Lecture 12 Flashcards
What are homeostatic mechanisms?
Act to counteract changes in the internal environment (exist at cell, tissue, organ, organism level) so internal conditions remain stable/constant
Not a steady state- dynamic equilibrium
What are the characteristics of a control system?
- stimulus (change)
- receptors to detect stimuli
- control centre (often hypothalamus/pituitary)-determines set points, analyses afferent input, determines response
- effector (causes change)
Give come examples of receptors:
Proprioceptors (coordination-self aware of where body is)
Nociceptors (sense pain)
Chemoreceptors (chemicals)
Thermoreceptors (heat)
What is the afferent pathway in a control system?
Communication between receptor to control centre
(Nervous system-AP’s/endocrine system-hormones)
A comes before e in alphabet so Afferent comes before Efferent
What is the efferent pathway in a control system?
Communication between the control centre and the effector
Nervous-AP’s/Endocrine-hormones
Give some examples of effectors:
- sweat glands (thermal regulation)
- muscle (reflex)
- kidney (regulation of water content in body)
These cause the change
Can the set point of a control centre vary?
It is dynamic- circadian/diurnal rhythm (things change with time) so must record time
What cues from the environment feed into circadian rhythm/biological clock?
- light
- temp
- exercise
- social interaction
- eating/drinking pattern
Which nucleus in the hypothalamus is responsible for the biological clock?
Small group of neurones in suprachiasmatic nucleus
What are some circadian rhythms?
- body temp (decreases when asleep)
- cortisol (peak first thing in morning, at minimum at midnight)
- melatonin
What is negative feedback + the hypothalamus/pituitary axis?
- response to reverse direction of change
- most common
(Hypothalamus secretes hormones which have trophic effects- effect secretions of other hormone- in anterior pituitary which travels in blood to target organ for that to secrete hormone)
-local blood supply between the hypothalamus and pituitary
What is long loop negative feedback?
From last hormone in system feeding back to anterior pituitary/hypothalamus
What is the short/ultrashort loop?
Short: Hormonal product from anterior pituitary is feeding back to hypothalamus
Ultrashort: hormone released from hypothalamus inhibits its own release
What is positive feedback? (Rare)
-response to change variable even more in the direction of change
(Used when rapid change is desirable)
- clotting
- ovulation
- Ferguson reflex (cycle of uterine contractions initiated by pressure at the cervix)
How do you regulate the amount of water in the body?
Osmoreceptors in hypothalamus
-Sense osmolality of blood
What is the difference between osmolarity and osmolality?
Osmolarity: number of osmoles per litre (volume)
Osmolality: number of osmoles per kg (mass)
Osmoles instead of moles (osmotically active particles)
E.g. dissolving NaCl (osmolarity will be double that of the molarity)
How does ADH work?
- high blood osmolality (body needs water)
- detected by osmoreceptors in hypothalamus- signals thirst centre= drinking to reduce osmolality of plasma
- hormones synthesised in hypothalamus transported down neurones to be stored in posterior pituitary which then secretes more ADH (other hormone from posterior pituitary is oxytocin)
- ADH signals to cells in collecting duct to increase number of Aquaporins allowing increased reabsorption of water
- small volume of urine
-low blood osmolality
-detected by osmoreceptors in the hypothalamus
-posterior pituitary secretes less ADH
-decreased absorption of water back into collecting duct
= more water lost in large volume of dilute urine
What are the 2 hormones in the posterior pituitary?
ADH
Oxytocin
Mechanism of glucose homeostasis:
-eat meal increases plasma glucose
-pancreas senses increase in glucose and releases insulin
-insulin stimulates glycogenesis in liver + stimulate glucose uptake into tissue via GLUT 4 in adipose/muscle tissue
= plasma glucose conc declines back to 5mM
-fasting decreases plasma glucose
-pancreas (detected by alpha cells in islets of langerhans) secretes glucagon
-stimulates glycogenolysis in liver so glucose released into blood
= plasma glucose increases back to 5mM
What is the endocrine system?
Collection of glands located throughout the body
(Hypothalamus, pituitary, thyroid, parathyroid, pineal, adrenal glands)
-hormones are chemical signals produced by endocrine glands and travel in blood to remote target site
Apart from endocrine glands, which organs and tissues release hormones?
- heart (ANP + BNP)
- liver (IGF1)
- stomach (Ghrelin + Gastrin)
- placenta
- adipose tissue (Leptin)
- kidney (EPO, Renin, calcitriol)
What are the mechanisms of communications via hormones?
Autocrine (Hormone signal acts back on cell of origin)
Paracrine (hormone signal carried to adjacent cells over short distance via interstitial fluid)
Endocrine (hormones in bloodstream)
Neurocrine (hormone down axon and released into bloodstream)
Can a neurotransmitter be a hormone?
Yes, dependent on the context.
E.g. dopamine
Similarities/ differences between endocrine and nervous system:
- both capable of secreting
- both can be depolarised
- both require interaction with specific receptors in target cells
- systems work in parallel to control homeostasis
- endocrine= slow, nervous= fast
- nervous= synapses and axons, endocrine= bloodstream
- both can be chemical but nervous is also electrical
What are the classifications of hormones?
Peptide/polypeptide hormones (largest group)
-all water soluble
Amino acid derivatives (amines-synthesised from aromatic AA’s)
-adrenal medulla hormones (water soluble- adrenaline/noradrenaline)
-thyroid hormones (lipid soluble)
Glycoproteins (large protein molecules)
-water soluble
Steroid (derived from cholesterol)
-lipid soluble
Which AA derivative hormones are water/lipid soluble?
Adrenal medulla: water soluble
Adrenaline/noradrenaline
How are lipid soluable hormones transported around the body?
Require binding protein to facilitate transport around blood (unbound form is biologically active, so when bound they aren’t active)
-we have specific binding proteins e.g. thyroxine binding protein
What factors can we modulate to alter hormone levels?
- Rate of production (most highly regulated)
- Rate of delivery (higher blood flow increases rate of delivery)
- Rate of degredation (hormones metabolised and secreted)
What unit do we use to measure hormones?
10^-12 picomolar concentration of hormones in blood
Hormones are present in very tiny concentrations
How do hormones exert their effect?
Bind to specific receptors on target cells to elicit a biological response
How do water soluable hormones enter cells?
-unable to pass through plasma membrane
Cell surface receptors used
-second messenger is used to relay hormone response through to cytoplasm
(G-protein: alpha > binding of hormone, dissociation of G protein, activates adenylyl cyclase, activation of cAMP, activation of PKA, phosphorylation of target proteins)
(Tyrosine kinase receptors: insulin-autophosphorylation of tyrosine residues, recruits adapter proteins + signalling complex, activates protein kinase, phosphorylation of protein)
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How do lipid soluble hormones work?
- readily pass through plasma membrane (steroid hormones)
- act as transcription factors
- bind to receptor which effects gene transcription
- bind to receptor in cytoplasm (type 1)
- receptor complex binds to nucleus and alters gene transcription
-hormone enters nucleus itself and binds to receptor in there (type 2)
Expression of new protein which mediates effect of hormone
Which method is faster?
Water soluable - as components are already in place
Because the lipid soluble acts as a TF to make the protein which will elicit the effect
What structure controls appetite?
Satiety centre is in the hypothalamus
-arcuate nucleus
What is a nuclei in the brain?
Collection of neurones with similar function
What is jet lag?
Long haul flights crossing time zones result in a mismatch between environmental cues and body clock
Which hormone is involved in setting the biological clock?
Melatonin from pineal gland
-high whilst asleep, some people take it to limit effects of jet lag
What is the normal blood osmolality range?
Between 275-295 mOsm/kg
What is the normal plasma glucose level?
5mM
Give some examples of peptide hormones:
- insulin
- glucagon
- growth hormone
Give some examples of amino acid derivative hormones:
- adrenaline (tyrosine)
- noradrenaline (tyrosine)
- thyroid hormones (tyrosine)
- melatonin (tryptophan)
Give some examples of glycoprotein hormones:
- luteinizing hormone
- follicle stimulating hormone
- thyroid stimulating hormone
Give some examples of steroid hormones:
- cortisol
- aldosterone
- testosterone
- progesterone
All derivatives of cholesterol
How are water soluble hormones transported?
Travel in simple solution dissolved in plasma of blood
Peptide hormones/adrenaline
What are the roles of carrier proteins in blood?
- increase solubility of hormone in plasma
- increase half life (stability)
- readily accessible reserve (release form binding proteins)
Why does obesity arise?
Chronic imbalance between energy intake and expenditure
BMI >30kg/m2
What neurones do you find in the arcuate nucleus?
- primary neurones (stimulatory/inhibitory)
- secondary neurones (integrate the signals from the primary neurone to produce a response)
What are the function of stimulatory/inhibitory primary neurones in the arcuate nucleus?
Stimulatory neurones -contain neuropeptide Y (NPY) + Agouti-related peptide (AgRP) -promote hunger Inhibitory neurones -contain pro-opiomelanocortin (POMC) -promote satiety
What are some hormonal signals from gut to hypothalamus?
Ghrelin
-peptide hormone released from stomach was when empty
-stimulates excitatory primary neurones to stimulate appetite
-filling of stomach inhibits ghrelin release
PYY (peptide tyrosine tyrosine)
-suppress appetite
-released by cells in ileum/colon in response to feeding
-inhibits excitatory primary neurones + stimulates the inhibitory ones
Give some examples of hormonal signals from body to hypothalamus:
Leptin
-released from adipose tissue
-suppress appetite (stimulates inhibitory neurones/inhibits excitatory neurones)
-induces expression of uncoupling proteins in mitochondria so energy is dissipated as heat
Insulin
-suppresses appetite similar mechanism to Leptin
-less important than Leptin
Amylin
-peptide hormone secreted by beta cells in pancreas
-suppress appetite (slow gastric emptying/decrease glucagon secretion)
What are the primary neurones also known as?
Stimulatory: orexigenic
Inhibitory: anorexigenic
What is an important receptor on the secondary neurone?
MC4 receptors: promotes satiety
What occurs if you have a leptin mutation?
Loss of function of leptin gene
= obesity
(Leptin injections given to reduce weight)
