Endocrinology Flashcards
What are the different types of hormones action?
Endocrine- cells release hormones from vesicles which then are secreted into the blood where they travel to tissues far away
Paracrine- hormones released act on nearby cells in same tissue
Autocrine- hormones released act on receptors on the same cell
What are hormones?
Chemical messengers of the endocrine system
How do hormones circulate in the body?
Either free or bound to binding protein
What is the purpose of binding proteins to hormones?
Provide reservoir of hormone to avoid fluctuations
Extend hormone life
Allow insoluble hormones to circulate
How are peptide hormones produced and what are some examples?
Protein sysnthesis in endocrine cells, often produced as prohormones/inactive precursors and then processed into active form
Insulin, oxytocin
What are steroid hormones derived of and what are some examples?
Cholesterol
Cortisol
How do peptide hormones act on target cells?
At cell surface receptor causing downstream signalling within a cell
How long to peptide hormone responses take?
Seconds to minutes
How to steroid hormones act on target cells?
At cytoplasmic or nuclear receptors
Circulate with binding protein due to being hydrophobic then are released through cell membrane alone due to being lipophilic
Cause regulation of gene transcription
How long do steroid hormone responses take?
Hours-days
How are hormone releases regulated?
Feedback mechanisms- negative feedback loops
Tropic hormones- stimulate release of another hormone from other endocrine glands
Neuronal control- neuronal stimulation causes stimulation or inhibition of hormone release
Describe the structure of the hypothalamus pituitary organ axis
Hypothalamus contains neuroendocrine cells
Posterior pituitary is continuous with hypothalamus so is neuronal and glandular
Anterior pituitary is only glandular and connects to hypothalamus by the hypophyseal portal circulation
How does the hypothalamus signal via the anterior pituitary?
Neuroendocrine cells release hypothalamic hormone into hypophyseal portal circulation
Hypothalamic hormone hormone binds to glandular cells in anterior lobe which secretes anterior lobe hormone into circulation
Explain how the hypothalamus signals via the posterior pituitary
Neuroendocrine cells secrete posterior lobe hormone into posterior lobe which enters the general circulation
What is the importance of the hypothalamus?
Focus point of information on internal wellbeing and produce hormones in response to changes
What is neuroendocrine function in the hypothalamus?
Neuroendocrine cells reside in nuclei in hypothalamus and detect levels on circulating hormones, metabolites, nutrients and electrolytes
Also respond to physiological stimuli such as stress and pain
What is the role of oxytocin?
Cause uterine contractions in labour and let down milk in lactation
What is the role of antidiuretic hormone?
Changing the rate of water reabsorption in the kidney
Explain the structure of the thyroid gland cells
Follicles with colloid/viscous proteinated centre surrounded by follicular/cuboidal epithelium
How are thyroid hormones synthesised?
Derived from tyrosine amino acid and incorporates iodine in the thyroid epithelial cell
Where does the tyrosine amino acid come from for thyroid hormone synthesis?
In polymer thyroglobulin
What are the two different thyroid hormones?
T4- thyroxine
T3- triiodothyronine
What is the features of T3?
Cause most physiological effects
Active receptor affinity
Loosely bound to protein in circulation
What are the features of T4?
Most of hormone released by thyroid gland
Less active receptor affinity
Tightly bound to protein in circulation
Acts as a pool for T3 as is converted to T3 in tissues
How does thyroid gland morphology change with activity of gland?
Unstimulated gland- cuboidal epithelium with follicles full of colloid
TSH stimulated- columnar epithelium with follicles collapsed due to increased colloid uptake for T3 and T4 production
How do thyroid hormones act on target cells?
Thyroid hormones diffuse or move through transporter into cell
Most T4 is converted to T3 by removal of one iodine
T3 diffuses into nucleus and binds to thyroid hormone receptor
Thyroid hormone receptor binding to promotor elements activate gene transcription and protein production
What systems do thyroid hormones cause affect on the body?
Normal childhood growth and critical CNS development
Cardiovascular
Basal metabolic rate
What is the cardiovascular effects of thyroid hormones?
Increased manufacture and incorporation of beta 1 adrenergic receptors causing increased responsiveness and sets sensitivity of heart to adrenaline and noradrenaline
Long term sensitivity of cardiac cells regulated by plasma levels of TH
What are the effects of thyroid hormone on basal metabolic rate and how does it happen?
Most important action
Increases basal metabolic rate
Oxidative metabolism increased in most cells as increased Na-K pump activity which uses more energy
Stimulates anabolic and catabolic reactions regarding fat, protein and carbohydrates
Stimulates protein synthesis
More glucose available and lipid metabolism for increased metabolic demand`
What is hypothyroidism and how is is caused?
Underproduction of TH
Caused by iodine deficiency or hashimotos disease (autoimmune destruction of thyroid cells)
What are the symptoms of hypothyroidism?
Weight gain Decreased metabolic rate Low appetite Cold intolerance Mental sluggishness Fatigue Low cardiac output Low force and rate of contraction
How is hypothyroidism treated?
Increased iodine
Replacement thyroid hormone
Why does the thyroid gland enlarge in hypothyroidism?
No T3 or T4 formation so no feedback control of TSH
TSH high which continues stimulation of production of thyroglobulin
What is hyperthyroidism and how is it caused?
Overproduction of thyroid hormone
Graves disease or follicular cell tumours
What are the effects of hyperthyroidism?
Goiter Increased metabolic rate Weight loss Nervousness Irritability Sleeplessness Fatigue Heat intolerance Increased force and rate of heart contractions
What is graves disease?
Thyroid stimulating immunoglobulin produced which binds to TSH receptor
Triggers overstimulation of thyroid increasing T3 and T4 synthesis
How is graves disease treated?
Antithyroid drugs
Thyroidectomy
Radioactive iodine to kill some thyroid cells
What is growth?
Increase in cell size/hypertrophy or increase in cell number/hyperplasia
How is growth controlled?
Hormones and growth factors to provide fuel and cell components
When is somatostatin released for growth hormone release inhibition?
Increases blood glucose
Increased free fatty acids
Obesity
Aging
When is growth hormone releasing hormone released for growth hormone release stimulation?
Decreased blood glucose Decreased free fatty acids Starvation Protein deficiency Trauma Stress Excitement Sleep Exercise
What is meant by dimal and pulsatile release of growth hormone?
Dimal- increased GH release in sleep
Pulsatile- pulses release across the day
Why is pulsatile release important?
Helps maintain homeostatic balance needed for essential processes
Acute effects of growth hormone?
Reduced lipogenesis and fat storage
Reduced glucose uptake and oxidation
Increased gluconeogenesis and glycogenolysis
Increased blood glucose
Increased amino acid uptake and protein synthesis
Reduced protein catabolism
What are the long term effects of growth hormone?
Causes insulin like growth factor 1 release from liver which mediates local growth
Explain the causes and effects of excess growth hormone
Causes- pituitary tumours
Giantism in childhood and acromegaly in adults
Explain the symptoms and causes of acromegaly
Symptoms- soft tissue swelling, generalised skull expansion
Causes- insulin resistance
What is the effect of growth hormone defecit?
Dwarfism- short stature in appropriate proportions, delayed maturation
What are the causes of growth hormone defecit?
Pituitary tumour
Explain what gene therapy is and what is its effects
Injections of recombinant hGH to increase muscle mass, bone density and decrease body fat
Doesn’t increase strength, functionality or performance
Can cause complications such as diabetes, hypertension and can increase cancer risk
What are the layers of the adrenal glands?
Cortex- glomerulosa, fasciculata and reticularis
Medulla
What does each layer of the adrenal glands produce?
Glomerulosa- mineralocorticoids
Fasciculata- glucocorticoids
Reticularis- androgens and oestrogens
Medulla- adrenaline/noradrenaline
What is the precursor for adrenal steroid synthesis and where is is acquired and stored?
Cholesterol
Acquired from GI tract or synthesised from acetate and stored in cortical cells
How do steroid hormones cause effect?
Act on cytoplasmic receptors in target tissues then translocates to nucleus where it modulates gene transcription of certain genes to cause protein synthesis to cause effect
What are the features of cortisol?
Hydrophobic so circulate bound to plasma protein
60-90 minute half life
What controls the release of glucocorticoids?
Tropic hormones and circadian release
What systems do glucocorticoids effect in the body?
Metabolic
Muscular
Nervous system
Inflammatory and immune response
How do glucocorticoids effect metabolism?
Stimulates gluconeogenesis and inhibits effects of insulin so decreased tissue uptake of glucose
Stimulates protein catabolism causing gluconeogenesis
Increased lipolysis in times of stress or starvation
Hyperglaecaemia
How does glucocorticoid insufficency effect cardiac, smooth and skeletal muscle?
Muscle fatigue
Cardiac insufficiency
Loss of vasomotor tome
General muscle weaknedd
What is the effect of different levels of glucocorticoids on nervous system?
Excess- hyperactivity, insomnia, euphoria, increased sensory activity
Insufficiency- lethargy, apathy, lack of concentration
How do glucocorticoids effect inflammatory and immune responses?
Inhibit cytokine secretion, immune cell proliferation and antibody synthesis
Increase susceptibility for infections
What is an example of a glucocorticoid?
Cortisol
What is an example of mineralocorticoids?
Aldosterone
What are the features of aldosterone?
Bound to plasma protein
15-30 minute half life
What is the role of aldosterone?
Regulate Na+ and K+ concentration in ECF
What stimulates release of aldosterone?
Changes in electrolyte and water balance
How are glucocorticoids used therapeutically?
Anti-inflammatories
Anti-allergic
Immunosuppression
Why do you need to be weaned off therapeutic glucocorticoids?
Withdrawal can cause hypocorticism as synthetic steroids reduce natural cortisol so the gradual decrease allows natural cortisol levels to build back up
What diseases are associated with hypercortisism and hypoadrenocorticism?
Hyper- cushings disease
Hypo- addisons disease
What are the different types of hypercortisism?
Primary- adenoma of adrenal cortex causing uncontrolled production of cortisol
Secondary- pituitary tumours causing uncontrolled ACTH so uncontrolled cortisol production
Latrogenic- widespread synthetic cortisol use
What are the symptoms of hypercortisism?
Upper body obesity Round face Extra neck fat Thin skin Weak bones Hyperglycaemia
What are the different types of hypoadrenocortisism?
Primary- autoimmune attack causing atrophy of adrenal cortex
Secondary- pituitary mutation
Latrogenic- abrupt withdrawal from steroid therapy
What are the symptoms of hypoadrenocortisism?
Muscle weakness
Poor CV function
Low blood pressure
What hormones are known as catecholamines?
Adrenaline and noradrenaline
What do catecholamines act on?
Receptors on adipose and pancreatic tissue and the CNS
How are adrenergic receptors for catecholamines regulated?
Affinity
Concentration of receptor
Receptor signalling and activation of second messengers
How are catecholamines secreted?
Adrenaline produced in adrenal medulla
Noradrenaline synthesised by chromaffin cells and noradrenergic receptors
Both produced by tyrosine undergoing enzymatic changes
Stored in granules until release on demand
What is hyperfunction of adrenal medulla?
Pheochromocytes are tumours arising from chromaffin cells, benign but secrete large quantities of catecholamines causing increased blood pressure and heart rate
What are the effects of glucose imbalance?
Excess- dehydration, microvascular damage such as blindness
Deficiency- CNS function effected as heavily glucose dependent
What are the two stages of glucose metabolism?
Anabolic
Catabolic
Explain the anabolic stage of glucose metabolism
Starts at food ingestion and several hours after
Caloric intake exceeds caloric demand
Plasma glucose levels increase
Energy gets stored
Explain the catabolic stage of glucose metabolism
4-6 hours after food intake
Caloric demand exceeds caloric intake
Plasma glucose decreases
Endogenous fuel mobilised from the liver, muscle and adipose and stored anabolic fuel released
Define glycogenesis
Glucose to glycogen which gets stored
Define glycogenolysis
Glycogen to glucose which is released into blood
Define glycolysis
Glucose to pyruvate
Define gluconeogenesis
Pyruvate to glucose
Which type of islet of langerhans cells produce which hormone
Alpha- glucagon
Beta- insulin
What do insulin and glucagon do?
Insulin- stores fuel in anabolic phase
Glucagon- mobilises fuel in catabolic phase
Describe key features of insulin
Peptide hormone
Receptor is receptor tyrosine kinase
Mainly targets liver, muscle and adipose
What stimulates insulin secretion?
Glucose, GI hormones and parasympathetic nerves which are activated on eating
What inhibits insulin release?
Sympathetic nervous system
What is the action of insulin of the blood?
Reduces glucose, amino acid and fatty acid levels
What is the action of insulin on the liver?
Binds to insulin receptor on target tissue when glucose enters hepatocyte
Glucose storage is increased due to increased glycogenesis and glycolysis and decreased gluconeogenesis
Lipogenesis increases so more fatty acids converted to lipid storage
Proteogenesis increased so more proteins are formed from amino acids
What is the effect of insulin on muscles?
Binds to receptor activating GLUT4 to insert into membrane so more glucose can enter the cell
Increased glucose storage from increased uptake, glycolysis and glycogenesis
Increased amino acid uptake and proteogenesis
What is the effect of insulin on adipose?
Increased glucose removal from the blood due to increased uptake and glycolysis
Increased fatty acid synthesis
increased lipogenesis
What is the main regulator of glucagon concentration?
Glucose concentration as glucose inhibits glucagon
Describe the action of glucagon?
Liver is main target
Increases glucose output by increased glycogenolysis and gluconeogenesis
Increases lypolysis by increasing fatty acids and ketone bodies to be used as fuel by muscles and CNS when glucose low
What are regulators of blood glucose, not insulin or glucagon?
Growth hormone
Glucocorticoids
Adrenaline
How does growth hormone regulate blood glucose?
Inhibition of insulin induces glucose utilisation
Inhibits lipogenesis and glucose uptake in adipose
Increases glycogenolysis and gluconeogenesis but protects protein
Increased blood glucose
How do glucocorticoids regulate blood glucose?
Protects from hypoglycaemia during stress
Stimulates gluconeogenesis and enhances glucagon and adrenaline
Inhibits effects of insuline
How does adrenaline regulate blood glucose?
Maintains glucose supply to the brain
Stimulates liver gluconeogenesis and glycogenolysis
Stimulates adipose lipolysis
What are the two types of diabetes?
Type 1- autoimmune disease destroying beta cells so are unable to produce insulin
Type 2- reduced beta cell function or insulin resistance in target cells
What are the symptoms of diabetes?
Dehydration Thirst Excessive urination Tiredness Weightloss Hunger Ketoacidosis
How does type 1 diabetes work?
Beta cells produce little or no insulin so high blood sugar but low glucose uptake
Glucagon breaks down fat, glycogen and proteins further increasing blood glucose
Glucose and ketone produced in huge excess causes high blood osmolality
Ketoacidosis and osmotic stress causes dehydration and glucosuria
How is type 2 diabetes caused?
Insulin resistant target tissues or impaired beta cell function
What are the treatments for diabetes?
Type 1- therapeutic insulin and glucose monitoring
Type 2- diet and exercise management, insulin when required
What are the roles of calcium in the body?
Component of skeleton and teeth Muscular contraction Blood coagulation Enzyme activity Neuronal excitability Hormone secretion
Where is calcium stored in the body?
99%- inorganic mineralised matrix of bone as hydroxyapatite
0.9%- endoplasmic reticulum
0.1%- extracellular fluid
Tiny amount free in cytosol
How is calcium stored in ECF?
50%- biologically active ionised Ca2+
5%- calcium salts
45%- protein bound
Which storage of calcium is regulated in the body?
ECF
How does Ca2+ act as a regulatory ion?
ECF has huge concentration compared to cytosol
Ca2+ influx into cytoplasm is controlled by Ca2+ ion channels so Ca2+ can act as signalling ion to activate intracellular processes
What are the 3 hormones that regulate calcium homeostasis?
Parathyroid hormone
Active vitamin D
Calcatonin
What are the main tissues involved in calcium regulation?
Gut
Bone
Kidneys
What is the parathyroid hormone and why and where is it released?
Peptide hormone
Released in response to falling circulating levels of calcium
Parathyroid gland (4 on dorsal aspect of thyroid gland)
How is parathyroid secretion controlled?
Stored in secretory granules of chief cells
Release is regulated by circulating concentration of calcium with low calcium promoting secretion
What is the slow and fast exchange effect on bone of the parathyroid hormone?
Slow- bone dissolution from osteoblast activity
Fast- release from bone fluid labile pool
How does the fast exchange in bone work regarding the parathyroid hormone?
Parathyroid hormone activates pathways to increase Ca2+ channels
Allows calcium management in and out of circulation
What is active vitamin D?
Steroid produced from cholesterol or acquired in the diet
When is active vitamin D produced?
In response to falling levels of blood calcium via parathyroid hormone
What are the actions of active vitamin D?
Longer term Ca2+ regulation
Increased absorbtion of Ca2+ from intesting so more Ca2+ can be stored in bone to protect it
Supports protein synthesis of Ca2+ channels, pumps and exchangers
What is calcitonin and how and where is it released from?
Peptide hormone
Released rapidly in response to high blood Ca2+ from C cells in thyroid gland
What is the role of calcitonin?
Reduce blood Ca2+ and prevent hypercalcaemia
Target bone and kidneys primarily to inhibit bone resorption and ca2+ absorption in kidneys
Acts as emergency hormone to prevent excess loss from skeleton in pregnancy
What disorders are associated with calcium homeostasis?
Rickets/osteomalacia
Hyperparathyroidism
Hypoparathyroidism
What are the causes and effects of rickets?
Causes- diet deficient in vitamin D, lack of sunlight and lack of renal 1 alpha hydroxylase
Effects- un mineralised cartilage, weak bones
What is hyperparathyroidism?
Excessive parathyroid hormone
What are the two types of hyperparathyroidism?
Primary- unregulated excessive parathyroid released
Secondary- chronic renal failure causing excess parathyroid hormone secretion
What is hypoparathyroidism?
Inadequate parathyroid hormone secretion
Describe how calcium ions can act as signalling receptors
Influx of Ca2+ into cells
Cellular function regulated by interaction with intracellular calcium binding proteins and calcium sensitive protein kinases
Biological response triggers
