Diabetic ketoacidosis
From Wikipedia, the free encyclopedia
Diabetic ketoacidosis (DKA) is a life-threatening complication in patients with
diabetes mellitus. Near complete deficiency of insulin and elevated levels of
certain stress hormones increase the chance of a DKA episode. DKA is more common
among Type I diabetics, but may also occur in Type II diabetics, particularly
during periods of increased physiologic stress, such as during an infection.
Patients with new, undiagnosed Type I diabetes frequently present to hospitals
with DKA. DKA can also occur in a known diabetic who fails to take prescribed
insulin, or in diabetics who fall sick due to illnesses such as pneumonia or a
kidney infection. DKA was a major cause of death in Type I diabetics before
insulin injections were available; untreated DKA has a high mortality rate.
Diabetes mellitus
Types of Diabetes
Diabetes mellitus type 1
Diabetes mellitus type 2
Gestational diabetes
Pre-diabetes:
Impaired fasting glycaemia
Impaired glucose tolerance
Disease Management
Diabetes management:
•Diabetic diet
•Anti-diabetic drugs
•Conventional insulinotherapy
•Intensive insulinotherapy
Other Concerns
Cardiovascular disease
Diabetic comas:
•Diabetic hypoglycemia
•Diabetic ketoacidosis
•Nonketotic hyperosmolar
Diabetic myonecrosis
Diabetic nephropathy
Diabetic neuropathy
Diabetic retinopathy
Diabetes and pregnancy
Blood tests
Blood sugar
Fructosamine
Glucose tolerance test
Glycosylated hemoglobin
Contents
[hide]
* 1 Biochemical Mechanism and Etiology
o 1.1 Ketone body production
o 1.2 Muscle wasting
o 1.3 Brain
o 1.4 Osmolality Changes and Dehydration
* 2 Symptoms and Signs
o 2.1 Laboratory results
* 3 Late signs
* 4 Complications
* 5 Treatment
* 6 References
[edit] Biochemical Mechanism and Etiology
DKA is characterized by high blood sugar, acidosis, and high levels of ketone
bodies. The pathogenesis of DKA is mainly due to acidosis. Excessive amounts of
ketone bodies lower the blood pH; a blood pH below 6.7 is incompatible with
life. Onset of DKA is often within 24 hours.
A key component of DKA is that there is little to no circulating insulin. DKA
occurs mainly, but not exclusively, in Type 1 diabetes because Type 1 diabetes
is characterized by a lack of insulin production in the pancreas. It is much
less common in Type 2 diabetes because the latter is closely related to cell
insensitivity to insulin, not -- at least initially -- to a shortage or absence
of insulin. Some Type 2 diabetics have lost their own insulin production and
must take external insulin; they have some susceptibility to DKA.
Although glucagon plays a role as an antagonistic hormone to insulin when there
are low blood glucose levels, mainly by stimulating the process of
glycogenolysis in hepatocytes (liver cells), insulin has a more critical role,
with more widespread effects throughout the body. The presence or absence of
insulin can by itself regulate most of the pathological effects of DKA; notably,
it has a short half-life in the blood of minutes (at least one suggestion is
about six), so blood insulin levels decrease rapidly following cessation of
insulin release by the pancreas, or by outside sources (eg, injection, though
some insulins do not quickly reach the blood, extending their duration of
activity).
Most cells in the body are sensitive to one or more of the effects of insulin;
the main exceptions are erythrocytes, neurons, some intestinal tissue, and
pancreatic beta-cells, none of which require insulin to absorb glucose from the
blood. Variation in cell-type sensitivity to insulin is due to the presence of
different glucose transporter (GLUT) proteins. Adipocytes and skeletal muscle
cells express GLUT-4 proteins, which move to the cell surface membrane when
stimulated by a secondary messenger cascade initiated by insulin docking at
membrane sensor proteins, thus enabling uptake of glucose. Conversely, when
insulin concentrations are low, these transporters dissociate from the cell
membrane and so prevent uptake of glucose.
Other effects of insulin include the following: stimulation of the formation of
glycogen from glucose and inhibition of glycogenolysis, stimulation of fatty
acid (FA) production from stored lipids and inhibition of FA release into the
blood, stimulation of FA uptake and storage, inhibition of protein catabolism
and of gluconeogenesis, in which glucose is synthesized from non-carbohydrate
substrates (such as laktate, alanine and Creb's cycle intermediates). A lack of
insulin therefore has many significant effects, several of which contribute to
increasing blood glucose levels, to increased fat metabolism and protein
degradation. Increased fat metabolism is one of the underlying mechanisms of DKA
(ketone bodies are produced during lipid metabolic processing).
Ketone body production
Under low-insulin conditions, regardless of circulating plasma glucose
concentration, the liver acts as though the body is starving and produces
another form of fuel, known as ketone bodies. This is an aspect of fat
metabolism (beginning with lipolysis) that makes ketone bodies as intermediate
products in the fatty acid-processing metabolic sequence. Two of the ketone
bodies beta-hydroxybutyrate and acetoacetate enter the blood and can be used as
fuel by some organs such as the brain, though the brain still requires a large
amount of glucose to function. If large amounts of ketone bodies are produced,
the metabolism is in the state termed ketosis; this condition is itself not
necessarily harmful, and is normal during times of relatively low carbohydrate
availablility (as, for instance, between meals). However, if produced in very
large quantities, unprocessed ketone bodies will cause the blood pH to drop,
leading to ketoacidosis.
Muscle wasting
Muscle wasting occurs primarily due to the lack of inhibition of protein
catabolism; insulin inhibits the breakdown of proteins and, since muscle tissue
is made of proteins, a lack of insulin encourages muscle wasting, releasing
amino acids both to produce glucose (by gluconeogenesis) and to provide
materials for the synthesis of ATP via partial respiration of the remaining
amino acids.
In individuals suffering from starvation, blood glucose concentrations are low
due to both low carbohydrate consumption and because most of the glucose
available is being used as a source of energy by tissues unable to use most
other sources of energy, such as neurons in the brain. Since insulin lowers
blood sugar levels by enabling many cells' glucose uptake, the normal bodily
mechanism here is to prevent insulin secretion, thus leading to similar fat and
protein catabolic effects as in type 1 diabetes. Thus, the muscle wastage
visible in those suffering from starvation also occurs in type 1 diabetics,
normally resulting in weight loss.
Brain
Normally, ketone bodies are produced in minute quantities, and are used by the
heart and brain as a supplementary energy source. In starvation conditions and
DKA, neurons (and therefore the brain) adapt to use ketone bodies as a major
energy source since glucose is in short supply.
Osmolality Changes and Dehydration
In non-starvation DKA, a lack of insulin leads to high blood glucose levels
(from both diet and unregulated gluconeogenesis in the liver). This often
significantly increases blood osmolality. At the same time, and also due to low
insulin permitted ketosis, large quantities of ketone bodies are produced, two
of which -- in addition to increasing the osmolar load of the blood -- are
acidic. As a result, the pH of the blood begins to move toward increasing
acidity. The normal pH of human blood is 7.35-7.45; in acidosis, the pH dips
below 7.35. Very severe acidosis may be as low as 6.9-7.1. (A pH of 6.8 or lower
is generally considered to be incompatible with life; i.e., fatal). The acidic
shift in the blood is significant because proteins (eg, body tissues, enzymes,
etc.) can be significantly (even permanently) denatured (ie, distorted and so
non-functional) by a pH that is either too high or too low, leading to
widespread tissue damage, functional deficits, organ failure, and ultimately
death.
Glucose begins to spill into the urine as the proteins responsible for
reclaiming it from urine (the SGLT family) reach maximum capacity (the renal
threshold for glucose). As glucose is excreted in the urine, it takes a great
deal of body water with it, resulting in dehydration. Dehydration further
concentrates the blood and worsens the increased serum osmolality. Severe
dehydration forces water out of cells and into the bloodstream, with further
functional derangement. This shift of intracellular water into the bloodstream
occurs at a cost as the cells themselves need the water to complete chemical
reactions that allow the cells to function as required.
Symptoms and Signs
It is important to note that to an untrained person the symptoms of acute DKA,
such as breath odor, are very similar to alcohol intoxication, and it is easy to
assume that the person is drunk instead of suffering from a diabetic emergency.
* Sluggishness, extreme tiredness.
* Extreme thirst, despite large fluid intake.
* Constant urination
* Fruity smell to breath, similar to nail polish remover.
* Hyperventilation, at first rapid and shallow, then progressively deeper and
less rapid.
* Extreme weight loss.
* Oral Thrush and/or persistent vaginal yeast infections may be present; this is
because the normal fungal flora present in the oral cavity and cervix is
disrupted
* Muscle wasting.
* Agitation / Irritation / Aggression / Confusion
* Vomiting, nausea
* Extreme pain in shoulders, neck and chest
Laboratory results
A high anion gap indicates that there is loss of bicarbonate (HCO3-) without
increase in Chloride (Cl-).
When acetoacetic acid and beta-hydroxybutyric acid dissociate, they produce an
H+ anion that will be immediately neutralized by bicarbonate if available. This
causes loss of bicarbonate which increases the anion gap
During treatment, a drop in HCO3- (bicarbonate) is compensated for by an
increase in Cl- from IV fluids. This is also known as hyperchloremic acidosis.
The effect causes the anion gap to move toward a normal value despite
persistence of metabolic acidosis. At patient presentation for treatment, both
types of acidosis may be present, and the elevation in the anion gap may be less
than expected for the degree of bicarbonate level reduction.
Serum potassium concentration is often elevated at presentation as insulin
deficiency results in potassium movement out of the cells into the extracellular
fluid. Insulin therapy lowers the potassium concentration by forcing it into the
cells and may cause severe hypokalemia, particularly in patients with a normal
or low serum potassium concentration at presentation.
Late signs
At this point, DKA is life-threatening and medical attention should be sought
immediately.
* Emesis (vomiting), although this is not always a sign of late-stage
ketoacidosis, and can occur both in early-stage ketoacidosis and in non-ketoacidic
hyperglycaemia.
* Confusion.
* Abdominal pain.
* Loss of appetite.
* Flu-like symptoms.
* Lethargy and apathy.
* Extreme weakness.
* Kussmaul breathing ("air hunger"). A type of hyperventilation where patients
breathe very deeply at a normal or increased rate. This is a sign of severe
acidosis.
* Unconsciousness (a variety of diabetic coma) after prolonged DKA. At this
stage, speedy medical attention is imperative.
Complications
People with diabetic ketoacidosis need close and frequent monitoring for
complications. Surprisingly, some of the most common complications of DKA are
related to the treatment:
* Hypokalemia and often, potassium depletion
* Cerebral edema [1]
* Hyperglycemia
* Ketoacidemia[citation needed]
* Fluid and electrolyte depletion [2]
* Aspiration
* Unrecognized renal tubular necrosis[citation needed]
* Pulmonary edema [3]
* Myocardial Infarction
Treatment
Treatment consists of hydration to lower the osmolarity of the blood,
replacement of lost electrolytes, insulin to force glucose and potassium into
cells, and eventually glucose simultaneously with insulin in order to correct
other metabolic abnormalities, such as elevated ketone levels. Many patients
require admission to a step-down unit or an intensive care unit (ICU) due to IV
administration of fluids, glucose, and insulin and so that vital signs, urine
output, and blood tests can be monitored frequently. Brain edema is not rare
during the treatment phase, is quite dangerous, and so this may suggest
intensive monitoring as well. In patients with severe alteration of mental
status, intubation and mechanical ventilation may be required. Survival is
largely dependent on how badly deranged the metabolism is at presentation to a
hospital, but today properly treated DKA is only occasionally fatal.
DKA occurs more commonly in type 1 diabetes because insulin deficiency is most
severe, though it can occur in type 2 diabetes. In about a quarter of young
people who develop type 1 diabetes, insulin deficiency and hyperglycemia lead to
ketoacidosis before the disease is recognized and treated. This can occur at the
onset of type 2 diabetes as well, especially in young people. In a person known
to have diabetes and being adequately treated, DKA usually results from omission
of insulin, mismanagement of acute gastroenteritis, the flu, or the development
of a serious new health problem (e.g., bacterial infection, myocardial
infarction).
Insulin deficiency switches many aspects of metabolic balance in a catabolic
direction. The liver becomes a net producer of glucose by way of gluconeogenesis
(from a few of the amino acids in protein) and glycogenolysis (from glycogen,
though this source is usually exhausted within hours). Fat in adipose tissue is
reduced to triglycerides and fatty acids by lipolysis. Muscle is degraded to
release protein for gluconeogenesis. The rise of fatty acid levels is
accompanied by increasing levels of ketone bodies (acetone, acetoacetate and
beta-hydroxybutyrate; only one, acetone, is chemically a ketone -- the name is
an historical accident). As ketosis worsens, it produces a metabolic acidosis,
with anorexia, abdominal distress, and often eventual vomiting. The rising level
of blood glucose increases the volume of urine produced by the kidneys as it
passes the renal threshold (an osmolar diuresis). The high volume of urination (polyuria)
also produces increased losses of electrolytes, especially sodium, potassium,
chloride, phosphate, and magnesium. Reduced fluid intake from vomiting combined
with amplified urination produce dehydration. As the metabolic acidosis worsens,
it induces obvious hyperventilation (termed Kussmaul respiration). Kussmaul's
respirations are essentially an involuntary attempt to remove carbon dioxide
from the blood that would otherwise form carbonic acid and further worsen the
ketoacidosis. See also arterial blood gas.
On presentation to hospital, patients in DKA are typically suffering dehydration
and breathing both fast and deeply. Abdominal pain and vomiting is also common
and may be severe. Consciousness level is typically normal until late in the
process, when obtundation (dulled or reduced level of alertness or
consciousness) may progress to coma. Dehydration can become severe enough to
cause shock. Laboratory tests typically show hyperglycemia, metabolic acidosis,
normal or elevated potassium, and severe ketosis. Many other tests can be
affected.
At this point the patient is urgently in need of intravenous fluids. The basic
principles of DKA treatment are:
* Rapid restoration of adequate circulation and perfusion with isotonic
intravenous fluids
* Gradual rehydration and restoration of depleted electrolytes (especially
sodium and potassium), even if serum levels appear adequate
* Insulin to reverse ketosis and lower glucose levels
* Careful monitoring to detect and treat complications
Treatment usually results in full recovery, though death can result from
inadequate treatment or a variety of complications, such as cerebral edema
(occurs mainly in children).
Management: refer to DKA flowchart in [1]. Also refer to full discussion in
chapter in endotext.com [4]().
References
1. ^ "Diabetic ketoacidosis". Diabetic ketoacidosis. Mayo Foundation for Medical
Education and Research (2006). Retrieved on 2007-06-15.
2. ^ "Diabetic Coma > Diabetic ketoacidosis". Diabetic ketoacidosis. Armenian
Medical Network (2006). Retrieved on 2007-06-15.
3. ^ "Diabetic ketoacidosis complications". Diabetic ketoacidosis. The Diabetes
Monitor (2007). Retrieved on 2007-06-15.
4. ^ http://diabetesmanager.pbwiki.com/Hyperglycemic-Crises%253A-Diabetic-Ketoacidosis-%2528DKA%2529%252C-And-Hyperglycemic-Hyperosmolar-State-%2528HHS%2529-
[show]
v • d • e
Endocrine pathology: endocrine diseases (E00-35, 240-259)
Pancreas/
glucose
metabolism
Diabetes mellitus types: (type 1, type 2, MODY), complications: (coma,
angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy)
Hypoglycemia · Hyperinsulinism · Zollinger-Ellison syndrome · insulin receptor (Rabson-Mendenhall
syndrome) · Insulin resistance
Hypothalamic/
pituitary axes
Pituitary
Hyperpituitarism (Acromegaly, Hyperprolactinaemia, SIADH)
Hypopituitarism (Sheehan's syndrome, Kallmann syndrome, Growth hormone
deficiency, Diabetes insipidus)
Adiposogenital dystrophy · Empty sella syndrome · Pituitary apoplexy · ACTH
deficiency
Thyroid
Hypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre,
Myxedema)
Hyperthyroidism (Graves disease, Toxic multinodular goitre, Teratoma with
thyroid tissue or Struma ovarii)
Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's
thyroiditis)
Euthyroid sick syndrome · Thyroid hormone resistance · Thyroid nodule
Parathyroid
Hypoparathyroidism (Pseudohypoparathyroidism) · Hyperparathyroidism (Primary,
Secondary, Tertiary)
Adrenal
Adrenocortical hyperfunction: Cushing's syndrome (Nelson's syndrome,
Pseudo-Cushing's syndrome) · Hyperaldosteronism (Conn syndrome, Bartter
syndrome) · Glucocorticoid remediable aldosteronism
CAH (Lipoid, 3β, 11β, 17α, 21α)
Adrenal insufficiency (Addison's disease, Waterhouse-Friderichsen syndrome) ·
Hypoaldosteronism
Gonads
ovarian (Polycystic ovary syndrome, Premature ovarian failure)
testicular (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase
deficiency) · Androgen receptor (Androgen insensitivity syndrome)
general (Hypogonadism, Delayed puberty, Precocious puberty)
Height
Gigantism · Dwarfism/Short stature (Laron syndrome, Psychogenic dwarfism)
Thymus
Abscess of thymus · Thymus hyperplasia
Multiple
Autoimmune polyendocrine syndrome · Carcinoid syndrome · Multiple endocrine
neoplasia (1, 2) · Progeria · Woodhouse-Sakati syndrome
see also congenital, neoplasia
[show]
v • d • e
Water-electrolyte imbalance and acid-base imbalance (E86-E87, 276)
Volume status
Dehydration/Hypovolemia · Hypervolemia
Electrolyte
Na+ Hypernatremia/Hyponatremia
K+ Hyperkalemia/Hypokalemia
Cl− Hyperchloremia/Hypochloremia
Acid-base
Acidosis
Metabolic: High anion gap (Ketoacidosis/Diabetic ketoacidosis, Lactic) · Normal
anion gap (Hyperchloremic, Renal tubular)
Respiratory
Alkalosis
Metabolic: Contraction alkalosis
Respiratory
Both
* This page was last modified on 7 January 2009, at 18:31.
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(See Copyrights for details.)