ENI - Hypoadrenocorticism Flashcards
What are the physiological effects of glucocorticoids?
- Increase gluconeogenesis and glycogenolysis
- Stimulate proteolysis and lipolysis
- Fight or flight/stress
Describe the control of aldosterone release
- RAAS
- Renin release stimulated by baroreceptors in wall of afferent arteriole, macula densa cells stimulated by reduction of Cl delivery and cardiac and arterial baroreceptors
- Drop in BP stimulates renin secretion
- Renin released, converts angiotensinogen to angiotensin I and then to angiotensin II
- Angiotensin II potent vasoconstrictor and stimualtes release of aldosterone from adrenal cortex
Where is aldosterone released from?
Zona glomerularis of adrenal cortex
Describe aldosterone function
- Central role in BP regulation
- Increases reabsorption of Na, Cl and hence water and distal tubule and collecting duct
- Stimulates secretion of K+ into tubular lumen
- Stimulates secretion of H+ in exchange for K+ in collecting tubules (acid base balance)
- Some vasoconstrictor properties
What is the name given to primary hypoadrenocorticism?
Addison’s disease
Describe primary hypoadrenocorticism
- Deficiency of glucocorticoids and mineralocorticoids
- Loss of 85-90% of adrenal cortex
- May be immune mediated destruction of adrenal gland, likely autoimmune
- Destruction of glomerulosa and fasciculata, may spare reticularis
- Aggressive management as corticosteroids are essential for life
Give causes of primary hypoadrenocorticism in dogs
- Idiopathic: probably immune mediated destruction
- Iatrogenic: drugs (drugs used to manage Cushing’s) or surgery (bilateral adrenalectomy)
Describe secondary hypoadrenocorticism
- Deficiency of ACTH
- Only cortisol deficient (electrolytes normal)
- Rare
- Pituitary (sometimes hypothalamic lesion) leading to reduced/absent ACTH
- Only affects glucocorticoid production
- mineralocorticoid function preserved
What can be an effect of aldosterone deficiency?
Electrolyte imbalances
Outline iatrogenic hypoadrenocorticism
- Exogenous steroids leading to adrenal atrophy (neg feedback, loss of stimulation, sudden removal means unable to produce enoguh quickly)
- Cortisol deficiency only
- May have signs of Cushing’s syndrome
- Can be life threatening
Describe the signalment of canine hypoadrenocorticism
- Younger females (4-6 years, 70% females)
- Some breed predispositions: standard poodles, bearded collies, Portugese water dog, Leonberge, great Dane, Rottweiler, WHWT, soft coated wheaten terrier
- Extremely rare in cats
Describe the signs of aldosterone deficiency
- Loss of Na, Cl, H2O
- Retention of K+, H+
- Pre-renal renal failure
- Failure to retain water
- Electrolyte imbalances, dehydration, hypovolaemia
Describe the signs of glucocorticoid deficiency
- Decreased stress tolerance (no stress response of immune cells)
- Gastrointestinal signs
- Weakness
- Appetite loss
- Anaemia
- Impaired gluconeogenesis
Describe the clincal signs of chronic hypoadrenocorticism
- Waxing waning with non-specific signs
- Worsened by stress
- Anorexia, vomiting, diarrhoea, PUPD, weakness, lethargy, depression
- Often appear normal between bouts, esp after fluid therapy or steroids
- GI signs common
- Cannot cope with additional stress e.g. long walk,concurren disease, increased acitivty that day
- Chronically losing sodium so unable to concentrate tubular fluid
Describe the clinical signs of acute hypoadrenocorticism
- Crisis, marked hypovolaemia and azotaemia
- Collapsed, close to death, extremely weak
- Recent history of vomiting/diarrhoea, may be fresh or digested bloof present
- Hypovolaemic shock
- Paradox bradycardia
- Abdominal pain
Why does paradox bradycardia occur in acute hypoadrenocorticism?
- Hyperkalaemia
- Has effect on action potential in heart
What would be seen on a complete blood count in cases of hypoadrenocorticism?
- Lack of stress leucogram (no neutrophilia or lymphopaenia)
- Anaemia (decreased erythrocytosis due to lack of cortisol and GI loss of blood)
What would be seen on blood biochemistry in cases of hypoadrenocorticism?
- Hyperkalaemia, hyponatraemia, hypochloridaemia
- Hypercalcaemia
- Hypoglycaemia (cortisol deficiency)
- Azotaemia
What would be seen on biochemistry and urinalysis in cases of hypoadrenocorticism?
- Azotaemia
- Decreased USG
- BUN and creatinine increased
What would be seen on ECG in cases of hypoadrenocorticism?
- Bradycardia
- Peaked T waves
- Widened QRS complexes
- Descreased P wave amplitude
- Disappearance of P waves
- Ventricular asystole (failure to contract)
What is the specific diagnostic test used for the definitive diagnosis of hypoadrenocorticism?
ACTH stimulation test
Describe the results of ACTH stimulation test in the diagnosis of hypoadrenocorticism
- Measure cortisol
- Flat line stimulation
- No response to ACTH injection i.e. cortisol stays at same level
Outline the management of hypoadrenocorticism
- Fluids
- Glucocorticoid hormone
- Mineralocorticoid
- May address high blood potassium
Explain how steroid withdrawal crises occur
- Exogenous steroids have a negative feedback effect on hypothalamus and pituitary
- Reduced stimulation of adrenal glands
- Atrophy over time
- When steroid removed, adrenals unable to produce own corticosteroids
- Crisis occurs
What is a phaechromocytoma?
Rare, catecholamine secreting tumour of the adrenal medulla
What is meant by a functional tumour?
Is able to produce hormones (and thus may have large effect even if small)
What type of receptor are adrenoceptors?
G-protein coupled
What is the action of alpha-2 receptors?
- Inhibit catecholamine release
- Situated on pre-synaptic emmrbane
- Catecholamines released into synapse, bind to alpha-1 receptors on post-synaptic membrane and pre-synaptic alpha-2 receptos
- Binding to the alpha-2 acts as negative feedback to stop secretion
What intracellular signalling pathway do alpha1 adrenoreceptors activate?
- Phospholipase C (via Gg)
- Increase activity of protein kinase C (PKC)
What intracellular signalling pathway do alpha2 adrenoreceptors activate?
- Adenylate cyclase via Gi
- Descrease activity of protein kinase A (PKA)
What intracellular signalling pathway do beta adrenoreceptors inhibit?
- Adneylate cyclase via Gs
- increase activity of protein kinase A (PKA)
