endocrine physiology

Question 1

homeostasis

Answer 1

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

Question 2

communication

Answer 2

vital to homeostasis
cells communicate with other cells, tissues and organs
central to this tissue-to-tissue communication is the endocrine system

Question 3

the endocrine system

Answer 3

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)

Question 4

function of the endocrine system

Answer 4

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

Question 5

hormones

Answer 5

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

Question 6

steroid hormones

Answer 6

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

Question 7

non-steroid (peptide) hormones

Answer 7

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

Question 8

feedback loops

Answer 8

hormone secretions are regulated by feedback systems
- negative feedback control most common

Question 9

negative feedback loops

Answer 9

1. stimulus activates endocrine gland
2. gland secretes hormone
3. target cell respond to hormone - reduces original stimulus
4. switches-off further hormone production by gland
   very important in maintaining hormones (and thus the processes they control) within normal physiologic range

Question 10

positive feedback loop

Answer 10

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

Question 11

endocrine glands

Answer 11

pituitary gland
pineal gland
thyroid gland
parathyroid gland
adrenal gland
endocrine pancreas
sex glands

Question 12

pituitary gland

Answer 12

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)

Question 13

pineal gland

Answer 13

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

Question 14

thyroid gland

Answer 14

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

Question 15

parathyroid gland

Answer 15

four glands, located at posterior of thyroid gland
produces parathyroid hormone (PTH)

Question 16

pancreas

Answer 16

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

Question 17

endocrine pancreas

Answer 17

primary role is to regulate blood glucose levels
alpha cells
- secrete glucagon
- increase blood glucose conc
beta cells
- secrete insulin
- decrease blood glucose conc

Question 18

adrenal glands

Answer 18

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

Question 19

endocrine system dysfunction

Answer 19

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

Question 20

GLUT4 translocation

Answer 20

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

Question 21

Diabetes mellitus

Answer 21

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

Question 22

type I diabetes mellitus

Answer 22

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

Question 23

type 1 diabetes mellitus: clinical manifestations

Answer 23

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

Question 24

type 1 diabetes: ketoacidosis

Answer 24

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

Question 25

type 2 diabetes mellitus

Answer 25

much more common than T1DM
major factor is insulin resistance which could be due to:
- decreased number of insulin receptors on cell membrane
- abnormal post-receptor signalling events within target cell
-> hyperinsulinaemia in early TD2M stages may be compensatory response to high blood glucose levels (e.g. with poor diet)
-> necessitates development of insulin resistance to prevent hypoglycemia
-> pancreas also cannot sustain constant high insulin secretion, causing beta cell dysfunction

Question 26

TD2M vascular complications

Answer 26

microvascular disease- of retina (blindness and kidneys)
macrovascular disease - coronary artery disease/ atherosclerosis
peripheral vascular disease - foot lesions, amputation

Question 27

sympathetic nervous system and the adrenal glands

Answer 27

E (epinephrine) accounts for 75-80% adrenal output; rest is NE (norepinephrine)
E and NE are released into bloodstream, acting as hormones
affects similar to normal neuronal sympathetic stimulation except:
- cells not innervated by sympathetic fibres are affected
- longer lasting since E and NE remain in blood for extended period

Question 28

E, NE and alpha/ beta receptors

Answer 28

two classes adrenergic membrane receptors:
1. alpha receptors - mostly found in sympathetic organs/ tissues
2. beta receptors - located on membranes of many organs

Question 29

receptor type determines E/ NE response

Answer 29

alpha receptors mostly stimulated by norepinphrine
both alpha and beta receptors stimulated by epinephrine
release of E induces a generalised sympathetic response throughout body

Question 30

hormonal regulation of exercise metabolism

Answer 30

various hormones work to ensure glucose and FFA availability for muscle energy metabolism
four hormones work to maintain circulating glucose during exercise:
- epinephrine
-norepinephrine
-glucagon
-cortisol

Question 31

epinephrine/ norepinephrine and glucose regulation

Answer 31

causes liver to release more glucose than is being used by muscles
after short explosive exercise blood glucose may be 40-50% > resting level

Question 32

fight or flight response and hormonal control of exercise metabolism

Answer 32

catecholamines central to fight or flight response
divergent effects of catecholamines, depending on the type of adrenergic receptor a tissue possesses
glucose supply during exercise maintained by:
- mobilisation of glucose from live glycogen stores
- mobilisation of FFA from adipose tissue
- gluconeogenesis from amino acids, lactic acid and glycerol

Question 33

factors influencing evaporation

Answer 33

temperature- increase evap
convective currents - increase
skin exposure - increase