All about Diabetic ketoacidosisBy: Haya M. Al-Malaq

Definition

•Diabetic ketoacidosis (DKA) is one consequence of untreated DM & is linked to an impaired glucose cycle.

•In a diabetic patient, DKA begins with deficiency in insulin.

•DKA has a 100% mortality rate if left untreated.

Causes • Infection (40%), missed insulin Tx (25%), and

newly diagnosed diabetes (15%). • UTIs• MI• CVA • Complicated pregnancy• Trauma• Stress• Surgery• Heavy use of conc. CHD beverages such as sodas. • Idiopathic (20-30%)

Mechanism

•A key component that there is no or very little circulating insulin so it occurs mainly in type 1 diabetes.

•Some type 2 diabetics have lost their own insulin production and must take external insulin; they have some susceptibility to DKA.

•Most cells in the body are sensitive to one or more of insulin's effects (except hepato, erythro, neurons some intestinal cells).

Mechanism

•The difference is due to different glu transporter (GLUT) prot.

•Most cells contain only GLUT-4 prot. which move to the cell surface memb. when stimulated by a 2nd messenger cascade initiated by insulin, thus enabling uptake of glu.

•Conversely, when insulin conc. are low, these transporters dissociate from cell memb. & so prevent uptake of glu.

Mechanism

Other effects of insulin include: • formation of glycogen from gluc & of

glycogenolysis; • fatty acid (FA) production from stored

lipids & , FA release into the blood • FA uptake and storage; protein

catabolism.•gluconeogenesis (from some aa, released

by prot catabolism).

So………..

•A lack of insulin has significant effects, which contribute to increasing blood glu levels, to increased fat metabolism and prot degradation.

Fat metabolism is one of the underlying causes of DKA.

Muscle Wasting • Insulin the breakdown of prot & since muscle

tissue is prot, a lack of insulin encourages muscle wasting.

• Releasing aa both to produce gluc (by gluconeogenesis) & for the synthesis of ATP via partial respiration of the remaining aa.

• In those with starvation, bl gluc conc are low due to both low consumption of CHD & b/c most of the gluc available is being used as a source of energy, such as neurons in the brain.

So…………

•Since insulin lowers bl glu levels, the normal bodily mechanism here is to prevent insulin secretion, thus leading to similar fat & prot catabolic effects as in type 1 diabetes.

Thus the muscle wastage visible in those suffering from starvation also occurs in type 1 diabetics, normally resulting in

weight loss.

Keton body production • Despite possibly high circulating levels of plasma

glu, the liver will act as though the body is starving if insulin levels are low.

• In starvation situations, the liver produces another form of fuel: ketone bodies.

• Ketogenesis, that is fat metabolic processing (beginning with lipolysis), makes ketone bodies as intermediate products in the metabolic sequence as FA (formerly attached to a glycerol backbone in TG) are processed.

Keton body production •The ketone bodies beta-hydroxybutyrate &

acetoacetate enter the bloodstream & are usable as fuel for some organs as brain.

• If large quantities of ketone bodies are produced, the metabolic imbalance known as ketosis may develop, though this condition is not necessarily harmful.

• -ve charge of ketone bodies causes <blood pH

Keton body production

•An extreme excess of ketones can cause ketoacidosis.

•In starvation conditions, the liver also uses the glycerol produced from TG metabolism to make glucose for the brain, but there is not nearly enough glycerol to meet the body's glucose needs.

Brain

•Normally, ketone bodies are produced in minuscule quantities, feeding only part of the energy needs of the heart and brain.

•In DKA, the body enters a starving state.

•Eventually, neurons (and so the brain) switches from using glu as a primary fuel source to using ketone bodies.

So………….• As a result, the bloodstream is filled with an

increasing amount of glucose that it cannot use (as the liver continues gluconeogenesis & exporting the glucose so made).

• This significantly increases its osmolality.

• At the same time, massive amounts of ketone bodies are produced, which, in addition to increasing the osmolar load of the blood, are acidic.

So…………• As a result, pH of the blood begins to move

downward towards an acidotic state.

• The normal pH is 7.35-7.45, in acidosis the pH dips below 7.35 (Very severe acidosis 6.9-7.1).

• The acidic shift in the blood is significant because the proteins (i.e.tissues, enzymes, etc.) in the body will be permanently denatured by a ph that is either too hi or too lo, leading to tissue damage, organ failure, & death.

So…………..•Glucose begins to spill into the urine as the

proteins responsible for reclaiming it from urine reach max capacity.

•As glu is excreted in the urine, it takes a great deal of body water with it, resulting in dehydration.

•Dehydration further concentrates blood &

worsens the increased osmolality of the blood.

So…………..

•Severe dehydration forces water out of cells and into the bloodstream to keep vital organs perfused.

•This shift of intracellular water into the bloodstream occurs at a cost as the cells themselves need the water to complete chemical reactions that allow the cells to function.

On presentation to hospital•Patients are typically dehydrated &

breathing fast & deeply. •Abdominal pain is common & may be severe. •Consciousness level is typically normal until

late in the process, when obtundation (dulled or reduced level of alertness or consciousness) may progress to coma.

•Dehydration can become severe enough to cause shock.

Signs • Sluggish, extreme tiredness. • Fruity smell to breath/compare to nail polish

remover. • Extreme thirst, despite large fluid intake. • Constant urniation/bedwetting. • Extreme weight-loss. • Vomiting • Confusion • Abdominal pain • Loss of appietite. • Flu-like syptoms.

Signs

•Unconsciousness

(AT THIS POINT THE PERSON IS IN DIABETIC COMA, GET TO AN

EMERGENCY ROOM IMMEDIATELY! )

Labs

•Hyperglycemia. •metabolic acidosis.•Normal or elevated K. •Severe ketosis.

Goal of therapy

•The goal of treatment is to correct the elevated blood glucose level by giving additional insulin.

•Replace fluids lost through excessive

urination and vomiting.

Treatment

•Admit to ICU & monitor VS.•Hydration to lower the osmolality of the

blood. •Replacement of lost electrolytes. • insulin to force glucose and K into the

cells, & eventually glucose simultaneously with insulin in order to correct other metabolic abnormalities, as elevated hyperkalemia & elevated ketone levels.

So……Principles of Treatment

•Rapid restoration of adequate circulation & perfusion with isotonic IV fluids.

•Gradual rehydration and restoration of depleted electrolytes (especially Na & K), even if serum levels appear adequate

•Insulin to reverse ketosis and lower glucose levels

•Careful monitoring to detect and treat complications

Prevention •Diabetics should learn to recognize the early

warning signs and symptoms of ketoacidosis. •Measurement of urine ketones in people

with infections or people on insulin pump therapy can give more information than glucose measurements alone.

• Insulin pump users need to frequently check to see that insulin is still flowing through the tubing, and that no blockages have occurred.

Management

•Case