Session 9 Flashcards
(47 cards)
0
Q
What are the sections of the kidney that produce hormones?
A
- Cortex: steroid hormones
- Medulla: amino acid hormone
1
Q
What hormones are produced by the anterior pituitary gland?
A
- Thyroid stimulating hormone (produced in thyrotrophs)
- Adrenocorticotrophic hormone (corticotrophs)
- Growth hormone (somatotrophs)
- Follicle stimulating hormone (gonadotrophs)
- Leuteinizing hormone (gonadotrophs)
- Prolactin (lactotrophs)
2
Q
What are the layers of the kidney cortex and what hormones do they produce?
A
- Zona Glomerulosa: mineralocorticoids (eg aldosterone)
- Zona Fasiculata: glucocorticoids (eg cortisol and corticosterone)
- Zona Reticularis: androgens (eg testosterone)
3
Q
What is secreted by the kidney medulla?
A
- Adrenaline (Hormone)
- Noradrenaline (neurotransmitter)
- Dopamine (neurotransmitter)
(All are catecholamines - derived from amino acid tyrosine)
4
Q
What controls the release of cortisol?
A
- ACTH secretion from tepee anterior pituitary gland
- (which is controlled itself by corticotrophin releasing factor (CRF) produced in the hypothalamus)
5
Q
What is CRF a secreted in response to?
A
- Stressors: Physical (temperature, pain); Chemical (hypoglycaemia); Emotional
6
Q
What is ACTH developed from?
A
- POMC
7
Q
Describe the presence of ACTH in the bloodstream
A
- Has a short half-life (8mins)
- Released in pulses that follow a circadian rhythm
- Peak plasma levels are in the morning, lowest levels at night
8
Q
How does ACTH cause the increase in the synthesis of free cholesterol?
A
- Is hydrophilic and interacts with high affinity receptors in the surface of cells in the Zona Fasiculata and Zona Reticularis
- Activates cholesterol esterase
- Increases conversion of cholesterol esters to free cholesterol
- Also stimulates conversion of cortisol from cholesterol
9
Q
What are the clinical consequences of the over-secretion of ACTH?
A
- Increased pigmentation (effect on tissues)
- Adrenal hyperplasia and over-production of cortisol (effect on a adrenal cortex)
10
Q
What is are the clinical consequences of under secretion of ACTH?
A
- Symptoms related to lack of glucocorticoids
- No symptoms related to lack of mineralocorticoids as aldosterone secretion is normal (not controlled by ACTH)
11
Q
What is the receptor for ACTH and how does it work?
A
- Melanocortin receptor type 2/MC2/corticoptrophin receptor
- Uses cAMP as a secondary messenger
12
Q
How is cortisol transported in the blood?
A
- Is lipophilic so is bound to plasma proteins
- Main transport protein is transcortin/corticosteroid-binding globulin (CBG)
13
Q
What is the active form of cortisol?
A
- Free in the plasma
14
Q
How does cortisol act on its target cells?
A
- Crosses the plasma membrane and binds to cytoplasmic receptors (as is lipophilic/hydrophobic)
- Hormone/receptor complex enters nucleus and interacts with specific regions of DNASE
- This changes the rate of transcription of specific genes
15
Q
What is cortisol a response to?
A
- Stress eg starvation
16
Q
What are the actions of cortisol?
A
- Increases proteolysis, lipolysis and gluconeogenesis to increase availability of major substrates
- ⬇️ amino acid uptake; ⬇️ protein synthesis ⬆️ proteolysis (not in liver) -> ⬆️ amino acids
- ⬆️ hepatic gluconeogenesis and glycogenolysis -> ⬆️glucose
- ⬆️ lipolysis in adipose tissue -> ⬆️ fatty acids (NB high levels of cortisol increases lipogenesis in adipose tissue)
- ⬇️ peripheral uptake of glucose (anti-insulin)
17
Q
What other tissues are directly affected by cortisol?
A
- Cardiac muscle
- Bone
- Immune system
18
Q
What is the function of aldosterone?
A
- Stimulates Na+ reabsorption in the kidney in exchange for K+ or H+
- Over secretion increases Na+ and water retention and loss of K+ -> hypertension and muscle weakness
- Under secretion does the opposite -> hypotension
19
Q
What is the function of androgens?
A
- Stimulates growth and development of male genital tract and male secondary sexual characteristics
- Over secretion produces effects in females: hair growth (hirsuitism); acne; menstrual problems; increased muscle bulk; deepening voice
20
Q
What is the function of oestrogens?
A
- Stimulates growth and development of female genital tract, breasts and female secondary characteristics
- Weakly anabolic and decrease circulating cholesterol levels
21
Q
What is the structure of cortisol?
A
- Member of C21 steroid family that differs from other steroids in: number of carbon atoms; presence of functional groups; distribution of C=C double bonds
- Are lipophilic so are transported bound to plasma proteins (~90% transcortin, ~10% free and active)
- Synthesised from cholesterol via progesterone in a series of enzyme catalysed reactions
22
Q
When is adrenaline secreted?
A
- As part of fright, flight or fight response
- In response to stress situations
23
Q
What are the effects of adrenaline?
A
- Cardiovascular system: ⬆️ cardiac output; ⬆️ blood supply to muscle
- CNS: ⬆️ mental alertness
- Carbohydrate metabolism: ⬆️ glycogenolysis in liver and muscle
- Lipid metabolism: ⬆️ lipolysis in adipose tissue
24
What are the clinical consequences of over-secretion of Adrenaline?
- Hypertension
- Anxiety
- Palpitations
- Pallor
- Sweating
- Glucose intolerance
(Usually due to a tumour - phaechromocytoma)
25
How does adrenaline act upon its target cells?
- Cannot cross cell membrane
- Binds to an adrenoreceptor on the outside of the cell
- A secondary messenger then affects cell activity
26
What can cause hypoactivity of the adrenal cortex?
- Diseases of the adrenal cortex (autoimmune destruction): reduces glucocorticoids and mineralocorticoids
- Disorders in pituitary or hypothalamus that lead to decreased secretion of ACTH or CRF: only reduces glucocorticoids
27
What is Addison's disease?
- Decreased activity (hypoactivity) of adrenal cortex
28
What can cause hyperactivity of adrenal cortex?
- Increased activity of adrenal cortex due to tumour (adenoma)
- Disoders in the secretion of ACTH caused by pituitary adenoma (Cushing's disease) or ectopic secretion of ACTH
(Both cause increased secretion of glucocorticoids)
29
What is Cushing's syndrome?
- Increased secretion of glucocorticoids
30
What is congenital adrenal hyperplasia?
- Caused by genetic defect in enzymes required for cortisol synthesis
- Lack of cortisol causes pituitary gland to secrete large amount of ACTH have as cortisol levels don't feedback
- ACTH causes adrenal cortex to enlarge (hyperplasia)
- Severity and consequences depend on which enzymes are affected
31
What abnormal functions of the adrenal cortex can cause clinical problems?
- Hypoactivity
- Hyperactivity
- Congenital adrenal hyperplasia
32
What are the clinical effects of excess cortisol secretions?
- Increased proteolysis and hepatic gluconeogenesis may -> hyperglycaemia with associated polyuria and polydipsia (steroid diabetes)
- Increased proteolysis -> wasting of proximal muscles -> thin arms, legs and muscle weakness
- Increased lipogenesis in adipose tissue -> deposition of fat in abdomen, neck and face (characteristic body shape, moon-shaped face and weight gain)
- Purple striae on lower abdomen, upper arms and thighs - caused by catabolic effects on protein structures in skin -> easy bruising because of thinning of skin and subcutaneous tissue
- Immunosuppresive, anti-inflammatory and anti-allergic reactions of cortisol -> increased susceptibility to bacterial infections and acne
- Back pain and rib collapse - osteoporosis caused by disturbances in calcium metabolism and loss of bone matrix protein
- Mineralocorticoid effects of excess cortisol -> hypertension due to sodium and fluid retention
33
Other than Cushing's disease, in what other situation can patients have symptoms of excess cortisol secretion?
- Long-term treatment with glucocorticoids for various chronic inflammatory conditions
34
What is affected by autoimmune destruction of the adrenal gland?
How does this present?
- Decreased cortisol production (glucocorticoid)
- Loss of mineralocorticoids also
- Acute emergency (Addisonian crisis) or chronic debilitating disorder (Addison's disease)
35
What are the clinical effects of too little cortisol secretion?
- Insidious onset with initial non-specific symptoms: tiredness; extreme muscle weakness; anorexia; vague abdominal pain; weight loss; occasionally dizziness
- Extreme muscle weakness and dehydration
- Increased pigmentation on: exposed areas of the body; points of friction; buccal mucosa; scars; palmar creases
- Decreased blood pressure due to sodium and fluid depletion
- Postural hypotension due to fluid depletion
- Hypoglycaemic episode especially when fasting
36
What exacerbates the effects of low cortisol secretion and what does this cause?
- Stress eg trauma or severe infection
| - Leads to nausea; vomiting; extreme dehydration; hypotension; confusion; fever; coma (Addisonial crisis )
37
How would an Addisonian crisis be treated?
- Intravenous cortisol
| - Fluid replacement (dextrose in normal saline)
38
What is important to measure when investigating suspected adrenocortical disease?
- Plasma cortisol
- Plasma ACTH
- 24hr urinary exertion of cortisol and breakdown products (17-hydroxysteroids)
39
What tests are used in the differential diagnosis of adrenocortical disease?
- Dexamethasone suppression tests
| - ACTH stimulation test
40
What is Dexamethasone and why is it used in diagnosing adrenocortical disease?
- A potent synthetic steroid
- When given orally it normally suppresses (by feedback inhibition) the secretion of ACTH and therefore cortisol
- In Cushing's disease, it causes suppression of cortisol by ~50% (although diseased pituitary is relatively insensitive to cortisol, it remains sensitive to potent synthetic steroids)
- Suppression does not occur when cortisol is too high due to adrenal tumours or ectopic ACTH production
41
What is Synacthen and why is it used in diagnosing adrenocortical disease?
- Is a synthetic analogue of ACTH
- When given intramuscularly, it normally increases plasma cortisol by >200 mmol/L
- A normal response usually excludes Addison's disease
42
What are steroid receptors?
- Part of a family of nuclear DNA-binding proteins that include thyroid and vitamin D receptors
- Have 3 main regions: hydrophobic hormone-binding region; DNA-binding region (rich in cysteine and basic amino acids); variable region
43
Why can cortisol act as a mineralocorticoid in high concentrations?
- There is homology in the hormone binding regions of the steroid receptors
- Cortisol can bind to the mineralocorticoid and androgen receptors with low affinity
44
How can ACTH lead to increased pigmentation?
- Precursor of ACTH is pro-opiomelanocortin (POMC)
- Post-translational processing of POMC at different sites produces biologically active peptides eg ACTH, MSH (melanocyte stimulating hormone) and endorphins
- MSH sequence is contained within the ACTH a sequence in POMC
- This gives ACTH some MSH-link activity when present in excess
45
What are the clinical consequences of over-secretion of ACTH?
- Occur with little/no negative feedback from cortisol to anterior pituitary- Addison's disease
- ACTH has effects on the adrenal cortex and on tissues (increased pigmentation due to partial MSH activity)
46
What are the key consequences of excess and deficiency of cortisol?
- Deficiency: - Excess:
~ Low glucose ~ High glucose
~ Weight loss ~ Weight gain
~ Nausea ~ Increased appetite
~ Hypotension ~ Hypertension
~ Cushingoid fat distribution
