Week 1 Flashcards
What are some advantages/disadvantages of nervous vs endocrine mechanisms?
Nerves provide very fine control, very precise, and very quick control of body parts (e.g. the tip of the finger). The downside is that the nervous system takes up quite a bit of space and energy. It also cannot control every cell in the body with the nervous system.
The endocrine system is chemically addressed. It sends hormones through the blood and therefore does not take up any space. It is recognized by any tissue that can “read” the hormone. However, while it takes up no space, it is comparatively slow generally speaking.
The endocrine system can also regulate things for extended amounts of time (i.e. decades), such as blood glucose. The nervous system “quickly loses interest”. For instance, when you sit down, you feel the chair, but quickly you forget the sensation of the chair unless you’re actively thinking about it.
Are the nervous system and the endocrine system completely dissociable? Give examples?
No, in many body processes, the endocrine system and the ANS interact with one another. Examples are SNS stimulation of the liver mobilizes glucose which is released through an endocrine mechanism.
What is a hormone?
A hormone is secreted by living cells, in trace amounts, and is transported, usually by the blood, to a distant site within the same organism where it is not used as a source of energy but acts to regulate or initiate reactions and produce an appropriate response.
Why does the definition of a hormone include the term “living cell”?
Because dead or dying cells release “pathological facts” or inflammatory mediators which are important, but are not considered to be hormones.
Compare the amounts expected to be found of plasma glucose vs plasma hormones (e.g. aldosterone)?
Hormones are found in trace amount in the blood. They are hardly comparable to substance like glucose which can be calculated using mmol (10-3), whereas hormones are usually measured in nanomoles (10-9) or picomoles (10-12).
How would a hormone be detected in a lab?
Antibodies raised in animals (e.g. mouse) responsive to the specific hormone would be injected in a tube and mixed with a plasma sample. Another antibody to the same hormone would be inputted, before a last antibody in large amount would be added which would be tagged with fluorescent lighting, which would allow for the detection of the hormone.
How do hormones travel in the blood? How does that affect their ability to diffuse into tissues?
If the hormone is water-soluble, it can travel freely in the blood. However, if it is lipid soluble, hormones are usually bound to binding proteins, through which they can travel. Only free hormones are able to diffuse into tissues, therefore protein-bound hormones are “unavailable” for distribution into tissues.
General Concepts of the Endocrine SystemWhat factors can affect the plasma levels of protein-bound hormones? How does that process occur? Give examples.
Different physiological processes/pathologies can cause a rise/drop in binding proteins which causes a rise in hormones bound to those proteins. Examples like pregnancy increase the number of binding proteins in plasma which causes an increase in protein bound hormones, while liver/kidney failure cause a drop in the amount of binding protein.
Agents that are released from cells to act on neighboring cells are referred to as? Give examples of hormones that have local effects.
Paracrine. Examples of hormones that have local effects as well as systemic effects are prostaglandins.
What makes glucose unable to be considered a hormone?
It is used as a source of energy. Hormones cannot be used in the body as a source of energy. Rather, they must act on receptors to exert their effects.
What is the physiological role of hormones? Give examples?
Either to regulate (stimulate or inhibit) reactions, or to start a physiological and anatomical process. Examples of those are blood glucose regulation through glucagon/insulin secretion by the pancreas, and the hormonal changes which trigger puberty respectively.
Give three different control mechanisms through which the activity of a hormone could be regulated?
- Gland secretion of the hormone
- Number of receptors
- Control of the secondary conversion of the hormone (if applicable)
What would be the effect of continuous receptor stimulation by a hormone? Give an example?
It would cause the downregulation of the receptors responsible for that hormone. An example is that long term high dose use of gonadotrophin (GnRH) is contraceptive because of a loss of sensitivity to GnRH.
What is the role of oxytocin in the scope of pregnancy?
Initiating uterine contraction during labor.
Why does oxytocin only cause uterine contraction at the end of pregnancy?
Because at the end of pregnancy the uterus is dominated by estrogen whereas earlier in gestation, it is dominated by progesterone.
Which hormone is responsible for milk let down in lactation?
Oxytocin
What is the essential role of most hormones? What is the relationship between the trigger which releases the hormone and the action of that hormone? Give examples.
Most hormones are in charge of homeostatic processes. These hormones usually work to work against the factor that triggered their release. For example, insulin secretion is stimulated by high plasma glucose concentration and acts to lower plasma glucose concentration.
What is the role of insulin and what triggers its release?
Insulin secretion is stimulated by high plasma glucose concentration and acts to lower plasma glucose concentration.
What is a diurnal rhythm in the scope of hormones? Give an example of a hormone with a diurnal rhythm?
A diurnal rhythm is a biological rhythm that is synchronized with the day/night cycle. An example of a hormone with a diurnal rhythm is cortisol (peaks at 9am and troughs throughout the evening/night).
Where are the adrenals located?
Suprarenal
What is the drainage of the adrenals?
The left adrenal drains into the left renal vein whereas the right drains directly into the inferior vena cava
What is the blood supply of the adrenals?
Liberal blood supply from; aorta, renal and phrenic arteries
What are the two anatomical zones of the adrenals?
The outer cortex and the inner medulla.
What is the role of the adrenal outer cortex?
Secretes steroid hormones
What are the different parts of the adrenal cortex? What does each one secrete?
Adrenal cortex is divided into three parts – GFR
- Zona Glomerulosa; secrete mineralocorticoids (e.g. aldosterone)
- Zona Fasciculata; secrete glucocorticoids (e.g. cortisol)
- Zona Reticularis; secrete sex hormones (e.g. oestrogen)
What is the adrenal medulla? What does it secrete?
It is the inner part of the adrenal gland. It secretes catecholamines like adrenaline and noradrenaline.
What is the universal precursor for all hormones in the adrenal?
Cholesterol
Describe the secretion patterns of cortisol?
It has a pulsatile secretion, and follows a diurnal rhythm – highest in the morning lowest at night)
How does cortisol travel in the blood?
Bound to Cortisol Binding Globulin
What receptors does cortisol act on?
Both glucocorticoid and mineralocorticoid receptors.
How does the body regulate cortisol activity on mineralocorticoid receptors?
Utilizes the hormone 11B-HSD2 to inactivate cortisol to cortisone (its inactive form).
Describe the process leading to cortisol being released from the adrenal?
The hypothalamus releases CRH (corticotrophin releasing hormone), which acts on the anterior pituitary to release ACTH, which acts on the adrenal to release cortisol.
What are the systemic effects of cortisol?
It’s a glucocorticoid, meaning it increases plasma glucose and works as an anti-insulin hormone. It prepares for starvation. It stimulates protein breakdown in muscles and increase fat mobilization, as well as increase gluconeogenesis, and decrease glucose and amino acid utilization.
What are the physiological effects of cortisol on the CV system and immune function?
It increases blood pressure, maintains fluid volume, and has immunosuppressive and anti-inflammatory effects.
Give an example of a mineralocorticoid?
Aldosterone
What are the systemic effects of aldosterone?
Preserves circulatory homeostasis in response to loss of water or salt. It acts on the distal convoluted tubule of the kidney to promote sodium reabsorption. This leads to increased water retention and increased blood volume.
Describe the RAAS system?
Juxtaglomerular cells detect hypovolemia through baroreceptors. This triggers the release of renin, which acts on angiotensin and converts it to angiotensin I. Angiotensin I is then converted to angiotensin II through the action of ACE (Angiotensin converting enzyme). Angiotensin II works on the adrenal gland to release more aldosterone. The aldosterone then works on the distal convoluted tubule to retain water and salt, which in turn causes an increased blood volume and blood pressure.
What is DHEA? What releases it and describe its concentrations throughout life?
DHEA is a sex hormone that is released by the adrenal gland (zona reticularis). It is heavily secreted in fetuses and secretion falls after birth. It resumes around the prepubertal period (7-8) where it is converted to active androgens and allows for the development of some features of prepuberty like some axillary or pubic hair.
What are the cells residing in the adrenal medulla that release catecholamines?
Chromaffin cells.
What is the difference in location in the body between adrenaline and noradrenaline?
Noradrenaline is found in multiple places around the body (including the adrenal medulla) whereas adrenaline is only found in the adrenal medulla.
What do chromaffin cells contain?
Granules of adrenalin or noradrenalin
What triggers the release of catecholamines in the adrenal?
Stimulation of the splanchnic nerve, and causes release of granules from chromaffin cells into circulation
What are the actions of catecholamines on the different body systems?
Systemic: Increase gluconeogenesis, increase glycogenolysis, increase lipolysis
CV: Increase heart rate, increase contractility of the heart muscle
Airways: Bronchodilation
What is the difference between primary and secondary Cushing’s syndrome?
Primary: ACTH independent – Something causing the releases of excess cortisol, driving the ACTH production down due to negative feedback (would expect to see high cortisol and low ACTH)
e.g. Adrenal tumor
Secondary: ACTH dependent – Pituitary tumor or ectopic source causing the release of excess ACTH, driving cortisol levels very high (would expect to see both cortisol and ACTH very high)
e.g. Lung carcinoma
What are the characteristics in the presentation of Cushing’s syndrome?
Glucocorticoid excess (cortisol) would cause the following:
- Muscle wasting
- Fat deposition in abdomen and face
- Hyperglycemia
- Hypertension
What is Addison’s disease? What are the types of Addison’s disease? What is the etiology and presentation of the disease?
Addison’s disease is a dangerously low level of glucocorticoid and mineralocorticoid. It can either be primary - due to direct insult to the adrenal gland, or secondary - due to pituitary dysfunction causing slowed release of ACTH. The patient would present with low plasma glucose, sodium, and potassium (mineralocrticoid and glucocorticoid deficiency), as well as dehydration and hypotension and hypovolemia. Lastly, there is a pigmentation of the skin.
What are the types of excess aldosterone production? What is the presentation?
Conn’s syndrome is a syndrome of primary excess aldosterone secretion. It is primary - due to direct excess secretion of aldosterone from the adrenal due to things such as an adrenal tumor.
Excess aldosterone can also be secondary due to excess stimulation of the adrenal due to low blood volume in conditions like heart failure or nephrotic syndrome.
A patient suffering from either primary or secondary excess aldosteron production would present with hypertension, and hypokalemia.
What would be a possible cause for excess adrenal medulla function and what would that translate to in production and presentation?
An excess in adrenal medulla would mean excess catecholamine production (Noradrenaline, adrenaline), and therefore, would translate to hypertension, tachycardia, sweating, weight loss. A hypo functioning adrenal medulla would not be clinically significant as noradrenaline is produced elsewhere in the body.
What hormones does the fetal adrenal produce? Why are they relevant?
The fetal adrenal produces DHEA and cortisol. DHEA is a precursor to estrogen (important in labor), and cortisol, which is important in maturing the fetal organs as well as initiating labor.
What is congenital adrenal hyperplasia? What is the most common one and describe it and its effects?
A condition which causes a deficiency of adrenal enzymes, with variable severity. 21-hydroxylase deficiency is the most common one and fetuses suffering from it cannot produce mineralocorticoids or glucocorticoids, resulting in upregulation of pituitary ACTH production. This results in some steroid compensation, although it mostly results in virilization as it upregulates the production of androgens as well, causing boy-like features in girls.
What are the two lobes of the pituitary?
Anterior pituitary and posterior pituitary
What are the embryological precursors to the anterior and posterior pituitary?
Anterior pituitary – roof of the mouth and posterior pituitary – floor of the brain
Where do the two lobes of the pituitary join?
In the sella turcica
What hormones are released by the posterior pituitary?
ADH and Oxytocin
How many amino acids make up oxytocin?
9
What triggers the release of oxytocin from the posterior pituitary?
Action potential passing down from the hypothalamus causes the release of oxytocin into the blood
What are the physiological effects of oxytocin?
Uterine contractions and milk let down in lactation.
What stimulates the hypothalamus to signal for the release of oxytocin?
Positive feedback, whereby the cervix will stretch, or the baby will suckle on the nipple which will send a signal along the spinal cord to the hypothalamus which will then generate an action potential which will travel to the posterior pituitary to release oxytocin.
What inhibits oxytocin?
Alcohol and stress
What is another name for ADH?
Vasopressin
How many amino acids make up ADH?
9
What triggers the release of ADH from the posterior pituitary?
Action potential passing down from the hypothalamus causes the release of oxytocin.
What are the physiological effects of ADH?
Cause water absorption in the kidney by reabsorbing water in the collecting duct.
What inhibits the effects of ADH?
Alcohol
What Hypothalamic diabetes insipidus?
A condition characterized by a lack of ADH
What can cause diabetes insipidus?
Injury to the hypothalamus or pituitary, tumor, inflammation, or infarction causing a loss of the ability to release ADH.
What is the result of diabetes insipidus?
Blood osmotic pressure rises, blood volume falls, increased water intake.
What is SIADH? What is its etiology and presentation?
Syndrome of inappropriate ADH secretion is a syndrome whereby patient will suffer from plasma levels of ADH higher than normal values should indicate. It comes often as a result of a cancer releasing ADH, and it causes water retention and blood and tissue osmolarity falls over days and weeks. Plasma Na+ concentration falls and cells are overhydrated and overexpanded.
What is the treatment for SIADH?
Removal of cause releasing extra ADH (usually tumor). Sometimes, we can also try to manage SIADH by using fluid restriction and slow infusion of NaCl (danger of central pontine myelinosis if done too fast).
What causes pituitary hormones to be released? Give 5 examples of this mechanism of action?
What causes growth hormone release? Where is this signal coming from?
Growth Hormone Releasing Hormone (GHRH) travels from the hypothalamus to the anterior pituitary to trigger the release of GH.
What releases Growth Hormone?
Anterior pituitary
What inhibits Growth Hormone?
Somatostatin
Describe the actions of Growth Hormone in the fasted state?
- Stimulates gluconeogenesis via amino acid breakdown
- Mobilizes fat
- Insulin inhibitor
Describe the actions of Growth Hormone in the fed state?
- Stimulates amino acid uptake and protein synthesis
- This promotes cell division and growth
What physiological factors cause the release of growth hormone?
- Low blood glucose concentration
- High plasma amino acid concentration
- Acute stress
What physiological factors cause the inhibition of growth hormone?
- High blood glucose
- Chronic stress
What are GH blood levels fairly irrelevant in diagnostic testing?
Because GH, just like cortisol, works with a diurnal rhythm, making GH levels very high in the morning, and very low in the afternoon therefore the pulsatile nature of GH secretion makes it a very unreliable and fluctuating value.
What are the possible causes of low Growth Hormone secretion in children? What would be the effect of such low levels of GH?
There are two main possible cause of growth hormone deficiency in children. The first one is a physiological inability to secrete GH (e.g. problem with anterior pituitary or hypothalamus releasing GHRH), or a secondary inhibition of GH by factors like chronic stress (e.g. parental divorce, school bullying). The effect would be a lack of growth in the child
What hormone inhibits GH in high levels (apart from somatostatin)?
Cortisol
How would one discern in a clinical setting between a primary (systemic) inability to produce GH vs a secondary inhibition of GH due to chronic stress?
Stress Test:
Inject insulin to drop the blood glucose concentration very low, and if the individual has an ability to produce GH, the body will produce GH to counterbalance the low blood glucose, even if it’s inhibited.
How would one discern between a high GH secretion vs an ectopic source secreting GH (e.g. tumor)?
Glucose Tolerance Test:
Inject 70 mg of glucose to raise the blood glucose concentration very high, and if the individual’s high GH levels are simply physiologically high, the body would stop the production of GH to counterbalance the high blood glucose.
In what way would Cushing’s syndrome affect stature in a child?
Cushing’s syndrome is a syndrome of inappropriate cortisol release. A side effect of the high cortisol levels would result in an inhibition of GH in the body, which would result in short stature of the child, unless the Cushing’s is resolved.
What is the role of Growth Hormone in fetuses?
Growth hormone is fairly useless in fetuses. It has no effect on growth in the womb.
What hormone is responsible for growth of fetuses in the womb?
Insulin
What is the result of too much growth hormone in children?
Gigantism
What three conditions are at risk of developing with growth hormone excess and why?
- Heart disease: overgrowth of soft tissue
- Diabetes mellitus: GH inhibits insulin
- Colorectal cancer
What is the result of excess growth hormone in adults? What are the characteristics?
It causes acromegaly; soft tissue growth, bone overgrowth
What is a common side effect of a pituitary tumor? Why?
Bitemporal hemianopia because the pituitary gland is very close to the optic chiasm and if the tumor grows, it presses on the optic chiasm.
What are hormones that the thyroid produces?
Thyroxine (T3), triiodothyronine (T4), thyrocalcitonin
What are the parathyroids? Where are they located?
4 glands located at the 4 poles of the thyroid gland.
What releases thyrocalcitonin hormone?
C cells in the parafollicular region of the thyroid.
What are thyroid hormones made up of?
Iodine containing modified amino acids
What drug inhibits the production and secretion of thyroid hormones (T3 and T4)?
Carbimazole
How do they determine clinically which parts of the thyroid gland is active?
They inject a low dose of radioactive iodine, and wait for the iodine to be taken up by the thyroid gland, at which point they take a gamma picture and causes the parts of the thyroid that have taken up the radio iodine (i.e. the active parts) to shine.
What is a major, but rare side effect of carbimazole and PTU?
Agranulocytosis – inhibition of white cell production
Describe the production of T3 and T4?
Iodide is taken up from the blood into the follicular cell. The iodide then diffuses across the cell into the colloid surface and is oxidized into iodine. It then binds to tyrosines and depending on the number of iodines binding, it can form T3 or T4. They are then packed into vesicles, get back into the follicular cell, which causes protease degradation of the vesicle, leaving T3 and T4 to diffuse out into the blood.
What stimulates the production and secretion of thyroid hormones?
Thyroid stimulating hormone (TSH)
What is the difference between T3 and T4?
T4 is a prohormone while T3 is an active hormone. T4 needs to be converted to T3 in order to become active.
How does T4 become activated? Where does this process mostly occur in the body?
T4 is converted to T3 through B-deiodination. This process mostly occurs in the liver.
What are the physiological effects of TSH?
Trigger the uptake, and oxidation of iodide, as well as thyroglobulin degradation and T3 and T4 release. Moreover, TSH is also trophic in nature and causes an enlargement of the gland in big concentrations
How do T3 and T4 travel in the blood?
Bound to plasma proteins mostly (99.95% for T4 and 99.5% for T3).
Which proteins do T3 and T4 bind to when traveling in the blood?
Albumin, pre albumin and mostly TBG (Thyroxine Binding Globulin)
How is the concentration of free T3 and T4 buffered?
It is buffered using the thyroid hormones that are bound to TBG. When free Thyroxine hormones enter a tissue and there is a drop in the concentration of free thyroxine hormones, TBG-bound hormones will then become free and vice versa.
What are instances in which TBG concentration would go up or down?
In pregnancy, TBG concentration goes up, while in kidney disease, TBG concentration goes down
What is the main effect of thyroid hormones (T3) on the body?
Raises the basal metabolic rate – increases oxygen and heat consumption.
What receptors do thyroid hormones affect and how?
Thyroid hormones increase the production of adrenergic beta receptors.
What is the role of thyroid hormone in the fetus?
Helps with the maturation of lungs, bones and the brain
Where is most of the calcium in the body found?
99% in bones and teeth
When do individuals attain peak bone mass?
Around the age of 30
What influences bone turnover?
Activity; the more activity is done to reinforce the bone, the less bone turnover there will be.
What is the calcium reservoir for the body?
Bones
How does calcium travel in the blood?
50% of calcium is free while the other 50% is bound to albumin
What is the corrected plasma calcium? What does it say about plasma calcium levels?
Corrected plasma calcium refers to the calcium concentration in the blood if there are normal albumin concentration levels. Comparing that to the plasma calcium levels allows doctors to know whether there is a problem with calcium or albumin (as calcium binds to albumin, if there is a hypocalcemia, it can be due to albumin instead of calcium).
What would be the change in calcium plasma concentration in acidosis? Alkalosis?
Calcium is positive, while albumin is negative. In acidosis, with an increase in H+ ions, albumin will bind to H+, thus decreasing the amount of calcium. In alkalosis, the opposite would happen; calcium binding would be enhanced in alkalosis.
What are the physiological roles of calcium?
- Calcium is part of the clotting cascade and required for the formation of fibrin
- Calcium controls neurotransmitter release at synapses
- Calcium is also responsible for excitation of muscle cells causing contractions
What is the effect of low plasma calcium concentration on nerve activity?
Nerves become leaky and hyperexcitable which can cause spontaneous activity.
Which hormones are responsible for calcium control?
- Parathyroid hormone (PTH)
- Vitamin D
- Calcitonin
What triggers the release of parathyroid hormone?
Fall in the extracellular calcium concentration
What is the action of parathyroid hormone on the kidney?
It increases reabsorption of calcium in the proximal tubule.
What is the action of parathyroid hormone on the bone?
PTH causes the transfer of calcium from calcium-rich fluid inside of the bone to the ECF. If more calcium is needed, it stimulates osteoclasts to resorb mineralized bone, and if more calcium is needed, it stimulates an increase in the number and size of osteoclasts.
What is the action of parathyroid hormone on vitamin D?
PTH stimulates the synthesis of vitamin D which acts to promote calcium absorption in the gut.
What is the physiological effect of vitamin D?
It increases calcium reabsorption in the gut.
How is vitamin D regulated in the body?
The active form of vitamin D in large amounts inhibits the precursor form that active vitamin D is synthesized from. This results in negative feedback for vitamin D.
What is thyrocalcitonin? What is its physiological effect on the body?
Calcitonin is a hormone released by the thyroid that works to lower the calcium concentration by antagonizing the actions of PTH.
What stimulus causes the release of calcitonin?
A rise in plasma calcium concentration.
What can cause hypocalcemia?
- Diet
- Lack of vitamin D
- Problems with PTH
What can cause hypercalcemia?
- Hypercalcemia of malignancy
- Acidosis – less albumin to bind to which raises the concentration of free calcium
- Hyperparathyroidism
