DM TYPE 1: Autoimmune destruction of beta cells the Islets of Langerhans within

the pancreas

Precipitating factors for DKA: Infection such as UTI, gastroenteritis, pneumonia, alcohol
or drug abuse, pancreatitis, stroke, trauma, Acute Myocardial Infarction

Decreased normal insulin secretion in the presence of glucose in the blood =

“FASTING STATE”

Decrease glucose transport from blood into Cortisol, growth hormone and Insulin normally regulates
muscles and other tissues catecholamine glucagon secretion

Glucagon secretion is uncontrolled in

the absence of insulin
Decreased glucose utilization as Lethargy
Brain does not require energy (glycolysis)
insulin for glucose transport
Increased Glycogenolysis

Switch to ketogenesis for ketone Polyphagia in response to increase Hyperglycemia

energy use in absence of glucose energy requirements

Weight loss Increase serum osmolarity

Lipolysis initiated in response
of fasting state

Free Fatty Acids (FFA) released from Polydipsia

adipocytes stored as triglycerides Osmotic diuresis secondary to
Osmotic fluid shift out of cells glucosuria
into intravenous space

Polyuria
FFA enters liver Dilutional
mitochondria hyponatremia
Dehydration
Increased glucagon promotes FFA
entry into liver mitochondria Beta oxidation of FFA
Decreased Renal Function
Acetyl-CoA produced in large numbers build
up in mitochondria

The Citric Acid Cycle is

normally used to produce Oxaloacetate is diverted away from the Citric Acetyl-CoA production exceeds
energy Acid Cycle in the fasting state in an attempt to oxidative capacity of the Citric
increase glucose production via glucogenesis Acid Cycle

Hyperglycemia

Citric Acid Cycle concurrently

slows down during fasting state

Acetyl-CoA diverted away from

the Citric Acid Cycle and
promotes ketogenesis

2x Acetyl-CoA bodies join to form

Acetoacetyl-CoA
Fasting state increases HMG-
CoA synthase production
HMG-CoA synthase helps form HMG-CoA from 1x
Acetoacetyl-CoA molecule

HMG-CoA lyase then forms

Acetoacetate (ketone body) which
breaks down

Acetone (ketone D-beta-hydroxybutyrate (ketone CO2

body) body released

Water soluble can cross Blood Brain

The only ketone body that
cannot be used as energy
Characterized as a Barrier (BBB) in the CNS
FRUITY ODOR in
DKA
Increased plasma ketone levels
of acetoacetate and D-beta-
hydroxybutyrate

Ketone bodies are Acetoacetate and D-beta- Circulating ketone bodies

acidic hydroxybutyrate are used as energy initiate systemic response
for organs, muscles and other tissues

Decreased serum pH
Nausea and vomiting
Confusion /decreased sensorium Abdominal pain and cramping

Metabolic Diabetic
Ketoacidosis

Extracellular H+ ions moves DKA estimated to occur at

Confusion and altered level of Compensatory release of CO2 into cells and exchange for K+ Blood Sugar Level (BSL) >15
consciousness to buffer acidosis ions mmol/L

Increased respiratory rate Hypokalemia may be in the

Diabetic Coma setting of normal serum K+
(tachypnea) = “Kussmaul
Respirations” levels (3.5-5.5)