What’s up fellow AMBOSSians! I’m Dr. Zeb, back with another question walkthrough
involving complications of diabetes mellitus and hyperglycemia.
You’re going to get several questions on your exam related to these topics,
so I’ll do my best to cover the most high-yield info as briefly as I can.
If you find this video helpful, let me know with a thumbs up or comment and subscribe for more.
And without further ado, let’s get started by reading the lead-in:
“Further evaluation of this patient is most likely to show which of the following findings?”
Alright, we need to figure out what this patient has. Let’s see if we get
lucky and have any confirmatory findings in the last sentence.
“Urine dipstick is positive for ketones and glucose.”
Ok, this is already a significant finding for building up our differentials. So let’s
put on our thinking caps and briefly consider how ketones are formed, in other words, ketogenesis.
Ketones include acetoacetate, beta-hydroxybutyrate, and acetone.
Acetoacetate is a product of fatty acid metabolism - so beta-oxidation - in the liver,
and can transform into beta-hydroxybutyrate that is excreted in urine or acetone that is exhaled.
Acetoacetate and beta-hydroxybutyrate can be converted into acetyl-CoA in
extrahepatic tissue, which enters the TCA cycle to be oxidized for energy.
When glucose metabolism meets the body’s energy demands, fatty acid metabolism
and ketone body formation are inhibited. But when ATP formation from metabolism of glucose
is insufficient, fatty acid metabolism is activated to make up for the deficit,
leading to an excess of ketones that can appear in the blood, urine, and breath.
So for differentials of ketonuria, we need to consider:
when does glucose metabolism decrease? It could be dietary-related, like
fasting or starvation, low-carb diets - so “keto diets” - or prolonged vomiting.
It can occur with states of higher demands, like pregnancy and prolonged illness or stress,
or endocrine conditions involving an excess hormone, such as hyperthyroidism,
hypercortisolism (so Cushing syndrome), catecholamines (like pheochromocytoma)
or growth hormone (so gigantism or acromegaly). It can also be other metabolic conditions like
diabetes mellitus, glycogen storage diseases, or renal glycosuria.
Now which of these matches also glucosuria? Obviously not dietary related or states of
higher demand, as we’d expect rather a deficit of glucose in general, including in urine.
So we’re left basically with the hormone and metabolic conditions at this point.
Now that we have some differentials, let’s read from
the top and start to narrow down our diagnosis. “A previously healthy 10-year-old boy is brought
to the emergency department by his mother 5 hours after the onset of abdominal pain and nausea.
Over the past 2 weeks, he has also had a 4-kg (8.8-lb) weight loss. The mother reports that
her son has been drinking more water than usual during this period.” - so polydipsia
Last week he wet his bed three times despite being completely toilet-trained since 3 years
of age.” - secondary nocturnal enuresis - likely due to polyuria
Alright, time to break out our illness scripts: What condition classically presents with weight
loss, polydipsia, and polyuria in a 10-year-old child? Exactly - diabetes mellitus type 1.
So what about the presenting symptoms of abdominal pain and nausea - what should
we be thinking of at this point? That’s right! Diabetic ketoacidosis, or DKA.
If you’re pressed on time, you could try to answer the question already here.
But since we’re here to learn and youtube has a 12-hour limit - don’t worry,
I'm not going to go 12 hours - let’s see if the rest of the vignette supports this hypothesis.
“He appears lethargic. His temperature is 37.8°C (100.0°F), pulse is 128/min,
respirations are 30/min, and blood pressure is 95/55 mm Hg. Physical examination shows
deep and labored breathing and dry mucous membranes.”
Alright, what type of breathing is classically described as deep and labored?
Yep, Kussmaul breathing, which is also a sign of DKA and other
metabolic acidoses. Remember mnemonic KUSSMAUL, as we’ve shown here in AMBOSS.
Dry mucous membranes indicate dehydration.
“The abdomen is soft, and there is diffuse tenderness to palpation
with no guarding or rebound.
Serum studies show sodium of 133,” so hyponatremia “potassium of 5.9,” so hyperkalemia
“chloride of 95, bicarbonate of 13,” so low, likely due to metabolic acidosis,
as bicarbonate binds excess protons to turn into carbonic acid, then CO2, that is exhaled to
compensate. Ultimately, this forms an anion gap. “urea nitrogen of 25, and creatinine of 1.1.” So
a BUN to creatinine ratio greater than 20 to 1, indicating prerenal azotemia,
which is consistent with decreased renal blood flow due to dehydration.
All of these signs are consistent with DKA. So to answer the question,
which of these findings would we expect? Decreased total body potassium is correct,
despite the hyperkalemia in the labs. How do we explain this paradox?
There are 3 main mechanisms involved. First, the insulin deficiency that constitutes
diabetes type 1 causes hyperglycemia and resulting hyperosmolality. This triggers potassium to shift
with water from cells into the extracellular space, leading to hyperkalemia and loss in urine.
Next, the insulin-driven cellular uptake of potassium via the sodium-potassium pump is absent.
Lastly, elevated protons in acidosis inhibit the sodium-hydrogen antiporter.
This decreases the intracellular sodium gradient, which also decreases activity
of the sodium-potassium pump, further increasing extracellular potassium.
So even though serum potassium can be normal or even elevated, total body potassium is reduced.
This is why it’s especially important when treating DKA with insulin replacement - which
reverses these mechanisms - to monitor potassium and be ready to supplement it
if below 5.3 mEq/L and maintain between 4 and 5. This will help
prevent hypokalemia and fatal arrhythmias from intracellular shifting of potassium.
If serum potassium is under 3.3, insulin shouldn’t even be given before potassium repletion.
Now, most importantly, what do you say to your attending who asks you to administer potassium?
… K+ Even though
we got the question correct, let’s see what we can learn or reinforce from the distractors.
Increased arterial blood pH would be consistent with alkalosis,
but DKA is a form of anion gap metabolic acidosis,
which also explains the decreased bicarbonate as we covered in the vignette.
As for increased total body sodium, DKA causes dilutional hyponatremia due to hyperglycemic
hyperosmolarity. Osmotic diuresis leads to a loss of water. While most sodium is preserved,
there is still a net loss of sodium in urine. So we’d expect rather normal or even reduced total
body sodium. Now
I was going to also tell another lame joke about sodium, but Na…
Regarding arterial pCO2: In response to DKA, a metabolic acidosis, the body compensates by
exhaling CO2, which comes from carbonic acid. As discussed with the lab values, this is formed from
bicarbonate that binds protons. So altogether, we would expect a decrease in arterial pCO2.
Now for hypervolemia, we already know we’d expect rather the opposite: hypovolemia and
dehydration because of osmotic diuresis. This is also consistent with the patient’s polydipsia,
nocturnal enuresis, dry mucous membranes, prerenal azotemia, hypotension, and tachycardia.
And finally, probably the trickiest distractor: A serum glucose concentration > 650 mg/dL. In DKA,
ketogenesis and symptoms deriving from absolute insulin deficiency already start at lower glucose
levels, so concentrations rarely exceed 600 mg/dL. However, another hyperglycemic crisis,
hyperosmolar hyperglycemic state (HHS) usually presents with serum glucose greater than 600.
When first learning DKA and HHS, it can be easy to get them mixed up,
so it’s important to remember key differences.
For example, HHS usually occurs in patients with type 2 diabetes as a result of
relative insulin deficiency - enough to keep ketone production in check - rather
than absolute deficiency. So these patients have normal to low ketone levels,
a normal anion gap, and higher pH and bicarbonate values - often even normal.
So why is HHS such a bad singer?
Because it can’t sing key tones…
Pff...
You can read more about DKA, HHS, and their differences in the “Hyperglycemic
crises” AMBOSS article. We also have a nice flowchart on management there.
As you know from my other videos, I like to briefly consider what other questions could
appear on the exam for a stem like this. Other correct options could have been:
Fruity breath, from exhaled acetone A decreased pH or anion gap metabolic acidosis
The question writers could have asked for the diagnosis - either type 1 diabetes or DKA itself.
Sometimes they’ll ask for a matching set of expected lab values.
Of course, they could have asked about the next best step of management, especially
for Step 2 or 3, which would be? Yeah, IV fluids and then insulin,
possibly also with dextrose if serum glucose is under 300 mg/dL.
Note that these would also be the next steps for HHS.
Making these extra associations will prepare you for any questions the NBME
will throw at you for this topic. So to recap, the key takeaways
of this question are: Formulate differentials for
ketonuria and know their pathophysiology. Suspect type 1 diabetes with a classic
presentation of polydipsia, polyuria, lethargy, and weight loss in a child.
Identify DKA based on common findings like acute abdominal pain, nausea,
and Kussmaul breathing or hyperventilation.
Know pathophysiological changes and expected lab findings of DKA, including:
elevated ketones leading to anion gap metabolic acidosis
total body potassium depletion due to osmotic diuresis,
despite normal or paradoxically elevated serum potassium.
And as a bonus takeaway: Know the key differences between the two hyperglycemic crises DKA and HHS,
which are summarized in this table in the AMBOSS article.
Alright, that’s it for this question walkthrough. You’re going to get
several diabetes questions and at least one hyperglycemic crisis question on every Step exam.
You can review these topics in more depth at AMBOSS for free for 5 days. There’s a link below.
If you found this helpful, please give the video a thumbs up and subscribe to our channel
and any of the AMBOSS or my social media links below. I’m collecting topics I can work on next,
so please leave a comment if you have any questions or requests for your next exams.
And as always: Remember that hard work pays off, so keep it up and stay positive. You’ve got this!