DKA Vignette

Question 1

1. Identify straightforward diabetic ketoacidosis (DKA)

Answer 1

Generally presents with:

• polyuria (urinating a lot),
• polydipsia (drinking a lot)
• and weight loss.

Suspicious for diabetes, must check blood glucose.

• rapid, deep breathing
• nausea and vomiting (suspicious for ketoacidosis –>check blood pH).

Metabolic disturbances in DKA include:

• hyperglycemia
• acidosis,
• K+ derangements,
• dehydration.

Question 2

2. Describe the major metabolic disturbances in DKA: GENERAL (DAPE)

Answer 2

• Dehydration
• Acidosis
• Potassium derangements
• Elevated blood sugar (hyperglycemia)

Question 3

2. Describe the major metabolic disturbances in DKA:

- Elevated blood sugar (hyperglycemia)

Answer 3

Elevated blood sugar:

(hyperglycemia) –> Insulin comes from the endocrine pancreas from the beta cells (which are from the islets of Langerhans).
- In hyperglycemia, generally have some sort of insulin deficiency –> glucose can’t be taken into the cell despite having an adequate supply of it = hyperglycemia (increased blood glucose levels).
- Body turns to other sources of energy, like lipids: lipolysis –>fatty acid oxidation in liver –>ketoacids (acetoacetate and betahydroxybutyrate).

o High blood sugar (>200 mg/dL)

Question 4

2. Describe the major metabolic disturbances in DKA:

- Acidosis

Answer 4

The acidosis seen in DKA is a result of beta oxidation of fatty acids. This process
generates hydrogen ions and ketone bodies (acetoacetate and betahydroxybutyrate)
which we can measure. To compensate for the excess acid, the body increases
respiratory volume and rate to hasten the elimination of carbon dioxide, taking
advantage of the equation fi the bicarbonate buffer system.
(H+) + (HCO3-) H2CO3 H2O +CO2
Recall that CO2 is very membrane permeable and readily removed from the body at a rate dependent on the volume of air ventilated per unit of time (usually discussed as
“minute ventilation,” and dependent on respiratory rate and the volume of air exhaled with each breath). The deep and rapid respirations seen in DKA are “Kussmaul
respirations.” Easy to remember: K for Kussmaul, K for ketoacidosis.

Question 5

2. Describe the major metabolic disturbances in DKA:

- Potassium derangements

Answer 5

Potassium derangements are also common and dangerous for patients with DKA.
As the patient fights dehydration, the body compensates by holding onto sodium more
avidly.
Increased sodium conservation in the distal convoluted tubule and cortical collecting duct of the nephron is mediated by aldosterone, which stimulates an antiport
mechanism whereby sodium is retained at the expense of potassium loss in the urine.
Therefore, patients in DKA are depleted in their total body potassium.
Recall, however, that most of the body’s potassium is intracellular.
Acidosis leads to influx of hydrogen ions into the cells, leading to a charge neutral efflux of potassium.
Therefore, the acidosis can cause an excess of extracellular potassium (hyperkalemia) despite the overalldepletion.
As you begin treating this patient, the large doses of
intravenous insulin which you will be providing lead to potassium shift intracellularly, lowering the blood potassium levels. Putting these processes together, you can see
that a patient in DKA may present with hyperkalemia but will manifest greater
potassium needs than most other patients you encounter.
Therefore, as you treat
this patient, you must continue to watch serum potassium levels and be prepared to make adjustments to the potassium content of IV fluids in order to prevent severe hyperkalemia and severe hypokalemia, both of which can lead to death. If this hasn’t sufficiently frightened you in to paying attention, note that potassium chloride is the
“lethal” part of the three drug lethal injection cocktail used by the majority of the 32 states with the death penalty.

DKA dont fuck around.Be a good doctor. dont fuck up treatment.

Question 6

2. Describe the major metabolic disturbances in DKA:

- Dehydration

Answer 6

The dehydration seen in DKA is largely the result of the osmotic diuresis secondary to hyperglycemia.
In the normal state, blood is filtered at the glomerulus, and as the filtrate
courses through the nephron, the parsimonious kidney reabsorbs all the glucose filtered.
After all, it is an energy source.
However, in diabetes the blood glucose (and therefore filtrate glucose) concentration rises above levels which can be reabsorbed
through facilitated diffusion because all the transporter proteins are working at capacity,band glucose is lost in the urine.
With an excess of glucose (osmols) in the filtrate, the
body is unable to reabsorb as much water as it would under normal conditions.
Therefore, large volumes of water are lost in the urine, even in the setting of
dehydration. Meanwhile, as the blood ketoacid concentration rises, the patient experiences nausea and vomiting, making it even more difficult for oral intake to keep up with urine volume loss, resulting in dehydration. Furthermore, dehydration leads to
an even further concentration of blood glucose, worsening the pace of the osmotic
diuresis, a spiral that can often only be reversed with IV hydration.

Question 7

3. Describe the stimulus for insulin release.

Answer 7

Insulin release isregulated by a glucose sensing system within the beta cells: glucose enters the cell
through the GLUT2 trans porter, undergoes glycolysis, leading to an increase in the intracellular ATP to ADP ratio. This change closes the ATP-sensitive potassium
channel, preventing outward leak of potassium ions. The resultant buildup of intracellular potassium (because there are other sodium/potassium channels actively antiporting against the gradient) 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. Membrane proteins in this system, including some I did not discuss here, are potential drug target sites and can be deranged in some forms of monogenic diabetes and hyperinsulinism.

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.

Question 8

4. Describe at least three target-site actions of insulin.

Answer 8

Insulin action can be summed up (and more easily remembered) by thinking of it as a signal to “lock up” energy. It stimulates uptake of glucose and triglycerides while promoting synthesis of fats, proteins, and glycogen. If you prefer bullet points:
Insulin actions:
Liver
 + glucose uptake, glycogen synthesis
 - gluconeogenesis
 - ketogenesis
 + lipogenesis

Muscle
 + glucose uptake, glycogen synthesis
 + protein synthesis

Adipose
 + glucose uptake
 + triglyceride uptake
 + lipid synthesis

Question 9

5. Describe the risk for cerebral edema in DKA.

Answer 9

-Cerebral edema, occurring in about 0.15-0.3% of all cases of pediatric DKA, is theleading cause of morbidity and mortality, with a death rate ~24%. A further 20% of patients with cerebral edema suffer long term neurologic outcomes.

-The pathophysiology of cerebral edema is multifold and incompletely understood.
-Acidosis leads to dysregulated cerebral blood flow and perhaps even disruptions at the level of
the blood brain barrier.
-Part of the process can be iatrogenic as we rehydrate the patient with relatively hypotonic fluids.
-Therefore, we aim to replace fluid losses more slowly than you would in cases of non-diabetic dehydration, preventing decreases in blood
sodium concentration and slowing the rate of decrease of blood glucose.
-Overly rapid rehydration and hypotonic IV fluids can precipitate cerebral edema.
-Cerebral edema presents
with:
mental status changes; headache; seizures; Cushing’s triad (hypertension,
bradycardia, irregular respirations); or fixed, dilated pupils.

Treatment for cerebral edema includes elevating the head of the bed, hyperventilating
the patient (if intubated) [N.B. Rapid decrease in serum CO2 constricts cerebral arteries
and therefore decreases cerebral blood flow], and giving IV mannitol or hypertonic saline. Mannitol is a sugar alcohol which is only slightly metabolized (if at all). Given via IV, it serves to raise the effective osmolality of the blood and pull water back from the brain in order to decrease swelling.

Two cardinal sins in DKA management are:
1) prematurely stopping the insulin infusion and
2) failing to use enough dextrose to
slowly bring the blood glucose into the target range.