endocrine physiology Flashcards
homeostasis
Claude Bernard - defined ‘milieu interieur’
‘the internal environment remains relatively constant though there are changes in the external environment
can vary within a narrow limit - termed ‘ normal physiological range’
successful compensation - homeostasis re-established
failure to compensate - illness / death
communication
vital to homeostasis
cells communicate with other cells, tissues and organs
central to this tissue-to-tissue communication is the endocrine system
the endocrine system
collection of glands that secrete hormones into circulation to be carried to distant organ(s)
nervous system and endocrine system work together to monitor and adjust physiologic activities
nervous system: short-term, very specific responses
- via chemical messengers (neurotransmitters)
endocrine system: longer-term metabolic processes
- via chemical messengers (hormones)
function of the endocrine system
glands of the endocrine system perform their function by synthesizing and releasing chemical messengers, termed hormones
specialized epithelial secretory cells manufacture specific hormones
hormones are then released systemically (via rich capillary supply to epithelial cells)
transport of hormones to rest of body conveys specific regulatory information among cells and organs
cells must bear a receptor for the hormone being broadcast in order to respond
hormones
hormones can communicate in different ways:
- endocrine
- autocrine
-paracine
-juxtacrine
hormones ultimately regulate cell function/ metabolism/ homeostasis via their effect on enzymes
hormones only affect cells that possess specific receptors for that hormone - target cells
magnitude of hormone effect dependent on:
- the number of target receptors
- concentration of the hormone
- affinity of receptor for hormone
- influence of other hormones
hormones fall under 2 main categories , which determine:
- steroid hormones
- non-steroid hormones
steroid hormones
lipid soluble: synthesised from cholesterol
circulate in blood bound to a carrier protein (e.g. albumin)
steroid hormones bound to binding proteins are ‘inactive’ (approx. 75% of total hormone)
small amount are ‘unbound’ and thus are in a ‘free’ or ‘active’ form
a large change in binding protein can affect free hormone concentration and thus hormonal effects
1. steroid hormones diffuse into cell
2. specific receptor located in either cytoplasm or nucleus
3. hormone- receptor complex activate gene expression
4. protein synthesis is induced
non-steroid (peptide) hormones
water-soluble and include protein hormones and catecholamines
have a high molecular weight and cannot diffuse across the cell membrane
hormone > receptor interaction termed ‘first messenger’
- i.e. first signal in an elaborate signal transduction cascade
feedback loops
hormone secretions are regulated by feedback systems
- negative feedback control most common
negative feedback loops
- stimulus activates endocrine gland
- gland secretes hormone
- target cell respond to hormone - reduces original stimulus
- switches-off further hormone production by gland
very important in maintaining hormones (and thus the processes they control) within normal physiologic range
positive feedback loop
rate of a process increases as the concentration of the product increases
process will continuously accelerate as long as substrate is available and product not consumed by other processes
endocrine glands
pituitary gland
pineal gland
thyroid gland
parathyroid gland
adrenal gland
endocrine pancreas
sex glands
pituitary gland
often termed the ‘master regulator’
pituitary is divided into 2 lobes:
- anterior lobe
- posterior lobe
both lobes are under direct control from hypothalamic hormones:
- posterior lobe stores hormones made by hypothalamic neurons and releases into circulation
-> secretes Prolactin, TSH, ACTH, GH, LH, FSH
- anterior lobe receives hypothalamic hormones via vessels, which stimulates further hormone release by pituitary
-> secretes Antidiuretic hormone (ADH) (prevents kidney water excretion)
-> oxytocin (responsible for uterus contraction and milk ejection during lactation)
pineal gland
produces melatonin (derivative of serotonin)
- release in rhythmic fashion
suppressed by light
- thus, most active at night time
modulates sleep patterns in circadian rhythms
- diminished photosensitive melatonin response may be related to some types of insomnia
thyroid gland
butterfly-shaped, located in the neck, inferior to the larynx
secretes two hormones:
- thyoxine (T4 - major hormone produced; 90%)
- triiodthyronine (T3: most T4 converted to T3 in target tissues, which has greatest metabolic effect)
involved in tissue development and macronutrient metabolism
- increase heat production and energy consumption
parathyroid gland
four glands, located at posterior of thyroid gland
produces parathyroid hormone (PTH)
pancreas
has dual functions:
- exocrine function
-endocrine function
endocrine part of pancreas = islets of Langerhans:
- make up 2-3% of pancreas weight
- 4 types of cells:
1. alpha cells - (20% of cell mass) produce glucagon
2. beta cells - (60-75 % cell mass) produce insulin
3. delta cells - (3-5% cell mass) produce gastrin/ somatostatin
4. F cells - (2% cell mass) produce pancreatic polypeptide
endocrine pancreas
primary role is to regulate blood glucose levels
alpha cells
- secrete glucagon
- increase blood glucose conc
beta cells
- secrete insulin
- decrease blood glucose conc
adrenal glands
pyramid shaped and sit on top of kidneys
each gland consists of 2 portions:
- outer adrenal cortex
80%of adult gland
glucocorticoids: anti-inflammatory, growth-suppression, gluconeogenesis
mineralocorticoids: epithelial cell ion transport, sodium retention via sodium pump activation
- inner adrenal medulla
20% of adult gland
released in response to stressors (fright, anger, exercise)
increases HR, cardiac output, blood glucose, muscle vasodilation
endocrine system dysfunction
dysfunction of the endocrine system via 3 main faults
1. abnormal hormone receptor function / level:
primarily affect non-steroid (water-soluble) hormones, such as insulin and include:
- decreased number of receptors
-impaired receptor function, leading to hormone sensitivity
- presence of antibodies against specific receptors, reducing available binding sites or exaggerated cell response if antibody mimics hormone
2. altered intracellular response to hormone-receptor complex:
causes impaired cellular hormone response. Causes include:
- inadequate second messenger
- faulty response of target cell to hormone-receptor complex
- faulty response of target cell to second messenger
3. hyper- or hyposecretion of hormones by glands:
-> high hormone production
-failure of negative feedback
- altered hormone degradation or inactivation by circulating antibodies
- ectopic hormone production by non-endocrine tissues
acromegaly/ gigantism
-> low hormone production
- dysfunctional endocrine gland
- malfunctioning secretory/ insufficient hormone precursors/ inability to convert precursors to active hormone
dwarfism
GLUT4 translocation
both insulin and exercise can stimulate GLUT4 recruitment to the cell surface (e.g. muscle and fat cells)
- independent of transcription or translation
these 2 physiological stimuli distinct signalling mechanism that lead to enhanced GLUT4-mediated glucose uptake
Diabetes mellitus
clinically heterogenous disorder with glucose intolerance in common
-> type I
results from the body’s failure to produce insulin
onset typically in early childhood
-> type II
onset typically in adulthood
insulin resistance - cells fail to use insulin properly
type I diabetes mellitus
80-90% of beta cells must be destroyed for hyperglycemia to occur
beta cell abnormalities present long before first clinical symptoms
- 85-90% of patients show autoantibodies against islet cells and/or insulin
- mutations in certain gene alleles (HLA-DR4 and HLA-DR3) associate with a 5-8 fold increased T1DM risk
-mutations in both alleles associated with 20-40 times increased risk
highest incidence in children aged 12 yrs
accounts for 10% of DM cases in the west
type 1 diabetes mellitus: clinical manifestations
glucose appearing in urine as renal glucose threshold is exceeded, causing osmotic diuresis and symptoms of polyuria and thirst
weight loss due to
- loss of CHO as fuel source causes excess use of fat for energy
- loss of inhibitory effect of insulin on protein breakdown
hypoglycemia
type 1 diabetes: ketoacidosis
lack of CHO = fat used as energy source
ketoacidosis worsens dehydration via kidneys trying to remove ketones through urine
pH falls and acetone exhaled gives breath sweet odour
diabetic coma can occur if ketoacidosis is severe enough
