Human Development Flashcards
(320 cards)
1
Q
Where are steroid receptors located?
A
Inside of cells
2
Q
What is a hormone?
A
A secreted bioactive messenger that travels in the blood (endocrine) to effect a target cell downstream.
3
Q
Describe endocrine release vs exocrine release?
A
Endocrine = into the blood stream
Exocrine = via ducts
4
Q
What does parathyroid hormone do?
A
Helps retain and increase serum calcium
5
Q
Explain the endocrine hierarchy (the hypothalamic-pituitary axis).
A
Hypothalamus
Pituitary
End organ
6
Q
The pituitary releases target hormones, what effect do these have on the HP axis?
A
They (for the most part) have a negative feedback effect on the axis. Their own synthesis and secretion controls their further synthesis and secretion.
7
Q
What is the HPT axis?
A
Hypothalamic, pituitary, thyroid axis
8
Q
What is the HPA axis?
A
Hypothalamic, pituitary, adrenal axis.
9
Q
How much does the thyroid gland weight?
A
10 grams
10
Q
What does the thyroid gland do?
A
Traps iodine from food and binds it to tyrosine to make thyroxine.
11
Q
Where is thyroxine stored?
A
In the thyroid gland.
12
Q
What type of hormone does the hypothalamus usually secrete?
A
Releasing hormones (e.g. thyrotropin RELEASING hormone)
13
Q
What type of hormone does the pituitary usually secrete?
A
Stimulating hormones (e.g Thyroid STIMULATING hormone).
14
Q
What X3 hormones does the thyroid secrete?
A
Thyroxine and Triiodothyronine
Also calcitonin (helps maintain plasma calcium levels by decreasing them when needed)
15
Q
Which thyroid hormone is T3 and which is T4?
Why are they named so?
A
T3 = Triiodothyronine T4 = Thyroxine
The number relates to the number of iodine’s in each chemical compound
16
Q
What do T3 and T4 do?
A
Alter BMR and pulse
17
Q
What is primary hypothyroidism? Or primary endocrine condition in general?
A
A condition caused by a ‘downstream’ gland (below hypothalamus and pituitary).
Primary hypothyroidism would therefore be an under functioning thyroid gland causing low levels of T3 and T4
18
Q
What happens to end organ function in primary hypothyroidism?
A
Action will decrease/reduce
19
Q
What happens to hypothalamic/pituitary function in primary hypothyroidism?
A
They will increase to try to compensate for the low effector organ action. Also there is no negative feedback.
20
Q
What is a secondary endocrine condition?
A
One in which the condition is due to a pathology of the pituitary gland
21
Q
What is a tertiary endocrine condition?
A
One in which the condition is due to pathology with the hypothalamus
22
Q
What is it called when the axis is working fine but the end organ is not responding to the hormones produced?
A
Resistance (as it is showing resistance to the hormones)
23
Q
Where is the temporal aspect of vision?
A
The outer half of of the visual field (the inner is nasal)
24
Q
In which bone is the sella turcica?
A
The sphenoid bone (remember transphenoidal as the surgical approach)
25
Which structure sits in the sella?
The pituitary gland
26
Which structure runs in the supra-sella space?
The optic chiasm
27
If the pituitary enlarges through a mass, where may it compress and on what structures?
Superiorly (on the optic chiasm)
Laterally (on the cavernous sinuses = CN 3, 4, i+ii of 5 and 6)
28
What is the embryology of the posterior pituitary?
It has Neural embryology
29
What is the embryology of the anterior pituitary?
It has oral embryology
30
What does the posterior pituitary release?
ADH and oxytocin
31
What does the anterior pituitary release?
TSH, ACTH, FSH, LH, GH and prolactin
32
How does bi-temporal hemianopia present and what may be its cause?
Lack of vision on both temporal halves of vision.
May be caused by a lesion/mass at the pituitary/optic chiasm.
33
What does GH do and where does it act?
Causes growth and metabolism through IGF-1
It acts on the liver
34
What does prolactin do?
Causes lactation from the breast
35
What does an insulin tolerance test check for and how?
It checks for GH and ACTH.
Insulin is given to make the patient hypoglycaemic, normal response is increases in GH and ACTH but if patient is hypopituitary they will not be able to make these.
36
If a patient has low T4 and high TSH, what is the pathology?
Primary hypothyroidism
37
If a patient has low T4 and low TSH, what is the pathology?
Hypopituitary causing secondary hypothyroidism
38
In hypopituitarism, why is prolactin high?
What is the name(s) given to this?
Prolactin regulation relies on dopamine secretion from the hypothalamus. If there is a mass compressing the pituitary stalk, this will inhibit dopamine from stopping prolactin release therefore seeing an increase in prolactin.
This is called the stalk effect of disinhibition hyperprolactinaemia
39
What is the name given to a benign tumour of glandular tissue?
An adenoma
40
What is a functioning tumour?
Give an example.
One which secretes excess hormones
E.g. prolactinoma
41
What drug is given for prolactinomas?
How does it work?
Carbergoline
It is a dopamine receptor agonist which helps to regulate prolactin release
42
What is diurnal variation?
Name a hormone which shows this.
Hormone release that follows a 24hr repeating pattern
Cortisol
43
What is paracrine?
Release that acts on surrounding cells
44
What is autocrine release?
Release which acts on self
45
What is neuroendocrine release?
Release from neuron to blood stream
46
Which type of hormones are tyrosine derivatives?
Name them in their pathway.
Tyrosine, DOPA, dopamine, NORAD, ADREN (in this pathway order)
Thyroxine (X2 tyrosine joined + iodines)
47
What does the adrenal medulla secrete?
Adrenaline and norad
48
What cells secrete:
- TSH
- Prolactin
- ACTH
- LH
- FSH
- GH
- TSH = thryotroph cells
- Prolactin = lactotroph cells
- ACTH = corticotroph cells
- LH = gonadotroph cells
- FSH = gonadotroph cells
- GH = somatotroph cells
49
What hypothalamic hormones stimulate release of:
- TSH
- Prolactin
- ACTH
- LH
- FSH
- GH
- TSH = thyrotropin releasing hormone
- Prolactin = thyrotropin releasing hormone has small effect
- ACTH = corticotropin releasing hormone
- LH = gonadotropin releasing hormone
- FSH = gonadotropin releasing hormone
- GH = growth hormone releasing hormone
50
What do somatostatin and dopamine do?
Where are they released from?
Somatostatin = inhibits the somatotroph cells from releasing growth hormone
Dopamine = inhibits the lactotroph cells from releasing prolactin
They are both hormones of the hypothalamus.
51
Name some peptide hormones
GnRH
GHRH
Prolactin
insulin
52
What are the two parts of a glycoproteins hormone?
Which part corresponds to what?
Alpha and beta
Alpha - specific to animal (humans)
Beta - specific to hormone (beta-FSH)
53
Which hormones are glycoproteins hormones?
Remember LFT’s (bloods but not bloods) plus one more
Therefore =
LH
FSH
TSH
hCG (placenta)
54
What is the difference between pulsatile and sustained GnRH release?
```
Pulsatile = release of LH and FSH
Sustained = inhibition of LH and FSH
```
55
Name some groups and hormones that are steroid hormones
```
Mineralcorticoids = aldosterone
Glucocorticoids = cortisol
Sex steroids (androgens) = oestrogen/progesterone/testosterone
```
56
What is the structure of the insulin receptor?
It is a pre-formed dimer
57
How does the insulin receptor work?
Insulin binds and causes auto-phosphorylation of the receptor
The receptor then binds to IRS (insulin receptor substrate)
This causes GLUT-4 channels to relocate to the cell membrane to increase glucose uptake into the cells
58
Steroid receptors are intracellular, name the X3 components.
Ligand binding domain
Transcription activating domain
DNA binding domain
59
In steroid receptor DNA binding domains, what are they made from?
What usually stops this section of the receptor binding to DNA to activate genes?
Zinc fingers
It is blocked by protein HSP90 (heat shock protein)
60
Which hormones circulate in free form and which in bound form?
Free form = catecholamines and protein/peptides
Bound form = thyroid hormones and steroid hormones
61
Of the hormones which circulate in bound form, what are they mainly bound to?
```
Aldosterone = no binding protein
Cortisol = corticosteroid binding protein
Androgens = sex hormone binding protein (Binding protein = same as saying binding globulin)
```
Thyroid hormones = thyroxine binding globulin
All of the above also in smaller percentages to albumin!
62
How are steroid hormones stored?
They are not!
63
What part of the hypothalamus are the hypothalamic releasing and inhibitory factors released?
The median eminence
64
List the six hormones released by the anterior pituitary
```
GH
LH
FSH
prolactin
TSH
ACTH
```
65
List the hypothalamic releasing and inhibiting hormones
CRH
GHRH
GnRH
TRH
Dopamine
somatostatin
66
What is the correct name for the anterior pituitary?
The adenohypophysis
67
What is the correct name for the posterior pituitary?
The neurohypophysis
68
What are the 2 parts of the adenohypophysis?
Pars distalis
| Pars tuberalis
69
What are the 2 parts of the neurohypophysis?
Pars nervousa
| Infundibulum (pituitary stalk)
70
What is POMC and what is its significance?
Pro-opiomelanocortin
Is the precursor molecule for both melanocyte-stimulating hormone and ACTH, therefore hyperpigmentation can be the symptom of some illnesses that also have a symptom of high cortisol production.
71
Which cells synthesise testosterone?
Which hormone stimulates this?
Leydig
LH
(Remember L for L)
72
Which cells facilitate spermatogenesis?
Which hormone stimulates this?
Sertoli cells
FSH
73
What does testosterone negatively feedback on?
The hypothalamus and anterior pituitary
74
What do the Sertoli cells produce to negatively feedback on the HPG axis?
Which part(s) of the axis does it act on?
Inhibin
The (anterior) pituitary
75
Other than uteric contractions, what does oxytocin stimulate post-partum?
Breast tissue for milk ejection
76
Name some D2 agonists.
What is D2?
D2 are dopamine receptors
D2 agonists include:
- carbergoline
- bromocriptine
77
Other than stimulating growth hormone receptors, what else does GH do?
Stimulates the liver to synthesise insulin like growth factor
78
What triggers growth hormone?
Low glucose
79
What type of release does growth hormone follow?
Diurnal
80
Why are D2 agonists given in hyper secretion of GH?
Usually they have no effect
In hyper secretion due to tumours, D2 receptors are present which means giving agonists will surprise GH release
81
What are the structural similarities and differences between oxytocin and ADH?
Both 9 AA’s long with 2 AA differences between them
82
What is another name for ADH?
Vasopressin
Or
Argentine vasopressin
83
What molecule transports oxytocin and ADH to the posterior pituitary from the hypothalamus?
Which version of this molecules transports oxytocin, and which ADH?
Neurophysins
Neurophysin 1 = oxytocin
Neurophysin 2 = ADH
84
Where in the hypothalamus is oxytocin and ADH synthesised?
The SON (supraoptic nucleus) and the PVN (paraventricular nucleus)
85
What two things detect changes to stimulate ADH release?
Name the type of receptors.
Hyperosmolarity - osmoreceptors in the hypothalamus
Decreased plasma volume - baroreceptors
86
Which type of ADH receptors cause:
1) water reabsorption
2) vasoconstriction
1) V2
| 2) V1
87
In what X2 ways does ADH act to maintain BP?
Relocates AQ2 aquapourin channels in the collecting tubules to increase water retention
Vasoconstriction blood vessels
88
How do the parathyroid and thyroid act to maintain serum calcium levels?
Calcitonin (from thyroid) = decreases calcium levels
| Parathyroid hormone = increases calcium levels
89
How and from which molecules are the thyroid hormones T3 and T4 synthesised?
Monoiodotyrosine (MIT) (tyrosine with 1 iodine) goes to Diiodotyrosine (DIT) (second iodine added)
These two can join to make T3, or X2 DIT’s can join to form T4
90
What is the structural difference between T3 and T4?
In T3 the iodine in the 5-prime position is missing
91
One thyroid hormone is converted to another. Which is which and where is it converted?
T4 converted to T3 in the peripheries
92
Which thyroid negatively feeds back and where does it do this?
T3
On the hypothalamus and pituitary (thyrotrophs)
93
Which thyroid cells secrete calcitonin?
The parafollicular cells
94
The thyroid gland consists of follicles, what is their structure?
Follicular cells creating a colloid filled central vacuole
95
How is tyrosine stored?
As thyroglobulin
96
Where is thyroglobulin stored
In the colloidal space
97
What would the colloidal space of the thyroid follicles look like if the gland is UNDER active?
Large colloidal space as all thyroglobulin is stored and not recruited for use to make thyroid hormones.
98
What would the colloidal space of the thyroid follicles look like if the gland is OVER active?
No colloidal space as all thyroglobulin recruited to synthesise thyroid hormones therefore none is stored.
99
How does iodine get into the follicular cells from the blood stream to begin thyroid hormone synthesis?
TSH receptors in the thyroid are GPCR’s which increase cAMP levels
cAMP then activates a Na/Iodine co-transporter into the cell
100
What is another name for TSH?
Thyrotropin, that is why TRH is called TRH! It stands for THYROTROPIN releasing hormone!
101
Which enzyme is responsible for adding the iodine to the tyrosine residues in thyroglobulin?
Where is this enzyme found?
Where does this process occur?
TPO = thyroid peroxidase
It is located in the apical membrane of the thyroid follicular cells
The process occurs in the colloidal space, NOT in the cell
102
How does iodine get from the follicular cells of the thyroid into the colloidal space?
Where is the protein responsible located?
Via the protein pump PENDRIN
it is located in the apical membrane of the thyroid follicular cells
103
How do T4 and T3 get from the colloidal space into the blood stream?
Via simple diffusion
104
What is the main thyroid hormone binding protein?
Thyroxine binging globulin/protein
105
What type of receptors do thyroid hormones interact with?
Nuclear receptors
106
Are thyroid hormones steroid hormones?
No, but they are lipophylic so behave in the same way:
- transported bound to proteins
- diffuse into cells and react with nuclear receptors
107
Which enzymes interconvert the thyroid hormones?
The deiodinator enzymes (D1, 2 and 3)
108
What does HYPOthyroidism do to body weight?
Increase it, as the thyroid hormones are involved in nasal metabolic rate and reactions
109
Name some signs of hypothyroidism.
Slow movements, course hair, period it’s, puffiness, dry skin
110
What type of conditions are hyper and hypothyroidism?
They are autoimmune
111
What is hashimoto’s and what is its full name?
What are the antibodies in hashimoto’s fighting against?
Hashimoto’s thyroiditis
It is a form of HYPOthyroidism caused by antibodies to thyroglobulin or TPO which stop T3 and T4 being synthesised
112
What is the name of the congenital iodine deficiency caused by failure of the mother to deliver sufficient thyroid hormones to the foetus?
Cretinism
113
What is the treatment for hypothyroidism?
Give thyroxine/levothyroxine (both T4) and Liothyronine (T3 sodium salts)
114
What is a goitre and how is it caused?
Low thyroid hormones stimulate the HPT axis to synthesise more releasing and stimulating hormones to counteract this. Without the presence of iodine this simple increases the size of the thyroid causing a goitre.
Goitres May however be apparent in both hypo and hyperthyroidism
115
What can be other causes of hypothyroidism?
Surgery for hyperthyroidism
Lack of dietary iodine intake
116
How is a goitre treated?
disease Goitrogen - decreases thyroid iodine uptake levels if the cause of the goitre is hyperthyroidism
117
Name some signs or hyperthyroidism.
Eye signs
Thyroid bruit
Pretibial myoedema
118
What is the difference between toxic and non-toxic goitres?
Which condition is most likely to see which type?
Toxic = build up of excess thyroid hormones = graves
Non-toxic = lack of thyroid hormones = hashimoto’s
119
What is an alternative term for hyperthyroidism?
thyrotoxicosis
120
What is the name given to the eye bulging seen in Graves’ disease?
What causes this along with pre-tibial myxoedema?
Exophthalmos and upper lid retraction
This and pre-tibial myxoedema is caused by antibodies stimulating glycosaminoglycans to deposit in the tissues of these areas
121
What antithyroid drugs can be given to treat hyperthyroidism?
How do these work?
Carbimazole
Propylthiouracil
These inhibit TPO and propylthiouracil also inhibits peripheral conversion of T4 to T3
122
What is the term given to someone who has normal thyroid function?
Euthyroid
123
What is the name given to decreased neutrophil count?
What is the name given to decreased white blood cell count?
Why are these relevant to the thyroid?
Neutropenia = decreases neutrophils
Agranulocytosis = decreased white blood cells
The can be as a side effect of hyperthyroid treatment with anti-thyroid drugs
The patient may therefore report with a sore throat and
124
What drugs can be given to those suffering from hyperthyroidism to combat the side effects the condition brings?
Beta blockers like propanalol, as hyperthyroidism result in increased sympathetic activity on the heart.
125
The drug carbimazole is a pro-drug, what is it converted to?
Methimazole
126
What radioactive treatment is there for hyperthyroidism?
How does this work?
Radiolabelled iodine (131-iodine)
This is taken up by the follicular cells where it emits beta radiation and kills them, decreasing thyroid function.
127
Thyroid surgery is an option in hyperthyroidism, what can be given prior to surgery and why?
LUGOL’s solution to decrease thyroid vascularity
128
There are X2 main types of hypothyroidism, what are they and what is the difference?
Hashimoto’s = thyroid enlarged
Atrophic thyroiditis = thyroid atrophied/destroyed
Both autoimmune
129
There are X2 more common types of hyperthyroidism, what are they and what is the difference?
Graves’ disease = autoimmunity
| Toxic thyroid nodule = single nodule over-functioning
130
Why can HCG be related to thyroid function?
What is HCG?
It is similar in structure to TSH therefore may cause over production of thyroid hormones
HCG = human chorionic gonadotropin = produced by placenta to maintain corpus luteum
131
What is the difference between thyrotoxicosis and hyperthyroidism?
Thyrotoxicosis = state of having too much thyroid hormone
Hyperthyroidism = thyroid gland itself is producing too much thyroid hormone
NB: the thyroid hormone may be coming from elsewhere such as excess thyroid replacement medication
132
When must radioiodine be avoided as a treatment for hyperthyroidism?
In those with eye disease
133
What is non-thyroidal illness?
When thyroid hormone levels/thyroid gland plays up during non-thyroid illnesses
134
What is the most common type of thyroid cancer?
Papillary thyroid cancer
135
What are the X2 layers of the adrenal glands?
Which is inner and which is outer?
Which layer is bigger (and by what percentage)?
```
Cortex = outer = 90%
Medulla = inner = 10%
```
136
What are the X3 layers of the adrenal cortex from outside to inside?
Each layer of cortex synthesised a different group of steroid hormones, which is synthesised in each layer?
Zona Glomerulosa = mineralcorticoids (aldosterone)
Zona Fasiculata = glucocorticoids (cortisol)
Zona reticularis = androgens (sex hormone precursor molecules which are converted to testosterone and oestrogen in the peripheries etc)
NB: remember GFR for “glomerular filtration rate”
137
What do the adrenal medullas synthesise?
What is the percentage of synthesis of each of these hormones?
Catecholamine hormones (80% adrenaline and 20% norad)
138
Which enzyme is needed for aldosterone synthesis?
Aldosterone synthase
139
Which enzyme is needed for cortisol synthesis?
17-alpha-hydroxylase
140
What type of receptor does ACTH act on to begin synthesis of lipids?
Explain the steps and relevant molecules in this pathway.
ACTH acts on a GPCR called the melanocortin 2 receptor (MC2R) to increase cAMP levels.
This activates Protein Kinase A which activates cholesterols ester hydrolyse (CEH) to liberate cholesterol from lipid droplets.
Desmolase is the first enzyme in this pathway and is also the rate limiting step
Cortisol and other adrenal hormone levels therefore increase
141
What is the main binding protein used to transport cortisol in the blood?
Corticosteroid binding globulin
142
What do glucocorticoids do to the immune system?
What molecules do glucocorticoids increase as part of this process?
They decrease the inflammatory process
They increase annexin-1 (lipoprotein-1)
143
Do glucocorticoids affect water and electrolyte balance?
Yes, they increase water retention and have a LARGER affinity for mineralcorticoid receptors than glucocorticoid ones!
144
How is cortisol stopped from acting on mineralcorticoid receptors, to which it has high affinity for?
The enzyme 11-beta-hydroxysteroid dehydrogenase (11-beta-HSD) converts it from its active form (Cortisol) to an inactive form (Cortisone)
This enzyme is expressed in aldosterone sensitive tissues so cortisol can not act here
This reaction is reversible, therefore in cortisol sensitive tissues (liver/muscle/adipose) where cortisol is needed, the 11-beta-HSD (2) isoform reverses this reaction so the active form (cortisol) is free to act as needed
145
What do glucocorticoids do to the bones?
In excess they can cause osteoporosis by promoting osteoclasts and inhibiting osteoblasts
146
What is the name of the syndrome associated with excess glucocorticoids?
Name some symptoms of this condition.
Cushing’s syndrome
- buffalo hump
- purple striae
- moon face
- thin limbs
- red cheeks
- hirtuism
- high BP
147
What is hirsutism and why may it be a sign of cushings?
Why may high BP also be a sign?
Female hair growth due to increased androgens
If the high glucocorticoid level is due to a response to high levels of ACTH (which causes the release of mineralcorticoids and androgens as well as glucocorticoids) then excessive androgen symptoms may also be seen.
High BP for the same reasons as above (increased levels of aldosterone)
148
In treating cushings, what drugs can be given and how do these work?
Metyrapone = 11-beta-hydroxylase inhibitor (NOT 11-beta-HSD!) which will reduce the synthesis of glucocorticoid (cortisol)
Pasireotise (SSTR5 agonist) = will be present if hypersecretion is cause by pituitary Adenoma as the tumour will express receptors for this.
Carbergoline = D2 receptor agonist = same reason as pasireotide
Mifeprestone = glucocorticoid receptor antagonist which damps down effects of glucocorticoid (cortisol)
149
What is the name of the autoimmune disease which causes low levels of adrenal hormones?
What is its proper name?
Addison’s disease = chronic adrenal insufficiency
150
Name some symptoms of Addison’s disease and explain why they happen.
- Hyperpigmentation = cortisol levels are decreased therefore ACTH stimulus increases to counteract this. ACTH comes from a precursor molecule called POMC which also produces melanocytes stimulating component - this causes skin hyperpigmentation.
- low BP = no aldosterone produces therefore sodium is lost as is water and plasma volume decreases, seeing a decrease in BP
151
What is the treatment for addisons?
Replacement therapy with a steroid
- mineralcorticoid replacement = fludrocortisone (fludro = think “fluid”)
- glucocorticoid replacement = hydrocortisone/prednisolone
152
What precursor to the sex hormones do the adrenal glands produce?
DHEA
Androstenedione
153
What is virilisation?
Development of male physical characteristics
154
How does the mineralcorticoid aldosterone work and what does it do?
Aldosterone works in the distal convoluted tubule and collecting ducts of the kidneys
It increases sodium channels in the apical membrane (ENaC) (Epithelium...)
It also increases Na+/K+ ATPase channels in the basolateral membrane
This causes increase sodium retention and therefore more water retention too, increasing plasma volume and BP
155
What drug inhibits aldosterone?
What type of drug is this?
Why is this drug different to other ‘loop diuretics’?
Spironolactone
It inhibits aldosterone by inhibiting the mineralcorticoid receptor to decrease blood pressure and aid water excretion (therefore is a diuretic)
It is potassium sparing
156
Why can stopping steroid doses quickly cause hypoadrenalism?
Because during the period of taking the steroid the adrenal glands may have atrophied (as not needed) therefore they can not cope when needed again
157
What is myalgia?
Muscle pain
158
What is the name of the test which checks response to stimulation of cortisol production?
Synacthen test
159
When must cortisol levels be measured and why?
In the AM as it is released in a diurnal pattern
160
What is meant by ACTH dependant and independent Cushing’s?
ACTH dependant = due to a pituitary issue causing excess ACTH (therefore all the adrenal hormones may be high)
ACTH independent = not due to a pituitary reason but rather a adrenal gland issue, therefore ACTH levels may be normal and not all of the adrenal hormones may be in excess
This is why hirtuism and increased BP may not always be signs or symptoms
161
What are the types of adrenal tumours that can cause Cushinoid effects?
Adenoma = benign glandular tissue tumour
Carcinoma = cancer of tissue lining organs
162
What disorder causes increased levels of catecholamines?
Pheocromocytoma
163
Why are pheo’s called the tumour of 10%?
Because:
- 10% are bilateral
- 10% are malignant
164
What are metanephrines?
These are the metabolites or the catecholamines
165
What types of drugs may you give to prevent a pheocromocytoma crisis?
Alpha blockers - to stop the chance of increases in TPR which will increase the BP and cause a crisis
Doxazosin
Phenoxybenzamine
166
What is hyperaldosteronism and what may it appear like?
High aldosterone levels
Appears with high BP, low potassium
167
Why is the renin levels low in hyperaldosteronism?
What is therefore a good test for hyperaldosteronism?
Renin is not needed (renin raises BP) as the BP is already chronically high, therefore it will be low
A good test is PRA (plasma renin aldosterone ratio)
168
What is the clinical syndrome associated with hyperaldosteronism?
Conn’s Syndrome
169
What is puerperium?
Period of time 6-weeks post-part I’m
170
How many weeks is a normal pregnancy?
40 weeks
171
How are the normal number of weeks in a term pregnancy split?
40 weeks into 3 trimesters of 13 weeks
```
Tri1 = 0-13 weeks
Tri2 = 13-26 weeks
Tri3 = 26-40 weeks
```
172
What is the EDD?
How is it calculated?
It is the expected due date
Calculated as the date of the last menstrual period (LMP) + 280 days or 40 weeks
173
What are the dates of the routine pregnancy scans and what do they test for?
12 weeks (11-13) = pregnancy dating scan
20 weeks = foetal anomaly scan
174
What is gravidity and parity?
What is the usual subscript?
Gravida = number of times (including current) the uterus has been pregnant
Parity = number of births (24+ weeks) alive or dead
Subscript = number of <24 week pregnancies or non-births *(ectopic/miscarriages/terminations)
Sometimes the subscript is included in the parity
175
What does blood pressure do in pregnancy?
What is classed as hypertension?
It decreases as the TPR decreases within the first trimester of pregnancy
Heart rate increases to try to compensate this
Around the start of trimester 3 the BP begins to rise and ends up 10-15mmHg greater than the resting BP by the end of pregnancy
Hypertension is BP > 140/90
176
What is PET?
Pre-eclampsia Toxaemia
- Hypertension
- Proteinuria
- Oedema
177
What is eclampsia?
Pre-eclampsia + convulsions
178
When does pre-eclampsia usually present?
20 weeks+
179
What is SF height and what does it indicate?
It is the height from the pubic symphysis to the fungus (top of uterus)
It is measure in cm and correlates directly with the number of weeks of the pregnancy +/-2cm
180
What is the oviduct?
Another name for the Fallopian tubes
181
What are the X2 main roles of the ovaries?
Gamete (oocyte) storage
Hormone production
182
What is folliculogenesis?
The maturation of oocytes ready for release
183
What is ovulation?
The release of mature oocytes from the ovaries
184
What are mature oocytes called once they have undergone ovulation?
Ova (ovum = singular)
185
In what structure do the oocytes mature?
A follicule
186
How many eggs does a woman have:
1) before birth
2) at birth
3) at FMP
4) at menopause
1) 7 mill
2) 2 mill
3) 0.5 mill
4) 0
187
What is the name given to a follicule which contains an un-matured oocyte?
Primordial follicule
188
How many eggs does a woman lose each month, and how many are released?
Only X1 egg is released (ovulation) but 15-20 are recruited and lost each month
189
What happens to the graafian follicule after it has ovulated its ova?
It remains as a corpus luteum which is important in synthesising and secreting progesterone which aids endometrial decidualization
190
How long is a normal monthly cycle?
28 days from start of period
191
How long does bleeding last for during the menstrual cycle?
3-7 days
192
At what day does a woman ovulate in her ovarian cycle?
Day 14 (12-16) in a 18 day cycle or 14 days before the last day of the cycle of the cycle is longer/shorter than 28 days
193
What is the name of a follicule in the tertiary stage of folliculogenesis?
Antral or graafian follicule
194
What are the X2 waves of ovarian follicule recruitment?
What are the time frames for each?
What controls each of these waves?
1) initial recruitment
Primordial follicules —> antral/graafian follicules (end of folliculogenesis)
3-4 months duration
Non-hormone driven
2) cyclic recruitment
Happens on day 1 of ovarian cycle
15-20 follicules only
Hormone driven (LH and FSH)
195
What are the X3 phases of the ovarian cycle (cyclic recruitment)?
How long is each phase?
What happens in each phase and what hormones drive this?
Days 0-10 = follicular phase
LH and FSH signal for 15-20 follicules to grow (cyclic recruitment)
Oestrogen matures X1 oocyte and the rest undergo atresia as FSH levels drop (due to synthesis of oestrogen from the follicules feeding back on the hypothalamus to stop synthesising GnRH)
Days 11-14 = ovulatory phase
Ovulation occurs
The oestrogen synthesised by the oocyte in this phase now STIMULATES (rather than inhibits like it did in the follicular phase) the release of GnRH and therefore LH and FSH release. It is LH that stimulates ovulation and oocyte release here.
Days 15-28 = luteal phase
Follicule remains as corpus luteum (stimulated by LH) to secrete progesterone to aid endometrial decidualization
The oestrogen and progesterone both feed back NEGATIVELY on the hypothalamus and anterior pituitary to stop GnRH and gonadotroph release. This is the first time feedback on the anterior pituitary occurs in these phases.
196
What is the FSH threshold/window concept?
FSH causes 15-20 follicules to grow
The maturing follicules produce oestrogen
The oestrogen negatively feeds back to decrease FSH levels and competing follicules undergo atresia, leaving only the most sensitive follicule (to FSH) to grow
197
How does IVF work in terms of egg collection?
IVF involves giving artificial FSH ago counteract the FSH drop and hopes that all 20 oocytes and follicules will grow for collection
198
Which enzyme is needed to convert testosterone to oestrogen?
Aromatase
199
What effect does progesterone have on the contractility of the uterus during pregnancy?
It surprises contractile activity
200
Name the X4 parts of the cervix?
Fundus
Body
Isthmus
Cervix
201
What is the menstrual cycle and how is it different to the ovarian cycle?
Menstrual cycle = series of monthly change in endometrium in response to hormone levels
Ovarian cycle = series of monthly changes in the ovary in response to hormone levels
202
What are the X2 phases of the menstrual cycle?
Which hormones drive each phase?
Days 0-5 = menses (bleeding)
1) proliferation phase (day 6-14)
Oestrogen driven
Endometrial lining becomes thickened
2) secretory phase (day 15-22)
Progesterone driven
Endometrial lining becomes oedematous and vascular
203
What is anovulation?
A lack of ovulation
204
How can the thyroid cause issues with anovulation?
If the patient is hypothyroid, there may be increases in TRH to counteract this
TRH also triggers prolactin release (mildly)
Prolactin can INHIBIT GnRH!!! (Key point here!)
This means that LH and FSH will be low causing anovulation
205
What drugs can be used to treat polycystic ovarian syndrome treated?
How do these drug work?
With clomiphene citrate
Causes FSH and LH secretion which drive follicular maturation and ovulation
Works by inhibiting oestrogen (ER) receptor to inhibit negative feedback on GnRH and gonadotropin release
OR...
Letrozole = inhibits aromatase therefore stopping oestrogen synthesis
206
What is tubal factor?
Ovulatory issued caused by an issue with the Fallopian tubes
207
What is meant by ovarian reserve?
The number and quality of follicules left in a woman’s ovaries at any one time
208
A trans-vaginal ultrasound may help determine antral follicle count, what is this?
The number of antral follicles present at the end of folliculogeneis
209
Where have primordial oocytes arrested at?
Prophase 1 of meiosis 1
210
Where have secondary oocytes arrested at?
Metaphase 2 of meiosis 2
211
What are polar bodies and what happens to them in meiosis?
They are the remnants of cell division in meiosis 1 (first polar body) and 2 (second polar body) where they cytoplasm has split unfavourable leaving them with next to none. These polar bodies die and are a method of giving the ovum the best possible chance of survival.
212
What is the menopause?
The last menstrual period?
213
Menopause is a retrospective diagnosis, what is meant by this?
It is diagnosed after 1 year of amenorrhoea
214
What happens to FSH in the menopause?
It is high to stimulate ovaries which are not producing (as they have run out of eggs) and no ova means no oestrogen so no negative feedback
215
What is the name given to the period of time pre and perimenopause?
The climacteric
216
Are vasomotor symptoms enough to diagnose menopause?
If the woman is >45 years of age with a uterus, yes
217
What happens to the bones in the menopause?
Osteoporosis can occur
218
What are the main hormones to replace in the menopause?
What does each one do?
Oestrogen = to replace lack of and therefore reverse symptoms of menopause
Progesterone = protects the endometrium from hyperplasia
Testosterone = increases energy and sexual desire
219
Each testicle is divided into many lobules, what are the tubes which each lobule contain called?
Seminiferous tubules
220
The testicular seminiferous tubules consist of X2 cell types.
What are each of these called and what do they do?
1) spermatagonial cells = spermatogenesis
2) Sertoli cells = nourishment of spermatogonial cells and separation of the maturing sperm cells from the spermatagonial stem cells by forming the blood-testicular barrier (the two compartments created are the adluminal compartment and the interstitial compartment. Lastly they release inhibin which inhibits FSH secretion from the anterior pituitary.
221
What cells sit between the seminiferous tubules and what do they do?
Leydig cells = synthesise testosterone
222
From the seminerfous tubules, where do the sperm cells travel to?
Rete testis - epididymis - ductus vas deferens
223
Where in the tubule do the spermatagonial cells sit?
Why do they sit here?
Spermatagonial cells are stem cells that sit at the base of the tubule
As they divide into spermatoids (mature sperm) they rise towards the tubule lumen from the base
224
How long does the process of spermatogenesis last?
72 days
225
What is the process called in which mature spermatoids undergo physical changes to make them more suitable for their function?
Spermiogenesis (re-packaging)
They become sperm shaped and achieve their tail as well as gain numerous mitochondria (to aid energy production for movement)
Their head also develops a membrane around the nucleus called an acrosome which contains the necessary lysosomal enzymes to break the ova membranes and penetrate it
226
What hormones are responsible for:
1) stimulating spermatogenesis
2) stimulating testosterone synthesis
And which cells are involved in each...?
1) FSH = spermatogenesis in the spermstoagonial cells
| 2) LH = testosterone synthesis in the leydig cells
227
What testes products inhibit:
1) hypothalamus and pituitary
2) pituitary only
And what cells synthesise each of these...?
1) testosterone = leydig cells
| 2) inhibin = Sertoli cells
228
Why is prolactin relevant for males?
It aids spermatogenesis
229
What is sperm capacitation?
The loss of cholesterol and calcium influx of sperm 4 hours after ejaculation which lightens them and hyper-activates them in order to help them travel to their required destination
NB: think capacitor = energy store
230
Which protein on the ova membrane helps bind sperm?
Zona pellucida 3 (ZP3)
231
What happens to an ova once it has been penetrated by a single sperm?
It tries to prevent polyspermatic penetration by releasing cortical granules to block further sperm from binding and penetrating
232
How does the male contraceptive work?
It causes an excess of testosterone which feeds back to decrease FSH secretion therefore decreasing spermatogenesis
233
What genetic anueploidy is 46 XXY?
Kleinfelter syndrome = a male with female features
234
How many couples are affected by infertility?
1/7
235
What is the probably of conceiving for a couple in the first 3 years?
84% in first year
49% of remaining 16% in year 2
14% of remaining 8% in year 3
236
What is meant by sub-fertility?
Low chances of conceiving
237
What is the difference between primary and secondary infertility?
```
Primary = never before been pregnant
Secondary = some form of previous pregnancy (miscarriage/termination)
```
238
Why are previous pregnancies good and bad for second time conception rates?
Increased chance of second conception
ALSO increased chance of tubal disease (post-partum infection/ecoptic pregnancies)
239
What is a simple way to check ovulation as a cause of sub-fertility?
Ask how often a woman’s periods are
240
Why are mumps important in terms of sub-fertility?
Adult mumps can cause testicular orchitis and be a cause of male factor infertility
241
When would you measure a woman’s progesterone levels to see if she is ovulating?
Day 21 bloods
OR
7 days before end of cycle if cycle is longer than 28 days
242
What is normal semen volume and density?
>1.5ml volume
>15x10^6/ml density
243
What is the normal motility and morphology of semen?
>40% motile
>4% normal morphology
244
What is a Hycosy and why is it done?
It is a hystero contrast sonogram (ultrasound)
It is done to assess tubal patency
245
What does a high AMH level tell toy about Ovarian Reserve?
It indicates a high number of eggs as the hormone is released from follicle grannulosa cells
246
What causes PCOS?
Elevated male androgens in females causing cysts on the ovaries
247
What is azoospermia?
Semen that contains no sperm
248
What is the difference between gestational age and embryonic age?
When is each used?
How do you calculate each?
```
Gestational age
= time zero is LMP
= used clinically
= calculated using obs wheel
= expressed as complete weeks + days (28+5/40)
```
Embryonic age
= time zero is time of ovulation/fertilisation = day 14
= expressed in days (56-63)
= calculated by multiplying number of weeks by 7 to get last day. Last day minus 7 = first day)
NB: gestational age is always X2 weeks more than embryonic age
249
By when is implantation completed?
4 days prior to expected period starting (day 24)
10 days (embryonically) post ovulation
250
What are the X3 stages of implantation?
1) apposition (lining up)
2) attachment
3) penetration
251
What X2 structural features of the:
1) blastocyst
2) endometrium
...aid attachment?
1) Microvilli on trophoblast section of blastocyst
| 2) Pinipodes on the endometrium
252
What group of molecules is required in penetration of the blastocyst?
What clinical consideration does this hint at?
Prostaglandins (COX1 and 2)
Therefore avoid aspirin and other anti-inflammatories
253
During apposition, what factors are involved in aiding this process?
Leukaemia inhibiting factor (LIF)
Epidermal growth factor (EGF)
254
What happens if the endometrium encounters a bad embryo?
The pinipodes flatten to decrease chances of attachment
255
When the trophoblast layer of the blastocyst divides, what are the two layers called and which is inner and which is outer?
What are the nuclei like in each of these?
Inner = cytotrophoblastic layer = mononucleated
Outer = syncytiotrophoblastic layer = multinucleated (like a syncitium!)
256
Which of the two divided trophiblastic layers produced hCG?
The syncitiotrophoblastic layer
257
What does hCG do?
It feeds back on the corpus luteum grannulosa cells to stop them apoptosis get so they can keep synthesising progesterone
258
What is left after the chorionic villi on the decidua capsularis degenerate and regress?
The chorion laevae
259
What is the name of the flourishing chorionic villi on the decidual plate?
The chorion frondosum
260
What are the structures in which the placenta is divided into?
Cotyledons
261
What is the difference between monozygotic and dizygotic twins?
Monozygotic = X1 egg
Dizygotic = X2 eggs
262
What is meant by chorionicity?
Number of placentas and chorionic membranes
263
What is the name of the process by which the bi-laminar disc grows into a tri-laminar disc?
Gastrulation
264
What is trisomy 13?
What is trisomy 18?
Patau
Edwards
265
What are the X3 layers created in gastrulation?
Ectoderm
Mesoderm
Endoderm
266
When are congenital malformations of the foetus most likely to occur?
In weeks 3-8 of the first trimester
267
What is placenta Previa?
Low lying placenta
268
What is placenta accreta?
Chorionic villi attach to myometrium
269
What is placenta increta?
Chorionic villi invade to myometrium
270
What is placenta percreta?
Chorionic villi invade to myometrium and serosa, even into other structures such as bowel or bladder
271
What causes placental regression?
Oxidative stress causing apoptosis as the spiral artery plugs are removed
272
What is the name of the cells which block the spiral arteries?
Trophoblastic (trophoblasts) plugging
273
How does maternal blood reach the foetus?
The maternal uterine artery blook bathes the chorionic villi, there is therefore no direct maternal/foetal blood contact
274
When does blood flow to the foetus begin?
Around weeks 10-12
275
What structure carries oxygenated blood from the chorionic villi to the foetus?
Foetal umbilical vein
276
What structure carries deoxygenated blood from the foetus to the placenta?
Foetal umbilical artery
277
In the second half of pregnancy, which GLUT transporter is responsible for glucose transfer from the mother to foetus?
GLUT 1
278
What is responsible for foetal growth, glucose or insulin?
When does this begin to be synthesised?
Foetally produced insulin, foetus has little capacity for self-gluconeogenesis
9-11 weeks
279
What is macrosomia?
What maternal factors can influence this?
Overweight at birth
Maternal obesity and diabetes
280
What happens to the amniotic fluid in the amniotic sac?
The foetus swallows this and excretes it, this cycles
281
What is the name for too much and too little amniotic fluid?
Oligohydramnios = too little
Polyhydramios = too much
282
What predominantly controls foetal heart rate?
Vagal (parasympathetic) stimulation
283
What is foramen ovale and what is its purpose?
Hole between atria in foetus so that oxygenated blood coming from foetal unbilical vein goes IVC - RIGHT SIDE - LEFT SIDE for distrubution
284
What is ductus arteriosus and what is its purpose?
Deoxygenated blood that does not pass through FO goes into pulmonary artery then INTO DESCENDING AORTA - unsure why?
285
What is ductus venosus and what is its purpose?
Blood entering from placental foetal umbilical vein is oxygenated but goes into IVC
286
At birth how much Hb is F and how much is A?
Why does HbF have higher affinity for oxygen?
HbF (80%)
HbA (20%)
HbF = less sensitive to DPG
287
Does BP or HR change with pregnancy?
Plasma volume increases
TPR decreases
BP does not change overal (drops in first tri, rises towards end)
HR increases 15%
288
What happens to RBC count in pregnancy?
Dilutional anaesmia, despite RBC rising
Hct falls from 40% to 30%
289
Can you get murmurs in pregnancy?
Yes, systolic very common, diastolic can happen too
290
What does the 12 week scan involve?
Pregnancy dating
Combined screening test:
- Foetal nuchal translucency (back of neck skin thickness)
- Maternal serum betaHCG and PAPP_A
291
What would the 12 week scan results for each of these look like:
- Tri21
- Tri13
- Tri18
Tri21
= Thickened TN
= High bHCG
= LOW PAPP_A
Tri13
= Thickened TN
= LOW bHCG
= LOW PAPP_A
Tri18 = same as Tri13 BUT with even LOWER bHCG and THICKER TN
292
What blood tests are done on the parents pre-conception to week 10?
Sickle cell and thalassaemia
293
What is the appropriate anticoagulant in pregnancy?
LMWH
294
What happens to the resp system in pregnancy?
Tidal volume increases
RR STAYS THE SAME!
Result can be resp alkalosis
295
Which way should you roll a pregnant lady to relieve aorto-caval compression?
To her left
296
Is a chest X-ray safe in pregnancy?
Yes
297
How long pre-conception should folic acid be started?
3 Months
298
What acronym describes the features of DiGeorge syndrome?
```
C - cardiac abnormalities (tetralogy of fallot)
A - Abnormal facies
T - thymic aplasia
C - cleft palate
H - hypocalcaemia/hypoparathyroidism
22 - chromosome 22 deletion
```
299
Name 2 X-linked recessive conditions?
Haemophilia and Duchenne muscular dystrophy
300
In haemophillia A, what clotting factors are low?
What about B?
A = low on factor 8
B = low on factor 9
301
What does the 20 week scan do?
It is a foetal anomaly scan which offers a quadruple test based on maternal serum markers
302
What is used to screen for NTD's?
How is this detectable in the mothers serum?
AFP (alpha foeto protein)
It crosses the chorion and amnion into the uterine vasculature and mothers circulation
Should drop in second trimester, if raised = increase chance of NTD
303
What NTD structural changes/signs may be seen on scan?
Lemon (head shape) or banana (curved cerebellar) sign
304
Describe pros vs cons of CVS vs Amniocentesis.
CVS = quicker but higher miscarriage risk (1%)
Amnio = slower but lower miscarriage risk (0.5%)
305
What is the anti-testis gene found on the X chromosome involved in ovary formation from bi-potential gonads?
DAX 1
306
What secreted AMH?
Sertoli cells of the testicle
307
Why is AMH important?
Helps mullarian ducts regress
308
What are the names of both ducts we have as well as the bi-potential gonads?
Which persists if male and which persists if female?
Male = wolffian
Female = mullarian
309
How many copies of DAX1 are needed to confer female and repress testis development?
What happens in turners?
Ovaries are not functional as X2 copies are needed
310
What stimulates mullalrian ducts to persist?
Purely a lack of AMH from the testis (as no testis as gonads have differentiated into ovaries!)
311
What stimulates the wolffian ducts to persist in males?
AMH and testosterone from the testis
312
What is testosterone converted into to help promote genital formation?
A more potent androgen = DHT (dihydrotestosterone)
313
What happens genitals wise in klinefelter?
XXY
2 copies of DAX 1 = testis regression = small pea shaped testis
Other female features
314
What happens in 5-alpha-reductase deficiency?
Enzyme is needed for testosterone to be converted to DHT, therefore variable appearance of genitalia as reduced stimulus
315
What would a child with weight in the 98th centile suggest?
Very overweight!
316
Who begins puberty first?
Girls
317
When does the largest foetal weight gain happen?
3rd Tri
318
Differentiate between SGA (Small for gestational age) and FGR (Foetal growth restriction).
How would this look plot on a growth chart?
Small = follows a curve but at a lower weight
Restriction = straight line, stops following line as has stopped growing
319
What can be a treatment for low PAPP_A levels?
Aspirn
320
What is Erbs Palsy?
A brachial nerve injury that may occur in labour due to shoulders getting stuck - leads to 'waiters tip' arm
Macrosomia is a risk factor
