Week 4 Flashcards
What do adrenal glands consist of and where are they located
The adrenal glands, located on the cephalad portion of
each kidney and consist of a
Cortex
Medulla
The adrenal cortex and adrenal medulla each have
separate endocrine functions.
Structure of Adrenal Gland
Cortex
>Zona glomerulosa
>Zona fasciculata
>Zona reticularis
Medulla
>Modified post-ganglionic neurons intimately connected to sympathetic neurons.
Adrenal Regulation
Adrenal glands interact with the hypothalamus and pituitary
gland in the brain.
The hypothalamus makes corticotropin-releasing hormone (CRH).
This stimulates the pituitary gland to make adrenocorticotropic hormone (ACTH).
The ACTH stimulates the adrenal glands to make and release hormones into the blood.
Both the hypothalamus and the pituitary gland can sense
whether the blood has the right amount of a hormone in it.
If there is too much or too little cortisol, these glands change the amount of CRH and ACTH they release.
Hormones of Adrenal Cortex
The adrenal cortex produces
• Glucocorticoids (primarily cortisol)
• Mineralocorticoids (primarily aldosterone)
• Androgens
Glucocorticoids
• Promote and inhibit gene transcription in many cells and
organ systems.
• Prominent effects include anti-inflammatory actions and
increased hepatic gluconeogenesis.
Mineralocorticoids
• Regulate electrolyte transport across epithelial surfaces,
particularly renal conservation of sodium in exchange
for potassium.
Adrenal androgens’
• Chief physiologic activity occurs after conversion
to testosterone and dihydrotestosterone.
Glucocorticoid-Cortisol
Affects glucose, protein, fat metabolism. Inhibits synthesis of protein in tissues. Promotes the use of fatty acids as energy source and decreases the use of glucose. Stimulates liver cells to synthesize glucose from non-carbohydrates (gluconeogenesis) and increases blood glucose concentrations
Effects of Glucocorticoid-Cortisol on Inflammation and Immune Function
Regulate adaptive immunity by inhibiting
lymphocyte activation and promoting lymphocyte
apoptosis.
At high concentrations, glucocorticoids also inhibit
the production of B cells and T cells.
Glucocorticoids have potent anti-inflammatory and
immunosuppressive properties.
Mineralocorticoid-Aldosterone
Affects the body's ability to regulate blood pressure. It sends the signal to organs, like the kidney and colon, that can increase the amount of sodium the body sends into the bloodstream or the amount of potassium released in the urine. The hormone also causes the bloodstream to re-absorb water with the sodium to increase blood volume
Androgen
The major sex hormone in men is
testosterone, which is produced
mainly in the testes
Hormones of Adrenal Medulla
Composed of chromaffin cells, which synthesize and secrete catecholamines (mainly epinephrine and lesser amounts of norepinephrine). Chromaffin cells also produce bioactive amines and peptides (eg, histamine, serotonin, chromogranins, neuropeptide hormones). Epinephrine and norepinephrine, the major effector amines of the sympathetic nervous system, are responsible for the “flight or fight” response
Adrenal Insufficiency
Most adrenal deficiency syndromes affect
output of all adrenocortical hormones
ADDISON’S DISEASE (Primary Adrenal Insufficiency)
In Addison’s disease,
There is increased excretion of Na and decreased excretion of K, chiefly in the urine
Low blood concentrations of Na and Cl and a high concentration of serum K result.
Inability to concentrate the urine, combined with
changes in electrolyte balance,
produces severe dehydration,
plasma hypertonicity, acidosis, decreased circulatory volume, hypotension, and circulatory collapse.
Pathophysiology Addison’s disease
Mineralocorticoid deficiency
Mineralocorticoids stimulate sodium reabsorption and
potassium excretion:
Deficiency results in increased excretion of sodium and
decreased excretion of potassium, chiefly in urine but also in sweat, saliva, and the gastrointestinal tract.
A low serum concentration of sodium (hyponatremia) and a high concentration of potassium (hyperkalemia) result.
Glucocorticoid deficiency
Contributes to hypotension and causes severe insulin sensitivity
and disturbances in carbohydrate, fat, and protein metabolism.
In the absence of cortisol, insufficient carbohydrate is formed from
protein; hypoglycaemia and decreased liver glycogen result.
Weakness follows, due in part to deficient neuromuscular function.
Glucocorticoid deficiency
Decreased cortisol blood levels result in increased pituitary
ACTH production and
increased blood levels of lipotropin, which has
melanocyte-stimulating activity and produces the
hyperpigmentation of skin and mucous membranes
characteristic of Addison’s disease.
Laboratory Findings for Addison’s disease
Abnormal serum electrolyte levels including low Na (< 130 mmol/L), high K (> 5 mmol/L), low HCO3 (15 to 20 mmol/L) and high BUN Diagnosed by demonstrating failure to increase plasma cortisol levels, or urinary free-cortisol excretion, upon administration of ACTH
SECONDARY ADRENAL INSUFFICIENCY
Patients with secondary adrenal insufficiency are not hyperpigmented, as are those with Addison's disease. They have relatively normal electrolyte levels. Hyperkalaemia and elevated BUN generally are not present because of the near-normal secretion of aldosterone in these patients.
SECONDARY ADRENAL INSUFFICIENCY Diagnosis
ACTH Stimulation Test
CRH Stimulation Test
Adrenal Hyperfunction
Distinct clinical syndromes depending on the hormone
involved:
Hypersecretion of aldosterone results
in hyperaldosteronism.
Hypersecretion of glucocorticoids results in Cushing
syndrome.
Hypersecretion of androgens results in adrenal virilism.
Hypersecretion
of epinephrine and norepinephrine results in symptoms
of pheochromocytoma.
Primary Aldosteronism
is a disease in which the adrenal gland(s)
make too much aldosterone which leads to
hypertension (high blood pressure) and low
blood potassium levels.
Increases the renal distal tubular exchange of
sodium for potassium and hydrogen
Progressive depletion of potassium and
hydrogen leads to hypokalemia and acidosis
Excess sodium reabsorption leads to
hypertension
Classification Primary – excess secretion by the adrenal glands Secondary – renin-mediated secretion Seen in congestive heart failure, nephritic syndrome, cirrhosis, renal artery hypertension, severe arteriolar nephrosclerosis, rare renin-secreting tumors
Pathophysiology of Primary Aldosteronism
Mechanisms by which this can occur are many: 1) an adrenal tumour that autonomously secretes aldosterone; 2) unilateral or bilateral hyperplasia of the zona glomerulosa that oversecretes aldosterone; 3) or germline or somatic mutations that induce aldosterone hypersecretion
Primary Aldosteronism Diagnosis
Patients with primary aldosteronism typically hav:
High plasma aldosterone > 15 ng/dL (> 0.42 nmol/L)
Low levels of PRA, with a ratio of plasma aldosterone (in
ng/dL) to plasma renin activity (in ng/mL/h) > 20.
Electrolytes
Low K+ and high Na+
Secondary Aldosteronism
Caused by something outside the adrenal glands. Occurs in states of low effective arterial blood volume, which activates the renin-angiostensin concentration and stimulates the distal reabsorption of sodium by the kidney to restore blood volume.
Adrenal Virilism
Is a syndrome in which excessive
adrenal androgens cause virilisation
Causes:
Androgen-secreting adrenal tumours
• secrete excess androgens, cortisol, or
mineralocorticoids (or all three).
Adrenal hyperplasia
• usually congenital; delayed virilising adrenal
hyperplasia is a variant of congenital adrenal
hyperplasia.
• Both are caused by a defect in production of
androgens.
• The defect is only partial in delayed virilising
adrenal hyperplasia, so clinical disease may not
develop until adulthood.
