Endocrinology chapter 14
Terms in this set (346)
What is an endocrine gland?
A group of cells which secrete "messenger" molecules directly into the bloodstream
What is endocrinology?
study of hormones and endocrine glands
What is a hormone?
The bioactive "messenger" molecule secreted by an endocrine gland into the blood
What is secretin and what does it do?
It is a hormone that is released when chyme arrives in the duodenum and is too acidic.
It stimulates the secretion of Bicarbonate (HCO3-)
relates to hormone's action on target cells at a distance from source
relates to hormone's action on nearby target cells
relates to hormone having an effect on its own immediate source
Compare and contrast the endocrine system and the nervous system
-Release of chemical hormone into blood
-Effect can be on many target cells
-Effect will take place over a relatively long time-span
-Release of chemical neurotransmitter across synapse
-Effect is restricted to those target cells actually innervated
-Effect is generated and lasts milliseconds
What are the three hormone classifications?
What is a pro-hormone?
They are the initial step of hormones. Prohormones are usually cleaved to generate the hormone.
Describe the steps for the synthesis of a polypeptide hormone
1/ The blood supply provides amino acids which can be used to synthesize the hormone.
2/Chosen pro-hormone is transcribed from the DNA and the mRNA moves into the cytoplasm and binds to the rER
3/ In the ribosome is where it is translated to produce the pro-hormone
4/ Pro-hormone is then endocytosed into the Golgi
5/ Golgi adds enzymes to cleave the pro-hormone which in turn leads to generation of the active hormone.
6/ Vesicle filled with the active hormone accumulates near the cell surface and is ready to be released into the blood via exocytosis once a signal arrives.
What is the precurosor for every steroid hormone?
Where are most of the steroid hormones produced?
Adrenal glands or the Gonads
How is cholesterol transported into the cell and stored?
It is delivered into the cell in the form of LDLs and then stored as Fatty Acid Esters.
Where are steroid hormones made?
Describe the process of steroid hormone synthesis
1/LDLs are delivered into the cells and stored as Fatty Acid Esters
2/Esterase enzymes break down the fatty acid esters to liberate cholesterol
3/Cholesterol gets into the mitochondria via StAR proteins. (this is the rate determining step - conc of StAR affects conc of hormone produced)
4/When cholesterol enters the mitochondria, there are many enzymes which allows the step-wise conversion of the cholesterol into the steroid hormone of choice
5/ THESE ENZYMES DETERMINE WHICH STEROID HORMONE IS PRODUCED AND VARY IN CELLS
How are amino acids transported from blood capillary to cell?
Specific amino acid transporters, not simple difussion
Where is the anterior pituitary gland located?
below the hypothalamus
What is the role of the Golgi apparatus in production of protein hormones?
Golgi packages and modifies using proteolytic enzymes to generate mature active hormone.
How are hormones released?
Via exocytosis after a signal is achieved
Protein polypeptide life in blood ?
Short as it is quickly metabolised
Where are the adrenal glands located?
on top of each kidney
What protein drives cholesterol into the mitochondria?
Are steroid hormones stored in cells?
No because they can freely diffuse through biological membranes. They remain in the blood stream.
Where are protein hormones stored?
In the cells within vesicles
How are steroid hormones transported in the blood?
bound to plasma proteins eg. albumin binds to most (low affinity) however some bind to specific proteins (high affinity)
However there is a small amount of free steroid hormone in the blood.
What is Albumin?
It is a plasma protein that is present in large amounts. It can bind to a large amount of most steroid hormone as there isn't a very specific interaction.
If a steroid hormone is heavily plasma protein bound, can it still access
How are protein hormones transported in the blood?
Protein hormones travel unbound. Others are stored in cell
Protein hormones travel unbound in the blood. What effect does this have on them?
They are sensitive to enzymatic breakdown and as a result have a very short half life of only a few minutes.
Explain the equilibrium between free hormones and protein bound hormone levels
At any given point, you have a certain amount of hormone and plasma protein and a lot of protein bound hormone. This Dynamic equilibrium can be shifted.
What happens if there is an increase in the uptake of steroid hormones by the tissue?
Stimulates endocrine cells to produce more of the steroid hormone.
Conc of hormone decrease causing a shift in the equilibrium. To balance this shift protein bound hormones release into the blood. This ensures there is a supply of hormone and essentially increases the amount of hormone available for the tissue to take in.
What happens if there is a rise in plasma protein levels (in terms of steroid hormones)
Give an example of when this occurs
Stimulates endocrine cells to produce more of the steroid hormone.
More protein means more of it is going to bind to steroid hormone therefore reducing the amount of free hormone present. Hence endocrine cells produce more steroid hormone to balance.
Occurs during pregnancy with cortisol
Describe the process of protein hormone signaling.
Protein hormones bind to the specific hormone receptor (as they are not lipid soluble and cannot simply diffuse in). The receptors are usually G-protein coupled receptors. They trigger reactions in the cell .
eg. ACTH binds to ACTH receptors in the adrenal gland. This activates Adenylate cyclase which causes an increase in production of cAMP from ATP. Which inturn activates protein kinase A. This phosphorylates Esterase and StAR protein which allows for the production of steroid hormones.
Describe the process of steroid hormone signaling
Only free steroid hormones can get into cells. They are very lipid soluble and can diffuse into the membranes. They bind to intracellular receptors. They then translocate to the nucleus and have a massive effect on DNA transcription etc
(they do this by changing the protein machinery within the cell)
What is negative feedback?
A system to keep body conditions within a set normal range by reversing any upward or downward shift
Describe the example of negative feedback in terms of ATCH and Cortisol
1/ Anterior pituitary is stimulated by stress.
2/ protein hormone ACTH is released
3/ ACTH acts on the adrenal gland to increase cortisol production
4/ cortisol enters the bloodstream and carries out its function to decrease stress
5/ cortisol returns to the anterior pituitary and switches ACTH off (end consequence is that the cortisol production is also switched off)
What is positive feedback?
Name an example of it occurring in the body
A given action promotes more of the same action until the stimulus is removed
LH and oestrogen
What are the two lobes of the pituitary gland?
Anterior lobe (adenohypophysis) and posterior lobe (neurohypophysis
What is the name of the bone lined cavity in which the pituitary gland lies?
Why is the sella turcica important from a clinical point of view?
If there is a tumour it will be constrained by the walls of the bone cavity.
What is the easiest way of distinguishing front from back in the brain?
Back- mammillary body
What is the posterior lobe (neurohypophysis) made up off?
Nerve axons derived from the base of the brain.
Which lobe in the pituitary gland requires a blood supply
Describe the hypothalamic- hypophysial portal circulation in the anterior pituitary gland.
-It starts with blood arriving in the SUPERIOR hypophyseal artery and this enters a capillary network in the median eminence.
-From this capillary network, blood drains to a second capillary network in the anterior pituitary - a portal network.
-A portal network is where blood from the systemic circulation drains from one capillary network to another before returning to the heart.
-From the secondary capillary system, blood would flow out into the venous system via the cavernous sinus.
-This system is critical for control of anterior pituitary function.
Describe the hypothalamo-adenohypophysial axis
1/ Hypothalamic neurosecretion released into the hypothalamo-hypophysial portal system. These activated neurons release chemicals from their nerve ending (they are not neurotransmitters but are hormones as they are directly released into the capillaries)
2/ The portal system carries these chemicals to their target cells in the anterior pituitary
3/The chemicals bind to the receptors and stimulate the release of anterior pituitary hormones into the circulation
What is the median eminence?
An area that lies between the top of the pituitary stalk and hypothalamus
What controls the release of hormones by the anterior pituitary ?
hypothalamus through hormones which are released by neurones which originate in the hypothalamus
What do the following ADENOHYPOPHYSIAL CELLS produce?:
What is the difference between protein and polypeptides?
Polypeptides tend to be smaller
What types of hormones are produced in the anterior lobe (ADENOHYPOPHYSIAL) and give one example of each.
1/proteins eg. Somatitiophin (growth hormone)
2/ Glycoproteins consisting of alpha and beta subunits eg. Thyroid stimulating hormone TSH
3/ Polypeptide eg ATCH (Adrenocorticotrophic)
How do hypothalamic hormones control adenohypophysial hormones?
There are two hypothalamic hormones that control each adenohypophysial hormone. One which stimulates release and one which inhibits it.
What does it mean that some hypothalamic hormones are dominant over their counterparts? Examples?
Some hormones can mask the affects of their counterpart. for example Somatroptophin releasing hormone is dominant over somatostatin and Dopamine is dominant over thyrotrophin releasing hormone.
What are the target cells for the following hormones?
Describe the action of producing IGF
1/ somatotrophin binds to receptors on the hepatocytes and stimulates the production of hormone from these cells
2/ The molecules produced used to be called somatomedins but are now called insulin-like growth factor (IGF) 1 and 2
Somatotrophin works in two ways. Pls explain
1/ it works directly by binding to somatotrophin receptors in general cells in the body
2/stimulates hepatocytes to produce IGF 1
What are the metabolic affects of somatotrophin?
Stimulation of amino acid transport into cells and protein synthesis
Stimulation of lipolysis leading to increased fatty acid production
Increased cartilaginous growth and somatic cell growth
Decreased glucose utilisation resulting in increased blood glucose concentration.
What stimulates the release of somatotrophin?
-HYPOGLYCEMIA: as the ultimate effect of growth hormone is to increase the blood glucose levels
-Certain glucogenic amino acids (as by stimulating somatotrophin release you increase amino acid movement into the cells and increase protein synthesis).
What inhibits the release of somatotrophin?
Direct- IGF 1 back to the pituitary
Indirect-IGF 1 back to the hypothalamus (Somatotrophin also has its own negative feedback effects to they hypothalamus)
What are the affects of prolactin?
-inhibits LH release (to prevent periods so the mother does not become pregnant again. Important as prolactin is rebased in high amounts when the baby is sucking)
- reduces sexual behaviour
-Effects immune system
What stimulates prolactin release?
suckling by baby (as there are tactile nerve pathways in the nipple which go back to the hypothalamus)
What two hypothalamic hormones control prolactin release? What are their roles?
-Thyrotrophin releasing hormone
What is the anterior pituitary glad made up off?
What is the posterior pituitary cell made off?
Describe the positioning of the nerves in the neurohypophysis
The cell bodies are in the hypothalamus however their nerve axons pass down through the pituitary stalk into the neurohypophysis
What is the hypothalamic nuclei?
A collection of cell bodies which send their axons to a particular place
What are the two main groups of cell bodies in the Hypothalamo-neurohypohysial system?
Paraventricular nuclei and the supraoptic nuclei.
What are the two main types of neurones in the Hypothalamo-neurohypohysial system?
Magnocellular and parvocellular
where do most magnocellular neurones terminate?
Neurohypophysis (posterior lobe)
Contrast Magnocellular and parvocellular neurones.
Magnocellular: large and originate in the Supraoptic and paraventricular neuclei but terminate in the neurohypophysis
Parvocellualar neurones: average sized and originate in the paraventricular nuclei but terminate in the median eminence (or other parts of the brain)
What is the role of the magnocellular neurones?
They release neurosecretions (hormones) into the neurohypophysis ((posterior lobe))
What types of neurones are supraoptic neurones?
Supraoptic neurones are magnocellular and have herring bodies. What are herring bodies?
They are specific to magnocellular neurones and are areas alone the axon where neurosecretions can be stored.
What types of neurones are paraventricular neurones composed of?
Magnoceullular and Parvocellular
what does AVP stand for?
How is Arginine Vasopressin produced. Include the by products.
Prohormone is broken down into arginine vasopressin, neurophysin (large protein ) and glycopeptide.
How is Oxytocin produced. Include the by products.
Prohormone is broken down into Oxytocin and neurophysin.
Compare and contrast oxytocin and AVP (arginine vasopressin)
-Both initially synthesised as prohormones
-AVP has phenylalanine and arginine instead of isoleucine and leucine
-When the pro-hormone is cleaved, the AVP prohormone produces glycopeptide but oxycontin doesn't
What roles does Vasopressin have?
1/ Stimulates water reabsorption by the principal cells
2/ Powerful vasoconstrictor
3/ works with CRH to control release of corticotrophin
What are the two groups of vasopressin receptors? What are the subgroups and where are they found + roles?
- V1a: found in vasculature in the brain (most important)
-V1b: Found in adenohypophysial cells (Corticotrophs (ACTH production))
V2: Associated with kidney collecting ducts and are responsible for clotting factor production
Explain how Vasopressin works in principal cells
1/Vasopressin binds to V2 receptors in principal cells and activates adenylate cyclase
2/ adenylate cyclase converts ATP to cAMP
3/ cAMP activates protein kinase A which stimulates the synthesis of Aquaporin 2 molecules
4/ The aquaporins accumulate to form aggraphores
5/ Under the influence of vasopressin, they migrate to the apical membrane and fuse with the membrane allowing water to flow through via osmosis
What are two stimuli which result in vasopressin release? and what detects them?
Dehydration (osmoreceptors located outside the blood brain barrier detection rise in plasma osmolarity)
Fall in blood pressure (Baroreceptors are stimulated by the increase in the blood pressure. SO when there is a reduction blood pressure baroreceptor signals drop so it removes tonic inhibition of vasopressin release)
What are the main target cells of oxytocin?
Myometrial cells in the uterus during child birth
Myoepithelial cells in the breast during lactation
What is oxytocin?
a hormone released by the pituitary gland that causes increased contraction of the uterus during labor and stimulates the ejection of milk into the ducts of the breasts.
Describe the neuroendocrine reflex arc of milk ejection
What is polydipsia?
excessive thirst due to lack of vasopressin (central diabetes insipidus) or due to tissue insensitivity (nephrogenic diabetes insipidus)
What is polyuria?
excessive urination due to lack of vasopressin (central diabetes insipidus) or due to tissue insensitivity (nephrogenic diabetes insipidus)
What is the most common cause of loss of sight, amputation and renal intervention in the UK
What is hypoglycemia?
low blood sugar
What is a risk of administering too much insulin?
What are the 4 hormones which increase glucose in the blood
What is Type 1 DM?
Elevated glucose where insulin is required to prevent ketoacidosis
What is type 2 DM?
T2DM is more common and is a considerable health burden. It is defined in terms of glucose but is also related to hypertension and dyslipidaemia. OBESITY IS NOT THE CAUSE OF IT but can trigger it.
What are some complications of diabetes?
What is MODY?
maturity onset diabetes of the young
Very rare, do no require insulin to prevent ketoacidosis but still develops quite young. It is due to single gene mutations.
What happens if the glucose concentration falls below normal 4-5mM
Hypoglycaemia. This results in impaired brain function. This is because the brain relies almost solely on glucose.
Hypoglycemia occurs when there is an imbalance between.....
diet, exercise and insulin
What hormones increase glucose levels?
Glucagon, Catecholamines, Somatotrophin and cortisol
what is paracrine control?
Hormone is secreted from one cell and acts on adjacent cells
What are the role of gap junctions?
Allow small molecules to pass directly between cells
What are the role of tight junctions in the islet of langerhans?
Form small intercellular spaces where fluid can collect
In the islets of langerhans what do the alpha, beta, and delta cells produce?
Alpha cells: glucagon
Beta cells: Insulin
Delta cells: Somatostatin
What is the role of glucagon?
increases blood glucose
What is the role of somatostatin?
inhibits insulin and glucagon secretion
What are the effects of insulin?
-Increased glucose transport into cells via GLUT4
-Increased amino acid
transport and increased
What stimulates beta-cells to function(release insulin)?
-certain amino acids
-parasympathetic activity (via beta-receptors)
-Certain gastrointestinal hormones (important as before the food we eat even affects the gut we are producing insulin)
What inhibits beta-cells to function (release insulin)?
-sympathetic activity (via beta-receptors)
What are the effects of glucagon?
-Increased hepatic glycogenolysis
-Increased lipolysis --> Increased gluconeogenesis
-increased amino acid transport into liver --> increased glucoeogenesis.
All this increases blood glucose
What is glucokinase?
alternative form of hexokinase, which is used to convert glucose into glucose-6-phosphate.
It is involved in the rate determining step that regulates insulin secretion
What is insulin?
a protein hormone
How is insulin and c-peptide related?
The c-peptide is used to connect both parts of proinsulin protein to produce insulin. It is produced in equimolar amounts.
How can C-peptide be used clinically?
Due insulins short half life, C-peptide is used to measure the concentration of insulin in the body.
Describe the process of insulin secretion by beta cells
1/ Glucose enters through Glucose transporter 2 (Glut 2)
2/ The ATP produced blocks the ATP sensitive potassium channels
3/ This leads to the opening of voltage dependent calcium channels
4/ Calcium rushes into the beta cell and insulin is secreted
What is the incretin effect?
Food stimulates more insulin secretion if given orally rather than intravenously.
What is GLP-1?
Glucagon like peptide-1 (GLP-1): Secreted from L-cells of the ileum and colon in response to nutrients in gut.
It stimulates insulin secretion by B-cells of the pancreas and suppresses glucagon.
Has a short half life due to rapid degradation. It also increases satiety (feeling of fullness).
Describe the structure of an insulin receptor
1/The alpha subunits recognise the shape of insulin
2/ insulin causes a conformational change the beta subunits
What affect does insulin have on glucose?
-Increase muscle uptake
What affect does insulin have on proteins
-Decrease proteolysis and increase of protein synthesis
What affect does insulin have on lipids?
Decrease lipolysis and decrease ketogenesis
What transporter is responsible for uptake of glucose through an insulin response?
Where is glycogen stored?
liver and muscles
What is glycogen?
Short term storage form of glucose
What affect does insulin and glucagon have on the liver?
- Insulin stimulates protein synthesis therefore gluconeogenic amino acids are being used to make proteins rather than glucose via gluconeogenesis.
-Glucagon does the opposite
What is gluconeogenesis?
The formation of glucose by non-glucose precursors.
Proteins and fats.
what affect does insulin have on adipocytes?
Promotes formation of triglyceride and storage of fat and inhibits lipolysis.
IN THE BLOOD HOWEVER it stimulates the lipolysis to break down fats so it can enter the small adipocytes
How does the liver use glycerol coming from adipocytes and food?
Glycerol is used to make triglycerides
Glycerol also can be used to make glucose (a form of gluconeogenesis)
What does HGO stand for?
Hepatic gluconeogenesis output.
What does the brain use as an energy source?
Glucose and ketone bodies. NOT FATTY ACIDS
What is glycogenolysis?
breakdown of glycogen to glucose
What effects does insulin and glucagon have on glycogenolysis?
insulin inhibits and glucagon promotes
What are ketone bodies?
They are three water soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction. The three molecules are Acetone, Acetoacetic acid and BETA- Hydroxybutryic acid
How does Glucagon and insulin affect ketone body synthesis in the liver?
Glucagon promotes the conversion of fatty acyl coA otolaryngologists ketone bodies
Insulin inhibits the conversion of fatty acyl coA otolaryngologists ketone bodies
What occurs during the fasted state?
-Increase in proteolysis
-Increase in lipolysis
-Increase in HGO (hepatic glucose output) from glycogen and gluconeogenesis
-Muscle to use lipid
-Brain to use glucose, later ketones
-Increased ketogenesis when very prolonged
What occurs during the fed state?
-stop HGO (hepatic glucose output)
-Increased protein synthesis
What is T1DM?
Type 1 diabetes mellitus. It is absolute insulin deficiency
How does T1DM present itself?
-Proteolysis with weight loss
-Glycosuria with osmotic symptoms (polyuria and polydipsia)
-Ketonuria (the excretion of abnormally large amounts of ketone bodies in the urine)
What are some of the metabolic changes associated with insulin induced hypoglycaemia.
- Increase in insulin so glucose enters the muscle
-increase in glucagon so HGO increases later with glycogenolysis and gluconeogenesis
What is insulin resistance?
It is when the insulin and receptor is normal however it does not have the same post receptor effect. (ie the body tissue does not respond to the insulin)
How does T2DM present?
-Less osmotic symptoms
What is the underlying cause of T2DM
How many lobes does the thyroid gland have?
Describe the anatomy of the thyroid gland
Located onto of the trachea
Has an isthmus ( connective tissue capsule that connects the two lobes of the thyroid) and a pyramid( the bit of tissue on the top of the isthmus which is present in some people) between the lobes
Colloid is the substance found inside the gland which is surrounded by follicular cells. Between the follicular cells are parafolicular cells.
What is the isthmus?
a connective tissue capsule that connects the two lobes of the thyroid
What is the pyarmid?
the bit of tissue on the top of the isthmus which is present in some people (important clinically because a thyroid tumour could be in the pyramid) located between the glands
What are follicular cells?
simple cuboidal epithelium that lines follicles
What are colloids?
proteinaceous substance found inside the follicles
What are parafollicular cells?
Between the follicles, lying in small nests, are the parafollicular cells that secrete the hormone calcitonin.
How is iodine pumped into the colloid from the blood
1/ When TSH binds to the receptor, it stimulates the iodine pump to pump iodide into the cell (from the blood) and then iodide is pumped out of the cell via the pendrin pumps into the colloid
What affects does TSH have on follicular cells and the production of T3 and T4
1/ TSH stimulates pumping of iodide into the colloid
2/ TSH stimulates production of thyroglobulin and transport into colloid (where it remain associated with apical membrane )
3/TSH then Stimulates TPO enzyme (thyroid peroxidase ) which converts iodide into iodine which can iodize thyroglobulin which allows for the production of T3 (triiodothyronine) and T4 (tetraiodothyronine) through coupling reaction
4/ TSH then stimulates Lysosomes to move towards the apical membrane which uptakes T3 and T4 and then transports them to the basolateral membrane where it is released into the blood
What is another word for tetraiodothyronine?
How is iodothyronine transported in the blood?
Mostly bound to plasma proteins
-Thyroxine-binding globulin -TGB (70-80%) (Specific)
-Albumin (10-15%)(loosely bound)
Only 0.05% of T4 and 0.5% of T3 is unbound and this is the bioactive component.
What is the main hormone product of the thyroid gland?
What happens to Thyroxine in target tissues and why? (2 possibilities)
The T4 is deiodinated to T3 as it is the more active form.
It can also be deiodinated to rT3 (reverse) but this is only when we want reduced metabolism as rT3 is inactive
What is the mechanism of action of iodothyronines?
1/iodothyronines enter the target cell readily so interact with intracellular receptors.
2/ This results in the nucleus releasing new proteins
3/the receptor also stimulates metabolic activity hence has an affect on mitochondria.
What are the roles of thyroxine?
-Fetal growth & development
-Increase Basal metabolic rate
-Increase metabolism of protiens carbs and fat
What is the latent period and half life of T3 and T4
T3: ~ 12h
T4: ~ 72h
T4 around 7-9 days
T3 around 2 days
What increases iodothyronine production?
Thyroid releasing hormone
What decreases iodothyronine production?
What is the parathyroid gland?
The parathyroid gland is a small endocrine gland that is found on the posterior surface of the thyroid gland.
Humans usually have four parathyroid glands. These glands are responsible for making and secreting parathyroid hormone and are involved in control of calcium
Draw the thyroid gland
What is the origin of the thyroid gland?
Back of the tongue
What is the mass of the thyroid gland?
What are the dimension s
which lobe of thyroid is larger?
right by 25%
What happens if you damage the recurrent laryngeal nerve?
Change in voice
What glands are found embedded in the thyroid?
What is thyroid agenesis?
Complete absence of the thyroid
What are there problems that can occur with thyroid development.
What is incomplete descent? (in relation to thyroid)
It is when the thyroid does not descend to the correct point in the neck. May be located at base of tongue to trachea
What is thyroglossal cyst?
It is when segment of duct persists and presents as a lump years later
What is cretinism?
Cretinism is a condition of irreversible mental growth due to untreated congenital deficiency due to lack of thyroxin.
What are some of the features of cretinism?
IQ is much lower than normal and there is stunted growth
What are some measures being taken to prevent cretinism?
All babies have a heel prick for a blood test for thyroid function (measuring TSH) at the same time as the Guthrie test (for phenylketonuria) at 5-10 days of age.
If TSH is abnormally high then thyroxine is immediately given
Where is thyroxine synthesised?
Thyroid follicular cell
Draw a thyroid follicle
Thyroglobulin vs. Thyroxine Binding Globulin
Thyroglobulin is iodinated to form thyroxine.
Thyroxine binding globulin is a protein which binds to thyroxine/other thyroid hormones- inactive until un bound
What is the role of the thyroid gland?
Normally responsible for the synthesis,storage and secretion of thyroid hormones which regulate growth, development and metabolic rate
Which of the two real genders is thyroid disease more common?
What is primary hypothyroidism (myxoedema) ?
Thyroid gland itself stops working resulting a decline in Thyroxine levels and increase in TSH levels
What is the HPT
Draw the HPT axis
THe hypothalamo-pituitary-thyroidal axis is essentially a route.
Thyroxine will have a direct negative feedback effect on the pituitary to inhibit production of more TSH and inhibits the hypothalamus to produce TRH
What are some features of primary hypothyroidism ?
-Depression and tiredness
-Weight gain with reduces appetite
How do you treat hypothyroidism?
-Thyroid hormone replacement usually just a tablet
What if you don't treat primary hypothyroidism?
What is hyperthyroidism?
overactive thyroid producing too ,much thyroxine
-raised basal metabolic rate
-Burn calories and lose wight
-TSH levels fall to zero
What causes hyperthyroidism?
Graves disease (whole gland is smoothly enlarged and the whole gland is overactive)
It is an autoimmune disease where antibodies bind to and stimulate the TSH receptor in the thyroid causing the thyroid gland to be overactive.
What are some of the clinical features of hyperthyroidism ?
Myopathy, Mood swings
Feeling hot in all weather
Increased appetite but weight loss
Tremor of hands
Sore eyes, goitre
What is pretibial myxedema?
The swelling (non-pitting) that occurs on the shins of patients with Graves' disease due to growth of soft tissue
Where does the left adrenal vein drain into?
Where does the right adrenal vein drain into?
How many views do each adrenal have?
What is the adrenal cortex composed of (outwards to inwards).
Where are catecholamines produced?
adrenal medulla by chromaffin cells
Where are corticosteroids produced?
Give some examples of corticosteroids produced by the adrenal cortex
(some sex steroids )
Give some examples of Catecholamines produced by the adrenal medulla
What hormones are produced by the Gonads?
Which layer of the cortex produces aldosterone?
Which layers of the cortex produces Cortisol?
what is the precursor for the production of aldosterone?
What are the precursors of androgens?
Which receptor does aldosterone bind to ?
Which receptor does cortisol bind to?
Mineralocorticoid receptor and glucocorticoid receptor
which is present at a higher concentration in the blood, cortisol or aldosterone?
Cortisol conc is 1000 fold more than aldosterone
What enzyme converts cortisol into cortisone (Inactive)?
Why is this relevant to aldosterone?
11b-hydroxysteroid dehydrogenase 2
Aldosterone takes over the role of cortisol in places like the kidney where cortisol is not functioning as it is converted to cortisone.
What do granular cells sense and what do they release ?
-Lowering of renal profusion pressure
-Decreased sodium concentration at the top of the loop of henle
-Increased renal sympathetic activity
How does Renin stimulate the production and release of aldosterone?
1/ Liver breaks down angotensinogen (protien produced in the liver) to Angiotensin 1
2/ ACE enzyme converts Angiotensin 1 to Angiotensin 2
3/Angiotensin 2 stimulates the zona glomerulosa to produce aldosterone
Other than regulating aldosterone release, what other effect does Angiotensin 2 have?
What are the roles of aldosterone?
-Stimulates NA+ reabsorption in the distal convoluted tubule and the collecting duct/
-Stimulates the K+ and H+ secretion in the distal convoluted tubule and the collecting duct (therefore affects pH)
Describe the mechanism of action of aldosterone ?????
1/ Aldosterone is a steroid hormone and passes through the cell membrane and binds to Intracellular receptors
2/ The hormone-receptor complex moves to the nucleus and attaches to the DNA and acts as a transcription factor
3/This produces protein pumps which pump sodium in and potassium out
What is Addison's disease?
Under secretion of the adrenal cortex.
What is Cushing's disease?
Excess cortisol produced by adrenal gland
Draw the adrenal system
Describe the anatomy of the adrenal glands
-Left adrenal vein drains into renal vien
What risk is there with a left adrenalectomy?
Due to close location of spleen there is a risk of damage to the spleen. Therefore we immunise with HIB and pneumoavax incase we need to remove spleen to prevent blood loss
Draw the micro-anatomy of the adrenal gland
What does aldosterone do?
Controls blood pressure
What hormone does the medulla of the adrenal gland produce?
What are the three types of hormones?
steroid, peptide, amine
How many carbons in cholesterol?
What regulates cortisol ?
How is cortisol regulates by ACTH? Draw the pathway
What is POMC?
A large precursor protein that is cleaved to form a number of smaller peptides including ACTH, MSH and endorphins
What is the main cause of addisons diseases ?
What are some of the presentations of addisons disease?
What does MSH do?
skin pigmentation which appears as a tan
What is POMC cleaved into?
ACTH, Beta-MSH(melanocyte stimulating hormone), and Beta-endorphin
How do we treat someone that is in an addisonian crisis
-Rehydrate with normal saline
-Give dextrose to prevent
What are some effects of excess cortisol? (cushings syndrome)
-Impaired glucose tolerance (T2DM)
-Weight gain (increase in fat but protein loss)
-Skin becomes thin and prone to bruising
-Striae (stretch mark as the protein required to synthesise skin doesn't function properly)
-Proximal myopathy (weak muscles)
-Mental changes (depression)
-Fat buildup in awkward places(moon face)
-Interscapular fat pad
List 4 possible causes of cushings syndrome
1/ Taking excess oral steroids (common problem especially when the steroids are used to treat other conditions)
2/Pituitary dependent cushings dieasase ( pituitary adenoma)
3/ Ectopic ACTH
What are some clinical signs of Cushings disease
-Diabetes,Hypertension and osteoporosis
What is the difference between cushing disease and fishings syndrome?
Syndrome is when the cause of the symptoms is unknown
What are the side effects of 'steroids'
What are gonads?
testes and ovaries
What are the functions of the Gonads?
Production of gametes for reproductions
Production of steroid hormones
-Males mostly Androgens (small amounts of oestrogen and progestogens)
-Females mostly oestrogen and progestogens small amounts of Androgens
What does gametogenesis mean?
production of eggs and sperm
What does steroidogenesis mean?
production of steroids
What are the names of the germ cells in males and female?
How do the number of germ cells change with age
Men: doesn't really change (maybe a small drop at old age)
Women: Great reduction from birth to puberty to menopause.
How does the rate of Atresia in females change with age?
Rapid at first with number of germ cells dropping from 6 million to 2 million. By puberty only 400,000. But then the rate of atresia slows down.
What are the steps of spermatogenesis?
1/ we start off with a germ cell in embryogenesis.
2/ They multiply rapidly to produce spermatogonia which are diploid
3/Around puberty, (when FSH is released) The spermatogonia divides by mitosis to produce primary spermatocytes
4/ They enter the first meiotic division to produce secondary spermatocytes which are haploid.
5/ secondary spermatocytes enter the second meiotic division to produce spermatids
6/Which then mature and differentiate into spermatozoa
When does gametogenesis begin?
How are males able to retain spermatogenic capability throughout their life?
Spermatogonia undergo differentiation and self-renewal; consequently, a pool of spermatogonia remains available for subsequent spermatogenic cycles throughout life.
Describe the stages of Oogenesis
1/FIrst there are germ cells
2/ They multiply to produce oogonia
3/ They further multiply again to produce primary oocytes
4/Once primary oocytes are formed they undergo the first meiotic division
5/However once they reach prophase their development is HALTED.
(note steps 1-5 are before birth)
6/ They remain dormant for the next 12-50 years
7/ At puberty some of the oocytes are rescued under the influence of FSH
8/Around the time of ovulation, they complete the first meiotic division to produce secondary oocyte and a polar body. (these r haploid)
9/The second meiotic diction occurs and won't complete until fertilisation.
10/ if fertilised then an ovum is produced.
Where are oogonia found initially?
Primordial follicles in fetus
What is atresia?
degeneration of primordial follicles
Where does spermatogenesis occur?
Describe the path taken by spermatozoa
Produced in the seminiferous tubules. Then travel down to the collection in the Rete Testis where they are concentrated and drained by the Vasa efferentia into the epididymis. They mature here and attain their motility until they are propelled via that Vas deferens via the urethra.
describe the cross section of the coiled seminiferous tubules
The spermatozoa is located in the lumen. Surrounded are sertoli cells and outside of that are spermatogonia. The sertoli cells are connected by tight junctions which keep out large protiens. Just outside of the sertoli cells are leydig cells.
How do the spermatogonia pass through the sertoli cells? What occurs in the sertoli cells?
The spermatogonia movie into the sertoli cells where they are enclosed into the cytoplasm of the cell. (here is where the spermatogenesis takes place). They are then released into the lumen.
What are the roles of sertoli cells?
They form the seminiferous tubules and synthesise FSH and androgen receptors.
In response to FSH they produce produce various molecules including INHIBIN
and are also intimately associated with developing spermatocytes.
What are leydig cells and their roles?
Lie outside the seminiferous tubules. They synthesise LH receptors .
In response to LH they secrete androgens.
Describe the anatomy of the Ovaries
The ovaries have follicles undergoing atresia and a Grrafian follicle.
What is the Grrafian Follicle in the ovary made up off?
Ovum surrounded by granulose cells which in turn are surrounded by thecal cells.
The ovum is located in follicular fluid
What is the name of a follicle that has reached its maximum size and is ready for ovulation?
What determines the hormones produced in tissue?
The type of enzyme present.
Name the steps in steroidogenesis that produce aldosterone, cortisol, testosterone, and oestrone from cholesterol.
How long does the menstrual cycle last?
Usually taken as lasting approximately 28 days (but can last from 20 to 35+ days)
What day of the cycle does ovulation occur?
What is the menstrual cycle consist of?
Ovarian cycle: Follicular phase --> ovulation ---> luteal phase
Endometrial cycle (uterus) : Proliferateive phase--> secretory phase
Describe the menstrual cycle
What is the endometrium?
lining of the uterus
What stimulates the proliferative phase in the endometrial cycle?
Oestrogen (17b-oestradiol) from the follicular phase in the ovarian cycle.
What is the proliferative phase?
A period of proliferation of the endometrium due to an increase in mitosis. There is also an increase in the number of progesterone receptors and oestrogen receptors (which affects the next stage).
What hormones are produced in leuteal phase and what do these do?
Progesterone and little 17b-oestradiol which induce a secretory phase.
What affect does Progesterone have on oestrogen?
What affect does progesterone have on the uterus lining?
Reverses the effect of oestrogen.
It makes the myometrium glands to become wider and this produces substances which inhibit implantation.
Describe how the ovarian cycle affects the endometrial cycle
How long does the follicular phase last?
How long does menstruation last?
LOOK AT LAZ's NOTES FOR MENSTRUL CYCLE PAGE 67
Describe the ovarian life cycle
1/ Pre-antral follicle (when exposed to enough FSH) will develop into antral follicle.
2/Under the influence of FSH, the antral follicle will grow bigger until they achieve their maximum size and become the graffian follicle
3/ Surge of LH occurs which ruptures the follicle realising the egg
4/After ovulation, the follicle is transformed into a corpus luteum which continues to secrete progesterone and oestrogen in the leutal phase of the cycle
5/ Surge of LH stimulates the egg to complete first meiosis
What receptors are present on the Thecal cells and the granulosa cells ?
Thecal: LH receptors
Granulosa: FSH receptors
How do thecal cells react to LH
How to granulosa cells reach to FSH?
They stimulate the aromatase enzyme to convert the androgens produced by the thecal cells to oestradiol
Why don't thecal cells convert androgens into oestradiol?
They don't have the aromatase enzyme .
Summarise the endometiral cycle
What is the precursor molecule for Testosterone and Oestrone?
Where is testosterone reduced to DHT
What is DHT?
dihydrotestosterone: potent form of testosterone
Where is Testosterone aromatised to oestrogen?
testes (Sertoli cells)
How is testosterone and DHT transported in the blood and seminiferous fluid?
IN blood: Binds to Sex hormone binding globulin (SHBG)
and ALBUMIN with 2 % being free (bioactive)
In seminiferous fluid: Androgen binding globulin
What is the role of Androgens in Foetus?
Development of male internal and external genitalia
Fetal growth (acting with other hormones)
Why do male babies tend to be larger than female babies?
Androgens present in male foetus promotes fetal growth
What are androgens?
male sex hormones
What is the role of androgens in adults?
-Needed for spermatogenesis
-Growth and development of:
secondary sex characteristics e.g. facial hair
-Protein and bone anabolism i.e. muscle / bone growth
-Behavioural: Male sexual behaviour
-Pubertal growth spurt (with GH)
What are oestrogens?
any substance (natural or synthetic) which induces mitosis in the endometrium
What are the reproductive effects of oestrogen?
-ENDOMETRIUM: Stimulates proliferation (mitosis) i.e. womb thickening
- MENSTURAL CYCLE: Triggers LH surge resulting in ovulation
- BREASTS: Stimulates growth of ductile system
What are the general effects of oestrogen? (not the reproductive effects)
- Feedback regulation on GnRH (negative and positive)
- stimulates osteoblasts
- Metabolic actions (e.g. on lipids)
- Behavioural effects
What are progestogens?
Any substance (natural or synthetic) inducing secretory changes in the endometrium
what is the endometrium
inner lining of the uterus
What are the effects of progestogens?
-Stimulates secretory activity in endometrium and cervix
-Increase in basal body temperature
-Stimulates growth of alveolar system in breast
Generally, how do steroid hormones promote protein production once entering a cell
They bind to a receptor. The receptor-hormone complex then acts as a transcription factor.
Describe the HYPOTHALAMO-PITUITARY-TESTICULAR AXIS
1/Neurones in the hypothalamus produce Gonadotrophin releasing hormone
2/ GnRH is released in pulses every hour or so
3/ The GnRH released triggers the anterior pituitary to release LH and FSH
4/ LH stimulates the Leydig cells to release testosterone
5) FSH stimulates the sertoli cell to release inhibin and also allows spermatogenesis to occur
Testosterone negatively inhibits LH and the GnRH and inhibin negatively inhibits FSH and the GnRH
Where does androgen production occur?
What stimulates and inhibits androgen production?
LH stimulates and testosterone inhibits (as testosterone inhibits LH and GnRH)
What stimulates Spermatogenesis and what inhibits
FSH and testosterone
Inhibin inhibits by having a negative feedback on FSH
Describe the HYPOTHALAMO-PITUITARY-OVARIAN AXIS
1/ Pulses from Hypothalamus release GnRH every 1 to 2 hours
2/ GnRH stimulates the anterior pituitary to release LH and FSH
3) this stimulates Ovaries to release oestradiol and inhibin
4) Oestradiol and Inhibin has a negative feedback on LH and FSH
What are the 5 stages of the menstrual cycle?
1) Early follicular phase
2) Early mid follicular phase
3)Mid follicular phase
What occurs during the early follicular phase? Talk about hormone levels.
1) 5-10 eggs start do grow in the ovaries. They are called developing follicles
2) They grow under the influence of FSH
3) The follicles release very little oestradiol. Therefore there is an increase in production of FSH and LH
What occurs during the early-mid follicular phase? Talk about hormone levels.
1) As the follicles grow, more oestradiol is produced under the stimulation of FSH and LH
2) One of the follicles starts to grow bigger than the others, this is the follicle which is producing alot of the oestradiol.
3) there is a unique positive feedback, where the Oestradiol simulates granulosa cells s to grow more therefore allowing it tp make more oestradiol
What occurs during the mid follicular phase? Talk about hormone levels.
1) As the oestradiol levels increase, the FSH levels reduce due to inhibition.
2)This causes all of the follicles to die, except for the Graafian follicle.
3) The largest follicle no longer requires FSH to develop and proliferate as it can make a lot of oestrogen locally.
What occurs during the late follicular phase? Talk about hormone levels.
1) The Oestradiol conc continues to increase due to the graffian follicle.
2) Once a threshold is reached it triggers positive feedback on GnRH (which is not usually the case)
3) causes a surge in LH secretion
4) This causes the follicle to break open allowing the egg to be released down the fallopian tube to the uterus.
What occurs during the luteal phase? Talk about hormone levels.
1) As the egg is released to the uterus, the remaining collapsed follicle forms into a corpus luteum
2) The corpus luteum stimulates the production of progesterone
3)The progesterone converts the womb lining into a secretory lining.
4)Oestrogen produced will exert a negative feedback on the hypothalamus pituitary axis therefore FSH and LH are inhibited.
5) if fertilisation does not occur, then period occurs.
absence of menstruation
Define primary amenorrhoea
if a women never had a single period
Define secondary amenorrhoea
if a women has had periods which then stop
Couple cannot get pregnant following 12 months of regular unprotected sex
Causes of infertility
Testicular failure e.g. mumps, Klinefelter syndrome (XXY)
Ovarian failure e.g. Turner syndrome (XO)
Polycystic ovarian syndrome (PCOS)
What is the most abundant metal in the human body?
What are some fo the roles of calcium?
-Strength in bones
-Intracellular second messenger
-Hormone/neurotransmitter stimulus-secretion coupling
-Blood coagulation (factor IV)
How is calcium present in the body?
Approx 99% is present as Complex hydrated calcium salts
Which form of calcium is bioactive
How is calcium present in the blood?
In blood, some is present as ionized calcium (Ca2+), some bound to protein and the tiny bit left as soluble salts
Only the free (unbound, ionised ) Ca2+ is bioactive
What is the total amount of calcium found in the blood?
2.5 ish mM
with 50% being unbound ionised and therefore biologically active
Which organs are involved in calcium regulation?
Kidneys maintain the equilibrium
gastro-intestinal tract absorbs (although most is lost as faeces)
What hormone increases Calcium ion concentration?
PARATHYROID HORMONE (PTH)
1,25 (OH)2 VITAMIN D3 (DIHYDROXY- CHOLECALCIFEROL, or CALCITRIOL)
What hormone decrease calcium ion concentration?
Were are the parathyroid glands located?
4 of them which are embedded into the thyroid glands towards the back
What hormone are released by parathyroid glands?
Where is calcitonin produced?
parafollicular cells of thyroid
How are calcium levels detected?
Where does PTH bind to?
Binds to transmembrane G-protein linked receptors
How many amino acids are there in PTH
What roles does PTH have on the kidneys, bones and small intestine?
Stimulates the kidneys to:
-Increased Calcium ion reasborption
-Increased phosphate ion exerction
-Stimulates 1 alpha hydroxylase activity which increases the synthesis of transporter which in turn stimulates the SMALL INTESTINES to increase calcium and phosphate absorption
There fore increasing bone resorption
What affect does PTH have on Calcium conc in blood
Describe PTH action in bone
PTH binds to PTH receptor on osteoblasts which activates signals. This stimulates osteoclast activating factors to release from the osteoblasts therefore increasing bone resorption
How is PTH regulated?
1) PTH increase Ca conc and synthesis of active Vitamin D3
2) Negative feedback from elevated serum ionized calcium levels. Inhibits parathyroid glands from releasing PTH
3) Vitamin D3 also has negative feedback
4) some nerve impulses from catecholamines can also decrease
What is 1,25 (OH)2 D3?
active form of vitamin D3 called Calcitriol
Describe DIHYDROXY-CHOLECALCIFEROLSYNTHESIS synthesis.
1) Cholecalciferol (vitamin D3) is obtained from diet or from UV light
2)A hydroxygroup is attached on the 25th position in the liver forming 25 hydroxy-cholecalciferol (25(OH)D3)
3) Another hydroxy group added in the 1st position in the kidneys to produce 1,25 DI-HYDROXY-CHOLECALCIFEROL also known as Calcitriol.
Why is cholecalciferol not useful on its own?
Not very bioactive
What two organs are vital for Calcitriol (active form of vitamin D3 production)
Kidney and liver
What are the roles of Calcitriol
1) Increased calcium absorption in the small intestine
2)Increased phosphate absorption in the small intestine
3)Increased osteoblast activity in the bone (but this is indirectly via increased calcium i n the blood)
4)Increased calcium and phosphate re-absoption in the kidneys
What is the role of fibroblast growth factor 23?
Regulate phosphate re-absorption
Describe how fibroblast growth factor 23 functions.
1) there is a high conc of phosphate ion (Pi) and Vitamin D3
2) FGF 23 stimulated
3) FGF 23 (PTH does the same in this case) inhibits the sodium/phosphate co transporter found in the kidney.
4) Therefore less phosphate and sodium is reabsorbed and more is released in the urine.
5) FGF3 then has a negative feedback loop with vitamin D3/ calcitriol
How does calcitonin work?
1) Calcitonin is rebased by parafollicular cells int he thyroid
2) they inhibit osteoclast activity
3) Therefore decrease plasma calcium ion.
4) they also increase urinary excretion of Calcium ions in the kidney
What is hypocalcemia?
low calcium levels in the blood
What can cause hypocalcaemia
3)Vitamin D deficiency
What are some clinical signs of hypocaclaemia?
Trousseaus sign and chvosteks sign.
What causes hypoparathyroidism?
Idipathic, Hypomagnesaemia (low magnesium)
What is pseudohypoparathyroidism?
kidney is unresponsive to PTH (looks like ur lacking PTH but u rnt...hence the name)
How do you clinically differentiate between hypoparathyroidism, Pseudo-Hypoparathyroidism and vitamin deficiency?
hypoparathyroidism: Low plasma Ca, High plasma phosphate and low PTH
Pseudo-hypoparathyroidism: Low plasma Ca, high plasma phosphate and high PTH
Vitamin D deficiency: Low plasma Ca, low plasma phosphate and high PTH
What causes primary hyperparathyroidism?
results in increased PTH and increased Calcium blood levels. But Adenomas do not function with negative feedback
What causes secondary hyperparathyroidism?
Renal failure (as calcium is not reabsorbed)
Calcium is low however the PTH is unable to fix this.
What causes tertiary hyperparathyroidism?
Initially have secondary hyperparathyroidism. Therefore high conc of PTH. Also the parathyroids grow to try deal with it. However after being cured (eg kidney transplant) and the PTH is effective. However the parathyroid glands became autonomous and therefore not affected by the negative feedback loop.
What are the effects of hyperparathyroidism?
-increased calcium and phosphate resorbtion therfore formation of renal stones
2) Gastro-intestinal tract
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