Calcium Metabolism and Adrenal Pathology Flashcards
Consequences of hypercalcaemia and hypocalcaemia?
Hypercalcaemia:
- Urolithiasis
- Renal impairment
- Muscle weakness
- Arrhythmias
Hypocalcemia
- Tetany, hyperreflexia
- Paresthesia (pins and needles)
What are the two types of indices for serum calcium?
What is the difference between them?
Total calcium (unadjusted, albumin adjusted)
Ionised calcium (uncorrected, pH corrected)
Ionised calcium is the form that is metabolically active. Protein bound calcium is not.
What is the relationship between albumin and total calcium?
IF albumin is low, correct the calcium upwards.
If albumin is high, correct the calcium downwards.
What is the purpose of pH adjustment of ionised calcium?
AFter the sample is taken:
- RBC metabolism produces acid, lowering pH
- Uncapped sample or ‘headspace’ may cause CO2 to evaporate, increasing pH
IF there is a chance of a pH change, use the adjusted value. If not, the unadjusted value is the correct value.
What is the relationship between pH and calcium-albumin binding?
Hydrogen ions also binds to albumin
Low pH = more H+ ions bound to albumin, less calcium can bind and ionised calcium increases.
Vice versa for high pH
What is the relationship between parathyroid hormone levels and hypercalcaemia?
High PTH indicates primary hyperparathyroidism (e.g. parathyroid adenoma) causing high calcium
Low PTH indicates hypercalcaemia (e.g. from malignancy) driving PTH levels down.
Hypophosphataemia is the hallmark sign of which syndrome?
What is the mechanism of action behind the hypophosphataemia?
Refeeding syndrome
Follows carbohydrate intake (refeeding) to treat nutrient deficiency.
The sudden spike in insulin causes an intracellular shift of phosphate, magnesium and potassium.
What are the consequences of refeeding syndrome
Hypophosphataemia driven
- Muscle weakness
- Rhabdomyolysis via ATP depletion and the consequent inability of muscle cells to maintain membrane integrity.
Causes and consequences of hyperphosphataemia?
Causes:
- Kidney disease
- Rhabdomyolysis
- Hypoparathyroidism
Consequences:
- Secondary hyperparathyroidism with chronic kidney disease
- Renal stones
Describe the normal function of the adrenal gland and what type of control they are undre
Paired glands, one on each pole of kidney
Cortex (90%) - produce corticoid hormones under endocrine control
Medulla - produce catecholamines under autonomic nervous system control
What are the three groups of steroid hormones produced by adrenal cortex and where are they produced?
Mineralocorticoids - Zona glomerulosa
Glucocorticoids - Zona fasciculata
Sex steroids - Zona reticularis
What is the main function of mineralocorticoids and the most important example?
Aldosterone
Maintain normal intravascular volume and pH through sodium retention and elimination of K+ and H+ ions.
What are the main actions of glucocorticoids?
What control are they under?
Under pituitary control - ACTH
Functions: Metabolic regulation (protein/carb/fat)
- Inhibit protein synthesis and increase protein breakdown
- Inhibit glucose uptake by cells and increase gluconeogenesis
- Redistribute fat
Describe the three important groups of sex steroids
Oestrogens - development and regulation of female repro system, feminising secondary sex characteristcs
Progestogens - menstrual cycle, pregnancy, lactation
Androgens - Spermatogenesis, masculinising secondary sex characteristics
What are the three major syndromes of hyperfunction of the adrenal cortex?
- Cushing syndrome (hypercortisolism)
- Conn syndrome (hyperaldosteronism)
- Adrenogenital or virilsing syndrome (hyperandrogenism)
What are the 3 important types of adrenal cortex hypofunction?
- Primary acute adrenal insufficiency
- Primary chronic adrenal insufficiency (Addison disease)
- Secondary adrenal insufficiency (ACTH deficiency)
Cause and 4 mechanisms to Cushing syndrome?
Are they ACTH dependent or independent?
Caused by excess glucocorticoid levels
- Exogenous - e.g. corticosteroids. ACTH independent
- Endogenous - ACTH from hypothalamus/pituitary = Too much cortisol production. Known as cushing disease - ACTH depedent
- Endogenous - Ectopic ACTH (e.g. small cell carcinoma of lung) = ACTH dependent
- Endogenous - adrenal cortical adenoma or primary cortical hyperplasia, ACTH is normal. ACTH independent
Symptoms of Cushing syndrome?
- Cataracts
- Ulcers
- Stria, skin thinning
- Hypertension
- Immunosuppression
- N
- Gain weight
- Osteoporosis
- Impaired wound healing
- Depression
Symptoms of Cushing syndrome?
- Cataracts
- Ulcers
- Stria, skin thinning
- Hypertension
- Immunosuppression
- N
- Gain weight
- Osteoporosis
- Impaired wound healing
- Depression
Two primary and two secondary causes of hyperaldosteronism.
What is the conseuqnece of this disease?
Primary
- Bilateral adrenal hyperplasia
- Adenoma - Conn syndrome
Secondary: Renin-angiotensin activation
- Decreased renal perfusion
- Arterial hypovolaemia
What is Conn syndrome?
Adenoma of the adrenal cortex (zona glomerulosa), resulting in overproduction of mineralocorticoids (aldosterone)
What are two causes of adrenogenital syndrome?
Excess androgens caused by:
- ADrenocortical neoplasms
- Congenital adrenal hyperplasia
Two mechanisms of adrenocortical sufficiency and the three patterns of disease?
- Primary hypoadrenalism
- Secondary hypoadrenalism - deficiency in ACTH
Three patterns
- Primary acute adrenocortical insufficiency
- Primary chronic adrenocortical insufficiency
- Secondary adrenocortical insufficiency
How does adrenocortical insufficiency present?
Hypoglycaemia, dehydration, weight loss
Weakness, tiredness, hypotension.
What is Addison’s disease?
What is a hallmark presentation?
Primary chronic adrenocortical insufficiency.
Presents with patchy, hard tanning of the skin
When might primary acute adrenocortical insufficiency airse?
- Sudden withdrawal of exogenous corticosteroids
- Adrenal haemorrhage
Causes of Addison’s disesae?
Rare:
- Autoimmune
- TB
- Metastatic malignancy
What ist he most common cause of secondary adrenocortical insufficiency?
Secondary adrenocortical insufficiency is caused by reduced ACTH output.
This is most common seen after prolonged administration of exogenous glucocorticoids causing pituitary atrophy through negative feedback.
Production of which corticoid hormones are impacted in secondary adrenocortical insufficiency?
Cortisol and adrenogens will be deficiency.
Aldosterone production will be normal, because it is controlled by the renin-angiotensin system rather than ACTH.
WHat is adrenal phaeochromocytoma?
Neoplasm of the adrenal medullary neuroendocrine cells.
Most are benign
Can be functional - more adrenaline/noradrenaline production.
What are the symptoms of adrenal phaeochromocytoma?
Due to increased A/NA production:
- Hypertension
- Sweating
- Palpitations
- Headache
