Endocrinology Flashcards
What are the three ways hormones are distributed through?
Endocrine – blood-borne, acting at distant sites
Paracrine – acting on adjacent cells
Autocrine – feedback on same cell that secreted hormone
Features of water-soluble hormones
Transport - unbound
Cell interaction - bind to surface receptor
Half-life - short
Clearance - fast
Features of fat-soluble hormones
Transport - protein bound
Cell interaction - diffuse into cells
Half-life - long
Clearance - slow
What are the 4 classes of hormones?
- Peptides
- Amines
- Iodothyronines
- Cholesterol derivatives and steroids
What are the different mechanisms used to control hormone secretion?
Basal secretion – continuously or pulsatile
Superadded rhythms e.g day-night cycle – ACTH, prolactin, GH and TSH
Release inhibiting factors – dopamine inhibiting prolactin, sum of positive and negative effects (GHRH and somatostatin on GH)
Releasing factors
What hormones does the posterior pituitary synthesise?
NONE! Oxytocin and vasopressin (ADH) is stored in the posterior pituitary but is synthesised in the hypothalamus.
What would stimulate vasopressin release?
Vasopressin is an antidiuretic hormone. It is stimulated to absorb water from the kidney.
*Hypertonic concentration
*Loss of blood volume
*Stress
What does vasopressin do?
*Vasoconstricts blood vessels
*Increased release of aldosterone which leads to increased absorption of water
*Stimulates the release of ACH which in turn stimulates the release of cortisol
Where is oxytocin released?
Posterior pituitary gland
Function of oxytocin?
- Uterine contraction during labour.
- Milk ejection
What hormones are produced in the anterior pituitary gland and what are they stimulated by?
TSH - stimulated by TRH from hypothalamus
ACTH - stimulated by CRH from hypothalamus
FSH and LH - stimulated by GnRH from hypothalamus
GH - stimulated by GHRH from hypothalamus
PRL - inhibited by dopamine from hypothalamus
What are the three ways that someone with pituitary dysfunction would present?
*Tumour mass effects
*Hormone excess
*Hormone deficiency
What investigations should be conducted in patients with pituitary dysfunction?
- Make a clinical diagnosis
- Hormonal tests
- If hormonal tests abnormal or tumour mass effects perform MRI pituitary
When is oxytocin released?
It is stimulated by cervical dilation
Where does growth hormone act?
In the liver
What hormone does GH stimulate?
Insulin-like growth factors (IGFs)
Functions of thyroid hormone
*Accelerates food metabolism
*Increases protein synthesis
*Stimulation of carbohydrate metabolism
*Enhances fat metabolism
*Increase in ventilation rate
*Increase in cardiac output and heart rate
*Brain development during foetal life and postnatal development
*Growth rate accelerated
Main function of cortisol?
Major metabolic and stress hormone
Describe the structure of the adrenal gland.
Adrenal gland is divided into the medulla and cortex.
The cortex is made up of three layers:
GFR
*Zona glomerulosa
*Zona fasciculata
*Zona reticularis
Where in the adrenal cortex are mineralocorticoids produced and give an example of one.
Zona glomerulosa.| - Aldosterone.
Where in the adrenal cortex are glucocorticoids produced and give an example of one.
Zona fasciculata.| - Cortisol androgens
Where in the adrenal cortex are androgens produced and give an example of one.
Zona reticularis.| - androstenedione and DHEA
What is released by the adrenal medulla?
Epinephrine and norepinephrine
What happens in the zona glomerulosa
Renin-angiotensin system
*Low Na, sympathetic
*Renin acts on zona glomerulosa producing aldosterone
*Increases absorption of Na+ and increased K+ excretion
*Blood volume increases and/or BP
What happens during stress?
Stress
*CRH released
*ACTH released
*Drives adrenal gland to release glucocorticoids (ie cortisol)
*Helps body overcome stress
What does FSH and LH stimulate?
Hypothalamus -> GnRH -> AP -> FSH/LH -> ovaries/testes.
FSH acts on granulosa cells to produce oestrogen and sertoli cells to stimulate spermatogenesis.
LH acts on theca cells to produce androgens or leydig cells to produce testosterone.
BMI thresholds
<18.5 underweight
18.5 - 24.9 normal
25.0 - 29.9 overweight
30.0 - 39.9 obese
>40 morbidly obese
What is obesity a risk factor of?
- Type II diabetes
- Hypertension
- Coronary artery disease
- Stroke
- Osteoarthritis
- Obstructive sleep apnoea
- Carcinoma
- Breast
- Endometrium
- Prostate
- Colon
How would you calculate BMI?
wt (kg)/ht (m^2)
Give a reason to why working night shifts could increase obesity?
Disruption of the Circadian rhythm, this could increase insulin resistance leading to obesity.
What are the two factors that can affect weight regulation?
- Genetics
- Environment
What are the three main organs that influence appetite regulation?
- GI tract
- Brain
- Adipose tissue
Why are the two factors that drive us to eat?
Internal physiological drive to eat
- feeling that prompts thought of food and motivates food consumption
External psychological drive to eat
- sometimes even in the absence of hunger (ie buffet)
What are the 4 main stages in the satiety cascade?
- Sensory
- Cognitive
- Post ingestive
- Post absorptive.
Which brain structure is responsible for appetite regulation?
Hypothalamus
Lateral hypothalamus - hunger centre
Ventromedial hypothalamic nucleus - satiety center
Which hormones suppress appetite?
- Leptin
- Insulin
- PYY
- CCK
- POMC
- CART
- GLP 1
- Serotonin
Which hormones increase appetite?
- Ghrelin
- NPY
- MCH
- AgRP
- Orexin
- Endocannabinoid
Where is leptin released from?
White adipose tissue
What is the mechanism of action of leptin on the hypothalamus?
*Leptin inhibits NPY and AgRP
*Leptin stimulates POMC and CART
*Appetite decreases
What might happen if someone was deficient in leptin?
They might become obese.
Where does CCK act on?
Stretches receptors on the pyloric sphincter
- Delays gastric emptying
- Gall bladder contraction
- Insulin release
Where is ghrelin expressed?
In the stomach
How does ghrelin stimulate appetite?
Ghrelin stimulates NPY and AGRP = increases appetite.
Which hormone decreases following gastric bypass surgery?
Ghrelin
What hormone might it be possible to use in the treatment of anorexia?
Ghrelin
What can POMC be broken down into? What roles do they play?
Three main hormones:
- ACTH
- MSH
- endorphin
What can POMC deficiency lead to?
- Pale skin
- Adrenal insufficiency
- Hyperphagia and obesity
What does high levels of agouti-related peptide (AgRP) cause?
Causes excess eating, increases appetite
What is the role of Malonyl CoA in satiety?
In a fasted state, action of different hormones will lead to activation of AMPK
Increased AMPK will reduce acetyl CoA Carboxylase and decrease malonyl CoA and increase appetite.
In a fed state, the opposite occurs.
In non diabetic humans how does metabolism occur during the fasting state?
*All glucose comes from liver (and a bit from kidney)
- Breakdown of glycogen
- Gluconeogenesis (utilises 3 carbon precursors to synthesise glucose including lactate, alanine and glycerol)
*Glucose is delivered to insulin independent tissues, brain and red blood cells
*Insulin levels are low
*Muscle uses FFA for fuel
*Some processes are very sensitive to insulin, even low insulin levels prevent unrestrained breakdown of fat
In non diabetic humans how does metabolism occur after feeding ?
*Rising glucose (5-10 min after eating) stimulates insulin secretion and suppresses glucagon
*40% of ingested glucose goes to liver and 60% to periphery, mostly muscle
*Ingested glucose helps to replenish glycogen stores both in liver and muscle
*High insulin and glucose levels suppress lipolysis and levels of non-esterified fatty acids (NEFA or FFA) fall
Define diabetes mellitus
A disorder of carbohydrate metabolism characterised by hyperglycaemia.