Diabetic Ketoacidosis: Pathophysiology
Diabetic Ketoacidosis: Pathophysiology
Diabetic Ketoacidosis: Pathophysiology
Diabetic Ketoacidosis
DKA is a life-threatening metabolic complication caused by an absence or
inadequate amount of insulin. Affecting mostly type 1 diabetics, it is
marked by three concurrent abnormalities: hyperglycemia, dehydration
and electrolyte loss, and metabolic acidosis.
Pathophysiology
DKA can be initiated by trauma or conditions such as new-onset diabetes,
heart failure, or stress. The body under stress → decrease in the amount
of insulin → reduction of glucose entering cells and increased glucose
production by the liver → hyperglycemia → liver attempting to get rid of
excess glucose by excreting glucose with water, Na+ and K+ → polyuria →
dehydration.
DKA can also be caused by a lack of insulin → increased breakdown of
fat → increased fatty acid and glycerol → fatty acids converted into
ketones → acidosis → increasing respiratory rate and abdominal pain,
and acetone breath.
Clinical Presentation
■ Hyperglycemia
■ Polyuria
■ Dehydration
■ Weakness
■ Headache
■ Polydipsia
■ Acetone or fruity breath
■ Poor appetite
■ Nausea and vomiting
■ Abdominal pain, usually generalized or epigastric
■ Rigid abdomen and irregular bowel sounds
■ Kussmaul’s respirations
■ Hypothermia
■ Tachycardia
■ Hypotension
■ Glycosuria
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■ Ketones in blood and urine
■ Metabolic acidosis: pH <7.3, bicarbonate <15 mmol/L, blood glucose
>14 mmol/L, and ketonuria
Diagnostic Tests
■ Electrocardiogram
■ Chest x-ray
■ Urinalysis (note presence of ketones)
■ CBC
■ Serum electrolytes, glucose and ketone levels, and blood urea nitrogen
■ Urine, sputum, and wound and blood cultures
■ Arterial blood gases (ABGs) and anion gap (8–16 mEq/L or 8–16 mmol/L
normal)
■ Plasma osmolarity
■ Cardiac enzymes
■ Amylase and lipase levels
Note: Serum and urine should be negative for ketones.
Management
■ Provide airway support.
■ Administer O2 (3–6 L via nasal cannula).
■ Monitor respiratory rate and rhythm and blood pH.
■ Monitor vital signs.
■ Assess for changes in mental status.
■ Assess for signs of hypokalemia.
■ Monitor serum glucose and ketone levels.
■ Provide insulin replacement (insulin drip).
■ Provide electrolyte replacement.
■ Provide fluid resuscitation and monitor intake and output.
Diabetes Insipidus
DI is a disease manifested by the excretion of a large volume of urine
caused by ineffective production of antidiuretic hormone (ADH) at the
posterior pituitary.
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Pathophysiology
The four types of DI include:
■ Central DI
■ No ADH secretion
■ Cause can be congenital or idiopathic:
• Tumors in the central nervous system
• Cerebrovascular disease or trauma
• Infection
• Granulomas
• Pregnancy
• Brain death
■ Nephrogenic DI
■ Secretion of ADH but no stimulation to the nephron’s collecting
tubules
■ Cause can be congenital or idiopathic:
• Obstruction that hinders normal urine excretion
• Chronic tubulointerstitial disease
• Medications
• Electrolyte imbalance
■ Dipsogenic DI
■ Caused by a defect or damage to the thirst mechanism in the hypo-
thalamus
■ Results in an abnormal increase in thirst with an increased fluid
intake that suppresses ADH secretion and increases urine output
■ Gestational DI
■ Occurs only during pregnancy
Clinical Presentation
■ Large volume of very diluted urine with a low specific gravity (volume
does not decrease even with restricted fluids)
■ Extreme thirst, especially for cold water and sometimes ice or ice
water
■ Craving for fluid
■ Dehydration
■ Symptoms of hypovolemic shock: Changes in level of consciousness
(LOC), tachycardia, tachypnea, and hypotension
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Diagnostic Tests
■ Fluid deprivation test
■ Desmopressin stimulation
■ ADH test
■ Plasma and urine osmolarity
■ Serum chemistries and electrolytes
■ Urinalysis
■ CT scan of head to detect cranial lesions
Management
■ Administer desmopressin; ineffective in nephrogenic DI.
■ Administer hydrochlorothiazide or indomethacin (Indocin) for nephro-
genic DI.
■ If surgery is needed, provide emotional support to patient and family.
■ Assess intake and output.
■ Monitor vital signs frequently.
■ Administer fluids as needed.
Adrenal Crisis
Acute crisis, also known as acute adrenal insufficiency, is a serious com-
plication of a dysfunctional adrenal gland causing difficulties producing
aldosterone and cortisol hormones.
Pathophysiology
Destruction of adrenal cortex → hindered secretion of aldosterone and
cortisol → Addison’s disease → hypoglycemia and hypovolemic shock.
Causes of adrenal crisis include:
■ Recently halted chronic corticosteroid therapy
■ Injury to or infection of the adrenal gland
■ Chronic adrenal insufficiency
■ Bilateral adrenalectomy
■ Medications that suppress adrenal hormones
■ Medications that enhance steroid metabolism
■ Sepsis
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Clinical Presentation
■ Serious weakness and fatigue
■ Hypoglycemia
■ Fever
■ Vomiting
■ Diarrhea
■ Altered mental status and confusion
■ Hypotension
■ Tachycardia
■ Dysrhythmias
■ Lack of response to vasopressors
Diagnostic Tests
■ Cosyntropin (ACTH) stimulation test
■ CT scan or ultrasound of the adrenal glands
Management
■ Assess vital signs.
■ Weigh daily.
■ Strictly monitor intake and output.
■ Monitor serum glucose levels frequently.
■ Administer IV fluids.
■ Administer cortisol replacement medications (hydrocortisone IV).
■ Insert nasogastric tube if vomiting.
■ Reorient and minimize stress.
■ Provide small frequent meals and nutritional supplements.
Thyroid Storm
Thyroid storm is a rare life-threatening complication of a severe form of
hyperthyroidism that is characterized by high fever, extreme tachycardia,
and altered mental status, and is precipitated by stress.
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Pathophysiology
Thyrotropin-releasing hormone (TRH) is released from the hypothalamus
after exposure to stress → the pituitary gland releasing thyroid-stimulating
hormone (TSH) → causes the release of thyroid hormone (T3 and T4) from
the thyroid gland → T3 active form of thyroid hormone → increased levels
of thyroid hormone leading to hyperthyroidism or thyrotoxicosis → if
precipitated by stress (surgery, infection, trauma, DKA, heart failure, pul-
monary embolism, toxemia of pregnancy, thyroid hormone ingestion,
radioiodine therapy, discontinuation of antithyroid), further increase in
serum TH → thyroid storm.
Clinical Presentation
■ High fever and hyperthermia
■ Severe tachycardia (>200 bpm) with heart failure and shock
■ Restlessness and agitation
■ Abdominal pain
■ Goiter
■ Nausea and vomiting
■ Nervousness
■ Tremor
■ Confusion
■ Delirium
■ Coma
Exaggerated symptoms of hyperthyroidism with disturbances of major
systems:
■ GI:
■ Weight loss
■ Diarrhea
■ Abdominal pain
■ CV:
■ Edema
■ Chest pain
■ Dyspnea
■ Palpitations
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Diagnostic Tests
■ Serum thyroid panel
■ Liver function tests
Management
“Triangle of Treatment”:
■ Decrease sympathetic outflow (beta blockers: esmolol–drug of
choice).
■ Decrease production of TH (propylthiouracil [PTU] or methimazole).
■ Decrease peripheral conversion of T4 to T3 (PTU, beta blockers, and
steroids).
■ Prevent cardiac collapse.
■ Administer humidified O2.
■ Monitor ABGs and provide continuous pulse oximetry monitoring.
■ Monitor vital signs frequently.
■ Administer IV fluids containing dextrose to replace liver glycogen.
■ Give beta blockers; if contraindicated, give calcium channel blockers
to prevent excessive hyperthermia.
■ Give acetaminophen; salicylates are contraindicated.
■ Monitor intake and output.
Pathophysiology
Malignant tumors, disorders of CNS and medications → increased secre-
tion of ADH → hyponatremia → increased water retention → stimulation
of renin-angiotensin system → increased excretion of sodium in urine.
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Clinical Presentation
■ Concentrated urine
■ Water retention
■ Lethargy
■ Dilutional hyponatremia
■ Signs and symptoms of hyponatremia:
■ Poor skin turgor and dry mucosa
■ Headache
■ Decreased saliva
■ Orthostatic hypotension
■ Anorexia, nausea, and vomiting
■ Abdominal cramps
■ Irritability, confusion, and disorientation
■ Seizures
Diagnostic Tests
■ Comprehensive metabolic panel
■ Urine Na+ and electrolytes
■ Serum and urine osmolarity
■ Ultrasound of kidneys
■ CT scan of head
Management
■ Monitor intake and output.
■ Weigh daily.
■ Monitor for CNS changes.
■ Assess for edema of extremities.
■ Institute fluid restrictions.
■ Closely monitor electrolytes.
■ Administer demeclocycline (Declomycin, Declostatin, Ledermycin) to
treat hyponatremia by inhibiting the action of ADH.
■ Administer conivaptan (Vaprisol) to treat hyponatremia.
■ Provide emotional support.
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