Endocrine Physiology Flashcards
Endocrine system
cells of endocrine produce chemical messengers within glands that influence tissues separated from the gland by some distance
2 main regularity systems
- nervous system: precise, rapid, short term regulation
- endocrine system: slower, more sustained over long term processes
2 glandular systems in the body
- exocrine glands: glands that empty their secretions into body cavities through tubular ducts
- endocrine glands: ductless system composed of glands that release secretions internally into bloodstream
Glands of endocrine system
pituitary gland, hypothalamus, thyroid gland, parathyroid glands, adrenal glands, pancreas, gonads
2 reasons why they are highly vascularized
- all hormones are made from dietary precursors so they need a large blood supply
- rely on bloodstream to transport hormones to target sites
Paracrine signaling
hormone is released from cell but it will act on neighboring cells rather than on distant target cells
Autocrine signalling
hormone is released into extracellular space and acts on cell which it was released
Endocrine signalling
hormone is released into bloodstream and acts on distant target sites
Neuroendocrine signalling
nerve cells release neurotransmitter to neuroendocrine cells which release hormone into bloodstream
7 hormone characteristics
- regulate homeostasis
- high potency
- specific receptors
- act with a delay
- have limited storage
- secreted irregularly in phases
- carried in blood by binding proteins
2 main groups of hormones
- steroid: derived from cholesterol
- protein: amines (derived from tyrosine), peptides, proteins
Steroid hormone synthesis
- cholesterol enters cell bound to LDL
- can be stored in cell as lipid droplets
- cholesterol can also be synthesized within cell from acetate
- moved to mitochondria where formed into pregnenolone intermediate
- further modified into steroid hormones
- lipid soluble so can diffuse out of cell
Protein hormone synthesis
- made from translation of messenger RNA in nucleus
- mRNA –> pre-hormone –> pro-hormone –> hormone
- hormones packaged into secretory vesicle after passage through Golgi and move to plasma membrane to release contents
Role of secretory vesicle
- protect hormone from proteolytic degradation
- provide a reservoir in sites of synthesis
- provide a transport mechanism along microtubules and microfilaments to site of release
- provide a release mechanism - exocytosis
- provide a quantal release
2 types of hormones in plasma
- bound to binding protein - inactive
- free - active
4 roles of binding protein
- increase solubility and concentration of lipid-soluble hormones
- increase size, protecting hormone from clearance and degradation
- inactive free hormones, providing a buffer against large and sudden hormone changes
- dynamically regulated with rate of secretion, rate of degradation, and rate of hormone binding to receptors
Hormones are released
episodically
- increased level of hormones in blood can be achieved by increase in frequency or amplitude of release
Negative feedback
- more common
- inhibits hormone secretion when levels are high
- increases hormone secretion when levels are low
Positive feedback
- rare
- allows events to be rapidly attained after catastrophic collapse of system
- hormone acts on target cell to product another hormone which will stimulate original target cell to release more
Hormone receptor pattern
lock (receptor) in key (hormone) interaction
Importance of cAMP second messenger system
- protein hormones are not lipid soluble and cannot cross cell membrane and must bind to membrane bound receptors to produce a response
Signal amplification
- allow for amplification of response following binding of a hormone to its receptor
2 receptors for steroid hormones
- nuclear: binds to receptors in nucleus and alter protein synthesis
- cytoplasmic: involved in intracellular transport and provide a reservoir of hormone
Up-regulation
- more receptors
- occurs at low hormone concentrations to increase activity
- increased receptor synthesis or decreased receptor degradation
Sensitization
- more affinity
- occurs at low hormone concentrations to increase activity
- conformation changes in lock structure to make stronger interactions
Down-regulation
- less receptors
- occurs at high hormone concentrations to decrease activity
- decreased receptor synthesis, increased degradation, internalized membrane receptors, dislocation of receptor and signal transduction system
Densitization
- less affinity
- occurs at high hormone concentrations to decrease activity
- conformation changes in lock structure to make weaker interactions
3 endocrine dysfuction
- primary defects in synthesis - problem of endocrine gland
- defect in regulation of hormone - problem in hormone action
- defect in hormone action - problem with target tissue
What/where is the hypophysis
- pituitary gland
- found in ventral part of base
- lie just below the hypothalamus
Posterior pituiary
- neural tissue
- down-growth from hypothalamus
- neurohypophysis
Anterior pituitary
- non-neural tissue
- andenohypophysis
Intermediate pituitary
- between anterior and posterior pituitary
- lost before birth in humans
- scattered endocrine cells remain
2 hypothalamus nuclei
- paraventricular nuclei
- supraoptic nuclei
How are nuclei hormones produced and transported
- hormones synthesized in cell bodies of nuclei
- long axons pass down the infundibulum (contains neuron axons and blood vessels)
- end in posterior pituitary gland
- stored there until stimulus propagates to axon terminals and triggers release by exocytosis
- hormones will enter blood stream
2 neural secretions from posterior pituitary
- Antidiuretic hormone/vasopressin
- Oxytocin
How is ADH produced in nerve
- first product is called pro-pressophysin
- converted to ADH and bound to neurophysin protein
- neurophysin transports small hormone down axon and release
- after release neurophysin dissociates from hormone and has no action
2 ADH actions
- vasoconstriction action
- anti-diuretic action
Vasoconstriction action
- causes contraction of blood vessels
- causes increase in blood pressure
- only occurs at high concentrations of hormones such as blood loss/hemorrhage
Anti-diuretic action
- control fluid balance in body by reducing urination
- increases permeability of the renal collecting duct
- increases number of water channels in collecting duct
- reduces glomerular filtration rate
- causes contraction of glomerulosa cells reducing surface area for filtration
Mechanism of ADH action
- ADH in circulation will travel to kidneys
- ADH binds to its receptor on collecting cell
- binding of ADH induces synthesis of second messenger (cAMP)
- cAMP causes up-regulation of aquaporin 2 protein via gene transcription
2 factors affecting ADH secretion
- plasma volume
- plasma osmolarity
What receptors are in hypothalamus
- osmoreceptors
- SON and PVN
Baroreceptors
- blood volume affects blood pressure
- changed in blood volume affect stretching of blood vessel walls
- found in aortic arch and carotid sinus
Main stimuli for ADH decrease
decrease in blood volume or increase in blood osmolarity
ADH response to dehydration steps
dehydration –> decrease blood volume –> decrease stretch of blood vessels –> decrease activity of baroreceptors –> decrease inhibition of inhibit afferents to hypothalamus –> increase neuron activity in hypothalamus –> increase release of ADH –> ADH acts on collecting ducts in kidneys to increase water reabsorption from urine
ADH response to overhydration steps
increased water –> increase extracellular fluid volume –> increase blood volume –> stimulate cardiovascular baroreceptors –> increases activity if inhibitory affects to hypothalamus –> decrease ADH release –> decrease water reabsorption –> increase water excretion and reduce blood volume
With an ____ in plasma osmolarity, there is ____ in plasma ADH levels
- increase
- increase
linear
With an ____ in mean arteriole pressure, there is ____ in plasma ADH levels
- decrease
- increase
Other factors that increase ADH secretion
- stress/emotion
- heat
- nicotine
- caffeine
Other factors that decrease ADH secretion
- cold
- alcohol
ADH deficiency
- diabetes insipidus
- hypothalamic/central - problem of ADH production
- nephrogenic - problem of ADH action
ADH excess
- syndrome of inappropriate ADH (SIADH)
- problem of ADH production and feedback failure
- low blood sodium levels
Polyuria
produce large amounts of dilute urine
Polydipsia
excessive thirst and fluid intake
Treatment for diabetes insipidus
- hypothalamic/central - ADH
- nephrogenic - other antidiuretics
Oxytocin release and production
- released from posterior pituitary
- produced in paraventricular nuclei (PVN) in hypothalamus
Oxytocin actions
- uterine myometrium: parturition, prevent hemorrhage, restoration of pre-pregnancy uterine size, stimulation of sperm movement in female tract, movement of cervix
- mammary myometrium: stimulates milk letdown
Effect of oxytocin in parturition
- positive feedback loop
- initial mild contractions lead to oxytocin release and further uterine contractions, putting more pressure against the cervix
Effect of oxytocin in milk let-down
- suckling causes release of oxytocin
- acts on receptors of myoepithelial cell which contract
- milk that is already synthesized is released into lumen
- positive feedback loop
- conditioned response - visual and auditory stimuli
Other functions of oxytocin
- released during sexual intercourse to stimulate orgasm
- social bonding
Regulation of oxytocin secretion
- genital tract or nipple stimuli
- stress lowers secretion
- psychogenic/physical
Oxytocin deficiency
- impaired delivery
- impaired lactation
Oxytocin excess
- no problems associated
Anterior pituitary
- produced hormones essential for growth and reproduction
- controlled by hypothalamus through blood supply
Median eminence-capillary bed
- receives axons from nuclei in hypothalamus
- gives rise to hypothalamo-hyposphyseal portal vessels
Hypothalamo-hyposphyseal portal vessels
- venous or portal blood vessels which run into anterior pituitary
Short portal vessel
- blood vessel which comes from capillary bed into posterior pituitary
Parvocellular neurons
- neurons with small cell bodies with short axons
- nuclei who axons end in median eminence
- product neural secretions that are released into blood vessels which carry secretions down to anterior pituitary
Magnocellular neurons
- neuroendocrine cells located in hypothalamus
- largest cells in brain
- synthesize oxytocin and ADH
- PVN and SON
5 secretions of anterior pituitary
- gonadotropins - stimulate gonad activity
- growth hormone (GH) - stimulate growth
- thyroid-stimulating hormone (TSH) - stimulate thyroid gland
- prolactin (PRL) - acts on mammary glands to affect milk formation
- adrenocorticotropin (ACTH) - acts on adrenal gland
7 hypothalamic releasing hormones
- GnRH - stimulates release of LH and FSH
- GHRH - stimulates release of GH
- TRH - stimulates release of TSH and prolactin
- PRFs - stimulates release of prolactin
- CRH - stimulates release of ACTH
- SRIF - inhibits release of GH and TSH
- PIFs - inhibits release of FSH and PRL
TSH
- stimulates thyroid gland
- secrete T3 and T4
ACTH
- stimulates adrenal cortex
- secrete cortisol
LH and FSH
- stimulate gonads
- secrete sex hormones and regulate growth and development of gamete production
Negative feedback in hypothalamic-anterior pituitary control system
- hormones released from target endocrine gland will have negative feedback on anterior pituitary and hypothalamus
- anterior pituitary hormones exert feedback on hypothalamus
Effect of growth hormone (GH)
- effects muscle, liver, adipose tissue
- induces protein synthesis on muscle and liver
- increases lipolysis
- induces production of somatomedins (insulin-like growth factors) to increase tissue growth
- hyperglycemia and hyperlipidemia
Control of growth hormone (GH)
- GHRH stimulates
- GHIH/somatostatin inhibits
- increased by deep sleep, stress, reduced blood glucose levels, increased blood amino acids, decreased blood fatty acids
- pronounced diurnal rhythm of GH release
3 inhibitory GH effects
- somatomedins from liver
- GH inhibits own release
- inhibited by products of lipolysis and glucose
Diurnal pattern of GH release
- 24 hour cycle
- number and amplitude of GH release episodes increased in dark, sleep and fasting
- frequent meals high in glucose and fatty acids suppress GH release
- frequent meals high in amino acids increase GH relrease
Deficiency of GH
- dwarfism in juveniles
- somatopause in adults
Types of dwarfism
- isolated growth hormone deficiency (Type 1) - defect in GH production
- Laron-type dwarfism - defect in GH action because receptor problems
- GH dwarfs - normal body proportions for people their age, just shorter in height
- thyroid dwarfs - have body proportions of individual much younger than themselves
Somatopause
- increase fat production
- decrease lean body mass
- metabolic disturbances
- impaired immune function
- thymic atrophy
Excess of GH in childhood
- pituitary gigantism
Excess of GH in adults
- acromegaly
- growth in face bones, hands, feet, cartilage
- protruding jaw
- internal organs increase
- increased glucose release leading to diabetes
- due to GH secreting tumor on pituitary
Prolactin
- released from anterior pituitary
- gonadal modulator
- mammary gland development
- involved in lactation or milk production
Prolactin releasing factors
- stimulate prolactin secretion
- TRH and oxytocin
- estrogen and testosterone increases prolactin secretion
- progesterone inhibits prolactin secretion
- mammary stimulation - suckling
Excess prolactin
- hyperprolactinemia
- gonadal dysfunction, amenorrhea, reduced libido
- treated with dopamine agonist
Prolactin deficiency
- hypoprolactinemia
- gonadal dysfunction, lactation impairment
Pituitary diabetes
- excess of all anterior pituitary hormones
- hyperglycemia
Hypopituitarism
- deficiency in pituitary hormone production
Panhypopituitarism
- affects all pituitary hormones
Hypothalamic-pituitary-thyroid axis
- hypothalamus releases thyrotropin - releasing hormone (TRH) into hypothalamohypopshyeal portal vessels
- TRH acts on anterior pituitary to release thyroid-stimulating hormone
- TSH acts on thyroid gland to product T3 and T4 which acts on target cells
Thyroid hormone effects
- increase metabolic rate and heat production
- enhance growth and CNS development
- enhance sympathetic activity
What inhibits the axis
- T3 and T4 at mainly at pituitary and at hypothalamus
- stress
What stimulates the axis
cold in infants
Thyroid stimulating hormone (TSH)
- peptide hormone produced by anterior pituitary
- stimulates growth of thyroid gland
- trophic hormone: affects growth, nutrition, function of thyroid gland
- stimulates biosynthesis of thyroid hormones
- glycoprotein hormones - contains sugar residues
Thyroid gland
- vascular structure - good blood supply
- capsule of connective tissue covering the thyroid gland which is made up of secretory parts called follicles
- follicles have cavities lined with epithelial cells and are filled with viscous protein rich substance called colloid
Colloid
- consists of glycoprotein called thyroglobulin
- thyroglobulin is synthesized in follicular cells and secreted into colloid
- colloid is site of thyroid hormone biosynthesis
Thyroglobulin
- precursor for thyroid hormones
- contains tyrosine residues which provide template
2 thyroid hormones
- have tyrosine amino acids residues with iodine attached to them
- thyroxine (T4) has 4 iodine
- triiodothyronine (T3) has 3 iodine
- T4 is degraded by deiodinase to T3
- T3 is more biologically active but more T4 is produced
Synthesis of thyroid hormones
- iodide is cotransported with sodium ions across basolateral membrane in follicle cell
- iodide diffuses to apical membrane of follicle cell
- thyroglobulin is made in follicle cells and released into colloid by exocytosis
- iodide is oxidized to iodine at luminal surface of follicle cell and attached to rings or tyrosine residues on TG
- addition of 1 iodine - MIT, addition of 2 iodine - DIT
- coupling of MIT to DIT (T3) or DIT to DIT (T4)
- thyroid hormone secreted into blood
Enzyme responsible for thyroid hormone production
thyroid peroxidase
Thyroid hormones are ____ soluble
- lipid
- need to be carried by binding protein in blood
- TBG - thyroid binding globulin
Thyroid hormone receptors
- found everywhere on most cells
Thyroid hormone action
- latent period
- long lasting responses
- increases oxygen and glucose uptake by most tissues
- increases basal metabolic rate - calorigenesis - heat
- promotes neural activity
- cardiovascular action
- intermediary metabolism
- growth and development
3 thyroid hormone receptors
- membrane bound receptors - linked to glucose channels to allow glucose to enter
- cytoplasmic receptors - reservoir of hormone, stimulate ATP production
- nuclear receptors - affect gene transcription and protein synthesis
Thyroid hormone excess
- hyperthyroidism
- increased basal metabolic rate
- most common type is Grave’s disease - autoimmune disease which antibodies develop against TSH receptors
3 causes of hyperthyroidism
- primary problem with thyroid gland: excess T3 and T4 and toxic goiter
- secondary problem with pituitary gland: increased TSH and goiter
- tertiary problem with hypothalamus: increased TRH and goiter
Grave’s disease
- large swelling in neck, overstimulation of thyroid gland
- exophthalmos, eye bulging
- heart palpitations
- increased sympathetic nervous system action
Thyroid hormone deficiency
- hypothyroidism
- decreased metabolic rate
5 causes of hypothyroidism
- deficiency of dietary iodine: increased TSH and goiter
- primary problem with thyroid gland: increased TSH and goiter
- Hashimoto’s thyroiditis: autoimmune disease where antibodies developed against T3 and T4 and goiter
- secondary problems with pituitary gland: low levels of TSH, no goiter
- tertiary problems with hypothalamus: low levels of TRH, no goiter
Hypothyroidism in utero
- cretinism
- severely stunted mental and physical development
- irreversible
Hypothyroidism in adults
- myxedema
- accumulation of hyaluronic acid and mucus edema under skin
- slow mentation and slow speech
- lethargic
- bradycardia
Only hormone that provides feedback inhibition on adrenal cortex
- cortisol
Adrenal cortex release mechanism
- hypothalamus releases CRH
- stimulates anterior pituitary to produce ACTH
- stimulates steroidogenesis in all zones of adrenal cortex
ACTH
- peptide hormone
- produced by cell called corticotrophs
- trophic hormone stimulates adrenal blood floow, adrenal growth, adrenal steroidogenesis
POMC processing
- make ACTH –> alpha-MSH (pigmentation)
- make beta-LPH –> beta-MSH (pigmentation) or beta-endorphin (opiate) –> met-enkephalin (opiate)
Adrenal cortex zones
- glomerular zone - aldosterone - salt/water retention
- fascicular zone - cortisol - sugar metabolism
- reticular zone - androgens - sex characteristics
Steroidogenesis in glomerular zone
- all steroids produced from cholesterol
- cholesterol –> pregnenolone –> progesterone –> corticosterone –> aldosterone
Aldosterone action
- steroid hormone
- upregulate/synthesize proteins that move Na+ into collecting ducts on kidneys
- acts on receptors in nucleus and cytoplasm
- activates mitochondrial enzymes that provide energy for Na+/K+ ATPase
Aldosterone secretion regulation
low plasma volume, low plasma Na+, acts on kidneys to release renin, renin converts angiotensinogen to angiotensin I, angiotensin I converted to angiotensin II by ACE, angiotensin II acts on adrenal cortex to promote aldosterone production, Na+ retention and K+ excretion
Renin
- enzyme secreted by juxtaglomerular cells of juxtaglomerular apparatus sensory for low Na+ concentrations
Excess aldosterone
- Conn’s syndrome
- increased Na+ retention and decreased K+ uptake, water retention and volume excess, hypertension
- decreased K+ uptake, increased urinary loss of K+, alkalosis, tetany, muscular weakness, dysrhythmia
Steroidogenesis in fascicular zone
- cholesterol –> pregnenolone –> cortisol
Cortisol actions
- increases blood glucose
- anabolic effects on liver
- catabolic effects on peripheral tissue (adipose tissue, skin, connective tissue, muscle)
- fatty acids, glycerol, amino acids used for glucogenesis
Cortisol actions in stress
- prevents inflammation
- prevents autoimmunity
- mobilizes glucose during stress
Control of cortisol secretion
stress/diurnal rhythm
- stimulates hypothalamus to release CRH, anterior pituitary to release ACTH, ACTH acts on adrenal cortex to make cortisol, increased plasma levels of cortisol
- levels are low at end of day and high during sleep
Primary cortisol deficiency
- Addison’s disease
- defect in adrenal cortex, no feedback inhibition
- levels of ACTH are very high leading to skin pigmentation
Secondary cortisol deficiency
- defect at level of pituitary
- pituitary does not produce ACTH and adrenal cortex will not be stimulated by cortisol
- no skin pigmentation
Addison’s disease
- reduced cortisol secretion
- hypoglycemia
- low Na+/high K+ levels in blood
- hypotension/hyperkalemia
Cortisol excess
- Cushing’s syndrome
- moon face, buffalo hump, hirsutism
- 3 causes: pituitary tumor, adrenal tumor, ectopic tumor
Cushing’s syndrome - pituitary tumor
- high production of ACTH stimulates adrenal cortex to produce too much cortisol
Cushing’s syndrome - adrenal gland tumor
- produces high levels of cortisol
- cortisol inhibits production of ACTH from pituitary through feedback regulation
Cushing’s syndrome - ectopic tumor
- can produce ACTH which stimulates cortisol production from adrenal cortex
- high levels of cortisol inhibit ACTH production from pituitary
- tumor is not inhibited from producing ACTH and cortisol levels remain high
Steroidogenesis in reticular zone
- cholesterol –> pregnenolone –> DHEA
Adrenal androgens/DHEA
- weak androgen converted to testosterone/estrogen
- secondary sexual characteristics
Adnrenogenital syndrome
- biosynthetic pathways that make aldosterone and cortisol are deficient and all precursors go to make DHEA
- excess androgens in adrenal cortex
Symptoms of adrenogenital syndrome in females
- masculinization of genitals
- male-pattern hair growth (hirsutism)
- male-type balding
- heavy arms and legs
- involution of breasts
Symptoms of adrenogenital syndrome in males
- pseudopuberty - sperm dysfunction
Calcium metabolism roles
- neurotransmission
- muscular contraction
- blood clotting
- cell cytoskeleton
- cell metabolism
- skeletal support
Phosphate metabolism roles
- glycolysis
- energy transfer
- cofactor for enzymes and skeletal support
3 hormones that regulate calcium and phosphate
- 2 hypercalcemic hormones: parathyroid hormone (PTH) and vitamin D3 (VD)
- 1 hypoglycemic hormone: calcitonin (CT)
Parathyroid gland
- embedded in thyroid gland
- 4 glands, 2 on each lobe of thyroid gland
PTH action
- increase plasma calcium
- decrease plasma phosphate
3 PTH target sites
- kidney: increase Ca2+ reabsorption, decrease PO43- reabsorption, increase vit D3 activation
- bone: increase bone resorption/breakdown
- GIT: indirect increase vit D3 formation
Feedback regulation of PTH
- hypercalcemia inhibits PTH
- hypocalcemia simulates PTH
- 1,25 (OH2) D3 inhibits PTH
Relationship of PTH
- linear
- low levels of plasma calcium stimulates
- high levels of plasma calcium inhibits
Where is PTH synthesized in
- parathyroid gland by chief cells
Main stimulus for PTH
- low plasma calcium
Hyperparathyroidism
- bones, stones, abdominal groans
- soft tissue calcification (kidney stones)
- weak bones and fractures
- GIT dysfunction
Primary hyperparathyroidism
- high PTH, high Ca2+, low PO43-, high 1,25 (OH2) D3
- problem with thyroid gland
- soft tissue calcification
- calcification of blood vessels - aneurysm - death
Secondary hyperparathyroidism
- consequence of low blood calcium that would stimulate PTH release
- rickets in children and osteolmalacia in adults
- renal failure
Primary hypoparathyroidism
- low PTH, low Ca2+, high PO43-, low 1,25 (OH2) D3
- increase neuromuscular activity
- tetany - muscle spasms
- asphyxia and death
- poor teeth and regular fillings
Trousseau’s sign
- hypoparathyroidism
- involuntary contraction of carpal muscles due to hypocalcemia and tetany
Chvostek’s sign
- hypocalcemia
- tap trigeminal nerve which runs along cheek
- tetany and snarl
Pseudohypoparathyroidism
- high PTH, low Ca2+, high PO43-, low 1,25 (OH2) D3
- tissue insensitivity to PTH action
- PTH receptors do not work
Calcitonin
- peptide hormone
- opposes action of PTH
- made in parafollicular cells (C-cells) in the thyroid gland adjacent to thyroid follicles
Calcitonin action
- decrease plasma calcium
- decrease plasma phosphate
3 calcitonin target sites
- kidneys: decrease Ca2+ reabsorption, decrease PO43- reabsorption, decrease vit D3 activation
- bone: decrease bone resorption/break down
- GIT: decrease Ca2+ absorption main site**
As plasma calcium increases, ____ release of calcitonin
- increase
Calcitonin clinical use
- no excess or deficiency syndromes
- treatment of postmenopausal osteoporosis - absence of estrogen, PTH action is not antagonized
- treatment of Padget’s disease - excessive osteoclast (bone breakdown) activity
Vitamin D3
- steroid hormone that regulates plasma calcium and phosphate levels
- 90% synthesized in the skin - photoisomerized by UV
- 10% synthesized by diet/supplements - D2 from plants
Vitamin D3 synthesis
- cholesterol –> liver –> 7-dehydrocholesterol –> skin –> vitamin D3
- vitamin D3 –> liver –> 25 hydroxyvitamin D –> kidney
- activating –> 1,25 dihydroxyvitamin D
- inactivating –> 24,25 vitamin D
- all through enzymes
1,25 vitamin D3 action
- increase plasma calcium
- increase plasma phosphate
3 1,25 vitamin D3 target sites
- kidney: increase Ca2+ reabsorption, increase PO43- reabsorption
- bone: promote PTH action
- GIT: increase absorption of Ca2+ and PO43-
GIT actions of vitamin D3
- promotes absorption of calcium from lumen to blood by genomic effects that synthesize proteins
- vit D diffuses across cell membrane and binds to nucleus receptors to impact gene transcription
- increase calcium channels, calcium binding proteins and calcium ATPase
Vitamin D3 stimulus
- increase PTH
- low Ca2+
Vitamin D3 deficiency
- rickets in juveniles
- osteomalacia in adults
- low vit D, low Ca2+, high PTH = poor bone formation and increased bone breakdown
Vitamin D3 excess
- toxicity
- hypercalcemia
- soft tissue calcification –> blood vessel calcification –> aneurysm –> death
2 pancreas gland
- exocrine - pancreatic juice for digestion, ducts
- endocrine - regulated blood sugar and found in Islet of Langerhans or pancreatic islets
3 cells pf pancreatic islets
- alpha - secrete glucagon
- beta - secrete insulin
- delta - somatostatin
Pancreatic islets hormones are ____
- paracrine
Somatostatin effects
- inhibit glucagon and insulin
Insulin effects
- inhibit glucagon
Glucagon effects
- stimulates insulin and somatostatin
Neural innervation of pancreatic islets
- sympathetic system through splanchnic nerve: increase glucagon and decrease insulin
- parasympathetic system through vagus nerve: increase insulin and decrease glucagon
Insulin structure
- proinsulin - single amino acid chain connected by C-peptide
- C-peptide cleaved off to produce bioactive insulin
- insulin has 2 polypeptide chains: A chain and B chain
Insulin action
- lower blood glucose
- anabolic - builds up tissues
- storage hormone - store glucose in cells, increase fat deposition in tissues, increase protein synthesis
Factors affecting insulin
- increasing concentrations of glucose, amino acids, fatty acids in blood
- hormones released by GIT in response to food
- ingesting food - parasympathetic stimulation
- stress - sympathetic inhibition
Insulin regulation
- increase plasma glucose levels –> stimulate beta cells to secrete insulin –> increase uptake of glucose by adipose tissue and muscle –> net uptake of glucose my liver –> decrease plasma glucose levels
Glucagon action
- catabolic peptide hormone - break down, fasting
- glucose: decrease glycogenesis, increase gluconeogenesis, increase glycogenolysis
- lipid: increase lipolysis, decrease lipogenesis
- protein: minor increase of degradation
Factors affecting glucagon
- nutrients: decrease glucose, increase amino acids
- GIT hormones: increase gastrin/CCK, decrease secretin
- neural stimuli: increase stress (sympathetic), increase food (parasympathetic)
Diabetes mellitus
- insulin deficiency and glucagon excess syndrome
- hyperglycemia –> osmotic diueresis –> cellular dehydration/volume depletion –> circulatory failture and renal function
- protein catabolism –> wasting syndrome
- ketogenesis –> acidosis –> diabetic coma and fruity breath
Symptoms of diabetes mellitus
- polyuria - large amounts of dilute urine
- polydipsia - excessive thirst
- polyphagia - excessive hunger
Type 1 diabetes mellitus
- insulin dependent and juvenile onset
- autoimmune disease attacks beta cells causing loss of insulin secretion
- treated with insulin injections
- 10-20%
Type 2 diabetes mellitus
- insulin independent and adult onset
- insulin resistance - decreased receptor response
- normal or high plasma insulin levels
- receptor downregulation
- associated with obesity
- 80-90%
Complications of diabetes mellitus
- cardiovascular disease (atherosclerosis, gangrene, hypertension)
- nephropathy, retinopathy, dermopathy, neuropathy, ulcers/infections
Insulin excess
- causes: insulin-secreting tumor, insulin overdose, reactive hypoglycemia
- symptoms: hypoglycemia, sympathetic activation, insulin shock
- treatment: glucose for diabetes, low carbohydrates for reactive hypoglycemia
