Endocrine Flashcards
Functions of the endocrine system
- Regulate metabolism, water and electrolyte balance
- Allow body to cope with stress
- Regulate growth
- Control reproduction
- Regulate circulation and RBC production
- Control digestion and absorption of food
3 types of hormones
Peptides, amines (catecholamines and thyroid hormone) and steroids
Basics characteristics of peptides
- Chains of amino acids
- ADH, GH
- Stored prior to release
- Hydrophilic
- Fast acting as it is easily stored in vesicle
Basics characteristics of peptides
- Chains of amino acids
- ADH, GH
- Stored prior to release
- Hydrophilic
- Fast acting as it is easily stored in vesicle
Basics characteristics of amines
- Derived from amino acid tyrosine
- All are stored
- Either hydrophilic in case of catecholamines (A, NA, dopamine) or lipophilic in thyroid hormone
Basics characteristics of steroids
- Derived from cholesterol when the appropriate conversion enzymes are present eg cortisol, testosterone or oestrogens
- Lipophilic
- Not stored, released by diffusion
Hydrophilic hormones in blood and action
(peptides and catecholamines)
- Transported in blood dissolved in plasma (some carried on binding proteins)
- Cant pass through cell membrane (lipophobic) therefore binds to receptor on cell surface
- Elicit response either by changing cell permeability or activating second messenger system (more common) to alter activity of intracellular proteins
- Vulnerable to metabolic inactivation so short term but fast responses
Lipophilic hormones in blood and action
(thyroid and steroids)
- Transported in blood mostly bound to plasma proteins where a small unbound amount is dissolved allowing it to be physiologically active.
- Free hormone easily passes through cell membrane where it binds to specific receptors within target cell ((normally in nucleus)
- Cause response by activating specific genes within target cell to cause formation or new intracellular proteins
- Less vulnerable to metabolic inactivation so effects last longer, this is due to being binded to plasma protein
5 key aspects of hormone activity regulation
- Secretion
- Transport
- Metabolism
- Excretion
- Target cell responsiveness
Control of hormone secretion
- Central
- Control by the brain (hypothalamus and pituitary gland) through a cascade of hormone releases
- Affected by negative feedback loops, neuroendocrine reflexes (milk secretion/ejection from suckling) and rhythms (diurnal - times of the day, cortisol and melatonin)
- Fast, slow or long term responses
- Direct
- Endocrine cells response directly to changes in ECF substance levels (glucose, calcium ect)
- Very rapid response for critical needs
- Very tightly regulated
- Example is glucagon and insulin in response to glucose levels in the blood
Regulation of hormones via transport
This is especially relevant for lipophilic hormones
- Availability of binding proteins can be altered. Some of these are specific for a particular hormone while some are non specific. (increase or decrease number)
- Equilibrium between carrier bound hormone in equilibrium with free hormone
- These binding proteins are synthesised in the liver meaning a deficiency (from liver disease) alters this balance between bound and free hormones in plasma
Regulation of hormones via metabolism
- Some hormones are activated via metabolism (thyroid hormone) where they then have much greater activity
- Inactivation mostly occurs in the liver is usually unregulated but may be effected in liver disease
- Metabolism occurs at much higher rate for hydrophilic hormone because they’re unbound making them accessible to blood and tissue enzymes rather than bound lipophilic hormones
Regulation of hormones via excretion
- Usually unregulated - makes urinary levels a good way to measure hormone levels
- Urinary excretion may be effected by kidney or urinary disease
Regulation of hormones via target cell responsiveness
- Amplification of hormones by using second messenger cascade
- Variations in receptor expression on target cell (number and type can be varied)
- Permissiveness, synergism and antagonism
- Presence or absence of one hormone can influence effects of another through receptor regulation, activation or inactivation
Hypothalamus to posterior pituitary
- Hypothalamus is able to act directly on the post
- Posterior is neural tissue (extension of the brain)
- Causes the release of two hormones:
- Vasopressin (ADH)
- Oxytocin
Hypothalamus to anterior pituitary
- Endocrine tissues (not neural) meaning that neurons from the hypothalamus secret releasing and inhibitory hormones into capillaries which will then have an effect on the anterior pituitary.
- There are releasing and inhibitory factors for all of the hormones secrete in ant pituitary
Hormones of anterior pituitary (4-2)
- Trophic hormones stimulate the activity of another endocrine gland - ACTH, TSH, LH, FSH
- Hormones that have a direct effect (prolactin and GH)
Aside from GH what else can influence growth
- Genetics
- Dietary impact (mainly AAs)
- Chronic disease or stressful environment as cortisol inhibits growth
- Other hormones such as thyroid hormone, insulin and sex steroids
Growth hormone secretion
Centrally controlled - increased by GHRH and decreased by somatostatin
Secretion is pulsatile with pulses during the day and more at night
Anabolic and metabolic actions of GH
Anabolic:
- Increase thickness and length of long bones
- Increase size and number of cells in soft tissue
Metabolic:
- Increases fat breakdown/increases circulating fatty acids
- Decreases glucose uptake by muscle
- These both increases available energy
GH MOI overview
Most tissues respond directly to growth hormone via Gh receptors - metabolism effects
Some effects are due to IGFs release at the liver after GH binding
Some are due to local release of IGFs at tissues
Indirectly mediated by somatomedins seen to have growth effects
Some are due to local production of GH in target tissue
IGF = somatomedins
Direction actions of GH by GH receptors (metabolism)
Muscle
- Stimulate AA uptake and decrease glucose uptake
- Inhibits proteins breakdown
- Increase and maintain muscle mass
Adipose tissue
- Stimulate lipolysis and decrease glucose uptake
- Causes a decrease in fat deposits
Liver
- Increases proteins synthesis and gluconeogenesis
- Therefore increase in metabolism
Indirection actions of GH through somatomedins (growth)
IGF-1
- Proliferation of chondrocytes at epiphyseal plates which will increase bone length
- Increases osteoblast activity to produce matrix = increase bone thickness
- Promotes soft tissue growth through hyperplasia (number) and hypertrophy (size)
IGF-2
- Promotes soft tissue and organ growth by increasing protein, RNA and DNA synthesis
Overall action of GH
Release nutrients so grow can occur and then stimulate this growth
In adolesces and people in growth stages this causes true growth
In adults this maintains muscle mass
Factors effecting synthesis and release of GH
GHRH causing release and GHIH (somatostatin) have already been mentioned, as well as feedback on GH +/- somatomedins is considered.
Also influenced by:
- Thyroid hormones - low TH = low growth
- Glucocorticoids - excess inhibits growth
- Sex steroids - synergistic important for growth spurt but iltimately promote close of epiphyses
- Insulin - deficiency = low growth while excess = higher growth
Excess GH
- GH hypersecretion in children = gigantism. Body proportions are normal
- GH hypersecretion in adults = acromegaly. The epiphyses are closed so cant get taller but patient has enlarged extremities (bones in hands, feet and face). Thickening soft tissue causes malformed or coarse facial features such as enlarge tongue, thickened lips or deep voice. Normally occurs due to pituitary tumor.
GH deficiency
- Hypo secretion in adult = no major symptoms
- Hyposecretion in children = pituitary dwarfism. Normally lack GH or GHRH, leads to short build and poor muscle development with excess subcutaneous fat (may appear normal in adults). If found early then replacement therapy can be used.
Calcium throughout the body
99% of calcium is in bones and teeth.
0.9% intracellular
0.1% extracellular - half of this is bound to plasma protein and the other half is free making it biologically active. This needs to be constantly maintained.
Most ingested Ca is not absorbed by GIT but lost in faeces.
Calcium regulation
Depends on hormonal control
Concerned with the balance maintained between ECF and three body compartments (GIT, Kidney and Bone)
Note the exchangeable and stable pool of calcium in bone. Cane be moved between suing resorption and deposition.
Three main hormones regulate Ca metabolism:
- Parathyroid hormone (PTH)
- Vitamin D
- Calcitonin
- Others include steroids, TH, GH and local factors
Acute and chronic control of calcium
Acute control:
- Maintain constant free Ca concentration in plasma
- Mostly by rapid exchange between bone and ECF
Chronic control:
- Maintain total Ca level in body long term
- Adjust GI absorption and urinary excretion
Bone cells
- Osteoblasts - synthesise and secret collagen and promote deposition of CaPO crystal (calcium phosphate)
- Osteoclasts - promote reabsorption
- Osteocytess - role in exchange of calcium between ECF and bone
Bone structure with reference to transfer
Bone fluid between mineralised cells and in the central canal
Bone is CaPO4 crystals
To be absorbed into ECF bone fluid needs to be moved to central canal via Ca pump on osteocyte
This process is much faster when done from the bone fluid rather than the mineralised bone
PTH secretion
Parathyroid glands are 4 small glands on the posterior surface of thyroid gland.
PTH is secreted from chief cells in direct response to changing plasma Ca concentrations. Increased Ca and decreased PO in plasma.
PTH is a peptide with a half life of <20 mins, has actions on bone, kidneys and GIT
PTH functions
Bone:
- Short term - stimulates Ca membrane pump in osteocytes so Ca moves from bone fluid to ECF in central canal
- Long term - stimulates osteoclasts (breakdown) and inhibits osteoblasts (no construction) so CA and PO increases in plasma
Kidney:
- Decreases Ca loss by increasing tubular reabsorption of CA and decreases tubular reabsorption of PO
GIT:
- Indirectly increases Ca and PO by increasing absorption by small intestine through activation of vitamin D3
Vitamin D3 function
- Produced either in the skin or ingested (50/50) and is activated by liver and kidney to vitamin D3
- Promotes absorption of Ca from intestine by increasing its transport across intestinal epithelium
- Promotes absorption of PO4 in intestine
- Increases bone resorption
- Stimulates Ca and PO reabsorption in kidneys
Therefore, maintains Ca and PO overall but is not fine control
Calcitonin function
- Produced in the C cells of the thyroid gland in response to high plasma Ca levels
- Decreases bone reabsorption by effecting osteoclasts
- Decreases CA reabsorption in kidneys
Therefore overall action is to decrease calcium and PO in plasma. Protects against hypercalcemia
Only produced when something is wrong, physiological role
PTH hypersecretion
- Most frequently caused by PTH secreting adenomas (tumors)
- Increased Ca mobilisation from bones causes softening and fractures
- Increased Ca excretion through kidneys causes polyuria (increased urination), polydipsia (increased thirst) and nephrocalcinosis (kidneys stones of calcium)
- Decreased excitability of nerves and muscles leads to weakness, depression and coma
- Hypercalcemia leads to nausea, constipation and increased incidence of peptic ulcers
Bones, stones and grones
PTH hyposecretion
- Most frequently caused by gland destruction, leads to severe hypocalcaemia
- Parathyroid glands are essential for life
- Hypocalcaemia causes increased nerve and muscle excitability
- Sever hypocalcaemia leads to death by asphyxiation via laryngospasm
- Mild hypocalcaemia causes cramps, twitches and tingles
Other causes of hypocalcaemia other than PTH hyposecretion
- High demand for Ca in pregnancy/lactation - causes tetany or paralysis
- Lack of vitamin D/sunlight - causes rickets in children and osteomalacia in adults
- Change in blood pH - alkalosis
- Pancreatitis
What is OP
Reduction in the mass (density) of bone and impairment of integrity of spongy bone
Weaker bone is prone to fracture
Progression from osteopenia to osteoporosis
Adolescent disease with a geriatric onset
- Bone mass gain is influence by genetic factors, physical activity, Ca intake and hormones - especially during growth phases
- Decreased bone mass and structural disruption leads to fractures even after minimal trauma
Risk factors for OP
- Poor nutrition (especially low calcium)
- Low oestrogen levels, early menopause or loss of normal menstruation
- Inadequate sunlight exposure (vitamin D deficiency)
- Smoking, excessive alcohol and caffeine intake
- Sedentary lifestyle
- Low testosterone
- Corticosteroid use (anti inflammatory)
- Aortic calcifications
Function of Sertoli cells
- Leydig cells cells produces testosterone
- With support from testosterone and FSH maintain tight junctions to create the seminiferous tubules, sperm matures in these tubules
- Nourish germ cells and support spermatogenesis
- Secret androgen binding proteins (ABP)
- Secretes inhibit which inhibits the actions of LH and FSH
- Convert testosterone to DHT or oestradiol which is more potent
Function of Leydig cells
- Produce testosterone and small amounts of other steroids eg oestradiol and dihydrotestosterone (DHT) in response to LH
- Testosterone either actions on adjacent Sertoli cells or is released into the blood and has actions outside testes. Most acts within testes
Androgens and how they’re carried
- Sex hormones such as testosterone or DHT
- Steroid hormones so when moving in blood need to be carried by binding proteins. These are produced in the testes or the liver.
- SHBG is one of the carrier proteins that is produced in liver that is increased by oestrogen, TH cirrhosis and decreased by androgen, glucocorticoid, GH and obesity.
- Once the androgen is free from carrier protein it can bind to androgen receptors on cells and causes its effect.
- Testosterone and DHT are in very small levels within the body (test = 5 ng/ml and DHT = 0.5 ng/ml)
Actions of Androgens
- Sex determination in foetus
- At puberty help with growth spurt and close epiphyses
- Development and maintenance of male secondary sexual characteristics (voice, hair ect)
- Development and maintenance of accessory sex organs and libido
- Anabolic actions, effects on brain and bone
What is metabolism in a general sense
- In a general sense it refers to all of the chemical reactions in the body
- Includes external work (energy used by SKM) and internal work (energy needed to sustain life)
- Basal metabolic rate is the energy needed to sustain bodily function and is determined by thyroid hormones.
- Increase in thyroid hormone will increase BMR and opposite
Thyroid structure and cells that relate to TH
Located over of the trachea
Contains follicles comprised of follicular cells and colloid that produce thyroid hormones T3 and T4 from tyrosine and iodine.
The 3 and 4 are from the number of iodine molecules
Colloid is fluid that has no connection with any other fluid in the body (ECF or ICF) and this is where thyroid hormone is stored. Follicular cells surround colloid.
Basics on TH
TH are amines, lipophilic and are transported in the plasma by carrier proteins meaning there is a balance between bound and free hormones.
Most TH is secreted as T4 which is then converted into T3 in tissues, T3 is four times more potent
Basically every tissue in the body is affected by TH
TH decreases with age and low TH more common for women
Synthesis of TH
- Iodine is actively pumped into the thyroid
- Thyroglobulin produced in the follicular cells and moved into colloid - TGB acts as a skeleton and also allows for storage of the lipophilic molecule.
Stores in colloid until released via lysosome
Release of TH
Hypothalamus release thyrotropin releasing hormone causing anterior pituitary to release thyroid stimulating hormone.
Functions of TH
- Increases basal metabolic rate and therefore heat production
- Increases metabolism by influences fuel metabolism (synthesis and breakdown of protein, fats and carbs)
- Sympathomimetic effect (mimics nervous system) - increases target cell responsiveness to catecholamines (NA/A) meaning it effects cardiac output by increasing HR and contractility
- TH promotes the effect of GH meaning it is permissive for growth and development especially in CNS
Thyroid tumors symptoms and types
There are 4 main types of tumors at the thyroid:
- Papillary thyroid cancer (most common)
- Follicular thyroid cancer
- Medullary thyroid cancer
- Anaplastic thyroid cancer
Symptoms include nodule in the thyroid region, enlarged lymph node, pain in anterior neck or vocal levels.
TH levels can be normal, low or high
Risk factors and treatment for thyroid tumors
Radiation exposure, enlarged thyroid, family history or thyroid disorders are all risk factors
Treatment through surgery, radiation, chemo and may need TH replacement after
Goitre is enlargement of the thyroid gland which may occur in hyper or hypothyroid states
Hyperthyroidisms causes and symptoms
Causes:
- Graves disease (most common)
- Excess TRH, TSH or TH production (from tumor in thyroid, pituitary or hypothalamus)
Symptoms:
- Increased metabolism, excessive sweating, increased appetite with weight loss, muscle weakness, anxiety and palpitations (CV system effected)
- Goitre
Graves disease
It is an autoimmune disease that produce antibodies that mimics thyroid stimulating immunoglobulin (TSI) which activates TSH receptor induce TH release
Risk factors include family history, autoimmune diseases and smoking. More common in females.
Symptoms are the same as normal hyper with exophthalmos (bulging eyes, eye lids cant close )
Treated with radioiodine therapy, anti thyroid medications or thyroid surgery
Primary and secondary causes of hypothyroidism
- Primary
- Thyroid gland failure
- Hashimoto’s thyroiditis (common with low idodine levels)
- Secondary
- Deficiency of TRH (hypothalamus) or TSH (pituitary gland)
- Inadequate supply of iodine
In pregnancy can cause congenital iodine deficiency syndrome in neonates
Symptoms and treatment of hypothyroidism
Symptoms include decreased metabolism, poor cold tolerance, excessive weight gain, fatigue, bradycardia, weal pulse, slow reflexes and mental function, myxoedema (puffy face) and goitre
Diagnosis through blood tests for TSH
Also more common in women
Prevented and treated with salt iodisation (where iodine deficient) or levothyroxine (synthetic TH)
Hashimoto’s thyroiditis
- Autoimmune disease where antibodies attack the thyroid gland
- Caused by combination of genetic and environmental factors
- More common in women, family history of autoimmune disorders
Symptoms and treatment:
- Goitre, decreased metabolism, poor cold tolerance, excessive weight gain, fatigue ect
- Diagnosis - blood tests for TSH, T4 and anti thyroid autoantibodies
- Treatment - Levothyroxine (synthetic TH)
Congenital iodine deficiency syndrome
Hypothyroidism in children
Symptoms include goitre, poor growth, thick skin, hair loss, enlarged tongue, protruding abdomen, delayed bone maturation and puberty, small adult stature, infertility
Cognitive and neurological impairment - cannot talk, stand or walk if severe and if it is mild then learning disabilities, reduced muscle tone and coordination
Prevention and treatment - Iodine supplementation of food, screening pregnant women and neonates. Lifelong administration of TH.
What is stress
State of mental or emotion strain or tension resulting from adverse or demanding circumstances
In physiology terms stress is the bodies response to stressful stimuli - stressors
This response may be acute to a single traumatic event or it can be chronic if the situation persists
What are stressors
Any stimulus which causes a disruption to homeostasis leading to specific behavioural, endocrine and autonomic changes
Stressors are divided into two types:
- Psychological
- Stimuli leading to fear, anxiety or frustration. Excitement is a good example
- The stimuli can be real or imagined, both having a response
- Physical
- Stimuli which may disrupt normal body function, caused either by internal factors or the environment
What is Acute stress and how is severity determined
- Acute stress response is normal and actually a beneficial adaptive response
- Increases focus and alert level whilst providing energy to response and cope with a stressful situation - focus attention and energy on something
- Extent of response dependent on severity of stressor and the individual
- Mild stress - improves mood, creates new memories, encourages creative thinking, promotes neural growth in brain and facilitates problem solving
- Severe stress - cause detachment, reduction in awareness, derealisation, depersonalisation and dissociative amnesia
Chronic stress
- Homeostasis is not able to be maintained when stress is prolonged or persistent
- The body will enter an exhausted state where damage to health can occur along with immune suppression, hypertension, GI disturbances, detrimental psychological effects around anxiety and mental dysfunction whilst also causing social withdrawal.
General adaptation syndrome for stress
This describes the response to stress and explains the stages of the bodies response:
- Alarm - Prepare fight or flight, heightened alert and energy mobilised
- Resistance - stay alert but keep on with normal functioning (adaption), homeostasis maintained
- Exhaustion - resources are depleted causing burnout to set in. Homeostasis cannot be maintained so function impaired causing long term damage
Acute physiological response to stress
- Increased CV function - HR, contractility, vasoconstriction (vasodilatation to muscles)
- Increased resp - RR and TV, bronchodilation
- Liberation of nutrients into the blood meaning increased blood glucose and fatty acids
- Skin - sweating, piloerection
- Sensory - mydriasis (pupil dilation), auditory exclusion, tunnel vision
- Muscle tension and shaking
- Inhibition of GI, contraction of sphincters
- Inhibition of lacriminal gland and salivation
- Relaxation of bladder, inhibition of erection
Coordination of acute stress response
Controlled by the hypothalamus and involves endocrine and sympathetic nervous systems
- Sympathetic
- Adrenalin from adrenal medualla, NA from neurons
- Inhibition of parasympathetic
- Endocrine
- Cortisol and corticosterone from adrenal cortex
- Vasopressin (ADH) from post pituitary - increases water retention for blood volume
- Activation of RAAS which dose same as above
- Insulin and glucagon from pancreases
Layers of the adrenal gland
Broken into the adrenal cortex (outer part) and adrenal medulla
The cortex has 3 layers, makes up 80% of adrenal gland
Cortex produces steroid hormones, takes cholesterol and tunes it into hormones
Medulla produces catecholamines (A and NA)
What is used in adrenal gland for steroid synthesis
cholesterol
Hormones produced in adrenal cortex
Mineralocorticoids - aldosterone
Produced in response to changes in ECF volume pressure and stress (increased pressure = decreased aldosterone)
Promotes water retention in kidneys by increasing Na reabsorption
Androgens - DHEA and androstenedione
Produced in males and females but in small amounts
Glucocorticoids - cortisol and corticosterone
Produced in response to stress, actions include:
- Increases available energy and AAs to allow body to cope with stress
- Increases vascular reactivity meaning vessels respond more to A/NA
- Improve mood and increase alertness
- Stimulates brain function by promoting neural growth in brain leading to improved memory, creative thinking and problem solving
- In chronic stress may be responsible for immune suppression and other health defects.
Adrenal medulla
Part of sympathetic nervous system
- Medullary ‘chromaffin’ cells are modified post ganglionic neurons - modified nerve cells that don’t have an axon.
- Produce the catecholamines in response to direction stimulation by sympathetic pre ganglion neurons from splanchnic nerve
- Hormones are release directly into the blood stream and act on distant tissue
A and NA
- Prepare for fight or flight
- Increases cardiac and resp function while also slowing kidney function, tense muscle and increases sweating
- Vasoconstriction to skin and organ but vasodilation to SKM
- Inhibits parasympathetic NS
- Acts on pancreas to reduces insulin secretion and increase glucagon secretion to cause net increase in blood glucose.
Stress disorders
Occurs when stress response become recurrent in the absence of stressor
- Acute stress disorder
- After 2 days and within 4 weeks or original stress
- Dissociation, re living the event, hyperarousal, avoidance of reminders, impaired social functioning
- Post traumatic stress disorder
- Occurs after 4 weeks of original
- Same symptoms as for ASD
Responses to chronic stress
- Immune suppression through excess glucocorticoid production, increasing risk of infection
- Hypertension (increased fluid) and CV disease - occur due to activation of ADH and RAAS
- Disruption of body weight - loss, obesity or redistribution
- Poor growth in children through suppression of GH production
- Inhibition of parasympathetic can lead to reproductive failure and poor digestion
- Psychological disorders such as anxiety depression, social withdrawal and increased substance abuse
Chronic stress effects on brain
These are driven by cortisol
- Amygdala - irreversible
- Increased emotional memory, response and anxiety
- Hippocampus - reversible
- Loss of explicit memory, depression
- Medial prefrontal cortex - reversible
- Loss of working memory
What is Cushing syndrome
Excess glucocorticoids (cortisol)
- Due to excess ACTH (hormone causing release) often from anterior pituitary tumor or adrenal tumor
- OR excess glucocorticoid administration
Symptoms and treatment for Cushing syndrome
Symptoms:
- Protein depletion → muscle weakness
- Poor healing and immunodeficiency
- Thin skin making it prone to damage, hirsutism (hairy)
- Obesity and body fat redistribution
- Type 2 diabetes, either get it or it becomes worse
- Buffalo hump
Treatment:
- Aim to reduce cortisol levels
- Surgery, radiotherapy or chemo is tumor. Medication. Diabetes management
- Decrease cortisol production in adrenal glands
- Decrease ACTH production in anterior pituitary
- Block effect of cortisol on tissues
What is Addison’s disease
Chronic failure of adrenal cortex meaning certain hormones are no longer produced
Symptoms and treatment for Addison’s disease
Symptoms:
- Electrolyte imbalance - loss of aldosterone
- Dehydration and hypotension due to decrease fluid retention
- Reduction in stress response
- Addisonian crisis - hyperglycaemia causes coma or death
- Loss of vascular reactivity
- Melanin pigmentation - loss of neg feedback causes increased production of ACTH (due to loss of cortisol) and melanocyte stimulating hormone
Treatment:
- Replace hormones → glucocorticoids, aldosterone
- Management of diet, stress and exercise to prevent crisis
Adrenogenital syndrome
Excess levels of androgens due to enzyme deficiency (21-hydroxylase) or adrenal tumor
Symptoms:
- Pre pubertal females - external genitalia appear male
- Pre pubertal males - opposite
- Adult females - virile characteristics (male), hirsutism, deep voice, increased muscularity, amenorrhea (not menstruating → infertility)
- Adult males - no effect
Treated through replacement of glucocorticoids and aldosterone
What is a stressor -> Physical vs Psychological
Any stimulus which causes a disruption to homeostasis leading to specific behavioural, endocrine and autonomic changes
Stressors are divided into two types:
- Psychological
- Stimuli leading to fear, anxiety or frustration. Excitement is a good example
- The stimuli can be real or imagined, both having a response
- Physical
- Stimuli which may disrupt normal body function, caused either by internal factors or the environment
Acute stress
- Acute stress response is normal and actually a beneficial adaptive response
- Increases focus and alert level whilst providing energy to response and cope with a stressful situation - focus attention and energy on something
- Extent of response dependent on severity of stressor and the individual
- Mild stress - improves mood, creates new memories, encourages creative thinking, promotes neural growth in brain and facilitates problem solving
- Severe stress - cause detachment, reduction in awareness, derealisation, depersonalisation and dissociative amnesia
Chronic stress
- Homeostasis is not able to be maintained when stress is prolonged or persistent
- The body will enter an exhausted state where damage to health can occur along with immune suppression, hypertension, GI disturbances, detrimental psychological effects around anxiety and mental dysfunction whilst also causing social withdrawal.
General adaptation syndrome and its 3 stages
This describes the response to stress and explains the stages of the bodies response:
- Alarm - Prepare fight or flight, heightened alert and energy mobilised
- Resistance - stay alert but keep on with normal functioning (adaption), homeostasis maintained
- Exhaustion - resources are depleted causing burnout to set in. Homeostasis cannot be maintained so function impaired causing long term damage
Physiological response to acute stress
- Increased CV function - HR, contractility, vasoconstriction (vasodilatation to muscles)
- Increased resp - RR and TV, bronchodilation
- Liberation of nutrients into the blood meaning increased blood glucose and fatty acids
- Skin - sweating, piloerection
- Sensory - mydriasis (pupil dilation), auditory exclusion, tunnel vision
- Muscle tension and shaking
- Inhibition of GI, contraction of sphincters
- Inhibition of lacriminal gland and salivation
- Relaxation of bladder, inhibition of erection
Coordination of stress between sympathetic nervous system and endocrine
Controlled by the hypothalamus and involves endocrine and sympathetic nervous systems
- Sympathetic
- Adrenalin from adrenal medualla, NA from neurons
- Inhibition of parasympathetic
- Endocrine
- Cortisol and corticosterone from adrenal cortex
- Vasopressin (ADH) from post pituitary - increases water retention for blood volume
- Activation of RAAS which dose same as above
- Insulin and glucagon from pancreases
Main chemical in steroid synthesis
Cholesterol
Layers of adrenal cortex and basic functions
Broken into the adrenal cortex (outer part) and adrenal medulla
The cortex has 3 layers, makes up 80% of adrenal gland
Cortex produces steroid hormones, takes cholesterol and tunes it into hormones
Medulla produces catecholamines (A and NA)
Steroid hormones procured in adrenal cortex
Mineralocorticoids - aldosterone
Androgens - DHEA and androstenedione
Glucocorticoids - cortisol and corticosterone
Glucocorticoids - cortisol and corticosterone functions
Produced in response to stress, actions include:
- Increases available energy and AAs to allow body to cope with stress
- Increases vascular reactivity meaning vessels respond more to A/NA
- Improve mood and increase alertness
- Stimulates brain function by promoting neural growth in brain leading to improved memory, creative thinking and problem solving
- In chronic stress may be responsible for immune suppression and other health defects.
Mineralocorticoids - aldosterone functions
Produced in response to changes in ECF volume pressure and stress (increased pressure = decreased aldosterone)
Promotes water retention in kidneys by increasing Na reabsorption
A and NA functions
- Prepare for fight or flight
- Increases cardiac and resp function while also slowing kidney function, tense muscle and increases sweating
- Vasoconstriction to skin and organ but vasodilation to SKM
- Inhibits parasympathetic NS
- Acts on pancreas to reduces insulin secretion and increase glucagon secretion to cause net increase in blood glucose.
Adrenal medulla when they produce, and how are hormones released?
- Medullary ‘chromaffin’ cells are modified post ganglionic neurons - modified nerve cells that don’t have an axon.
- Produce the catecholamines in response to direction stimulation by sympathetic pre ganglion neurons from splanchnic nerve
- Hormones are release directly into the blood stream and act on distant tissue
When do acture and PTSD occur
Occurs when stress response become recurrent in the absence of stressor
- Acute stress disorder
- After 2 days and within 4 weeks or original stress
- Dissociation, re living the event, hyperarousal, avoidance of reminders, impaired social functioning
- Post traumatic stress disorder
- Occurs after 4 weeks of original
- Same symptoms as for ASD
Responses to chronic stress
- Immune suppression through excess glucocorticoid production, increasing risk of infection
- Hypertension (increased fluid) and CV disease - occur due to activation of ADH and RAAS
- Disruption of body weight - loss, obesity or redistribution
- Poor growth in children through suppression of GH production
- Inhibition of parasympathetic can lead to reproductive failure and poor digestion
- Psychological disorders such as anxiety depression, social withdrawal and increased substance abuse
How does the hypothalamus cause a stress response at the adrenal cortex and medulla
The sympathetic nervous system can act directly on the adrenal medulla to elicit a response causing adrenalin.
The hypothalamus can release CRH which will stimulate ACTH to be released from ant pituitary resulting in Cortisol release at adrenal cortex
What is Phenotopic sex and how is it determined
Determined by the presence of musculising hormones
In males the presence of testosteron causes Woffian ucts to convert into sexual organs. While the presence of Wallarian inhibitory factor causes their degeneration.
In females the lack of testosterone causes degeneration of woffian ducts. Lack of mullerian inhibitory factors causes them to develop into female sexual organs.
What occurs in puberty
Increase in GnRP triggers production of gonadotrophins (LH and FSH) from anterior pituitary.
These have different effects in males and females.
LH and FSH function in males
LH produce leydig cell which then produces testosterone
FSh and test -> sertolie cell -> spermatogenesis
Inhibin can selectively inhibit LH of FSH
LH and FSH in females before and after ovulation
LH and FSH are produced in a cyclic pattern in response to GnRH hormone pulses. They both act on the developing follicle causing it to produce oestrogen. An LH surge then causes ovulation of the follicle where it now becomes the CL. The CL produces progesterone and LH help to stimulate the growth of the CL.
Breast development
In conception progesterone levels dont decline because the CL desnt undergo luteolysis
The embryo produces hCG for 8 days after conception which has LH like activity and prevents breakdown.
Placenta will form which produces progesterone as well as hPC for breast development
What is CRH
Released by baby to trigger birth
Why do breast not lactate until after birth
Increased levels of progesterone and oestrogen prevent lactation, once the placenta is lost so too are these hormones.
How dose the hypothalamus cause the adrenal cortex to produce cortisol
Increased amounts of CRH release from the hypothalamus causes the anterior pituitary to produce increased ACTH causing the adrenal cortex to produce cortisol
Site of action for LH and FSH in developing follicle
LH acts on thecal cells to convert cholesterol to androgen
FSH act on granulosa cells to convert androgen to estrogen
Estrogen and LH surge relationship
LH surge follows rise in estrogone in follicle
