Physiology Flashcards
1
Q
Where is the thyroid gland located?
A
Anterolateral to larynx and trachea
2
Q
Where are the parathyroid glands located?
A
Posterior aspect of each thyroid lobe
3
Q
What do thyroid follicles surround and what does it contain?
A
The colloid:
- Tyrosine-containing thyroglobulin filled sphere
4
Q
What is the process by which T3 and T4 are made and stored?
A
- Iodine taken up by follicle cells
- Iodine attaches to tyrosine residues on thyroglobulin:
-Forms two units
> Monoiodotyrosin unit (MIT)
> Diiodotyrosine unit (DIT) - Coupling of MIT and DIT:
- MIT + DIT -> T3
- DIT + DIT -> T4
- Stored in colloid thyroglobulin until required
5
Q
What thyroid hormone is secreted in larger amounts?
A
T4 (90% of secreted hormone)
6
Q
Which thyroid hormone is more potent?
A
T3 (~4 times more potent than T4)
7
Q
Where is T4 converted to T3?
A
Liver
Kidneys
8
Q
What thyroid hormone is the major biologically active hormone?
A
T3
9
Q
Why do T3 and T4 bind to plasma proteins?
A
They are lipophilic
10
Q
What plasma proteins do thyroid hormones bind to?
A
Thyroxine-Binding Globulin -> ~70%
Thyroxin-Binding Prealbumin -> ~20%
Albumin -> ~5%
11
Q
What is the other name for thyroxine-binding prealbumin?
A
Transthyretin
12
Q
What are the features of T3 binding? What does this allow?
A
Bound 10-20 times less avidly by TBG
Not bound significantly by TTR
This allows more rapid onset and offset of action
13
Q
What does the metabolic state correlate closer to; level of free hormone of level of total plasma concentration?
A
Level of free hormone
14
Q
How does Ninewells asses thyroid hormones?
A
Measure fT3 and fT4
15
Q
What can cause increased levels of thyroxine-binding globulin?
A
Pregnancy Newborn Oral contraceptive (Increased oestrogen) Tamoxifen Hep A Chronic Hepatitis Billiary cirrhosis
16
Q
What can cause decreased levels of thyroxine-binding globulin?
A
Androgens
Cushing's
Acromegaly
Severe systemic illness
Chronic liver disease
Nephrotic syndrome
Drugs:
- Phenytoin
- Carbamazepine
17
Q
How do carbimazole and propylthiouracil work?
A
Inhibit thyroperoxidase:
- Enzyme needed to produce MIT and DIT
18
Q
What does increased TBG cause?
A
Increased total T4
Normal fT4
19
Q
What does decreased TBG cause?
A
Reduced total T4
Normal fT4
20
Q
How do T3 and T4 increase the basal metabolic rate?
A
Increase the number and size of mitochondria
Increase oxygen use and ATP hydrolysis
Increase synthesis of respiratory chain enzymes
21
Q
How much of thermogenesis do T3 and T4 contribute to?
A
~30%
22
Q
What effects do T3 and T4 have on carbohydrate metabolism?
A
Increase blood glucose:
- Stimulate glyogenolysis + gluconeogenesis
Increase insulin-dependent glucose uptake
23
Q
What effects do T3 and T4 have on lipid metabolism?
A
Mobilise fats from adipose
Increase fatty acid oxidation
24
Q
What effects do T3 and T4 have on protein metabolism?
A
Increase protein synthesis
25
What effects do T3 and T4 have on growth?
GHRH production and secretion requires T3 and T4
Permissive actions:
- Glucocorticoid-induced GHRH release
- Allows GH and somatomedin activity
26
What effects do T3 and T4 have on the foetal and neonatal brain?
Myelinogenesis
| Axonal growth
27
How do changes in T3 and T4 concentrations affect the CNS?
```
Hypothyroid:
- Slow intellectual functions
Hyperthyroid:
- Nervousness
- Hyperkinesis
- Emotional lability
```
28
What affect does T3 and T4 have on the SNS?
Increases responsiveness to adrenaline and NA:
- By increasing the number of receptors
Also increases force and rate of heart contractions
29
What happens to TRH in cold temperatures (in kids)?
TRH is released:
| -> TSH released -> T3 and T4 release
30
What effect does stress have on thyroid hormone regulation?
Inhibits TRH and TSH release
31
When are thyroid hormones highest and lowest?
Highest at night
| Lowest in the morning
32
What family of 3 enzymes help activate and deactivate T3 and T4?
Deiodinase enzymes
33
How do the deiodinase enzymes work?
Add/Remove an idoine atom in the outer ring of T3 and T4
34
What enzyme activates T4 to T3 in tissues?
D2
35
Where is D1 found?
Liver
| Kidney
36
Where is D2 found?
Heart and skeletal muscle
CNS
Fat
Thyroid and pituitary
37
Where is D3 found?
Foetal tissue and placenta
| Brain -> Except pituitary
38
Weight gain, bradycardia, fatigue, cold intolerance, myxoedema (adults) and cretinism (kids) are signs of what?
Hypothyroidism
39
How does cretinism present?
Dwarfism
| Reduced mental functioning
40
Why does thyroid-stimulating Ig cause Grave's (hyperthyroidism)?
Acts like TSH:
- Unchecked by T3 and T4
- No negative feedback
41
What causes exophthalmos in Grave's?
Water-retaining carbohydrates build up behind eyes
42
What can a pituitary adenoma compress?
Optic chiasm -> Bitemporal hemianopia
CNs iii, iv and vi:
- iii -> Eye down and out
- iv -> Superior oblique paralysis -> Vertical diplopia
- vi -> Lateral rectus paralysis -> Horizontal diplopia
43
What else can a pituitary adenoma result in?
```
Hypoadrenalism
Hypothyroidism
Hypogonadism
DI
GH deficiency
```
44
What are physiological causes of raised PRL?
Breast feeding
Pregnancy
Stress
Sleep
45
What drugs can cause a raised PRL?
Dopamine antagonists (Metoclopramide)
Antipsychotics
Antidepressants (TCSa and SSRIs)
Others (Oestrogens and Cocaine)
46
What are pathological causes of a raised PRL?
```
Hypothyroidism
Stalk lesions:
- Iatrogenic
- RTA
Prolactinoma
```
47
How do women present with a raised PRL?
Early
Galactorrhoea (30-80%)
Oligo-/Amenorrhoea
Infertility
48
How do men present with a raised PRL?
```
Late
Impotence
Abnormal visual field
Headache
Anterior pituitary dysfunction
```
49
In a patient with a raise PRL, what might we see in a pituitary MRI?
Micro-/Macroprolactinoma
Pituitary stalk lesion
Optic chiasm compression
50
How is a prolactinoma treated?
```
Dopamine agonists:
- Bromocripton -> PO tds
- Quinagolide -> PO od
- Cabergoline -> PO twice weekly
> Least side effects (most commonly used)
```
51
What causes acromegaly?
GH excess
52
What soft tissue features of acromegaly are there?
Thickened skin
Large jaw
Sweaty
Large hands
53
What cardiac features are present in acromegaly?
Hypertension
| CHF
54
What are some other features of acromegaly?
```
Vascular headaches
Snoring/Sleep apnoea
DM
Mass effects:
- Visual fields
Colonic polyps and cancer
```
55
How do we diagnose acromegaly?
```
IGF-1:
- Age and sex matched
Glucose tolerance test:
- 75g PO suppression test
- Check GH at 0, 30, 60, 90 and 120 minutes
- Normal -> GH suppressed to
```
56
What will the result of a glucose tolerance test be in a patient with acromegaly?
No suppression
Paradoxical rise
GH remains >1μg/L
57
Why does glucose suppress GH?
GH stimulates an increase in blood glucose levels
| So if glucose is raised, negative feedback will cause GH levels to drop
58
What is the first line treatment for acromegaly?
Pituitary surgery
| Followed by external radiotherapy to pituitary fossa
59
What is the second line treatment and when is it commenced?
```
Drug treatment:
- Cabergolin
- Octreotide (Somatostatin analogue)
- Pegvisomat
If on GTT retest, GH is still >1μg/L
```
60
At what GH level is a patient clinical safe from further progression of acromegaly?
GH
61
What effects do somatostatin analogues have in acromegaly?
```
Reduce GH in most
Shrink the tumour by 30-50%:
- 6-12 months for effect
- Recurs 6 weeks if stopped
Relieves headaches 1 hours post-op
Improve surgical outcomes
```
62
What are some side effects of somatostatin analogues?
```
Local stinging
Short term:
- Flatulence
- Diarrhoea
- Abdominal pain
Long term:
- Gastritis (
```
63
How does pegvisomat work?
GH antagonist:
| - Binds to GH receptor competitively
64
How is pegvisomat administered?
S/C injection:
| - 10-30mg/dayy
65
What effects does pegvisomat have?
No decrease in tumour size
Reduces IGF-1
May increase serum GH
66
Why is pegvisomat the last line therapy?
20mg does costs £36000/year
67
What cancers must be screened for after acromegaly has been treated?
Colon
| Tubulo-villous adenoma
68
What CVS risk factors need monitored after acromegaly treatment?
BP
Lipids
Glucose
69
What regulates aldosterone?
RAAS
| Plasma K+
70
What encourages the hypothalamus to increase CRH production and, hence, increase cortisol production?
Stress
Illness
Time of day (Peak at 9am)
71
When is the RAAS activated?
When blood pressure falls
72
How does angiotensin ii correct BP?
Directly by vasoconstriction
Indirectly via aldosterone:
- Increases Na+ reabsorption in kidney
- Hence water reabsorption increases
73
What are the 6 classes of steroid receptors?
```
Glucocorticoid
Mineralocorticoid
Progestin
Oestrogen
Androgen
Vitamin D
```
74
What effect does cortisol have on the CVS?
Increases cardiac output
Increases BP
Increases renal blood flow -> Increases GFR
75
What effect does cortisol have on the CNS?
Mood lability
Euphoria
Decreased libido
76
What effect does cortisol have on bone and connective tissue?
Increased rate of osteoporosis
Reduces serum calcium
Reduces collagen formation
Reduces wound healing
77
What effect does cortisol have on metabolism?
Increases blood glucose
Increases lipolysis
Increases proteolysis
78
What effect does cortisol have on the immune system?
Reduced capillary dilation
Reduced leucocyte migration
Reduced macrophage activity
Reduced cytokine production
79
What are the three main principles of using corticosteroids for clinical treatments?
Reduce inflammation -> Supraphysiological dose
Immunosuppression -> Supraphysiological dose
Replacement therapy -> Physiological dose
80
Which administration route is better for corticosteroids; IM or IV?
IM
81
What are corticosteroids used to treat (mainly)?
```
Allergy
Inflammatory disease:
- RA
- UC
- Crohn's
Malignancy
```
82
What effects does aldosterone have?
Na+/K+ balance:
- Increases Na+ reabsorption
- Increases K+/H+ secretion (and hence excretion)
Increases blood pressure:
- Water follows Na+ -> Increased water reabsorption
Regulates ECV
83
In which of these locations are mineralocorticoid receptors not found:
- Kidneys
- Heart
- Salivary glands
- Gut
- Sweat glands
Heart
84
Where does primary adrenal insufficiency arise?
Adrenal gland
85
What can cause primary adrenal insufficiency?
Addison's
CAH
Adrenal TB/Malignancy
86
What can cause secondary adrenal insufficiency?
Lack of ACTH
Exogenous steroid
Pituitary/Hypothalamic disorders
87
What causes Addison's Disease?
Autoimmune destruction of adrenal cortex
88
True or false; Addison's is the most common cause of adrenal insufficiency?
False
It is only the most common cause of primary adrenal insufficiency
Exogenous steroids are the most common cause overall
89
What is Addison's disease associated with?
T1DM
Thyroid disease (Grave's)
Pernicious anaemia
90
What are the clinical features of Addison's disease?
```
Weight loss
Fatigue
Hypotension -> Dizziness
GI:
- Abdominal pain
- Vomiting
- Diarrhoea
Oligo-/Amenorrhoea
Skin pigmentation:
- Skin creases
- Buccal surfaces
```
91
What biochemistry is seen in primary adrenal insufficiency:
- CRH
- ACTH
- Cortisol
- Aldosterone
- Renin
- Na+
- K+
```
CRH is high
ACTH is high
Cortisol is low
Aldosterone is low
Renin is high
Na+ is low
K+ is high
```
92
What is the definitive diagnosis of primary adrenal insufficiency?
```
Short synACTHen test:
- Measure plasma cortisol
> Before
> 30 minutes after IV/IM ACTH
Normal result:
- Baseline -> >250nmol/L
- Post-ACTH -> >550nmol/L
Cortisol will barely rise on the synacthen test
```
93
Should we delay treatment of adrenal insufficiency to confirm diagnosis?
NO
94
How do we treat adrenal insufficiency?
```
Hydrocortisone (cortisol replacement):
- IV first if unwell
- 15-30mg daily -> Divided doses
- Mimic diurinal rhythm
> 10 mg in the morning
> 5mg at lunch and at night
Fludrocortisone (aldosterone replacement):
- Monitor BP and K+
```
95
What causes secondary adrenal insufficiency?
Lack of CRH and ACTH (hypothalamic disease) or ACTH (pituitary disease)
96
What is the commonest cause of secondary adrenal insufficiency?
Exogenous steroids:
- High dose prednisolone
- Dexamethasone
- Inhaled corticosteroid
97
What are the clinical features of secondary adrenal insufficiency?
Similar to Addison's:
- Except no hyperpigmentation (since no ^ ACTH)
- And aldosterone production is intact
98
How is secondary adrenal insufficiency treated?
Hydrocortisone only
99
What is Cushing's syndrome?
Excess cortisol
100
What are the clinical features of Cushing's syndrome?
```
Easy bruising
Facial plethora
Striae
Proximal myopathy
Central obesity
Acne
Amenorrhoea
Hypertension
Osteoporosis
```
101
What are the ACTH-dependent causes of Cushing's syndrome?
```
Pituitary adenoma -> Cushing's DISEASE (68%)
Ectopic ACTH:
- Carcinoid
- Carcinoma (SCLC)
Ectopic CRH
```
102
What are ACTH-independent causes of Cushing's syndrome?
```
Adrenal adenoma (10%)
Adrenal carcinoma (8%)
Nodular hyperplasia (1%)
```
103
What causes primary Hypercortisolism/Primary Cushing's syndrome?
Adrenal adenoma
104
What causes secondary Cushing's syndrome?
Pituitary adenoma (Cushing's Disease)
105
How can Cushing's Syndrome be screened for?
Overnight dexamethasone suppression test
24hr urinary free cortisol
Late night salivary cortisol
106
What is the definitive diagnostic test for Cushing's Syndrome?
Low dose dexamethasone:
- 0.6mg every 6 hours for 2 days
- Repeat to confirm
107
What is the commonest cause of cortisol excess?
Prolonged high dose steroid therapy:
- Chronic suppression of ACTH production
> Adrenal atrophy
108
What is Conn's syndrome?
Primary aldosteronism due to an adrenal adenoma
109
What causes primary aldosteronism?
Autonomous production:
- Independent of Angiotensin ii and K+
Usually due to:
- Adrenal hyperplasia -> Bi-/Unilateral
- Adrenal adenoma -> Conn's syndrome
- Familial
110
True or false; Primary aldosteronism is the commonest secondary cause of hypertension?
True
111
What are the clinical features of primary aldosteronism?
Significant hypertension
Hypokalaemia
Alkalosis
112
What effects do aldosterone exert on the CVS?
```
Increase cardiac collagen
Synthesis of:
- Cytokines
- ROS
Na+ retention
Altered endothelial function:
- Increased pressure response
Increased SNS outflow
```
113
What is the net effect of all the CVS functions of aldosterone?
Increased BP
LVH
Atheroma
114
What is the commonest cause of primary aldosteronism?
Bilateral adrenal hyperplasia (60%)
115
What percentage of primary aldosteronism cases are Conn's syndrome (adrenal adenoma)?
30%
116
In what conditions are K+ channel mutations seen?
Adrenal aldosterone-producing adenomas
| Hereditary hypertension
117
What is the function of the KCNJ5 channel and what happens if it is mutated?
Rectifying selective channel:
- Maintains membrane hyperpolarisation
Most mutations are gain-of-function and result in Na+ entry and depolarisation
118
What is the first step in diagnosing primary aldosteronism?
Confirm aldosterone excess:
- Measure plasma aldosterone and renin
> Calculate aldosterone-renin ratio (ARR)
If ARR is raised:
- Saline suppression test
- Give 2L of saline
> Failure to suppress aldosterone by >50%
> Primary aldosteronism
119
What is the second step in diagnosing primary aldosteronism?
Confirm subtype:
- Adrenal CT -> Demonstrates adenoma
- Adrenal vein sampling -> Confirms adenoma
120
What surgical technique can be used to treat primary aldosteronism and when is it used? What does it cure?
```
Unilateral laparoscopic adrenalectomy
Only if adrenal adenoma (confirmed on vein sampling)
Cures:
- Hypokalaemia
- 30-70% of hypertension
```
121
When is medical treatment used in primary aldosteronism and what drugs are used?
In bilateral adrenal hyperplasia
Drugs:
- Spironolacton
- Eplerenone
122
What is the commonest enzyme deficiency in CAH? What is the mode of inheritance
21-hydroxylase deficiency:
- 1 in 120,000 live births
- Autosomal recessive
123
What is classical 21-hydroxylase deficiency?
Total deficiency
Salt-wasting
Simple virilising
124
What is non-classical 21-hydroxylase deficiency?
Particl deficiency
| Hyperandrogenaemia
125
How is CAH diagnosed?
Basal/Stimulated 17-OH Progesterone will be very high:
- >242nmol/L
- Normal is
126
Which of the following is not a presenting feature in males with classical CAH:
- Presentation at 2-3 weeks old
- Poor weight gain
- Clear biochemistry
- Acne
Acne
127
What is the main presenting feature in females with classical CAH?
Ambiguous genitalie
128
Which of the following is not a feature of non-classical CAH:
- Hirsutism
- Poor growth
- Acne
- Oligomenorrhoea
- Precocious puberty
- Infertility
Poor growth
129
How is CAH treated in children?
Glucocorticoids
Mineralocorticoids
Surgery
Achieve maximum growth
130
How is CAH treated in adults?
Control androgens
Restore fertility
Avoid steroid over-replacement
131
What do the following clinical signs indicate:
- Labile hypertension
- Postural hypotension
- Paroxysmal sweating
- Headaches
- Pallor
- Tachycardia
Phaeochromocytoma
132
What are some symptoms of phaeochromocytomas?
```
Classical triad:
- Hypertension
- Headache
- Sweating
Palpitations
SoB
Constipation
Anxiety
Weight loss
Flushing
```
133
What complications can phaeochromocytomas cause?
```
LVF
Myocardial necrosis
CVA
Shock
Paralytic ileus
```
134
What happens to the following in phaeochromocytomas:
- Glucose levels
- Potassium
- Haematocrit
- Calcium
- pH
```
Hyperglycaemia
Hypokalaemia
Increased haematocrit
Mild hypercalcaemia
Lactic acidosis
```
135
When should we investigate for phaeochromocytoma?
```
FHx
Hypertension:
- Resistant
- If younger than 50
Classical symptoms
Hypertension + Hyperglycaemia
```
136
How do we investigate phaeochromocytoma?
Confirm catecholamine excess:
- Two 24hr urinary catecholamines
- Plasma (At time of symptoms)
137
How can we identify the source of the catecholamine excess?
```
MRI:
- Abdomen
- Whole body
Meta-Iodobenzyguanidine (MIBG)
PET Scan
```
138
How do we treat phaeochromocytoma medically?
Full α and β blockade:
- α before β
> If β done first -> Unopposed α-stimulation
-> Malignant arrhythmia
- Phenoxybenzamine (α-blocker)
- Propanolol/Atenolol/Metoprolol
Fluid/Blood replacement
139
How do we treat phaeochromocytoma surgically?
Laparoscopic surgery:
- Total excision
- Tumour debulking
140
What syndromes are phaeochromocytomas associated with?
```
MEN2
Von-Hippel-Lindau Syndrome
Succinate Dehydrogenase mutations
Neurofibromatosis
Tuberose sclerosis
```
141
What is the mode of inheritance of MEN2?
Autosomal dominant
142
What causes MEN2?
Activating mutations in tyrosine kinase receptor:
| - RET proto-oncogene
143
What is MEN2 associated with?
Medullary thyroid cancer
Parathyroid hyperplasia
Bilateral phaeochromocytomas
144
What causes Von-Hippel-Lindau Syndrome?
VHL gene mutations -> Autosomal dominant:
- HIF protein accumulation
- Cell proliferation
145
What tumours does Von-Hippel-Lindau Syndrome tend to cause?
Haemangioblastomas (CNS + retina)
Endolymph tumours
Phaeochromocytomas/Paragangliomas
146
What succinate dehydrogenase gene mutations can cause phaeochromocytomasa?
Inactivating mutations in SDH B, C + D:
| - Destabilises HIF-1α
147
What do SDH-D mutations cause?
Head and neck paragangliomas
| >70% penetrance
148
What do SDH-B mutations cause?
Malignant paragangliomas
149
What are catecholamines also raised in?
CHF
150
What sort of secretion do catecholamines usually have?
Episodic:
| - Normal levels in plasma and urine may vary
151
What sort of tumours are less-efficient at catecholamine synthesis?
Malignant and extra adrenal:
| - Dopamine > NA > Adrenaline
152
What drugs can cause hypercalcaemia?
Vitamind D
| Thiazides
153
What granulomatous diseases can cause hypercalcaemia?
Sarcoidosis
| TB
154
What high calcium turnover diseases can result in hypercalcaemia?
Bedridden
Thyrotoxic
Paget's
155
What are the biochemical features of primary hyperparathyroidism?
Increased serum calcium
Increased/Inappropriately normal serum PTH
Increased urine calcium excretion
156
What malignant mechanisms can result in hypercalcaemia?
```
Metastatic bone destruction
PTHrp from solid tumours:
- Squamous cell lung cancer
- Breast cancer
Osteoclast activating factors
```
157
How can we diagnose hypercalcaemia caused by malignancy?
Increased calcium and ALP
Xray/CT/MRI
Isotope bone scan
158
What is the acute treatment of hypercalcaemia?
Fluids:
- Rehydrate -> 0.9% saline 4-6L/24hrs
Consider loop diuretics once rehydrated
Bisphosphonates:
- Single does -> Reduces calcium in 2-3 days
- Max effect at one week
Occasionally steroids:
- Prednisolone -> 40-60mg/day for sarcoidosis
Salmon calcitonin
159
When is Cinacalcet used?
Tertiary hyperparathyroidism
| Parathyroid cancer
160
What are indications for parathyroidectomy?
```
End organ damage:
- Bone disease
> Osteitis Fibrosa Cystica
> Brown tumours
> Pepper pot skull (Multiple myeloma)
- Gastric ulcers
- Renal stones
- Osteoporosis
Calcium >2.85mmol/L
Age
```
161
What causes primary hyperparathyroidism? What biochemistry is seen?
```
Primary parathyroid overactivity:
- Adenoma
Biochemistry:
- Raised PTH
- Raised calcium
- Normal renal function
```
162
What causes secondary hyperparathyroidism? What biochemistry is seen?
Physiological response to hypocalcaemia
Biochemistry:
- Raised PTH
- Reduced calcium
163
What causes tertiary hyperparathyroidism? What biochemistry is seen?
```
Autonomous parathyroid activity after secondary
Biochemistry:
- Raised PTH
- Raised calcium
- Other electrolytes skewed
```
164
What inheritance does Hypocalciuric Hypercalcaemia have?
Autosomal dominant
165
What mutations are present in Hypocalciuric Hypercalcaemia?
Deactivating mutations in Calcium-sensing receptor
166
How is Hypocalciuric Hypercalcaemia diagnosed?
Mild hypercalcaemia
Reduced urinary calcium
PTH may be slightly raised
Genetic screening
167
When does oogenesis begin?
In utero
168
When does oogenesis restart after suspension?
Puberty
169
When is oogenesis complete?
At fertilization
170
When does oogenesis cease?
Menopause
171
What are the primordial germ cells and what do they do?
Earliest recognisable female germinal cell
Capable of mitosis
Migrate to genital ridge by week 6 gestation
172
What is oogonia?
Completion of last pre-meiotic division -> Oocytes
173
When oocytes enter meoisis, what happens?
1st meiotic division -> Primary oocytes
| 2nd meiotic division -> Secondary oocytes
174
What is the polar body?
First body is one of the two products in first stage of meiosis
175
What does the presence of two polar bodies signify?
Sperm entry and completion of second meiotic division
176
What happens during the follicular phase of the menstrual cycle?
Egg matures
| Ready for oculation at midcycle
177
What signifies the end of the follicular phase?
Ovulation
178
What happens during the luteal phase of the menstrual cycle?
Development of corpus luteum
| Induces preparation of reproductive tract for pregnancy
179
What is the primary follicle?
Before birth, the primary oocyte is surrounded by a single layer of granulosa cells - Primary follicle
180
How many primary follicles are there at birth and what is each capable of?
~2 million
| Each can produce a single ovum
181
What happens to the primary follicles until puberty?
Degenerate to scar tissue -> Atresia
182
What is the secondary follicle?
```
Oocyte grows (x1000) and follicle expands:
- Differentiates under hormonal influence
```
183
What happens to secondary follicles after puberty?
```
~400 are ovulated
The rest (99.98%) undergo atresia
```
184
What happens to follicular cells left behind after ovulation?
Undergo luteinisation:
| - Become the corpus luteum
185
What does the corpus luteum secrete and what is this important for?
Progesterone:
| - Prepares uterine lining for implantation
186
After ovulation, how long does the corpus luteum continue to grow?
8-9 days
187
What is the maximum length of time the corpus luteum can survive without fertilisation?
14 days
188
What does the corpus luteum do if fertilisation does occur?
Persists
| Produces increasing amounts of progesterone (+oestrogen) until after pregnancy
189
Where does FSH act and what does it do?
Acts on ovaries
Stimulates follicle development
Stimulates secretion of oestradiol
Stimulates ovulation
190
Where does LH act and what does it do?
```
Acts on ovaries
Stimulates:
- Follicle maturation
- Ovulation
- Development of corpus luteum
- Oestrogen secretion
```
191
What happens during the follicular phase?
1. Hypothalamus secretes GnRH
2. Anterior pituitary secretes FSH + LH
3. Up to 15 follicles are 'rescued' and begin to mature:
- Granulosa and theca cells develop
192
What do the theca cells produce?
Androgens
193
What do the granulosa cells do?
Convert androgens to oestradiol by aromatase
194
What does oestradiol to?
Thickens endometrium
| Thins cervical mucus
195
What does oestrogen do?
Suppresses FSH production:
| - Selection of dominant follicle
196
What does the granulosa in the dominant follicle express?
LH receptor
197
What causes more GnRH release and when? What does this result in?
High oestrogen levels at the mid-cycle:
| - Causes FSH + LH surge from anterior pituitary
198
Put the following steps of ovulation in order:
- Follicle wall weakens
- LH + FSH levels fall
- Cumulus oophorus loosens
- Ovulation -> Oocyte, Zona Pellucida and cumulus
- Inc in follicular fluid + number of granulosa
- COC picked up by oviduct
1. Inc in follicular fluid + number of granulosa
2. Cumulus oophorus loosens
3. Follicle wall weakens
4. Ovulation -> Oocyte, Zona Pellucida and cumulus
5. COC (cumulus-oocyte complex) picked up by oviduct
6. LH + FSH levels fall
199
What causes the corpus luteum to degenerate and what does it form?
At 12 days, if there is no hCG from an embryo the corpus luteum degenerates -> Corpus Albicans
200
What is the function of hCG?
Maintains the corpus luteum
201
When does the placenta take over progesterone production from the corpus luteum?
At 6 weeks gestation
| Corpus luteum -> Corpus albicans
202
What is the function of progesterone during pregnancy?
Supports pregnancy
| Suppresses ovulation
203
What role does FSH have in spermatogenesis?
Initiates spermatogenesis (with testosterone)
Causes Sertoli cells to express:
- Androgen Binding Globulin (ABG)
- Inhibin
204
What role does FSH have in spermatocytogenesis?
Leads to development of Sertoli cells:
| - Act as nursing cells for spermatids
205
What role does LH have in spermatocytogenesis?
Promotes Leydig cell secretion of testosterone:
| - Initiates spermatogenesis
206
When does spermatocytogenesis occur?
In males at the age of puberty (10-14 years)
207
What role does LH have in spermatogenesis?
Causes interstitial Leydig cells to secrete testosterone
208
What role does testosterone have?
```
Decreases release of:
- GnRH
- LH
Converted to dihydrotestosterone:
- Enlargement of male sex organs
- Secondary sexual characteristics
- Anabolism
Binds to ABG made by Sertoli cells:
- Increases its concentration in luminal fluid
> Enables spermatogenesis
> Enables sperm maturation in epididymis
```
209
What does inhibin do?
Decreases secretion of FSH
