DKA & HHS

PATHOGENESIS

DR MOHAMMAD DAOUD

CONSULTANT ENDOCRINOLOGIST

KAMC -JEDDAH

OBJECTIVES

Introduction

Definitions

Pathogenesis

S & S

Management

ACUTE DIABETIC COMPLICATIONS

1-Hyperglycemia : High

-Diabetic Ketoacidosis (DKA)..Type 1 DM

-Hyperosmolar Hyperglycemia Syndrome

(HHS) ..Old Type 2 DM

2-Hypoglycemia : Low

WHAT CONTROLS YOUR BLOOD SUGAR?

When we eat …blood sugar (Glucose)

increases

This stimulates insulin secretion

Insulin moves the glucose out of the

Blood Cells

GLUCOSE :FACTS

Carbohydrates (Glucose) are the main

calorie source for our body

Extra CHO are stored as:

Glycogen (liver and muscles)

OR

Fat (Adipose tissue)

GLUCOSE :FACTS

The brain relies almost exclusively on

glucose as a fuel, but cannot synthesize or

store it

Adequate uptake of glucose from the

plasma is essential for normal brain function

and survival

GLUCOSE PHYSIOLOGY

Glycogen Breakdown -Liver

Increased Glucagon

Energy

Fat Synthesis

Glycogen

Synthesis

Glucose release to blood

(+) Pancreas secretion

of Glucagon

Blood

Glucose

Pool(+) Pancreas secretion of

Insulin

(+) Circulating Insulin

Uptake of glucose by cells

Decrease blood glucose

GLUCOSE :FACTS

In case of CHO shortage ( ex: Starvation)

OR

Unable to use CHO ( ex: No insulin as in

DKA)

Body shifts gear to other sources of energy

GLUCOSE :FACTS

Other sources of energy …

Protein breakdown to amino acids

and glucose synthesis

Fat breakdown into FFA and

ketones formation (with acidosis)..

Minimal amount of Insulin can prevent Ketogenesis

WHAT CONTROLS YOUR BLOOD SUGAR?

-Insulin …Lowers

-Glucagon…Increases

-Other hormones

Amount of CHO load

Physical activity

Stress factors Counter Regulatory Hormones

HYPERGLYCEMIA

Hyperglycemia basic processes are :

1-Impaired/decreased glucose use

2-Increased gluconeogenesis(Make up of glucose from other sources)

3-Increased glycogenolysis (breakdown of Glycogen to Glucose )

HYPERGLYCEMIA

Due to variable reasons…

Insulin deficiency (Absolute / Relative)

Insulin Resistance

Excess counter regulatory hormones (Glucagon, Cortisol…)

Defected secretion of GLP-1…

Electrolyte LossesRenal Failure

Shock CV Collapse

INSULIN DEFICIENCY

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Hyperglycemia

Hyper-osmolality

Δ MS

Lipolysis

FFAs

Acidosis

Ketones

CV Collapse

Glycosuria

Dehydration

VS

Type 1DM

Immune system stops

insulin from being made

All ages :

More in younger

age groups

Type 2 DM

-Not enough insulin

-Insulin resistance)

Combination of the two

Alpha cell defect

Others: GLP-1 , SGLT2

Affects older age group

Can affect children

VS

Treatment ?

Type 1 DM

The insulin must be replaced

By injection or continuous infusion

Type 2 DM

Lifestyle changes (TLC)

Medications : tablets and/or Insulin

DIABETIC HYPERGLYCEMIC CRISES

Diabetic Ketoacidosis

(DKA)

Hyperglycemic

Hyperosmolar State (HHS)

Younger, type 1 diabetes Older, type 2 diabetes

No hyperosmolality Hyperosmolality

Volume depletion Volume depletion

Electrolyte disturbances Electrolyte disturbances

Acidosis No acidosis

DIABETIC KETOACIDOSIS (DKA)

PATHOPHYSIOLOGY

Unchecked gluconeogenesis Hyperglycemia

Osmotic diuresis Dehydration

Unchecked ketogenesis Ketosis

Dissociation of ketone bodies

into hydrogen ion and anions

Acidosis

Anion-gap metabolic

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Often a precipitating event is identified

(infection, lack of insulin administration)

HYPEROSMOLAR HYPERGLYCEMIC STATE

(HHS) PATHOPHYSIOLOGY

Unchecked gluconeogenesis Hyperglycemia

Osmotic diuresis Dehydration

• Presents commonly with renal failure

• Insufficient insulin for prevention of hyperglycemia but

sufficient insulin for suppression of lipolysis and ketogenesis

• Absence of significant acidosis

• Often identifiable precipitating event (infection, MI)

Major body water loss

DKA 5-7 L

HHS 8- 10 L

HYPERGLYCEMIA

PRECIPITATING FACTORS

Stress: through excess counter regulatory hormones:

-Glucagon

-Catecholamines (Adrenaline and Nor-Adrenaline)

-Cortisol

Medications: Steroids, Thiazides ,Beta blockers,…

Stopping DM medications

Acute illness: Infections (ex;UTI, Pneumonia) ,MI (ACS),

Stroke , Acute Pancreatitis, Burn

Others: Trauma ,Alcohol, Drug abuse (cocaine )

Feeding (NGT/ PEG/ TPN)

DKA -PRECIPITATING FACTORS

Inadequate insulin treatment

Noncompliance

Insulin error or insulin pump malfunction

Poor “sick-day” management

New onset diabetes (20 -25%)

Acute illness

Infection ,CVA, MI ,Acute pancreatitis

Drugs:

Steroids ,Clozapine or olanzapine

Cocaine Lithium ,Terbutaline

HHS -PRECIPITATING FACTORS

Acute illness :

Infection : Pneumonia UTI, Sepsis

CVA, MI, Pancreatitis , PE, Severe burns…

Endocrine

Acromegaly ,Thyrotoxicosis,

Cushing's syndrome

Drugs

Ex ;Steroids Thiazides,TPN

Previously undiagnosed DM

HYPERGLYCEMIA

WHAT IS DKA?

Severe hyperglycemia ; 250-300 mg/dl

Ketonemia : ketone bodies in the blood

(β-OH-butyric acid, Acetoacetic acid and Acetone)

Acidosis: PH <7.3

= Lack of insulin

Hyperglycemia

Ketosis

Acidosis

Adapted from Kitabchi AE, Fisher JN. Diabetes Mellitus. In: Glew RA, Peters SP, ed. Clinical

Studies in Medical Biochemistry. New York, NY: Oxford University Press; 1987:105.

DKA : DEFINITION

HYPERGLYCEMIA

DKA

Inadequate insulin &

excess glucagon,catecholamines…

Body cannot burn glucose properly

Glucose builds up in the bloodstream

HYPERGLYCEMIADKA

Symptoms of DKA include:

Nausea, vomiting Abdomen/Stomach pain

Frequent urination Excessive thirst

Weakness, fatigue Speech problems

Confusion /Unconsciousness

HYPERGLYCEMIADKA

Signs of DKA include:

Kussmaul respirations : Heavy, deep breathing

Fruity breath – the smell of ketoacid

Tachycardia

Supine hypotension,

Orthostatic drop of BP (feel dizzy when standing)

Dry mucous membranes Poor skin turgor

Confusion /Unconsciousness

HYPERGLYCEMIA

DKA

Inadequate insulin …

Fat comes out of fat cells (Free Fatty Acids)….

Free Fatty Acids >> Liver (Mitochondria/ Glucagon)

Used as an alternative energy source

Makes ketoacids ( ketones) out of the fat

HYPERGLYCEMIA

HHS

1- Severe hyperglycemia

2- S. Osmolality > 320 msom/kg

3- Severe dehydration

4- No ketonemia

5- No acidosis

HHS

There is just enough insulin

to keep fat in fat cells and

prevent ketone /acids formation

ketone levels are usually normal in HHS.

Hyperglycemi

a

Hyperosmolarit

y

Ketoacidosis

HHS

DKA

Take Home

Messages

HYPERGLYCEMIC CRISIS

DKA & HHS

• LIFE THREATENING EMERGENCIES

• DKA …MOSTLY TYPE 1 –YOUNG

INSULIN DEFICIENCY -ACIDOSIS

• HHS….TYPE 2 DM –OLDER

WORSE DEGREE OF DEHYDRATION

• BOTH: SIMILAR PRECIPITATING FACTORS

ELECTROLYTES DISTURBANCES

DKA VS HHS

Diabetic Ketoacidosis

(DKA)

Hyperglycemic

Hyperosmolar State (HHS)

Absolute (or near-absolute)

insulin deficiency, resulting in

• Severe hyperglycemia

• Ketone body production• Systemic acidosis

Severe relative insulin deficiency,

resulting in

• Profound hyperglycemia and

hyperosmolality (from urinary free water losses)

• No significant ketone

production or acidosis

Develops over hours to 1-2 days Develops over days to weeks

Most common in type 1 diabetes,

but increasingly seen in type 2

diabetes

Typically presents in type 2 or

previously unrecognized

diabetes

Higher mortality rate

DKA & HHS

• EARLY AGGRESSIVE MANAGEMENT

• HYDRATION

• INSULIN

• ELECTROLYTES DISTURBANCES RX

• LOOK FOR PRECIPITATING FACTORS : TREAT AND TEACH TO AVOID ..IF POSSIBLE

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PREDISCHARGE CHECKLIST

• EDUCATION

• DIET INFORMATION

• TREATMENT GOALS

• “SURVIVAL SKILLS” TRAINING

• “MEDIC-ALERT” BRACELET

• PROVIDE :

GLUCOSE MONITOR AND STRIPS

MEDICATIONS, INSULIN, NEEDLES

• CONTACT PHONE NUMBERS

Thank You

Any Questions ?