DKA vignette Flashcards
Insulin is a
hormone that is central to regulating carbohydrate and fat metabolism in the body.
Insulin function
- Promotes glucose uptake in the muscle
- Promote storage of carbohydrate as glycogen
- Decrease formation of glucose in the liver (gluconeogenesis)
- Promotes storage of fatty acids as triglycerides and decreases the formation of ketone bodies
____ in the ____ release insulin in two phases.
Beta cells
slets of Langerhans
The first phase insulin release is
rapidly triggered in response to increased blood glucose levels.
The second phase is a
sustained, slow release of newly formed vesicles that are triggered independently of sugar.
description of the first phase
Glucose enters the beta cells through the glucose transporter GLUT2
• Glucose goes into glycolysis and the respiratory cycle where multiple high-energy ATP
molecules are produced by oxidation
• Dependent on the ATP:ADP ratio, and hence blood glucose levels, the ATP-dependent
potassium channels (K+) close and the cell membrane depolarizes
• On depolarization, voltage controlled calcium channels (Ca2+) open and calcium flows into the
cells
• Significantly increased amounts of calcium in the cells causes release of previously synthesized
insulin, which had been stored in secretory vesicles.
DKA results from a _____; in response the body _______
shortage of insulin
switches to burning fatty acids and producing acidic ketone bodies
the cause most of the symptoms and complications
the body switching to burning fatty acids and producing acidic ketone bodies
the body switching to producing ketone bodies causes
o This drives the reaction:
Ketones accumulate in the blood as an acid resulting in excess H+ (turn the blood acidic)
Excess CO2 is eliminated through the lungs: Kussmaul respirations (labored breathing pattern – form of hyperventilation)
Ketones also participate in
osmotic diuresis and lead to further electrolyte losses
o Accompanying this is the release of various counterregulatory hormones such as glucagon and adrenaline, as well as cytokines
o Cytokines lead to increased markers of
inflammation, even in the absence of infection
Prior to treatment, the patient’s potassium levels change:
o The majority of the K+ is intracellular
o In acidosis, H+ extracellular is exchanged for K+ intracellular
o K+ is lost in the urine
o The net result is total body K+ depletion in the face of normal or high normal K+ level in the blood
The most dangerous DKA complication is ____
cerebral edema;
_____ is the main cause of death in children with DKA.
cerebral edema
cerebral edema causes
Some maintain that it is the result from overvigorous fluid replacement, but the complication may develop before treatment has been commenced.
Risk factors for cerebral edema:
Risk factors for cerebral edema: o Severe DKA o High BUN o More severe acidosis o Lower pCO2 o Higher [K+] o Patients with their first episode of DKA o Young (less than 5 years of age) o Longer duration of symptoms o Dehydration o Increased inflammation and coagulation
Treatment complications:
that can increase cerebral edema risk
Treatment complications:
o Lesser rise in [Na+] during treatment
o Insulin within the first hour of fluid therapy
o Bicarbonate administration
o High volume of fluid administered over first 4 hrs o Early ↓ in effective plasma osmolality
What causes death in cerebral edema?
The swelling of brain tissue leads to raised intracranial
pressure, ultimately leading to death.
1. permeability of capillaries in brain is hitherto water than glucose
2. free water travels down the osmotic gradient into the brain causing swelling in the closed box of the skull
The first signs of cerebral edema are
often subtle changes in mental status. Patients may become newly combative, or complain of onset of a new headache.
Cerebral edema can be avoided with
careful and slow decrease in blood glucose levels and slow fluid replacement.
Insulin is a ______ released by the _____
51 amino acid protein released by the beta cells of the pancreas.
glucose enters the cell through the
GLUT2 transporter
undergoes glycolysis, leading to an increase in the intracellular ATP to ADP ratio.
The increase in intracellular ATP closes the ATP-sensitive potassium channel, preventing
outward leak of potassium ions.
The resultant buildup of intracellular potassium, causes
depolarizes the membrane, activating a voltage-gated calcium channel and leading to calcium influx.
The increased intracellular calcium ion concentration leads to
exocytosis of preformed insulin-containing secretory granules.
Once released from the beta cell into the bloodstream, human insulin has a half-life of about_____
5 minutes, allowing for minute-by-minute fine control of blood sugar.
Insulin actions: Liver
+ glucose uptake, glycogen synthesis
- gluconeogenesis
- ketogenesis
+ lipgenesis
insulin actions in muscles
+ glucose uptake, glyocgen sythesis
+ protein synthesis
insulin actions in adipose
+ glucose uptake
+ triglyceride uptake
+ lipid synthesis
The intravenous insulin serves two purposes:
decreasing the blood glucose concentration and halting ketoacid production.
However, it invariably takes a longer time to resolve the _____than to ____
ketoacidosis
decrease the glucose to normal levels.
Therefore, you will paradoxically need to start an intravenous infusion of dextrose hours
before stopping the intravenous insulin.
Two cardinal sins in DKA management are
prematurely stopping the insulin infusion and failing to use enough dextrose to bring the blood glucose slowly into the target range.
The acidosis seen in DKA is a result of
beta oxidation of fatty acids
Cerebral edema, occurring in about _____ of all cases of pediatric DKA, is the leading cause of morbidity and mortality, with a death rate
0.15-0.3%
~24%.
identify straightforward DKA
- Ill appearance, rapid breathing, nausea/vomiting/belly pain, dehydration
- Hyperglycemia, Ketones in blood/urine, acidosis (low pH and HCO3-)
the major metabolic disturbances in DKA
o High blood sugar (>200 mg/dL)
o Acidosis (low pH and HCO3-)
o Potassium may be high or low (typically normal to elevated blood levels
early on, but with risk of falling potassium during treatment)
o Dehydration
stimulus for insulin release:
Glucose enters the beta cells in the pancreas–>
increased ATP/ADP ratio–>
closes a channel to cause rising intracellular potassium–>
increasing intracellular potassium depolarizes the membrane–>
Calcium ions influx –>
leads to insulin exocytosis
Describe at least three target-site actions of insulin.
- Liver – store glucose (as glycogen) and lipid, stop lipid and glycogen breakdown
- Muscle – store glucose, make protein
- Adipose – store glucose and triglyceride (incorporated into chains of fats)
treatment factors
can cause/exacerbate Cerebral edema
Rapid drops in glucose and sodium from too much or too hypotonic
IV fluid
Cerebral edema Presents with
mental status changes, headache, Cushing’s triad,
fixed/dilated pupils.
Cerebral edema treatment
raise the osmolality of the blood.
