DIABETIC

KETOACIDOSIS
E.SHAY

OUTLINE
What is Diabetic ketoacidosis
Pathophysiology
The Anion Gap & Metabolic Acidosis
Osmotic Diuresis and Electrolytes
Potassium
Treatment
Hyperosmolar Hyperosmotic Non-Ketotic Syndrome
Research
Question Review
MCAD DEFICIENCY EXTRA SLIDE

WHAT IS DIABETIC
KETOACIDOSIS?
An acute metabolic complication of

Diabetes Mellitus characterized by:

Hyperglycemia
Hyperketonemia
Metabolic Acidosis

What type of diabetes is it usually

seen in?

Type 1 Diabetes type 1 why?

Kerl, Marie E. "Diabetic ketoacidosis: pathophysiology and clinical and laboratory presentation." Compendium 23.3 (2001): 220-8.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in diabetes." Diabetes care 27 (2004): S94.

Acute infection
(particularly
ate pneumonia and UTI)
b
r
ce
a
x
MI
e
Stroke
Pancreatitis
Trauma
Corticosteroids
Thiazide diuretics
Sympathomimetics

PATHOPHYSIOLOGY
Insulin Deficiency

Disinhibition
of lipolysis
(insulin normally
inhibits lipolysis)

FFA formation

Hyperglycemia
and Cellular
starvation
Increased
Glucagon Release

Hepatic
glycogenolysis

Ketogenesis

Acetoacetic acid

B-hydroxybutyrate

Hepatic
gluconeogenesis

Hyperglycemia

Hyperosmolarity

Oh, Man S., and Hugh J. Carroll. "The anion gap." New England Journal of Medicine 297.15 (1977): 814-817.

THE ANION GAP

Total Serum Cations = Total Serum Anions
Na + K + UC = (Cl- + HCO-3) + UA
Na + K (Cl- + HCO-3) = UA UC
Anion Gap = UA UC
What are some of the unmeasured anions
and cations?
Oh, Man S., and Hugh J. Carroll. "The anion gap." New England Journal of Medicine 297.15 (1977): 814-817.

THE ANION GAP

What do you notice?

More unmeasured anions!
- Hence the term anion gap
Oh, Man S., and Hugh J. Carroll. "The anion gap." New England Journal of Medicine 297.15 (1977): 814-817.

Metabolic Acidosis & The

Anion Gap
Na + K (Cl- + HCO-3) = UA UC
Anion Gap = UA UC
In DKA INCREASE IN KETONES (Acid)
- Increases acidity (decreases pH)
- Bicarbonate consumed - > Increased Anion gap
Metabolic acidosis
Frequently associated with anion gap
How does body compensate for metabolic acidosis?
- Rapid deep breathing (Kussmaul)

Oh, Man S., and Hugh J. Carroll. "The anion gap." New England Journal of Medicine 297.15 (1977): 814-817.

KUSSMAUL BREATHING
PATTERN

Lmellick. "Kussmaul Breathing Pattern."YouTube. YouTube, 14 May 2014. Web. 16 Dec. 2016.
<https://www.youtube.com/watch?v=TG0vpKae3Js>.

Kerl, Marie E. "Diabetic ketoacidosis: pathophysiology and clinical and laboratory presentation." Compendium 23.3 (2001): 220-8.

OSMOTIC DIURESIS AND

ELECTROLYTES
Hyperosmolarit
y

Hyperglycemia

Think of concept of osmosis!

Fluid will move across a semipermeable membrane from
an area of lesser particle concentration to an area of
greater concentration

Where does water move?

Intravascular
Cl
N
Space
N
a

a Cl
N
a

Interstitial Space
N
a

Cl

N
a
Little
glucose

Cl
Cl

N
a

Cl

Movement of
water

Loads of
glucose

Cl

N
a

N
a

N
a

N
a
Cl

Dilution can result in:

Hyponatremia
Hypochloremia

OSMOTIC DIURESIS AND

ELECTROLYTES

Kerl, Marie E. "Diabetic ketoacidosis: pathophysiology and clinical and laboratory presentation." Compendium 23.3 (2001): 220-8.

This is not the only place osmotic effect is

occurring
Remember you want to get rid of excess glucose
How?

Urine!
As glucose leaves renal tubules
it brings water along for the ride

Wasting of ions
BUT Dehydration relative increases of some of
these ions.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in diabetes." Diabetes care 27 (2004): S94.

POTASSIUM
The Body

Vast majority of
Potassium is
intracellular

K
K
K

Insul
in

The Cell
K

K
K

K K
K

Insulin

K K

What does
insulin usually
do to potassium
- Pushes it into
cell (Same as
glucose)

Kerl, Marie E. "Diabetic ketoacidosis: pathophysiology and clinical and laboratory presentation." Compendium 23.3 (2001): 220-8.

Kitabchi, Abbas E., et al. "Hyperglycemic crises in diabetes." Diabetes care 27 (2004): S94.

POTASSIUM

Without Insulin

The Body
K

K
K

K
K

Hyperkalemia

(Serum)
Intracellular

potassium depleted

K
K

Insul
in

The Cell
K
K

K
K
K

Total Body Potassium

depleted (why?)
K

K
K

Insulin

Metabolic acidosis
Osmotic diuresis (renal

wasting)
Vomiting

Keep Potassium Levels in mind for treatment!

TREATMENT
- IV fluids
IV insulin
Push Potassium

intracellularly
Can lead to rapid fall in

potassium

Supplement with

Potassium and Glucose

Umpierrez, Guillermo E., Mary Beth Murphy, and Abbas E. Kitabchi. "Diabetic ketoacidosis and hyperglycemic hyperosmolar
syndrome." Diabetes Spectrum 15.1 (2002): 28-36.

HYPEROSMOLAR
HYPERGLYCEMIC
NON-KETOTIC SYNDROME
Usually seen in older type 2 diabetes patients
Characterized by
hyperglycemia
Hyperosmolarity
Dehydration
Absence of ketoacidosis
No ketoacidosis because there is insulin present which

inhibits lipolysis
Mortality is ten times higher than DKA
Pasquel, Francisco J., and Guillermo E. Umpierrez. "Hyperosmolar hyperglycemic state: a historic
review of the clinical presentation, diagnosis, and treatment." Diabetes Care 37.11 (2014): 3124-3131.

DKA VS HHS

Kitabchi, Abbas E., et al. "Hyperglycemic crises in diabetes." Diabetes care 27 (2004): S94.

CLOSED-LOOP INSULIN DELIVERY IN

INPATIENTS WITH TYPE 2 DIABETES: A
RANDOMISED, PARALLEL-GROUP TRIAL
Background: Diabetics need better

methods of blood glucose control

Question: Can an artificial pancreas

work?

Methods: Randomized controlled trial

with 40 participants at a single center

Primary outcome: Time spent in the

target glucose concentration range of

56100 mmol/L during the 72 h study
period

Thabit, Hood, et al. "Closed-loop insulin delivery in inpatients with type 2 diabetes: a randomised, parallel-group
trial." The Lancet Diabetes & Endocrinology (2016).

Closed-loop insulin delivery in inpatients with

type 2 diabetes: a randomised, parallel-group
trial

Thabit, Hood, et al. "Closed-loop insulin delivery in inpatients with type 2 diabetes: a randomised, parallel-group trial." The Lancet Diabetes &
Endocrinology (2016).

A 13-year-old girl collapses while playing basketball. On

arrival at the emergency department, she is obtunded. On
physical examination, she is hypotensive and tachycardic
with deep, rapid, labored respirations. Laboratory studies
show serum Na+, 151 mmol/L; K+, 4.6 mmol/L; Cl, 98
mmol/L; CO2, 7 mmol/L; and glucose, 521 mg/dL. Urinalysis
shows 4+ glucosuria and 4+ ketonuria levels, but no protein,
blood, or nitrite. Which pathologic abnormality is most likely
to be present in her pancreas at the time of her
collapse?
Other
findings
ALoss of islet beta cells
BAcute inflammation of islets
CAmyloid replacement of islet beta cells
DChronic inflammation of islets
EHyperplasia of alpha cells
FPancreatic neuroendocrine tumor

you might
expect?
- Fruity breath
- Vomiting
- Abdominal
pain
- Dry skin

Klatt, Edward C., and Vinay Kumar. Robbins and Cotran review of pathology. Chapter 24, 371-391 Elsevier Health Sciences, 2015.

MCAD DEFICIENCY (EXTRA

SLIDE)
Deficiency in enzyme Medium-chain acyl-CoA

dehydrogenase (MCAD)

involved in mitochondrial fatty acid -oxidation, which fuels

hepatic ketogenesis
Seizures may occur. Hepatomegaly and liver disease are
often present during an acute episode, which can quickly
progress to coma and death.
Autosomal recessive (ACADM gene)
Therefore prevents body from converting certain fats to

energy, particularly during periods without food

Signs and symptomstypically appear during infancy or

early childhood (if not identified on newborn screen):

vomiting,
lethargy
hypoglycemia

Matern, Dietrich, and Piero Rinaldo. "Medium-chain acyl-coenzyme A dehydrogenase deficiency. Gene Reviews (2015).