RA18 Endocrine Flashcards
Endocrine
Phys 35 Endocrine System General Concepts
Hormome travels through the blood circulation to act on distant target cells
Distant-signalling
Paracrine
Phys 35 Endocrine System General Concepts
Hormone is secreted into the interstital fluid to act locally on nearby target cells
Nearby-signalling
Autocrine
Phys 35 Endocrine System General Concepts
Hormone is secreted into interstitial fluid to act on the cell that produced it
Self-signalling
How are hormones regulated? (3 ways)
Phys 35 Endocrine System General Concepts
- Rate of hormone production (+ve/-ve feedback)
- Rate of hormone delivery (perfusion, mass action law)
- Rate of hormone excretion/degredation (half-life)
Peptide hormones
- Consists of/derived from?
- Synthesis
- Storage
- Solubility in plasma
- Carrier
- Receptors
- Response time
- Half life (effect time)
- Examples
Phys 35 Endocrine System General Concepts
- Consists of 3 or more amino acids
- Pre-prohormone in RER -> cleave signal sequence -> prohormone in Golgi aparratus -> packaged and trimmed -> active hormone in secretory vesicle
- Stored in secretory vesicles
- Soluble
- Not bound to carrier
- Bind cell surface receptors -> activate second messenger cascade
- Fast acting
- Short half life
- E.g. glucagon, insulin
Steroid hormones
- Consists of/derived from?
- Synthesis
- Storage
- Solubility in plasma
- Carrier
- Receptors
- Response time
- Half life (effect time)
- Examples
Phys 35 Endocrine System General Concepts
- Derived from cholesterol
- Cholesterol -> pregnenolone (rate limiting step)
- Synthesised on demand (by adrenal cortex, gonads, placenta), NOT stored
- Insoluble
- Bound to carrier
- Bind intracellular receptors -> activate gene transcription
- Slow acting
- Long half life
- E.g. estrogen, cortisol
Amino acid derivatives: thryoid hormones
- Consists of/derived from?
- Solubility in plasma
- Carrier
- Receptors
- Response time
- Half life (effect time)
- Examples
Phys 35 Endocrine System General Concepts
- Derived from amino acids (tyrosine)
- Insoluble
- Bound to carrier
- Bind intracellular receptors -> activate gene expression
- Slow acting
- Long half life
- E.g. T3, T4
Amino acid derivatives: catecholamines
- Consists of/derived from?
- Solubility in plasma
- Carrier
- Receptors
- Response time
- Half life (effect time)
- Examples
Phys 35 Endocrine System General Concepts
- Derived from amino acids (tyrosine)
- Soluble
- Not bound to carrier
- Bind cell surface receptors -> activate second messenger pathway (signal cascade)
- Fast acting
- Short half life
- E.g. epinephrine, norepinephrine
Where are carrier proteins synthesised?
Phys 35 Endocrine System General Concepts
Liver
Function of carrier proteins
Phys 35 Endocrine System General Concepts
- Extend half life of hormones in circulation (protect hormones from degredation/excretion)
- Sequester hormones from target cell receptor (i.e. hormones bound to carrier cannot bind to receptor; only free hormones are active)
Total hormone concentration in the blood
Phys 35 Endocrine System General Concepts
Bound (to carrier) + free
Plasma insoluble hormones bind to (…) receptors. Plasma soluble hormones bind to (…) receptors.
Phys 35 Endocrine System General Concepts
Plasma insoluble hormones bind to intracellular receptors. Plasma soluble hormones bind to cell surface receptors.
Adaptation/desensitisation of receptors
Phys 35 Endocrine System General Concepts
Chronically elevated level of hormone -> diminished cell response
Rebound of receptors
Phys 35 Endocrine System General Concepts
Prolonged absence of hormone -> increased receptor numbers -> hyperactive with return of hormone
Inactivation of hormonal response (3 ways)
Phys 35 Endocrine System General Concepts
- Removal of hormone from circulation
- Down regulation of hormone (sequestration i.e. endocytosis of receptor, uncoupling of receptor from donwstream signalling)
- Removal of stimulus (negative feedback)
Hypothalamic-Pituitary-Adrenal (HPA) axis
Phys 35 Endocrine System General Concepts
Hypothalamus secrete CRH -> anterior pituitary secrete ACTH -> adrenal cortex secrete cortisol -> inhibit CRS and ACTH
CRH: corticotropin-releasing hormone
ACTH: adrenocorticotropic hormone
Hyposecretion vs hypersecretion vs resistance
Disorder/dysregulation in endocrine system
Phys 35 Endocrine System General Concepts
- Hyposecretion: secrete insufficient hormone
- Hypersecretion: secrete excess hormone
- Resistance: unresponsive to hormone (can lead to hyposecretion)
Primary vs secondary vs tertiary endocrine pathology/deficiency
Phys 35 Endocrine System General Concepts
- Primary: defect in target endocrine gland (adrenal cortex)
- Secondary: defect in proximal regulator (pituitary) of target gland
- Tertiary: defect in distal regulator (hypothalamus) of target gland
Hormone levels in primary vs secondary vs tertiary endocrine pathology
Phys 35 Endocrine System General Concepts
Primary:
- Defect in adrenal cortex
- Low cortisol, high ACTH and CRH
Secondary:
- Defect in pituitary
- Low cortisol and ACTH, high CRH
Tertiary:
- Defect in hypothalamus
- Low cortisol, ACTH, CRH
Bioassay test for cortisol hyposecretion
Phys 35 Endocrine System General Concepts
- Stimulation test
- Give ACTH to promote cortisol secretion
- If cortisol increases -> HPA axis is intact
- If cortisol remains low -> adrenal cortex or pituitary (loss of trophic effect of ACTH on adrenal cortex) is dysfunctional
Bioassay test for cortisol hypersecretion
Phys 35 Endocrine System General Concepts
- Suppression test
- Give dexamethasone at midnight to suppress ACTH secretion -> prevents increase in cortisol in the morning
- If cortisol is suppressed -> HPA axis is intact
- If cortisol remains high -> adrenal cortex or pituitary is dysfunctional
What are the regions of the adrenal gland? (2)
Phys 36 Adrenal Gland
- Adrenal cortex (outer region)
- Adrenal medulla (inner region)
What are the layers of the adrenal cortex, from outer to inner layer? (3)
Phys 36 Adrenal Gland
- Zona glomerulosa
- Zona fasciculata
- Zona reticularis
What hormones does each layer of the adrenal cortex secrete?
Phys 36 Adrenal Gland
Zona glomerulosa: mineralocorticoids (salt)
- Aldosterone
Zona fasciculata: glucocorticoids (sugar)
- Cortisol
Zona reitcularis: androgens (sex)
- Estrogen
- Testosterone
Sugar, salt, sex
Aldosterone
- Site of synthesis
- Action
- Regulation
- Made in zona glomerulosa of adrenal cortex
- Increase blood vol/pressure by increasing reabsorption of sodium + excretion of potassium by kidney
- Regulated by Renin-Angiotensin-Aldosterone system (RAAS)
Hyperaldosteronism
- Cause
- Effects
- Example
Cause:
- Hypersecretion of aldosterone
Effects:
- Hypertension (reabsorption of Na+ -> increased blood vol + pressure)
- Hypokalemia (excretion of K+)
Example:
- Primary hyperaldosteronism (Conn’s syndrome)
Cortisol
- Site of synthesis
- Action
- Regulation
- Made in zona fasciculata of adrenal cortex
- Increase blood glucose (by increasing insulin resistance and mobilising fuel), anti-inflammatory (decrease immune system function)
- Regulated by hypothalamic-pituitary-adrenal (HPA) axis
Metabolic effects of cortisol in:
- Liver
- Skeletal muscle
- Adipose tissue
Liver:
- Increase gluconeogenesis
- Increase glycogenolysis
Skeletal muscle:
- Decrease protein synthesis
- Increase protein degradation
- Decrease glucose uptake
Adipose tissue:
- Increase lipid degradation
Net result: mobilise fuel stores to increase plasma glucose
Cortisol levels are (…) in the morning and (…) at night
Cortisol levels are highest in the morning and lowest at night
Issues with excess use of cortisol
- Bone breakdown: osteoporosis, avascular necrosis of joints, osteoarthritis
- Insulin resistance: type 2 diabetes
- Immune suppresion: increased risk of infections
Cushing’s syndrome
- Cause
- Clinical features
- Caused by excess cortisol (hypercortisolism)
- Thinning of hair, facial plethora, dorsocervical and supraclavicular fat pads, weight gain, thin limbs with muscle atrophy, purple striae on abdomen due to thinning of skin
Cushing’s disease: dysfunction in pituitary gland (ACTH) specficially
What are the levels of cortisol and ACTH in primary vs secondary Cushing’s syndrome?
Primary:
- High cortisol (due to overactive adrenal gland)
- Low ACTH (due to -ve feedback from cortisol)
Secondary:
- High cortisol
- High ACTH (due to overactive pituitary gland that does not respond to -ve feedback)
Addison’s disease
- Cause
- Cortisol vs ACTH levels
- Clinical manifestations
- AKA adrenal insufficency
- Deficiency in all adrenal cortex hormones, especially glucocorticoids and mineralcorticoids (main source of androgens = gonads)
- Low cortisol, high ACTH
- Excess ACTH -> excess α MSH -> hyperpigmentation of skin
- Deficient aldosterone + cortisol -> low Na+ and high K+ -> hyponatremia, hyperkalemia, hypotension, salt craving
Catecholamines (epinephrine, norepinephrine, dopamine):
- Site of synthesis
- Action/metabolic effects
- Made in adrenal medulla
- Activate sympathetic system (fight or flight response)
-> increase cardiac output
-> constrict blood vessels to peripheral tissues and gut to increase oxygen delivery to muscles
-> dilate smooth muscle in bronchi/bronchioles to increase oxygenation of blood
-> inhibit insulin release to maintain blood glucose levels
-> increase lipolysis in adipose tissue to raise blood glucose
Pheochromocytoma
- Cause
- Clinical features
- Caused by excess catecholamines
- Five Ps: pain, pallor, palpitations, pressure (hypertension), perspiration
What kind of cells comprise the thyroid gland?
Thyroid follicles
- Epithelium = single layer of cuboidal follicular cells
- Fluid filled space = colloid -> contains thyroglobulin
