Week 3: Endocrine 1 Flashcards
What are the two main systems that regulate the physiological activity of the body?
The endocrine system
The nervous system
What are the key differences between the endocrine and the nervous system?
Nervous: faster acting, shorter lasting, specific targets, reliant on nerves and neurotransmitters
Endocrine : slower, longer lasting, general targets (can have multiple), hormones are secreted by cells and travel in the blood
What is the key idea of the endocrine response?
Secreting cell releases hormone into the blood, travels in the blood to a target cell, binds to a receptor to bring about an effect.
What are the bodies major endocrine glands?
Pituitary - functional, controls role of other glands
Thyroid - metabolism
Parathyroid - calcium levels
Stomach and GIT
Pancreas
Adrenal - cortisol, mineralcorticoids and adrenaline
Hypothalamus - regulate homeostasis , is neuroendocrine in function
Gonads
What glands have an endocrine and an exocrine function?
Pancreas
Gonads
Placenta
How does the action of water soluble and lipid soluble hormones vary?
Lipid soluble - slower activating but longer lasting
What are the three major classifications of hormones and how are they different?
Different by there structural origin
Peptide - (protein and peptide)
Steroid - cholesterol
Amine - amino acids mainly tryptophan or tyrosine
What classifications of hormones are water soluble?
Polypeptide and amine
What classification of hormones are lipid soluble?
Steroid hormones
What is the mechanism of action of steroid hormones?
Synthesised upon stimulation
Released from neurons
Travel in the blood bound to proteins
Diffuse across cell membranes as hydrophobic in nature
Act on cytoplasmic/nuclear receptors
Cause mRNA expression and alter protein synthesis
What is the mechanism of action of peptide and amine hormones? **
Are premade and released on stimulation
Travel freely in the blood
Bind to membrane receptors
Act via second messengers to regulate enzyme activity often by phosphorylation/dephosphorylation
What hormones are an example of the steroid hormone mechanism?
Reference not memorise
Glucocorticoids
Estrogen
testosterone
Progesterone
Aldosterone
Thyroid Hormone (although is amine hormone)
Vitamin D
What hormones are an example of the adenylyl cyclase cAMP mechanism?
Reference not memorise
ACTH
LH and FSH
TSH
ADH (V2 receptor)
CRH
PTH
Calcitonin
Glucagon
What hormones are an example of phospholipiase C mechanism of action?
GnRH
TRH
GHRH
ADH (v1 receptor)
Oxytocin
What hormones are an example of tyrosine kinase mechanism?
Insuline
IGF-1
Growth hormones
Prolactine
What is the hypothalamic-pituitary relationship?
Hypothalamus> Pituitary anterior> Glands/targets
Hormone from H acts on P
hormone from P acts on target tissue
Pituitary can be thought of as the functional unit of the hypothalamus
Hormones produces later in the change act on earlier glands by a mechanism of negative feedback
What is the difference betwen endocrine and exocrine glands?
Endocrine - release into blood, no system of ducts
Exocrine - release into epithelial surface, via a surface of ducts
What hormones are released by which gland in the HPA axis in stress?
H - CRH
Anterior P - ACTH
Adrenal gland - cortisol
Cortisol has negative feedback on the hypothalamus
What hormones are released by which gland in the HPThyroid axis?
H - TRH
Anterior pituitary - TSH
Thryoid - T3 and T4
T4 is converted to T3
T3 has negative feedback on Hypothalamus.
What is more common positive or negative feedback in the endocrine system?
Negative feedback
What is meant by negative feedback?
A regulatory mechanism of the endocrine system
Self limiting
When a hormone produced later in the series can act on a gland earlier in the process to reduce its activity, hence decreasing its own production
What is meant by positive feedback?
A regulatory mechanism of the endocrine system
Self - propelling
When a hormone produced later in the series can act on a gland earlier in the process to increase its activity, hence increasing its own production
What are the two division of the pituitary gland?
How are these division different?
Anterior pituitary (adenohypophysis) - protusion from ectoderm from roof of mouth (rathke pouch), contains blood vessels and is able to synthesise and store hormones
Posterior pituitary (neurohypophysis) - derived from neuroectoderm and is unable to synthesise but can store / release hormones
How does the posterior pituitary gland connect to the hypothalamus?
The paraventricular nucleus and supraoptic nucleus in the hypothalamus connect to the posterior pituitary gland by nerve bundles in the hypothalamohypophyseal tract
nervous tissue connection
In the infundibulum
How does the anterior pituitary gland connect to the hypothalamus?
Hypothalamus inhibiting and releasing hormones are produced and stored in nerve terminals
On stimulation are released into median eminence
capillary plexus that connects to the anterior pituitary by the hypothalamic-hypophysial portal vessel.
Vascular connection
by the pars tuberalis.
What is the main hormones produced in the supraoptic nucleus of the hypothalamus?
ADH
What is the main hormone produced in the paraventricular nucleus of the hypothalamus?
Oxytocin
What is a good student freindly way to remember the roles of the hypothalamus, Pituitary and target gland?
Hypothalamus - CEO
pituitary - Manager
Target gland - worker
How are hormones released from the posterior pituitary gland?
Supraoptic nucleus - synthesise ADH
Paraventricular nucleus - synthesise oxytocin
Secreted when stimulates from nerve terminal in the posterior pituitary gland
What are the different hormones secreted by the anterior pituitary gland?
Growth Hormone
Thyroid -stimulating hormone
Adrenocorticotropic hormone
FSH and LH
Prolactin
What cell type in the anterior pituitary secretes growth hormone?
Somatotrophs
What cell type in the anterior pituitary gland secretes TSH?
Thyrotrophs
What cell type in the anterior pituitary gland secretes ACTH?
Corticotrophs
What cell type in the anterior pituitary gland secretes FSH and LH?
Gonadotrophs
What cell type in the anterior pituitary gland secretes Prolactin (PRL)?
Lactotrophs
Describe the cell distribution in the anterior pituitary gland?
Somatrophs - 20%
Corticotrophs, Lactotrophs, Gondaotrophs - 15% each
Thyrotrophs - 5% each
What is meant by a primary, secondar, tertiary endocrime disorder?
Primary - problem with target gland
Secondary - problem with posterior/anterior pituitary gland
Tertiary - problem with hypothalamus
What are the two difference classifications (activity based) of endocrine disorders?
Hypersecretion
Hyposecretion
What are the common causes of a hypersecretion endocrine disorder?
Hormone secreting tumours
Hyperplasia of gland
Autoimmune stimulation
Ectopically produced peptide hormone (by tissue that do not normally secrete)
What are the common causes of a hyposecretion endocrine disorder?
Autoimmune disease
Tumours
Infection
Hemorrhage
What hypothalamus hormones typically increase pituitary activity?
TRH - increase TSH
CRH - increase ACTH
GHRH - increase GH
GnRH - increase FSH and LH
What hypothalamus hormones have an inhibitory effect on pituitary activity?
PIF/Dopamine - decrease prolactin
GH-RIH (somatostatin) - decrease Growth hormone
Describe how the release of growth hormone (somatotrophin) is controlled.
Hypothalamus activate pituitary gland by releasing GHRH
Hypothalamus inhibits the pituitary gland by releasing GHIH (somatostatin)
Growth hormone is secreted in a pulsatile manner
What is the role of growth hormone?
Anabolic hormone
Most important hormone for an normal adult to growth to size
growth of skeletal and soft tissue
Metabolic effect on carbohydrates, lipid and protein metabolism
What factors promote/inhibit growth hormone release?
Released more at young age, during stress, and favoured by sleep
Decreased by old age and obesity
What are the two different mechanisms of growth hormone to bring about its effects?
Direct - GH binds to GH receptors in target tissue
Indirect - GH binds to GH receptor in the liver and causes Insulin-like Growth Factor-1 IGF1 release/ somatomedins which bind to receptors to bring about effects
What are the effects of the direct actions of Growth hormone?
Acts on fat to increase lipolysis
Acts on glucose metabolism to increase blood sugar
What are the effects of the indirect actions of growth hormone?
Acts on the skeleton to increase cartilage formation and bone growth
Acts on the extrasekeletal (soft tissue) to increase protein synthesis, cell growth and proliferation
Contrast the effects of ACTH, TSH and GH on glucose levels.
All increase glucose levels
Growth hormone does this directly by antagonising insulin
ACTH and TSH do this indirectly by causing the release of glucocorticoids e.g cortisol and thyroid hormones respectivlyq
What is pituitary dwarfism?
Impaired GH secretion by anterior pituitary
Children show decreased rate of growth and small stature
Normal brain development and intellectualism
Have decreased plasma GH and IGF-1
Treat by giving subcutaneous GH
What is laron dwarfism?
Defective GH receptors in target tissue - causes GH insensitivity
Patients have decreased IGF-1 but elevated GH
Treat by giving IGF-1
What is growth hormone deficiency like in adults?
If GH deficiency occurs after the fusion of the epiphyseal plate of long bones (20yrs) height is not affected
patients develop increased body fat, reduced muscle mass, fatigue and decreased physical fitness
What is Gigantism?
Excess growth hormone secretion in childhood
Only effective is before epiphyslea plate fusion in long bones
Rapid increase in height and weight
Often have large feet, hands and coarsening of frontal features with frontal bossing and prognathism (projection of jaw)
May be due to a tumour in the anterior pituitary that hyper secretes GH
What is acromegaly?
Increased growth hormone secretion in adults
Above age 20yrs epiphyseal plate in long bones is fused
Excessive soft tissue, skeletal and internal organ growth
Acral bony overgrowth - frontal bossing
increased hand and foot size
Mandibular enlargement with prognathism
Often have increased headaches, high BP, excessive sweating and increase blood glucose
What is the treatment for acromegaly?
Somatostanin analogues (lanreatoide, Octreotide. Pasierotide)
Describe the effect of prolactin in teh body.
Normally serum level is at very low levels in males and females
Increases only during pregnancy and breastfeeding in women
Main function is breast development and milk production (NOT ejection)
Causes anovulation in the ovary
Can suppress sex drive in males and females
What is a prolactinoma?
How does it often present?
The most common pituitary tumour
May be micro (<10mm) or macro (>10mm)
Can press on the optic nerve causing visual defects, headaches
Increased prolactin also causes infertility, secondary hypogonadism and osteoporosis
What are the symptoms of prolactinoma only present in males?
Loss of libido
low sperm count
Erectile dysfunction
Low testosterone
Gyneocomastia
Often slower to present than female symptoms
What are the symptoms of prolactinoma only present in females?
Loss of menstration
Anovulation
Loss of sexual drive
Galactorrhea (milk production without pregnancy or lactation)
What are the potential treatments for prolactinomas?
Dopamine agonist - Bromocriptine
Surgical and radiotherapy - for intolerance or resistance to drug
What is the prohormones for all posterior pituitary hormones?
Neurophysin
What is the action of oxytocin?
Acts of myoepithelial cells in the mammary gland to cause milk ejection
Acts of smooth muscles of the myometrium (uterus) to cause contraction to expul the featus and placenta
Positive feedback from suckling on breast and stretch of cervix
What is the action of ADH?
ADH acts on V2 receptors to increase water permeability of the principal cells in the later distal tubule and CD
Acts on V1 receptors in the vascular smooth muscle to cause contraction and increase peripheral resistance (increase BP)
What can stimulate the release of ADH?
Increase plasma osmolarity
Stress and cortisol
Decreased blood pressure and volume
RAAS
Vomiting
What is another name for ADH?
Anrginei vasopressin
What can inhibit the release of ADH?
Alcohol (ethanol)
Diuretics
ANP
Elevated BP, BV
Decreased plasma osmolarity
What pathological condition can cause a decrease in ADH?
Hypothalamus disorder (hypo)
Pituitary tumour
What pathological states can cause a failure to respond to circulating ADH?
Disease: polycystic kidneys
Infection: chornic pyelorephitis
Drugs: lithium
Congenital: mutation in gene encoding V2 receptor (x-linked recessive)
What is Diabetes Inspidus?
Pathological state
Due to decreased ADH action
2 types: Neurogenic (central) DI (lack of ADH secretion) and nephrogenic DI (mutation in V2 receptors so unresponsive to ADH)
What are the symptoms of Diabetes inspidus?
Polydypsia (excessive thirst)
Polyuria (increased urination) potentially nocturia
Pass large volumes (>3L in 24hours) of very dilute durine (dehydration)
Hypenatermia
May also have anorexia, epigastric fullness, fatigue
How do you test for diabetes inspidus?
High plasma osmolarity
Low urine osmolarity
Serum electrolytes - hypernateremia
Water deprivation tests follwed by ADH test
What occurs in the water deprivation test?
How are results interpreted to indicate diabetes inspidus?
Patient must not eat or drink for 8 hours before test - creates water deprivation
Then urine sample is taken and urine osmolarity measured is low indicates diabetes inspidus is high rule out DI - this is commonly primary polydypsia.
Give patient artificial ADH and weight eight hours
Repeat urine test: low osmolarity indicates neprhogenic DI as unable to respond to ADH, high urine osmolarity indicates neurogenic DI as kidney able to respond to artificial ADH
What are the treatments for Diabetes inspidus?
Central/neurogenic - synthetic AVP analogue desmopression (DDAVP)
Nephrogenic - adequate fluid intake and salt restriction in diet
What is SIADH?
Syndrome of Inappropriate use of ADH
Associated with disorders where there is an increase in ADH
What are the common causes of SIADH?
Small cell lung cancer
Severe Brain trauma
Sepsis or infection of brain (meningitis)
What are the symptoms of SIADH?
Plasma ADH is abnormally high
Highly concentrated low volume urine
Blood hyponatermia and low osmolarity
Patients may have normal or elevated BP
Can trigger fatal seizures
How do you treat SIADH?
Stop fluid intake and treat the underlying cause
What makes up the Hypothalamic Pituitary Gonadal Axis?
hypothalamus releases GnRH in a pulsatile manner
Stimulates pituitary gland to release FSH and LH from gonadotropic cells
FSH and LH act on gonads to release sex hormones
What are the actions of FSH and LH in females?
FSH - stimulates gamete (egg) production
LH - produces oesotrogen and progesterone, matures the follicles of the egg, trigger ovulation.
Sex hormones have a key role in bone metabolism
What are the actions of FSH and LH in males?
FSH - stimulates gamete (sperm) production
LH - stimulates production of testosterone.
Sex hormones have a key role in bone metabolism
What factors can affect the activitiy of the HP-Gonadal axis?
What are the consequences of this?
Environmental factors - stress, exercise and weight loss
Deregulation of HPA leads to menapause in females
HPA activity generally decreases in males over time but at a slower rate than in females.
What is hypopituitarism?
Deficiency in one or more of the hormones in the pituitary
What is panhypopituitaryism?
A condition of inadequate or absent production of all anterior pituitary hormones
What are the potential causes of hypopituitarism?
May be congenital or acquired defects in pituitary gland
Imapired function of hypothalamus - leading to decrease hypophysiotropic hormones
Common causes are compression (tumour), gene mutation, blockage in blood flow (ischemia), iatrogenic or chronic inflammation
