Endocrinology Flashcards
(118 cards)
1
Q
What do hormones do
A
secrete specialised cells into the blood and act on specific receptors in target tissues
2
Q
GAP junctions
A
message transmitted directly from cell to cell
specificity depends on anatomical location - cells have to be next to each other to form GAP junction
wave of depolarisation spreads through gap junction
3
Q
Synaptic
A
Message transmitted across synaptic cleft
Specificity depends on anatomical location and receptors
4
Q
Paracrine and autocrine
A
Message transmitted by diffusion in ISF
Specificity depends on receptors
5
Q
Autocrine
A
cell releases chemical and acts on receptors on same cell
6
Q
Paracrine
A
chemical released into local interstatial space and acts on receptors in the local area
7
Q
Endocrine
A
Message transmitted by circulating body fluids
Specificity depends on receptors
8
Q
Endocrine system
A
endocrine cells within endocrine glands release hormones which are conveyed by the blood stream and act on distant cells
9
Q
Hormone
A
chemical messenger, synthesised by specialised cells, secreted into the blood in small amounts which acts on a specific receptor in target organs to regulate cellular function
10
Q
Non classical endocrine tissues
A
Kidney, heart muscle, endothelium, platelets, adipocytes, white blood cells
11
Q
Characteristics of hormones
A
- high affinity
- synergistic - effect of 2 greater than 1
- permissive - presence of 1 is necessary for another to have an effect
- antagonistic - 2 hormones can oppose each other
- competitive
12
Q
what are the classes of hormones based on chemical structure
A
- steroid hormones
- peptide hormones
- amino acid hormones
13
Q
Steroid hormones
A
e.g. cytosol
synthesised by cholesterol on demand - hard to store
Small hydrophobic (lipophilic) molecules
Circulate in bound form - hydrophobic
Act on intracellular receptors which bind to DNA to regualte gene transcription
Slow long lasting effects
14
Q
What are steroid hormones actions on receptors
A
Conformational change -releases protein inhibitory complex
Phosphorylation of proteins is not a direct result of steroid hormone binding to its receptor
15
Q
Peptide hormones
A
e.g. growth hormone
synthesised from amino acids
3-332 amino acids long
synthesised as preprohormones and stored prior to release
Act on cell surface receptors then via 2nd messenger systems to cause effect in target cells - pathway is dependent on receptor not hormone
16
Q
Amino acid hormones
A
e.g. thyroid hormone, epinephrine
Synthesised from tyrosine
Stored for instant release
Different modes of action
17
Q
Mechanisms of hormone release
A
- Continuous e.g. TH under control of TSH
- Pulsatile e.g. gonadotrophon releasing hormone (GnRH)
- Circadian e.g. melatonin
- Exocytosis on stimulus e.g. insulin
18
Q
Mechanisms of hormone activation
A
- Post release modification: steroids – oestrogens from androgens
Vitamin D
Angiotensinogen -> angiotensin II
19
Q
Control of hormone effects
A
- Modification: increases/decreases hormone activity e.g. vitamin D
- Degradation: hormone broken down/excreted e.g. oestrogen
- Receptor down-reguation: e.g. adrenergenic receptors
- Termination of intracellular effects: e.g. phosphatases
- Negative feedback
a. By the regulated metabolite (glucose/insulin)
b. By the hormone itself (cortisol)
c. By the tropic hormone released by the pituitary
20
Q
Which of the following hypothalamic hormones plays a role in the hypothalamic-pituitary-adrenal axis?
A
Corticotropin-releasing hormone
21
Q
In which cell type of the anterior pituitary is adrenocorticotropic hormone synthesised, stored and released?
A
Corticotrophs
22
Q
Basic structure of the adrenal gland
A
4-5g each
Made up of 2different cell types which produce very different hormones
on the kidneys
steroid hormones produced from cortex (outer), amino acid hormones(adrenaline) produced in inner layer
23
Q
Capsule
A
Outermost layer
Fibrous tissue
Provides protection and support
24
Q
Cortex
A
Middle layer
Comprises 80-90% of adrenal weight
Derived from mesodermal tissue which differentiates and becomes a steroidogenic cell
Comprises
Has 3 distinct zones
25
Zona glomerulosa
Outer cortex
Balls of cells
15% cortical volume
Produces aldosterone
Lacks 17 alpha-hydroxylase
26
Aldosterone
Major mineralocorticoid (controls salt + water balance)
50-70% bound to albumin in plasma - hydrophobic
half life = 15-20 minutes
primary action on kidney, colon and salivary glands to maintain normal Na+ concentration and ECF volume
Upregulates ENaC (epithelial sodium channel
Upregulates and activates Na+/K+ ATPase
27
Zona fasiculata
Middle cortex
Bundles of cells
Large lipid containing cells (75% cortical hormone)
Produces CORTISOL and ANDROGENS (biggest product)
lack of CYP11B2 gene
28
Zona glomerulosa
Inner cortex
Network of cells
Compact cells with less lipid (10% cortical volume)
Produces CORTISOL and ANDROGENS (can go round the body and be converted to be more active e.g. testosrerone and oestrogens)
Lack of CYP11B2 gene
29
Cortisol
Hydrocortisone
Major glucocorticoid
>90% bound to plasma proteins
Half life 60-90 minutes
Effects nearly all tissues by binding to its receptor and controlling gene transcription
30
What are the 8 effects of cortisol
1. Stimulates hepatic gluconeogenesis
2. Inhibits glucose uptake in muscle and adipose tissue – blood glucose levels rise
3. Stimulates muscle catabolism
4. Inhibits bone formation
5. Leads to loss of collagen and connective tissue
6. Increases vascular sensitivity to epinephrine and norepinephrine
7. Can modulate behaviour and cognitive function
8. Inhibits gonadal release of testosterone, oestrogen and progestins
31
Glucocorticoids
Anti-inflammatory and immunosuppression:
* Inhibits cytokine production and thus T cell proliferation
* Inhibit prostaglandin and leukotriene production
32
Cortisol
Appreciable affinity for mineralocorticoid receptors
Cortisol is converted to cortisone - inactive forms - migrates against effects of cortisol
33
Medulla
10-12% od adrenal weight
Derived from neural crast tissues
Early stages of sympathetic nervous system
Major product is epinephrine
Highly specialised part of the sympathetic nervous system
Potential to become neurones but do not deveop that way - bathed in locally produced cortisol
Adrenalin e- neurotransmitter of sympathetic nervous system
34
Hypothalamus pituitary axis
Major site of interaction between the nervous and endocrine system
Exerts control over several endocrine glands and a number of physiological activities e.g. balance, appetite
35
Hypothalamus
region of the brain which plays a key role in homeostasis
36
Pituatary gland
2 lobes: posterior pituitary and anterior pituitary
37
Posterior pituitary
The posterior lobe is of neural origin – aka the neurohyophysis
Consists of axons and nerve endings of neurones whose cell bodies reside in the hypothalamus
Hormones are produced in cell bodies of neurones, travel down nerves and are released on demand
includes efferent vein, pituitary stalk, magnocellular neurones and optic chiasm
38
Anterior pituitary
Anterior lobe originates from Rathke’s pounch – aka adenohypophysis
Consists of endocrine tissue
Includes Secretory cells, parvocellular neurones, hypophyseal portal vessels
39
Posterior pituitary hormones and their functions
Oxytocin - uterine smooth muscle contraction, breast myoepithelial contraction
Antidiuretic hormone (ADH) - water retention by the kidney
40
Where are the Posterior pituitary hormones produced and stored
Produced: magnocellular neurones of the hypothalamus
Stored: posterior pituitary
41
What does the hypothalamus release
Hypophysiotropic hormones that act upon the anterior pituitary
42
What are the hypophysiotropic hormones, target tissues and major functions
1. Thyotropin-releasing Hormone (TRH)
Thyrotrophs, lactotrophs
Stimulates thyroid-stimulating hormone (TSH) and prolactin release
2. Gonadotropin- releasing hormone (GnRH)
Gonadotrophs
Stimulate follicle-stimulating hormone and luteinizing hormone (LH) release
3. Corticotropin-releasing hormone(CRH)
Corticotrophs
Stimulates adrenocorticotropic hormone (ACTH) and prolactin release
4. Growth hormone-releasing hormone (GHRH)
Somatotrophs
Stimulates growth hormone (GH) release
5. Growth hormone-inhibiting hormone (somatostatin)
Somatotrophs
Inhibition of growth hormone (GH) release, also of gastrin, VIP, glucagon and insulin
6. Dopamine
Lactotrophs
Inhibits prolactin release
43
What are anterior pituitary hormones controlled by
Hypophysiotropic hormones
44
What is the endocrine cell, what hormone do they release and what are the major functions
1. Thyrotrophs- Thyroid Stimulating Hormone (TSH)
Stimulates thyroid hormone release
2. Gonadotrophs- Follicle-stimulating hormone (FSH)
Stimulates sex steroid production
3. Gonadotrophs-Luteinizing hormone (LH) Stimulates sex steroid production
4. Corticotrophs- Adrenocorticotropic hormone (ACTH)
Stimulates cortisol release
5. Somatotrophs-Growth hormone (GH) Stimulates growth
6. Lactotrophs- Prolactin
Stimulates milk production
45
What does somatroph release
growth hormone
46
Growth hormone (somatotropin)
191 amino acid peptide hormone
synthesised by somatotrophs in the anterior pituitary
released in response to GHRH
release inhibitied by growth hormone-inhibiting hormone
stimulates growth, cell reproduction and regeneration
Stress, sleep, hypoglycaemia reduce growth hormone release
47
Acute metabolic actions of GH (direct)
* Release fatty acids from adipose tissue and enhances their conversion to acetly-CoA
* Reduced glucose metabolism and uptake in to cells, especially the liver. Diabetogenic, i.e. anti-insulin
* Increased gluconeogenesis in the liver
* Increased production of insulin-like growth factor (IGF-1) - hepatic
48
Long term affects of GH (via IGF-1)
Growth promoting action on bone, epiphyseal cartilage, soft tissue, gonads, viscera
Promotes amino acid uptake and protein synthesis
Insulin-like endocrine effects on tissues
49
What are the roles of the thyroid glandn
1. Cardiovascular
Increases cardiac output and systolic pressure (heart rate & stroke volume)
Can change protein expression in cells e.g. increased response of androgenic receptors
2. Metabolic
Increased basal metabolic rate (glycolysis, oxygen consumption and thermogenesis)
Produces uncoupling proteins and you get more heat as a result
3. Neurological
Essential for maintaining emotional tone
Improves alertness, memory, reflexes and wakefulness
4. Growth and development
Essential for foetal neural development, and bone growth after birth
50
What is the major product of the thyroid and the most active thyroid hormone
Tetradiothyronine /T4
Triiodothyronine /T3
51
Thyroid composition
15-20g
2 lobes with connecting isthmus
rich blood supply
2 pairs of parathyroids on rear of the thyroid
52
what do parathyroids di
control release of parathyroid hormone - separate from the thyroid
53
Thyroid gland
functional units = follicles
single layer of cells surrounding a pool of colloid
production and storage of thyroid hormones in colloid
size of thyroid varies with its state of stimulation
C cells secrete calcitonin - involved in calcium homeostasis
54
How are thyroid hormones produced
Iodination and coupling of tyrosine
55
Thyroglobulin
Glycoprotein synthesised by follicular cells and released into the colloid by exocytosis
At the apical follicular membrane-colloid boarder, tyrosine residues within thyroglobulin are iodinated in the presence of the enzyme thyroperoxidase
56
Thyroid hormones
Precursors monoidotyrosine (T1) and diidotyrosine (T2) are coupled under the control of thyroperoxidase to form active hormones:
o Thyroxine (T4)
o Triiodothyronine (T3)
57
Thyroid hormone daily secretion, activity and freeness
Daily secretion: 100nmoles of T4 and about 5nmoles of T3
T3 is 3 -8 times more active than T4
Only about 0.4% of T3 and 0.04% of T4 are “free” in blood
58
3 major thyroid transporting proteins
1. Thyroxine-binding globulin (~ 70% of T3 & T4 bound with high affinity)
2. Thyroxine-binding prealbumin (aka transthyretin) (~ 10-15% of T4, tenfold greater affinity for T4 than T3)
3. Albumin (~ 15-20% circulating T3 & T4, rapid dissociation makes it major source of free hormone to tissues)
59
what is the half life of the thyroid hormones
T3= 1 day
T4 = week
60
The hypothalamic-pituitary-thyroid axis controls
* The hypothalamus releases thyrotropin-releasing hormone (TRH) which acts on the anterior pituitary
* In response to TRH, the anterior pituitary releases thyroid stimulating hormone (TSH) into the blood
* In response to TSH the thyroid releases thyroid hormones
* Negative feedback by T3 and T4 caused by rise in levels in the blood to prevent our bodies overdoing it
61
What does TSH act on the thyroid gland to increase
1. Iodide uptake
2. Thyroglobulin synthesis
3. Iodination of thyroglobulin
4. Pinocytosis of colloid
5. Lysosomal activity
6. Size of thyroid cells (cuboidal to columnar)
62
Enzymes controlling the deiodination of T4 and the metabolism of the thyroid hormone
Type 1 deiodinase: results in active or inactive T3
Type 2 deiodinase: results in active T3
Type 3 deiodinase: results in inactive T3 (reverse T3)
1+2 deiodinase act on outer ring of T4 producing T3
1 + 3 deiodinase act on the inner ring of T4 producing inactive rT3 (reverse T3)
63
What do T3 and T4 require to move across membranes?
transport proteins
64
Thyroid hormone receptors
4 Thyroid hormone receptors - TR α 1 & 2 and β 1 & 2
TR alpha 2 does not bind T3 where others have higher affinity for T3 than T4
Receptor bound to hormone response element and represses transcription
Key target is increased transcription of genes encoding mitochondrial uncoupling proteins
65
Gonad
an organ that produces gametes; a testis or ovary.
66
What are the dual functions of the gonads
1. Secrete sex hormones
2. Gametogenesis
67
Gametogenesis
Production of gametes for sexual reproduction; reproduction spermatogenesis (happens every 24 hours through the whole reproductive lifespan) and oogenesis (cyclical -1 egg per month)
68
What sex hormones do the gonads secrete
testes - large amounts of androgens, small amounts of oestrogens
ovaries - large amounts of oestrogens , small amounts of androgens , progesterone to prepare uterus for pregnancy
69
Process of egg release
1. Egg released from either side , ovary -> pelvic space
2. Oviduct moves egg -> uterus and allows sperm to move in opposite direction
3. uterus supports implantation and the growth and development of the foetus which is supported by the cervix
70
The Endomemtrium
Grows in first half of menstrual cycle
If fertilisation doesnt take place, the endometrium is shed off
Supported by the myometrium (muscle)
71
Oogenesis
Oocytes are formed in the developing ovary- arrest in prophase in meiosis 1 and exist within primordial follicles
Start at 11 week gestation
Derived from follicular cells in the ovarian membrane
Ovarian reserve - eggs that can be ovulated in the life cycle of a female
72
Primordial follicles at different life stages
1. At birth = ~7 000 000
Most die before puberty
2. At menarche (when period starts) = ~30 000 eggs
Most die (atresia- programmed cell death)
3. Develop further = ~30,000
Most die before they can be released
4. Released by ovulation = ~500
At menopause there is inefficient fimbriae for the cycle to work
73
What happens in the ovarian cycle
Maturation of oocytes and release of an ovum
Regular cycle of ~28 day duration on average (21-35 days)
Occurs in line with uterine cycle as part of the menstrual cycle
74
3 phases of the ovarian cycle
1. follicular
a. pre-antral
b. antral
c. pre-ovulatory
2. ovulation
3. luteal
75
1. Folliuclar phase
Mutation of follicles - several months
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1a preantral phase
Number recruited to develop each cycle
Paracrine factors stimulate growth
Antimulerian hormone limirs number developing at same time
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1b Antral phase
o Appearance of fluid filled atria
o Increased layers of zona granulosa
o Thicker zona pellucida
o Theca interna is more apparent
o Growth dependent on pituitary FSH (follicle stimulating hormone)
o Dominant follicle selected and becomes a significant steroidogenic gland
theca cells able to catalyse androgen production from cholestrerol
78
How do FSH levels decline in the antral phase
granulosa cells contain aromatase so they can convert the androgen to oestrogen causing levels to decline and the ones that can resist the FSH drop is the most dominant follicle
79
What happens to mature pre antral follicles over 25 days
Double in diameter
several layers granulosa cells appear
80
What do thecal cells do
produce significant amounts of androstenedione which is converted to oestradiol by granulosa cells.
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1c. pre ovulatory phase
1. Dominant (Graafian) follicle responds to a surge in LH by completing 1st meiotic division and arresting in metaphase of meiosis II
2. Haploid secondary oocyte (egg) and polar body
3. FSH increases LH (luteinizing hormone) receptor and enzyme expression in granulosa cells – progesterone production
4. Inflammatory cytokines and hydrolytic enzymes released by theca and granulosa cells
Only progresses beyond metaphase 2 if the ovum is fertilisedo
82
Polar body
Small haploid cell that is formed concomitantly as an egg cell during oogenesis, but generally does not have the ability to be fertilised
83
Ovulation
release of ovum from ovary -> fallopian tube
32-36 hour duration
Involves an inflammatory event that erodes the wall of the ovary and follicle
oocyte, zona pellucida and corona radiata released in to peritoneal cavity before being captured by the oviduct
Corona radiata (centre of oocyte) is crucial for the capture of the oocyte by the fimbriae and movement through the oviduct
Remnants of the follicle in the ovary go on to form the corpus luteum
84
What is ovulation triggered by
surge in LH
85
Luteal Phase
Formation of the corpus luteum
12-15 days
Granulosa cell fills with lipid
major product = progesterone
Oestrogen initially decrease due to LH surge but then rebounds
If no pregnancy, degenerates in to corpus albicans. Oestrogen and progesterone levels fall allowing FSH and LH levels to rise
If pregnancy, placenta releases human chorionic gonadotrophin which enables the corpus luteum to persist
86
Stages of the luteal phase
1. LH receptors now on thecal and granulosa cells. LH surge triggers luteinisation. Increased LH transiently inhibits aromatase activity and thus oestrogen levels drop. This drop in oestrogen helps to turn off its positive feedback effect that causes increased LH release.
2. If pregnancy syncytiotrophoblasts of the placenta release human chorionic gonadotrophin which maintains the existence of the corpus luteum. Produces hormones for first 8 weeks before placenta can take over in pregnancy
3. Corpus albicans, atretic corpus luteum. Cellular elements have degenerated and macrophages phagocytose the dead cells. Fibrous tissue is left behind. It will continue to shrink in size, eventually forming a small scar on the side of the ovary.
87
Important hypothalamic and pituitary hormones
1.Gonadotropin releasing hormone (GnRH)
Release is pulsatile, high frequency = LH, low frequency = FSH
60-90 mins = high frequency and induced LH release, greater than 120 mins = low frequency (between bursts) promotes FSH release.
2. FSH
Stimuates recruitment and growth of immature molecules
Upregulates CYP19 gene exrpression and activity
Induces LH receptor expression in granulosa cells
3. Luteinising hormone
Acts on theca cells (in follicles) to promote androgen production
Surges trigger ovulation
Acts on granulosa cells to secrete progesterone
Maintains corpus luteum
88
What is the effect of high levels of oestrogen on LH
positive feedback effect
some FSH release
89
Important ovarian hormones
Oestrogens
Progesteronen
Inhibin A and B
90
Oestrogens
Oestradiol, oestriol, oestrone
Prepares reproductive tract for potential fertilisation and pregnancy
Dominant hormone secreted pre-ovulation (follicular phase)
Cervix becomes receptive to sperm. Increases secretion and motility/cilia of uterine tubes. Promotes uterine/endometrial growth/regrowth.
91
Progesterone
Promotes uterine and uterine tube secretions to maintain and support potential fertilisation and implantation of an egg
Dominant hormone secreted post-ovulation (luteal phase)
92
Inhibin A and B
Secreted by granulosa cells (corpus luteum and follicular phase, respectively) and represses FSH secretion
93
What happens at the end of the ovarian cycle
1. Demise of the corpus luteum
2. Decrease oestrogen and progesterone production
3. Release of negative feedback and FSH increases
4. Crop of antral follicles recruited and start to grow
94
Stages of the early follicular phase
1. Follicles produce low levels of oestrogen
2. Oestrogen negatively feeds back on FSH
3. Loss of progesterone and higher oestrogen increases frequency of GnRH pulses
4. LH to FSH secretion ratio increases
5. Decreased FSH leads to follicular atresia leaving dominant one
95
Stages of late follicular phase
1. Dominant follicle produces >oestrogen
2. High oestrogen levels (>200pg/ml) positively feedback on LH
3. LH surge enhanced by progesterone
4. Oocytes completes meiosis I
5. Ovulation is triggered
6. Transient drop in oestrogen ends surge
Transient drop in oestrogen is due to high levels of LH inhibiting aromatase
96
97
Stages of luteal phase
1. Corpus luteum forms
2. High progesterone negatively feeds back and blocks positive feedback of high oestrogen, so FSH and LH levels drop
3. Corpus luteum begins to regresses
4. Progesterone and oestrogen levels fall
5. Negative feedback lifted and FSH rises
98
Hypo-pituitary dwarfism
Cause: insufficient growth hormone - results from trauma, infarction or a space occupying lesion/tumour that compresses normal tissues
99
Which of the following is not a feature of growth hormone excess in adulthood?
Gigantism
100
Pituitary gigantism
Cause: Excessive GH secretion early in life - leads to excessive linear growth
101
Hypogonadism
represses gonads and delays closure of the epiphesyeal growth plates meaning linear growth continues for longer than would be expected (as teenagers)
Excessive GH
102
Acromegaly
Excessive GH secreted in adulthood
Symptoms: enlarged jaw, hands and feet
Can lead to problems regulating plasma glucose, blood pressure and can result in heart and kidney failure
103
Which of the following has a direct effect on thyroid gland function?
TSH
104
Which of the following is not true in relation to the effects of thyroid hormone?
They decrease thermogenesis
105
Hypothyroidism in new borns/infants
Decreased mental capacity
Short stature
Neural – important role in development – early development of the foetus is dependent upon small amounts of thyroxine passing through the placenta from the maternal blood, the developing foetal thyroid then takes over.
Growth and Development - Essential for foetal neural development, and bone growth after birth
106
Hypothyroidism in children
decreased mental capacity and growth
107
Hypothyroidism in adults
autoimmune disorder targeting thyroperoxidase and/or thyroglobulin, is the most common cause of hypothyroidism
General tiredness and lethargy
Cold intolerance
Weight gain
Bradycardia
Mental slowness
Depression (in about 50% of cases)
Puffy hands and face
Increased expression of proteins involved in metabolic pathways
108
Treatmeant of hypothyroidism
T4
109
Hyperthyroidism
Increased metabolism resulting in intolerance to heat and weight loss
Can get a catabolic state with loss of muscle mass and muscle weakness – exacerbates the sympathetic response
Heat intolerance
Weight loss
Warm moist skin
Tachycardia (atria fibrillation and heart failure)
Fine tremor of fingers
110
Graves disease
Increased metabolism resulting in intolerance to heat and weight loss
Can get a catabolic state with loss of muscle mass and muscle weakness – exacerbates the sympathetic response
Heat intolerance
Weight loss
Warm moist skin
Tachycardia (atria fibrillation and heart failure)
Fine tremor of fingers
111
Adrenocorticotropic hormone is release from which tissue?
Anterior pituitary
112
What effect does cortisol have on the inflammatory and immune response?
Inhibits the response
113
In which layer of the adrenal gland is aldosterone produced?
Zona glomerulosa
114
Addisons disease
Adrenocorticoid insufficiency. 80% autoimmune with adrenal atrophy. The remainder a result of infection, malignancy or medication.
Cortisol deficiency
1. Weakness
2. Fatigue
3. Decreased appetite
4. Hypoglycaemia
Mineralocorticoid deficiency
1. Excessive renal Na+ loss
2. Dehydration
3. Hypotension
4. Hyponatraemia
5. Hyperkalaemia
6. Acidosis
115
Cushing’s syndrome is a disorder of glucocorticoid excess. Which of the following is a symptom of Cushing’s syndrome?
Central obesity with muscle wasting in arms and legs
116
Cushings syndrome
Chronic glucocorticoid (cortisol) excess
Commonly iatrogenic (chronic glucocorticoid therapy)
Can result from pituitary or adrenal abnormality, or ectopic ACTH
Cushing’s disease results from a pituitary tumour
Removal of pituitary tumour as Cushing’s disease, removes the excessive stimulation of the adrenals and drive for cortisol production.
Symptoms: weight gain, moon face, atrophy of epidermis, hypertension, acne, osteoporosis
117
Effects of aldosterone in addisons disease
Acts on the nuclear mineralocorticoid receptors within principal cells of the kidney nephron
Up regulates and activates Na+/K+ ATPase, stimulating ATP hydrolysis leading to phosphorylation of the pump and a conformational change in the pump exposes the Na+ ions to the outside
The phosphorylated form of the pump has a low affinity for Na+ ions, hence reabsorbing sodium (Na+) ions and water into the blood, and secreting potassium (K+) ions into the urine.
Aldosterone upregulates epithelial sodium channel (ENaC) increasing apical membrane permeability for Na+.
118
Effects of cortisol in addisons disease
Stimulates hepatic gluconeogenesis
Inhibits glucose uptake in muscle and adipose tissue
Stimulates muscle catabolism
Inhibits bone formation
Leads to loss of collagen and connective tissue
Increases vascular sensitivity to epinephrine and norepinephrine
Can modulate behaviour and cognitive function
Inhibits gonadal release of testosterone, oestrogen & progestins
Anti-inflammatory and immunosuppression:
Inhibits cytokine production and thus T cell proliferation
Inhibit prostaglandin and leukotriene production
