Endocrinology Session 1 Flashcards
What do homeostatic mechanisms do?
Counteract changes in the internal environment so that conditions remain stable.
What happens when homeostasis fails to happen?
Disease
What are the characteristics of a control system?*
- Communication
- Control centre
- Receptor
- Effector
- Feedback
What is the role of communication?
Allows signal release (hormones) or action potentials in the nervous system. Afferent branches signal towards the brain while efferent branches signal the motor output away from the brain.
What is the role of the control centre?
Determining the reference set point, analysing the input and producing an appropriate set point.
What are the 2 control centres and what is their involvement?
- Hypothalamus (diencephalon)
Endocrine system control - Medulla oblongata (brain stem)
Ventilation and cardiovascular system
What is the role of the receptor?
- Required to detect stimuli
- Specialised nerve endings (chemoreceptors/thermoreceptors/proprioceptors/nociceptors)
- Communicate via afferent nerves
What is the role of the effector?
- Causing change
- Receive communication from efferent pathways
- e.g. sweat glands
What is negative feedback?*
- Response in a way to reverse the direction of change and bring it back to normal.
- Overshoots set point several times until resting at the set point.
What is a long loop in the negative feedback system?*
The last released hormone can feed back on either one of the components of the pathway.
What is a short loop in the negative feedback system?*
Hormone feeding back to the first component (eg. TSH to hypothalamus to prevent release of TRH)
What is positive feedback?
Stimulus produces a response in which the effect is increased rather than counteracted. Easy to let out of control and can be catastrophic when inappropriate.
What are some examples of positive feedback?
- Blood clotting (failure causes haemorrhaging)
- Ovulation (buildup of FSH releases oocyte)
What is the hypothalamic-pituitary-adrenal system?*
- Hypothalamus, pituitary and adrenal glands
- Corticotropin released from hypothalamus into local circulation
- Binds to receptors on anterior pituitary and stimulates adenocorticotrophic hormone release (ACTH)
- Transported to the cortex of adrenal glands
- Binds to receptors of zona fasciculata
- Releases CORTISOL into circulation
What are biological rhythms?*
- Variances in the set point of the control centre during the day
- ‘Biological clock’ is in the suprachiasmatic nucleus
What keeps the body on a 24-hour cycle?
Exogenous zeitgebers (cues from the environment)
- Light
- Temperature
- Exercise
- Social interactions
What hormone is responsible for setting the circadian rhythm?
- Melatonin
- Released from pineal gland
Why are circadian rhythms clinically important?
Cortisol levels vary in patients throughout the day - should be taken into consideration when measuring.
What are the water components in the body?*
50-60% of lean body mass
ICF: 2/3, around 28L ECF: 14L, divided into: - Interstitial fluid: 11L - Plasma: 3L \+ 2L of red cells to give 5L of blood.
How is osmotic pressure of blood plasma measured?
Osmoreceptors in hypothalamus
What is osmolaLity?
Numbers of osmoles per Kg of solution
What is osmolaRity?
Numbers of osmoles per L of solution
What is an osmole?
The amount of substance that dissociates in solution to form one mole of osmotically active particles (eg. 1 mM of NaCl = 2mOsm, 1 from Na and 1 from Cl)
What does one molar of solution contain?
One mole of substance in one litre.
What is the reference range for serum osmolality and when is it relevant?
- 275-295mOsmol/kg
- Treating hyponatremia
What is the role of antidiuretic hormone in body fluid homeostasis?*
- High level of osmolality detected so body needs to conserve water
- Detected by osmoreceptors in hypothalamus (supraoptic and paraventricular nuclei)
- Posterior pituitary secretes more ADH
- Increased reabsorption of water from urine into kidney collecting ducts via more aquaporins
- Normal osmolality returns
And vice versa.
Describe homeostatic control of plasma glucose*
Slide 10 :)
What is the endocrine system and what are its products?*
- Collection of glands located throughout the body
- Produces hormones
What are hormones?
Chemical signals produced by endocrine glands or tissues that travel in the bloodstream to cause an effect on their target tissues.
What are the major endocrine glands?*
- Hypothalamus
- Adrenal gland
- Ovaries/testes
- Thymus
- Pineal gland
- Hypothalamus
- Pituitary gland
- Thyroid
What other organs and tissues produce hormones?
Heart: ANP/BNP
Liver: IGF-1
Stomach: Gastrin/ghrelin
What is autocrine communication?
Hormone signal acts back on the cell of its origin.
What is paracrine communication?
Hormone signal carried to adjacent cells over a short distance in the interstitial fluid.
What is endocrine communication?
Hormone signal released into the bloodstream and carried to distant target cells.
What is neurocrine communication?
Hormone originates in neurone, transported down axon and released into bloodstream to be carried into distant target cells.
What are the features of the endocrine system?*
- Hormone signals
- Chemical nature
- Conveyed in bloodstream
- Fast
- Via receptors
What are the features of the nervous system?*
- Signals are neurotransmitters and action potentials
- Chemical and electrical signals
- In synapses and axons
- Act on receptors
- Slow
What are peptide/polypeptide hormones?
- Short chains of amino acids
- Water soluble
What are examples of peptide hormones?
- Insulin
- Glucagon
- Growth hormone
What are glycoprotein hormones?
- Large protein molecules often made up of subunits
- Have carbohydrate side chains
- Water soluble
What are examples of glycoprotein hormones?
- Lutenising hormone
- Follicle stimulating hormone
- Thyroid stimulating hormone
What are amino acid derivative hormones?
- From aromatic amino acids
- Thyroid: lipid soluble
- Adrenal medulla: water soluble
What are examples of amino acid derivative hormones?
- Adrenaline
- Thyroxine
- Triiodithyronine
What are steroid hormones?
- Cholesterol derivatives
- Lipid soluble
What are examples of steroid hormones?
- Cortisol
- Aldosterone
- Testosterone/oestrogen
Which hormones can be transported in the blood when dissolved in plasma?
Adrenaline and peptide hormones
Which hormones bind to proteins in the blood for transport?
Lipophilic (steroid and thyroid)
- Thyroid bind to thryoxine binding globulin (TBG)
- Only FREE form biologically active
What are the roles of carrier proteins?
- Increase solubility in plasma
- Increase half-life
- Provide a reserve
What determines hormone levels in the blood?
- Rate of production (synthesis and secretion)
- Rate of delivery (blood flow)
- Rate of degradation (metabolism and excretion)
How do hormones exert their effects?*
- Bind to specific receptors
- Response in cell only if cell expresses the receptor for the hormone
How do water soluble hormones exert their effects through GPCR?*
- Alpha subunit dissociates
- Adenylyl cyclase activated
- Second messenger (cAMP) forms
- PKA activated
- PKA phosphorylates target proteins
How do water soluble hormones exert their effects through tyrosine kinase?*
- Dimerisation (2 molecules combine)
- Autophosphorylation of specific tyrosines
- Recruitment of adapter proteins and signalling complex
- PKB activated
- Target proteins phosphorylated
What are tropic hormones?
Hormones which have endocrine glands as their targets.
How do lipid soluble hormones act?*
Diffusing across the plasma membrane and binding to intracellular receptors
- Bind type I/II
- Receptor binds to specific DNA sequence (HRE/hormone receptor element)
- Binds in the promoter region of specific genes
- mRNA produced, so new protein and cellular response
How do type I lipid soluble hormones act?*
- Cytoplasmic receptor binds hormone
- Hormone-receptor complex enters nucleus and binds to DNA
How do type II lipid soluble hormones act?*
- Hormone enters nucleus
- Binds to pre-bound receptor on DNA
- Binding relieves repression of gene transcription
What happens when energy intake = energy expenditure?
Body weight is stable
What happens when energy intake > energy expenditure?
Energy stores/fat will increase
What happens when energy intake < energy expenditure?
Energy stores deplete
Where is the satiety centre?*
Hypothalamus (arcuate nucleus plays role in controlling appetite)
What signals does the primary neurones in the arcuate nucleus process?*
Neuronal, nutrient and hormonal signals
- Synapse with secondary neurones in other regions of hypothalamus
- Signals integrated to alter feeding behaviour
What are the stimulatory neurones?
- Neurones in the arcuate nucleus
- Contain neuropeptide Y and Agouti-related peptide
- PROMOTE HUNGER
What are the inhibitory neurones?
- Primary neurones in the arcuate nucleus
- Contain pro-opiomelanocortin (POMC) which yields neurotransmitters like alpha-MSH and beta-endorphin
- PROMOTE SATIETY
What is ghrelin and how does it act?
- Peptide hormone released from stomach wall when it is empty
- Stimulates excitatory primary neurones in arcuate nucleus
- Stimulates appetite
- Release inhibited when stomach full
What is peptide tyrosine tyrosine/peptide YY?
- Short peptide hormone released by cells in ileum and colon in response to feeding
- Inhibits the excitatory neurones
- Stimulates inhibitory neurones
- Suppresses appetite
- If injected into mice, makes them anorexic
What is amylin?
- Peptide hormone secreted by beta-cells in pancreas
- Suppresses appetite
- Slows gastric emptying
- Decreases glucagon secretion
What is leptin?
- Peptide hormone released into blood by adipocytes
- Stimulates POMC inhibitory neurones
- Inhibits AgRP/NPY neurones
- Suppresses appetite
- Induces expression of uncoupling proteins in mitochondria
- Energy released as heat
What is insulin?
Hormone that suppresses appetite in a similar manner to leptin.
How is appetite controlled?**
SLIDE 27 KEY
What happens when some humans have a loss of leptin gene function?
- Present as overweight
- Rapid weight loss and remarkable response to leptin injection
- Will not respond if ‘common’ obesity (leptin resistance)
