S6 Intro to Endocrine System Flashcards
What does failure in homeostasis lead to?
Leads to disease
What are the characteristics of a control systems of a control system
- Stimulus
- Receptor - detects the stimuli
- Control centre - receives communication from the afferent pathway
- Effector - receives communication from the efferent pathway - causes change
- Negative feedback back to stimulus
What are some examples of receptor types?
- chemoreceptors
- thermoreceptors
- proprioreceptors
- nociceptors
How does communication via the afferent and efferent pathways occur in homeostasis?
- nervous system - action potentials
* endocrine system - hormones
What does the control centre do?
- determines the normal parameters
- analyses afferent input
- determines response
What are some examples of effectors?
- sweat glands
- muscle
- kidney
What are biological rhythms?
Set points/normal parameters of control centres can vary e.g. the circadian rhythm
The circadian rhythm, the biological clock, is made up of a small group of neurones in the brain called what?
Suprachiasmatic nucleus
What are cues from the environment called in terms fo circadian rhythm?
Zeitgebers
What cues from the environment keep the body on a 24 hour cycle
- light
- temperature
- social interaction
- exercise
- eating/drinking pattern
What hormone and from where are involved in setting biological clock?
Melatonin from the pineal gland
What is negative feedback?
Response in a way to reverse the direction of change (most common)
What is positive feedback?
Response in a way so as to change the variable even more in the direction of the change (rare)
E.g. blood clotting ovulation
What are the loops involved in negative feedback? Use hormone 1, 2 and 3 as examples
- ultrashort loop - the hormone released by the hypothalamus inhibits release of more hormone
- short loop - hormone 1 stimulates the anterior pituitary gland to release hormone 2, hormone 2 can inhibit the hypothalamus releasing more hormone 1
- long loop - hormone 2 stimulates target gland to produce hormone 3 which inhibits either the anterior pituitary releasing hormone 2 or the hypothalamus releasing hormone 1
How much total body water in percentages do males and females have?
Males - 50 to 60%
Females - 45-50%
In an average 70kg man, with 42 litres of total body water, how much of this is intracellular fluid and extracellular fluid (interstitial fluid and blood plasma)?
Intracellular fluid - 28 litres (2/3)
Extracellular fluid - 14 litres (1/3)
* interstitial fluid 11 litres
* blood plasma 3 litres (+ 2 litres of RBCs so 5 litres of blood)
What is the osmotic pressure of blood plasma monitored by?
Osmoreceptors in hypothalamus
What is the difference between osmorlarity and osmolality?
Osmolarity - number of osmoles per litre of solution (volume)
Osmolality - number of osmoles per kg of solution (mass)
What is an osmole?
The amount of substance that dissociates in solution to form one mole of osmotically active particles
(1mM of NaCl is 2 mOsmol/L (1mOsmol from Na+ and one from Cl-)
What is one mole in terms of atoms/molecules/ions
6.02x10(23)
How many moles of a substance does a 1 molar (1M) solution contain in 1 litre?
1 mole
When is serum osmolality useful clinically?
Useful when treating hyponatraemia (low Na+ in blood)
Reference range is 275-295 mOsmol/kg
How does ADH control body fluid homeostasis when theres high blood osmolality (too little water)?
- Detected by osmoreceptors
- The posterior pituitary gland secretes more ADH
- There’s increased reabsorption of water from urine into blood in collecting ducts in the kidney
- A small volume of concentrated urine is produced and a normal blood osmolality is obtained
How does ADH control body fluid homeostasis when theres low blood osmolality (too much water)?
- Detected by osmoreceptors in the hypothalamus
- Posterior pituitary gland secretes less ADH
- So there’s less reabsorption of water from urine into the blood in collecting ducts in the kidney
- A large volume of dilute urine is produced and a normal blood osmolality is obtained
How are plasma glucose levels maintained by homeostasis in the fed state?
- Eating food increases plasma glucose
- The pancreas secretes insulin
- Insulin stimulates glycogenesis in the liver and stimulates glucose uptake into tissue (GLUT4)
- Plasma glucose declines and normal plasma glucose level obtained (about 5mM)
How are plasma glucose levels maintained by homeostasis in the fasting state?
- Fasting decreases plasma glucose
- Pancreas secretes glucagon
- Glucagon stimulates glycogenolysis in the liver and glucose is released into the blood
- Plasma glucose increases and a normal plasma glucose level is obtained (5mM)
What are the major endocrine glands?
- hypothalamus
- pituitary gland
- pineal gland
- thyroid gland
- parathyroid gland
- thymus
- adrenal gland
- pancreas
- ovary
- testes
What is the endocrine system?
A collection of glands located throughout the body which produce hormones (chemical signals) that travel in the blood stream to cause an effect on other tissues that
What non-endocrine organs secrete hormones?
- heart (ANP and BNP)
- stomach (gastrin and ghrelin)
- adipose (leptin)
- kidney (erythropoietin, renin, calcitriol)
- liver (IGF1)
- placenta (inhibin, placental lactogen)
What are the 4 mechanisms of communication via hormones?
- autocrine
- paracrine
- endocrine
- neurocrine
What are the 4 classes of hormones?
- peptide/polypeptide
- amino acid derivatives
- glycoproteins
- steroids
Describe the peptide/polypeptide group of hormones. Give examples of some hormones. Are they water soluble or lipid soluble?
- largest group
- insulin, glucagon, growth hormone
- water soluble
Describe the amino acid derivatives group of hormones. Give examples of some hormones. Are they water soluble or lipid soluble?
- synthesised from aromatic amino acids
- adrenaline (tyrosine), noradrenaline (tyrosine), thyroid hormones (tyrosine), melatonin (tryptophan)
- adrenal medulla hormones are water soluble, thyroid hormones are lipid soluble
Describe the glycoproteins group of hormones. Give examples of some hormones. Are they water soluble or lipid soluble?
- large protein molecules, made up of subunits, carbohydrate side chain
- LH, FSH, TSH
- water soluble
Describe the steroids group of hormones. Give examples of some hormones. Are they water soluble or lipid soluble?
- derived from cholesterol, steroidogenic tissues convert cholesterol into different hormones
- cortisol, aldosterone, testosterone
- lipid soluble
Which hormones travel in blood in simple solution?
Peptides and adrenaline
How do most hormones travel in the blood?
Bound to proteins
Free hormone + binding protein bound hormone
What is the role of carrier proteins in terms of transporting hormones?
- increase solubility of hormone in plasma
- increases the half-life
- readily accessible reserve
What are the 3 main factors that determine hormone levels in blood?
- rate of production
- rate of delivery
- rate of degradation
How do hormones exert their effects?
By binding to specific receptors
What type of receptors do water voluble hormones bind to?
Cell surface receptors e.g GPCRs (adrenaline) and tyrosine kinase (insulin)
Explain how insulin binding to insulin receptor (tyrosine kinase) causes a response.
- Autophosphorylation of specific tyrosines
- Recruitment of adapter proteins and signalling complex
- Activation of protein kinase
- Phosphorylation of target proteins
- Cellular response
Explain how adrenaline binding to adrenaline receptor (GPCR) causes a response.
- Dissociation of G protein alpha subunit
- Activation of effector protein e.g. adenylyl cyclase
- Formation of second messenger e.g. cAMP
- Activation of protein kinase e.g PKA
- Phosphorylation of target proteins
- Cellular response
What type of receptors do lipid soluble hormones bind to?
Intracellular receptors
How do lipid soluble hormones bind to intracellular receptors?
- Lipid soluble hormones diffuse across plasma membrane
- Binds to type 1 or type 2 receptors
- Receptor bind to specific DNA sequence called hormone response element (HRE) in promotor region of specific genes
- Expression of new protein mediates effects of hormones Giving a cellular response
What are type 1 and 2 intracellular receptors?
Type 1 - cytoplasmic receptor which binds to hormone forming a complex which then enters the nucleus to bind to DNA
Type 2 - hormone enters the nucleus and bind to a pre-bound receptor on DNA e.g. thyroid hormone. Binding relives repression of gene transcription
What is control of appetite controlled by?
The appetite control centre (satiety centre) located in the hypothalamus
The arcuate nucleus (cluster of neurones in hypothalamus) has a role in controlling appetite
What are the two types of neurones in the arcuate nucleus?
- stimulators neurones containing neuropeptide Y (NPY) and agouti-related peptide (AgRP) - promote hunger
- inhibitory neurones containing pro-opiomelanocortin (POMC) which contains NTs like alpha-MSH and beta-endorphin - promotes satiety
What hormones are released from the gut and act on the hypothalamus?
- Ghrelin - peptide hormone released from stomach wall when stomach is empty, stimulates excitatory primary neurones in arcuate nucleus so stimulates stomach (filling of the stomach inhibits ghrelin release)
- PPY (peptide tyrosine tyrosine) - short peptide hormone released by cells in the ileum and colon in response to feeding and stimulates inhibitory neurones so suppresses appetite
What are the effects of PYY injections/inhibited response?
Injection leads to anorexia
Inhibited response after eating food leads to obesity
What is leptin? Where does it have an effect? How does it effect oxidative phosphorylation?
A peptide hormone released into blood by adipocytes
Effects arcuate nucleus - stimulates inhibitory POMC neurones and inhibits excitatory AgRP/NPY neurones
Suppresses appetite
Induces expression of uncoupling proteins in mitochondria so energy therefore dissipated as heat
What is the effect of insulin on appetite control?
Suppresses appetite in a similar way to leptin but is less important
What is amylin? What does it do?
A peptide hormone secured by beta cells in the pancreas
Suppresses appetite decreases glucagon secretion and slows gastric emptying
What is an analogue for amylin? What is it used to treat?
Pramlintide
Type 2 diabetes
What does loss of function mutation in leptin gene result in? How can it be used clinically?
Loss of weight
Administered to patients with common obesity however many can have leptin resistance
What also has an accessory input into control of appetite that is hard to control?
Hedonic inputs
What pathways in control of appetite are orexigenic and anorexigenic?
Orexigenic - stimulatory primary neurone
Anorexigenic - inhibitory primary neurone
