Hormones Flashcards
(140 cards)
1
Q
What is the endocrine system and what is it made up of?
A
Organs that secrete a hormone into the blood are called endocrine glands - release ‘chemical messengers’
- brain (pituitary + pineal gland), hypothalamus, thymus, pancreas, thyroid, adrenal glands, ovaries and testes
2
Q
How can hormones act?
A
Can be autocrine, paracrine or act on far off hormones
3
Q
How do hormones regulate on a whole body level?
A
Regulation and integration of:
- ionic fluid balance
- energy balance (metabolism)
- coping with the environment
- growth and development
- reproduction
4
Q
How do hormones regulate on a cellular level?
A
Regulation of:
- cell division
- differentiation
-death (apoptosis)
- motility
- secretion
- nutrient uptake
5
Q
How do hormones regulate on a molecular level?
A
Regulation of:
- gene transcription
- protein synthesis and degradation
- enzyme activity
- protein conformation
- protein-protein interactions
6
Q
What are the 3 types of hormones?
A
Steroid hormones -
- cholesterol derivatives, eg testosterone, oestrogen and cortisol
Peptide hormones -
- eg growth hormone, oxytocin, parathyroid hormone
Amino acid-derived hormones
- eg thyroid hormones and catecholamines
*travel free in plasma or need to bind to protein to remain in circulation
7
Q
What is endocrine feedback?
A
The nervous system and endocrine system are tightly integrated
- the hypothalamus receives sensory inputs
- detect changes in both the internal and external environments
- negative feedback
- some positive feedback loops (eg oxytocin + partitution)
External conditions
Hypothalamus
Releasing hormone
Anterior pituitary
Tropic hormone
Endocrine gland
Hormone
8
Q
What is the mechanism is action for steroid hormones?
A
Composition - cholesterol
Location of receptor - cytosol/nucleus
Mechanism of action - bind DNA/modify transcription
Speed of effect - slower
Longevity of effects - more permanent
Examples - testosterone, oestrogen
9
Q
What is the mechanism of action of peptide hormones?
A
Composition - amino acids
Location of receptor - cell surface
Mechanism of action - 2nd messengers
Speed of effect - rapid
Longevity of effects - temporary
Examples - ADH, growth hormone
10
Q
Why is the pituitary gland important?(analogy)
A
The pituitary gland in the master of an endocrine orchestra
-adrenals, ovaries, testes, thyroid
11
Q
What is the pituitary gland? What is the general structure?
A
- a small structure at the base of the brain which releases hormones that in turn controls the activity of the body’s other hormone glands
- hypothalamus
- infundibular stalk
- optic nerve/optic chiasm
- pituitary gland
12
Q
What are the 2 lobes of the pituitary gland and what do they do?
A
Anterior lobe (pars distalis)
- portal blood vessels connect pituitary and hypothalamic capillary beds
Posterior lobe (pars nervosa)
- nerve fibres that originate in the hypothalamus and transport hormones to posterior pituitary
13
Q
What 2 hormones are released by the posterior pituitary?
A
Hormones secreted in response to nerve impulses
Oxytocin
Vasopressin (anti-diuretic hormone, ADH)
14
Q
What does oxytocin do?
A
- controls milk release from lactating breast
- controls uterine contraction at onset of labour
15
Q
What does vasopressin (ADH) do?
A
Acts on kidneys to absorb water
16
Q
What are the (2) cell bodies like in the posterior pituitary?
A
Cell bodies - paraventricular nucleus and supra optic nucleus
- both nuclei produce both hormones
- both produced from the same pro-hormone
17
Q
What is the mechanism of oxytocin?
A
Interaction of oxytocin with its receptors raises the level of intracellular calcium in the myoepithelial cells of the mammary glands
- myoepithelial cells contract (in response to oxytocin) forcing milk into ducts
18
Q
What is the neuroendocrine reflex of suckling?
A
Suckling
Hypothalamus
Posterior pituitary
Oxytocin
Milk squeezed out
19
Q
What does the anterior pituitary do?
A
- regulator of the endocrine system
- secretes 6 different hormones
- most of which regulate the secretions of other endocrine organs (tropic hormones)
20
Q
What 6 hormones are produced by the anterior pituitary?
A
- growth hormone
- prolactin
- adrenocorticotropic hormone (ACTH)
- thyroid stimulating hormone (TSH)
- follicle stimulating hormone
- luteinising hormone
21
Q
What does ADH regulate?
A
Blood osmolarity and urine output
22
Q
What happens if ADH is present and when ADH is NOT present?
A
ADH present - collecting duct is highly permeable to water, small volume of concentrated urine produced (increased aquaporins )
No ADH present - collecting duct is not permeable to water, large volume of dilute urine produced (minimal open aquaporins)
23
Q
What does increased plasma osmolarity stimulate?
A
Increased plasma osmolarity eg haemorrhage / dehydration stimulates osmoreceptors in hypothalamus
24
Q
What is the link between alcohol and ADH?
A
Alchohol inhibit the secretions of anti-diuretic hormone (ADH) from the posterior pituitary
25
What hormones does the hypothalamus control?
- corticotropin releasing hormone (CRH)
- gonadotropin releasing hormone (GRH)
- thyrotropin releasing hormone (TRH)
- growth hormone releasing hormone (GHRH)
- dopamine (DA)
- somatostatin (SS)
26
What are the 5 different cell types and what hormones are they found in?
Somatrophs - growth hormone
lactotrophs - prolactin
Corticotrophs - adrenocorticotropic hormone (ACTH)
Gonadotrophs - FSH & LH
Thyrotrophs - thyroid stimulating hormone (TSH)
27
What are the target organs of FSH and LH?
Ovaries and tests
28
What is the target organ of ACTH?
Adrenal glands
29
What is the target organ of TSH?
Thyroid glands
30
What is the target organ of growth hormone?
Bone, skeletal muscle
31
What is the target organ of prolactin?
- mammary glands
32
What is growth hormone and what does it do?
- synthesised and stored in somatrophs
- principle targets bone and skeletal muscle
- stimulates growth in children and adolescents but continues to exert important effects throughout adult life
33
What are the direct metabolic effects of HG?
- anabolic
- glucose sparing (conserve glucose for CNS) with an anti-insulin action, protects against hypoglycaemia
34
What effect does GH have on muscle?
- decreases glucose uptake
- stimulates amino acid uptake/protein synthesis
- inhibits protein breakdown - increased muscle mass
35
What effect does GH have on adipose tissue?
- decreases glucose uptake
- increases lipolysis (decrease in fat deposits)
36
What effects does GH have on the liver?
- increases gluconeogenesis
- increases protein synthesis
- stimulates IGF production
37
What is GH excess (gigantism) and how is it caused?
Usually the result of pituitary tumour secreting growth hormone
GH excess - gigantism
- abnormally high linear growth due to excessive IGF whilst the epiphyseal growth plates are open during (children)
- normal body proportions as soft tissues are also affected
38
What are the indirect effects of GH?
- GH actions via insulin-like growth factors
Growth hormone - liver - IGF
39
What effect does IGF have on skeletal growth?
- cartilage formation
- bone deposition - lengthening + thickening
- growth promoting- bone response to GH ceases when growth plates fuse
40
What effect does IGF have on soft tissue growth?
- protein synthesis
- cell proliferation
41
What is somatopause?
Growth hormone decline
- decrease in lean body mass
- decline in bone mineral density
- increase in body fat
42
What is GH excess: acromegaly?
Increased growth hormone later in life after fusion of epiphyses (growth plates)
Usually due to pituitary tumour
43
What are the features of Acromegaly?
Course facial features
Enlarged hands and feet
Protruding jaw and separation of teeth
Enlarged tongue and thickened lips
Deep voice
Cardiomegally
Diabetes
44
What is GH insuffiency in children?
Pituitary dwarfism
- slow growth rate below 3rd centile on age/height or bone chart
- normal body proportions
- poor muscle development, excessive subcutaneous fat
GH insufficiency in adults = no major symptoms
45
What is the thyroid gland?
- discrete organ, adheres to the trachea
- 2 large asymmetrical flat lobes connected by isthmus
- regulated by the hypothalamus and pituitary
- the thyroid gland has a rich blood supply
46
How is the thyroid gland developed?
- fully developed by week 12 of gestation
- capable of producing T3/T4 at 14 weeks
- responsive to TSH at 22 weeks
- thyroid hormones crucial for subsequent fetal growth and development
47
What is the histology of the thyroid gland?
- functional unit = follicle (200-300um in diameter)
- 1000s in each gland
- each follicle consists of a layer of follicular cells (simple cuboidal epithelial) surrounding a colloid-filled activity
48
What are the hormones produced in the thyroid?
- triodothyronine (T3) and thyroxine (T4)
- the thyroid secretes about 80-100um of T4 but only 5um of T3 per day
- however T3 has a much greater biological activity (about 10x) than T4
- T4 and T3 contain 4 and 3 atoms of iodine per molecule, respectively hence the name
Hormone class= amino acid derived, tyrosine, iodinated
49
What is rT3? What are the half life of T3, T4 and rT3?
RT3 (reverse T3) from T4 is biologically inactive
- <0.5% of T3 and T4 present in free form
- in plasma bound to thyroxine-binding globulin+albumin
T3 half life = 1-3 days
T4 half life = 5-7 days
RT3 half life = -5hrs
50
What are the 2 principle raw materials for thyroid hormone synthesis?
1) Tyrosine
2) Iodine
51
What is tyrosine?
- provided by thyroglobulin
-secreted by follicular cells into lumen of follicle as colloid
52
What is iodine?
- iodine is essential requirement (min 75um per day)
- iodide is pumped into follicular cells against concentration gradient (40x blood concentration)
- dietary iodide is oxidised to iodine
53
What is the process of T3 and T4 synthesis in colloid?
1) Thyroglobin is synthesised and discharged into the follicle lumen
2) Iodide (I-) is trapped (actively transported in)
3) Iodide is oxidised to iodine using enzyme thyroid peroxidase (TPO)
4) Iodine is attached to tyrosine in colloid, forming DIT (2 iodine) and MIT (1 iodine)
5) Iodinated tyrosines are linked together to form T3 and t4
6) Thyroglobulin colloid is endocytosed by thyroid hormone binding globulin and combined with a lysosome
7) Lysosomal enzymes cleave T4 and T3 from thyroglobulin and hormones diffuse into bloodstream
54
What is the major advantage of T3 and T4 synthesis?
- the thyroid gland is capable of storing many weeks worth of thyroid hormone (coupled to thyroglobulin)
- if no iodine is available for this period, thyroid secretion will be maintained
55
What are the effects of thyroid hormone?
- 90% of thyroid hormone released is t4
- t3 has a much greater biological activity
- enzymatic conversion of T4 into t3 in peripheral tissues (liver, kidneys and skeletal muscle)
56
What is levothyroxine?
Levothyroxine (l-thyroxine) is a synthetic thyroid hormone that is chemically identical toT4
57
What do thyroid hormones do once released into blood stream?
- thyroid hormone binds to intracellular receptors
- complex with thyroid response elements (TRE) that bind DNA and influence gene expression
58
What does T3-THR do?
T3-THR complex binds to thyroid response elements within DNA
- stimulates transcription/translation of a number of proteins within metabolism
59
What thyroid functions are stimulated by TSH?
- promoting the release of thyroid hormones into bloodstreams
- increasing the activity of the iodide pump and iodination of tyrosine to increase production of thyroid hormones
60
What do the transcribed proteins t3 and t4 do?
- increase cellular metabolism
- increase cellular oxygen consumption
- increase cellular glucose uptake
- increase circulation and respiration
And promote nervous system and skeletal development
61
What can T3 and T4 clinically help maintain?
- energy levels
- weight
- thermoregualtion
- heart rate
- GI motility
- mood
62
What are the cardiovascular effects of t3 and t4?
- increases cardiac output, increased heart rate and contractivity
- increases basal metabolic rate
- important in temperature regulation and adaption to cold environments
- O2 consumption and heat production
- increases mobilizations and utilisation of glucose, fat, proteins
63
What effects on growth and maturation do the thyroid hormones have?
- bone growth
- synergy with growth hormone
- CNS development and function
- Thyroid hormone deficiencies can result in mental impairment and short stature
- respiratory effects
- skeletal muscle function
- regulation of reproductive function
- synergy with catecholamines
64
What is the process of thyroid hormone regulation?
Stimuli - stress, cold stress, low metabolic rate
-
Thyrotropin-releasing hormone (TRH)(hypothalamus)
-
Thyroid-stimulating hormone (TSH)(anterior pituitary)
-
Thyroxine (T4) and T3 (thyroid) (negative feedback)
-
Metabolic rate and heat production, enhancement of growth and CNS development, enhancement of sympathetic activity
65
What is meant by ‘hypothyroid’?
- under active thyroid
- in general metabolic rate decreases and weight gain
66
What is meant by ‘hyperthyroid’?
- over active thyroid
- in general metabolic rate increases and weight loss
67
What are the symptoms of hypothyroidism?
- dry, cold skin
- sensitivity to cold
- weight gain despite loss of appetite
- impaired memory
- mental dullness
- lethargy
68
Clinical exam, diagnosis and treatment of hypothyroidism?
Clinical exam -
- reduced metabolic rate
- reduced cardiac output
Diagnosis -
- low plasma levels of free t3 and t4
Treatment -
- thyroxine (dose determined by TSH monitoring)
69
What are the symptoms of hyperthyroidism?
- loss of weight
- excessive sweating/intolerance to heat
- palpitations and an irregular heartbeat
- anxiety and nervousness
- exopthalamus
70
Clinical exam and treatment of hyperthyroidism?
Clinical exam -
Raised metabolic rate + oxygen consumption
- increased heart rate and hypertension
Treatment
- surgical removal of all or part of the thyroid
- ingestion of radioactive iodine that destroys active thyroid cells
- drugs that interfere with the glands ability to make T3 and T4
71
What is Graves’ disease?
- abnormal antibodies mimic TSH
- activates TSH receptor inducing T3 and T4 release
- characterised by goitre, exopthalamus and lid retraction
72
What is iodine deficiency?
Endemic goitre
- insufficient dietary iodine
- insufficient amounts of T3 and T4
- abnormally high TSH
- abnormal growth of the thyroid due to graphic effects of TSH
73
What is Hashimoto’s disease?
Most common hypothyroids
- autoimmune disease
- antibodies against thyroglobulin or thyroid peroxidase
- interferes with thyroid hormone synthesis
- antibodies also against TSH receptor
- prevents stimulation of T3 and T4 release
74
What is congenital hypothyroidism?
- thyroid hormones are essential for normal brain development and growth
- cretinism - 1 in 4000 births
- intellectual disability
- short disproportionate body
- thick tongue and neck
- lack of gland or incorrect hormone biosynthesis
- intellectual disability if treatment later than 3 months
75
What is the structure of the adrenal glands?
- a pair that lies above the kidneys
- each gland enclosed in a fibrous capsule surrounded by fat
- each gland equivalent to 2 endocrine glands
Inner = adrenal medulla
Outer = adrenal cortex (under hormone control)
- function independently but share a common blood supply and play a role is response to stress
76
How heavy are the adrenal glands? What is the blood supply like?
6-10g (half the weight of thyroid glands
- rich blood supply - adrenal arteries arise directly from the aorta
- blood flows through the cortex and drains into the medulla
77
How are the adrenal glands developed?
- at 7 weeks of life, the primitive adrenal medullary tissue begins to invade the cortex
- at birth, the medullary cell mass is fully surrounded by the cortex
- cortical differentiation into a zona glomerulus, zona fasciculata, zona reticularis is not complete until later in childhood
78
What is the adrenal medulla and what does it do?
- modified part of the sympathetic nervous system
- enlarged and specialised sympathetic ganglion
- secrete catecholamines hormones
- Adrenaline (epinephrine)
- noradrenaline (norepinephrine)
79
What is the mechanism behind catecholamine release?
- catecholamine release occurs as part of a general sympathetic stimulation
- important in the fight or flight-response (fear, anger, stress, excitement etc)
- prepares the body for acute stress
1) stress causes sympathetic nervous signals to adrenal medullae
2) adrenal medulla release catecholamines into blood stream
3) fight or flight response causes reactions in multiple parts of the body
- catecholamines are rapidly inactivated
80
What are the cardiovascular effects of adrenaline?
- increases heart rate and stroke volume
- increase in blood pressure (systolic)
- vasodilation of coronary and skeletal muscle blood vessels
- vasocontriction of blood vessels to ‘non-essential’ tissues (GIT, skin, kidneys)
- bronchodilation
81
What are the receptors for adrenaline?
A1, a2, b1+2+3
- adrenaline interacts primarily with beta receptors
82
What are the metabolic effects of adrenaline?
- increases the amount of energy for immediate use
- liver converts glycogen to glucose
- metabolic rate increases
- blood flow changes, reducing digestive system activity and urine output
83
What is the structure of the medulla?
Medulla is chiefly composed of chromaffin cells
- specialised postganglionic neurons
- preganglionic = splanchnic nerve fibres
- neurotransmitter is acetylcholine
Epinephrine secreted in response to acetylcholine released from splanchnic nerve fibres
80% of the medulla secretions is adrenaline (epinephrine)
20% is noradrenaline (norepinephrine)
84
What are the 3 morphological distinct zones in the adrenal cortex and what do they produce?
Zona glomerulosa - mineralocorticoids (aldosterone)(SALT)
Zona fasciculata - glucocorticoids (cortisol)(SUGAR)
Zona reticularis - gonadocorticoids (androgens) (SEX)
85
How does cholesterol progress into 3 new steroid hormones?
Starting point for all steroid biosynthesis -
Cholesterol (C27)
-
Pregnenolone (C21)
- series of hydroxylation reactions
Progestagens (C21)
-
Glucocorticoids, mineralcorticoids, androgens
86
What are adrenal androgens?
- insignificant amounts of testosterone
- adrenal glands produce dehydropianodrosterone (DHEA), dehydroepianndrosterene sulfate (DHEA-S) and androstenedione
- testosterone (and oestrogen) precursors
- converted to testosterone, DHEA and DHEA-S bind less efficiently to the androgen receptors (weak steroids)
- controlled by ACTH ( anterioir pituitary)
87
What is 21 hydroxylase deficiency?
High circulating testosterone levels lead to masculinisation of fetal external genitalia to variable degrees
88
What effects do adrenal androgens have in males?
- the contribution of testosterone derived from the adrenal glands pales to significance in comparison to the normal output of testosterone from the testes
Role is not fully understood -
- male secondary characteristics
- aggression in young boys
either over-secretion or under secretion of adrenal androgens usually does not have any noticeable consequences in males
89
What are the effects of adrenal androgens in females?
The ovaries make testosterone but most of it is immediately converted to oestrogen
- in females, the adrenal glands are the primary source of testosterone
- secrete half of the total androgenic requirement
- responsible for growth of pubic and auxiliary hair and sex drive
- kick starts puberty, maintain muscle and bone mass
90
What happens when there is excessive production of adrenal androgens? What medication is there for this?
- overproduction of ACTH, adrenal tumour, Cushing’s syndrome
- masculinisation of females
- acne, hirsitism, irregular periods, breast shrinkage
- play a role in polycystic ovary syndrome (PCOS)
- patients with PCOS have adrenal androgen excess
Anti-androgen blocks androgen receptors
- cyproterone acetate and ethinylestradiol
91
What is DHEA?
- apart from providing androgen precursors, it is not clear what other roles, if any, the zona reticulum plays in adult humans
- DHEA-S is the most abundant circulating hormone in young adults
92
What and where is aldosterone produced? Control of release?
- mineralocorticoid - zona glomerulosa
- essential to life-absence leads to circulatory failure and death within a few days if adrenal cortex is removed
- aldosterone secretion is regulated by the plasma levels of sodium and potassium via the renin-angiotensin system
Response to renin-angiotensin system (RAAS)
- decreased ECF volume (hypovolaemia or hypotension)and decreased renal blood flow
- response to high plasma potassium
93
What are the principle action of aldosterone?
- control ECF volume
- conserve body sodium
- stimulates reabsorption in renal distal convoluted tubules in exchange for potassium
94
What is and where is cortisol produced?
Glucocorticoids: zona fasciculata
- wide range of actions: essential for life
- stress is a powerful stimulator of cortisol production
- stress = physical trauma, intense heat or cold, infection, mental or emotional trauma
95
What does cortisol do?
- mediates the body’s response to stress in response to endocrine signals
- metabolic effects
- cortisol increases plasma glucose and FFA concentration
- provide energy substates to body tissues for their response to the stress event that stimulated cortisol production
96
What are the effects of increased cortisol?
Increased catabolism: cortisol increases skeletal muscle catabolism. Amino acids are then converted into glucose (gluconeogenesis)
Increased lipolysis: liberate free fatty acids and triglycerides from adipose tissue used as an energy source
Increased intake: stimulates appetite. If the stressful event doesn’t involve physical activity - weight gain
97
What can long term stress and cortisol production lead to?
Cortisol causes fat stores and excess circulating fat to be relocated and deposited deep in the abdomen, enhancing obesity
- may contribute to emotional instability
- anti-inflammatory - blocks the processes which leads to inflammation (in high doses)
- immunosuppressive - fall in antibody production and number of circulating lymphocytes
- used clinically to treat patients following transplants
98
How is cortisol release regulated?
Secretion of both the glucocorticoids and adrenal androgens are controlled by ACTH secretion
- ACTH stimulates enzymes involved in the cortisol and androgen synthesis
- cortisol acts to counteract the effects of stress
- stress = physiological, biochemical and emotional
99
What is Cushing’s syndrome? What are the symptoms? What is the treatment?
Adrenal cortex hyper function
- overproduction of cortisol
- as a result of an adrenal tumour or pituitary tumour
- redistribution of body fat
- muscle wastage
- thin skin, bruising, abnormal pigmentation
- changes in CHO and protein metabolism
- hyperglycaemia, hypertension (cortisol in excess binds aldosterone receptor)
- cortisol has weak mineralocorticoid activity
Treatment - surgery, radiation, medication
100
What is Conns disease?
- mineralocorticoid excess
- rare
- overproduction of aldosterone
- retention of sodium, loss of potassium and alkalosis
- hypertension through expansion of plasma volume
101
What is addisons disease?
Adrenal cortex hypofunction
- rare
- damage to adrenal glands, autoimmune disease or pituitary damage
- deficits in glucocorticoids and mineralcorticoids
- progressive weakness, lassitude and weight loss
- pigmentation of skin and mucosal membranes
Main cause:
- autoimmune destruction of adrenal cortex
102
Describe the physiological use of calcium?
- calcium plays a fundamental role at the microscopic and macroscopic level
- structural component of bones and teeth (99%) calcium
- maintains normal excitability of nerve and muscle cells
- involved in neurotransmitter and hormone release
- muscle contraction (skeletal and cardiac)
- activation of many enzymes
- coagulation of blood
- milk production and more
103
Where does calcium occur in nature?
In nature: does not exist freely
- occurs mostly in soil systems as limestone (CaCO3), gypsum (CaSO42H2O) and fluorite (CaF2)
104
Where does calcium occur in the body?
In the body: the most abundant mineral
- average adult body contains approximately 1kg (0.1% in ECF, 1% in cells, 99% in skeleton - hydroxyapatite)
- bones can serve as large reservoirs, releasing calcium when ECF concentration decreases and storing excess calcium
105
What are the 3 types of calcium found in plasma?
Plasma calcium concentration is 2.2-2.6mM
1) Protein bound calcium
2) ionised of free calcium
3) Complexed or chelated calcium
106
What is protein-bound calcium?
Cannot diffuse through membranes and thus is not usable by tissues
107
What is ionised or free calcium?
Physiologically active form (free ionised calcium is tightly regulated +-5%)
108
What is complexed or chelated calcium?
Bound to phosphate, bicarbonate, sulfate, citrate and lactate
109
What is hypocalcemia?
- too low: involuntary muscle contraction
- neuronal hyper-excitability (tetany)
- low ionised calcium levels in the extracellular fluids increases the permeability of neuronal membranes to sodium ions
- causes progressive depolarisation which increases the possibility of actions potentials
110
What is hypercalcemia? What are the symptoms?
- too high: depression and kidney stones
High ca2+ - neurons - Na+ channels less likely to open (harder to depolarise, less excitable)
- confusion, hallucination, stupor
- slow muscle contraction (constipation, muscle weakness)
- slower or absent reflexes (classic symptom)
111
What does the exist of hypo/hypercalcemia suggest about maintaining calcium levels?
Essential that intra and extracellular levels maintained within narrow limits
112
What are the 3 control points for calcium?
Absorption - via intestines
Excretion - via kidneys/urine
Temporary storage - via bones
Calcium must be in a soluble and ionised form before it can be absorbed
- regulation is closely associated with phosphate
113
What are the 3 cell types found in bone?
osteoblasts
Osteoclasts
Osteocytes
114
What are osteoblasts?
Synthesise and secrete collagen and promote deposition of calcium phosphate crystals. Secrete factors that activate osteoclasts
115
What are osteoclasts?
Promote resorption of bone
116
What are the 2 ways calcium is regulated?
Acute control
Chronic control
117
What are osteocytes?
Essential role is exchange of calcium between ECF and bone
118
What is meant by acute control of calcium?
- must maintain constant free ca2+ concentration in the plasma
- mostly by rapid exchange between bone and ECF
119
What is meant by chronic control of calcium?
- maintain total level in the body long term
- adjust GIT absorption and urinary excretion
120
Plasma Ca2+ concentration is determined by what 3 things?
- net absorption of Ca2+ from the GIT
- net excretion of Ca2+ in urine
- exchange of Ca2+ with bone
121
What are the 3 hormones controlling plasma Ca2+ concentration?
1- parathyroid hormone
2 - 1,25-dihydroxycholecalciferol (calcitrol, activated vit D)
3 - calcitonin
122
What is the parathyroid gland?
- PTH gland monitors the concentration of calcium in the blood perfusing the glands
- about 4 on the back of thyroid
- removal - fatal hypocalceamia
123
What is parathyroid hormone? PTH
- peptide hormone
- stored within the chief cells
- half life of 5 minutes
- secreted continuously at a low rate
- released in response to low blood calcium
- exerts its effects on bone, gut and kidneys
124
What does the parathyroid hormone do? (PTH) What key enzyme does it activate?
- main target tissue is the kidney and bone
- increased reabsorption of calcium from the urine
- fast acting; decreased urinary calcium in minutes
- increases the expression of the enzyme 1a-hydroxylase (activates vitamin D)
- bone: increases osteoclast activity, indirectly causing increase in born resorption
PTH - no direct effect on intestine
125
What are the mechanisms activated when there is low calcium in the blood?
- low calcium
- parathyroid glands
- parathyroid hormone
Kidney: reabsorption and PO4 secretion
1a-hydroxylase - vitamin D
Bone resorption - increased calcium
feedback - hypercalcemia - inhibits PTH secretion
126
What are the 2 types of vitamin D and where can they be obtained?
- vitamin D2 (ergocalciferol): plant sources
- vitamin D3 (cholcalciferol): obtained from the diet (animal sources), food supplements and synthesised in the skin in the presence of sunlight
127
What is vitamin D2 and D3 converted to and why?
- D2 and D3 relatively inactive
- converted to 1,25-dihydorxycholecalciferol
Aka 1,25-dihydroxyvitamin D Bone resorption
1,25-(Oh)2D3
- calcitrol
128
What is the process of synthesising vitamin D from the sun?
Sunlight - (skin)
7-dehydrocholesterol
VitD3
Liver:dietary sources
Kidney: 1a-hydroxylase
1,25-hydroxyvitamin D3 (maintains calcium levels)
Active form of vitD3
129
Why is vitamin D not a true vitamin?
Vitamin D is not a true vitamin as people whose skin is exposed to sufficient sunlight do not need a dietary source
- unusual if the production of a hormone is unregulated, it is the conversion process that is actively regulated
130
What are the actions of calcitrol? (1,25-dihydrocholecalciferol)
- acts on cells of the GIT to increase production of calcium transport proteins
- leads to an increase in calcium uptake from GIT
- the only mechanism that can increase calcium stores
- bone: increases the secretion of osteoclast activating factors (indirect effect(
131
What does the release of 1a-hydroxylase do?
Kidney release 1a-hydroxylase
1,25(OH)2d3
+ small intestine, increased calcium absorption
- inhibits secretion of PTH
132
What is calcitonin and what is it secreted by?
- secreted by the c-cells (parafollicular cells) of the thyroid gland. Minor importance in adults
- lowers the level of free plasma calcium
- inhibition of osteoclast activity: bone resorption reduced (direct effect)
- increased excretion of calcium and phosphate by the kidneys
133
What are the hormones involved in the regulation of plasma calcium?
- major hormonal regulators: PTH, 1,25(OH)2D3 and possibly calcitonin
- others - growth hormone, adrenal glucocorticoids and thyroid hormones, oestrogens and androgens
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What is (primary) hyperparathyroidism and what does it cause?
- inappropriate (autonomous) secretion of PTH, resulting in hypercalcemia
- elevated PTH and raised serum calcium (and low serum phosphate)
- 85% of cases are caused by a single parathyroid adenoma
- presentation: bones, stones, abdominal groans and physchic moans
- brain tumours and osteoclast cysts
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What are the 3 key things that hyperparathyroidism causes?
Increased bone resorption
Increased GIT absorption
Decreased renal excretion
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What does hypocalcemia in children cause?
Vitamin D definciency - rickets
- bone remodelling impaired
- failure of calcification
- rickets: skeletal deformities of weight bearing bones in children
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What are the causes of vitamin D deficiency?
- poor diet
- malabsorption
- decreased sunlight
- liver or kidney disease
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What are the causes and treatments of hypocalcemia in adults?
Vitamin D deficiency: osteomalacia
- pseudofractures - weakening or softening of the bone, causing pain in back, pelvis and hips
Causes:
Vitamin D deficiency
Kidney disease or failure
Treatment
- dietary changes or supplements
- for kidney failure: medication to balance mineral and hormone levels
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What does vitamin D deficiency lead to?
Vitamin D deficiency leads to hypocalcemia
- hypocalcemia leads to increased excitability of nervous tissue (pins and needles, tetany, muscle cramps, convulsions)
- vitamin D defiency leads to reduction in intestinal calcium absorption
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Is hypocalcaemia in vitamin D deficient patients likely to become severe?
No, compensatory rise in PTH (body will keep sacrificing bones stores)
