THE UNIVERSITY OF NEW SOUTH WALES

MEDICAL SOCIETY

Beginnings, Growth and

Development A EOC
Revision Tutorial
Vineet Gorolay and Amy Chur-Yee Liu

www.medsoc.org.au

Overview
Vineet:
- Physiology: hormone loops + menstrual
cycle
- Anatomy: urogenital diaphragm
Amy:
- Biochemistry: folate metabolism
- Physiology/pharmacology: adrenergic and
cholinergic mechanisms
www.medsoc.org.au

Reproductive Physiology

Key Concepts
Hormone feedback loops
Ovarian cycle
gamete support
steroidogenesis

Uterine cycle
preparation for implantation
cyclical regeneration

Clinical Relevance
Physiological symptoms
menstrual cycle
menopause

Family planning
conception
contraception (physiological, pharmacological)

Diagnosis of infertility

Key Concepts
Hormone feedback loops
Ovarian cycle
gamete support
steroidogenesis

Uterine cycle
preparation for implantation
cyclical regeneration

Hormone Feedback Loops

Question 1:
Describe, with the aid of a diagram, the hormonal regulation of
oestrogen production in the ovaries of the female reproductive tract.
Include the full names of all hormones involved (not just the
abbreviations) and indicate any feedback loops that regulate the
process. [10 marks]

Hormone Feedback Loops

Positive Feedback

Hypothalamus secretes GnRH which which travels

via the hypothalamicpituitary portal vein to act on
the anterior pituitary. [1 mark]

Gonadotrophs in anterior pituitary secrete

gonadotropins (LH and FSH) which stimulate
ovaries. [1 mark]

LH acts on theca cells, stimulating release of

progestins and androgens. [1 mark]

Androgens converted by granulosa cells into

oestrogens (oestradiol). [1 mark]

Granulosa cells produce oestrogens, inhibins (A&B)

and activins. [1 mark]

Hormone Feedback Loops

Negative Feedback

Inhibins and activins negatively feed back onto

anterior pituitary. [1 mark]

Progestins exert negative feedback upon the

hypothalamus and anterior pituitary. [1 mark]

Oestrogens (oestradiol) usually exerts negative

feedback upon the hypothalamus and anterior
pituitary. [1 mark]

The exception: rapid rise in oestradiol exerts

positive feedback upon the anterior hypothalamus
prior to ovulation. [1 mark]

Ovarian Cycle
Question 2:
Lucille is a 23 year old woman who presents with her husband for pre-conception
counseling. A careful history reveals that she has a regular 28-day menstrual cycle
and her menstrual flow lasts 4 days. This diagram depicts the hormonal changes
during the menstrual cycle.

With reference to the above diagram, outline the physiological events in the ovarian
cycle.

Ovarian Cycle
With reference to the above diagram, outline the physiological
events in the ovarian cycle.
The ovarian cycle consists of the follicular phase (prior to ovulation) and
luteal phase (after ovulation) and can be further subdivided as shown
below. [1 mark]

Early
Follicular

Mid Follicular

Late
Follicular

Early Luteal

Late Luteal

Ovarian Cycle
Early Follicular
The early follicular phase is driven by a gradual rise in FSH, causing
differentiation of primary follicles. [1 mark]
Developing follicles release oestradiol and inhibin B, which suppress FSH
secretion. [1 mark]

Early
Follicular

Ovarian Cycle
Mid Follicular
One follicle becomes dominant, and its granulosa cells are increasingly
sensitive to FSH, and its theca cells to LH. It secretes large amounts of
oestradiol. [1 mark]
Other follicles undergo atresia. [1 mark]

Mid Follicular

Ovarian Cycle
Late Follicular
Oestradiol production from the dominant (Graafian) follicle reaches a peak,
signalling maturity, and exerts positive feedback on the anterior pituitary. [1
mark]
The resulting LH surge occurs 2-3 days later, and triggers ovulation (within 12
hours). [1 mark]

Late
Follicular

Ovarian Cycle
Early Luteal
The follicular remnants become the corpus luteum, which secretes progesterone to
maintain the uterine lining and inhibits folliculogenesis. [1 mark]
Granulosa and theca cells differentiate into granulosa lutein and theca lutein cells
respectively. [1 mark]
After ovulation, the oocyte completes meiosis I and enters the uterine (Fallopian) tubes.
[1 mark]

Early Luteal

Ovarian Cycle
Late Luteal
In absence of implantation, the corpus luteum degenerates into the corpus
albicans. [1 mark]
Secretion of oestradiol and progesterone diminish, resulting in shedding of
uterine endometrium (menses) and restoration of gonadotropin secretion.
[1 mark]

Late Luteal

Anatomy

Clinical Relevance
None?

Key Concepts
Pelvic walls, floor, and urogenital diaphragm
Female internal and external genitalia
Male internal and external genitalia

Clinical Relevance
History and Physical Examination
Catheterisation
Interpreting radiological investigations
Anaesthesia (local, regional)
Obstetric/gynaecological/urological procedures
Radiotherapy

Key Concepts
Pelvic walls, floor, and urogenital diaphragm
Female internal and external genitalia
Male internal and external genitalia

Urogenital Diaphragm
Question 1:
You are assisting at a vaginal delivery. You notice that the patients
perineum is at risk of tearing and decide to perform an episiotomy.
Describe the structures (both superficial and deep) of the female
perineum and how you would make your incision so as to facilitate
delivery. [10 marks]

Urogenital Diaphragm
Typical Medical Student Answer

Urogenital Diaphragm
A More Thoughtful Approach
Draw:
Bony landmarks/orientation [bonus mark]
Orifices [1 mark]
Deep perineal space + external anal sphincter [2
marks]
Superficial perineal space [2 marks]

Outline
Perineal body [2 marks]
Effects of tears [2 marks]
Course of episiotomy [1 mark]

Urogenital Diaphragm
A More Thoughtful Approach
Draw:
Bony landmarks/orientation

pubic symphysis
ischiopubic rami
ischial tuberosity
coccyx

Urogenital Diaphragm
A More Thoughtful Approach
Draw:
Bony landmarks/orientation
Orifices
urethra
vagina
anus

Urogenital Diaphragm
A More Thoughtful Approach
Draw:
Bony landmarks/orientation
Orifices
Deep perineal space
deep transversus perinei
sphincter urethrae
external anal sphincter

Urogenital Diaphragm
A More Thoughtful Approach
Draw:
Bony landmarks/orientation
Orifices
Deep perineal space
Superficial perineal space

bulb of vestibule
greater vestibular gland
bulbospongiosus
corpus cavernosum (clitoris)
ischiocavernosus

Urogenital Diaphragm
A More Thoughtful Approach
Outline:
Perineal body
fibromuscular site of attachment for two sphincters and
four paired muscles
external anal sphincter
sphincter urethrae

levator ani (paired)

bulbospongiosus (paired)
superficial transversus perinei (paired)
deep transversus perinei (paired)

functions to stabilise pelvic and perianal viscera

Urogenital Diaphragm
A More Thoughtful Approach
Outline:
Perineal body
Effects of tears

Weakening of pelvic floor

Vaginal prolapse
Uterine prolapse
Urinary incontinence

Urogenital Diaphragm
A More Thoughtful Approach
Outline:
Perineal body
Effects of tears
Course of episiotomy
Posterolateral incision

vaginal wall
bulbospongiosus
superficial transversus perinei
part of levator ani
skin of ischioanal fossa/perineum

Take Home Messages

(1) Understand rather than rote learn
(2) Structure your answers logically
(3) Use diagrams to maximise efficiency

Folate Metabolism

What is
folate?

Clinical
relevancewhy is it
important?

Folate and I-C

metabolism

Folate
biosynthesis
and forms in
the body

What is folate?
- Vitamin
Water soluble
B9

Clinical relevance
Folate deficiency:
1. Anaemia (macrocytic, megaloblastic)
2. Neural tube defects

At-risk groups:

Pregnancy

Malabsorption

diseases

Alcoholics

Elderly

Medications

Biosynthesis
Occurs in higher plants and microorganisms but not in humans.

Forms of folate in the body

Folate and 1-C metabolism

One carbon metabolism is centered around folate. PolyglutamylFH4 derivatives are needed to supply chemical groups containing single
carbon atoms for biosynthetic reactions such as the synthesis of
nucleotides for DNA.
Tetrahydrofolate Derivatives

Folate and 1-C metabolism

Most of the 1-C fragments are interchangable and reversible on
tetrahydrofolate derivatives EXCEPT for the methyl group.

methionine synthase

Practice Questions
Question 1:
a) Imagine you are folate present in a green leafy vegetable. Describe
your journey as you are eaten by a human and transition through
different forms to the active form.
b) Methotrexate is a drug that exploits folate metabolism in
humans. Briefly explain the rationale for its use and its
mechanism of action. (5 marks)
c) Explain the effect of vitamin B12 deficiency on folate
metabolism (4 marks).

Sample Answer 1b)

Methotrexate is a drug that exploits folate metabolism in humans. Explain its
mechanism of action and the rationale for its use (5 marks).
Methotrexate is an antimetabolite drug whose indications include cancers (e.g.
leukaemia), autoimmune diseases (e.g. rheumatoid arthritis) and medical termination of
pregnancy. (1 mark).
The structure of methotrexate is extremely similar to that of folic acid (1 mark). The only
difference is that an amino group replaces a hyroxyl group on nitrogen 5 and a methyl
group replaces a hydrogen atom on nitrogen 10 *bonus mark*. Because of its similar
structure, its mechanism of action is as a competitive inhibitor (1 mark) of dihydrofolate
reductase which is needed in the two-step reduction of folic acid to its active form,
tetrahydrofolate (1 mark). Methotrexate is a highly potent inhibitor as it binds 100 times
more tightly than the folic acid *bonus mark*.
The rationale for its use is that the greatest need for folate is in rapidly dividing cells or
those with a high need for 1-C metabolism, such as cancer cells, therefore its effect is
concentrated in these cells (1 mark). However it is also toxic to host cells.

Sample Answer 1c)

Explain the effect of vitamin B12 deficiency on
folate metabolism (4 marks).
Vitamin B12 (cobalamin) is a water soluble vitamin that consists
of a protoporphyrin ring with a central cobalt atom. Vitamin B12 is
intimately related to folate metabolism because it is a coenzyme
for methionine synthase (1 mark).

Methionine synthase is needed for the utilisation of 5-methyl-FH4

as shown in the diagram *bonus mark*, which is the only
irreversible tetrahydrofolate derivative and therefore the dominant
derivative in the tissues and serum (2 marks).
Vitamin B12 deficiency creates a methyl-tetrahydrofolate trap because it esssentially
traps all the tetrahydrofolate as unusable f 5-methyl-FH4 (1 mark) and causes a
deficiency in all other folate derivatives.
One of the effects of B12 deficiency includes a macrocytic anaemia like that seen in
folate deficiency *bonus mark*.

Adrenergic and Cholinergic

Mechanisms

Divisions of the
nervous system

Action of
receptors in the
autonomic
nervous system

The autonomic
nervous system

Neurotransmitters
of the autonomic
nervous system

Divisions of the nervous system

The nervous system can be separated into parts based on structure
and function.

Central nervous
system (CNS)

Brain and spinal

cord

Peripheral
nervous system
(PNS)

Nerves and
ganglia outside
CNS

Somatic nervous
system

Skin and
voluntary
muscle

Autonomic
nervous system

Organs and
visceral
elements

Structure

NERVOUS
SYSTEM

Function

The autonomic nervous system

Parasympathetic

Sympathetic

Originates in the
craniosacral
region (cranial
nerves + S2-S4)

Originates in the
thoracolumbar
region (T1-L3)

Vegetative
(homeostatic)
function

Emergency (fight
or flight) function

Innervates viscera
only

Innervates viscera
+ peripheral
regions of the
body

Neurotransmitters of the ANS

The two main neurotransmitters of the ANS are acetylcholine (ACh)
and noradrenaline.

Action of Receptors in the ANS

Practice Questions
Question 1:
Propanolol is a drug that can be used to treat conditions such as
angina.
a) Explain the mechanism of action of this drug (2 marks).
a) Explain why this medication is contraindicated in patients with
diabetes (3 marks).

Sample Answer 1a)

Explain the mechanism of action of propanolol (2 marks).
Propanolol is a pure -adrenergic antagonist (1 mark) which potently
blocks 1 and 2 receptors equally to reduce heart rate and contractility to
lower cardiac output and arterial pressure (1 mark) Its effect depends on
the degree of sympathetic activity- its action is greatest in patients during
excitement or exercise *bonus mark*.

Sample Answer 1b)

b) Explain why propanolol is contraindicated in patients with
diabetes (3 marks).
Patients with diabetes may experience episodes of hypoglycaemia where
blood glucose levels are low. The sympathetic response to hypoglycaemia
produces symptoms, particularly tachycardia, that warn patients that of the
urgent need to consume carbohydrate (1 mark). -receptor antagonists
such as propanolol mask this symptom by reducing heart rate (1 mark)
and also diminishes the action of adrenaline (e.g. via an Epipen) on
release of glucose from the liver (gluconeogenesis) (1 mark).
Therefore use of -receptor antagonists should generally be avoided in
patients with poorly controlled diabetes, and there is a theoretical
advantage in using 1 selective agents as glucose release from the liver is
controlled by 2 receptors *bonus mark*.

All the best!

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