorption and can cause unchecked ketone body production (through fatty acid metabolism) potentially leading to dangerous glucose and ketone levels in the blood. Hyperglycemia results in glucose overloading the kidneys and spilling into the urine
(transport maximum for glucose is exceeded). Dehydration results following the osmotic movement of water into urine
(Osmotic diuresis), exacerbating the acidosis
.
In alcoholic ketoacidosis, alcohol
causes dehydration and blocks the first step of gluconeogenesis
. The body is unable to synthesize enough glucose to meet its needs, thus creating an energy crisis resulting in fatty acid
metabolism, and ketone body formation.
Ketone bodies
Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting...
, formed by the breakdown of fatty acids and the deamination
Deamination
Deamination is the removal of an amine group from a molecule. Enzymes which catalyse this reaction are called deaminases.In the human body, deamination takes place primarily in the liver, however glutamate is also deaminated in the kidneys. Deamination is the process by which amino acids are...
of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s. The two common ketones produced in humans are acetoacetic acid
Acetoacetic acid
Acetoacetic acid is the organic compound with the formula CH3CCH2CO2H. It is the simplest beta-keto acid group and like other members of this class is unstable.- Synthesis and properties :...
and β-hydroxybutyrate
Beta-hydroxybutyrate
beta-Hydroxybutyric acid is a ketone body. It is a chiral compound having two enantiomers, D-3-hydroxybutyric acid and L-3-hydroxybutyric acid. Like the other ketone bodies , levels of beta-hydroxybutyrate are raised in ketosis...
.
Ketoacidosis is a pathological metabolic state marked by extreme and uncontrolled ketosis
Ketosis
Ketosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...
. In ketoacidosis, the body fails to adequately regulate ketone production causing such a severe accumulation of keto acid
Keto acid
Keto acids are organic compounds that contain a carboxylic acid group and a ketone group. The alpha-keto acids are especially important in biology as they are involved in the Krebs citric acid cycle and in glycolysis...
s that the pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
of the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
is substantially decreased. In extreme cases ketoacidosis can be fatal.
Ketoacidosis is most common in untreated type 1 diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, when the liver breaks down fat
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
and proteins in response to a perceived need for respiratory substrate. Prolonged alcoholism may lead to alcoholic ketoacidosis. Fasting leads to ketosis but not ketoacidosis.
Ketoacidosis can be smelled on a person's breath. This is due to acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
, a direct byproduct of the spontaneous decomposition of acetoacetic acid
Acetoacetic acid
Acetoacetic acid is the organic compound with the formula CH3CCH2CO2H. It is the simplest beta-keto acid group and like other members of this class is unstable.- Synthesis and properties :...
. It is often described as smelling like fruit or nail polish remover. Ketosis may also smell, but the odor is usually more subtle due to lower concentrations of acetone.
Pathophysiology
Ketoacidosis occurs when the body is producing large quantities of ketone bodiesKetone bodies
Ketone bodies are three water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver and kidney. They are used as a source of energy in the heart and brain. In the brain, they are a vital source of energy during fasting...
via the metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
of fatty acids (ketosis
Ketosis
Ketosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...
) and the body is producing insufficient insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
to slow this production. The excess ketone bodies can significantly acidify the blood. The presence of a high concentration of glucose in the blood (hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
) caused by the lack of insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
can lead to further acidity. In healthy individuals this normally does not occur because the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
produces insulin in response to rising ketone/blood glucose concentration.
Acidity results from the dissociation of the H+ ion at physiological pH of metabolic ketone bodies such as acetoacetate, and β-hydroxybutyrate
Beta-hydroxybutyrate
beta-Hydroxybutyric acid is a ketone body. It is a chiral compound having two enantiomers, D-3-hydroxybutyric acid and L-3-hydroxybutyric acid. Like the other ketone bodies , levels of beta-hydroxybutyrate are raised in ketosis...
.
Acetone has no easily liberated proton, and is thus non-acidic in human biochemical environments
Etiology
Two common types are diabeticDiabetic ketoacidosis
Diabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances...
and alcoholic ketoacidosis.
In diabetic
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
patients, ketoacidosis is usually accompanied by insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
deficiency, hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
, and dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
. Particularly in type 1 diabetics the lack of insulin in the bloodstream prevents glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
absorption and can cause unchecked ketone body production (through fatty acid metabolism) potentially leading to dangerous glucose and ketone levels in the blood. Hyperglycemia results in glucose overloading the kidneys and spilling into the urine
Glycosuria
Glycosuria or glucosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reclaim all of the filtered glucose back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to...
(transport maximum for glucose is exceeded). Dehydration results following the osmotic movement of water into urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
(Osmotic diuresis), exacerbating the acidosis
Acidosis
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
.
In alcoholic ketoacidosis, alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
causes dehydration and blocks the first step of gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
. The body is unable to synthesize enough glucose to meet its needs, thus creating an energy crisis resulting in fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
metabolism, and ketone body formation.
See also
- Diabetic ketoacidosisDiabetic ketoacidosisDiabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances...
- Keto acids
- Kussmaul breathingKussmaul breathingKussmaul breathing is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis but also renal failure. It is a form of hyperventilation, which is any breathing pattern that reduces carbon dioxide in the blood due to increased rate or...
- Low-carbohydrate dietLow-carbohydrate dietLow-carbohydrate diets or low-carb diets are dietary programs that restrict carbohydrate consumption usually for weight control or for the treatment of obesity. Foods high in digestible carbohydrates are limited or replaced with foods containing a higher percentage of proteins and fats...
External links
- The Merck Manual - Diabetic Ketoacidosis
- Alcoholic Ketoacidosis
- Lancet case study Atkins diet-induced Ketoacidosis