Endocrine Physiology Flashcards
(131 cards)
1
Q
Define the Endocrine system
A
Integrates and controls organ function via the secretion of chemicals from cells, tissues or glands which are then carried in the blood to target organs, distal from the site of hormone synthesis, where they influence the activity of the target organ
2
Q
What are paracrine chemicals?
A
Act local to the site of synthesis, do not travel to distant sites e.g. histamine
3
Q
What are autocrine chemicals?
A
act in/on the same cell that synthesises the hormone e.g. cytokines
4
Q
What are exocrine chemicals?
A
released from exocrine glands via ducts to the external environment including the GI tract e.g. saliva, sweat, bile
5
Q
How do endocrine hormones communicate?
A
Travel in the blood to their target organ/tissues. (presence of specific receptors)
6
Q
What happens in neural communication?
A
Neurotransmitters released from presynaptic - travel across synaptic cleft - to postsynaptic cell to influence activity. (acts locally)
7
Q
What is neuroendocrine?
A
Endocrine and nervous system combine. Nerves release hormones which enter blood and travel to their target cells.
8
Q
The response of a target cell to any 1 hormone is highly specific, but how can the same hormone have a different affect in different target cells?
A
The hormone Insulin:
Target tissue:
skeletal muscle / adipose tissue –> which leads to and increase glucose uptake
However, if the liver was the target tissue –> response would be increased glycogenesis
decreased gluconeogenesis.
9
Q
What is the function of endocrine hormones?
A
Bring about changes in the activity of their target cells and tissues.
10
Q
What are the 6 main features of an endocrine hormone?
A
- Produced by a cell or groups of cells
- Secreted from those cells into the blood
- Transported via the blood to distant targets
- Exert their effects at very low concentrations
- Act by binding to receptors on target tissues
- Have their action terminated, often via negative feedback loops.
11
Q
What are the 3 classifications of endocrine hormones?
A
- Peptide or protein hormones - composed of chains of amino acids (most common) *short half-life in plasma.
- Amine hormones - all derived from one or two amino acids (tyrosine)
- Steroid hormones - all derived from cholesterol
* longer half-life
12
Q
Peptide hormones:
What are preprohormones?
A
The initial hormone produced by ribosomes - large and inactive. Nut contain one or more copy of the active hormone in their amino acid sequence.
13
Q
What do proteolytic enzymes do?
A
Break prohormone down into active hormone and other fragments in the golgi apparatus.
14
Q
What is C-peptide and what is its clinical importance?
A
Inactive fragment cleaved from the insulin prohormone.
Clinically - levels of C-peptide in plasma or urine are often measured to indicate endogenous insulin production from the pancreas.
15
Q
Action of peptide hormones:
A
Water soluble - easily transport via blood but not cross cell membrane.
Generally create relatively fast biological responses.
16
Q
What do most peptide hormones work by?
A
Modulating either GPCR or tyrosine kinase linked signalling pathways.
These pathways phosphorylate existing proteins in the cell and modify their function.
17
Q
Amine hormones:
Which are derived from tyrosine?
A
Dopamine (CNS neurotransmitter)
Norepinephrine (neurotransmitter)
Epinephrine (hormone released by adrenal medulla)
* similar mechanism to peptide hormones
18
Q
What is melatonin derived from and what does it do?
A
Derived from tyrosine
Regulates circadian rhythm
19
Q
How do steroid hormones work?
A
Synthesised directly as needed. Highly lipophilic so cannot be retained within lipid membranes. Once synthesised they diffuse across membrane into the ISF and the blood. Transported bound to carrier proteins such as albumin
* alter protein synthesis
20
Q
What are steroid hormones produced by?
A
- Gonads (testes and ovaries) - sex steroids
- Placenta - hCG, sex steroids
- Kidney - Vit D3
- Adrenal cortex - corticosteroids
21
Q
What determines which steroid hormone is produced?
A
Different cells having different enzymes synthesising different derivatives of cholesterol.
22
Q
What are the actions of steroid hormones?
A
Receptors located inside cell - trigger either activation or repression of gene function within nucleus = genomic effect.
Slow process
23
Q
Physiological activity of lipophilic hormones:
What are the physiological important fractions?
A
Unbound free steroid/thyroid hormones in plasma - can diffuse across capillary walls to target cells.
24
Q
What determines hormone concentration in the plasma?
A
Balance between secretion and degradation/excretion
*secretion is responsive to neg feedback reflexes.
25
What determines endocrine hormone concentration in the plasma?
Balance between secretion and degradation/excretion
| *secretion is responsive to neg feedback reflexes.
26
What do some endocrine pathways respond to?
Neural feedback loops e.g. adrenaline
| - Specialised cells in adrenal medulla release adrenaline into blood stream
27
What happens when prolonged exposure to low hormone concentration in plasma occurs?
Often leads to up-regulation of receptor number (increases tissue sensitivity to hormone)
28
What happens when prolonged exposure to high hormone concentration in plasma occurs?
Typically leads to down-regulation of receptor number (decreases tissue sensitivity to hormone)
29
What are permissive effects?
Presence of one hormone enhances the effect of another e.g. epinephrine with thyroid present greatly increases lipolysis.
30
What are antagonistic effects?
The presence of one hormone reduces the effect of another
| e.g. growth hormone impairs the response to insulin by decreasing number of insulin receptors on tissues.
31
What is the hypothalamus-pituitary axis?
Hypothalamus and pituitary gland together are principle organisers of the endocrine system
32
How are the hypothalamus and the pituitary gland connected?
Directly via a stalk called the infundibulum.
33
What is the difference between the posterior and anterior pituitary?
Posterior - extension of the neural tissue
| Anterior - true endocrine gland of epithelial origin.
34
Describe the pituitary gland and its location
Bean-shaped and bean sized endocrine gland
| Located in a hypothaseal fossa (pocket) in sphenoid bone directly below hypothalamus.
35
What are tropic hormones?
Neurohormones secreted into capillaries travelling to anterior pituitary. Govern release of anterior pituitary hormones.
36
What are non-tropic hormones?
Neurohormones produced in the hypothalamus and travel to posterior pituitary (via axons of hypothalamic neurons where they are released into blood)
37
What are all hormones released by the hypothalamus and the posterior pituitary?
Neurohormones
38
What are all hormones released by the anterior pituitary?
Endocrine
39
What are the 5 hypothalamic "releasing hormones"?
1. Thyrotropin releasing hormone (TRH)
2. Corticotropin releasing hormone (CRH)
3. Growth hormone releasing hormone (GHRH)
4. Gonadotropin releasing hormone (GnRH)
5. Prolactin Releasing Hormone (PRH)
40
What are the 2 hypothalamic "inhibiting hormones"?
1. Growth hormone inhibiting hormone (GHIH)
| 2. Prolactin Inhibiting hormone (PIH) Dopamine
41
What is the hypothalamus-hypophyseal portal system?
Network of tiny vessels which transfer trophic hormones from hypothalamus to anterior pituitary.
Short distance - very rapid and dynamic
42
Features of the anterior pituitary
- true endocrine tissue
- epithelial origin
- connected to hypothalamus via capillary portal system
- makes up 2/3rds of gland
43
Features of posterior pituitary
- neuroendocrine tissue
- neural tissue origin
- neural connection to hypothalamus
- secrets neurohormones made in hypothalamus
- makes up 1/3rd of gland
44
Name 5 tropic hormones released from the anterior pituitary gland
1. TSH aka thyrotropin
2. Adrenocorticotrophic Hormone (ACTH) aka corticotropin
3. Follicle Stimulating Hormone (FSH)
4. Luteinising Hormone (LH)
5. Growth Hormone (GH)
45
What is the 6th hormone released from ant. pituitary?
Prolactin - directly stimulates milk production from the breast during lactation
46
Anterior pituitary feedback control:
| What are the 3 integration centres?
1. hypothalamus
2. anterior pituitary
3. target endocrine cell
47
How can hormones act as negative feedback signals?
Hormones themselves act as a negative feedback signal.
| Each hormone feeds back to inhibit hormone secretion by integrating centres earlier in the reflex.
48
1. What is feedback from endocrine target?
| 2. What is feedback from anterior pituitary to hypothalamus?
1. Long-loop feedback
| 2. Short-loop feedback
49
What hormones does the posterior pituitary store and release?
2 peptide neurohormones:
- vasopressin (aka anti-diuretic hormone; ADH)
- oxytocin
50
Where are the hormones (posterior pituitary) synthesised?
Magnocellular neurons - cell bodies in specific areas of the hypothalamus.
51
How are theses hormones (post.) released?
Do not synapse with other neurons, their terminals end directly on capillaries.
Hormones transported to the nerve terminal in posterior p ready for release. Released directly into blood stream.
52
What is the main function of vasopressin and what triggers it and what is its mode of action?
Regulates water balance.
Release triggered by - increase in plasma osmolarity and decrease in plasma volume/blood pressure
Mode - kidney collecting ducts - increase water reabsorption
vascular smooth muscle - increase blood pressure
53
What is hyposecretion?
Too little hormone secreted
54
What is hypersecretion?
Too much hormone secreted
55
What are 1st order disorders?
Those in which the defect is in the cells that secrete the hormone
56
What is secondary disorders?
Those in which there is too little or too much trophic hormone from pituitary.
57
What is tertiary disorders?
Rare - relate to hypothalamic defects.
58
Body energy = energy intake - energy output:
| What determines energy intake?
The balance of activity in the feeding centre ( promotes feelings of hunger and drive to eat) and the satiety centre 9 promotes feelings of fullness by suppressing the feeding centre)
59
What is the glucostatic theory?
Food intake is determined by blood glucose: as [BG] increases, the drive to eat decreases
60
What is the lipostatic theory?
Food intake is determined by fat stores: as fat stores increase, the drive to eat decreases.
61
What are the 3 categories of energy output?
1. Cellular work - transporting molecules across membranes; growth and repair; storage of energy.
2. Mechanical work - movement, either on large scale using muscle or intracellularly.
3. Heat loss - associated with cellular and mechanical work accounts for half our energy output.
62
What 3 elements affect metabolism?
1. Extracting energy from nutrients in food
2. Storing that energy
3. Utilising that energy for work
63
What 2 endocrine hormones produced in the pancreas maintain [BG]?
Insulin and Glucagon
64
Islets of Langerhans:
| 4 types of islet cells, what are they?
Alpha cells produce GLUCAGON
Beta cells produce INSULIN
Delta cells produce SOMATOSTATIN
65
What is insulin?
Peptide hormone produced by pancreatic beta cella that stimulates glucose uptake by cells. Converted to proinsulin in the ER.
*Only hormone which lowers [BG]
66
What is glucose stored as in 1. liver and muscle 2. liver and adipose tissue?
1. Glycogen
| 2. Triacylglycerols
67
What is the primary action of insulin?
Binds to tyrosine kinase receptors on cell membrane of insulin-senestive tissues (muscles and adipose tissue) to increase glucose uptake by these tissues.
68
What is the specific glucose transporter which resides in cytoplasm of unstimulated muscle and adipose tissue?
GLUT 4 - stimulated by insulin it allows transport.
69
What tissues are insulin dependent?
Muscle and fat (60%)
70
Is the liver insulin-sensitive?
No, GLUT 2 transporters - however, glucose transport into hepatocytes is affected by insulin status.
71
What is insulins half life? and where is it mainly degraded?
- about 5 minutes
| - degraded principal in the liver and kidneys.
72
What stimuli increases insulin release?
1. increased [BG]
2. Increased [amino acids]plasma
3. Glucagon (insulin required to take up glucose created via gluconeogenesis stimulated by glucagon)
4. Other (incretin) hormones controlling GI secretion and motility e.g. gastrin, secretin, CCK.
5. Vagal nerve activity
73
What stimuli inhibit insulin release?
1. Low [BG]
2. Somatostatin (GHIH)
3. Sympathetic alpha 2 effects
4. Stress e.g. hypoxia
74
What is the difference between IV glucose and oral glucose in terms of insulin response?
- IV glucose - increase insulin by direct effect of increase in glucose on beta cells
- Oral loading of the same amount of glucose - increases insulin by both direct effect on beta cells and vagal stimulation of beta cells, plus incretin effects. (more)
75
What is glucagon?
| What is its half life?
Peptide hormone produced by alpha - cells of the pancreatic islet cells.
Half life 5-10 mins.
76
What is glucagon primary purpose?
Raise blood glucose, glucose mobilising hormone - acting mainly on the liver.
77
What are the actions of Glucagon?
Primarily opposes the action of insulin, forming part of glucose counter-regulatory control system. Most active in post-absorptive state.
78
What are glucagon receptors? And when these are activated what happens?
1. G-protein coupled linked to cAMP system - activate specific liver enzymes.
2. Results in increased glycogenolysis, increased gluconeogenesis
3. Formation of ketones from fatty acids.
* Net result is elevated [BG]
79
Amino acids are also a potent stimulus for glucagon secretion. What would happen if it wasn't?
Increase glucose - increase insulin and decrease Glucagon. And vice versa.
Amino acids in the plasma stimulate the release of both.
Adaptation to adjust for the composition of a meal very high in protein.
80
A high protein meal with very little carbohydrate would have what effect?
aas - increase insulin - decrease [BG]
aas - increase glucagon - increase [BG]
* this is to maintain [BG]
81
What stimuli promote glucagon release?
1. LOW [BG]
2. High [amino acids] prevents hypoglycaemia following insulin release in response to aa.
3. sympathetic innervation and epinephrine, beta 2 effect
4. cortisol
5. Stress e.g. exercise, infection
82
What stimuli inhibit glucagon release?
1. Glucose
2. Free fatty acids (FFA) and ketones
3. insulin
4. somatostatin
83
Generally, what would an increase in parasympathetic activity do to insulin and glucagon?
Increase insulin and to a lesser extent increase glucagon.
84
What would an increase in sympathetic activity do to insulin and glucagon?
Promotes glucose mobilisation, increases glucagon, increases epinephrine and inhibition of insulin. Fight or flight response.
85
What is somatostatin?
Peptide hormone, secreted by D-cells of the pancreas.
86
What is the main pancreatic action of somatostatin?
Inhibit activity in the GI tract.
| Not counter-regulatory but strongly suppresses the release of both insulin and glucagon in a paracrine fashion.
87
What effect does exercise have on [BG]?
Glucose entry into skeletal muscle is increased during exercise. Increases insulin sensitivity of muscle and causes an insulin-independent increase in the number of GLUT-4 transporters in muscle membrane.
88
What happens in non-active muscle what happens with insulin?
Insulin binds to its receptor, which then leads to glucose transporters, GLUT-4, migrating to the cell membrane, allowing glucose to enter.
89
What happens in active muscle with insulin?
GLUT 4 transporters can migrate to membrane without insulin present.
90
What factors regulate growth?
1. Growth hormone release from ant pituitary - regulated by balance of GHRH vs GHIH release from hypothalamus
2. Thyroid hormones
3. Insulin
4. Sex steroids
5. Availability of nutrients
6. Stress
7. Genetics
91
What is growth hormone?
Peptide hormone released from ant pituitary, aka somatotropin.
92
What controls the release of GH?
2 hypothalamic neurohormones with opposing action:
Growth Hormone Inhibiting Hormone (GHIH)
Growth Hormone Releasing Hormone (GHRH)
93
What are the two broad actions of GH?
1. Growth and development (indirect)
| 2. Regulation of metabolism (direct)
94
Growth and Development:
| How does the GH contribute to growth and what is required for stimulation?
GH is the dominant influence on the rate at which children grow after 10 months.
GH requires permissive action of thyroid hormones and insulin before it will stimulate growth.
95
What mediates Growth-promoting effect of GH?
Stimulation of both cell size (hypertrophy) and cell division (hyperplasia) in its many target tissues.
96
What is IGF-1 and what affect does it have on GH?
GH effect is almost entirely indirect being achieved through action of insulin-like growth factor-1 (IGF-1) - somatomedin C.
97
What is the effect of IGF-1 Negative feedback loop on GH release?
IGF exhibits neg feedback on GH release both via inhibiting GHRH and stimulating GHIH.
Additional neg feedback loop of GH on GH release from somatotrophs in pituitary.
98
What are GH/IGF-1 effects on bone growth?
1. GH stimulates chondrocyte precursor cells in the epiphyseal plates to differentiate into chondrocytes.
2. during differentiation, the cells begin to secrete IGF-1 and to become responsiveness to IGF-1
3. IGF-1 then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation of bone growth
99
How does GH directly affect regulation of metabolism?
1. Increases gluconeogenesis in liver
2. Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue
3. Makes adipocytes more sensitive to lipolytic stimuli
4. Increases amino acid uptake and protein synthesis in almost all cells = anabolic effect.
100
How is GH secreted?
Secretion rate undergoes rapid spontaneous fluctuations as well as increase or decrease in response to specific stimuli.
Majority of GH released during first 2 hours of sleep.
GHRH may have sleep inducing qualities
101
What controls GH secretion?
Nutritional status. Mediated via modulation of control of GHRH/GHIH release from the hypothalamus.
102
What stimuli increase GHRH secretion? (increase GH)
1. Actual or potential decrease in energy supply to cells.
2. Increased amounts of amino acids in the plasma
3. Stressful stimuli e.g. infection
4. Delta sleep
5. Oestrogen and testosterone (growth spurt in puberty)
103
What stimuli increase GHIH secretion? (decrease GH)
1. Glucose
2. FFA
3. REM sleep (subjects deprived of REM sleep have increase GH secretion)
4. Cortisol (although inhibitory effect on growth may be more to do with increase protein catabolism than stimulating GHIH release)
104
What 3 factors affect physiology of growth?
1. Hormones
2. Nutrition
3. Genetics
105
What hormones affect growth, and how?
GH, IGF-1, thyroid hormones, sex steroids, glucocorticoids and insulin.
Sex hormones = minor influence until puberty.
Thyroid hormone = development of nervous system in utero and early childhood. Ossification of cartilage and teeth maturation.
106
Why do injury and disease stunt growth?
Increase protein catabolism
107
What are the 2 periods of rapid growth in humans?
1. Infancy: amazing growth spurts 2.5cm in a few days and then nothing i.e. episodic, mechanism not known
2. Puberty: due to androgens and oestrogens, produce spikes in GH secretion that increase IGF-1 - increases growth. Before the epiphyseal plates fuse, GH/IGF-1 promote bone elongation and increased height, weight and body mass.
108
Hypersecretion of GH: Endocrine tumours usually the cause - what are the 2 kinds?
Giantism: XS GH due to a pituitary tumour before epiphyseal plates of long bones close.
Acromegaly: XS GH due to a pituitary tumour after epiphyseal plates have sealed. Long bones cannot increase so there is no longitudinal growth and no increase in height.
109
What is the role of calcium in the body?
1. Signalling - e.g. neurotransmitters/hormone
2. Blood clotting
3. Apoptosis
4. Skeletal strength
5. Membrane Excitability - Ca decreases Na permeability = most critical in short term homeostasis
110
What is the calcium distribution in the body?
Bones 99%
Intracellular 0.9% (mostly stored inside mitochondria and Sarcoplasmic Reticulum) Free [Ca]
Extracellular fluid 0.1% (nearly half ECF Ca is bound to protein. 0.05% calcium in the body free in solution and physiologically active.
111
Extracellular Calcium Stores: What does calcium have a high affinity for?
Proteins and in plasma around 40% is bound to plasma proteins.
112
What 3 forms of calcium are there in the blood?
1. Protein bound - 40% (80% albumin and 20% globulin
2. Free (ionised) - 50%
3. Complexes (Anions) - 10%
* Only free calcium is physiologically active
113
How does binding capacity of plasma proteins change?
With pH.
Increased binding under alkalotic conditions. e.g. hyperventilate
Decreased binding under acidosis conditions.
114
What determines total body calcium?
Calcium from diet and calcium excretion at kidney and faeces.
Distribution between bone and ECF is crucial.
115
What is the functions of bone?
Provide mechanical support and to maintain calcium balance.
116
What are osteoblasts and what do they do?
Bone-building cells
| highly active, lay down a collagen extracellular matrix which they then calcify.
117
What cells are responsible for mobilising bone? And how do they do this?
Osteoclasts. They secrete hydrogen ions to dissolve the calcium salts and also provide proteolytic enzymes to digest extracellular matrix.
118
What are the 2 key hormones that act to increase calcium plasma concentration?
1. Parathyroid hormone (PTH) polypeptide hormone produced by parathyroid glands.
2. Calcitriol (active form of Vit D3) steroid hormone produced from Vit D by the liver and kidneys
119
Secretion of PTH:
| When is it released and how does it act?
Released in response to decrease in free calcium phosphate concentration.
Acts to increase concentration by:
1. Stimulating osteoclasts to increase resorption of Ca and phosphate in bone.
2. Inhibiting osteoblasts to reduce Ca deposition in bone.
3. Increasing reabsorption of Ca from the kidney tubules.
4. Increasing renal excretion of phosphate.
5. Stimulates the kidney to synthesis calcitriol from Vit .
120
Calcitriol - active Vit D3, How is it formed and stimulated?
Produced in 2 steps 1. Liver 2. kidneys - from dietary Vit D or precursors activated by sunlight. Stimulated by prolactin in lactating women.
Formed from cholesterol derivatives by action of UV light on skin.
121
What are the 3 main actions of Calcitriol?
1. Increase absorption of Calcium from the gut.
2. Facilitates renal absorption of Calcium
3. Mobilises calcium stores in bone by stimulating osteoclast activity.
complement those of PTH.
122
What is the direct effect of Vit D3?
To release Calcium from bone- net Vit D effect is to increase plasma calcium concentration and increase mineralisation of bone.
123
What happens in Vit d deficiency?
PTH works hard to maintain plasma calcium concentration and in doing so continually removes calcium from bone.
Leads to calcium and phosphate deficiency.
124
What key hormone acts to decrease calcium concentration in the plasma?
Calcitonin - produced by thyroid gland, secretion stimulated by increase in calcium concentration in plasma (paget's disease)
125
What endocrine hormones alter Ca balance?
1. Cortisol - inhibits osteoblasts.
2. Insulin - increases bone formation and antagonises
the action of cortisol
3. Oestrogen - promotes bone formation via oestrogen receptors.
4. GH - constant stimulus for bone formation
5. Prolactin - promotes calcium absorption from gut.
126
What is hyperplasia?
Increased number and secretory activity of cells
127
What is atrophy?
Diminution of cells due to lack of stimulation
128
Pituitary Glands histology:
| What are the 3 major cells and what do they stain?
1. Acidophils - pink - secretes GH and PRL
2. Basophils - dark purple - secrete ACTH, TSH, FSH, LH
3. Chromophobes - pale
129
What is the tanner method in staging of puberty?
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B - 1 to 5 (brest development)
G - 1 to 5 (genital development)
PH - 1 to 5 (pubic hair)
AH - 1 to 3 (axillary hair)
T - 2ml to 20ml
SO e.g. statement as B3PH3 or G2 PH2 6/6
```
130
What is the Prader Orchidometer?
Used for testicular maturation - Bead size equivalent to testicle size.
131
What are the most important pubertal stages?
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Breast budding (Tanner stage B 2) in girl
Testicular enlargement (Tanner Stage G2-T 3-4ml) in boy
- theses are the earliest objective signs of puberty and when present puberty will usually progress onwards.
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